The effect of shortening vasoactive drug durations alongside endoscopic therapy in esophageal variceal bleeding: an updated systematic review and meta-analysis.

Background: The recommended duration of vasoactive drugs in esophageal variceal bleeding (EVB) spans 2-5 days. Prior meta-analyses of randomized trials include only a few studies that compared short vs. long vasoactive drug durations approximating this time range, including older management techniques, and only assessed variceal rebleeding at 5 days. We identified several additional randomized controlled trials (RCTs) assessing rebleeding at various durations, with updated management of EVB. Methods: We performed an updated systematic review and meta-analysis assessing the effect of shortening the vasoactive drug duration by 48-72 h. The primary outcome was rebleeding within 5 days. Secondary outcomes included rebleeding, mortality due to rebleeding, and all-cause mortality within 4-6 weeks (extended period) with subgroup analysis by vasoactive drug and type of endoscopic therapy. Length of stay, blood transfusion requirements and terlipressin-related adverse events were additional secondary outcomes. Results: Our comprehensive search strategy and screening process yielded 14 RCTs with 1060 patients (75.1% male): 7 trials used terlipressin, 4 octreotide, and 3 somatostatin. Shortened durations combined with band ligation led to similar rebleeding, with a trend towards less rebleeding when populations with more severe liver disease were excluded. There was greater rebleeding and mortality over an extended period when shorter durations were combined with sclerotherapy. Longer durations were associated with a longer hospital stay and, for terlipressin, more adverse events. Conclusions: Shorter vasoactive drug durations combined with band ligation in selected populations appear safe. Higher powered RCTs are needed, involving patients with different degrees of severity of EVB and liver disease.

Demographics and Outcomes of Extracorporeal Membrane Oxygenation in COVID-19 Patients: National Database Analysis.

INTRODUCTION: The effectiveness of extracorporeal membrane oxygenation (ECMO) in treating COVID-19 patients has been variable. To gain a better insight, we examined the outcomes of ECMO in COVID-19 patients using data from the 2020 National Inpatient Sample database. METHODS: We analyzed data from adult hospital admissions where COVID-19 was the primary diagnosis. The primary outcome was all-cause inpatient mortality. Secondary outcomes were length of stay (LOS), cost, and discharge disposition. RESULTS: We identified 1,048,025 COVID-19 admissions, of which 98,528 were on mechanical ventilation (MV), and only 1.8% received ECMO. In-hospital mortality of mechanically ventilated patients who received ECMO was 49%, compared to 59% with no ECMO (p < 0.001). ECMO treatment was associated with a reduced risk of mortality (HR = 0.67, p < 0.0001, CI 0.57-0.79) even after adjustment for confounders and other comorbidities. Patients on ECMO had significantly extended hospital stays and were more likely to be discharged to an acute care facility. Younger and male patients were more likely to receive ECMO treatment. Females had a lower mortality risk, while race and obesity were not associated with an increased risk of death. CONCLUSION: ECMO treatment may offer survival benefits in severe COVID-19. Based on our findings, we suggest early ECMO treatment for patients with a high mortality risk.

Integration of a personalised mobile health (mHealth) application into the care of patients with brain tumours: proof-of-concept study (IDEAL stage 1).

Objectives: Brain tumours lead to significant morbidity including a neurocognitive, physical and psychological burden of disease. The extent to which they impact the multiple domains of health is difficult to capture leading to a significant degree of unmet needs. Mobile health tools such as Vinehealth have the potential to identify and address these needs through real-world data generation and delivery of personalised educational material and therapies. We aimed to establish the feasibility of Vinehealth integration into brain tumour care, its ability to collect real-world and (electronic) patient-recorded outcome (ePRO) data, and subjective improvement in care. Design: A mixed-methodology IDEAL stage 1 study. Setting: A single tertiary care centre. Participants: Six patients consented and four downloaded and engaged with the mHealth application throughout the 12 weeks of the study. Main outcome measures: Over a 12-week period, we collected real-world and ePRO data via Vinehealth. We assessed qualitative feedback from mixed-methodology surveys and semistructured interviews at recruitment and after 2 weeks. Results: 565 data points were captured including, but not limited to: symptoms, activity, well-being and medication. EORTC QLQ-BN20 and EQ-5D-5L completion rates (54% and 46%) were impacted by technical issues; 100% completion rates were seen when ePROs were received. More brain cancer tumour-specific content was requested. All participants recommended the application and felt it improved care. Conclusions: Our findings indicate value in an application to holistically support patients living with brain cancer tumours and established the feasibility and safety of further studies to more rigorously assess this.

Bootleg Biology: a Semester-Long CURE Using Wild Yeast to Brew Beer.

Laboratory exercises for undergraduates that involve authentic discovery and research have been shown to increase student learning and engagement. To bring these advantages into the microbiology curriculum, we developed a semester-long course-based undergraduate research experience for a laboratory based on brewing beer with wild yeast. This set of lab exercises uses many of the same protocols found in traditional microbiology lab curricula-isolating and maintaining pure cultures, staining and microscopy, use of aseptic technique, PCR, gel electrophoresis, and media preparation-and integrates them into a novel and exciting project that enables students to be active participants in the scientific method. Students are assessed on their ability to brew beer successfully and to stain and visualize microorganisms; they are also assessed for knowledge gains in the traditional portion of the course, their ability to use their brewing knowledge in other settings, and their attitudes about science. After completing the course, students showed gains in general microbiology knowledge and their engagement with science.

Natural killer cells: a review of biology, therapeutic potential and challenges in treatment of solid tumors.

Natural killer (NK) cells lead immune surveillance against cancer and early elimination of small tumors. Owing to their ability to engage tumor targets without the need of specific antigen, the therapeutic potential of NK cells has been extensively explored in hematological malignancies. In solid tumors, however, their role in the clinical arena remains poorly exploited despite a broad accumulation of preclinical data. In this article, we review our current knowledge of NK cells' biology, and highlight the challenges facing NK cell antitumor strategies in solid tumors. We further summarize the abundant preclinical attempts at overcoming these challenges, present past and ongoing clinical trial data and finally discuss the potential impact of novel insights on the development of NK cell-based therapies.

IgG4-related hypophysitis presenting as diabetes insipidus with tubulo-interstital nephritis and mediastinal lymphadenopathy.

UNLABELLED: IgG4-related disease (IgG4-RD) is a rare but increasingly recognised condition, emerging as a clinical entity following the observation of the associations of autoimmune pancreatitis. IgG4-RD is characterised by extensive infiltration of IgG4-positive plasma cells into multiple organs and raised serum IgG4 levels. Clinical manifestations of IgG4 disease classically include autoimmune pancreatitis, lacrimal or salivary gland infiltration (formerly known as Mikulicz disease) and retroperitoneal fibrosis. More rarely, IgG4 disease can cause pituitary hypophysitis. Although most frequently described in middle-aged males, the epidemiology and pathogenesis of the disease remain largely undefined. Nevertheless, an understanding of the wide variety of clinical manifestations of this multi-system condition is undeniably important given the often excellent outcomes following treatment. We describe an unusual presentation of IgG4 disease with isolated diabetes insipidus secondary to pituitary hypophysitis. The patient in question subsequently developed chest pain secondary to mediastinal lymphadenopathy and tubulo-interstitial nephritis leading to renal dysfunction. He was successfully treated with oral steroids and had regular follow-up, and remains well at follow-up 2 years later. LEARNING POINTS: IgG4 disease, although rare, is increasing in prevalence largely due to increased recognition of its clinical manifestations, including autoimmune pancreatitis, lacrimal or salivary gland infiltration, retroperitoneal fibrosis and, more rarely, lymphocytic hypophysitis presenting as diabetes insipidus.IgG4 disease is highly treatable, and symptoms may show complete resolution with administration of steroids, highlighting the importance of correct and timely diagnosis.Causes of lymphocytic hypophysitis are varied and not distinguishable radiologically. Given the difficulty in biopsying the pituitary, careful attention must be paid to the systemic clinical presentation to provide clues as to the underlying disorder.