Evidence that large granular lymphocytes from B-CLL patients with hypogammaglobulinemia down-regulate B-cell immunoglobulin synthesis [published erratum appears in Blood 1989 Jun;73(8):2232]

B-chronic lymphocytic leukemia (CLL) patients frequently suffer from moderate to severe hypogammaglobulinemia. This complication is a serious cause of morbidity and mortality in this disorder. There is recent evidence that natural killer (NK) cells modulate B-cell immunoglobin (Ig) synthesis/secretion. The authors therefore evaluated the circulating NK cells from B-CLL patients on their ability to regulate mitogen-induced B-cell Ig synthesis. Blood, NK cells (CD16+, CD3-) from three B-CLL patients with hypogammaglobulinemia were able to clearly down-regulate the pokeweed mitogen (PWM)-induced-B-cell Ig secretion. In contrast, CD16+, CD3- cells from age-sex-matched controls or B-CLL patients with normal Ig were either nonregulatory or enhanced mitogen-induced B-cell Ig secretion. An alternative explanation for hypogammaglobulinemia in B-CLL patients is the immunomodulation of B- cell Ig production/secretion by CD16+, CD3- blood cells.     

Detection of lung perfusion abnormalities using computed tomography in a porcine model of pulmonary embolism

The purpose of this study was to identify perfusion defects of the lung using computed tomography (CT). A balloon catheter was placed in a lobar pulmonary artery of six anesthetized, ventilated, juvenile pigs to simulate occlusive segmental embolus. Contrast medium was injected via a central venous catheter at rates of 1.5, 3, 4.5, and 9 ml/s in each pig. A 40-second single-level cine CT was acquired distal to the inflated balloon during suspended inspiration. Three computer-manipulated images (time to maximal enhancement, change in maximal attenuation, maximal contrast minus precontrast subtraction) were generated using custom software and compared with the unmodified maximal enhancement and precontrast images. Two independent observers identified perfusion defects and scored the level of confidence (5-point scale) on all five images. Regions of interest were drawn in perfused and nonperfused lung and time-attenuation curves were generated. Perfusion defects were accurately (99.8 +/- 0.3%) and confidently (4.5 +/- 0.6) detected and there was excellent interobserver agreement (Kappa 0.99 +/- 0.02) on all computer-manipulated images. There was a significant increase in confidence (p < 0.05) between contrast medium injection rates of 1.5 and 9 ml/s. A linear relationship exists (r = 0.88) between injection rate and change in maximal attenuation. In conclusion, perfusion defects of the lung are seen using computer-manipulated CT images.     

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

ABSTRACT: BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within [PLUS-MINUS SIGN]1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. METHODS: Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa--to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL from baseline. RESULTS: A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was [LESS-THAN OR EQUAL TO]29 weeks. Overall, the proportion of patients with hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2--13) to 54% (Weeks 18--25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. CONCLUSIONS: The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.Trial registrationClinicalTrials.gov registration: NCT00228449.     

Changes in frailty-related characteristics of the hip fracture population and their implications for healthcare services: evidence from Quebec, Canada

Summary

This study provides evidence that a number of frailty-related characteristics (older age, de novo admission to long-term care (LTC), comorbidities [Charlson Index, osteoporosis, osteoporosis risk factors, sarcopenia risk factors, and dementia]) have increased in the hip fracture population from 2001–2008. This will have significant impact on community resources, as the number of people discharged to the community is also increasing.

Introduction

The aim of this study is to estimate secular changes in the prevalence of selected frailty-related characteristics among the hip fracture population in the Canadian province of Quebec (2001–2008) and the potential impact of these changes on healthcare services.

Methods

The Quebec hospitalization database was used to identify nontraumatic hip fractures for the purposes of calculating age- and sex-specific rates. Also estimated were time trends for selected frailty-related characteristics and discharge destinations.

Results

A significant decline in fracture rates was evident for all age groups except for those <65; sex differences were also observed. Almost all frailty-related characteristics increased over time, ranging from 2 to 14 % per year, which translates to an estimated increase from 16 to 112 %, over the study period. For those whose prior living arrangement was LTC, rates of hip fractures declined significantly (women OR?=?0.93, 0.91–0.95; men OR?=?0.97, 0.94–0.99). In-hospital mortality and discharge to inpatient rehabilitation decreased, while discharges back to community and to LTC increased.

Conclusions

Although hip fracture rates decreased for older hip fracture patients, the absolute number and prevalence of specific frailty-related characteristics increased. Policy makers should review care models to ensure that adequate resources are provided to the community to offset the expected increase in demand arising from ongoing changes in patients’ characteristics.