Reduced Access to Acute Hand Care and Potential Role of Telemedicine in Tennessee During the COVID Pandemic.

INTRODUCTION: Previous studies have identified that there is limited, although expanding, access to acute hand care in Tennessee. Because of the rapid changes that occurred in health delivery and access during the coronavirus disease pandemic, we reassessed access to acute hand care, with particular interest in the utilization of telemedicine to assess if this increased access. METHOD: We surveyed Tennessee hospitals listed by the Tennessee Hospital Association on their management of hand trauma and availability of telemedicine programs. Census data including population demographics such as race, age, income, and county size were merged with the survey data. Descriptive analysis was performed comparing the 2021 cohort with the historic 2018 cohort and between counties that had hand care versus counties that had no hand care. RESULT: Survey response rate was 71.4% (n = 80 of 112). Telemedicine was used in 80% of the hospitals for other specialties but was not used for hand care. Overall, counties that offered hand trauma care reduced from 60% to 26% from 2018 to 2021 ( P < 0.001). This change was associated with a significant reduction of acute hand care among counties that were classified micropolitan (from 56.3% to 6.7%, P < 0.01). Percentage of hand specialists on staff and 24/7 specialists availability remained low and were similar to the availability in 2018. CONCLUSIONS: There was a decrease of acute hand care access in Tennessee during the coronavirus disease pandemic despite widespread utilization of telemedicine for other specialty consults. Expansion of telemedicine in acute hand care, targeted to micropolitan areas, may help to reduce variability in access to care.

How Person-Centred Is Cardiac Rehabilitation in England? Using Bourdieu to Explore Socio-Cultural Influences and Personalisation.

The National Health Service (NHS) cardiac rehabilitation patient care pathway has remained largely unchanged for many years despite, on average, half of all eligible patients declining to engage. To investigate reasons for non-engagement, we explored the experiences of ten cardiac patients who participated in cardiac rehabilitation, dropped out, or declined, as well as experiences of seven people deemed significant others by participants. Our ethnographic study involved participant observations, repeat in-depth semi-structured interviews, and reflexive journaling. Reflexive thematic analysis was conducted, focusing on participants' lived experiences. Utilising Bourdieusian concepts of habitus, capital, and field, this article highlights how personal biography, material conditions, and dispositional inclinations combine to make cardiac health care decision-making individual and complex. Despite this, health professionals were not always attuned to specific circumstances arising from differences in patients' experiences and lifeworlds. By considering service improvement recommendations that acknowledge socio-cultural influences, cardiac rehabilitation can work towards providing patients and their significant others with more appropriate, personalised, and person-centred support.

The Impact of Higher BMI on Wound Complications Following Adolescent Breast Reduction: A Retrospective Study of 1215 Cases.

BACKGROUND: Macromastia is a physically and psychologically distressing condition for adolescents. While reduction mammaplasty is often the best treatment, risk factors for adolescent wound complications remain unclear. This study aims to investigate the impact of obesity and other predictors of postoperative wound complications following adolescent reduction mammaplasty using a national database. METHODS: The 2012-2019 National Surgical Quality Improvement Program Pediatric (NSQIP-P) databases were reviewed to identify primary reduction mammaplasty encounters. World Health Organization Body Mass Index (BMI), alongside patient and case characteristics, were assessed for association for 30-day wound disruption or surgical site complications. Statistical analyses were performed to identify independent predictors for complications and determine a potential BMI cutoff for risk stratification. RESULTS: There were 1215 patients with an average age of 16.6 years. The average BMI was 30.7 kg/m2, and 593 (48.8%) patients were nonobese while 622 (51.2%) were obese. The incidence of complications was 5.27%. Independent predictors of complications included a BMI 35-39.9, BMI > 40, and an American Society of Anesthesiologists (ASA) Classification > 3. A receiver operating characteristic curve determined that a BMI of 34.6 can be a potential cutoff for increased complication risk. CONCLUSIONS: Higher obesity increases risk of wound complications; however, complication rates remain low. A BMI of 34.6 is a potential screening metric for counseling and monitoring patients. Reduction mammaplasty should remain a viable option as it can significantly improve quality of life. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Nationwide Clinical Practice Patterns of Anesthesiology Critical Care Physicians: A Survey to Members of the Society of Critical Care Anesthesiologists.

BACKGROUND: Despite the growing contributions of critical care anesthesiologists to clinical practice, research, and administrative leadership of intensive care units (ICUs), relatively little is known about the subspecialty-specific clinical practice environment. An understanding of contemporary clinical practice is essential to recognize the opportunities and challenges facing critical care anesthesia, optimize staffing patterns, assess sustainability and satisfaction, and strategically plan for future activity, scope, and training. This study surveyed intensivists who are members of the Society of Critical Care Anesthesiologists (SOCCA) to evaluate practice patterns of critical care anesthesiologists, including compensation, types of ICUs covered, models of overnight ICU coverage, and relationships between these factors. We hypothesized that variability in compensation and practice patterns would be observed between individuals. METHODS: Board-certified critical care anesthesiologists practicing in the United States were identified using the SOCCA membership distribution list and invited to take a voluntary online survey between May and June 2021. Multiple-choice questions with both single- and multiple-select options were used for answers with categorical data, and adaptive questioning was used to clarify stem-based responses. Respondents were asked to describe practice patterns at their respective institutions and provide information about their demographics, salaries, effort in ICUs, as well as other activities. RESULTS: A total of 490 participants were invited to take this survey, and 157 (response rate 32%) surveys were completed and analyzed. The majority of respondents were White (73%), male (69%), and younger than 50 years of age (82%). The cardiothoracic/cardiovascular ICU was the most common practice setting, with 69.5% of respondents reporting time working in this unit. Significant variability was observed in ICU practice patterns. Respondents reported spending an equal proportion of their time in clinical practice in the operating rooms and ICUs (median, 40%; interquartile range [IQR], 20%-50%), whereas a smaller proportion-primarily those who completed their training before 2009-reported administrative or research activities. Female respondents reported salaries that were $36,739 less than male respondents; however, this difference was not statistically different, and after adjusting for age and practice type, these differences were less pronounced (-$27,479.79; 95% confidence interval [CI], -$57,232.61 to $2273.03; P = .07). CONCLUSIONS: These survey data provide a current snapshot of anesthesiology critical care clinical practice patterns in the United States. Our findings may inform decision-making around the initiation and expansion of critical care services and optimal staffing patterns, as well as provide a basis for further work that focuses on intensivist satisfaction and burnout.

Structure and Dynamics of Three Escherichia coli NfsB Nitro-Reductase Mutants Selected for Enhanced Activity with the Cancer Prodrug CB1954.

Escherichia coli NfsB has been studied extensively for its potential for cancer gene therapy by reducing the prodrug CB1954 to a cytotoxic derivative. We have previously made several mutants with enhanced activity for the prodrug and characterised their activity in vitro and in vivo. Here, we determine the X-ray structure of our most active triple and double mutants to date, T41Q/N71S/F124T and T41L/N71S. The two mutant proteins have lower redox potentials than wild-type NfsB, and the mutations have lowered activity with NADH so that, in contrast to the wild-type enzyme, the reduction of the enzyme by NADH, rather than the reaction with CB1954, has a slower maximum rate. The structure of the triple mutant shows the interaction between Q41 and T124, explaining the synergy between these two mutations. Based on these structures, we selected mutants with even higher activity. The most active one contains T41Q/N71S/F124T/M127V, in which the additional M127V mutation enlarges a small channel to the active site. Molecular dynamics simulations show that the mutations or reduction of the FMN cofactors of the protein has little effect on its dynamics and that the largest backbone fluctuations occur at residues that flank the active site, contributing towards its broad substrate range.

Nerve blocks for occipital headaches: A systematic review and meta-analysis.

Migraine surgeons have identified six "trigger sites" where cranial nerve compression may trigger a migraine. This study investigates the change in headache severity and frequency following nerve block of the occipital trigger site. This PRISMA-compliant systematic review of five databases searched from database inception through May 2020 is registered under the PROSPERO ID: CRD42020199369. Only randomized controlled trials utilizing injection treatments for headaches with pain or tenderness in the occipital scalp were included. Pain severity was scored from 0 to 10. Headache frequency was reported as days per week. Included were 12 RCTs treating 586 patients of mean ages ranging from 33.7 to 55.8 years. Meta-analyses of pain severity comparing nerve blocks to baseline showed statistically significant reductions of 2.88 points at 5 to 20 min, 3.74 points at 1 to 6 weeks, and 1.07 points at 12 to 24 weeks. Meta-analyses of pain severity of nerve blocks compared with treatment groups of neurolysis, pulsed radiofrequency, and botulinum toxin type A showed similar headache pain severity at 1 to 2 weeks, and inferior improvements compared with the treatment groups after 2 weeks. Meta-analyses of headache frequency showed statistically significant reductions at 1 to 6-week follow-ups as compared with baseline and at 1 to 6 weeks as compared with inactive control injections. The severity and frequency of occipital headaches are reduced following occipital nerve blocks. This improvement is used to predict the success of migraine surgery. Future research should investigate spinous process injections with longer follow-up.

Activating the 'peerness' of youth leaders in a community sports programme through techne and phronesis.

Peer-to-peer approaches engage groups of people considered to share one or more characteristics that identify them as peers and draw on rationales of credibility, identification and role modelling in peer-to-peer interactions. Despite the popularity of the approach, the ways in which the peer leadership component specifically contributes to health promotion is not thoroughly understood. We suggest that a first step for making use of peer leader characteristics is to make explicit what the peer leadership component is expected to bring to a programme. To approach such an understanding, we investigated how peer leaders can be supported in activating their 'peerness' in health promotion programmes, using as a case the peer leader education of a youth-led, peer-to-peer community sports programme, implemented by the non-profit street sports organization, GAME. We analysed the peer leader training programme's learning objectives and field notes from observations of the training programme. The empirical material was analysed using an abductive approach by drawing upon contemporary interpretations of two forms of knowledge originally proposed by Aristotle. In so doing, this article explores how the development of techne (practical knowledge) and phronesis (practical wisdom) was supported in a peer leader training programme for young people. Findings suggest that supporting the development of both these types of knowledge can strengthen programme planners' attention to the contribution of peers. Concurrently, an emphasis on promoting phronesis in peer leader training can support and encourage peer leaders in activating their 'peerness' in peer-to-peer health promotion programmes.

Peer-to-peer approaches are commonly used in the health promotion. Peer-led programmes engage groups of people considered to share one or more characteristics that identify them as peers. Peer leaders are suggested to be credible sources of information and provide identification and role modelling to their peers. However, despite the popularity of the approach, the ways in which peer leaders specifically contribute to health promotion are not thoroughly understood. It is thus unclear how the 'peerness' of peer leaders is activated in health promotion programmes. In this study, we investigated how peer leaders can be supported in activating their 'peerness' during peer-led activities. To do so, we observed and analysed the peer leader training programme of a youth-led community sport programme, implemented by the non-profit organization, GAME. As a theoretical framework, we employed two forms of knowledge originally proposed by Aristotle; namely, techne (practical knowledge) and phronesis (practical wisdom). Our results suggest that supporting the development of both these types of knowledge can strengthen programme planners' attention to the contribution of peers. Concurrently, an emphasis on promoting phronesis in peer leader training can support and encourage peer leaders in activating their 'peerness' in peer-to-peer health promotion programmes.

Nationwide Estimates of Gender-Affirming Chest Reconstruction in the United States, 2016-2019.

BACKGROUND: Section 1557 of the Affordable Care Act, introduced in 2016, increased access to gender-affirming surgeries for transgender and gender diverse individuals. Masculinizing chest reconstruction (e.g., mastectomy) and feminizing chest reconstruction (e.g., augmentation mammaplasty), often outpatient procedures, are the most frequently performed gender-affirming surgeries. However, there is a paucity of information about the demographics of patients who undergo gender-affirming chest reconstruction. OBJECTIVES: The authors sought to investigate the incidence, demographics, and spending for ambulatory gender-affirming chest reconstruction utilizing nationally representative data from 2016 to 2019. METHODS: Employing the Nationwide Ambulatory Surgery Sample, the authors identified patients with an International Classification of Diseases diagnosis code of gender dysphoria who underwent chest reconstruction between 2016 and 2019. Demographic and clinical characteristics were recorded for each encounter. RESULTS: A weighted estimate of 21,293 encounters for chest reconstruction were included (17,480 [82.1%] masculinizing and 3813 [27.9%] feminizing). Between 2016 and 2019, the number of chest surgeries per 100,000 encounters increased by 143.2% from 27.3 to 66.4 (P < 0.001). A total 12,751 (59.9%) chest surgeries were covered by private health insurance, 6557 (30.8%) were covered by public health insurance, 1172 (5.5%) were self-pay, and 813 (3.8%) had other means of payment. The median total charges were $29,887 (IQR, $21,778-$43,785) for chest reconstruction overall. Age, expected primary payer, patient location, and median income varied significantly by race (P < 0.001). CONCLUSIONS: Gender-affirming chest reconstructions are on the rise, and surgeons must understand the background and needs of transgender and gender diverse patients who require and choose to undergo surgical transitions.

ID-MAM: A Validated Identity and Multi-Attribute Monitoring Method for Commercial Release and Stability Testing of a Bispecific Antibody.

Post-translational modifications (PTMs) that impact the safety or efficacy of protein therapeutics are critical quality attributes (CQAs) that need to be controlled to ensure product quality. Peptide mapping with online mass spectrometry (MS) is a powerful tool that has been used for many years to monitor PTM CQAs during product development. However, operating peptide mapping methods with high-resolution mass spectrometers in GMP compliant, commercial quality control (QC) labs can be difficult. Peptide mapping is also required as an identity test in several countries. To address these two different needs, we utilized high-resolution peptide mapping for comprehensive characterization during development and then developed and validated a targeted multi-attribute monitoring (MAM) method using the low-resolution Waters QDa MS system with a fully automated data processing workflow that is suitable for identity (ID) testing, sequence variant control, and CQA quantitation in commercial QC labs. The ID-MAM method was validated for the quantitation of three selected PTM CQAs (CDR isomerization, Fc Met oxidation, and CDR Met oxidation) to ensure control of the oxidation and isomerization degradation pathways of a bispecific antibody (BsAb). This ID-MAM method was successfully validated in six labs (three analytical development and three QC labs) across four countries for commercial release and stability testing of a BsAb. CQA results obtained with the ID-MAM method were similar to results obtained using high-resolution peptide mapping, and the method was robust and reproducible. To our knowledge, this ID-MAM method is the first MS-based peptide mapping method implemented in GMP compliant QC labs for commercial release and stability testing of a biotherapeutic.

Persistent SARS-CoV-2 infection in patients with secondary antibody deficiency: successful clearance following combination casirivimab and imdevimab (REGN-COV2) monoclonal antibody therapy.

BACKGROUND: There is growing evidence that antibody responses play a role in the resolution of SARS-CoV-2 infection. Patients with primary or secondary antibody deficiency are at increased risk of persistent infection. This challenging clinical scenario is associated with adverse patient outcome and potentially creates an ecological niche for the evolution of novel SARS-CoV-2 variants with immune evasion capacity. Case reports and/or series have implied a therapeutic role for convalescent plasma (CP) to secure virological clearance, although concerns have been raised about the effectiveness of CP and its potential to drive viral evolution, and it has largely been withdrawn from clinical use in the UK. CASE PRESENTATION: We report two cases in which persistent SARS-CoV-2 infection was cleared following administration of the monoclonal antibody combination casirivimab and imdevimab (REGN-COV2, Ronapreve). A 55-year-old male with follicular lymphoma, treated with B cell depleting therapy, developed SARS-CoV-2 infection in September 2020 which then persisted for over 200 days. He was hospitalised on four occasions with COVID-19 and suffered debilitating fatigue and malaise throughout. There was no clinical response to antiviral therapy with remdesivir or CP, and SARS-CoV-2 was consistently detected in nasopharyngeal swabs. Intrahost evolution of several spike variants of uncertain significance was identified by viral sequence analysis. Delivery of REGN-COV2, in combination with remdesivir, was associated with clinical improvement and viral clearance within 6 days, which was sustained for over 150 days despite immunotherapy for relapsed follicular lymphoma. The second case, a 68-year-old female with chronic lymphocytic leukaemia on ibrutinib, also developed persistent SARS-CoV-2 infection. Despite a lack of response to remdesivir, infection promptly cleared following REGN-COV2 in combination with remdesivir, accompanied by resolution of inflammation and full clinical recovery that has been maintained for over 290 days. CONCLUSIONS: These cases highlight the potential benefit of REGN-COV2 as therapy for persistent SARS-CoV-2 infection in antibody deficient individuals, including after failure of CP treatment. Formal clinical studies are warranted to assess the effectiveness of REGN-COV2 in antibody-deficient patients, especially in light of the emergence of variants of concern, such as Omicron, that appear to evade REGN-COV2 neutralisation.

Treatment With Angiotensin II Is Associated With Rapid Blood Pressure Response and Vasopressor Sparing in Patients With Vasoplegia After Cardiac Surgery: A Post-Hoc Analysis of Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) Study.

OBJECTIVE: The present study investigated outcomes in patients with vasoplegia after cardiac surgery treated with angiotensin II plus standard-of-care vasopressors. Vasoplegia is a common complication in cardiac surgery with cardiopulmonary bypass and is associated with significant morbidity and mortality. Approximately 250,000 cardiac surgeries with cardiopulmonary bypass are performed in the United States annually, with vasoplegia occurring in 20%to-27% of patients. DESIGN: Post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. SETTING: Multicenter, multinational study. PARTICIPANTS: Sixteen patients with vasoplegia after cardiac surgery with cardiopulmonary bypass were enrolled. INTERVENTIONS: Angiotensin II plus standard-of-care vasopressors (n = 9) compared with placebo plus standard-of-care vasopressors (n = 7). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was mean arterial pressure response (mean arterial pressure ≥75 mmHg or an increase from baseline of ≥10 mmHg at hour 3 without an increase in the dose of standard-of-care vasopressors). Vasopressor sparing and safety also were assessed. Mean arterial pressure response was achieved in 8 (88.9%) patients in the angiotensin II group compared with 0 (0%) patients in the placebo group (p = 0.0021). At hour 12, the median standard-of-care vasopressor dose had decreased from baseline by 76.5% in the angiotensin II group compared with an increase of 7.8% in the placebo group (p = 0.0013). No venous or arterial thrombotic events were reported. CONCLUSION: Patients with vasoplegia after cardiac surgery with cardiopulmonary bypass rapidly responded to angiotensin II, permitting significant vasopressor sparing.

Robotic Cardiac Surgery Part I: Anesthetic Considerations in Totally Endoscopic Robotic Cardiac Surgery (TERCS).

The application and evolution of total endoscopic robotic cardiac surgery (TERCS) has become greater as institutions and surgeons become more comfortable with robotic technology. Over the years many improvements have been made to facilitate technically challenging cardiac procedures using robotics and increase overall survival and quality of life for these patients. However, a dedicated multidisciplinary approach led by a core group of clinicians is necessary for good patient experience and outcomes. In addition, good communication and performance improvement measures with attention to detailed perioperative management are essential to a successful robotic cardiac program.

Robotic Cardiac Surgery Part II: Anesthetic Considerations for Robotic Coronary Artery Bypass Grafting.

Coronary artery bypass grafting represents one of the most commonly performed cardiac surgeries worldwide. Recently, interest has increased in providing patients with a less invasive approach to cardiac surgery, such as thoracotomy and endoscopic techniques using robotic technology as an alternative to traditional sternotomy. As the population gets older, the need for additional methods to provide care for sick patients will continue to expand. These advancements will further allow physicians to provide cardiac surgical procedures with less pain and faster recovery for patients.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2019.

This highlights in our specialty for 2019 begin with the ongoing major developments in transcatheter valve interventions. Thereafter, the advances in left ventricular assist devices are reviewed. The recent focus on conduit selection and robotic options in coronary artery bypass surgery are then explored. Finally, this special articles closes with a discussion of pulmonary hypertension in noncardiac surgery, anesthetic technique in cardiac surgery, as well as postoperative pneumonia and its outcome consequences.

Updated List of Light-Sensitive Oral Medications.

The Campbell University Drug Information Center supports health professionals by providing responses to drug-related inquiries. An inquiry was received by the Drug Information Center for a comprehensive list of oral solutions which should be protected from light. In investigating this request for information, a list of light-sensitive oral prescription drug products published in Hospital Pharmacy in 2009 was identified. This discovery highlighted the need for both an updated list and one which distinguished oral solid products and oral liquid products. The purpose of this project was to update the previously published list and to distinguish between oral solid and liquid dosage forms. The process of updating this list entailed several professional resources. A list of all oral products was obtained and then sorted to clearly identify which products were available in oral solid dosage form only, oral liquid dosage form only, and both dosage forms. Once delineated, the product labels for each medication were scoured for language indicating the product is light sensitive.

Bacillus thuringiensis Cry1Da_7 and Cry1B.868 Protein Interactions with Novel Receptors Allow Control of Resistant Fall Armyworms, Spodoptera frugiperda (J.E. Smith).

Two new modified Bacillus thuringiensis (Bt) proteins, Cry1Da_7 and Cry1B.868, with activity against fall armyworms (FAW), Spodoptera frugiperda (J.E. Smith), were evaluated for their potential to bind new insect receptors compared to proteins currently deployed as plant-incorporated protectants (PIPs) in row crops. Results from resistant insect bioassays, disabled insecticidal protein (DIP) bioassays, and cell-based assays using insect cells expressing individual receptors demonstrate that receptor utilizations of the newly modified Cry1Da_7 and Cry1B.868 proteins are distinct from each other and from those of commercially available Bt proteins such as Cry1F, Cry1A.105, Cry2Ab, and Vip3A. Accordingly, these two proteins target different insect proteins in FAW midgut cells and when pyramided together should provide durability in the field against this economically important pest.IMPORTANCE There is increased concern with the development of resistance to insecticidal proteins currently expressed in crop plants, especially against high-resistance-risk pests such as fall armyworm (FAW), Spodoptera frugiperda, a maize pest that already has developed resistance to Bacillus thuringiensis (Bt) proteins such as Cry1F. Lepidopteran-specific proteins that bind new insect receptors will be critical in managing current Cry1F-resistant FAW and delaying future resistance development. Results from resistant insect assays, disabled insecticidal protein (DIP) bioassays, and cell-based assays using insect cells expressing individual receptors demonstrate that target receptors of the Cry1Da_7 and Cry1B.868 proteins are different from each other and from those of commercially available Bt proteins such as Cry1F, Cry1A.105, Cry2Ab, and Vip3A. Therefore, pyramiding these two new proteins in maize will provide durable control of this economically important pest in production agriculture.

High-throughput LC-MS quantitation of cell culture metabolites.

Monitoring cell culture metabolites, including media components and cellular byproducts, during bio manufacturing is critical for gaining insights into cell growth, productivity and product quality. Historically, cell culture metabolite analysis was a complicated process requiring several orthogonal methods to cover the large number of metabolites with diverse properties over wide concentration ranges. These off-line analyses are time consuming and not suitable for real time bioreactor monitoring. In this study, we present a high-throughput LC-MS method with a 17-min cycle time that is capable of simultaneously monitoring 93 cell culture metabolites, including amino acids, nucleic acids, vitamins, sugars and others. This method has high precision and accuracy and has been successfully applied to the daily profiling of bioreactors and raw material qualification. Information obtained in these studies has been used to identify limiting amino acids during production, which guided adjustments to the feed strategy that prevented the potential misincorporation of amino acids. This type of metabolite profiling can be further utilized to build predictive process models for adaptive feedback control and pave the road for continuous manufacturing and real-time release testing.

Heparin-Induced Thrombocytopenia: A Review for Cardiac Anesthesiologists and Intensivists.

Patients undergoing cardiovascular surgery may be exposed to heparin before surgery, during cardiopulmonary bypass (CPB), or in the immediate postoperative period. For this reason, cardiovascular surgery patients are at increased risk for heparin-induced thrombocytopenia (HIT), occurring in 1 to 3% of patients. The diagnosis of HIT can be difficult, if based solely on the development of thrombocytopenia, because cardiac surgical patients have multiple reasons to be thrombocytopenic. Several clinical scoring systems have been developed to reduce unnecessary testing and better define the pretest probability of HIT, which we will review in detail with a diagnostic algorithm. In addition, we will cover the prevention and treatment HIT.

Copenhagen Consensus statement 2019: physical activity and ageing.

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term 'older adults' represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults' fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual's physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.

Vasoplegia After Cardiovascular Procedures-Pathophysiology and Targeted Therapy.

Vasoplegic syndrome, characterized by low systemic vascular resistance and hypotension in the presence of normal or supranormal cardiac function, is a frequent complication of cardiovascular surgery. It is associated with a diffuse systemic inflammatory response and is mediated largely through cellular hyperpolarization, high levels of inducible nitric oxide, and a relative vasopressin deficiency. Cardiopulmonary bypass is a particularly strong precipitant of the vasoplegic syndrome, largely due to its association with nitric oxide production and severe vasopressin deficiency. Postoperative vasoplegic shock generally is managed with vasopressors, of which catecholamines are the traditional agents of choice. Norepinephrine is considered to be the first-line agent and may have a mortality benefit over other drugs. Recent investigations support the use of noncatecholamine vasopressors, vasopressin in particular, to restore vascular tone. Alternative agents, including methylene blue, hydroxocobalamin, corticosteroids, and angiotensin II, also are capable of restoring vascular tone and improving vasoplegia, but their effect on patient outcomes is unclear.