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id stringlengths 24 24	contexts_ids listlengths 1 157	split stringclasses 1 value	question stringlengths 13 215	type stringclasses 4 values	answer stringlengths 2 3.15k	exact_answer stringlengths 1 3.15k	contexts listlengths 1 157	concepts stringlengths 3 7.42k
5a897601fcd1d6a10c000008	[ 12007552, 22516994, 24705033, 8235662, 23172751, 28123902, 11480850, 16761499, 28116652, 12945718, 10955328, 15468356, 16354890, 25861457, 27365721, 17477466, 19762400, 16681575, 10685800, 28243944, 7993706, 2195948, 16150398, 27795838 ]	train	A SLEDAI score is associated with Systemic Lupus Erythematosus. What is a SLEDAI score?	summary	Disease activity of Systemic Lupus Erythematosis was evaluated according to the SLE Disease Activity Index (SLEDAI) score which score disease activity based on a number of parameters.	Disease activity of Systemic Lupus Erythematosis was evaluated according to the SLE Disease Activity Index (SLEDAI) score which score disease activity based on a number of parameters.	[ "Both the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus \nErythematosus Disease Activity Index (SLEDAI) are valid and reliable measures of \ndisease activity in systemic lupus erythematosus (SLE). However, more study of \ntheir responsiveness is needed. The purpose of this study was to compare the \nresponsiveness of SLAM-R and SLEDAI to disease activity changes relevant to \nphysicians and patients. Patients were evaluated monthly for up to 12 months. At \neach visit, the physician completed SLAM-R and SLEDAI. Patients and physicians \nassessed whether relevant improvement or worsening of disease activity had \noccurred since the previous visit. Based on repeated measurements, effect size \n(ES), standardized response mean (SRM), and control-standardized response mean \n(CSRM) were calculated for each response category, with bootstrap-based 95% \nconfidence intervals (CIs). Seventy-six patients contributed 471 score changes. \nFor physicians' responses, the CSRMs for SLAM-R and SLEDAI were -0.47 versus \n-0.42 for improvement, 0.04 versus 0.003 for no change, and 0.65 versus 0.66 for \ndeterioration. For patients, the CSRMs for SLAM-R and SLEDAI were -0.31 versus \n-0.18 for improvement, -0.08 versus 0.06 for no change, and 0.48 versus 0.05 for \ndeterioration. Only for SLAM-R did the 95% CIs exclude zero when improvement or \ndeterioration were detected. Similar results were found for ES and SRM. Both \nSLAM-R and SLEDAI are responsive to changes in SLE disease activity important to \nphysicians. Only SLAM-R is responsive to changes important to patients. These \ndifferences may result from the inclusion of subjective SLE manifestations in \nSLAM-R.", "OBJECTIVE: To evaluate the outcomes of pregnancies in patients with systemic \nlupus erythematosus (SLE).\nMETHODS: A retrospective observation was made on 41 patients with SLE delivered \nin our hospital and the disease activity of the patients and neonatal conditions \nwere followed up for one year after delivery. The impact of the disease \nduration, the use of cyclophosphamide, the highest systematic lupus \nerythematosus disease activity index (SLEDAI) score during the disease and the \nantepartum SLEDAI score to the outcome of delivery were analyzed.\nRESULTS: The disease duration of SLE was (3.5±3.1) years, the highest SLEDAI \nscore during the disease was 10.6±3.1. The antepartum SLEDAI score was 6.2±1.6, \nthe postpartum SLEDAI score was 6.4±2.9. The SLEDAI score in one year after \ndelivery was 5.4±2.1, which in patients with disease duration more than 4 years \nwas higher than that in patients with disease duration less than 4 years \n(P=0.03). All the deliveries were live births. The gestational age at birth was \n(37.6±3.3) weeks, and the body weight was (2 510.0±756.9) g. These figures were \nsignificantly lower than those of the healthy women (P=0.03 and P=0.008, \nrespectively). Four (9.8%) newborns were diagnosed as neonatal lupus.\nCONCLUSION: The risks of premature and low weight baby rates are increased in \npatients with SLE. The proper timing of pregnancy and conception will improve \npregnancy outcomes.", "Systemic lupus erythematosus (SLE) is a connective tissue disease characterized \nby the formation of autoantibodies and immune complexes. Lupus nephritis is one \nof the hallmark features of SLE. CXCL10 is a chemokine secreted by IFNg- \nstimulated endothelial cells and has been shown to be involved in the \npathological processes of autoimmune diseases. The objective was to measure \nurinary CXCL10 in SLE patients, to compare levels between nephritis and \nnon-nephritis groups and to study its correlation with other variables. Sixty \nlupus patients were enrolled in our trial. Thirty patients had lupus nephritis \nand the other 30 were without evidence of lupus nephritis. Thirty healthy \nsubjects were willing to participate as a healthy control group. Renal biopsy \nwas performed for lupus nephritis group. Urinary CXCL10 was measured using the \nELISA technique. Serum creatinine, C3, C4 and 24 h urinary proteins were \nmeasured. Lupus activity was assessed using systemic lupus erythematosus disease \nactivity index (SLEDAI) scoring system. Renal activity was measured using renal \nactivity scoring system. CXCL10 was significantly higher in lupus nephritis \npatients than in lupus patients without nephritis. CXCL10 was significantly \ncorrelated with renal activity score, 24 hours urinary proteins and the SLEDAI \nscore. It is highly valid predictor of SLE nephritis with high sensitivity and \nspecificity. CXCL 10 a highly sensitive and specific non-invasive diagnostic \ntool for lupus nephritis patients.", "The course and prognostic value of disease activity measured by the validated \nSystemic Lupus Erythematosus Disease Activity Index (SLEDAI) was investigated in \n68 newly diagnosed black Caribbean cases. A high percentage of patients had \nclinical renal involvement (78%). Disease activity at onset was mild to moderate \n(SLEDAI < or = 10) in 36% of patients; about half never reached a higher SLEDAI \nscore, whereas the other half advanced to higher disease activity (SLEDAI > 10). \nSLEDAI scores decreased significantly over time from diagnosis. Within 3 months \nafter disease onset, 54% of patients reached their maximum SLEDAI scores. There \nwere no differences in clinical features or survival between these patients and \nthose with later (mean, 35 months) maximum disease activity, although the latter \nhad more frequent disease flares. Overall survival was poor (91% and 56% at 1 \nand 5 years, respectively). High persistent disease activity (weighted average \nof SLEDAI scores > 10) was independently associated with decreased survival, \nwhereas a high initial SLEDAI, a high maximum SLEDAI, and an increase number of \nflares were not. The main cause of death was infection, which often was \nassociated with active disease (mean SLEDAI at death, 16 +/- 8.9). SLEDAI was a \npractical and reliable way of evaluating disease activity but was of limited \nprognostic value.", "OBJECTIVES: To evaluate treatment with the peptide-based agent, Lupuzor, in a \ndouble-blind, randomised, placebo-controlled study of patients with systemic \nlupus erythematosus.\nMETHODS: Patients who met ≥4 of the American College of Rheumatology criteria, \nhad a score of ≥6 on the Systemic Lupus Erythematosus Disease Activity Index \n2000 (SLEDAI-2K) and did not have an A score on the British Isles Lupus \nAssessment Group (BILAG)-2004 scale were eligible. 149 intention-to-treat (ITT) \npatients were randomly assigned to receive Lupuzor (200 μg) subcutaneously every \n4 weeks (n=49; group 1) or every 2 weeks (n=51; group 2) or placebo (n=49; group \n3) in addition to standard of care (SOC). A target population (136 ITT patients) \nconsisting of patients having a clinical SLEDAI score ≥6 at week 0 was \nconsidered. The clinical SLEDAI score is the SLEDAI-2K score obtained by \nomitting low complement and increased DNA binding components.\nRESULTS: In the ITT overall population, 53.1% in group 1 (p=0.048), 45.1% in \ngroup 2 (p=0.18) and 36.2% in the placebo group achieved an SLE Responder Index \n(SRI) response at week 12. In the target population, the results were more \nimpressive: 61.9% in group 1 (p=0.016), 48.0% in group 2 (p=0.18) and 38.6% in \nthe placebo group achieved an SRI response at week 12. An interim analysis \nincluding 114 patients from the target population demonstrated an even better \nefficacy (according to SLEDAI score) in group 1 compared with placebo (67.6% vs \n41.5% (p<0.025) at week 12 and 84.2% vs 45.8% (p<0.025) at week 24). The most \ncommon adverse event was a mild injection-site erythema.\nCONCLUSIONS: Lupuzor/200 µg given three times at 4-week intervals during 12 \nweeks in addition to SOC is efficacious and generally well tolerated.", "To determine the expression of mTOR, Becline-1, LC3 and p62 in the peripheral \nblood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) and assess \ntheir relationship with disease activity and immunologic features. The \nexpression of mTOR, Becline-1, LC3 and p62 was detected by RT-PCR in 81 SLE \nsubjects and 86 age- and sex-matched healthy controls. Data regarding \ndemographics and clinical parameters were collected. Disease activity of SLE was \nevaluated according to the SLE Disease Activity Index (SLEDAI) score. \nIndependent sample t-test was used to analyze the expression of mTOR, Becline-1, \nLC3, and p62 in the two groups. Pearson's or Spearman's correlation was \nperformed to analyze their relationship with disease activity and immunologic \nfeatures. The mean levels of Becline-1, LC3 and p62 mRNA were significantly \nhigher in SLE patients than the controls (9.96×10-4 vs 7.38×10-4 for Becline-1 \nwith P<0.001; 4.04×10-5 vs 2.62×10-5 for LC3 with P<0.001; 9.51×10-4 vs \n7.59×10-4 for p62 with P=0.008). However, the levels of mTOR mRNA in SLE \npatients were not significantly different from that in controls. Correlation \nanalysis showed that Becline-1, LC3 and p62 mRNA levels correlated positively \nwith SLEDAI, IgG and ds-DNA, negatively with C3. Our results suggested that \nautophagosomes formation were activated and their degradation were blocked in \nSLE. Moreover, the maintenance of autophagy balance can improve disease activity \nand immune disorders in SLE patients.", "The objective of this study was to assess the incidence and risk factors of \ninfections in 200 SLE outpatients. All outpatients with active or inactive SLE \nwithout infections in the previous month were included. They were assessed every \n3 months. Major infections were those requiring hospitalization and parental \nantibiotic therapy; minor infections required oral or topical therapy. \nSociodemographic, disease activity using the Systemic Lupus Erythematosus \nDisease Activity Index (SLEDAI), therapy and laboratory variables were \nevaluated. After a follow-up of 22+/-7 months, 65 (32%) patients had infections; \n35% of those were major. The most common sites for infection were urinary (26%), \nskin (23%), systemic (12%), and vaginal (9%). At infection onset, 50 of 65 \npatients (77%) had disease activity, with a mean SLEDAI score of 6.1. The \nvariables significantly associated with infection in the univariate analyses \nwere the presence of disease activity, SLEDAI score, renal activity, prednisone \ndose, and IV cyclophosphamide. The only variable associated with infection in \nthe multivariate analyses was a SLEDAI score of 4 or higher. Most infections in \nSLE outpatients were single, minor, non-life threatening, and associated with \ndisease activity independently of sociodemographic and therapeutic factors.", "Mononuclear cells play a cardinal role in the pathogenesis of systemic lupus \nerythematosus (SLE). A high urine cytology score has been reported to be \nassociated with lupus nephritis in relapse. The objective of this study was to \nexamine the urinary mononuclear cell population of patients with lupus \nnephritis, and explore its correlation with lupus disease activity. We studied \n12 patients with active lupus nephritis, 17 patients with lupus nephritis in \nremission, 12 SLE patients with no history of renal disease and 13 healthy \nsubjects. Clinical disease activity was quantified by the SLE Disease Activity \nIndex (SLEDAI). Mononuclear cell species in the urinary sediment were examined \nby immunocytochemistry. Patients with active lupus nephritis had significantly \nmore mononuclear cells in the urinary sediment. The number of CD3+ cell was \nsignificantly elevated in the active lupus nephritis than the others (P < \n0.001), while there was no significant difference in the number of CD20+ and \nCD56+ cell among patient groups. The total urinary mononuclear cell correlated \nsignificantly with the overall SLEDAI score (r = 0.58, P < 0.001) as well as the \nrenal score (r = 0.57, P < 0.001). The number of urinary CD3+, but not CD20+ or \nCD56+, cell significantly correlated with the overall SLEDAI score (r = 0.46, P \n= 0.003) as well as the renal score (r = 0.40, p = 0.011). In nine patients with \nrenal biopsy, the histological activity index correlated with the total urinary \nmononuclear cell (r = 0.75, P = 0.02), CD3+ (r = 0.69, P = 0.04) and CD20+ cell \n(r = 0.69, P = 0.04). We conclude that urinary mononuclear cell was markedly \nelevated in patients with active lupus, and the urinary mononuclear cell count \ncorrelated significantly with the SLEDAI score and histological activity. CD3+ \nand CD20+ cells are the major component of urinary mononuclear cell in SLE \npatients and their number correlates with lupus disease activity.", "We sought to evaluate a possible link between parvovirus B19 infection and the \nclinical and laboratory expression of systemic lupus erythematosus (SLE). SLE \npatients were examined to evaluate their clinical status and disease activity. A \ncomplete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was \nobtained for each patient. In addition, we determined the level of systemic \ninvolvement throughout the course of the disease. Blood levels of IgM and IgG \nantibodies to parvovirus B19, levels of anti-dsDNA, C3, and C4 were measured. A \nPCR real-time assay was used to determine the presence of parvovirus B19 genetic \nmaterial. The viral genome was found in sera of 2 of 51(3.9%) patients with SLE. \nThere was no correlation between viral serology and the clinical and serological \nparameters of the disease. More SLE patients with secondary antiphospholipid \nsyndrome (APS) had IgG and IgM antibodies to the virus (p < 0.029 and p < 0.018, \nrespectively). These patients also had a higher titer of IgG antibodies to \nparvovirus B19 compared to SLE patients without APS. In this group of SLE \npatients, no association was found between parvovirus infection and the presence \nor activity of SLE. The results of the study suggest an association between \nparvovirus infection and antibody production directed against phospholipids.", "The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most \ncommonly used measure of disease activity for children with systemic lupus \nerythematosus (SLE). For headaches to be scored in the SLEDAI as a symptom of \nactive disease, they have to be nonresponsive to narcotic analgesia. This may \naffect the overall estimation of disease activity, especially because headaches \nare common among children with SLE and narcotic analgesia is rarely used for \nheadache therapy in paediatrics. Moreover, the importance of headaches for the \ndevelopment of damage and their relation to other clinical parameters and \noutcomes has not been well described for children with SLE. We reviewed the \nmedical charts of an inception cohort of children (n = 63) who were newly \ndiagnosed with SLE. Information on headaches and other disease parameters was \nobtained. Disease activity and damage were measured using the SLEDAI and the \nSystemic Lupus International Collaboration Clinics/American College of \nRheumatology Damage Index (SDI), respectively. It has been shown that the \naccumulated burden of active disease as measured by serial SLEDAI scores over \ntime is one of the best predictors of eventual damage to children with SLE. \nNew-onset or significant increase of severe and/or persistent headaches (LHA) \nwere reported in 43% of the patients during a mean follow-up of 3.6 years. LHA \noccurred preferentially among patients with elevated levels of antiphospholipid \nantibodies (aPL) (P < 0.02) and only 6% of all LHA episodes were treated with \nnarcotics and thus considered for the measurement of disease activity in the \nSLEDAI. LHA were unrelated to proxy-measures of disease activity, such as the \nneed to intensify therapies. When used in children, the insensitivity of the \nSLEDAI to capture LHA did not seem to decrease the responsiveness of the SLEDAI \nto detect clinically important worsening of disease, or negatively impact on its \nability to predict damage.", "OBJECTIVE: To evaluate the prevalence, disease course, and survival of patients \nwith systemic lupus erythematosus (SLE) in a population of over 120,000 North \nAmerican Indians (NAI), and contrast the results to those in the non-Indian \npopulation.\nMETHODS: The regional arthritis center database and the medical records of all \nrheumatologists, hematologists, nephrologists, and general internists with > 1 \npatient with SLE were searched for cases of SLE diagnosed between 1980 and 1996. \nA random survey of 20% of family physicians serving this population suggested \nthat > 85% of all SLE cases were identified. Demographics, SLE Disease Activity \nIndex (SLEDAI) scores, Systemic Lupus International Collaborating \nClinics/American College of Rheumatology (SLICC/ACR) damage scores. clinical \nmanifestations, and therapy for NAI were contrasted with the results in \nCaucasians (CAUC).\nRESULTS: We identified 257 cases meeting the ACR criteria for SLE diagnosed \nbetween 1980 and 1996. There were 49 NAI cases, resulting in a prevalence of \n42.3/100,000, compared to a prevalence of 20.6/100,000 for the remainder of the \npopulation. NAI patients were younger at diagnosis, had higher SLEDAI scores at \ndiagnosis, and had more frequent vasculitis, proteinuria and cellular casts. \nThere were no treatment differences at diagnosis or at 2 years, but NAI patients \nwere significantly more likely to receive treatment with prednisone or \nimmunosuppressives at the last clinic visit. The NAI patients had similar damage \nscores at diagnosis, but significantly higher scores at 2 years and at the last \nclinic visit. NAI ethnicity increased the likelihood of death more than 4-fold.\nCONCLUSION: The prevalence of SLE was increased 2-fold in the NAI population. \nNAI patients had higher SLEDAI scores at diagnosis and more frequent vasculitis \nand renal involvement, required more treatment later in the disease course, \naccumulated more damage following diagnosis, and had increased fatality.", "OBJECTIVE: To assess the validity, reliability, and feasibility of the Systemic \nLupus Activity Measure-Revised (SLAM-R), the Mexican version of the Systemic \nLupus Erythematosus Disease Activity Index (MEX-SLEDAI), and a Modified \nSLEDAI-2000 (SLEDAI-2K) compared with the SLEDAI-2K in a multiethnic population \nof patients with SLE.\nMETHODS: We studied 92 SLE patients from 3 US geographic areas (Alabama, Texas, \nand Puerto Rico). Assessment occurred during regular outpatient, inpatient, or \nstudy encounters. A trained physician scored the 4 instruments and also assessed \ndisease activity globally [physician global assessment (PGA)]. Convergent (with \nSLEDAI-2K) and construct validity (with PGA) were determined by Spearman rank \n(rs) correlation test. Level of agreement between the instruments was assessed \nusing Bland-Altman plots. Discriminant validity (distinguishing clearly active \nvs mildly/nonactive disease) was assessed considering the SLEDAI-2K (and the \nPGA) as the gold standard. Feasibility was explored by cost analyses.\nRESULTS: The SLAM-R, the MEX-SLEDAI, and the Modified SLEDAI-2K were highly \ncorrelated with the SLEDAI-2K (rs = 0.566, 0.755, 0.924, respectively) and with \nthe PGA (rs = 0.650, 0.540, 0.634, respectively). The 3 instruments showed good \nagreement with the SLEDAI-2K (Bland-Altman plots). The Modified SLEDAI-2K had \nbetter discriminant validity than the SLAM-R and the MEX-SLEDAI. The Modified \nSLEDAI-2K was the least expensive instrument.\nCONCLUSION: The SLAM-R, the MEX-SLEDAI, and the Modified SLEDAI-2K are adequate \noptions for assessment of SLE disease activity; they are also less costly than \nthe SLEDAI-2K.", "BACKGROUND: The effects of estrogen-containing contraceptives on disease \nactivity in women with systemic lupus erythematosus have not been determined.\nMETHODS: We conducted a single-blind clinical trial involving 162 women with \nsystemic lupus erythematosus who were randomly assigned to combined oral \ncontraceptives, a progestin-only pill, or a copper intrauterine device (IUD). \nDisease activity was assessed at 0, 1, 2, 3, 6, 9, and 12 months according to \nthe Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The primary \noutcome was global disease activity, which we estimated by measuring the area \nunder the SLEDAI curve. Secondary outcomes included the maximum SLEDAI score, \nchange in SLEDAI score, incidence of lupus flares, median time to first flare, \nsystemic lupus erythematosus treatment, and adverse events. The results were \nanalyzed by the intention-to-treat method.\nRESULTS: At baseline, all demographic features and disease characteristics were \nsimilar in the three groups. The mean (+/-SD) SLEDAI score was 6.1+/-5.6 in the \ngroup assigned to combined oral contraceptives, 6.4+/-4.6 in the group assigned \nto the progestin-only pill, and 5.0+/-5.3 in the group assigned to the IUD (54 \npatients in each group) (P=0.36). Disease activity remained mild and stable in \nall groups throughout the trial. There were no significant differences among the \ngroups during the trial in global or maximum disease activity, incidence or \nprobability of flares, or medication use. The median time to the first flare was \nthree months in all groups. Thromboses occurred in four patients (two in each of \nthe two groups receiving hormones), and severe infections were more frequent in \nthe IUD group. One patient receiving combined oral contraceptives died from \namoxicillin-related severe neutropenia.\nCONCLUSIONS: Global disease activity, maximum SLEDAI score, incidence of flares, \ntime to first flare, and incidence of adverse events were similar among women \nwith systemic lupus erythematosus, irrespective of the type of contraceptive \nthey were using.", "OBJECTIVE: Current disease activity measures for systemic lupus erythematosus \n(SLE) are difficult to score or interpret and problematic for use in clinical \npractice. Lupus Foundation of America (LFA)-Rapid Evaluation of Activity in \nLupus (REAL) is a pilot application composed of anchored visual analogue scores \n(0-100 mm each) for each organ affected by lupus. This study evaluated the use \nof LFA-REAL in capturing SLE disease activity.\nMETHODS: In a preliminary test of LFA-REAL, this simplified, organ-based system \nwas compared with the most widely used outcome measures in clinical trials, the \nBritish Isles Lupus Assessment Group 2004 Index (BILAG), the SLE Disease \nActivity Index (SLEDAI) and the Safety of Estrogens in Lupus Erythematosus \nNational Assessment (SELENA) SLEDAI Physician's Global Assessment (SS-PGA). The \nlevel of agreement was analysed using Spearman rank correlations.\nRESULTS: 91 patients with SLE with mild to severe disease activity were \nevaluated, their median SLEDAI score was 4.0 (range 0-28) and BILAG score 8.0 \n(0-32). The median SS-PGA was 38 mm (4-92) versus the total REAL 50 mm (0-268), \nwhich expands in range by additive organ scores. Thirty-three patients had \nmoderate to severe disease activity (≥1.5 on SS-PGA landmarks). The median \nSS-PGA score of this group was 66 mm (50-92) versus median REAL score of 100 mm \n(59-268), confirming ability to detect a wider distribution of scores at higher \ndisease activity. Total REAL correlated with SLEDAI, BILAG and SS-PGA \n(correlation coefficient=0.816, 0.933 and 0.903, respectively; p<0.001 for all). \nIndividual LFA-REAL organ scores for musculoskeletal and mucocutaneous also \ncorrelated with corresponding BILAG domain scores (correlation coefficient=0.925 \nand 0.934, p<0.001).\nCONCLUSIONS: In this preliminary exercise, there were strong correlations \nbetween LFA-REAL and validated lupus disease activity indices. Further \ndevelopment may be valuable for consistent scoring in clinical trials, grading \noptimal assessment of change in disease activity and reliable monitoring of \npatients in practice.", "BACKGROUND: Therapeutic decisions in systemic lupus erythematosus (SLE) are \nbased on the disease activity and nature of organ involvement. There are various \nclinical and laboratory methods to assess the lupus flares.\nMETHODS: Fifty one SLE patients with active disease (lupus flare) were studied. \nSystemic lupus erythematosus disease activity index (SLEDAI), C3, C4 and \nanti-double stranded DNA levels were estimated and repeated monthly till \nremission. After remission these tests were done three monthly. Values of \nserological parameters were then correlated with SLEDAI score.\nRESULT: Thirteen (25.4%) patients had predominantly renal involvement while 38 \n(74.6%) patients had non-renal affliction. Musculoskeletal and mucocutaneous \nsymptoms were the commonest features of lupus flare (90%). It was observed that \n12 out of 13 (92.3%) patients with active renal involvement had low C3 levels \nand 11 (84.6%) had low C4 levels. The anti-dsDNA levels were elevated in all \npatients with predominant renal flare. In non-renal flare anti-dsDNA titre was \nraised only in 35% cases. Low C3 and C4 levels were noticed in 43% and 53% of \nnon-renal flares respectively. Significant positive correlation was noticed \nbetween SLEDAI score and anti-dsDNA levels (0.01 level two-tailed prediction) \nand a significant negative correlation was observed with SLEDAI and C3, C4 \nlevels (0.01 and 0.05 levels, two-tailed prediction) in our patients. On \nsubgroup analysis it was noticed that this correlation is stronger for renal \nlupus. Negative correlation of SLEDAI and complement levels was not observed in \nnon-renal flares.\nCONCLUSION: Calculation of SLEDAI is a vital clinical tool for assessment of SLE \npatients. Serial estimation of anti-dsDNA titre, C3 and C4 levels help us \ndiagnose lupus flare and make appropriate therapeutic decisions in patients with \nhigh SLEDAI score.", "OBJECTIVE: To determine the flare rate and the change in Safety of Estrogens in \nLupus Erythematosus: National Assessment Systemic Lupus Erythematosus Disease \nActivity Index (SELENA SLEDAI) score with disease flare in pediatric systemic \nlupus erythematosus (pSLE).\nMETHODS: A retrospective chart review of 62 patients with pSLE (ages 5-20 yrs). \nA flare was defined as the start of, or increase in, the dose of corticosteroids \nand/or the addition of an immunosuppressive medication. All pre-flare, flare, \nand post-flare visits were recorded with a SELENA SLEDAI score calculated for \neach visit. The flare rate was calculated by dividing the total number of flares \nin the cohort by the total followup years.\nRESULTS: Sixty-two patients were eligible. Forty-seven patients had 112 flares. \nThe average number of flares/patient was 1.8 +/- 2.0 and the mean inter-flare \ntime was 15.4 +/- 17.9 months. The flare rate in pSLE was 0.46 \nflares/patient-year of followup. The median time to first flare from the date of \ndiagnosis was 14.3 months. Patients with cytopenia, pleuritis, or pericarditis, \nor a positive antibody to Smith nuclear antigen at the time of diagnosis had a \nsignificantly higher flare rate than those who did not. The average SELENA \nSLEDAI score at presentation was 12.5 +/- 5.4, at the pre-flare visit 6.3 +/- \n3.5, and during a flare 7.9 +/- 5.1.\nCONCLUSION: This is the first large study to report a flare rate (0.46 \nflares/patient-year of followup) in pSLE. The flare rate was similar to what has \nbeen reported in pSLE previously but significantly lower than that reported in \nadults with lupus. The average change in the SELENA SLEDAI score with disease \nflare is 2 points.", "The objective of this study is to determine if digital vasculitis (DV), a \nclinical manifestation with a high systemic lupus erythematosus disease activity \nindex (SLEDAI) score, is associated with lupus severity. DV and other clinical \nmanifestations defined according to the SLEDAI were evaluated in 168 consecutive \npatients with systemic lupus erythematosus (SLE). Two groups were defined \naccording to presence (DV+, n = 27) or absence of DV (DV-, n = 141) at the time \nof evaluation. The exclusion criterion was the presence of antiphospholipid \nsyndrome (Sapporo's criteria). The two groups were comparable with regard to age \n(P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P = \n0.78). Compared to the DV- group, the DV+ group had a significantly higher \nfrequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01), \nhaematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional \nsymptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were \nsimilar in both groups (P = 0.57 and P = 1.00, respectively). The evaluation of \neach SLEDAI parameter confirmed that the DV+ group had higher frequencies of \nmild manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral \nulcers (P = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, \nboth groups had similarly increased anti-dsDNA (P = 0.78) and decreased \ncomplement levels (P = 0.29). In conclusion, DV in patients with SLE identifies \na subgroup of a mild disease. The high 'weighted' index attributed to this \nalteration in the SLEDAI score should therefore be revised.", "BACKGROUND: Lupus band test still has no clearly defined position within either \ndiagnostic or disease activity measuring tools for systemic lupus erythematosus \n(SLE).\nOBJECTIVES: We tested the hypothesis that positive LBT correlates with global \nactivity of SLE measured by the SLE Disease Activity Index (SLEDAI) score.\nMETHODS: In total, 90 SLE patients who underwent biopsy of sunprotected \nnon-lesional (SPNL) skin were studied prospectively. The skin specimen was \nprocessed for standard direct immunofluorescence. The patients were classified \ninto groups as negative and positive LBT, and the latter were further subdivided \non the basis of the type and morphology of the deposits. Every patient was \nthoroughly examined and assigned a SLEDAI score. The relationship between LBT \nfindings and SLEDAI score was analysed.\nRESULTS: The disease was significantly more active in patients with positive LBT \nand in those with a higher number of deposited immunoreactants. Almost all \npatients with renal involvement had a positive LBT.\nCONCLUSIONS: LBT on SPNL skin may be a good marker of severe disease at \npresentation, particularly when three immunoglobulins are found at the \ndermoepidermal junction.", "OBJECTIVE: To determine whether Systemic Lupus Erythematosus Disease Activity \nIndex (SLEDAI) scores correlate with the clinician's impression of level of \ndisease activity.\nMETHODS: In total, 230 patients with SLE followed at the University of Toronto \nLupus Clinic who had 5 visits 3 months apart in 1992-93 were studied. At each \nvisit a standard protocol was completed. A clinician who did not know the \npatients or their SLEDAI scores evaluated each patient record and assigned a \nclinical activity level. \"Flare\" was defined by new or increased therapy for \nactive disease, an expression of concern, or use of the term \"flare\" in the \nphysician's notes. The SLEDAI score was calculated from the database.\nRESULTS: SLEDAI scores described a range of clinical activity as recognized by \nthe clinician. Median SLEDAI scores ranged from 2 (inactive disease) to 8 \n(persistently active or flare). When the clinician assessed the patient to be \nimproved, the median SLEDAI score decreased by 2. When the clinician assessed \nthat the patient was experiencing a flare, the SLEDAI score increased by a \nmedian of 4.\nCONCLUSION: Based on our data we propose the following outcomes for patients \nwith SLE: flare, an increase in SLEDAI > 3; improvement is a reduction in SLEDAI \nof > 3; persistently active disease is change in SLEDAI +/- 3; and remission a \nSLEDAI of 0. These outcomes will allow a more complete description of a \npatient's response to therapeutic intervention in a responder index.", "Author information:\n(1)Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la \nSalud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, \n44340, Guadalajara, Jalisco, Mexico.\n(2)Unidad de Investigación Biomédica 02 (UIEC), UMAE Hospital de Especialidades, \nCentro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, \nAvenida Belisario Domínguez 1000, Col. Independencia Oriente, 44340, \nGuadalajara, Jalisco, Mexico.\n(3)Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de \nCiencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. \nIndependencia, 44340, Guadalajara, Jalisco, Mexico.\n(4)Departamento de Fisiología, Centro Universitario de Ciencias de la Salud \n(CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, \n44340, Guadalajara, Jalisco, Mexico.\n(5)Laboratorio de Investigación y Desarrollo Farmacéutico, Centro Universitario \nde Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino \nGarcía Barragán 421, 44430, Guadalajara, Jalisco, Mexico.\n(6)Departamento de Inmunología y Reumatología, Hospital General de Occidente, \nSecretaria de Salud, Av Zoquipan 1050, Seattle, 45170, Zapopan, Jalisco, Mexico.\n(7)Programa Internacional de Medicina, Universidad de Autónoma de Guadalajara, \nAv. Patria 1201, Col. Lomas del Valle, 45129, Zapopan, Jalisco, Mexico.\n(8)Unidad Médica Familiar 4 y 8, Departamento de Epidemiologia, Instituto \nMexicano del Seguro Social (IMSS), Fidel Velázquez Sánchez 1531, Atemajac del \nValle, 44218, Guadalajara, Jalisco, Mexico.\n(9)Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la \nSalud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, \n44340, Guadalajara, Jalisco, Mexico. dralauragonzalez@prodigy.net.mx.\n(10)Departamento de Medicina Interna-Reumatología, Instituto Mexicano del Seguro \nSocial (IMSS), Hospital General Regional 110, Av Circunvalación Oblatos 2208, \nColonia Circunvalación Oblatos, 44716, Guadalajara, Jalisco, Mexico. \ndralauragonzalez@prodigy.net.mx.\n(11), Avenida Salto del Agua 2192, Colonia Jardines del Country, 44210, \nGuadalajara, Mexico. dralauragonzalez@prodigy.net.mx.", "In this article, assessment of disease activity in systemic lupus erythematosus \n(SLE), including available instruments and their use in patients with SLE, is \ndiscussed. Several validated measures, including the SLAM (Systemic Lupus \nActivity Measure), SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), \nLAI (Lupus Activity Index), ECLAM (European Consensus Lupus Activity \nMeasurement), and that of the BILAG (British Isles Lupus Activity Group) are now \navailable and should be included in studies of new laboratory measures, \ntherapeutic trials, and studies of outcome and prognosis. The prognosis of SLE \nhas improved over the past 4 decades, including 20-year survival rates. With \nimproved survival, other outcome measures such as specific organ function and \nhealth status need to be considered. Administration of hydroxychloroquine \nremains an important part of therapy for SLE. The use of cyclophosphamide should \nbe reserved for severe manifestations of the disease. Newer forms of therapy, \nparticularly immunotherapy, have been tested in animal models.", "It is difficult to measure clinical disease activity in systemic lupus \nerythematosus because many organs can be involved simultaneously and the \ncorresponding symptoms are not easy to quantify. Disease activity is poorly \ndefined and there is no consensus on what disease activity means or how it \nshould be measured. More than 60 systems have been devised but none of them is \ncommonly used because they do not have the 3 characteristics necessary for such \na tool: validity, reliability and sensitivity. Three recent systems, BILAG \n(British Isles Lupus Assessment Group), SLEDAI (Systemic Lupus Erythematosus \nDisease Activity Index) and SLAM (Systemic Lupus Activity Measures) are very \nvalid. Comparisons of their reproducibility are in progress; however, more \ninformation is needed concerning their sensitivity and the feasibility of making \nthese systems easy to manage for physicians.", "The assessment of disease activity in systemic lupus erythematosus (SLE) is a \ntask faced by clinicians in every day care, but it is also required for clinical \nresearch and in randomised controlled trials. It is crucial to distinguish \ndisease activity from infection, chronic damage and co-morbid disease. Over the \npast 20 years, many indices have been developed to objectively measure lupus \ndisease activity and several of these have been validated. The most widely used \nindices are the British Isles Lupus Assessment Group (BILAG) index, the European \nConsensus Lupus Activity Measurement (ECLAM), the Systemic Lupus Activity \nMeasure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) \nand the Lupus Activity Index (LAI). All these indices have been validated and \nhave excellent reliability, validity and responsiveness to change. In addition \nto the assessment of disease activity, the evaluation of damage using the \nvalidated SLICC/ACR damage index and health-related quality of life is advised \nfor clinical research.", "BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune \nconnective-tissue disease involving multiple organs and systems. Some evidence \nhas demonstrated that disease activity could be associated with increased risk \nof organ damage.\nOBJECTIVES: The aim of this study was to determine the association between \nsystemic lupus erythematosus Disease Activity Index (SLEDAI) scores and \nsubclinical cardiac involvement.\nMETHODS: This cross-sectional study was conducted on 45 SLE patients (88% \nfemale; mean age: 31.2 ± 8.2 years) from 2011 to 2013 in Mashhad, Iran. The \npatients had no clinical signs and symptoms of cardiac problems or risk factors \nfor cardiovascular disease and were selected consecutively. All patients \nunderwent complete echocardiographic examinations (using two dimensional (2D) \ntissue Doppler and 2D speckle tracking). Disease activity was evaluated by using \nthe SLEDAI.\nRESULTS: Patients with higher SLEDAI scores had higher pulmonary artery pressure \nrates (r = 0.34; P = 0.024; 95% CI (0.086 to 0.595)) and SLE durations (r = \n0.43; P = 0.004; 95% CI (0.165 to 0.664). The correlation between disease \nduration and left ventricular mass was also significant (r = 0.43; P = 0.009; \n95% CI (0.172 to 0.681)), even after adjusting for age (r = 0.405; P = 0.016). \nThere was no correlation between SLEDAI scores or disease duration and the \nleft/right ventricle systolic function parameters. This was true while assessing \nthe right ventricle's diastolic function. A statistically significant \ncorrelation was found between mitral E/E' as an index of left ventricle \ndiastolic impairment and the SLEDAI scores (r = 0.33; P = 0.037; 95% CI (0.074 \nto 0.574)) along with disease duration (r = 0.45; P = 0.004; 95% CI (0.130 to \n0.662); adjusted for age: r = 0.478; P = 0.002).\nCONCLUSIONS: Echocardiography is a useful noninvasive technique for screening \nsubclinical heart problems in SLE patients. Although disease activity in general \nshould suggest a closer follow-up, regular scanning would enable earlier \ndetection of cardiovascular involvement and should not be confined to cases with \nhigher SLEDAI indices or longer disease durations." ]	['http://www.disease-ontology.org/api/metadata/DOID:8857', 'http://www.disease-ontology.org/api/metadata/DOID:9074', 'https://meshb.nlm.nih.gov/record/ui?ui=D008180']
5a96c886fcd1d6a10c00002a	[ 24690977, 28319627 ]	train	A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no?	yesno	Conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick, Ambyomma ameriacanum.	yes	[ "Delayed hypersensitivity disorders and food allergies are often challenging for \nthe clinician and patient alike. A recent discovery of an IgE antibody specific \nto galactose-α-1,3-galactose, which is a carbohydrate abundantly expressed on \ncells and tissues of beef, pork, and lamb, adds one more tool to aid the \nclinician in making the appropriate diagnosis. A link has been discovered \nbetween the bite of the Lone Star Tick (Amblyomma americanum) and the \ndevelopment of sensitivity to galactose-α-1,3-galactose. With a high prevalence \nof Lone Star Tick populations inhabiting major U.S. Army Installations, and the \ntype of duty required by our Service members, it could potentially affect \nsusceptible individuals. We describe a case of an active duty soldier who went 4 \nyears searching for this elusive diagnosis and connection and discuss why it \nshould remain in the differential diagnosis when treating military health care \nbeneficiaries.", "Amblyomma americanum, also known as the lone star tick, is found in much of the \neastern United States. Since the mid-20th century, the lone star tick has been \nimplicated in human disease. Today, A americanum remains an important vector for \ntick-borne illness. In addition to others, species of Rickettsia, Ehrlichia, and \nBorrelia are all transmitted by the lone star tick. Recently described \nconditions such as Southern tick-associated rash illness and anaphylaxis to red \nmeat following tick bites have been attributed to the lone star tick. Impressive \nlocal reactions also can result after bites from A americanum. Early treatment \nof tick-borne illness is crucial to ensure good patient outcomes. Tick-control \nmeasures also are an important part of disease management in endemic areas. We \ndiscuss the tick's biology, human illnesses associated with A americanum, and \nmethods to control tick numbers and eliminate disease in local reservoirs." ]	['https://meshb.nlm.nih.gov/record/ui?ui=D017282']
602346eb1cb411341a000090	[ 33139264, 34245216, 34522691, 34377156, 34051880, 34798793, 33442538, 33213161, 34189869, 33549983, 33663220, 34853653, 34771637, 32984090, 32349374, 34167423 ]	train	A combination of which two drugs was tested in the IMbrave150 trial?	list	IMbrave150 trial tested a combination of atezolizumab and bevacizumab for advanced hepatocellular carcinoma.	['atezolizumab', 'bevacizumab']	[ "On May 29, 2020, the FDA approved atezolizumab for use in combination with \nbevacizumab, for the treatment of adult patients with unresectable locally \nadvanced or metastatic hepatocellular carcinoma (HCC) with no prior systemic \ntreatment. The approval was based on data from Study IMbrave150, which randomly \nallocated (2:1) patients to receive either atezolizumab plus bevacizumab \n(atezolizumab-bevacizumab) or sorafenib. Overall survival (OS) and independently \nassessed progression-free survival (PFS) in the intent-to-treat population were \nthe primary endpoints. At the time of the primary analysis, the estimated median \nOS could not be estimated in the atezolizumab-bevacizumab arm and was 13.2 \nmonths in the sorafenib arm [HR, 0.58; 95% confidence interval (CI), 0.42-0.79]. \nThe estimated median PFS was 6.8 months (95% CI, 5.8-8.3) and 4.3 months (95% \nCI, 4.0-5.6) in the atezolizumab-bevacizumab and sorafenib arms, respectively. \nAdverse reactions occurring in >20% of patients receiving \natezolizumab-bevacizumab were hypertension, fatigue/asthenia, and proteinuria. \nAdverse reactions occurring in >20% of patients receiving sorafenib were \npalmar-plantar erythrodysesthesia, diarrhea, hypertension, and decreased \nappetite. Hemorrhage was reported more frequently in patients receiving \natezolizumab-bevacizumab (25%) than in patients receiving sorafenib (17%). An \nevaluation for the presence of varices is recommended within 6 months of \ninitiation of atezolizumab-bevacizumab in patients with HCC. Approval of \natezolizumab-bevacizumab is likely to change the treatment paradigm for HCC, \ngiven that treatment with atezolizumab-bevacizumab resulted in improved OS and \nPFS compared with sorafenib, an accepted standard of care for first-line \ntreatment of patients with unresectable HCC.See related commentary by Castet et \nal., p. 1827.", "AIM: A clinical trial (IMbrave150) indicated the efficacy and safety of \natezolizumab plus bevacizumab for patients with unresectable hepatocellular \ncarcinoma (HCC). In this study, we evaluated this therapeutic combination in a \nreal-world setting, with a focus on patients who did not meet the IMbrave150 \neligibility criteria.\nMETHODS: In this multicenter study, patients with unresectable HCC treated with \natezolizumab plus bevacizumab between October 2020 and May 2021 were screened. \nIn patients who did not meet IMbrave150 eligibility criteria, treatment \nresponses and safety at 6 and 12 weeks were evaluated.\nRESULTS: Atezolizumab plus bevacizumab was initiated in 64 patients, including \n46 patients (71.9%) who did not meet IMbrave150 eligibility criteria. Most of \nthese patients had a history of systemic therapy (44/46). The objective response \nrate and disease control rate observed using Response Evaluation Criteria in \nSolid Tumors 1.1 were 5.2% and 82.8% at 6 weeks and 10.0% and 84.0% at 12 weeks, \nrespectively; these rates were similar between patients who met and did not meet \nthe IMbrave150 criteria. Ten patients experienced progressive disease (PD) at \n6 weeks. Portal vein tumor thrombosis was significantly associated with PD \n(p = 0.039); none of the 15 patients with hepatitis B virus-related HCC \nexperienced PD (p = 0.050). The most common adverse events of grade 3 or higher \nwere aspartate aminotransferase elevation (n = 8, 13.8%) and the safety profile \nwas similar between patients who met and did not meet the IMbrave150 criteria.\nCONCLUSION: Most patients treated with atezolizumab plus bevacizumab did not \nmeet the IMbrave150 criteria; however, the combination therapy showed good \nsafety and efficacy at the early treatment phase.", "Portal vein involvement is considered one of the most fearful complications of \nhepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is \nassociated with aggressive tumor biology (high grade), high tumor burden (number \nand size of lesions), high levels of serum markers (AFP), poor liver function \n(deranged LFT), and poor performance status of patients. The Barcelona Clinic \nLiver Cancer staging system places HCC patients with PVTT in advanced stage \n(BCLC Stage-C). This group contains a fairly heterogeneous patient population, \npreviously considered candidates for palliative systemic therapy with sorafenib. \nHowever, this provided modest overall survival (OS) benefit. The results of a \nrecent Phase III (IMbrave150) trial favor the combination of atezolizumab and \nbevacizumab over sorafenib as a standard of care in advanced unresectable HCC. \nWhile only lenvatinib proved to be non-inferior against sorafenib in a phase III \n(REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and \ncabozantinib (CELESTIAL) have been approved second-line therapy in phase III \nclinical trials. Recently, the data on the prospect of other modalities in the \nmanagement of HCC with PVTT is mounting with favorable results. Targeting \nmultiple pathways in the HCC cascade using a combination of drugs and other \nmodalities such as RT, TACE, TARE, and HAIC appear effective for systemic and \nloco-regional control. The quest for the ideal combination therapy and the \nsequence set is still widely unanswered and prospective trials are lacking. With \nthe armament of available therapeutic options and the advances and refinements \nin the delivery system, down-staging patients to make them eligible for curative \nresection has been reported. In a rapidly evolving treatment landscape, \nperforming surgery when appropriate, in the form of LR and even LT to achieve \ncure does not seem farfetched. Likewise, adjuvant therapy and prompt management \nof the recurrences holds the key to prolong OS and DFS. This review discusses \nthe management options of HCC patients with PVTT.", "In light of positive efficacy and safety findings from the IMbrave150 trial of \natezolizumab plus bevacizumab, this novel combination has become the preferred \nfirst-line standard of care for patients with unresectable hepatocellular \ncarcinoma (HCC). Several additional trials are ongoing that combine an immune \ncheckpoint inhibitor with another agent such as a multiple kinase inhibitor or \nantiangiogenic agent. Therefore, the range of first-line treatment options for \nunresectable HCC is likely to increase, and healthcare providers need succinct \ninformation about the use of such combinations, including their efficacy and key \naspects of their safety profiles. Here, we review efficacy and safety data on \ncombination immunotherapies and offer guidance on monitoring and managing \nadverse events, especially those associated with atezolizumab plus bevacizumab. \nBecause of their underlying liver disease and high likelihood of portal \nhypertension, patients with unresectable HCC are at particular risk of \ngastrointestinal bleeding, and this risk may be exacerbated by treatments that \ninclude antiangiogenic agents. Healthcare providers also need to be alert to the \nrisks of proteinuria and hypertension, colitis, hepatitis, and reactivation of \nhepatitis B or C virus infection. They should also be aware of the possibility \nof rarer but potentially life-threatening adverse events such as pneumonitis and \ncardiovascular events. Awareness of the risks associated with these therapies \nand knowledge of adverse event monitoring and management will become \nincreasingly important as the therapeutic range broadens in unresectable HCC.", "BACKGROUND: Understanding patients' experience of cancer treatment is important. \nWe aimed to evaluate patient-reported outcomes (PROs) with atezolizumab plus \nbevacizumab versus sorafenib in patients with advanced hepatocellular carcinoma \nin the IMbrave150 trial, which has already shown significant overall survival \nand progression-free survival benefits with this combination therapy.\nMETHODS: We did an open-label, randomised, phase 3 trial in 111 hospitals and \ncancer centres across 17 countries or regions. We included patients aged 18 \nyears or older with systemic, treatment-naive, histologically, cytologically, or \nclinically confirmed unresectable hepatocellular carcinoma and an Eastern \nCooperative Oncology Group (ECOG) performance status of 0 or 1, with disease \nthat was not amenable to curative surgical or locoregional therapies, or \nprogressive disease after surgical or locoregional therapies. Participants were \nrandomly assigned (2:1; using permuted block randomisation [blocks of six], \nstratified by geographical region; macrovascular invasion, extrahepatic spread, \nor both; baseline alpha-fetoprotein concentration; and ECOG performance status) \nto receive 1200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously once \nevery 3 weeks or 400 mg sorafenib orally twice a day, until loss of clinical \nbenefit or unacceptable toxicity. The independent review facility for tumour \nassessment was masked to the treatment allocation. Previously reported coprimary \nendpoints were overall survival and independently assessed progression-free \nsurvival per Response Evaluation Criteria in Solid Tumors 1.1. Prespecified \nsecondary and exploratory analyses descriptively evaluated treatment effects on \npatient-reported quality of life, functioning, and disease symptoms per the \nEuropean Organisation for Research and Treatment of Cancer (EORTC) \nquality-of-life questionnaire for cancer (QLQ-C30) and quality-of-life \nquestionnaire for hepatocellular carcinoma (QLQ-HCC18). Time to confirmed \ndeterioration of PROs was analysed in the intention-to-treat population; all \nother analyses were done in the PRO-evaluable population (patients who had a \nbaseline PRO assessment and at least one assessment after baseline). The trial \nis ongoing; enrolment is closed. This trial is registered with \nClinicalTrials.gov, NCT03434379.\nFINDINGS: Between March 15, 2018, and Jan 30, 2019, 725 patients were screened \nand 501 patients were enrolled and randomly assigned to atezolizumab plus \nbevacizumab (n=336) or sorafenib (n=165). 309 patients in the atezolizumab plus \nbevacizumab group and 145 patients in the sorafenib group were included in the \nPRO-evaluable population. At data cutoff (Aug 29, 2019) the median follow-up was \n8·6 months (IQR 6·2-10·8). EORTC QLQ-C30 completion rates were 90% or greater \nfor 23 of 24 treatment cycles in both groups (range 88-100% in the atezolizumab \nplus bevacizumab group and 80-100% in the sorafenib group). EORTC QLQ-HCC18 \ncompletion rates were 90% or greater for 20 of 24 cycles in the atezolizumab \nplus bevacizumab group (range 88-100%) and 21 of 24 cycles in the sorafenib \ngroup (range 89-100%). Compared with sorafenib, atezolizumab plus bevacizumab \nreduced the risk of deterioration on all EORTC QLQ-C30 generic cancer symptom \nscales that were prespecified for analysis (appetite loss [hazard ratio (HR) \n0·57, 95% CI 0·40-0·81], diarrhoea [0·23, 0·16-0·34], fatigue [0·61, 0·46-0·81], \npain [0·46, 0·34-0·62]), and two of three EORTC QLQ-HCC18 disease-specific \nsymptom scales that were prespecified for analysis (fatigue [0·60, 0·45-0·80] \nand pain [0·65, 0·46-0·92], but not jaundice [0·76, 0·55-1·07]). At day 1 of \ntreatment cycle five (after which attrition in the sorafenib group was more than \n50%), the mean EORTC QLQ-C30 score changes from baseline in the atezolizumab \nplus bevacizumab versus sorafenib groups were: -3·29 (SD 17·56) versus -5·83 \n(20·63) for quality of life, -4·02 (19·42) versus -9·76 (21·33) for role \nfunctioning, and -3·77 (12·82) versus -7·60 (15·54) for physical functioning.\nINTERPRETATION: Prespecified analyses of PRO data showed clinically meaningful \nbenefits in terms of patient-reported quality of life, functioning, and disease \nsymptoms with atezolizumab plus bevacizumab compared with sorafenib, \nstrengthening the combination therapy's positive benefit-risk profile versus \nthat of sorafenib in patients with unresectable hepatocellular carcinoma.\nFUNDING: F Hoffmann-La Roche and Genentech.", "INTRODUCTION: The treatment algorithm of advanced hepatocellular carcinoma (HCC) \nhas evolved since the introduction of immunotherapy. The IMbrave150 trial set \natezolizumab-bevacizumab as a new standard-of-care first-line treatment for \nunresectable HCC patients. However, for patients with intermediate or advanced \nstage with portal vein thrombosis but without distant metastases, 90Yttrium \ntransarterial radioembolization (90Y-TARE) is considered the treatment of \nchoice.\nAREAS COVERED: We discuss the main evidence regarding the use of 90Y-TARE in \nHCC, the recent progress of immunotherapy in this tumor, and the preclinical \nrationale of combining VEGF blockade with the other two treatment strategies.\nEXPERT OPINION: HCC has an extremely heterogeneous tumor immune \nmicroenvironment. This may explain the inconsistent outcomes obtained with \nimmune-checkpoint inhibitors. The identification of patients who could benefit \nmost from immunotherapy is crucial; however, reliable markers of response are \nlacking. Radiation therapy and VEGF inhibition have an established synergism \nwith immunotherapy, mainly linked to enhanced antigen presentation and reduced \nimmunosuppressive immune infiltrate. Combining an immune-checkpoint inhibitor \nwith VEGF blockade and 90Y-TARE might hence overcome primary resistances \nobserved when each of these treatments is administerd alone.", "Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since \nthe introduction of the molecular targeted agent sorafenib in 2007. Sorafenib \nincreased the available treatment options for patients with extrahepatic spread \nand vascular invasion and improved survival in patients with advanced HCC; \nhowever, various shortcomings such as low response rates and relatively high \ntoxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at \ndeveloping new molecular targeted agents to provide more treatment options and \nsecond-line agents for patients with disease progression or intolerance to \nsorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all \nfirst-line and second-line clinical trials conducted during this period failed. \nHowever, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and \nregorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in \nquick succession from clinical trials and became available for clinical use. In \naddition, nivolumab and pembrolizumab were approved as second-line agents after \nsorafenib. A recent phase III trial (IMbrave150) showed that combination \nimmunotherapy with atezolizumab plus bevacizumab increases overall survival \ncompared with sorafenib therapy; Food and Drug Agency already approved this \ncombination therapy, and worldwide approval is expected soon. This review \ndescribes the recent advances in systemic therapy and the use of tyrosine kinase \ninhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal \nantibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors \n(nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the \nsimilarity of their efficacy and safety profiles to those in the general \npopulation.", "Hepatocellular carcinoma remains a serious global disease. Its incidence is \nincreasing. Standard procedures have been developed for each stage. The \ncomplexity of this disease shows that the selection of patients in stage 0/A for \ndifferent types of surgical treatment is very complicated. Treatment methods of \nstage B, especially locoregional treatment represented by TACE (transarterial \nchemoembolization or radioembolization of TARE), radiofrequency ablation and \nothers, move freely to lower and higher stages as adjunctive therapy. Lenvatinib \ncan replace TACE with equal efficacy in cases where locoregional treatment \ncannot be used. Until 2016, the only systemic treatment option for stage C was \nsorafenib. Lenvatinib became a second-line drug to show non-inferiority to \nsorafenib in OS. Retrospective analyzes revealed that patients who responded to \nthe treatment with lenvatinib or sorafenib had a median survival of over 22 \nmonths. Sequential treatment with sorafenib and regorafenib in the RESOURCE \nstudy with a median survival of more than 24 months was similar. Ramucirumab was \neffective only in patients with high AFP levels. The study demonstrated the \nimportance of selecting patients according to prognostic factors (extrahepatic \nspread and vascular invasion). Second-line cabozantinib has shown the same \nbenefit as regorafenib. In the second line, immunotherapy represented by anti \nPD-1 antibodies nivolumab and pembrolizumab was used. Sequential administration \nafter sorafenib prolonged the median overall survival of about 22 months. We \ncurrently have sorafenib and lenvatinib in the first line, regorafenib, \ncabozantinib, ramucirumab (AFP 400 μg/L), pembrolizumab and nivolumab in \nthe second line. The possibilities of monotherapy have been exhausted. The \ndiscovery of a synergistic effect of angiogenesis inhibitors, which convert a \ncold tumor into a hot one and facilitate the efficacy of anti-PD-1 / anti-PDL-1 \nantibodies, has led to a highly effective combination therapy. In study \nIMbrave150, the combination of atezolizumab and bevacizumab was successfully \nused compared to sorafenib in the first-line treatment. Additional studies are \ncurrently underway using other tyrosin kinase inhibitors - regorafenib, \nlenvatinib and cabozantinib - in combination with nivolumab, ipilimumab and \npembrolizumab. This development of treatment at all stages evoked with renewed \nurgency the need to find a suitable way to search for the early stages of HCC \nand to create a more effective system for selecting patients for the most \nappropriate treatment.", "BACKGROUND: IMbrave150 is a phase III trial that assessed \natezolizumab + bevacizumab (ATEZO/BEV) versus sorafenib (SOR) in patients with \nunresectable hepatocellular carcinoma (HCC) and demonstrated a significant \nimprovement in clinical outcomes. Exploratory analyses characterized objective \nresponse rate (ORR), depth (DpR), and duration of response (DoR), and patients \nwith a complete response (CR).\nMETHODS: Patients were randomized 2:1 to intravenous ATEZO (1200 mg) + BEV \n(15 mg/kg) every 3 weeks or oral SOR (400 mg) twice daily. Tumors were evaluated \nusing Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and \nHCC-modified RECIST (mRECIST). ORR by prior treatment and largest baseline liver \nlesion size, DoR, time to response (TTR), and complete response (TTCR) were \nanalyzed.\nRESULTS: For both criteria, responses favored ATEZO/BEV versus SOR regardless of \nprior treatment and in patients with lesions ≥3 cm. Median TTR was 2.8 months \nper RECIST 1.1 (range: 1.2-12.3 months) and 2.8 months per mRECIST (range: \n1.1-12.3 months) with ATEZO/BEV. Patients receiving ATEZO/BEV had a greater DpR, \nper both criteria, across baseline liver lesion sizes. Characteristics of \ncomplete responders were similar to those of the intent-to-treat population. In \ncomplete responders receiving ATEZO/BEV per mRECIST versus RECIST 1.1, \nrespectively, median TTCR was shorter (5.5 vs. 7.0 months), mean baseline sum of \nlesion diameter was longer (5.0 [SD, 5.1] vs. 2.6 [SD, 1.4] cm), and mean \nlargest liver lesion size was larger (4.8 [SD, 4.2] vs. 2.3 [SD, 1.0] cm).\nCONCLUSIONS: These data highlight the improved ORR, DpR, and CR rates with \nATEZO/BEV in unresectable HCC.", "Hepatocellular carcinoma (HCC) represents the most commonly diagnosed liver \ncancer worldwide, and the overall survival of patients with unresectable disease \nis poor. In the last five years, immune checkpoint inhibitors (ICIs) have \nrevolutionized the treatment scenario of several hematological and solid tumors, \nand these agents have been actively explored in unresectable HCC. Firstly, \npromising findings of phase I and II clinical studies reporting durable \nresponses and a tolerable safety profile have led to the assessment of ICIs as \nsingle agents in phase III clinical studies; however, the latter have provided \ncontroversial results, and the activity of ICI monotherapy seems limited to a \nsmall subgroup of patients. Conversely, the IMbrave150 trial recently showed \nthat, among patients with previously untreated unresectable HCC, treatment with \natezolizumab plus bevacizumab resulted in significantly longer overall survival \nand progression-free survival compared to sorafenib monotherapy. In addition, \nthe activity of several other ICIs is under investigation, as combination \nimmunotherapy as well as combinations of immunotherapy with antiangiogenic \nagents. Nonetheless, there are currently no validated predictive biomarkers able \nto guide treatment choice in this setting, where the identification of specific \npredictors of response to ICIs represents a major challenge. In this review, we \naim to provide a critical overview of recent evidence on biochemical predictors \nof response to ICIs in patients with unresectable HCC, especially focusing on \nPD-L1, TMB, MSI, and other emerging biomarkers.", "Hepatocellular carcinoma (HCC) is a common cancer globally and a leading cause \nof cancer-related deaths. Although early-stage disease may be curable by \nresection, liver transplantation or ablation, many patients present with \nunresectable disease and have a poor prognosis. Combination treatment with \natezolizumab (targeting PD-L1) and bevacizumab (targeting VEGF) in the recent \nIMbrave150 study was shown to be effective with an acceptable safety profile in \npatients with unresectable HCC. Herein, we discuss this novel combination in the \ncontext of the liver immune environment, summarize the mechanism and \npharmacokinetics of atezolizumab and bevacizumab, and examine recent data on \nother immune checkpoint inhibitor combination strategies as well as future \ndirections in the treatment of patients with advanced HCC.", "BACKGROUND: Despite the use of current standard therapy, the prognosis of \npatients with unresectable hepatocellular carcinoma (HCC) is poor, with median \nsurvival times of 40 mo for intermediate HCC (Barcelona Clinic Liver Cancer \n[BCLC] stage B) and 6-8 mo for advanced HCC (BCLC stage C). Although patients \nwith early-stage HCC are usually suitable for therapies with curative intention, \nup to 70% of patients experience relapse within 5 years. In the past decade, the \nUnited States Food and Drug Administration has approved different immunogenic \ntreatment options for advanced HCC, the most common type of liver cancer among \nadults. Nevertheless, no treatment is useful in the adjuvant setting. Since \n2007, the multi-kinase inhibitor sorafenib has been used as a first-line \ntargeted drug to address the increased mortality and incidence rates of HCC. \nHowever, in 2020, the IMbrave150 trial demonstrated that combination therapy of \natezolizumab (anti-programmed death-ligand 1 [PD-L1]) and bevacizumab \n(anti-vascular endothelial growth factor [VEGF]) is superior to sorafenib, a \nsingle anti-programmed death 1/PD-L1 antibody inhibitor used as an anti-cancer \nmonotherapy for HCC treatment.\nAIM: To conduct a systematic literature review to evaluate the evidence \nsupporting the efficacy and safety of atezolizumab/bevacizumab as preferred \nfirst-line drug therapy over the conventional sorafenib or atezolizumab \nmonotherapies, which are used to improve survival outcomes and reduce disease \nprogression in patients with unresectable HCC and non-decompensated liver \ndisease.\nMETHODS: A comprehensive literature review was conducted using the PubMed, \nScopus, ScienceDirect, clinicaltrials.gov, PubMed Central, Embase, EuropePMC, \nand CINAHL databases to identify studies that met the inclusion criteria using \nrelevant MeSH terms. This systematic review was conducted according to the \nPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines \nand risk of bias (RoB) were assessed using the Cochrane RoB 2 tool and Sevis.\nRESULTS: In the atezolizumab/bevacizumab group, an improvement in overall tumor \nresponse, reduction of disease progression, and longer progression-free survival \nwere observed compared to monotherapy with either sorafenib or atezolizumab. \nHypertension and proteinuria were the most common adverse events, and the rates \nof adverse events were comparable to those with the monotherapy. Of the studies, \nthere were two completed trials and two ongoing trials analyzed using high \nquality and low bias. A more thorough analysis was only performed on the \ncompleted trials.\nCONCLUSION: Treatment of HCC with atezolizumab/bevacizumab combination therapy \nwas confirmed to be an effective first-line treatment to improve survival in \npatients with unresectable HCC and non-decompensated liver disease compared to \nmonotherapy with either sorafenib or atezolizumab.", "Atezolizumab plus bevacizumab combination therapy was approved worldwide for use \nin 2020. A 30% objective response rate with 8% complete response (CR) was \nachieved in a phase 3 IMbrave150 trial. Here, the change in the treatment \nstrategy for hepatocellular carcinoma (HCC) using atezolizumab plus bevacizumab \ncombination therapy is reviewed. The phase 3 IMbrave150 clinical trial was \nsuccessful because of the direct antitumor effect of bevacizumab, which shifted \nthe suppressive immune microenvironment to a responsive immune microenvironment, \nin addition to its synergistic effects when combined with atezolizumab. The \nanalysis of CR cases was effective in patients with poor conditions, \nparticularly tumor invasion in the main portal trunk (Vp4), making the \ncombination therapy a breakthrough for HCC treatment. The response rate of the \ncombination therapy was 44% against intermediate-stage HCC. Such a strong \ntumor-reduction effect paves the way for curative conversion (ABC conversion) \ntherapy and, therefore, treatment strategies for intermediate-stage HCC may \nundergo a significant shift in the future. As these treatment strategies are \neffective in maintaining liver function, even in elderly patients, the \ntransition frequency to second-line treatments could also be improved. These \nstrategies may be effective against nonalcoholic steatohepatitis-related \nhepatocellular carcinoma and WNT/β-catenin mutations to a certain degree.", "For over a decade, sorafenib remained the only systemic agent with proven \nclinical efficacy for patients with advanced hepatocellular carcinoma (HCC). \nRecent years have seen a proliferation of agents. In the first line, lenvatinib \nwas found to be non-inferior to sorafenib in terms of overall survival (OS), \nwith significantly better progression-free survival and objective response rate. \nMeanwhile, encouraging efficacy signals were observed in phase I/II studies of \nimmune checkpoint inhibitors as monotherapy in HCC. Although subsequent phase \nIII trials failed to demonstrate statistically significant benefit in OS, other \nclinically meaningful outcomes were observed, including long-term disease \ncontrol with a favorable toxicity profile. In addition, a synergistic response \nhas been postulated based on the interplay between antiangiogenic molecular \ntargeted agents and immunotherapy. On this basis, interest has turned toward \ncombination strategies of immunotherapy with these standard-of-care medications \nin the hope of improving treatment efficacy for advanced HCC, while maintaining \ntolerable safety profiles. Indeed, preliminary results from phase I studies of \nlenvatinib plus pembrolizumab and atezolizumab plus bevacizumab have proved \nfavorable, prompting phase III investigations in the frontline setting, and for \natezolizumab plus bevacizumab, these positive findings have been substantiated \nby recent reporting of phase III data from IMbrave150. In this review, we will \npresent the currently available data on combination therapy atezolizumab plus \nbevacizumab in advanced HCC, and compare these findings to other promising \ncombination treatments, most notably that of lenvatinib plus pembrolizumab.", "A successful phase III trial for the combination of atezolizumab and bevacizumab \n(the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been \nreported. This is groundbreaking because nivolumab and pembrolizumab, both \nprogrammed cell death-1 (PD-1) antibodies, have failed to show efficacy as \nfirst- and second-line therapeutics, respectively, in phase III clinical trials. \nImmunotherapy with a combination of atezolizumab and bevacizumab resulted in \nbetter survival than treatment with sorafenib for the first time since sorafenib \nwas approved in 2007. The high efficacy of the combination of PD-1/programmed \ndeath ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) antibodies \nis not only due to their additive effects on tumor growth, but also to their \nreprogramming of the immunosuppressive microenvironment into an \nimmunostimulatory microenvironment. These results were confirmed in a phase Ib \ntrial that showed significantly longer progression-free survival in the \natezolizumab plus bevacizumab group than in patients that received atezolizumab \nalone. These results demonstrate that immunotherapy with a combination of \nPD-1/PD-L1 and VEGF inhibitors is effective and may result in a reprogramming of \nthe tumor microenvironment. The results of an ongoing phase III trial of a PD-1 \nantibody in combination with the VEGF receptor tyrosine kinase inhibitor (TKI) \nare highly anticipated.", "Introduction: The treatment of unresectable hepatocellular carcinoma (HCC) has \nradically changed after the approval of the combination of atezolizumab plus \nbevacizumab as first-line treatment. A strong preclinical rationale exists to \nsupport the combination of bevacizumab, an anti-vascular endothelial growth \nfactor monoclonal antibody (mAb), and atezolizumab, an anti-programmed death \nligand 1 mAb. The efficacy of the combination was first assessed in the phase Ib \nGO30140 study, and the combination was then proven superior to the prior \nstandard of care, sorafenib, in the phase III IMbrave150 trial.Areas covered: \nThis article focuses on the mechanism of action of atezolizumab and bevacizumab, \ntheir synergistic action, and the two clinical trials leading to approval. We \nalso collected the body of post-hoc analyses and meta-analyses to help guide the \ndecision-making process in terms of patient selection and subsequent \ntreatments.Expert opinion: Atezolizumab plus bevacizumab are the current \nstandard of care for first-line treatment of unresectable or metastatic HCC and \ntreatment-naïve patient should be treated with the combination, unless \ncontraindications to the drugs. Since all the available agents for further lines \nof treatment have been approved for sorafenib-pretreated patients, prospective \ntrials, post-hoc analyses, and real-world data assessing valid treatment \nsequencing are strongly needed." ]	nan
515d7693298dcd4e5100000c	[ 22954629, 12872232, 20641139, 12422360, 12915006 ]	train	A common problem in proteomics is the contamination of samples with exogenous proteins (often from other species). These proteins can be found in specific databases. List some contaminants.	list	Some common contaminants in proteomics are proteases (used for the digestion of the proteins), keratins (usually from the skin), proteins originated from the serum of the culture media and antibodies if used in the experiment.	['Proteases', 'Keratins', 'Bovine serum proteins', 'Antibodies']	[ "Mass spectrometry is widely used in bioanalysis, including the fields of \nmetabolomics and proteomics, to simultaneously measure large numbers of \nmolecules in complex biological samples. Contaminants routinely occur within \nthese samples, for example, originating from the solvents or plasticware. \nIdentification of these contaminants is crucial to enable their removal before \ndata analysis, in particular to maintain the validity of conclusions drawn from \nuni- and multivariate statistical analyses. Although efforts have been made to \nreport contaminants within mass spectra, this information is fragmented and its \naccessibility is relatively limited. In response to the needs of the \nbioanalytical community, here we report the creation of an extensive manually \nwell-annotated database of currently known small molecule contaminants.\nAVAILABILITY: The Mass spectrometry Contaminants Database (MaConDa) is freely \navailable and accessible through all major browsers or by using the MaConDa web \nservice http://www.maconda.bham.ac.uk.", "Unmatched masses are often observed in the experimental peptide mass spectra \nwhen database searching is performed with the ProFound program. Comparison \nbetween theoretical and experimental mass spectra of standard proteins shows \nthat contamination accounts for most of the unmatched masses. In this \nretrospective analysis, the top 100 most probable contaminating masses, as \nlisted in order of their probability, are statistically filtered out from 118 \ndifferent experimental peptide mass fingerprinting (PMF) maps. Most of the \ninterfering masses originate from trypsin autolysis and human keratins. \nSubtraction of known contaminants from raw data and using cleaner masses for \nsearching can enhance protein identification by PMF.", "Cell culture is a fundamental tool in proteomics where mammalian cells are \ncultured in vitro using a growth medium often supplemented with 5-15% FBS. \nContamination by bovine proteins is difficult to avoid because of adherence to \nthe plastic vessel and the cultured cells. We have generated peptides from \nbovine serum using four sample preparation methods and analyzed the peptides by \nhigh mass accuracy LC-MS/MS. Distinguishing between bovine and human peptides is \ndifficult because of a considerable overlap of identical tryptic peptide \nsequences. Pitfalls in interpretation, different database search strategies to \nminimize erroneous identifications and an augmented contaminant database are \npresented.", "FindPept (http://www.expasy.org/tools/findpept.html) is a software tool designed \nto identify the origin of peptide masses obtained by peptide mass fingerprinting \nwhich are not matched by existing protein identification tools. It identifies \nmasses resulting from unspecific proteolytic cleavage, missed cleavage, protease \nautolysis or keratin contaminants. It also takes into account post-translational \nmodifications derived from the annotation of the SWISS-PROT database or supplied \nby the user, and chemical modifications of peptides. Based on a number of \nexperimental examples, we show that the commonly held rules for the specificity \nof tryptic cleavage are an oversimplification, mainly because of effects of \nneighboring residues, experimental conditions, and contaminants present in the \nenzyme sample.", "Immunoprecipitation (IP) and coimmunoprecipitation (co-IP) are key techniques \nfor studying protein-protein interactions. These methods utilize immobilized \nProtein A or Protein G to isolate antibody-bound target antigens. The main \ndisadvantage of traditional IP and co-IP is that the conditions used to elute \nthe precipitated antigen also release the antibody thus contaminating the \nantigen and destroying the antibody support. To overcome these problems, we \ndescribe two methods to generate a reusable antibody support by cross-linking \nthe antibody to immobilized Protein A or Protein G, or by coupling it directly \nto the resin (see Scheme 1). Antibody cross-linking can be done in 1 h while \nantibody coupling requires 4 h. IP or co-IP is accomplished by incubating the \nantibody resin with the protein sample. Washes and elutions are carried out in a \nspin column to reduce resin loss and decrease assay time. Target proteins are \neluted with 0.1 M glycine (pH 2.8) and the resin-bound antibody is \nre-equilibrated in phosphate-buffered saline (PBS) for reuse. Our studies have \ndemonstrated that the immobilization efficiency for the antibody coupling method \nwas similar for several species of antibody. Furthermore, we illustrate that \nusing both methods of antibody immobilization yield IP and co-IP results similar \nto traditional protocols but eliminate the antibody heavy and light chain \ncontamination." ]	nan
5312280ce3eabad02100000a	[ 11037190, 21968521, 20635402, 8898827, 18463369, 15362573, 22436252, 22426657, 23966756, 9973290, 16723886, 9128751, 20644152, 23077562, 21596366, 21048783, 23713105, 10754001, 15340753, 18576213, 19335127, 17431895, 19918425, 24167642, 15675355, 15675354, 18174554, 16164190, 10757474, 16475235, 17138018, 8937199, 21631222 ]	train	Abnormalities in which chromosomes were linked to the Moyamoya disease?	list	chromosomes 3, 6, 8, 12, 15, 17, 21, X and Y were implicated in the Moyamoya disease.	['3', '6', '8', '12', '15', '17', '21', 'X', 'Y']	[ "Moyamoya disease is a specific chronic cerebrovascular occlusive disease first \nreported by Japanese surgeons in 1957. The disease is characterized by stenosis \nor occlusion of the terminal portions of the bilateral internal carotid arteries \nand abnormal vascular network in the vicinity of the arterial occlusion. It may \ncause ischemic attacks or cerebral infarction, which is more frequent in \nchildren than in adults. In adults, cerebral hemorrhage may occur. The disease \nis distributed in all age groups, but the highest peak is in childhood at less \nthan 10 years of age. The characteristic histopathologic features of the \nsteno-occlusive arteries are fibrocellular thickening of the intima containing \nproliferated smooth muscle cells and prominently tortuous and often duplicated \ninternal elastic lamina. There is usually no atheromatous plaque in the arterial \nwall. Etiology of the disease is still unknown; however, multifactorial \ninheritance is considered possible because of a higher incidence of the disease \nin Japanese and Koreans and approximately 10% of familial occurrence among the \nJapanese. Recent genetic studies suggest some responsible genetic foci in \nchromosomes 3, 6 and 17.", "A 20-year-old woman presented with mental retardation and a history of stroke \nrelated to moyamoya disease at the age of 8 years. She had cognitive impairment \nwhich became more pronounced after the stroke. This patient's parents were first \ncousins and six close family relatives had strokes in their 60s or 70s. The \npatient's 16-year-old sister had learning disability, chronic muscle pain, and \nan ECG suggestive of previous hypoxemic heart injury. The two sisters had \nsimilar dysmorphic facial appearance including a prominent philtrum, bulbous \nnose, and severe acne. They both had increased subcutaneous tissue in their \nfaces, whereas their bodies were slim. Both sisters were found to have elevated \nlevels of rheumatoid factor, C-reactive protein, and erythrocyte sedimentation \nrate on repeat measurements. Partial autoimmunity screening in one of the \npatients was negative. Chromosome analysis and array comparative genomic \nhybridization analyses were also normal. Nerve conduction findings in the \nyounger sister were consistent with distal, predominantly motor, demyelinating \nneuropathy localized to the lower extremities. We propose that these two sisters \nsuffer from a new autosomal recessive syndrome. Carrier status for this \ncondition may predispose to later onset stroke.", "Aortic dilation and dissection are well-recognized cardiac abnormalities in \nwomen with Turner syndrome (TS), although the underlying pathophysiology is not \nfully understood. We report on a 46-year-old Hispanic woman who was previously \ndiagnosed with moyamoya disease on magnetic resonance imaging after a \npresentation with stroke-like symptoms. Her features were consistent with TS and \nchromosome analysis revealed mosaicism in which 17% of the cells showed a \npseudoisodicentric Y chromosome: 45,X (25)/46,X psu idic (Y)(11.2) (5). A \npreceding screening transthoracic echocardiogram had shown a bicuspid aortic \nvalve (BAV) with an aortic diameter of 3.2 cm; at the time of moyamoya \ndiagnosis, the aorta was 3.5 cm with mild aortic stenosis and mild aortic \nregurgitation. Four years later, the patient had had an acute aortic dissection, \nStanford type A, which was repaired successfully. This case report is the third \nindividual with TS associated with moyamoya disease and the first associated \nwith dissection. The small number of cases does not allow detailed analysis \nother than noting patient age (two older than 40 years), karyotype (two others \nassociated with isochrome Xq), and associated cardiac risk factors (one with \nBAV). Although this may be a chance occurrence, we hypothesize that moyamoya \ndisease could be a manifestation of the vasculopathy in TS.", "BACKGROUND AND PURPOSE: Moyamoya disease is a chronic occlusive cerebrovascular \ndisorder characterized by progressive stenosis of the supraclinoid internal \ncarotid artery, with the secondary development of enlarged basal collateral \nvessels. It may occur as a primary disease or as a syndrome in association with \na variety of conditions, and its pathogenesis remains unexplained. There are \nrelatively few reports describing the occurrence of moyamoya in Down syndrome. \nThe aim of this study is to describe the clinical and radiological features of \nmoyamoya syndrome associated with Down syndrome (MM-DS) and to explore theories \nof moyamoya pathogenesis in these patients.\nMETHODS: Seven children with MM-DS underwent brain imaging, transfemoral \nangiography, and serial neurological exams. Neurological deficits, poststroke \nrecovery, radiographic infarct characteristics, and angiographic abnormalities \nwere reviewed.\nRESULTS: The clinical and radiological features of primary moyamoya disease \noverlap with those of MM-DS. Hemiplegia and aphasia were the most common \npresentations. Motor recovery was excellent in five of seven cases. Cerebral \ninfarcts were superficial or deep and can occur in a watershed distribution. \nAngiography demonstrated involvement of the internal carotid artery and its \nbranches bilaterally in all seven cases and the posterior cerebral arteries in \nfour cases.\nCONCLUSIONS: The clinical and radiological features of MM-DS overlap with \nprimary moyamoya disease. We postulate that a protein encoded on chromosome 21 \nmay be related to the pathogenesis of moyamoya disease. Although the neuronal \nsubstrate is abnormal in Down syndrome patients, recovery from hemiplegic stroke \nin patients with MM-DS is comparable to recovery in patients with primary \nmoyamoya.", "BACKGROUND: Moyamoya disease (MMD) is an idiopathic steno-occlusive \ncerebrovascular disease that represents an important cause of stroke. However, \netiology of the disease has remained largely unknown.\nMETHODS: We previously showed that the inheritance pattern of MMD is autosomal \ndominant with incomplete penetrance. Here, we report the genome-wide parametric \nlinkage analysis for MMD in 15 extended Japanese families. We conducted linkage \nanalyses under two diagnostic classifications: narrow and broad. Affected \nmember-only analysis was applied due to incomplete and age-dependent penetrance \nof the disease.\nRESULTS: Under both classifications, significant evidence of linkage was only \nobserved on chromosome 17q25.3, with maximum multipoint logarithm of odds (lod) \nscores of 6.57 (under the narrow classification) and 8.07 (under the broad \nclassification) at D17S704. Haplotype analysis revealed segregation of a disease \nhaplotype in all families but one, and informative crossovers enabled mapping of \nthe MMD locus to a 3.5-Mb region between D17S1806 and the telomere of 17q, \nencompassing 94 annotated genes.\nCONCLUSIONS: Our data suggest that there is a major gene locus for autosomal \ndominant moyamoya disease on chromosome 17q25.3.", "Moyamoya disease (MIM 252350) is characterized by stenosis or occlusion of the \nterminal portions of the bilateral internal carotid arteries and by abnormal \nvascular networks at the base of the brain. There is a high incidence of \nmoyamoya disease in Asia, especially in Japan. Multifactorial inheritance is \nestimated with lambda(s)>40. Previous linkage studies have indicated that \nsusceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. \nIn the present study, we searched for loci linked to the disease in 12 Japanese \nfamilies using 428 microsatellite markers and found significant evidence for \nlinkage to 8q23 [maximum LOD score (MLS) of 3.6] and suggestive evidence for \nlinkage to 12p12 (MLS=2.3). The present study revealed a novel locus for \nmoyamoya disease.", "BACKGROUND: Single-gene disorders related to ischemic stroke seem to be an \nimportant cause of stroke in young patients without known risk factors. To \nidentify new genes responsible of such diseases, we studied a consanguineous \nMoroccan family with three affected individuals displaying hereditary \nleucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis \npigmentosa that appears to segregate in autosomal recessive pattern.\nMETHODS: All family members underwent neurological and radiological \nexaminations. A genome wide search was conducted in this family using the ABI \nPRISM linkage mapping set version 2.5 from Applied Biosystems. Six candidate \ngenes within the region linked to the disease were screened for mutations by \ndirect sequencing.\nRESULTS: Evidence of linkage was obtained on chromosome 17q24.2-25.3. Analysis \nof recombination events and LOD score calculation suggests linkage of the \nresponsible gene in a genetic interval of 11 Mb located between D17S789 and \nD17S1806 with a maximal multipoint LOD score of 2.90. Sequencing of seven \ncandidate genes in this locus, ATP5H, FDXR, SLC25A19, MCT8, CYGB, KCNJ16 and \nGRIN2C, identified three missense mutations in the FDXR gene which were also \nfound in a homozygous state in three healthy controls, suggesting that these \nvariants are not disease-causing mutations in the family.\nCONCLUSION: A novel locus for leucoencephalopathy with ischemic stroke, \ndysmorphic syndrome and retinitis pigmentosa has been mapped to chromosome \n17q24.2-25.3 in a consanguineous Moroccan family.", "Stroke in trisomy 21 may be due to cardioembolism, atherosclerosis, vasculitis, \nmoyamoya disease, sinus venous thrombosis, internal carotid hypoplasia or \ninfections like endocarditis with septic emboli, meningitis or brain abscess. In \nrare cases, however, stroke etiology remains unexplained. We present a 19 year \nold Caucasian girl with trisomy 21 with a 47XX+21 karyotype who suffered at age \n11 years from a transient ischemic attack with left hemiparesis, and at age \n17 years from an ischemic stroke in the territory of the right cerebral medial \nartery. She suffered from arterial hypertension, obesity and \nhypercholesterolemia. Since blood coagulation studies, immunologic parameters, \nblood cultures, 24-h Holter monitoring, transthoracic and transesophageal \nechocardiography, magnetic resonance angiography of the extra- and intracranial \nvessels, thoracic and abdominal aorta and renal arteries did not provide any \nexplanation for the stroke, implantation of a loop recorder is considered in \norder to detect episodes of clinically silent atrial fibrillation.", "A 14-year-old boy was admitted to our hospital after being diagnosed at a local \nclinic with bilateral carotid artery stenoses (Moyamoya disease) and mild \nthyrotoxicosis. A blood examination showed suppressed TSH and elevated \ntriiodothyronine and thyroxine levels; however, he was negative for \nanti-thyrotropin receptor antibody (TRAB) and thyroid stimulating antibody \n(TSAB). Concern about a possible thyroid crisis led us to administer thiamazole \n(MMI) and potassium iodide (KI), following which \nencephalo-duro-arterio-synangiosis (EDAS) of the left side was performed \nsuccessfully. After about 1 mo, he became positive for TRAB and TSAB. He was \nthought to have Graves' disease and Moyamoya disease coincidentally. Several \nfactors are considered to be involved in the coincidental onset of these two \ndiseases.", "Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the \nterminal portion of the internal carotid artery. Moyamoya disease is prevalent \namong patients <10 years of age. Although most cases appear to be sporadic, \napproximately 10% occur as familial cases. The incidence of familial cases has \nbeen increasing because noninvasive diagnostic equipment, such as \nmagnetic-resonance imaging and magnetic-resonance angiography, can detect the \ndisease in almost all affected patients, including asymptomatic patients, during \nscreening studies. In this study, we performed a total genome search to identify \nthe location of a familial moyamoya disease gene in 16 families, assuming an \nunknown mode of inheritance. A linkage was found between the disease and markers \nlocated at 3p24.2-26. A maximum NPL score of 3.46 was obtained with marker \nD3S3050. This is the first genetic locus found to be involved in the molecular \npathogenesis of familial moyamoya disease.", "OBJECTIVE: The genes encoding tissue inhibitor of metalloproteinase (TIMP) 4 and \nTIMP2 span chromosomes 3p24.2-p26 and 17q25, respectively, which are the \nlocations of familial moyamoya disease (FMMD) genes. We investigated single \nnucleotide polymorphisms of the TIMP2 and TIMP4 genes in FMMD patients to \ndetermine genetic predispositions.\nMETHODS: Eleven blood samples from FMMD patients were recruited. Controls \nincluded 50 blood samples from patients with nonfamilial moyamoya disease (MMD) \nand another 50 blood samples from non-MMD persons. We evaluated the promoter \nregions, exon-intron junctions, and the exons of the TIMP2 and TIMP4 genes by \ndirect sequencing, and compared single nucleotide polymorphisms frequencies \namong the study groups.\nRESULTS: A significantly higher frequency of a heterozygous genotype was found \nin the TIMP2 promoter region at position -418 in FMMD; that is, the G/C \nheterozygous genotype at position -418 was observed in nine of 11 patients with \nFMMD, in 16 out of 50 nonfamilial MMD control participants, and in 14 out of 50 \nnon-MMD control participants (FMMD versus nonfamilial MMD: odds ratio, 9.56; 95% \nconfidence interval, 1.85-49.48; P = 0.005; and FMMD versus non-MMD: odds ratio, \n10.50; 95% confidence interval, 2.02-54.55; P = 0.001). This base at position \n-418 corresponds to the third base of the GAGGCTGGG sequence, an Sp1 binding \nsite. Thus, changes in this position may influence Sp1 binding and subsequent \ntranscription of the gene.\nCONCLUSION: Our findings suggest that the presence of a G/C heterozygous \ngenotype at position -418 in TIMP2 promoter could be a genetic predisposing \nfactor for FMMD.", "Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs \nfrequently in children. The etiology is unknown. We examined changes in \nbiological characteristics and responsiveness to serum mitogens during the in \nvitro cellular aging of arterial smooth muscle cell strains derived from \npatients with moyamoya disease (HMSMC) and compared them with those of cells \nfrom age-matched control patients (HCSMC). HMSMC had a normal human diploid \nchromosome constitution. HMSMC and HCSMC had almost the same in vitro life span \nand the age-related patterns of biological parameters were essentially the same. \nHowever, the doubling time at the early passages was significantly longer in \nmoyamoya SMC than control SMC, although there was no significant difference at \nthe late passages. Furthermore, the poor responsiveness of moyamoya SMC to \nplatelet-derived growth factor was retained throughout the life span in vitro. \nThese results support the hypothesis that functional alterations in vascular \ncells are involved in the mechanism of development of intimal thickening in \nmoyamoya disease.", "OBJECTIVE: We report a detailed description of a family affected by a hereditary \nmultisystem disorder associated with moyamoya syndrome.\nMETHODS: In this family case report, we evaluated 9 members of the same family \noriginating from Algeria. Investigations included neuroimaging, cardiologic and \nophthalmologic evaluation, hormonal testing, hemoglobin electrophoresis, \nchromosomal karyotyping, muscle biopsy for morphology, immunohistochemistry and \nenzyme assays, mtDNA mutation screening, and haplotype analysis of 2 loci \npreviously linked to moyamoya, on chromosomes 10 (ACTA2) and 17.\nRESULTS: Five males related through a maternal lineage were affected, suggesting \nan X-linked inheritance. Four of them had symptomatic moyamoya syndrome with an \nonset of acute neurologic manifestations between 4 and 32 years. \nHypergonadotropic hypogonadism, azoospermia, short stature of postnatal onset \n(-2 to -4 SD in adulthood), premature graying of hair, and dysmorphism were \npresent in all patients. The other features of the disease included early \ncataract in 4, dilated cardiomyopathy in 3, and partial growth hormone \ndeficiency in 2 members. Muscle biopsy data did not reveal signs of a \nmitochondrial disorder. All conditions known to be associated with moyamoya \nsyndrome such as Down syndrome, neurofibromatosis, and sickle cell disease were \nexcluded. We also excluded linkage to the 2 loci previously reported to be \ninvolved in autosomal dominant syndromic and nonsyndromic moyamoya. Carrier \nfemales had normal phenotype and clinical history.\nCONCLUSIONS: These data strongly suggest that this family is affected by a \nhereditary moyamoya multisystem disorder with X-linked recessive pattern of \ninheritance.", "We conducted a case-control study to investigate whether vascular endothelial \ngrowth factor (VEGF -2578, -1154, -634, and 936) and kinase insert domain \ncontaining receptor (KDR -604, 1192, and 1719) polymorphisms are associated with \nmoyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, \n20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, \n23.0±16.1 years; 56.8% female) were included. The subjects were divided into \npediatric and adult groups. Among the 64 surgical patients, we evaluated \ncollateral vessel formation after 2 years and divided patients into good \n(collateral grade A) or poor (collateral grade B and C) groups. The frequencies \nand distributions of four VEGF (-2578, -1154, -634, and 936) and KDR (-604, \n1192, and 1719) polymorphisms were assessed from patients with moyamoya disease \nand compared to the control group. No differences were observed in VEGF -2578, \n-1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the \ncontrol group and moyamoya disease group. However, we found the -634CC genotype \noccurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the \nKDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = \n0.024). Patients with the CC genotype of VEGF -634 had better collateral vessel \nformation after surgery. Our results suggest that the VEGF -634G allele is \nassociated with pediatric moyamoya disease and poor collateral vessel formation.", "Author information:\n(1)INSERM UMR-S-740; Université Paris, 7 Denis Diderot, 10 Avenue de Verdun, \n75010 Paris, France.\n(2)Program in Genomics of Differentiation, National Institute of Child Health \nand Human Development, National Institutes of Health, Bethesda, MD 20892.\n(3)Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier \nLariboisière-Saint-Louis, Service de Neurologie, Centre de Référence des \nMaladies Vasculaires Rares du Cerveau et de l'Oeil, F-75010 Paris, France.\n(4)Hospices Civils de Lyon, Groupe Hospitalier Est, Hôpital Femme-Mère-Enfant, \nService de Neurologie Pédiatrique, 69677 Bron, France.\n(5)Division of Pediatric Endocrinology, Lyon University Pediatric Hospital, \nINSERM U.870, Centre d'Investigation Clinique 201, Université Claude Bernard \nLyon 1, Hospices Civils de Lyon, Lyon, France.\n(6)Department of Neurosurgery, Stanford Stroke Center and Stanford Institute for \nNeuro-Innovation and Translational Neurosciences, Stanford University School of \nMedicine, Stanford, California, USA.\n(7)First Department of Neurology, Eginition Hospital, National and Kapodestrian \nUniversity of Athens, School of Medicine, 11528 Athens, Greece.\n(8)Assistance Publique des Hôpitaux de Paris, Plateforme de Génomique \nConstitutionnelle du Groupe Hospitalo Universitaire Nord, Hôpital Bichat, \nF-75010 Paris, France.\n(9)INSERM UMR-S-740; Université Paris, 7 Denis Diderot, 10 Avenue de Verdun, \n75010 Paris, France; Assistance Publique des Hôpitaux de Paris, Groupe \nHospitalier Lariboisière-Saint-Louis, Laboratoire de Génétique, Centre de \nRéférence des Maladies Vasculaires Rares du Cerveau et de l'Oeil, F-75010 Paris, \nFrance. Electronic address: tournier-lasserve@univ-paris-diderot.fr.", "Moyamoya disease (MMD) shows progressive cerebral angiopathy characterized by \nbilateral internal carotid artery stenosis and abnormal collateral vessels. \nAlthough ∼ 15% of MMD cases are familial, the MMD gene(s) remain unknown. A \ngenome-wide association study of 785,720 single-nucleotide polymorphisms (SNPs) \nwas performed, comparing 72 Japanese MMD patients with 45 Japanese controls and \nresulting in a strong association of chromosome 17q25-ter with MMD risk. This \nresult was further confirmed by a locus-specific association study using 335 \nSNPs in the 17q25-ter region. A single haplotype consisting of seven SNPs at the \nRNF213 locus was tightly associated with MMD (P = 5.3 × 10(-10)). RNF213 encodes \na really interesting new gene finger protein with an AAA ATPase domain and is \nabundantly expressed in spleen and leukocytes. An RNA in situ hybridization \nanalysis of mouse tissues indicated that mature lymphocytes express higher \nlevels of Rnf213 mRNA than their immature counterparts. Mutational analysis of \nRNF213 revealed a founder mutation, p.R4859K, in 95% of MMD families, 73% of \nnon-familial MMD cases and 1.4% of controls; this mutation greatly increases the \nrisk of MMD (P = 1.2 × 10(-43), odds ratio = 190.8, 95% confidence interval = \n71.7-507.9). Three additional missense mutations were identified in the \np.R4859K-negative patients. These results indicate that RNF213 is the first \nidentified susceptibility gene for MMD.", "A 7-year-old white girl presented with left hemiparesis and ischemic stroke \nsecondary to moyamoya syndrome, a progressive cerebrovascular occlusive disorder \nof uncertain but likely multifactorial etiology. Past medical history revealed \nhearing loss and developmental delay/intellectual disability. Routine karyotype \ndemonstrated extra chromosomal material on 6p. Single nucleotide polymorphism \nmicroarray revealed a previously unreported complex de novo genetic \nrearrangement involving subtelomeric segments on chromosomes 6p and 12q. The \nduplicated/deleted regions included several known OMIM-annotated genes. This \nnovel phenotype and genotype provides information about a possible association \nof genomic copy number variation and moyamoya syndrome. Dosage-sensitive genes \nin the deleted and duplicated segments may be involved in aberrant vascular \nproliferation. Our case also emphasizes the importance of comprehensive \nevaluation of both developmental delay and congenital anomalies such as \nmoyamoya.", "BACKGROUND AND PURPOSE: Moyamoya disease is a cerebrovascular disease of unknown \ncause that mainly affects Japanese children. The incidence of familial \noccurrence accounts for 9% of cases. The characteristic lesions of moyamoya \ndisease are occasionally seen in neurofibromatosis type 1, of which the \ncausative gene (NF1) has been assigned to chromosome 17q11.2.\nMETHODS: To determine whether a gene related to moyamoya disease is located on \nchromosome 17, we conducted microsatellite linkage analyses on 24 families \ncontaining 56 patients with moyamoya disease. Leukocyte DNA extracted from the \nfamily members was subjected to polymerase chain reaction for a total of 22 \nmicrosatellite markers on chromosome 17. The amplified polymerase chain reaction \nfragments were analyzed with GeneScan on an automated sequencer.\nRESULTS: Two-point linkage analysis gave a maximum log(10) odds (LOD) score of \n3.11 at the recombination fraction of 0.00 for the marker at locus D17S939. The \naffected pedigree member method also showed a significantly low P value (<1. \n0x10(-5)) for the 5 adjacent markers at 17q25. Multipoint linkage analysis also \nindicated that the disease gene is contained within the 9-cM region of D17S785 \nto D17S836, with a maximum LOD score of 4. 58.\nCONCLUSIONS: A gene for familial moyamoya disease is located on chromosome \n17q25.", "OBJECTS: The pathogenesis of moyamoya disease is still unknown. The present \nstudy aimed to find out the responsible genes that are located in the 17q25 \nlocus.\nMETHODS: Considering the function, we selected nine genes as candidates from a \ntotal of 65 genes identified in the 9-cM region of D17S785-D17S836 in chromosome \n17q25, and performed sequence analysis on the DNA samples obtained from a \npedigree of familial moyamoya disease, which showed a complete linkage to the \nregion by a haplotype analysis. Also, we attempted to identify candidate genes \nthat have not been known but might be functionally relevant to the disease among \na total of 2,100 expressed sequence tag (EST) sequences using bioinformatics \ntechniques.\nRESULTS AND CONCLUSION: The sequence analysis could detect no mutation in the \nnine genes. Nor could we identify a novel candidate gene by the EST analysis. \nFurther studies using alternative approaches are warranted to clarify the \npathogenesis of moyamoya disease.", "The neurofibromatoses are genetic disorders of the nervous system that primarily \naffect the development and growth of neural (nerve) cell tissues. The \nneurofibromatoses are classified as neurofibromatosis type 1 (NF1) and \nneurofibromatosis type 2 (NF2). NF1 is the more common type of the \nneurofibromatoses. The gene responsible for NF1 is located on the chromosome \nregion 17q11.2 and for familial moyamoya disease on chromosome 17q25. This \narticle reports on a 20-year-old female with neurofibromatosis-1 who developed \nmoyamoya syndrome. More extensive reports and further investigations of such \nfamilies having this combination will certainly provide a better understanding \nof this link in the near future.", "Moyamoya, meaning a \"hazy puff of smoke\" in Japanese, is a chronic, occlusive \ncerebrovascular disease involving bilateral stenosis or occlusion of the \nterminal portion of the internal carotid arteries (ICAs) and/or the proximal \nportions of the anterior cerebral arteries and middle cerebral arteries (MCAs). \nThe Ministry of Health and Welfare of Japan has defined 4 types of moyamoya \ndisease (MMD): ischemic, hemorrhagic, epileptic, and \"other.\" The ischemic type \nhas been shown to predominate in childhood, while the hemorrhagic type is more \noften observed in the adult population. The highest prevalence of MMD is found \nin Japan, with a higher female to male ratio. Studies have shown a possible \ngenetic association of MMD linked to chromosome 17 in Japanese cases as well as \nin cases found in other demographics. During autopsy, intracerebral hematoma is \nfound and most commonly serves as the major cause of death in patients with MMD. \nMoyamoya vessels at the base of the brain are composed of medium-sized or small \nmuscular arteries emanating from the circle of Willis, mainly the intracranial \nportions of ICAs, anterior choroidal arteries, and posterior cerebral arteries, \nforming complex channels that connect with distal positions of the MCAs. Off of \nthese channels are small tortuous and dilated vessels that penetrate into the \nbase of the brain at the site of the thalamoperforate and lenticulostriate \narteries. On angiography, there is the characteristic stenosis or occlusion \nbilaterally at the terminal portion of the ICAs as well as the moyamoya vessels \nat the base of the brain. Six angiographic stages have been described, from \nStage 1, which reveals a narrowing of the carotid forks, to Stage 6, in which \nthe moyamoya vessels disappear and collateral circulation is produced solely \nfrom the external carotid arteries. Cases with milder symptoms are usually \ntreated conservatively; however, more severe symptomatic cases are treated using \nrevascularization procedures. Surgical treatments are divided into 3 types: \ndirect, indirect, and combined/other methods. Direct bypass includes superficial \ntemporal artery-MCA bypass or use of other graft types. Indirect procedures \nbring in circulation to the intracranial regions by introducing newly developed \nvasculature from newly approximated tissues. These procedures may not be enough \nto prevent further ischemia; therefore, a combination of direct and indirect \nprocedures is more suitable. This article will give a review of the \nepidemiology, natural history, pathology, pathophysiology, and diagnostic \ncriteria, including imaging, and briefly describe the surgical treatment of MMD.", "Chromosomal rearrangements causing microdeletions and microduplications are a \nmajor cause of congenital malformation and mental retardation. Because they are \nnot visible by routine chromosome analysis, high resolution whole-genome \ntechnologies are required for the detection and diagnosis of small chromosomal \nabnormalities. Recently, array-comparative genomic hybridization (aCGH) and \nmultiplex ligation-dependent probe amplification (MLPA) have been useful tools \nfor the identification and mapping of deletions and duplications at higher \nresolution and throughput. Smith-Magenis syndrome (SMS) is a multiple congenital \nanomalies/mental retardation syndrome caused by deletion or mutation of the \nretinoic acid induced 1 (RAI1) gene and is often associated with a chromosome \n17p11.2 deletion. We report here on the clinical and molecular analysis of a \n10-year-old girl with SMS and moyamoya disease (occlusion of the circle of \nWillis). We have employed a combination of aCGH, FISH, and MLPA to characterize \nan approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in \nthis patient, with the proximal breakpoint within the RAI1 gene. Further, \ninvestigation of the genomic architecture at the breakpoint intervals of this \nlarge deletion documented the presence of palindromic repeat elements that could \npotentially form recombination substrates leading to unequal crossover.", "INTRODUCTION: In this report we discuss an unusual cause of subarachnoid \nhaemorrhage in association with neurofibromatosis.\nCASE PRESENTATION: A previously fit 55-year-old man developed sudden onset \nheadache with loss of consciousness. He was comatose on admission with no focal \nneurological signs. Numerous neurofibromas and café-au-lait patches were noted, \nindicating neurofibromatosis type 1 which had not been previously diagnosed. \nComputer Tomography brain revealed a grade IV subarachnoid haemorrhage in \nassociation with numerous vascular lesions on cerebral angiography.\nCONCLUSION: A rare cause of subarachnoid haemorrhages was identified and is \ndiscussed in detail.", "PATIENT: Male, 42 FINAL DIAGNOSIS: Moyamoya disease (MMD) Symptoms: Aphasia • \nconcentration difficulty • dysarthria • personality change\nMEDICATION: - Clinical Procedure: - Specialty: Radiology.\nOBJECTIVE: Rare disease.\nBACKGROUND: Moyamoya disease (MMD) was first described in 1957 as \"hypoplasia of \nthe bilateral internal carotid arteries.\" The characteristic appearance of the \nassociated network of abnormally dilated collateral vessels on angiography was \nlater likened to \"something hazy, like a puff of cigarette smoke,\" which, in \nJapanese, is Moyamoya. This paper describes the fulminant course of the disease \nin a Hispanic male involving the corpus callosum.\nCASE REPORT: A 42-year-old Hispanic male with progressive aphasia, slow \nmentation, and sudden onset of sensorimotor symptoms with gait disturbance was \nfound to have multiple intracranial supratentorial infarcts of variable stages \nof evolution involving, but not limited to, the anterior corpus callosum, \nfollowed by rapid development of further infarcts. Angiography demonstrated \nright ACA occlusion, left supraclinoid ICA occlusion with a Moyamoya pattern of \ncollateralization, and diffuse arteriopathy. A fulminant course ensued and the \npatient did not survive the acute phase of ischemic disease.\nCONCLUSIONS: Moyamoya disease may rarely present in North American Hispanic \nmales, with advanced atypical clinical and imaging features involving the \nanterior corpus callosum and having a fulminant course.", "Moyamoya disease is a well-known cerebrovascular disorder of unknown \npathogenesis affecting terminal portion of internal carotid arteries and causing \nischemic attacks. Its familial occurrence suggests genetic background. We \nhypothesized that paternally imprinted gene might be associated with this \ndisorder. To identify the expressed sequence tags (ESTs) with monoallelic \nexpressions on chromosome 3, we used mouse A9 hybrid cells having human \nchromosome 3. Two ESTs showed only maternal expression in mouse A9 hybrid cells, \nand four showed non-expression in the lymphocytes derived from moyamoya \npatients. Although these ESTs are clustered on the same 150 kb region, we \nfinally failed to identify cDNA in this region.", "Moyamoya disease is a cerebrovascular disorder of unknown etiology. Its high \nincidence in East Asia and accumulation in family members suggest a genetic \nbackground. A high incidence of maternal inheritance implicates genomic \nimprinting in this disorder. Based on this hypothesis, we studied the \nassociation between moyamoya disease and IGF2R gene on chromosome 6, but found \nno evidence for such association between them. On the other hand, heterogeneous \nexpressions of IGF2R were confirmed in the lymphocytes. Some individuals showed \nmonoallelic expression and others showed biallelic expression.", "We present familial Moyamoya disease in two European children and emphasize the \nimportance of familial factors in the pathogenesis of this disease and its \nappearance not only in Asians but in the Western population as well. The first \npatient, a Greek female infant, also has coagulation disorders. Her mother, also \nsuffering from Moyamoya and other family members, have similar coagulation \ndisorders (Factor V Leiden, Methylene-tetrahydrofolic reductase and Factor II \n20210A mutations). The second patient, a Scottish boy, is unique in that \nfamilial Moyamoya affects five members of three consecutive generations of his \nmaternal family. Genetic analysis in the Greek family demonstrated no \nabnormality on chromosome 3p26, as in other cases. However, the mitochondrial \nDNA and Y chromosomal genotype showed that affected members had the same \nsequence of the Mitochondrial 3 portion of D-loop with Japanese patients. These \nfindings suggest that the pathogenesis of Moyamoya may vary across races and \nethnic groups.", "We reported an autopsy case of Down's syndrome with moyamoya syndrome. A \n30-year-old male with Down's syndrome suffered from a cerebral infarction and \ndied of brain herniation. Cerebral angiography showed vascular abnormalities \nthat were the same as moyamoya disease. Pathological findings revealed multiple \nstenosis of main trunk of the cerebral arteries. Pathologically, the stenosed \nvessels showed eccentric intimal thickness with cholesterin deposit, unlike \nmoyamoya disease. There are only two previous reports of autopsied cases of \nDown's syndrome with moyamoya syndrome. We postulate that a protein encoded on \nchromosome 21 may be related to the pathogenesis of Down's syndrome with \nmoyamoya syndrome.", "Genetic factors have been suggested to contribute to the etiology of moyamoya \ndisease. The authors have previously reported an association between moyamoya \ndisease and several alleles for human leukocyte antigens (HLA). To further \nspecify the genetic component of moyamoya disease, a linkage study of moyamoya \ndisease using markers on chromosome 6, where the HLA gene is located, was \nperformed. The 15 microsatellite markers of chromosome 6 were studied in 20 \naffected sibling pairs. From an identical-by-descent analysis of these markers, \nan allele with possible linkage to moyamoya disease was identified. Sharing of \nthe allele among affected members in 19 families was investigated, considering \nthe haplotype. The marker, D6S441, might be linked to moyamoya disease. \nConsidering the haplotype, the allele was shared among the affected members in \n16 (82%) of the 19 families, but not in two others. In one family, sharing of \nthe allele could not be determined because of low heterozygosity. Further \nstudies are necessary to clarify multiple genetic factors that are definitely \nlinked with moyamoya disease.", "OBJECTIVES: To identify whether any mutations of candidate genes including SHH, \nZIC2, SIX3, and TGIF exist in a Taiwanese family segregated with \nholoprosencephaly (HPE) and moyamoya disease.\nMETHODS: Genotypes of the candidate genes SHH, ZIC2, SIX3, and TGIF were \ndetermined in the family members who were available for analysis by sequencing. \nIn addition, genomic regions of another 50 unrelated Taiwanese (100 chromosomes) \nwere studied to verify whether the nucleotide changes we found were mutations or \npolymorphisms.\nRESULTS: A novel missense mutation 377T > C and two polymorphisms (420A > G and \n487C > T) in the TGIF gene were identified. No mutations in SHH, ZIC2 and SIX3 \nwere found. The mother of the three HPE fetuses was found to be afflicted with \nmoyamoya disease. A brief review of the mutations as well as polymorphisms \nreported in the TGIF gene up to 2005 is given.\nCONCLUSION: Molecular diagnosis can help genetic counseling in HPE, which is a \nheterogeneous disorder with its phenotypic and genotypic spectrum highly widened \nand variable. The possible association between TGIF mutation and moyamoya \ndisease noted in our study also appeared to be novel.", "A female, 2 years and 7 months of age, was admitted to the hospital with stupor \nand nystagmus following projectile vomiting. She had been prenatally diagnosed \nwith trisomy 12p with a familial pericentric inversion of chromosome 12 \noriginating from her mother. She manifested developmental delay and some \ndysmorphic features of the face and limbs compatible with the clinical features \nof trisomy 12p. Four-vessel cerebral angiography revealed severe stenosis and \nocclusion of the supraclinoid portion of the right and left internal carotid \narteries with numerous collateral vessels in the vicinity of the occlusion. \nThese features are consistent with moyamoya syndrome. This report presents the \nfirst case of moyamoya syndrome with trisomy 12p with a familial pericentric \ninversion of chromosome 12.", "We report a case of Prader-Willi syndrome (PWS) complicated with juvenile \nstroke. The patient is a 19-year-old man with right hemiplegia, who has had a \nhistory of non-insulin-dependent diabetes mellitus (NIDDM) for ten years. The \ndiagnosis of PWS was confirmed genetically by the method of fluorescence in situ \nhybridization which showed the deletion of chromosome 15. His brain MRI revealed \nabnormal signal intensities in the left basal ganglia and around the right \ntrigone of the lateral ventricle. Angiographic examination showed occlusions of \nbilateral proximal middle cerebral arteries with basal moyamoya vessels. The \nleft vertebral artery was also occluded at its origin. Only a few cases of PWS \ncomplicated with stroke have been reported before and, to date, there has been \nno case with arterial occlusion similar to our case. Though the cause of these \narterial occlusions is unknown, it may be related to arteriosclerosis following \nNIDDM.", "OBJECT: Moyamoya disease (MMD) is a rare cerebrovascular disorder involving \nstenosis of the major vessels of the circle of Willis and proximal portions of \nits principal branches. Despite concerted investigation, the pathophysiology of \nthe disorder has not been fully elucidated. Currently, the major proteins \nbelieved to play an active role in the pathogenesis include vascular endothelial \ngrowth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth \nfactor (HGF), transforming growth factor-β₁ (TGFβ₁), and granulocyte \ncolony-stimulating factor (G-CSF). In terms of the genetics, recent literature \nsuggests a low penetrance autosomal dominant or polygenic mode of transmission \ninvolving chromosomes 3, 6, 8, 12, and 17 for familial MMD. This review \nsummarizes the current knowledge on the histopathology, pathophysiology and \ngenetics of MMD.\nMETHODS: A PubMed/Medline systematic study of the literature was performed, from \nwhich 45 articles regarding MMD pathophysiology were identified and analyzed.\nCONCLUSIONS: Moyamoya disease is characterized by the intimal thickening and \nmedia attenuation of the proximal vessels of the circle of Willis as well as the \ndevelopment of an aberrant distal vascular network. The primary proteins that \nare currently implicated in the pathophysiology of MMD include VEGF, bFGF, HGF, \nTGFβ₁, and G-CSF. Furthermore, the current literature on familial MMD has \npointed to a low penetrance autosomal dominant or polygenic mode of \ntransmittance at loci on chromosomes 3, 6, 8, 12, and 17." ]	['http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009072', 'http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002875', 'http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005694', 'http://www.disease-ontology.org/api/metadata/DOID:13099', 'http://www.disease-ontology.org/api/metadata/DOID:0080014']
5313058de3eabad02100000e	[ 23096483, 21511940, 24156003, 8457417, 23969004, 16943469, 19547821, 19037900, 20624239, 19830065, 11154546, 18596536, 2533403, 19646556 ]	train	Abnormality in which vertebral region is important in the Bertolotti's syndrome?	factoid	Lumbosacral vertebral region is implicated in the Bertolotti's syndrome. Lumbosacral transitional vertebra is an anatomical variation of the fifth lumbar vertebra in which an enlarged transverse process can form a joint or fusion with the sacrum or ilium. Patients often complain of intractable sciatica that arises from impingement of the nerve root extraforaminally by compression caused by the enlarged transverse process.	lumbosacral	[ "BACKGROUND AND INTRODUCTION: In 1991, a deceased human male was found frozen in \na glacier pool in the Italian Alps in north west Italy, and is now carefully \npreserved in the South Tyrol Museum of Archaeology, in Bolzano, Italy. The \nbodily tissues of the 5,300 year old male (colloquially referred to as the \nIceman or Ötzi) were well preserved despite damage related to freezing, and \nglacial movement. Associated articles of well-preserved clothing, tools, weapons \nand other devices were also present and have been studied in detail. Clinical \nexamination and imaging investigations have also shown that the Icemen had \nexperienced possible illnesses in his lifetime and had identifiable areas of \narthritis and musculoskeletal injury. This report includes some key observations \non the musculoskeletal state of Ötzi and reference to the involvement of tattoo \nmarkings. Some aspects about the aetiology of his abnormalities and inflammatory \narthritis are considered along with possible treatments that he might have \nemployed.\nMETHODS AND RESULTS: We (WFK and MK) undertook a clinical musculoskeletal \nexamination of the Iceman, details of which with available photographs and \nradiographic imaging pertaining to the musculoskeletal findings of the Iceman \nare reported here. The skin of the Iceman has numerous linear carbon tattoos, \nwhich are not of a decorative type. These have been presumed to possibly be \n\"medicinal\" tattoos administered for therapeutic reasons and may have been used \nin acupuncture-like treatment of pain. Spinal imaging identified areas of spinal \ndamage and our observations have provided clues as to possible sites of spinal \ninitiated pain and hence sites for administration of the \"medicinal\" tattoos. We \nobserved body areas of the Iceman, in which imaging demonstrated arthritis and \nother forms of long-term musculoskeletal damage, but which do not have adjacent \nor corresponding \"medicinal\" tattoos. We contend that the back and leg \n\"medicinal\" tattoos correspond directly to sites of chronic right knee and right \nankle pain, and left thoracolumbar pain. They also correspond to lower lumbar \nand sciatic referred radicular pain which may have a contributory cause related \nto the presence of a transitional lumbar 5 vertebra. Using recent published data \n(Keller et al. in Nature Commun 3:698, 2012. doi: 10.1038/ncomms1701 ) of the \ngenome structure of the Iceman, we suggest some potential causes of the \nosteoarthritis or inflammatory joint injury may relate to presence of coronary \nheart disease (CHD) and Lyme disease (Borrelia burgdorferi) infection. We \nspeculate on possible medical applications of natural products for \nself-medication.\nCONCLUSIONS: These observations highlight several diagnostic features of \nmusculoskeletal conditions in the Iceman with the possibility that tattoos may \nhave been used for diagnosis or location of his painful states. The origins of \nhis musculoskeletal conditions are unclear but there are indications that Lyme \ndisease and CHD may have been factors. The associations or use of natural \nproducts may give insights into their applications at the time of the life of \nthe Iceman.", "Patients with Bertolotti's syndrome have characteristic lumbosacral anomalies \nand often have severe sciatica. We describe a patient with this syndrome in whom \nstandard decompression of the affected nerve root failed, but endoscopic \nlumbosacral extraforaminal decompression relieved the symptoms. We suggest that \nthe intractable sciatica in this syndrome could arise from impingement of the \nnerve root extraforaminally by compression caused by the enlarged transverse \nprocess.", "BACKGROUND: Bertolotti's syndrome (BS), a form of lumbago in lumbosacral \ntransitional vertebrae, is an important cause of low back pain in young \npatients. The purpose of this study was to assess the etiology of low back pain \nand the efficacy of treatment offered to patients with BS.\nMETHODS: All patients of BS Castellvi type1a during a period of 6 months were \nenrolled in the study. The patients underwent interventional pain procedures for \ndiagnosis and pain relief. Response to the therapy was assessed based on VAS and \nODI scores. A 50% decrease in VAS score or a VAS score less than 3 would be \nconsidered adequate pain relief.\nRESULTS: All 20 patients diagnosed with BS during the 6-month observation period \nhad scoliosis. Common causes of back pain were the ipsilateral L5-S1 facet \njoint, neoarticulation, the SI joint, and disc degeneration. Responses to \nvarious interventions for pain relief were different and inconsistent from \npatient to patient. In particular, responses to interventions for neoarticular \npain were generally poor.\nCONCLUSIONS: Pain in patients with BS does not usually respond to interventional \npain treatment. A very dynamic treatment approach must be pursued while managing \nBS patients, and the treatment plan must be individualized at various stages in \norder to obtain satisfactory pain relief.", "We surgically treated 16 patients with Bertolotti's syndrome (chronic, \npersistent low back pain and radiographically diagnosed transitional lumbar \nvertebra). Eight had posterolateral fusion and another eight resection of the \ntransitional articulation. Thirteen patients had in addition to the chronic low \nback pain, suffered from repeated episodes or chronic sciatica. In six cases \nwith resection treatment, local injections were administered at the transitional \narticulation before deciding for resection of the transitional joint; each \npatient reported transient relief of pain, while this preoperative test did not \ncorrelate with successful outcome of treatment. Six patients had to be treated \nwith second operations. Ten of the 16 operatively treated patients showed \nimprovement of the low back pain, and this result was similar in the group \ntreated with fusion and in that treated with resection. Seven had no low back \npain at follow-up, and the improvement according to the Oswestry pain scale was \nsimilar in the two groups, and statistically significant. Eleven patients still \nhad persisting episodes of sciatica (versus 13 preoperatively). The average \ndisability according to the Oswestry total disability scale was 30%, \ncorresponding with moderate outcome, and both operatively treated groups did \nequally well. At follow-up the first disc above the fused segments was found to \nbe degenerated in seven out of eight cases, and in the group treated with \nresection the first disc above the transitional vertebra was degenerated in five \ncases.(ABSTRACT TRUNCATED AT 250 WORDS)", "Painful L5/S1 pseudoarthrosis has been previously managed with posterior \nexcision and/or lumbar fusion. To our knowledge, the anterior approach for L5/S1 \npseudoarthrectomy in the treatment of Bertolotti's syndrome has not been \ndescribed. We present two patients with severe symptomatic L5/S1 pseudoarthroses \nthat were successfully excised via an anterior retroperitoneal approach with 2 \nyear clinical and radiological follow-up. The literature regarding surgical \ntreatments for Bertolotti's syndrome is reviewed. The technique for an anterior \nretroperitoneal approach is described. This approach has been safe and effective \nin providing long term symptomatic relief to our two patients. Further studies \ncomparing the outcomes of anterior versus posterior pseudoarthrectomy will guide \nthe management of this condition.", "Bertolotti's syndrome is characterised by anomalous enlargement of the \ntransverse process(es) of the most caudal lumbar vertebra which may articulate \nor fuse with the sacrum or ilium and cause isolated L4/5 disc disease. We \nanalysed the elective MR scans of the lumbosacral spine of 769 consecutive \npatients with low back pain taken between July 2003 and November 2004. Of these \n568 showed disc degeneration. Bertolotti's syndrome was present in 35 patients \nwith a mean age of 32.7 years (15 to 60). This was a younger age than that of \npatients with multiple disc degeneration, single-level disease and isolated disc \ndegeneration at the L4/5 level (p </= 0.05). The overall incidence of \nBertolotti's syndrome in our study was 4.6% (35 of 769). It was present in 11.4% \n(20 patients) of the under-30 age group. Our findings suggest that Bertolotti's \nsyndrome must form part of a list of differential diagnoses in the investigation \nof low back pain in young people.", "OBJECTIVE: Bertolotti's syndrome is a spine disorder characterized by the \noccurrence of a congenital lumbar transverse mega-apophysis in a transitional \nvertebral body that usually articulates with the sacrum or the iliac bone. It \nhas been considered a possible cause of low back pain.\nMETHOD: We analyzed the cases of Bertolotti's syndrome that failed clinical \ntreatment and reviewed the literature concerning this subject.\nRESULTS: Five patients in our series had severe low back pain due to the \nneo-articulation and two of them were successfully submitted to surgical \nresection of the transverse mega-apophysis. Taking into account the clinical and \nsurgical experience acquired with these cases, we propose a \ndiagnostic-therapeutic algorithm.\nCONCLUSION: There is still no consensus about the most appropriate therapy for \nBertolotti's syndrome. In patients in whom the mega-apophysis itself may be the \nsource of back pain, surgical resection may be a safe and effective procedure.", "STUDY DESIGN: A case report and literature review is presented.\nOBJECTIVE: To review relevant data for the management of Bertolotti's syndrome \nand to determine whether the transverse process-ilium articulation may be a pain \ngenerator.\nBACKGROUND: Bertolotti's syndrome is associated with axial low back pain \nsecondary to arthritic changes; the pain generator in the disorder is unclear.\nMETHODS: We present a case report of symptomatic Bertolotti's syndrome managed \nwith intra-articular steroid injections.\nRESULTS: A patient with Bertolotti's syndrome had significant relief of axial \npain after steroid injection of the ilium-transverse process articulation.\nCONCLUSIONS: Steroid therapy may be a non-surgical alternative for the treatment \nof symptomatic Bertolotti's syndrome.", "OBJECTIVE: Describe the clinical presentation, diagnostic evaluation, and \nsuccessful treatment of a case of symptomatic unilateral lumbosacral junction \npseudarticulation using a novel radiofrequency nerve ablation technique.\nCASE: A 56-year-old female patient who had suffered with low back and right \nupper buttock pain for 16 years experienced incomplete relief with L4/5 facet \njoint radiofrequency ablation. She was found to have an elongated right L5 \ntransverse process that articulated with the sacral ala (Bertolotti's syndrome). \nFluoroscopically guided local anesthetic/corticosteroid injection into the \npseudarthrosis eliminated her residual right buttock pain for the duration of \nthe local anesthetic only. Complete pain relief was achieved by injecting local \nanesthetic circumferentially around the posterior pseudarthrosis articular \nmargin. Accordingly, bipolar radiofrequency strip thermal lesions were created \nat the same locations. Complete pain relief and full restoration of function was \nachieved for 16 months postprocedure.\nCONCLUSION: This case report describes a novel radiofrequency technique for \ntreating symptomatic lumbosacral junction pseudarticulation that warrants \nfurther evaluation.", "INTRODUCTION: Lumbosacral transitional vertebra is an anatomical variation of \nthe fifth lumbar vertebra in which an enlarged transverse process can form a \njoint or fusion with the sacrum or ilium. The association of that variant with \nlow back pain and the change in the biomechanical properties of the lumbar spine \nis called Bertolotti's syndrome.\nCASE PRESENTATION: We report a case of a 40-year-old male patient with chronic \nlow back pain extending to the left buttock, just above the ipsilateral \nsacroiliac joint. Radiographic investigation revealed an anomalous enlargement \nof the left transverse process of the fifth lumbar vertebra forming a \npseudarthrosis with the infrajacent ala of the sacrum.\nCONCLUSION: In young patients with back pain the possibility of Bertolotti's \nsyndrome should always be taken in account.", "STUDY DESIGN: Case report of surgically treated mechanical low back pain from \nthe facet joint contralateral to a unilateral anomalous lumbosacral articulation \n(Bertolotti's syndrome).\nOBJECTIVES: To describe the clinical presentation, diagnostic evaluation, and \nmanagement of facet-related low back pain in a 17-year-old cheerleader and its \nsuccessful surgical treatment with resection of a contralateral anomalous \narticulation.\nSUMMARY OF BACKGROUND DATA: Lumbosacral transitional vertebrae are common in the \ngeneral population. Bertolotti's syndrome is mechanical low back pain associated \nwith these transitional segments. Little is known about the pathophysiology and \nmechanics of these vertebral segments and their propensity to be pain \ngenerators. Treatment of this syndrome is controversial, and surgical \nintervention has been infrequently reported.\nMETHOD: A retrospective chart analysis and radiographic review were performed.\nRESULTS: Repeated fluoroscopically guided injections implicated a symptomatic \nL6-S1 facet joint contralateral to an anomalous lumbosacral articulation. \nEventually, a successful surgical outcome was achieved with resection of the \nanomalous articulation.\nCONCLUSION: Clinicians should consider the possibility that mechanical low back \npain may occur from a facet contralateral to a unilateral anomalous lumbosacral \narticulation, even in a young patient. Although reports of surgical treatment of \nBertolotti's syndrome are infrequent, resection of the anomalous articulation \nprovided excellent results in this patient, presumably because of reduced \nstresses on the symptomatic facet.", "OBJECTIVE: This article aims to provide more insight into the presentation, \ndiagnosis, and treatment of Bertolotti's syndrome, which is a rare spinal \ndisorder that is very difficult to recognize and diagnose correctly. The \nsyndrome was first described by Bertolotti in 1917 and affects approximately 4 \nto 8% of the population. It is characterized by an enlarged transverse process \nat the most caudal lumbar vertebra with a pseudoarticulation of the transverse \nprocess and the sacral ala. It tends to present with low back pain and may be \nconfused with facet and sacroiliac joint disease.\nMETHODS: In this case report, we describe a 40-year-old man who presented with \nlow back pain and was eventually diagnosed with Bertolotti's syndrome. The \ncorrect diagnosis was made based on imaging studies which included computed \ntomographic scans, plain x-rays, and magnetic resonance imaging scans. The \npatient experienced temporary relief when the abnormal pseudoarticulation was \ninjected with a cocktail consisting of lidocaine and steroids. In order to \nminimize the trauma associated with surgical treatment, a minimally invasive \napproach was chosen to resect the anomalous transverse process with the \naccompanying pseudoarticulation.\nRESULTS: The patient did well postoperatively and had 97% resolution of his pain \nat 6 months after surgery.\nCONCLUSION: As with conventional surgical approaches, a complete knowledge of \nanatomy is required for minimally invasive spine surgery. This case is an \nexample of the expanding utility of minimally invasive approaches in treating \nspinal disorders.", "Bertolotti's syndrome refers to the association of back pain with lumbosacral \ntransitional vertebrae. Such vertebrae were observed in 140 of 2,000 adults with \nback pain over a 4-year period of study. Each patient had radiographic \nevaluation of the lumbar spine by plain films as well as a sectional imaging \nmodality (magnetic resonance [MR] or computed tomography [CT]). The overall \nincidence of structural pathology (eg, spinal stenosis and disc protrusion) \ndetected by CT or MR was not apparently higher in patients with transitional \nvertebrae, but the distribution of these lesions was significantly different. \nDisc bulge or herniation, when it occurred, was nearly nine times more common at \nthe interspace immediately above the transitional vertebra than at any other \nlevel. Spinal stenosis and nerve root canal stenosis were more common at or near \nthe interspace above the transitional vertebra than at any other level. \nDegenerative change at the articulation between the transverse process of the \ntransitional vertebra and the pelvis was an uncommon occurrence; when seen there \nwas no significant correlation with the reported side of pain. It is postulated \nthat hypermobility and altered stresses become concentrated in the spine at the \nlevel immediately above a lumbar transitional vertebra. Accelerated disc and \nfacet joint degeneration at this level may then result.", "The availability of hybrid devices that combine the latest single-photon \nemission computed tomography (SPECT) imaging technology with multislice computed \ntomography (CT) scanning has allowed us to detect subtle, nonspecific \nabnormalities on bone scans and interpret them as specific focal areas of \npathology. Abnormalities in the spine can be separated into those caused by pars \nfractures, facet joint arthritis, or osteophyte formation on vertebral bodies. \nCompression fractures can be distinguished from severe degenerative disease, \nboth of which can cause intense activity across the spine on either planar or \nSPECT imaging. Localizing activity in patients who have had spinal fusion can \nprovide tremendous insight into the causes of therapeutic failures. Infections \nof the spine now can be diagnosed with gallium SPECT/CT, despite the fact that \ngallium has long been abandoned because of its failure to detect spine infection \non either planar or SPECT imaging. Small focal abnormalities in the feet and \nankles can be localized well enough to make specific orthopedic diagnoses on the \nbasis of their location. Moreover, when radiographic imaging provides equivocal \nor inadequate information, SPECT/CT can provide a road map for further \ndiagnostic studies and has been invaluable in planning surgery. Our ability to \nlocalize activity within a bone or at an articular surface has allowed us to \ndistinguish between fractures and joint disease. Increased activity associated \nwith congenital anomalies, such as tarsal coalition and Bertolotti's syndrome \nhave allowed us to understand the pathophysiology of these conditions, to \nconfirm them as the cause of the patient's symptoms, and to provide information \nthat is useful in determining appropriate clinical management. As our experience \nbroadens, SPECT/CT will undoubtedly become an important tool in the evaluation \nand management of a wider variety of orthopedic patients." ]	['http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013131', 'http://www.disease-ontology.org/api/metadata/DOID:225', 'http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577']
5a981e66fcd1d6a10c00002f	[ 23519746, 26280340, 17137436, 28106792, 23145009, 16762931, 10682170, 18497723, 10863169, 26543426, 17125447, 19108808, 12137304, 15827427, 26871396, 11276389, 15940204, 12148078, 17469041 ]	train	According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.	list	Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity.	['obesity', 'hypertension', 'dyslipdemia']	[ "Obesity and overweight are nowadays very prevalent worldwide. They are known to \nbe linked with an increased risk of developing cardiovascular comorbidities and \nmortality. Abdominal obesity is frequently associated with a collection of \nmetabolic disorders that include elevated blood pressure, characteristic lipid \nabnormalities (low high-density lipoprotein cholesterol and high triglycerides) \nand increased fasting glucose, with an underlying situation of insulin \nresistance, which has been defined as metabolic syndrome, conferring a high \ncardiovascular risk profile to these subjects. A multidisciplinary approach is \nrequired, including lifestyle changes and pharmacological and surgical \napproaches. Intensive management of all the risk factors of the metabolic \nsyndrome is also needed to reduce body weight and waist circumference, lessen \ninsulin resistance and avoid the development of new-onset diabetes and \ncardiovascular disease associated with this entity. This article will review the \nrecently published literature and guideline updates on this topic, although it \nis not yet included in the highlights.", "Metabolic syndrome is a cluster of conditions that synergistically increase the \nrisk of cardiovascular disease, type 2 diabetes, and premature mortality. The \ncomponents are abdominal obesity, impaired glucose metabolism, dyslipidemia, and \nhypertension. Prediabetes, which is a combination of excess body fat and insulin \nresistance, is considered an underlying etiology of metabolic syndrome. \nPrediabetes manifests as impaired fasting glucose and/or impaired glucose \ntolerance. Impaired fasting glucose is defined as a fasting blood glucose level \nof 100 to 125 mg/dL; impaired glucose tolerance requires a blood glucose level \nof 140 to 199 mg/dL 2 hours after a 75-g oral intake of glucose. In patients \nwith prediabetes, the rate of progression to diabetes within 3 years can be \ndecreased by approximately 58% with lifestyle modifications. These include \nweight loss through exercise (30 minutes or more of moderate physical activity \non most, preferably all, days of the week) and dietary modifications. \nRecommended diets are high in fruits, vegetables, whole grains, and fish. \nConsumption of sweetened beverages, including diet soda, should be avoided. For \npatients who do not achieve goals with lifestyle modifications, metformin can be \nconsidered. Weight loss drugs and bariatric surgery are appropriate for select \npatients. Hypertension and dyslipidemia should be managed according to current \nguidelines.", "Metabolic syndrome (MS) refers to the clustering of cardiometabolic risk factors \n- including abdominal obesity, hyperglycaemia, dyslipidaemia and elevated blood \npressure - that are thought to be linked to insulin resistance. MS is associated \nwith increased risk of cardiovascular disease and type 2 diabetes. MS is common, \naffecting a quarter to a third of adults, and its prevalence is rising, in \nparallel with increasing obesity and population ageing. Operational definitions \nof MS have been proposed by the World Health Organization and the National \nCholesterol Education Program. Recently, the International Diabetes Federation \nproposed a global definition that emphasised the importance of central \nadiposity. In cardiovascular risk assessment, MS encapsulates the contribution \nof non-traditional risk factors and provides a clinically useful framework for \nearly identification of people at increased long-term risk. It should be used in \nconjunction with standard algorithms based on conventional risk factors, which \nbetter predict short-term risk. Management of MS should emphasise lifestyle \ninterventions (eg, physical activity, healthy diet and weight reduction) to \nreduce long-term risk of cardiovascular disease and diabetes. Those at increased \nshort-term risk should also have individual risk factors treated according to \nestablished guidelines.", "Metabolic syndrome (MetS) is generally defined as a cluster of metabolically \nrelated cardiovascular risk factors which are often associated with the \ncondition of insulin resistance, elevated blood pressure, and abdominal obesity. \nDuring the past decades, MetS has become a major public health issue worldwide \nin both adults and children. In this study, data from the China Health and \nNutrition Surveys (CHNS) was used to assess the prevalence of MetS based on both \nthe National Cholesterol Education Program Adult Treatment Panel III \n(NCEP-ATPIII) guidelines and the International Diabetes Federation (IDF) \ncriteria, and to evaluate its possible correlates. A total of 831 children aged \n7-18 years were included in this study, and 28 children were classified as \nhaving MetS as defined by the modified NCEP-ATPIII definition, which yielded an \noverall prevalence of 3.37%. Elevated blood pressure was the most frequent MetS \ncomponent. The results of logistic regression models revealed that increased \nbody mass index (BMI), hyperuricemia, and insulin resistance (IR) were all \nassociated with the presence of MetS. To conclude, our study revealed the \nprevalence of MetS in Chinese children at the national level. Further \nlarge-scale studies are still needed to identify better MetS criteria in the \ngeneral paediatric population in China.", "The waist circumference cut point for diagnosing the metabolic syndrome in \nsub-Saharan African subjects is based on that obtained from studies in European \npopulations. The aim of this study was to measure the prevalence of obesity and \nrelated metabolic disorders in an urban population of African females, a group \nat high risk for such diseases, and to determine the appropriate waist cut point \nfor diagnosing the metabolic syndrome. Anthropometry and fasting lipid, glucose \nand insulin levels were measured in a cohort of 1251 African females \nparticipating in the Birth to Twenty cohort study in Soweto, Johannesburg. The \nwaist circumference cut points for diagnosing metabolic syndrome (as defined \nusing the new harmonised guidelines), insulin resistance, dysglycaemia, \nhypertension and dyslipidaemia were obtained using receiver operator \ncharacteristic curve analysis. The prevalence of obesity, type 2 diabetes and \nmetabolic syndrome were 50.1%, 14.3% and 42.1%, respectively. The appropriate \nwaist cut point for diagnosing metabolic syndrome was found to be 91.5 cm and \nwas similar to the cuts points obtained for detecting increased risk of insulin \nresistance (89.0 cm), dysglycaemia (88.4 cm), hypertension (90.1 cm), hypo-high \ndensity lipoproteinaemia (87.6 cm) and hyper-low density lipoproteinaemia (90.5 \ncm). The present data demonstrates that urban, African females have a high \nprevalence of obesity and related disorders and the waist cut point currently \nrecommended for the diagnosis of the metabolic syndrome (80.0 cm) in this \npopulation should be increased to 91.5 cm. This latter finding demonstrates a \nclear ethnic difference in the relationship between abdominal adiposity and \nmetabolic disease risk. The similar waist cut points identified for the \ndetection of the individual components of the metabolic syndrome and related \ncardiovascular risk factors demonstrates that the risk for different metabolic \ndiseases increases at the same level of abdominal adiposity suggesting a common \naetiological pathway.", "\"The metabolic syndrome\" is the name for a clustering of risk factors for \ncardiovascular disease and type 2 diabetes that are of metabolic origin. These \nrisk factors consist of atherogenic dyslipidemia, elevated blood pressure, \nelevated plasma glucose, a prothrombotic state, and a proinflammatory state. \nThere are 2 major, interacting causes of the metabolic syndrome-obesity and \nendogenous metabolic susceptibility. The latter typically is manifested by \ninsulin resistance. The metabolic syndrome is accompanied by a 2-fold increase \nin the risk of cardiovascular disease and a 5-fold increase in the risk of type \n2 diabetes. A clinical diagnosis of the metabolic syndrome is useful because it \naffects therapeutic strategy in patients at higher risk. However, there are 2 \nviews about the best therapeutic strategy for patients with the metabolic \nsyndrome. One view holds that each of the metabolic risk factors should be \nsingled out and treated separately. The other view holds that greater emphasis \nshould be given to implementing therapies that will reduce all of the risk \nfactors simultaneously. The latter approach emphasizes lifestyle therapies \n(weight reduction and increased exercise), which target all of the risk factors. \nThis approach is also the foundation of other therapies for targeting multiple \nrisk factors together by striking at the underlying causes, as in the \ndevelopment of drugs to promote weight reduction and to reduce insulin \nresistance. Treating the underlying causes does not rule out the management of \nindividual risk factors, but it will add strength to the control of multiple \nrisk factors.", "Insulin resistance syndrome (IRS), also termed syndrome X, is a distinctive \nconstellation of risk factors for the development of type 2 diabetes mellitus \nand cardiovascular disease. The syndrome's hallmarks are glucose intolerance, \nhyperinsulinemia, a characteristic dyslipidemia (high triglycerides; low \nhigh-density lipoprotein cholesterol, and small, dense low-density lipoprotein \ncholesterol), obesity, upper-body fat distribution, hypertension, and increased \nprothrombotic and antifibrinolytic factors. Insulin resistance, caused by a \ncomplex of genetic and environmental influences, is now recognized not just as a \nmechanism contributing to hyperglycemia in type 2 diabetes, but also as an early \nmetabolic abnormality that precedes the development of overt diabetes. The \nclinical definition of insulin resistance is the impaired ability of insulin \n(either endogenous or exogenous) to lower blood glucose. In some \ninsulin-resistant individuals, insulin secretion will begin to deteriorate under \nchronic stress (glucose toxicity) and overt diabetes will result. If not, \nindividuals will remain hyperinsulinemic, with perhaps some degree of glucose \nintolerance, together with other hallmarks of the IRS. The statistical \ncorrelation between hypertension and impaired glucose tolerance is clear, \nalthough the mechanism is not yet fully understood. Epidemiologic evidence of \ninsulin resistance as an independent risk factor for atherosclerosis and \ncoronary heart disease (CHD) completed the evolving concept of IRS as the common \nsoil for the development of both diabetes and CHD. No single laboratory test \nexists for diagnosis of IRS. Rather, IRS remains a clinically evident syndrome \nthat can be suspected on the basis of physical and laboratory findings. This \nidentifies individual patients whom the clinician should screen for associated \ncomorbid conditions, aggressively control cardiovascular risk factors, and \ntailor drug therapy for optimal benefit. This article provides practical \nguidelines to achieve these goals and specific strategies to ameliorate \ncardiovascular and metabolic risk in the IRS.", "The metabolic syndrome is a constellation of risk factors including glucose \ndysregulation, central obesity, dyslipidemia, and hypertension. There are \nmultiple definitions that have been described by various health organizations. \nHowever, we do know that insulin resistance plays a major role as the underlying \ncause for the development and potentiation of the metabolic syndrome. At \npresent, it is unclear if the diagnosis of metabolic syndrome is greater than \nthe sum of its parts. However, the presence of more than one of the associated \nrisk factors should indicate that a patient is at increased risk for developing \ndiabetes, cardiovascular disease and death. Thus, the primary care physician \nshould aggressively treat the metabolic risk factors in their patients to \nprevent the onset and progression to more severe disease.", "Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the \ngeneral population. It is more common in men than in women. A large segment of \nthe adult population of industrialized countries develops the metabolic \nsyndrome, produced by genetic, hormonal and lifestyle factors such as obesity, \nphysical inactivity and certain nutrient excesses. This disease is characterized \nby the clustering of insulin resistance and hyperinsulinemia, and is often \nassociated with dyslipidemia (atherogenic plasma lipid profile), essential \nhypertension, abdominal (visceral) obesity, glucose intolerance or \nnoninsulin-dependent diabetes mellitus and an increased risk of cardiovascular \nevents. Abnormalities of blood coagulation (higher plasminogen activator \ninhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have \nalso been found in metabolic syndrome X. This review summarizes the present \nknowledge of abnormalities in this syndrome. Each risk factor is reviewed, and \npotential criteria for diagnosis and therapeutic targets are discussed. Because \npatients with metabolic syndrome X accumulate cardiac risk factors, they should \nbe given special attention in terms of diagnosis and treatment.", "This article reviews the relationship between metabolic syndrome (MetS) and \nnephrolithiasis, as well as the clinical implications for patients with this \ndual diagnosis. MetS, estimated to affect 25% of adults in the United States, is \nassociated with a fivefold increase in the risk of developing diabetes, a \ndoubling of the risk of acquiring cardiovascular disease, and an increase in \noverall mortality. Defined as a syndrome, MetS is recognized clinically by \nnumerous constitutive traits, including abdominal obesity, hypertension, \ndyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), \nand hyperglycemia. Urologic complications of MetS include a 30% higher risk of \nnephrolithiasis, with an increased percentage of uric acid nephrolithiasis in \nthe setting of hyperuricemia, hyperuricosuria, low urine pH, and low urinary \nvolume. Current American Urological Association and European Association of \nUrology guidelines suggest investigating the etiology of nephrolithiasis in \naffected individuals; however, there is no specific goal of treating MetS as \npart of the medical management. Weight loss and exercise, the main lifestyle \ntreatments of MetS, counter abdominal obesity and insulin resistance and reduce \nthe incidence of cardiovascular events and the development of diabetes. These \nrecommendations may offer a beneficial adjunctive treatment option for \nnephrolithiasis complicated by MetS. Although definitive therapeutic \nrecommendations must await further studies, it seems both reasonable and \njustifiable for the urologist, as part of a multidisciplinary team, to recommend \nthese important lifestyle changes to patients with both conditions. These \nrecommendations should accompany the currently accepted management of \nnephrolithiasis.", "Approximately 2500 Americans die from cardiovascular disease (CVD) each day. \nEach year, CVD claims more lives than the next four leading causes of death \ncombined. Direct and indirect costs of CVD are estimated to be Dollars 403.1 \nbillion in 2006. Despite advancements in conventional therapy, the residual risk \nof CVD continues to rise. One component of the cardiometabolic risk is metabolic \nsyndrome. Metabolic syndrome is a constellation of interrelated risk factors of \nmetabolic origin including abdominal obesity, atherogenic dyslipidemia, elevated \nblood pressure, elevated plasma glucose level, and prothrombotic and \nproinflammatory states that promote atherosclerotic CVD and increase the risk of \ntype 2 diabetes mellitus. Approximately 47 million residents of the United \nStates have metabolic syndrome. Abdominal obesity and insulin resistance appear \nto be its predominant underlying risk factors. Abdominal adiposity is considered \nhigh-risk fat, and it is associated with insulin resistance, hyperglycemia, \ndyslipidemia, hypertension, and prothrombotic and/or proinflammatory states. \nDespite notable advances in cardiovascular risk management, the prevalence of \ncardiovascular events and type 2 diabetes remains high. First-line therapy for \nindividuals with metabolic syndrome should be directed to the major CVD risk \nfactors, namely, elevated low-density lipoprotein cholesterol levels, \nhypertension, and diabetes, and it should emphasize lifestyle modification. \nUntil additional research better defines the most appropriate therapies, \nconventional cardiovascular risk factors, such as lipid levels, blood pressure, \nand diabetes, should be managed in individuals with metabolic syndrome according \nto nationally accepted clinical guidelines.", "Clinical investigations designed to determine risk profiles for the development \nof cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually \nperformed in homogenous populations and often focus on body mass index (BMI), \nwaist circumference (WC), and fasting triglyceride (TG) levels. However, there \nare major ethnic differences in the relationship of these risk factors to \noutcomes. For example, the BMI risk threshold may be higher in blacks than in \nwhites and higher in women than in men. Furthermore, a WC that predicts an obese \nBMI in white women only predicts a BMI in the overweight category in black \nwomen. In addition, overweight black men have a greater risk of developing type \n2 DM than do overweight black women. Although TG levels are excellent predictors \nof insulin resistance in whites, they are not effective markers of insulin \nresistance in blacks. Among the criteria sets currently available to predict the \ndevelopment of CVD and type 2 DM, the most well known is the metabolic syndrome. \nThe metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, \nlow high-density lipoprotein (HDL) levels, fasting hyperglycemia, and \nhypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 \nfactors must be present. For central obesity and low HDL, the metabolic syndrome \nguidelines are sex specific. Diagnostic guidelines should also take ethnic \ndifferences into account, particularly in the diagnosis of central obesity and \nhypertriglyceridemia.", "Metabolic Syndrome X is a clinical entity which comprises the following factors: \ndiabetes mellitus, arterial hypertension, high levels of triglyceride and/or low \nlevels of HDL cholesterol, central obesity and microalbuminuria (by WHO \ncriteria). The first goal of this study was to determine the frequency of the \nMetabolic Syndrome X (MSX) in patients with acute myocardial infarction compared \nwith the general population. The second goal of the study was to examine the \nfrequency of heart failure and reinfarction rate in the patients with myocardial \ninfarction, with and without MSX. Furthermore, the relationship between gender \nand MSX was analyzed. A total of 101 patients with acute myocardial infarction \ntook part in randomized trial (32 women and 69 men). MSX and all of its \ncomponents were diagnosed according to WHO criteria. To determine statistical \nsignificance of our results, we used chi2 test and t-test for independent \nsamples. From 101 patient 48 had MSX (47.52%), while in the general population \nincidence of MSX is 3-4%. The reinfarction and the heart failure rate were \nsignificantly higher in the group of patients with MSX (p = 0.0067 and p = \n0.0217, respectively). To conclude, the results of the present study confirm \nthat MSX is a high risk factor for myocardial infarction and its complications.", "Metabolic syndrome, defined as a cluster of obesity, hypertension, dyslipidemia, \nand insulin resistance/glucose intolerance, has been identified as a major risk \nfactor for coronary heart disease in women. Nurses should increase their \nawareness of metabolic syndrome to help identify and treat the current estimated \n47 million US residents who have metabolic syndrome.", "BACKGROUND: Metabolic syndrome (MetS) is a collection of clinical conditions, \nincluding central obesity, hypertension, glucose intolerance and dyslipidemia. \nThe long-term inflammatory and metabolic dysfunction associated with MetS may \ncontribute to osteoarthritic processes leading up to total joint arthroplasty \n(TJA). The purpose of this study was to investigate levels of metabolic \nbiomarkers and the prevalence of MetS in patients undergoing TJA.\nMETHODS: Under IRB approval, citrated plasma samples were collected from 41 \npatients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and \nday 1 postoperatively. Control group consisted of 25 healthy human plasma \nsamples (female and male, 18-35 years old) purchased from George King Biomedical \nInc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, \nIL-6, insulin, resistin, TNF-α, IL-1a, leptin, and PAI-1 using metabolic \nbiochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III \nguidelines were used to evaluate which patients met MetS criteria.\nRESULTS: Levels of IL-6, resistin, TNF-a, IL-1a, leptin, and PAI-1 were \nsignificantly elevated in patients undergoing TJA compared to normal. C-peptide \nand insulin were both decreased in TJA compared to normal. No significance was \nfound when comparing TJA to normal for ferritin. TNFα was significantly lower in \nTJA+MetS compared to TJA-MetS, while other biomarkers showed no difference in \nTJA±MetS populations. Insulin & c-peptide both showed a significant decrease in \nTJA-MetS compared to normal, but levels in TJA+MetS patients were not \nsignificantly different from controls. Resistin showed significant increases in \nTJA+MetS vs. normal, but not in TJA-MetS vs. normal.\nCONCLUSIONS: Overall, the differing metabolic profile seen in patients \nundergoing TJA suggest ongoing metabolic dysfunction. Insulin and c-peptide \npatterns among the different test groups hint toward a complex and dysfunctional \nmetabolic process involved, with leptin and underlying insulin resistance \nplaying a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to \nnormal, suggests that while elevated resistin levels may be associated with the \nosteoarthritic process, levels are further attenuated by MetS, which is highly \nprevalent in this population. Increased TNFα in TJA-MetS compared to TJA+MetS \nmay be an artifact of differing sample populations or a true complication of the \ncomplex pathophysiology and medical regimen seen in patients with both OA and \nMetS. The lack of difference seen in the remaining biomarkers suggest that \nhaving MetS as a comorbidity does not contribute to the elevated levels seen in \npatients undergoing TJA.", "The metabolic syndrome is a complex association of several risk factors \nincluding insulin resistance, dyslipidemia, and essential hypertension. Insulin \nresistance has been associated with sympathetic activation and endothelial \ndysfunction, which are the main mechanisms involved in the pathophysiology of \nhypertension and its related cardiovascular risk. According to the Sixth Report \nof the Joint National Committee, and guidelines of the World Health \nOrganization/International Society of Hypertension, the presence of multiple \nrisk markers suggests that both hypertension and risk factors should be \naggressively managed in order to obtain a better outcome. Primary prevention of \nobesity at different levels--individual, familial, and social-- starting early \nin childhood has proven to be cost effective, and will be mandatory to reduce \nthe world epidemic of obesity and its severe consequences.", "Metabolic syndrome is widely spread in population especially among subjects with \nrisk factors of atherosclerosis related diseases. Since 1988 criteria of \nmetabolic syndrome have undergone substantial transformation. Technical \ndifficulties related to detection of insulin resistance created obstacles to \napplication of the term \"metabolic syndrome\" in clinical practice. In 2001 \nexperts of National Cholesterol Education Program in USA suggested new set of \ncriteria. The presence of 3 or more of the following 5 components (abdominal \nobesity, hypertriglyceridemia, low level of high density lipoprotein \ncholesterol, hypertension and high fasting blood glucose) allows to diagnose \nmetabolic syndrome. These worldwide used criteria do not imply detection of \ninsulin resistance. Feasibility of this approach has been confirmed by analysis \nof correlation between presence of markers of insulin resistance and that of \nmetabolic syndrome according to novel criteria. This analysis has shown that \ncombination of 3 or more components is significantly associated with insulin \nresistance.", "Insulin resistance represents a common metabolic abnormality leading to \ncardiovascular disease, the major cause of morbidity and mortality in most parts \nof the world. Insulin resistance is also associated with an increased risk of \ntype 2 diabetes which is strongly associated with obesity. The insulin \nresistance of obese people and subjects with type 2 diabetes is characterised by \ndefects at many levels, affecting insulin receptor concentration, glucose \ntransport mechanisms and the activities of intracellular enzymes. Around 25% of \nwestern populations show some features of the insulin resistance syndrome (often \nreferred to as syndrome X or the metabolic syndrome) ie, a clustering of \nmetabolic, atheromatous risk factors, including hypertriglyceridaemia, \nhyperinsulinaemia, hyper-tension, hypercholesterinaemia and obesity. However, \nthe known metabolic cardiovascular risk factors associated with the insulin \nresistance syndrome do not sufficiently explain the excess vascular risk \nattributed to this syndrome. The observation, that increased plasma plasminogen \nactivator inhibitor 1 (PAI-1) levels were associated with insulin resistance and \natherothrombosis added for the first time a pathological basis for an \nassociation of the insulin resistance syndrome not only with metabolic, \natheromatous (atherosclerotic) risk but also with atherothrombotic risk. It is \nvery likely that not only PAI-1, but also other abnormalities in haemostatic \nvariables contribute to this excess vascular risk. Knowledge of how haemostatic \nvariables cluster with classical metabolic risk factors associated with the \ninsulin resistance syndrome could help to better understand the pathogenesis of \ncardiovascular diseases. Indeed, many coagulation and fibrinolytic proteins have \nbeen shown to be associated with features of the insulin resistance syndrome and \nthese associations suggest that some coagulation and fibrinolytic proteins have \na role in atherothrombotic disorders, principally through an association with \nother established metabolic (atheromatous) risk factors in the presence of \nunderlying insulin resistance. Interestingly, new therapeutic approaches in the \nprevention and treatment of insulin resistance do show some influence on \ncoagulation and fibrinolysis. The newest drugs are the thiazolidinediones, a \ntotally novel class of insulin sensitisers. They have the potential to offer \nimprovements both in glycaemic control and in cardiovascular events.", "The metabolic syndrome is a clustering of risk factors which predispose an \nindividual to cardiovascular morbidity and mortality. There is general consensus \nregarding the main components of the syndrome (glucose intolerance, obesity, \nraised blood pressure and dyslipidaemia [elevated triglycerides, low levels of \nhigh-density lipoprotein cholesterol]) but different definitions require \ndifferent cut points and have different mandatory inclusion criteria. Although \ninsulin resistance is considered a major pathological influence, only the World \nHealth Organization (WHO) and European Group for the study of Insulin Resistance \n(EGIR) definitions include it amongst the diagnostic criteria and only the \nInternational Diabetes Federation (IDF) definition has waist circumference as a \nmandatory component. The prevalence of metabolic syndrome within individual \ncohorts varies with the definition used. Within each definition, the prevalence \nof metabolic syndrome increases with age and varies with gender and ethnicity. \nThere is a lack of diagnostic concordance between different definitions. Only \nabout 30% of people could be given the diagnosis of metabolic syndrome using \nmost definitions, and about 3540% of people diagnosed with metabolic syndrome \nare only classified as such using one definition. There is currently debate \nregarding the validity of the term metabolic syndrome, but the presence of one \ncardiovascular risk factor should raise suspicion that additional risk factors \nmay also be present and encourage investigation. Individual risk factors should \nbe treated." ]	['https://meshb.nlm.nih.gov/record/ui?ui=D024821', 'https://meshb.nlm.nih.gov/record/ui?ui=D007333']
61f5914e882a024a1000000d	[27582220,34554383,33135381,34366359,34506904,34827546,34550687,29067304,29686315,29181491,34697913,(...TRUNCATED)	train	Aducanumab can be used for treatment of which disease?	factoid	Aducanumab is approved for treatment of Alzheimer's disease.	Alzheimer's disease	["Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) \nplaques and neurofib(...TRUNCATED)	nan
53189656b166e2b80600001c	[9600226,12536227,19272424,9759660,10967182,16691119,11005264,12722831,15854770,10867800,22370907,10(...TRUNCATED)	train	Against which protein is the antibody used for immonostaining of Lewy bodies raised?	factoid	"alpha-Synuclein is a presynaptic protein, which was identified as a specific component of Lewy bodi(...TRUNCATED)	alpha-Synuclein	["A mutation in the alpha-synuclein gene has recently been linked to some cases of \nfamilial Parkin(...TRUNCATED)	"['http://www.uniprot.org/uniprot/SYUA_SERCA', 'http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=ui(...TRUNCATED)
515a9d86d24251bc050000a7	[ 18288611, 15822917, 16335978, 19327347, 21906361, 15952730, 18412540, 23300121 ]	train	"Albumin depletion is a common first step for proteomic analysis of CSF fluid. What is the advantage(...TRUNCATED)	summary	"Depletion of the high abundant protein Albumin from CSF samples is improving the detection of lower(...TRUNCATED)	"Depletion of the high abundant protein Albumin from CSF samples is improving the detection of lower(...TRUNCATED)	["Glycoproteins in cerebrospinal fluid (CSF) are altered in Alzheimer's Disease \n(AD) patients comp(...TRUNCATED)	"['http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005441', 'http:(...TRUNCATED)

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RAG Datasets

Collection of popular open-source RAG datasets for evaluation • 6 items • Updated 3 days ago