Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

BACKGROUND Acute pancreatitis(AP) is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs. Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity. Polyethylene glycols(PEGs) are nonimmunogenic, non-toxic water-soluble polymers widely used in biological, chemical, clinical and pharmaceutical settings.AIM To evaluate the protective effect of a 35-k Da molecular weight PEG(PEG35) on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.METHODS Wistar rats were assigned at random to a control group, a cerulein–induced AP group and a PEG35 treatment group. AP was induced by five hourly intraperitoneal injections of cerulein(50 μg/kg/bw), while the control animals received saline solution. PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42 J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α(TNFα), staurosporine or cerulein. The severity of AP wasdetermined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42 J-treated cells. Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage.RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats. The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas. In contrast, pancreatic tissue m RNA expression of interleukin 10 was markedly increased. PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats. Furthermore, the activation of pro-inflammatory markers and inflammationinduced cell death in pancreatic acinar cells treated with TNFα, cerulein or staurosporine was significantly reduced by PEG35 treatment, in a dose-dependent manner.CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42 J-treated cells through the attenuation of the inflammatory response and associated cell death. PEG35 may be a valuable option in the management of AP.     

Sentinel lymph node biopsy with preoperative CT lymphography and intraoperative indocyanine green fluorescence imaging for N0 early tongue cancer: A long-term follow-up study

PurposeThis study evaluated the usefulness of sentinel lymph node (SLN) biopsy with preoperative computed tomographic lymphography (CTL) and intraoperative indocyanine green (ICG) fluorescence imaging for N0 early tongue cancer.MethodsTwenty-seven patients with N0 early oral tongue cancer underwent CTL with a 128-slice multi-detector row CT scanner to detect SLN on the day before resection of primary tumor and SLN biopsy under ICG fluorescence guidance. We identified the location and number of SLNs mapped by CTL and evaluated whether CTL-enhanced SLNs could be identified intraoperatively as ICG fluorescent lymph nodes. Prognosis was also evaluated.ResultsSLNs were detected by CTL in 26 of 27 patients (96.3%). The total and mean numbers of SLNs were 41 and 1.5, respectively. All SLNs enhanced by CTL could be identified intraoperatively as ICG fluorescent lymph nodes. Two SLNs were found under ICG fluorescent guidance in only one patient without SLN enhanced by CTL. Among the 27 patients, five (18.5%) had SLN with metastasis. Median follow-up was 76 months (range 44–82 months). During follow-up, three of 22 patients without SLN metastasis had occult cervical lymph node metastasis. The 5-year overall survival rate was 100%.ConclusionSLN biopsy with preoperative CTL and intraoperative ICG fluorescence imaging is a feasible and reliable procedure, without radioisotope tracers, for neck management in cases of early tongue cancer.     

Symptom improvement in dry eye subjects following intranasal tear neurostimulation: Results of two studies utilizing a controlled adverse environment

PurposeTo evaluate the safety and effectiveness of the intranasal tear neurostimulator (ITN) in improving dry eye symptoms assessed in a controlled adverse environment (CAE®).MethodsStudy 1: Multicenter, subject-masked, randomized-sequence, crossover design. Single intranasal (active) and extranasal (control) ITN administration during CAE exposure. Study 2: Single-arm, open-label design. Intranasal ITN administration ≥2 times/day for 45 days, CAE assessment at days 0 and 45. In both studies, upon CAE entry, and every 5 min thereafter, subjects assessed eye dryness score (visual analog scale, 0–100 mm; EDS-VAS), and ocular discomfort score (ODS; Ora Calibra™, 0–4), for ≈2 h. Study 1: when ODS was ≥3 at 2 consecutive timepoints, subjects applied ITN intranasally or extranasally for ≈3 min, and again when achieving the same ODS criteria in randomized sequence. Study 2: days 0 and 45, ITN was applied for ≈3 min employing the same ODS criteria as Study 1.ResultsStudy 1: Significantly greater pre- to post-application reductions in mean [SEM] EDS (−16.5 [1.7] vs −3.1 [1.7], P < 0.0001) and ODS (−0.93 [0.08] vs −0.34 [0.08], P < 0.0001; n = 143) with intranasal vs extranasal stimulation. Study 2: On day 0 (n = 52) and day 45 (n = 48), significant pre- to post-application reductions in mean [SEM] EDS (−15.9 [2.7] and −15.2 [2.4]; P < 0.0001), and ODS (−1.3 [0.2] and −1.3 [0.1]; P < 0.0001). Few device-related adverse events were reported, none serious.ConclusionsAcute symptom relief is significant with the ITN and remains undiminished after daily use.     

Ovarian cancer screening: Current status and future directions

Ovarian cancer is the third most common gynaecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease which carries significant mortality. Improvements in treatment have only resulted in modest increases in survival. This has driven efforts to reduce mortality through screening. Multimodal ovarian cancer screening using a longitudinal CA125 algorithm has resulted in diagnosis at an earlier stage, both in average and high risk women in two large UK trials. However, no randomised controlled trial has demonstrated a definitive mortality benefit. Extended follow up is underway in the largest trial to date, UKCTOCS, to explore the delayed reduction in mortality that was noted. Meanwhile, screening is not currently recommended in the general population Some countries offer surveillance of high risk women. Novel screening modalities and longitudinal biomarker algorithms offer potential improvements to future screening strategies as does the development of better risk stratification tools.     

急性心力衰竭代偿期患者早期康复活动方案的构建及应用效果

目的 构建急性心力衰竭代偿期患者四阶梯式早期康复活动方案并评价其效果,以期为急性心力衰竭代偿期患者开展早期康复活动提供参考。方法 成立早期康复活动研究团队、在文献检索及半结构化访谈后形成急性心力衰竭代偿期患者四阶梯式早期康复活动的初步方案,经过专家论证后形成最终方案。采用方便抽样法选择2017年4月—2019年6月在北京市某三级甲等医院CCU住院的急性心力衰竭代偿期患者200例为研究对象,试验组与对照组各100例,试验组采用四阶梯式早期康复活动方案,对照组采用常规活动方案。采用明尼苏达生活质量量表、6 min步行试验、住院时间、第1秒用力呼气量、脑利纳肽水平等作为监测指标。结果 试验组明尼苏达生活质量得分（52.64±5.60）分,低于对照组（56.89±6.59）分（t=-4.877,P< 0.001）;试验组6 min步行试验距离（279.86±84.66） m,优于对照组（248.78±93.73） m（t=2.441,P=0.016）;试验组CCU住院时间（8.97±2.80） d,少于对照组（10.48±3.80） d（t=-3.182,P=0.002）;试验组第1秒用力呼气量（2.18±0.49） L,高于对照组（1.92±0.35） L（t=4.338,P< 0.001）;试验组脑利纳肽水平（697.88±135.58） pg/ml,低于对照组（755.29±141.74） pg/ml（t=-2.905,P=0.004）。结论 四阶梯式早期康复活动方案根据患者的心功能制订了个体化的活动策略,通过团队管理的手段保障其早期活动的安全性,能够切实提高急性心力衰竭患者的生活质量、促进患者心肺功能的快速康复、缩短住院时间。     

Role of subcutaneous implantable loop recorder for the diagnosis of arrhythmias in Brugada syndrome: A United Kingdom single-center experience

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Optimisation of the organ donor and effects on transplanted organs: a narrative review on current practice and future directions

Mortality remains high for patients on the waiting list for organ transplantation. A marked imbalance between the number of available organs and recipients that need to be transplanted persists. Organs from deceased donors are often declined due to perceived and actual suboptimal quality. Adequate donor management offers an opportunity to reduce organ injury and maximise the number of organs than can be offered in order to respect the donor's altruistic gift. The cornerstones of management include: correction of hypovolaemia; maintenance of organ perfusion; prompt treatment of diabetes insipidus; corticosteroid therapy; and lung protective ventilation. The interventions used to deliver these goals are largely based on pathophysiological rationale or extrapolations from general critical care patients. There is currently insufficient high-quality evidence that has assessed whether any interventions in the donor after brain death may actually improve immediate post-transplant function and long-term graft survival or recipient survival after transplantation. Improvements in our understanding of the underlying mechanisms following brain death, in particular the role of immunological and metabolic changes in donors, offer promising future therapeutic opportunities to increase organ utilisation. Establishing a UK donor management research programme involves consideration of ethical, logistical and legal issues that will benefit transplanted patients while respecting the wishes of donors and their families.