Treatment of obesity with intragastric injection of botulinum toxin. Is it worth the pinch? An overview of systematic reviews and meta-analysis.

BACKGROUND AND AIMS: Αvaialble evidence regarding the effectiveness of intragastric injection of botulinum toxin in reducing anthropometric indices of subjects with obesity is conflicting. We evaluated the existing evidence and perform a meta-analysis to assess the efficacy of intragastric botulinum toxin in treating obesity. METHODS: We identified published systematic reviews evaluating the efficacy of intragastric injection of botulinum toxin in patients with overweight or obesity and additionally performed a systematic literature search to retrieve randomized controlled trials on this topic. A random-effects meta-analysis was performed to synthesize the existing studies. RESULTS: A total of four systematic reviews were included in our overview of systematic reviews and six randomized controlled trials were included in our meta-analysis. Compared to placebo, intragastric injection of botulinum toxin was ineffective in reducing body weight and body mass index after the application of the Knapp-Hartung adjustment (MD = -2.41 kg, 95%CI = -5.21 to 0.38, I2 =59% and MD = -1.43 kg/m2, 95%CI = -3.04 to 0.18, I2 =62%, respectively). Moreover, treatment with intragastric injection with botulinum toxin was not superior to placebo in decreasing waist and hip circumference. CONCLUSIONS: Based on the available evidence, intragastric injection with botulinum toxin is an ineffective procedure in reducing body weight and body mass index when the Knapp-Hartung method was applied.

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure.

Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. Patients with PaO2/FiO2 < 100 mmHg were analysed. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n = 26) or SOC plus monotherapy with either IL-1-receptor antagonist anakinra (n = 19) or tocilizumab (n = 11). COMBI was significantly associated with lower in-hospital mortality and intubation rate, shorter duration of hospitalization, and prolonged overall survival after a median follow-up of 110 days. In vitro, COVID-19 plasma induced tissue factor/thrombin pathway in primary lung fibroblasts. This effect was inhibited by the immunomodulatory agents of COMBI providing a mechanistic explanation for the clinical observations. These results support the conduct of randomized trials using combined immunomodulation in COVID-19 to target multiple interconnected pathways of immunothrombosis.

Nutrition Interventions in Pediatric Pancreatitis: Guidelines We Can Trust.

OBJECTIVE: Despite the fact that pediatric pancreatitis is an uncommon disease, its prevalence has increased in recent years. Nevertheless, until 4 years ago, the lack of nutritional guidelines for pediatric pancreatitis was evident, with all recommendations being based on clinical practice guidelines (CPGs) for adults. The aim of the present study was to review and critically appraise guidelines for the medical nutrition therapy (MNT) of pediatric pancreatitis. METHODS: A comprehensive search was performed in electronic databases (PubMed, Scopus, National Institute for Health and Care Excellence), the International Guidelines Network, BMJ best practice, and the Scottish Intercollegiate Guidelines Network to identify CPGs on the MNT of pediatric pancreatitis. The validated AGREE II tool was used for guidelines appraisal by a team of 3 independent multidisciplinary reviewers. RESULTS: A total of 4 CPGs were retrieved with pediatric pancreatitis MNT information. Out of the 4 advising bodies in total, the joint society paper published by the ESPGHAN/NASPGHAN received the highest score in almost all domains, whereas the Belgian consensus obtained the lowest score in all domains but stakeholder involvement, and was not recommended by 2 out of 3 reviewers. CONCLUSIONS: Pediatric pancreatitis guidelines appear heterogenous in quality, rigour, and transparency. Our study points out existing gaps and biases in the CPGs, and delineates the need for improving the domains identified as being of low-quality.