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.     

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.     

大数据时代的药品安全主动监测:对照选择的挑战与机遇

电子医疗数据已成为大数据时代开展药品安全主动监测的重要资源。基于此确认药品与不良事件是否存在关联，要回归传统的流行病学研究设计，选取恰当的对照进行对比。本文主要阐述不同对照选取的原理、适用情形，介绍、评价并比较各种对照选取的思路与参数，引入对照选择批量化实现的进展性成果，以期为我国利用电子医疗数据开展上市后药品安全性监测提供方法学参考。     

Pharmacokinetics, metabolism and renal excretion of sulfatroxazole and its 5-hydroxy- and N4-acetyl-metabolites in man

Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes.     

Piracetam and fipexide prevent PTZ-kindling-provoked amnesia in rats

Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the nootropic drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in piracetam- and fipexide-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of the two drugs are considered. The favourable effects of nootropic drugs in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.     

Transitional properties of the mechanically evoked perioral reflex from infancy through adulthood

The organization of motor responses in the orbicularis oris muscle following the delivery of punctate mechanical inputs to vermilion skin of the lips was studied in a group of young infants, school-age children, and adults during periods of voluntary lip muscle activation. A specially designed multi-point array skin contactor, coupled to a position-servo controlled linear motor, was highly effective in driving the early component of the perioral reflex (R1). Overall, the evoked R1 response obtained from the infant was of variable amplitude relative to the children and adults, lacked response specificity, and occurred it a longer latency. This brainstem mediated sensorimotor action appears to take on several characteristics of the adult form by the age of 12. The emergence and maturation of mechanically evoked perioral reflexes is discussed in relation to the acquisition of motor skills, including speech and smiling.     

Acoustic rhinometry in nasal provocation test in perennial allergic rhinitis

Acoustic rhinometry is one method to evaluate nasal geometry by an acoustic reflection technique. The aim of this study was to investigate the changes in acoustic rhinometry after nasal provocation in patients with exclusively perennial allergic rhinitis. In 19 patients, acoustic rhinometry and active anterior rhinomanometry were performed before and after nasal provocation test. There was a statistically significant nasal flow reduction measured by active anterior rhinomanometry after nasal provocation (p < 0.05) and a median symptom score of four points, both indicating a positive response to nasal provocation. On the other hand, there was no statistically significant change in the values of acoustic rhinometry after nasal provocation (p > 0.05). In patients with exclusively perennial allergic rhinitis, acoustic rhinometry does not seem to significantly change after nasal provocation. In contrast, active anterior rhinomanometry values decreased significantly after nasal provocation. The presented results indicate that acoustic rhinometry does not seem to be a diagnostic method superior to active anterior rhinomanometry in this context.     

A review of the effect of pesticide formulations on male fertility

Experimental studies suggest that large numbers of chemicals, environmental and industrial pollutants affect the male reproductive system. At present, almost no information is available on the effects of these adverse agents on human reproduction. Recent reports, however, suggest that in the past 50 years male fertility has declined based on qualitative and quantitative measurements of normal sperm. This study identifies‐among the active ingredients and solvents included in pesticide formulations registered in Italy‐the chemical agents with experimental evidence of male reproductive toxicity. Documents produced by international agencies and organizations such as IARC, EPA, WHO, and original papers from the international literature were systematically reviewed. The results indicate that several pesticide products notified in the Italian Registry contain active ingredients and/or solvents severely affecting testicular function and sperm morphology in laboratory animals. Therefore, exposure to reproductive toxicants occurring among manufacturers and users of pesticide formulations registered in Italy suggest further epidemiologic surveys should be conducted in this area.