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.     

Effets de l’halothane sur les gaz du sang et l’équilibre acido-basique artériels chez le rat intact et chez le rat chémodénervé

L’halothane diminue la réponse ventilatoire à l’hypoxie et l’activité des chémorécepteurs artériels périphériques, réalisant une «chémodénervation chimique». Afin d’évaluer le rôle de cette «chémodénervation chimique» dans les modifications de l’équilibre acido-basique et des gaz du sang artériel provoquées par l’halothane, ces paramètres ont été mesurés chez des rats intacts éveillés, puis anesthésiés, et chez des rats chémodénervés, éveillés puis anesthésiés. Le niveau de l’anesthésie pouvant être modifié par la chémodénervation anatomique, l’ED₅₀ inspirée d’halothane a été mesurée chez six rats avant et après chémodénervation anatomique. D’éventuelles modifications hémodynamiques dues à l’halothane et /ou à la chémodénervation anatomique pouvant interférer avec les résultats, la pression artérielle systémique et la fréquence cardiaque ont été mesurées chez six rats intacts éveillés, puis anesthésiés, et chez les six mêmes rats chémodénervés, éveillés puis anesthésiés. Chez neuf rats intacts et chez 19 rats chémodénervés, le pH artériel, la concentration artérielle de bicarbonates, et les gaz du sang artériel (PaO₂ et PaCO₂) ont été mesurés avant et après administration d’halothane. La chémodénervation anatomique ne modifia ni l’ED₅₀ inspirée (1,1%), ni la pression artérielle moyenne et la fréquence cardiaque. Les effets hémodynamiques de l’halothane furent comparables chez les rats intacts et chez les rats chémodénervés. Les modifications des gaz du sang et de l’équilibre acido-basique provoquees par l’halothane chez les rats intacts, et par la chémodénervation anatomique chez les rats éveillés, ne furent pas significativement différentes: diminution significative de PaO₂ et de pHa, augmentation significative de PaCO₂ Chez les rats chémodénervés, l’halothane provoqua une diminution supplémental de PaO₂ et une augmentation supplémentaire de PaCO₂. Le fait que l’halothane et que la chémodénervation anatomique modifient de la même manière les gaz du sang et l’équilibre acido-basique est en faveur de l’action «chémodénervatrice chimique» de l’halothane. Mais les effets additionnels de l’halothane chez l’animal chémodénervé anatomiquement confirment que les effets de l’halothane sur les gaz du sang et l’équilibre acido-basique résultent de multiples points d’impact sur le système respiratoire.     

Effets de l’halothane sur la ventilation et les gaz du sang artériel chez le rat avec ou sans paralysie diaphragmatique

Certains patients atteints de paralysie diaphragmatique ou de dysfonctionnement diaphragmatique maintiennent leur ventilation par la mise en jeu d’autres muscles que le diaphragme. L’anesthésie, modifiant le fonctionnement de ces muscles, représente un risque potentiel chez ces patients. Afin d’évaluer ce risque, nous avons étudié les effets de l’halothane sur la ventilation et sur les gaz du sang artériel sur un modèle de paralysie diaphragmatique bilatérale, le rat phrénicectomisé. L’étude a été réalisée sur 43 rats. L’efficacité de la phrénicectomie a été contrôlée par l’observation directe, après laparotomie. La laparotomie n’entraine pas de modification des gaz du sang. Chez 23 rats, une laparotomie a été effectuée et une artère carotide a été cathétérisée. Chez 11 rats témoins, les nerfs phréniques ont été abordés, sans être sectionnés. Chez 12 rats, les phréniques ont été sectionnés. La ventilation a été mesurée par une technique pléthysmographique, chez les rats éveillés, avant et après l’opération, puis chez les mêmes rats anesthésiés avec 1,1%, d’halothane inspiré. Les gaz du sang ont été mesurés après l’opération chez les rats éveillés, puis anesthésiés. Chez les 23 rats opérés on observe, après l’opération, une diminution du poids et de la température centrale, plus importante chez les phrénicectomisés que chez les témoins. Chez les 11 rats témoins, après l’opération, la ventilation augmente, sans modification des gaz du sang. Chez ces rats, l’halothane provoque une diminution de la ventilation minute et de la PaO₂ et une augmentation de la PaCO₂. La phrénicectomie entraine chez les 12 rats, éveillés, une augmentation de la ventilation minute, une hypoxémie et une hypercapnie. Chez ces rats, l’halothane entraine le décès dans trois cas, une diminution de la ventilation minute et une hypercapnie et une hypoxémie importantes chez les neuf autres rats. Les modifications des gaz du sang sont plus importantes que chez les témoins anesthésiés. Chez le rat intact, l’halothane provoque des modifications des gaz du sang comparables à celles observées chez d’autres espèces et chez l’homme. La présente étude confirme les effets de l’halothane sur les muscles respiratoires autres que le diaphragme. Elle met en évidence le risque respiratoire majeur que l’anesthésie peut fair courir aux patients dont la ventilation est maintenue par d’autres muscles que le diaphragme.     

Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.     

Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes

Anti-CV2 autoantibodies have recently been discovered in patients with paraneoplastic neurological diseases (PND). These disorders are associated with neuronal degeneration, mediated by autoimmune processes, in patients with systemic cancer. Anti-CV2 autoantibodies recognize a brain protein of 66 kDa developmentally regulated and specifically expressed by a subpopulation of oligodendrocytes in the adult brain. Here, we demonstrate that anti-CV2 sera recognize several post-translationally modified forms of Ulip4/CRMP3, a member of a protein family related to the axonal guidance and homologous to the Unc-33 gene product in Caenorhabditis elegans. The sequence of the human Ulip4/CRMP3 was determined and the gene localized to chromosome 10q25.2-q26, a region mutated in glioblastomas and containing tumour suppressor genes. The identification of the Ulip/CRMP proteins as recognized by anti-CV2 sera should provide new insights into the role of Ulip/CRMPs in oligodendrocytes and into pathophysiology of PND.