Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Belatacept for Maintenance Immunosuppression in Lung Transplantation

Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS). In the third year posttransplant, he developed hemolytic uremic syndrome (HUS) attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed

Early Cardiac Catheterization is Associated with Improved Survival in Comatose Survivors of Cardiac Arrest Without STEMI

AIM: To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent. METHODS: We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest. RESULTS: A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p=0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p=0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18-0.70, p=0.003). CONCLUSIONS: In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram

Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography.

OBJECTIVES: The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear. METHODS: A retrospective evaluation of a post-cardiac arrest registry was performed. RESULTS: The database consisted of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%). Overall survival was greater in those with STEMI compared with those without (55.1% vs. 41.3%; p = 0.001), whereas in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (54.7% vs. 57.9%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI (80.2% vs. 33.2%; p = 0.001). The majority of culprit vessels were occluded (STEMI, 92.7%; no STEMI, 69.2%; p \u3c 0.0001). An occluded culprit vessel was found in 74.3% of STEMI patients and in 22.9% of no STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93.3% vs. 78.7%; p \u3c 0.003). CONCLUSIONS: Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography

Measuring mental wellbeing among adolescents : a systematic review of instruments

Globally, promoting mental wellbeing among adolescents is of great public health and social significance. However, less is known about advances in measures of mental wellbeing, relevant for use in mental health interventions, which are age-appropriate and acceptable for use among adolescents. Comprehensive assessment includes multiple aspects of mental wellbeing, as well as positive indicators of feeling and functioning. This review used systematic review methods, guided by PRISMA, to identify and assess comprehensive instruments in terms of their content, conceptual relevance for youth, and responsiveness to change. Ryan and Deci’s framework for mental wellbeing, grounded in hedonic and eudaimonic perspectives, was applied to assess the preponderance of feeling and functioning items for each instrument. The review identified 11 instruments that fit specified inclusion criteria. Only four of the scales were developed for adolescents. Though the scales varied in their preponderance of items, all scales encompassed at least one indicator of both feeling and functioning. Findings emphasize the importance of validating adult-developed instruments for youth and ensuring the instrument’s cultural and conceptual relevance within groups of adolescents. As promoting mental wellbeing becomes critical to the field of practice, practitioners need access to relevant and acceptable measures