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Background and study aims There is a consensus among gastroenterology organizations that elective endoscopic procedures should be deferred during the COVID-19 pandemic. While the decision to perform urgent procedures and to defer entirely elective procedures is mostly evident, there is a wide “middle ground” of time-sensitive but not technically urgent or emergent endoscopic interventions. We aimed to survey gastroenterologists worldwide using Twitter to help elucidate these definitions using commonly encountered clinical scenarios during the COVID-19 pandemic. Methods A 16-question survey was designed by the authors to include common clinical scenarios that do not have clear guidelines regarding the timing or urgency of endoscopic evaluation. This survey was posted on Twitter. The survey remained open to polling for 48 hours. During this time, multiple gastroenterologists and fellows with prominent social media presence were tagged to disseminate the survey. Results The initial tweet had 38,795 impressions with a total of 2855 engagements. There was significant variation in responses from gastroenterologists regarding timing of endoscopy in these semi-urgent scenarios. There were only three of 16 scenarios for which more than 70 % of gastroenterologists agreed on procedure-timing. For example, significant variation was noted in regard to timing of upper endoscopy in patients with melena, with 44.5 % of respondents believing that everyone with melena should undergo endoscopic evaluation at this time. Similarly, about 35 % of respondents thought that endoscopic retrograde cholangiopancreatography should only be performed in patients with choledocholithiasis with abdominal pain or jaundice. Conclusion Our analysis shows that there is currently lack of consensus among gastroenterologists in regards to timing of semi-urgent or non-life-threatening procedures during the COVID-19 pandemic. These results support the need for the ongoing development of societal guidance for these “semi-urgent” scenarios to help gastroenterologists in making difficult triage decisions.

Gastrointestinal (GI) melanomas are a rare diagnostic entity. Although there have been cases of melanomas solely in the GI tract, many debate their true origin: the gut versus a distant, undetected primary lesion that regressed known as melanoma of unknown primary. We present a case that involved diagnosing a GI melanoma and then backtracking to find a possible primary source. We review the most recent literature regarding possible etiologies of primary GI melanomas and how to differentiate whether it has a primary, metastatic, or unknown origin.

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TAFRO syndrome is a rare constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction, and organomegaly. Its pathogenesis involves an excessive and inappropriate cytokine storm, most notably from IL-6, causing multiorgan failure; however, its etiology is undetermined. Starting in 2012, TAFRO syndrome was first identified in Japan as an atypical variant of Castleman's disease. Previous reports include various different treatment protocols with inconsistent survival outcomes. Here we report the first known American, EBV positive but HIV and HHV-8 negative, male with TAFRO syndrome. He was successfully treated with an unusual three-drug regimen including tocilizumab, etoposide, and rituximab. We review the literature of TAFRO syndrome, discuss its possible viral etiology, and propose an original treatment regimen.

Background and study aims Little is known about outcomes of advanced endoscopic resection (ER) for patients with inflammatory bowel disease (IBD) with dysplasia. The aim of our meta-analysis was to estimate the safety and efficacy of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for dysplastic lesions in patients with IBD. Methods We performed a systematic review through Jan 2021 to identify studies of IBD with dysplasia that was treated by EMR or ESD. We estimated the pooled rates of complete ER, adverse events, post-ER surgery, and recurrence. Proportions were pooled by random effect models. Results Eleven studies including 506 patients and 610 lesions were included. Mean lesion size was 23 mm. The pooled rate of complete ER was 97.9 % (95 % confidence interval [CI]: 95.3 % to 99.7 %). The pooled rate of endoscopic perforation was 0.8 % (95 % CI:0.1 % to 2.2 %) while bleeding occurred in 1.6 % of patients (95 %CI:0.4 % to 3.3 %). Overall, 6.6 % of patients (95 %CI:3.6 % to 10.2 %) underwent surgery after an ER. Among 471 patients who underwent surveillance, local recurrence occurred in 4.9 % patients (95 % CI:1.0 % to 10.7 %) and metachronous lesions occurred in 7.4 % patients (95 %CI:1.5 % to 16 %) over a median follow-up of 33 months. Metachronous colorectal cancer (CRC) was detected in 0.2 % of patients (95 %CI:0 % to 2.2 %) during the surveillance period. Conclusions Advanced ER is safe and effective in the management of large dysplastic lesions in IBD and warrants consideration as first-line therapy. Although the risk of developing CRC after ER is low, meticulous endoscopic surveillance is crucial to monitor for local or metachronous recurrence of dysplasia.

Reactive oxygen species (ROS) are generated in the vascular wall upon stimulation by pro-inflammatory cytokines and are important mediators of diverse cellular responses that occur as a result of vascular injury. Member of the NADPH oxidase (NOX) family of proteins have been identified in vascular smooth muscle cells (VSM) as important sources of ROS. In this study, we tested the hypothesis that NOX4 is a proximal mediator of IL-1β-dependent activation of PKCδ and increases IL-1β stimulated c-Jun kinase (JNK) signaling in primary rat aortic VSM cells. We found that stimulation of VSM cells with IL-1β increased PKCδ activity and intracellular ROS generation. SiRNA silencing of NOX4 but not NOX1 ablated the IL-1β-dependent increase in ROS production. Pharmacological inhibition of PKCδ activity as well as siRNA depletion of PKCδ or NOX4 blocked the IL-1β-dependent activation of JNK. Further studies showed that the IL-1β-dependent upregulation of iNOS expression was inhibited through JNK inhibition and NOX4 silencing. Taken together, these results indicate that IL-1β-dependent activation of PKCδ is modulated by NOX4-derived ROS. Our study positions PKCδ as an important redox sensitive mediator of IL-1β-dependent signaling and downstream activation of inflammatory mediators in VSM cells.