A survival analysis was applied to 1,453 patients treated between 1972 and 1978 in 33 French dialysis centers and prospectively followed up in the computerized Diaphane Dialysis Registry. 198 deaths (overall mortality = OM) were registered, of which 87 (43%) were secondary to cardiovascular complications (cardiovascular mortality = CVM). Risk factors for OM and CVM (p values < 0.05) were age, male sex, nephroangiosclerosis or diabetic nephropathy as the primary renal disease, elevated systolic and diastolic blood pressure and two weekly dialysis rather than three. In contrast with the results observed for the general population, a high body mass index and elevated cholesterol, triglycerides and uric acid were not found to be associated with significantly increased CVM or OM. On the contrary, low body mass index ( < 20 kg/m²), low cholesterol ( < 4.5 mmol/l) and low mean predialysis blood urea ( < 4.6 mmol/l) were associated with increased OM and CVM, and more especially with high stroke mortality. Results for urea but not for cholesterol remain significant after adjustment for age, sex, weekly dialysis schedule and body mass index. They suggest that, in addition to elevated blood pressure, a poor nutritional state and/or low protein intake may be important factors for explaining the high cardiovascular mortality, particularly for strokes, observed in dialyzed patients.

To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls. Ninety percent of the IIH patients were women; the mean age was 33. Obesity and recent weight gain were much more common among patients than controls. Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%). Daily occurrence of these symptoms was much more common among patients than controls. Controls also reported these and other IIH symptoms, but at lower frequencies. Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives. We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications. The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily.

No abstract

In a double-blind zinc trial in low-income, pregnant adolescents thought to be at risk for poor zinc nutriture, subjects were randomly assigned to receive 30 mg zinc (gluconate) or placebo. Response to zinc was related to maternal weight. Infants of normal-weight mothers given zinc had reduced rates of prematurity (p = 0.05) and assisted respiration (p = 0.006). Underweight multiparas given zinc had longer gestational lengths (p = 0.008) than did subjects given the placebo. Multiple stepwise regression analysis, used to identify predictors of infant size, revealed that 14-26% more variance was accounted for in the zinc than in the placebo group. Except for gestational age, the predictors selected were entirely different in the two groups. The zinc group had a positive toxemia screen more often, which did not appear to affect outcome. Zinc supplementation improved pregnancy outcome in normal-weight women and in underweight multiparas. The nonresponse in underweight primiparas was perhaps due to multiple limiting factors.

Sample size determination for case-control studies of chronic disease are often based on the simple 2 X 2 tabular cross-classification of exposure and disease, thereby ignoring stratification which may be considered in the analysis. One consequence of this approach is that the sample size may be inadequate to attain a specified power and size when performing a statistical analysis on J 2 X 2 tables using Cochran's (1954, Biometrics 10, 417-451) statistic or the Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) statistic. A sample size formula is derived from Cochran's statistic and it is compared with the corresponding one derived when the data are treated as unstratified, and also with two other formulas proposed for stratified data analysis. The formula developed yields values slightly higher than one recently proposed by Muñoz and Rosner (1984, Biometrics 40, 995-1004), which assumes that both margins of each 2 X 2 table are fixed, while the present study considers only the case-control margin to be fixed.

No abstract

Heparin-induced thrombocytopenia (HIT) type II is a serious complication of heparin therapy. It presents initially as thrombocytopenia, and is associated with thrombosis in 20-50% of the cases. HIT is related to the presence of heparin-induced antibodies (HIA), which show specificity for the PF4-heparin (PF4-H) complex. The FcgammaRIIa receptor has been suggested to participate in the pathogenic mechanism of HIA. Since patients undergoing chronic hemodialysis (HD) are exposed repeatedly to heparin, we studied the prevalence of HIA and their eventual relationship with thrombocytopenia and/or thrombosis, and the possible participation of the FcgammaRIIa polymorphism. We studied 207 patients with chronic renal failure (CRF) undergoing HD. As a control we included 130 blood donors and 28 patients with CRF without HD. The HIA patients were studied with the use of a PF4-H ELISA. Additionally, in some positive cases for the previous test, a 14C- serotonin release assay (14C-SRA) was performed. The polymorphism FcgammaRIIa H/R131 was studied by polymerase chain reaction (PCR) with allele-specific primers. Thirty-seven patients (17.9%) undergoing HD presented with HIA. The majority of these antibodies were IgG, IgM, and IgA. The HIA investigated presented specificity against the PF4-H complex, but not against PF4 alone (P<0.001). Twelve out of 22 (54.5%) PF4-H antibodies were positive when tested with the 14C-SRA. The distribution of the FcgammaRIIa polymorphism in patients and healthy controls was 42.6% and 41.6% for H/H131, 41% and 48.9% for the H/R131 isoform, and 16.4% and 9.5% for the R/R131 isoform, respectively. No statistically significant difference in the FcgammaRIIa isoform distribution was found. Twenty-nine out of 156 patients (18.5%) presented thrombocytopenia, and 21/207 (12.4%) had thrombosis of the native vein arterio-venous fistula (AVF). We did not find any statistically significant between HIA and thrombocytopenia or thrombosis. An important proportion of patients with CRF undergoing HD developed HIA, but these cases were not associated with thrombocytopenia or thrombosis of AVF. The frequency of the FcgammaRIIa polymorphism did not statistically differ between HIT type II and normal controls.

Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell – associated neurotoxicity syndrome (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) receptor was administered 1 hour prior to infusion of anti-CD19 CAR-T cells with CD3ζ/4-1BB costimulatory signaling used to treat non-Hodgkin lymphoma patients. Relapsed/refractory lymphoma patients treated with anti-CD19 CAR-T cells were included in this analysis. Cytokine plasma levels were measured by electrochemiluminescence before lymphodepleting chemotherapy, prior to infusion and then on days 2, 4,6, and 14 days after treatment. Twenty patients were treated. Cell products included locally manufactured anti-CD19 CAR-T (n=18) and tisagenlecleucel (n=2). There were no adverse events attributed to tocilizumab. Ten patients had grade 1–2 CRS at a median of 4 (range 3-7) days. There were no cases of grade ≥3 CRS. Five patients had ICANS, grade 1 (n=4) and grade 4 (n=1). Laboratory studies obtained prior to lymphodepleting chemotherapy were comparable between patients with and without CRS, except for interleukin (IL)-15 plasma concentrations. patients with CRS had higher post-infusion ferritin and C reactive protein, with more marked increases in inflammatory cytokines, including IL-6, IL-15, IFN-γ, fractalkine and MCP-1. Fifteen patients (75%) achieved CR and 2 (10%), PR. One-year OS and PFS estimates were 83% and 73%. Prophylactic tocilizumab was associated with low CRS incidence and severity. There were no adverse events associated with tocilizumab, no increase in frequency or severity of ICANS and excellent disease control and overall survival.