Optimal donation of kidney transplants after controlled circulatory death

Controlled donation after circulatory death (cDCD) is used for “extended criteria” donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12–1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20–2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31–2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.     

Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...     

Influence of HRT on prognostic factors for breast cancer: a systematic review after the Women's Health Initiative trial

INTRODUCTION: Mortality due to breast cancer has been reported to be the same or even lower in HRT users than in non-users. This has been attributed to earlier diagnosis and to better prognosis. Nevertheless, more advanced disease in HRT users was reported recently by the Women's Health Initiative (WHI) study. The objective of this study was to assess, using a systematic review of current literature, whether the data of the WHI study are in contradiction to observational data. METHODS: We selected 25 studies, for which we evaluated the methodology, the characteristics of the studied populations, confounding breast cancer risk factors and prognostic indicators. RESULTS: The WHI study, showing a worsening of some prognostic parameters, is in contradiction to most published observational studies. Most observational studies are retrospective, not well matched and did not consider most confounding factors. Their methodology and selection criteria varied considerably and the number of patients was often small. No differences in the distributions of histology, grade or steroid receptors were observed in the WHI trial, while this was the case in some of the observational studies. Other parameters (S phase, protein Neu, Bcl-2 gene, protein p53 and E-cadherin, cathepsin D) were not reported in the WHI trial. CONCLUSIONS: In view of these data, the current clinical message to patients should be changed: one can no longer declare that breast cancers developed while using HRT are of better prognosis.     

Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate

 As it is suggested that the androgen receptor mechanism is required for prostatic development, we attempted to determine the appearance, expression and distribution of the androgen receptor in embryonic, infantile and pubertal human prostate. Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp riboprobe, the androgen receptor expression in paraffin sections of fetal, infantile, and pubertal prostates was studied at the protein and RNA level. Under highly standardized conditions, application of the polyclonal antibodies resulted in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands. No immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal antibody to pubertal and adult specimens, immunoreactivity of the androgen receptor was positive in nuclei of adluminal and basal epithelial cells, in interstitial and vascular smooth muscle cells and vascular endothelium, whereas ganglionic cells and enteroendocrine cells were negative. In situ hybridization with the digoxigenin-labeled riboprobe gave clear positive results already in epithelium of very young fetal specimens. A semiquantitative visual evaluation of in situ hybridizations showed that intermediate intensity of expression was increased in pubertal and adult specimens, whereas strong expression was reduced in prostatic epithelium. Conclusions: The essential findings are: (1) an early expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction of monoclonal antibodies against the androgen receptor in the same specimens, (3) a decrease of androgen receptor mRNA expression, but increase in immunoreactivity of the androgen receptor protein with the onset of glandular maturation during puberty. Accepted: 29 September 1997     

Rehabilitative techniques for athletes after reconstruction of the anterior cruciate ligament

A wide spectrum of protocols is available for rehabilitation after anterior cruciate ligament reconstruction, and little agreement exists on the specifics of strengthening exercises or the sequence of activities. In this article, we discuss the current rehabilitative techniques used at the Mayo Clinic for athletes who have undergone anterior cruciate ligament reconstruction. These techniques are based on established principles of rehabilitation, clinical experience, and new information about the related biomechanics of the knee. An illustrative case reflects the benefits of this rehabilitation program, which lasts up to 1 year and is divided into five stages. The early stages focus on protected mobilization and a strengthening program that emphasizes closed rather than open kinetic chain exercises. Later, neuromuscular-proprioceptive training and sport-specific agility training redevelop the reaction time and the "coordination engrams" necessary for athletic competition. High-quality surgical care and a closely supervised rehabilitation program, based on kinesiologic and biomechanical factors as they pertain to the anterior cruciate ligament, are necessary for a successful outcome.     

The Relative Importance of Mutagens and Carcinogens in the Diet

Known mutagens and carcinogens in the diet were compiled and the risk of cancer was estimated on the basis of average exposure levels in Switzerland and carcinogenic potencies from rodent bioassays. The analysis showed that, except for alcohol, the sum of all known dietary carcinogens could only explain a few percent of the cancer deaths attributed by epidemiologists to dietary factors. The discrepancy was explained by a “carcinogenicity” of excess macronutrients. This hypothesis was based on an evaluation of dietary restriction experiments in rats and mice, where a dramatic reducing effect on spontaneous tumour formation was seen. From these experiments, a "carcinogenic potency" was deduced for food in excess (TD₅₀ approximately 16 g/kg per day). Overnutrition in Switzerland was converted into excess food intake and the cancer risk estimated on the basis of the TD₅₀ value. The resulting risk of 60,000 cases per one million lives would allow to explain by overnutrition almost all "diet-related" cancer deaths in humans.