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Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic patterns of predominant right colon ulcerations. It can lead to significant morbidity and frequent interruption of cancer treatment. Early recognition and prompt intervention are critical to improving patient outcomes.

Background In the United States, more than a third of patients are referred to specialists each year; however, most of these referrals do not lead to completed appointments. At the Grady Health System (GHS), our large safety net hospital system, the initial gastroenterology (GI) referral process suffered from multiple inefficiencies, creating barriers to care. We aimed to improve GI referrals with both a triage and a direct-to-endoscopy program to relieve systemic barriers to GI care at GHS especially around colorectal cancer screening. Methods Given wait times for GI services and employee dissatisfaction with navigating patients through the referral process, a GI smart order set was built using the Epic electronic medical record. The process took 8 months and included automated anesthesia screening as well as periprocedural guidance on blood thinners. We measured time from placement of referral for screening colonoscopy to scheduling of the screening colonoscopy to assess improvement in wait times for GI services. Key results In our pre-implementation survey, 60% of providers placed at least one urgent referral a month, and 55% of providers were either somewhat or very dissatisfied with the referral process. This led to the creation of multiple unofficial and only partially successful bypasses to expedite GI care. With the new GI smart order set, there was a 93% reduction over 12 months in the time from providers screening colonoscopy referral request to procedure scheduling from an average of 422 to 28 days. In addition, overall rates of colorectal cancer screening increased approximately 6% from 43.5 to 49% since the order set was implemented. Conclusions This novel outpatient GI referral smart order set addressed multiple barriers to care and created a novel triage mechanism as well as a direct-to-endoscopy referral stream. This model can be used to improve triaging and increase access to GI and other specialist services.

A large number of studies have reported that sensory gating disorders represented by P50 inhibition may be involved in the pathophysiological process of schizophrenia. However, few studies have explored the relationship between sensory gating disorders and cognitive dysfunction in patients with schizophrenia. This study aimed to explore sex differences in the relationship between cognitive and P50 deficits in patients with chronic schizophrenia, which has not been reported. A total of 183 chronic schizophrenia patients (128 males and 55 females) and 166 healthy controls (76 males and 90 females) participated in this study. The MATRICS Consensus Cognitive Battery (MCCB) was measured for cognitive function and P50 components for the sensory gating in all participants. The Positive and Negative Syndrome Scales (PANSS) was used to assess the psychopathological symptoms in patients. Female patients performed significantly better than male patients in several cognitive domains of MCCB (all p < 0.01). There were no significant differences in P50 components between male and female patients (all p > 0.05). Further analysis showed that in female patients, latency of S2 was negatively correlated with reasoning and problem-solving domain of MCCB (p < 0.05), and P50 ratio was negatively correlated with social cognition domain of MCCB (p < 0.05). In male patients, there was no any correlation between P50 and cognitive domains of MCCB. Our results suggest that there is a sex difference in the association between P50 deficiency and cognitive impairment in Chinese Han patients with schizophrenia.

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease. Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

Background As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs. Methods We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology. Results Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28–1.50; absolute risk difference: 5% [95% CI: 4–6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty). Conclusions There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care. Systematic review registration PROSPERO CRD42020201256 (Sept 2, 2020).