The Erythrocyte Membrane Disturbances in Protein-Energy Malnutrition: Nature and Mechanisms

In protein-energy malnutrition (PEM), as observed in Kivu, the RBC have an increased ratio of surface area to volume which is demonstrated by the presence of target cells on light microscopy and cup cells with scanning electron microscopy. The osmotic fragility is decreased. These abnormalities can be attributed to the accumulation of cholesterol and phosphatidylcholine (PC) in the RBC membrane. The molar ratio of cholesterol to phospholipids is moderately increased. Several findings suggest that the cholesterol and PC build-up results from disturbed exchanges in these lipids between the RBC and the plasma lipoproteins. Firstly, the osmotic fragility of a patient's RBC gradually becomes normal when the cells are transfused into a healthy recipient. Secondly, the cholesterol flux between the RBC and the plasma LDL seems to be low. Thirdly, the increase in RBC PC cannot be explained by a diminished fatty acids transport between the deep RBC PC pool and the RBC phosphatidylethanolamine (PE) pool. Finally complex disturbances of the plasma lipoproteins are obvious. It is improbable that the cholesterol and PC build-up accounts for the premature RBC destruction which has been described in Kivu PEM. However, the observation of an increased fatty acid turnover in RBC PC and PE, as well as other data previously obtained in Kivu PEM, lead to the conclusion that membrane peroxidation may be a major cause of the shortened erythrocyte life-span in this syndrome.     

Gender differences in alcohol consumption and adverse drinking consequences: cross-cultural patterns

Aims: To examine the consistency and/or variability of gender differences in drinking behavior crossculturally. Design, setting, participants: Women's and men's responses in 16 general population surveys from 10 countries, analyzed by members of the International Research Group on Gender and Alcohol. Measurements: Comparable measures of drinking, versus abstention, typical drinking frequencies and quantities, heavy episodic drinking, intoxication, morning drinking, and alcohol-related family and occupational problems. Findings: Women and men differed little in the probability of currently drinking versus abstaining, but men consistently exceeded women in typical drinking frequencies and quantities and in rates of heavy drinking episodes and adverse drinking consequences, while women were consistently more likely than men to be life-time abstainers. In older age groups, both men and women drank smaller quantities of alcohol and were more likely to stop drinking altogether, but drinking frequencies did not change consistently with age. Conclusions: A theoretical synthesis proposes that gender roles may amplify biological differences in reactions to alcohol, and that gender differences in drinking behavior may be modified by macrosocial factors that modify gender role contrasts.     

Diet as a system: an observational study investigating a multi-choice system of moderately restricted low-protein diets

Background

There is no single, gold-standard, low-protein diet (LPD) for CKD patients; the best compliance is probably obtained by personalization. This study tests the hypothesis that a multiple choice diet network allows patients to attain a good compliance level, and that, in an open-choice system, overall results are not dependent upon the specific diet, but upon the clinical characteristics of the patients.

Methods

Observational study: Three LPD options were offered to all patients with severe or rapidly progressive CKD: vegan diets supplemented with alpha-ketoacids and essential aminoacids; protein-free food in substitution of normal bread and pasta; other (traditional, vegan non supplemented and tailored). Dialysis-free follow-up and survival were analyzed by Kaplan Meier curves according to diet, comorbidity and age.Compliance and metabolic control were estimated in 147 subjects on diet at March 2015, with recent complete data, prescribed protein intake 0.6 g/Kg/day. Protein intake was assessed by Maroni Mitch formula.

Results

Four hundreds and forty nine patients followed a LPD in December, 2007- March, 2015 (90% moderately restricted LPDs, 0.6 g/Kg/day of protein, 10% at lower targets); age (median 70 (19–97)) and comorbidity (Charlson index: 7) characterized our population as being in line with the usual CKD European population. Median e-GFR at start of the diet was 20 mL/min, 33.2% of the patients were diabetics. Baseline data differ significantly across diets: protein-free schemas are preferred by older, high-comorbidity patients (median age 76 years, Charlson index 8, GFR 20.5 mL/min, Proteinuria: 0.3 g/day), supplemented vegan diets by younger patients with lower GFR and higher proteinuria (median age 65 years, Charlson index 6, GFR 18.9 mL/min; Proteinuria: 1.2 g/day); other diets are chosen by an intermediate population (median age 71 years, Charlson index 6; GFR 22.5 mL/min; Proteinuria: 0.9 g/day); (p?<0.001 for age, Charlson index, proteinuria, GFR). Adherence was good, only 1.1% of the patients were lost to follow-up and protein intake was at target in most of the cases with no differences among LPDs (protein intake: 0.47 (0.26–0.86) g/Kg/day). After adjustment for confounders, and/or selection of similar populations, no difference in mortality or dialysis start was observed on the different LPDs. Below the threshold of e-GFR 15 mL/min, 50% of the patients remain dialysis free for at least two years.

Conclusion

A multiple choice LPD system may allow reaching good adherence, without competition among diets, and with promising results in terms of dialysis-free follow-up. The advantages with respect to a non-customized approach deserve confirmation in further comparative studies or RCTs.

     

Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease.

To investigate human immunodeficiency virus type 1 (HIV-1) pathogenesis in infected individuals and examine the correlation of HIV-1 expression with extent of clinical and pathologic disease, we studied spinal cords from acquired immunodeficiency syndrome patients with a wide range of spinal cord pathology. By performing in situ hybridization with HIV-1-specific riboprobes, we detected HIV-1 RNA in all 10 cords from acquired immunodeficiency syndrome patients with a common, characteristic pathologic entity called vacuolar myelopathy but not in 10 control cords from HIV-1-infected and uninfected patients. In the cords from individuals with vacuolar myelopathy, the level of HIV-1 RNA expression correlated directly with extent of spinal cord pathology and clinical findings. These data support a role for HIV-1 in the pathogenesis of tissue damage and related clinical disease in infected individuals.     

Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 ± 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0-8.9, 9.0-9.9, and ≥10%, compared with 7.0-7.9% (reference), was 1.06 (95% CI 1.01-1.12), 1.05 (0.99-1.12), and 1.19 (1.12-1.28), respectively, and for time-averaged A1C was 1.11 (1.05-1.16), 1.36 (1.27-1.45), and 1.59 (1.46-1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0-6.9%, HR 1.05 [95% CI 1.01-1.08]; 5.0-5.9%, 1.08 [1.04-1.11], and ≤5%, 1.35 [1.29-1.42]) compared with 7.0-7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175-199, 200-249, 250-299, and ≥300 mg/dL, compared with 150-175 mg/dL (reference), was 1.03 (95% CI 0.99-1.07), 1.14 (1.10-1.19), 1.30 (1.23-1.37), and 1.66 (1.56-1.76), respectively. Hence, poor glycemic control (A1C ≥8% or serum glucose ≥200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk.     

SAMITAL® improves chemo/radiotherapy-induced oral mucositis in patients with head and neck cancer: results of a randomized, placebo-controlled, single-blind Phase II study

Purpose

This randomised, placebo-controlled single-blind trial investigated the safety and efficacy of SAMITAL®, a formulation of highly standardised botanical extracts, in the treatment of chemo/radiotherapy-induced oral mucositis (OM) in patients with head and neck cancer.

Methods

Patients received SAMITAL® or placebo four times daily for up to 50 days during scheduled chemo/radiotherapy. Severity of OM was monitored according to a modified WHO severity scale, and pain and quality-of-life assessments were based on the effect of symptoms of OM on relevant daily activities, according to a visual analogue scale.

Results

Mean scores for the severity of OM were significantly (p?<?0.05 versus baseline) reduced from day 31 until the end of treatment in patients treated with SAMITAL® (n?=?20). No significant improvement was observed in the placebo group (n?=?10). Pain reduction was significant from day 4 till end of treatment with SAMITAL® and from days 7 to 21 in placebo patients. SAMITAL® also significantly improved quality of life, as shown by improvements in scores for relevant daily activities including eating, drinking and sleeping. All SAMITAL® patients completed the treatment period, but no placebo recipients completed treatment. No severe adverse events were observed with SAMITAL®, and systemic absorption of relevant active ingredients was undetectable.

Conclusions

SAMITAL® significantly decreased the severity of chemo/radiotherapy-induced OM in patients with head and neck cancer, with no treatment-related adverse events. Pain relief lasted through the treatment period, and improvements in quality of life were reflected by the significant benefits of SAMITAL® on activities like drinking, eating and speaking.     

Age as a predictor of outcome for women with DCIS treated with breast-conserving surgery and radiation: The University of Texas M. D. Anderson Cancer Center experience

PURPOSE: To analyze the long-term outcome of breast conservation therapy in patients with ductal carcinoma in situ (DCIS) in a single institution and to analyze the prognostic importance, if any, of young patient age. METHODS AND MATERIALS: The hospital records of 150 patients with DCIS treated with surgical excision and radiotherapy at our institution between 1980 and 1997 were retrospectively reviewed. For most of the patients, intraoperative specimen radiographs or postoperative mammograms were available for use in assessing that an adequate surgical resection had been performed. The median patient age was 53 years (range 32-81), with 13% of patients or=40 years, p = 0.39). In all cases of local recurrence, patients underwent surgery with or without chemotherapy, and disease control was achieved. CONCLUSION: The results of this study demonstrate high rates of long-term overall survival, disease-specific survival, and local control in patients with DCIS of the breast treated conservatively with segmental mastectomy and radiotherapy. On the basis of the excellent long-term local control and 100% disease-specific survival rates, we found that patient age does not affect the outcome if the margins are clear. Continued studies in young patients treated with breast conservative therapy for DCIS are needed.