CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.

CARM1 (coactivator associated arginine methyltransferase 1) has recently emerged as a powerful regulator of skeletal muscle biology. However, the molecular mechanisms by which the methyltransferase remodels muscle remain to be fully understood. In this study, carm1 skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253). In addition to lower mitophagy and autophagy flux in skeletal muscle, carm1 mKO led to increased mitochondrial PRKN/parkin accumulation, which suggests that CARM1 is required for basal mitochondrial turnover and autophagic clearance. carm1 deletion also elicited PPARGC1A (PPARG coactivator 1 alpha) activity and a slower, more oxidative muscle phenotype. As such, these carm1 mKO-evoked adaptations disrupted mitophagy and autophagy induction during food deprivation and collectively served to mitigate fasting-induced muscle atrophy. Furthermore, at the threshold of muscle atrophy during food deprivation experiments in humans, skeletal muscle CARM1 activity decreased similarly to our observations in mice, and was accompanied by site-specific activation of ULK1 (Ser757), highlighting the translational impact of the methyltransferase in human skeletal muscle. Taken together, our results indicate that CARM1 governs mitophagic, autophagic, and atrophic processes fundamental to the maintenance and remodeling of muscle mass. Targeting the enzyme may provide new therapeutic approaches for mitigating skeletal muscle atrophy.

A Review of COVID-19's Impact on Radiology Residents' Academics and Wellness in North America.

BACKGROUND: The COVID-19 pandemic caused major disruptions in radiology departments throughout North America. Radiology residency programs were forced to make dramatic changes to their training programs, which had major impacts on resident academics and wellness. The goal of this review is to evaluate the impact of COVID-19 on radiology residents' academics and wellness in North America, while also identifying effective measures taken by programs to mitigate the effects of the pandemic. METHODS: The search strategy involved database search via PubMed, Embase, and Web of Science with specific key words related to COVID-19, radiology residents, education, wellness, and virtual learning. Studies discussing the education and wellness of radiology residents in North America published after 2020 were included. The data were analyzed using a narrative synthesis approach. RESULTS: The three main domains affected by the pandemic include the residency curriculum, research, and resident wellness. The decline in case volume and diversity of cases had negative overall impact on education of radiology residents, but simulated cases and virtual learning proved its value during the pandemic and may have lasting implications for the postpandemic world. Research initiatives transitioned to a remote format with greater emphasis on quality improvement and COVID-19-related studies. Reduced face-to-face interaction opportunities made it difficult to establish strong and meaningful interpersonal connections and had a negative impact on resident wellness, mentorship, and professional development. Implementing mentorship programs and virtual "town hall meetings" were effective measures to maintain connections during times of social distancing. Finally, the COVID-19 pandemic introduced unprecedented stressors and challenges for radiology residents that negatively impacted their mental health and wellness. Incorporating wellness initiatives such as wellness hours and team-building activities and using social media were helpful in promoting wellness and mental health for radiology residents. CONCLUSION: The COVID-19 pandemic has had a significant impact on the academics and wellness of radiology residents across North America but has taught us many lessons that can help us navigate the ongoing challenges of the pandemic, the postpandemic world, and future pandemics.

Role of artificial intelligence and machine learning in the diagnosis of cerebrovascular disease.

Introduction: Cerebrovascular diseases are known to cause significant morbidity and mortality to the general population. In patients with cerebrovascular disease, prompt clinical evaluation and radiographic interpretation are both essential in optimizing clinical management and in triaging patients for critical and potentially life-saving neurosurgical interventions. With recent advancements in the domains of artificial intelligence (AI) and machine learning (ML), many AI and ML algorithms have been developed to further optimize the diagnosis and subsequent management of cerebrovascular disease. Despite such advances, further studies are needed to substantively evaluate both the diagnostic accuracy and feasibility of these techniques for their application in clinical practice. This review aims to analyze the current use of AI and MI algorithms in the diagnosis of, and clinical decision making for cerebrovascular disease, and to discuss both the feasibility and future applications of utilizing such algorithms. Methods: We review the use of AI and ML algorithms to assist clinicians in the diagnosis and management of ischemic stroke, hemorrhagic stroke, intracranial aneurysms, and arteriovenous malformations (AVMs). After identifying the most widely used algorithms, we provide a detailed analysis of the accuracy and effectiveness of these algorithms in practice. Results: The incorporation of AI and ML algorithms for cerebrovascular patients has demonstrated improvements in time to detection of intracranial pathologies such as intracerebral hemorrhage (ICH) and infarcts. For ischemic and hemorrhagic strokes, commercial AI software platforms such as RapidAI and Viz.AI have bene implemented into routine clinical practice at many stroke centers to expedite the detection of infarcts and ICH, respectively. Such algorithms and neural networks have also been analyzed for use in prognostication for such cerebrovascular pathologies. These include predicting outcomes for ischemic stroke patients, hematoma expansion, risk of aneurysm rupture, bleeding of AVMs, and in predicting outcomes following interventions such as risk of occlusion for various endovascular devices. Preliminary analyses have yielded promising sensitivities when AI and ML are used in concert with imaging modalities and a multidisciplinary team of health care providers. Conclusion: The implementation of AI and ML algorithms to supplement clinical practice has conferred a high degree of accuracy, efficiency, and expedited detection in the clinical and radiographic evaluation and management of ischemic and hemorrhagic strokes, AVMs, and aneurysms. Such algorithms have been explored for further purposes of prognostication for these conditions, with promising preliminary results. Further studies should evaluate the longitudinal implementation of such techniques into hospital networks and residency programs to supplement clinical practice, and the extent to which these techniques improve patient care and clinical outcomes in the long-term.

In-Hospital Amantadine Does Not Improve Outcomes After Severe Traumatic Brain Injury: An 11-Year Propensity-Matched Retrospective Analysis.

BACKGROUND: Disruption of dopamine neurotransmission is associated with functional impairment after severe traumatic brain injury (sTBI). This has prompted the study of dopamine agonists, such as amantadine, to assist recovery of consciousness. Randomized trials have mostly addressed the posthospital setting, with inconsistent findings. Therefore, we evaluated the efficacy of early amantadine administration on recovery of consciousness after sTBI. METHODS: We searched the medical records of all patients with sTBI admitted to our hospital between 2010 and 2021 who survived 10 days postinjury. We identified all patients receiving amantadine and compared them with all patients not receiving amantadine and a propensity score-matched nonamantadine group. Primary outcome measures included discharge Glasgow Coma Scale, Glasgow Outcome Scale-Extended score, length of stay, mortality, recovery of command-following (CF), and days to CF. RESULTS: In our study population, 60 patients received amantadine and 344 did not. Compared with the propensity score-matched nonamantadine group, the amantadine group had no difference in mortality (86.67% vs. 88.33%, P = 0.783), rates of CF (73.33% vs. 76.67%, P = 0.673), or percentage of patients with severe (3-8) discharge Glasgow Coma Scale scores (11.11% vs. 12.28%, P = 0.434). In addition, the amantadine group was less likely to have a favorable recovery (discharge Glasgow Outcome Scale-Extended score 5-8) (14.53% vs. 16.67%, P < 0.001), had a longer length of stay (40.5 vs. 21.0 days, P < 0.001), and had a longer time to CF (11.5 vs. 6.0 days, P = 0.011). No difference in adverse events existed between groups. CONCLUSIONS: Our findings do not support the early administration of amantadine for sTBI. Larger inpatient randomized trials are necessary to further investigate amantadine treatment for sTBI.

Call to Action: Creating Resources for Radiology Technologists to Capture Higher Quality Portable Chest X-rays.

Background Patient rotation, foreign body overlying anatomy, and anatomy out of field of view can have detrimental impacts on the diagnostic quality of portable chest x-rays (PCXRs), especially as the number of PCXR imaging increases due to the coronavirus disease 2019 (COVID-19) pandemic. Although preventable, these "quality failures" are common and may lead to interpretative and diagnostic errors for the radiologist. Aims In this study, we present a baseline quality failure rate of PCXR imaging as observed at our institution. We also conduct a focus group highlighting the key issues that lead to the problematic images and discuss potential interventions targeting technologists that can be implemented to address imaging quality failure rate. Materials and methods A total of 500 PCXRs for adult patients admitted to a large university hospital between July 12, 2021, and July 25, 2021, were obtained for evaluation of quality. The PCXRs were evaluated by radiology residents for failures in technical image quality. The images were categorized into various metrics including the degree of rotation and obstruction of anatomical structures. After collecting the data, a focus group involving six managers of the technologist department at our university hospital was conducted to further illuminate the key barriers to quality PCXRs faced at our institution.. Results  Out of the 500 PCXRs evaluated, 231 were problematic (46.2%). 43.5% of the problematic films with a repeat PCXR within one week showed that there was a technical problem impacting the ability to detect pathology. Most problematic films also occurred during the night shift (48%). Key issues that lead to poor image quality included improper patient positioning, foreign objects covering anatomy, and variances in technologists' training. Three interventions were proposed to optimize technologist performance that can lower quality failure rates of PCXRs. These include a longitudinal educational curriculum involving didactic sessions, adding nursing support to assist technologists, and adding an extra layer of verification by internal medicine residents before sending the films to the radiologist. The rationale for these interventions is discussed in detail so that a modified version can be implemented in other hospital systems.  Conclusion This study illustrates the high baseline error rate in image quality of PCXRs at our institution and demonstrates the need to improve on image quality. Poor image quality negatively impacts the interpretive accuracy of radiologists and therefore leads to wrong diagnoses. Increasing educational resources and support for technologists can lead to higher image quality and radiologist accuracy.

Quantity and quality of complementary and alternative medicine recommendations in clinical practice guidelines for type 2 diabetes mellitus: A systematic review.

AIMS: Approximately 70% of Americans with diabetes have used complementary and alternative medicine (CAM) in the past year. Healthcare providers often receive minimal training on these therapies and subsequently rely on clinical practice guidelines (CPGs) to supplement their knowledge about the safe and effective use of CAM for the treatment/management of type 2 diabetes mellitus (T2DM). The purpose of this systematic review is to determine the quantity and assess the quality of CAM recommendations in CPGs for the treatment and/or management of T2DM. DATA SYNTHESIS: MEDLINE, EMBASE, and CINAHL were systematically searched from 2009 to 2020, in addition to the Guidelines International Network and the National Center for Complementary and Integrative Health websites. CPGs containing treatment and/or management recommendations for T2DM were eligible; those with CAM recommendations were quality-assessed with the AGREE II instrument twice, once for the overall CPG and once for the CAM sections. Twenty-seven CPGs were deemed eligible, of which 7 made CAM recommendations. Mean scaled domain percentages were (overall, CAM): scope and purpose (89.7%, 79.8%), clarity of presentation (85.7%, 48.4%), stakeholder involvement (67.9%, 28.2%), applicability (54.8%, 20.2%), rigour of development (49.7%, 35.7%), and editorial independence (44.1%, 44.1%). CONCLUSIONS: Quality varied within and across CPGs; domain scores across CAM sections generally scored lower than the overall CPG. Given that CAM therapies for T2DM are only represented in one-quarter of eligible CPGs and are of lower quality, a knowledge gap exists for healthcare providers who seek evidence-based information on this topic in order to effectively counsel inquiring patients.

Quality of complementary and alternative medicine information for type 2 diabetes: a cross-sectional survey and quality assessment of websites.

BACKGROUND: The global prevalence of diabetes mellitus is projected to reach approximately 700 million by the year 2045, with roughly 90-95% of all diabetes cases being type 2 in nature. Patients with type 2 diabetes mellitus (T2DM) frequently seek information about complementary and alternative medicine (CAM) online. This study assessed the quality of publicly accessible websites providing consumer health information at the intersection of T2DM and CAM. METHODS: An online search engine (Google) was searched to identify pertinent websites containing information specific to CAM for T2DM patients, and the relevant websites were then screened with an eligibility criteria. Consumer health information found on eligible websites were then assessed for quality using the DISCERN instrument, a 16-item standardized scoring system. RESULTS: Across the 480 webpages identified, 94 unique webpages remained following deduplication, and 37 eligible webpages belonged to and were collapsed into 30 unique websites that were each assessed using the DISCERN instrument. The mean overall quality score (question 16) across all 30 assessed websites was 3.55 (SD = 0.86), and the mean summed DISCERN score was 52.40 (SD = 12.11). Eighty percent of websites presented a wide range of CAM treatment options with the associated benefits/risks of each treatment, but in 56.7% of the websites, the sources used to collect information were unreliable. CONCLUSION: This study identified, assessed, and presents findings on the quality of online CAM information for T2DM. Although there were several high scoring websites, there was variability across most of the individual DISCERN items in the assessed websites. This study highlights the importance of awareness among healthcare providers regarding the reliability of online information about CAM treatment and management options for T2DM. Healthcare providers should be aware of patients' information seeking behaviour, guide them in navigating through the content they encounter online, and provide them with resources containing trustworthy and reliable information.

Attitudes toward medical cannabis among family physicians practising in Ontario, Canada: a qualitative research study.

BACKGROUND: Medical cannabis has been legally available in Canada since 2001, but its benefits and harms remain uncertain. We explored attitudes toward medical cannabis among family physicians practising in Ontario. METHODS: Between January and October 2019, we conducted a qualitative study of Ontario family physicians using semistructured telephone interviews. We applied thematic analysis to interview transcripts and identified representative quotes. RESULTS: Eleven physicians agreed to be interviewed, and 3 themes regarding medical cannabis emerged: reluctance to authorize use, concern over harms and lack of practical knowledge. Participants raised concerns about the limited evidence for, and their lack of education regarding, the therapeutic use of cannabis, particularly the harms associated with neurocognitive development, exacerbation of mental illness and drug interactions in older adults. Some participants thought medical cannabis was overly accessible and questioned their role following legalization of recreational cannabis. INTERPRETATION: Despite the increasing availability of medical cannabis, family physicians expressed reluctance to authorize its use because of lack of knowledge and concerns regarding harms. Family physicians may benefit from guidance and education that address concerns they have surrounding medical cannabis.

Web-information surrounding complementary and alternative medicine for low back pain: a cross-sectional survey and quality assessment.

BACKGROUND: Low back pain (LBP) is expected to globally affect up to 80% of individuals at some point during their lifetime. While conventional LBP therapies are effective, they may result in adverse side-effects. It is thus common for patients to seek information about complementary and alternative medicine (CAM) online to either supplement or even replace their conventional LBP care. The present study sought to assess the quality of web-based consumer health information available at the intersection of LBP and CAM. METHODS: We searched Google using six unique search terms across four English-speaking countries. Eligible websites contained consumer health information in the context of CAM for LBP. We used the DISCERN instrument, which consists of a standardized scoring system with a Likert scale from one to five across 16 questions, to conduct a quality assessment of websites. RESULTS: Across 480 websites identified, 32 were deemed eligible and assessed using the DISCERN instrument. The mean overall rating across all websites 3.47 (SD = 0.70); Summed DISCERN scores across all websites ranged from 25.5-68.0, with a mean of 53.25 (SD = 10.41); the mean overall rating across all websites 3.47 (SD = 0.70). Most websites reported the benefits of numerous CAM treatment options and provided relevant information for the target audience clearly, but did not adequately report the risks or adverse side-effects adequately. CONCLUSION: Despite some high-quality resources identified, our findings highlight the varying quality of consumer health information available online at the intersection of LBP and CAM. Healthcare providers should be involved in the guidance of patients' online information-seeking.

Intravenous iron therapy for patients with preoperative iron deficiency or anaemia undergoing cardiac surgery reduces blood transfusions: a systematic review and meta-analysis.

OBJECTIVES: The benefits of preoperative intravenous (IV) iron treatment in cardiac surgery patients with preoperative anaemia or iron deficiency have not been well-established. We performed a systematic review and meta-analysis to determine the effects of treating preoperative anaemia or iron deficiency with IV iron in adult cardiac surgery patients. METHODS: We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online and Excerpta Medica Database for randomized controlled trials (RCTs) and observational studies comparing IV iron to oral iron or no iron. We performed title and abstract, full-text screening, data extraction and risk of bias assessment independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence. RESULTS: We identified 4 RCTs and 7 observational studies. Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality [relative risk 0.39, 95% confidence interval (CI) 0.23-0.65; P < 0.001, very low quality], units transfused per patient (mean difference -1.22, 95% CI -1.85 to -0.60; P < 0.001, very low quality), renal injury (relative risk 0.50, 95% CI 0.36-0.69; P < 0.001, very low quality) and hospital length of stay (mean difference -4.24 days, 95% CI -6.86 to -1.63; P = 0.001, very low quality). Pooled data from RCTs demonstrated a reduction in the number of patients transfused with IV iron compared to oral or no iron (relative risk 0.81, 95% CI 0.70-0.94; P = 0.005, moderate quality). The pooled estimates of effect from RCTs for mortality, hospital length of stay, units transfused per patient and renal injury were consistent in direction with observational studies. CONCLUSIONS: This meta-analysis suggests that IV iron improves postoperative morbidity in adult cardiac surgery patients with preoperative anaemia or iron deficiency. A large, rigorous, placebo-controlled, double-blinded, multicentre trial is needed to clarify the role of IV iron in this patient population. CLINICAL TRIAL REGISTRATION: International prospective register of systematic reviews ID Number CRD42019122844.

Complementary medicine mention and recommendations are limited across hypertension guidelines: A systematic review.

OBJECTIVE: The purpose of this study was to determine the quantity of complementary medicine (CM) recommendations and their quality across clinical practice guidelines (CPGs) for the treatment and/or management of hypertension. DESIGN/SETTING: A systematic review was conducted to identify hypertension CPGs. MEDLINE, EMBASE and CINAHL were searched from 2008 to 2018, alongside the Guidelines International Network and the National Centre for Complementary and Integrative Health websites. Eligible articles were assessed with the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. OUTCOME/RESULTS: From 1445 unique search results, 18 CPGs for the treatment and/or management of hypertension published in 2008 or later were eligible for review, though only 1 contained CM recommendations. This CPG was published by the European Society of Cardiology and the European Society of Hypertension, and made a recommendation regarding the Mediterranean diet. The scaled domain percentages of this CPG overall scored significantly better than the CM section across every domain, and were as follows: (overall, CM): scope and purpose (88.9 %, 66.7 %), clarity-of-presentation (88.9 %, 0.0 %), stakeholder involvement (66.7 %, 16.7 %), applicability (60.4 %, 0.0 %), rigor-of-development (35.4 %, 15.6 %), and editorial independence (4.2 %, 0.0 %). CONCLUSION: A lack of CM treatment recommendations exists in CPGs for the treatment and/or management of hypertension. Given that it is known that a high proportion of patients with hypertension seek CM, current hypertension guidelines' lack of CM treatment and/or management recommendations reflects a large gap in guidance for both clinicians and patients.