Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project)

OBJECTIVES: The genetic background to RA is incompletely understood. As new cytokine-targeted therapies emerge, early predictors of disease severity are becoming increasingly important. The inflammasomes are essential regulators of cytokine production. We investigated whether two polymorphisms in the genes encoding cryopyrin (CIAS1) and TUCAN (CARD8) influence susceptibility and disease course in RA. METHODS: Genotype frequencies were assessed in 174 Swedish patients with early RA and 360 population-based controls without rheumatic disease. Genotypes were categorized according to the presence (+) or absence (-) of two wild-type alleles and compared between patients and controls. In the RA patients, antibodies towards cyclic citrullinated peptides (anti-CCP) and the 'shared epitope' (SE) were assessed, and medication and measures of disease activity were monitored regularly during 3 yrs. RESULTS: The combination of CIAS1/TUCAN -/-, as compared with CIAS1/TUCAN +/+, was significantly more common among patients than in controls [odds ratio (OR) 2.2, 95% CI 1.03-4.6]. This association was strengthened when patients were divided into anti-CCP+ [OR 2.8 (1.1-6.7)] or presence of > or = 1 SE copy [OR 2.8 (1.3-6.2)]. At most time-points during the 3-yr follow-up, patients with CIAS1/TUCAN -/- showed significantly higher disease activity. Furthermore, CIAS1/TUCAN -/- patients proved to be much more likely to receive TNF-blocking therapy [relative risk 20 (2.6-149)]. CONCLUSIONS: Compound polymorphisms in CIAS1 and TUCAN associate with RA susceptibility and severity. The cryopyrin inflammasome needs further attention regarding a possible aetiopathogenetic connection with RA.     

Incidence and risk factors for sexually transmitted infections among women in an Alabama HIV clinic

The objectives of this study were to assess the prevalence and incidence of curable sexually transmitted infections (STI), i.e., gonorrhea, chlamydial infection, or trichomoniasis, in a cohort of HIV-infected women. The study population was derived from women seeking primary care at an outpatient university HIV clinic who were participants in a women's natural history study. Enrollees (n = 225) were predominantly African-American, heterosexually infected, with mean age 35 years. Mean entry CD4+ T cell count was 405 cells/mm3. Over 6% were STI positive at initial screening. Subsequently, the combined curable STI incidence was 4.82/1000 woman-months over a median of 33 months of observation. Of 36 incident STIs, trichomoniasis was most common (n = 32). Predictors for acquisition of a curable STI included absenteeism at scheduled clinic appointments, RR = 1.99 (1.28, 3.08), and a higher CD4+ T cell count, RR = 1.15 (1.0028, 1.3115) for 100 cells. Interventions to prevent curable STI in HIV-infected women are warranted in primary care settings.     

Risk Stratification Among Survivors of Cardiac Arrest Considered for Coronary Angiography

BackgroundThe American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.ObjectivesThis study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.MethodsUsing the INTCAR (International Cardiac Arrest Registry), the impact of each proposed “unfavorable feature” on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.ResultsSeven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH <7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted <40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.ConclusionsPatients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.     

Prevalence and predictors of intestinal helminth infections among human immunodeficiency virus type 1-infected adults in an urban African setting

Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1-infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1-infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care.     

Severe α1-antitrypsin deficiency (PiZ homozygosity) with membranoproliferative glomerulonephritis and nephrotic syndrome, reversible after orthotopic liver transplantation

Background/Aims: Nephropathy associated with α₁-antitrypsin deficiency is assumed to be an unusual entity. We describe the case of a 23-year-old woman with severe α₁-antitrypsin (PiZ homozygosity) deficiency who developed hepatic cirrhosis in childhood, and glomerulonephritis and nephrotic syndrome in adult life.Methods/Results: A renal biopsy was consistent with membranosproliferative glomerulophritis. An immunofluorescence study revealed the presence of α₁-anti-trypsin (PiZ) in the subendothelial region of the glomerular basement membrane. The renal disease was reversible after orthotopic liver transplantation.Conclusions: The presence of abnormal PiZ protein in the subendothelial region of the glomerular basement membrane may suggest a possible role for this protein in the pathogenesis of glomerulonephritis. The case should add impetus to the search for α₁-antitrypsin deficiency in any patient presenting with combined liver and renal disease, in the absence of evidence of hepato-renal syndrome, and illustrates that liver transplantation alone may reverse the neophropathy associated with α₁-antitrypsin deficiency.