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.     

Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Protective activities of ellagic acid and urolithins against kidney toxicity of environmental pollutants: A review

Oxidative stress and inflammation are two possible mechanisms related to nephrotoxicity caused by environmental pollutants. Ellagic acid, a powerful antioxidant phytochemical, may have great relevance in mitigating pollutant-induced nephrotoxicity and preventing the progression of kidney disease. This review discusses the latest findings on the protective effects of ellagic acid, its metabolic derivatives, the urolithins, against kidney toxicity caused by heavy metals, pesticides, mycotoxins, and organic air pollutants. We describe the chelating, antioxidant, anti-inflammatory, antifibrotic, antiautophagic, and antiapoptotic properties of ellagic acid to attenuate nephrotoxicity. Furthermore, we present the molecular targets and signaling pathways that are regulated by these antioxidants, and suggest some others that should be explored. Nevertheless, the number of reports is still limited to establish the efficacy of ellagic acid against kidney damage induced by environmental pollutants. Therefore, additional preclinical studies on this topic are required, as well as the development of well-designed clinical trials.     

Effect of Electroacupuncture on Spermatogenesis in Rats with Oligozoospermia of Insufficiency of Shen (Kidney) Essence Syndrome

Objective: To assess the effect of electroacupuncture(EA) on expression of cytoskeletal proteins from Sertoli cells(SCs) and spermatogenesis in rats with oligozoospermia of insufficiency of Shen(Kidney)essence syndrome(OIKES).Methods: Twenty healthy male Sprague-Dawley rats were randomly assigned to four groups using a random number table: control,tripterygium glycosides(TG) treatment,sham and EA groups(n=5 in each group).A rat model of OIKES was established by oral gavage with TG.The EA group was treated with TG and received EA at Shenshu(BL 23) and Zusanli(ST 36) acupoints for 20 min,once daily for 30 days,while the sham group received EA at identical acupoints with skin penetration without stimulation.After 30 days,the ?nal body weight and coef?cients for the testis and epididymis were calculated and sperm parameters were measured.Immunohistochemical analyses were performed to detect expression of vimentin and α-tubulin in SCs and proliferating cell nuclear antigen(PCNA) immunoreactivity in germ cells.Apoptosis in germ cells was quanti?ed by the transferase biotin-dUTP nick end labeling assay.Results: Compared with the control group,the final body weight and testis/epididymis coefficients of rats in the TG-treated group were not significantly different,but the sperm count and motility were lower(P0.05).Expressions of vimentin and α-tubulin were also signi?cantly weaker(P0.01).The PCNA immunoreactivity of germ cells was decreased(P=0.059),whereas the apoptotic index of germ cells was increased signi?cantly(P0.01).In contrast,EA at BL 23 and ST 36 acupoints signi?cantly improved the ?nal body weight as well as the sperm count,concentration and motility(P0.01 or P0.05).EA increased expression of vimentin and α-tubulin in SCs markedly,and signi?cantly enhanced PCNA immunoreactivity with decreased apoptosis in germ cells(P0.01 or P0.05).Conclusions: EA at BL 23 and ST 36 acupoints has protective effects on spermatogenesis in rats with OIKES.This effect seems to be achieved by attenuating TG-induced disruption of cytoskeletal protein in SCs.     

补肾纳气法治疗小儿支气管哮喘的临床分析

目的：探讨分析补肾纳气法治疗小儿支气管哮喘的临床效果。方法方便选取该院儿科于2013年3月—2014年11月收治的小儿支气管哮喘患者67例，根据随机数字法分为对照组33例和观察组34例，对照组患者予以氨茶碱片治疗，观察组患者实施补肾纳气法治疗，观察两组患者的治疗效果，进行临床对照性分析。结果对照组患者不良反应发生率24.2%，观察组患者不良反应发生率5.8%，观察组不良反应发生率明显低于对照组(P﹤0.05)；对照组患者总有效率60.6%，观察组患者总有效率85.3%。观察组患者治疗后总有效率明显高于对照组(P﹤0.05)。结论补肾纳气法治疗小儿支气管哮喘的临床效果好，应用价值高，值得在临床实践中推广应用。     

Polio infrastructure strengthened disease outbreak preparedness and response in the WHO African Region

IntroductionThe continuous deployments of polio resources, infrastructures and systems for responding to other disease outbreaks in many African countries has led to a number of lessons considered as best practice that need to be documented for strengthening preparedness and response activities in future outbreaks.MethodsWe reviewed and documented the influence of polio best practices in outbreak preparedness and response in Angola, Nigeria and Ethiopia. Data from relevant programmes of the WHO African Region were also analyzed to demonstrate clearly the relative contributions of PEI resources and infrastructure to effective disease outbreak preparedness and response.ResultsPolio resources including, human, financial, and logistic, tool and strategies have tremendously contributed to responding to diseases outbreaks across the African region. In Angola, Nigeria and Ethiopia, many disease epidemics including Marburg Hemorrhagic fever, Dengue fever, Ebola Virus Diseases (EVD), Measles, Anthrax and Shigella have been controlled using existing polio Eradication Initiatives resources. Polio staffs are usually deployed in occasions to supports outbreak response activities (coordination, surveillance, contact tracing, case investigation, finance, data management, etc.). Polio logistics such vehicles, laboratories were also used in the response activities to other infectious diseases. Many polio tools including micro planning, dashboard, guidelines, SOPs on preparedness and response have also benefited to other epidemic-prone diseases. The Countries’ preparedness and response plan to WPV importation as well as the Polio Emergency Operation Center models were successfully used to develop, strengthen and respond to many other diseases outbreak with the implication of partners and the strong leadership and ownership of governments. This review has important implications for WHO/AFRO initiative to strengthening and improving disease outbreak preparedness and responses in the African Region in respect to the international health regulations core capacities.