Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation.Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up.ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0).ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.     

Emergency Care EMTALA Alterations During the COVID-19 Pandemic in the United States

The coronavirus 2019 pandemic has affected almost every aspect of health care delivery in the United States, and the emergency medicine system has been hit particularly hard while dealing with this public health crisis. In an unprecedented time in our history, medical systems and clinicians have been asked to be creative, flexible, and innovative, all while continuing to uphold the important standards in the US health care system. To continue providing quality services to patients during this extraordinary time, care providers, organizations, administrators, and insurers have needed to alter longstanding models and procedures to respond to the dynamics of a pandemic. The Emergency Medicine Treatment and Active Labor Act of 1986, or EMTALA, is 1 example of where these alterations have allowed health care facilities and clinicians to continue their work of caring for patients while protecting both the patients and the clinicians themselves from infectious exposures at the same time.     

Deepm5C: A deep-learning-based hybrid framework for identifying human RNA N5-methylcytosine sites using a stacking strategy

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Bench to bedside: recent advances in lung cancer pathological research with implications for diagnostic clinical practice

After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.     

Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Percutaneous renal mass biopsy: historical perspective,current status,and future considerations

Introduction: Percutaneous renal mass biopsy has evolved over the last decade with improvements on previous pitfalls including low tissue yield, high non-diagnostic rates, and complications. As understanding of tumor biology and natural history of renal cortical neoplasms has improved, percutaneous renal mass biopsy is poised to have an expanding role in an area characterized by individualized management and refined risk stratification.

Areas covered: This review summarizes the evolution of renal mass biopsy to its current state with respect to outcomes, indications, and clinical guidelines.

Expert opinion: With improved understanding of differential biological potential of renal cortical neoplasms combined with technical improvements in diagnostic yield and accuracy, utilization of renal mass biopsy is becoming an important adjunct to patient care in a broad range of clinical scenarios, including active surveillance, thermal ablation, and use of primary systemic therapy in localized and advanced settings.     

Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.     

Coupling online control and inhibitory systems in children with Developmental Coordination Disorder: Goal-directed reaching

For children with Developmental Coordination Disorder (DCD), the real-time coupling between frontal executive function and online motor control has not been explored despite reported deficits in each domain. The aim of the present study was to investigate how children with DCD enlist online control under task constraints that compel the need for inhibitory control. A total of 129 school children were sampled from mainstream primary schools. Forty-two children who met research criteria for DCD were compared with 87 typically developing controls on a modified double-jump reaching task. Children within each skill group were divided into three age bands: younger (6–7 years), mid-aged (8–9), and older (10–12). Online control was compared between groups as a function of trial type (non-jump, jump, anti-jump). Overall, results showed that while movement times were similar between skill groups under simple task constraints (non-jump), on perturbation (or jump) trials the DCD group were significantly slower than controls and corrected trajectories later. Critically, the DCD group was further disadvantaged by anti-jump trials where inhibitory control was required; however, this effect reduced with age. While coupling online control and executive systems is not well developed in younger and mid-aged children, there is evidence of age-appropriate coupling in older children. Longitudinal data are needed to clarify this intriguing finding. The theoretical and applied implications of these results are discussed.