Standardizing Postoperative Complications—Validating the Clavien-Dindo Complications Classification in Cardiac Surgery

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A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer

Background MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.Methods This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).Results A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.Conclusion Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC.ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03332498","term_id":"NCT03332498"}}NCT03332498.Subject terms: Cancer immunotherapy, Colorectal cancer     

The clinicopathologic spectrum of segmental membranous glomerulopathy

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Bi-allelic pathogenic variations in DNAJB11 cause Ivemark II syndrome,a renal-hepatic-pancreatic dysplasia

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Review of Over 15 Years Postmarketing Safety Surveillance Spontaneous Data for the Human Rotavirus Vaccine (Rotarix) on Intussusception

Introduction

Rotavirus (RV) is the most common cause of acute gastroenteritis in children <5 years of age worldwide, and vaccination reduces the disease burden. Evidence from postmarketing surveillance studies suggested an increased risk of intussusception (IS) in infants post-RV vaccination. An overall positive benefit–risk balance for the human RV vaccine (HRV) Rotarix (GlaxoSmithKline [GSK], Belgium) has been established and recent findings indicate an indirect effect of reduced IS over the long term.

Objective

The aim of this study was to discuss spontaneous data from the GSK worldwide safety database on IS post-Rotarix administration.

Methods

The database was reviewed for all spontaneous IS cases from 2004 to 2020. Additionally, an observed versus expected (O/E) analysis was done for adverse events attributed to IS. Data were reviewed as overall worldwide and stratified by region (Europe/USA/Japan) and dose.

Results

A male predominance of IS patients was observed, consistent with earlier reports. The most frequently reported events in confirmed IS cases (Brighton Collaboration Working Group [BCWG] level 1) with time to onset ≤ 30 days post-vaccination were vomiting (55.8%), haematochezia (47.2%), and crying (21.1%). The observations from the IS spontaneous cases review and results of the O/E analysis are consistent with the known IS safety profile of RV vaccines: a transient increased incidence of IS post-vaccination (primarily in Europe/Japan/worldwide), mostly within 7 days postdose 1.

Conclusion

Since the outcomes of early IS management are favourable over delayed management, healthcare professionals should inform parents about the importance of seeking immediate medical advice in case of unusual behaviour of the vaccinated infant. GSK continues to monitor the IS risk post-Rotarix administration through routine pharmacovigilance activities.

Graphic abstract

     

Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear cells: protective effects of curcumin and α-tocopherol

The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0–21?μg/ml) for 6, 12, and 24?h, and in combination with curcumin (9.2?μg/ml) or α-tocopherol (4.3?μg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p?相似文献