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.     

Living with the financial consequences of cancer: A life course perspective

Abstract

Purpose

Financial hardship can be a major cause of distress among persons with cancer, resulting in chronic stress and impacting physical and emotional health. This paper provides an analysis of the lived experience of cancer patients’ financial hardship from diagnosis to post-treatment.     

RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma

IntroductionSelective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.Patients and MethodsPatients with RCC, unsuitable for, or who declined conventional therapy, were eligible. A single transfemoral micro-catheter administration of yttrium-90 (Y-90) resin microspheres (SIR-Spheres) was delivered super selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of “imminent stasis,” in a dose-escalation design. Post-SIRT follow-up was 12 months. Study endpoints included safety and toxicity 30-days and 12-months post-SIRT and tumour response (RECIST v1.1).ResultsIn total, 21 patients were enrolled, mean (SD) age was 75 (9.3) years, WHO performance status was 0 in 81%, 12 (57%) had stage 3 chronic kidney disease, and 7 (33%) had prior contralateral nephrectomy. Overall, 71% of patients completed 12 months of follow-up. Intended doses were delivered without any dose-limiting toxicity. Seventeen out of 21 (81%) patients experienced an adverse event (AE) from any cause within 30 days post-SIRT; all SIRT-related AEs were grade 1 to 2. Best overall tumour responses were partial response 1/21 (4.8%), stable disease 19/21 (90.5%) and progressive disease 1/21 (4.8%).ConclusionThis study demonstrated good tolerability of SIRT at all dose levels including “imminent stasis” in treating primary tumours in RCC patients otherwise unsuitable for conventional therapy. SIRT with Y-90 resin microspheres may be a feasible treatment option for RCC.     

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.     

Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon decemmaculatus

Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon decemmaculatus is a widely distributed, endemic fish from Neotropical America. It attains high densities in the shallow water assemblages of Argentina and Brazil. The aim of this study was to assess the acute toxicity of chlorpyrifos to C. decemmaculatus. The mean 96-h LC₅₀ of three independent determinations was 105.3 (±?3.1) μg/L. Sublethal effects were observed. Swimming behavioral changes at each chlorpyrifos exposure concentration were reported. C. decemmaculatus represents a good model for ecotoxicological risk assessment.     

Evaluation of neurobehavioral abnormalities and immunotoxicity in response to oral imidacloprid exposure in domestic chickens (Gallus gallus domesticus)

ABSTRACT

Domestic chickens (Gallus gallus domesticus) were exposed to imidacloprid by gavage once daily for 7 consecutive days at 0, 0.03, 0.34, 3.42, 10.25, and 15.5 mg/kg/day (n = 20 per group; 5 6-week-old males, 5 6-week-old females, 5 9-week-old males, and 5 9-week-old females). The severity and duration of neurobehavioral abnormalities were recorded. Components of the innate and adaptive immune system were assessed with 7 standard functional assays. Temporary neurobehavioral abnormalities were observed in a dose-dependent manner, including muscle tremors, ataxia, and depressed mentation. Based upon mean clinical severity scores, the no observed adverse effect level (NOAEL) was 3.42 mg/kg/day, and the lowest observed adverse effect level (LOAEL) was 10.25 mg/kg/day. The effective dose value for the presence of any neurobehavioral abnormalities in 50% of the test group (ED₅₀) was 4.62 ± 0.98 mg/kg/day. The ED₅₀ for an adjusted score that included both severity and duration of neurobehavioral abnormalities was 11.24 ± 9.33 mg/kg/day. These ED₅₀ values are equivalent to a 1 kg bird ingesting 29 or 70 imidacloprid treated soybean seeds respectively. Immunotoxicity was not documented, possible causes include the assays were insensitive, relevant immune functions were not examined, or imidacloprid is not immunotoxic at this dosing schedule in this species. Neurobehavioral abnormalities were a more sensitive indicator of the sublethal effects of imidacloprid than immunotoxicity.     

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。