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DescriptionCoronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP.MethodsThese guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations.Recommendation 1 (outpatient)The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence).Recommendation 2 (inpatient)The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2.Recommendation 3 (inpatient)The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence).Recommendation 4 (inpatient)The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence).Recommendation 5 (prophylaxis)The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence).Good clinical practice statementCCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Sex differences in sports performances continue to attract considerable scientific and public attention, driven in part by high profile cases of: 1) biological male (XY) athletes who seek to compete in the female category after gender transition, and 2) XY athletes with medical syndromes collectively known as disorders or differences of sex development (DSDs). In this perspective, we highlight scientific evidence that informs eligibility criteria and applicable regulations for sex categories in sports. There are profound sex differences in human performance in athletic events determined by strength, speed, power, endurance, and body size such that males outperform females. These sex differences in athletic performance exist before puberty and increase dramatically as puberty progresses. The profound sex differences in sports performance are primarily attributable to the direct and indirect effects of sex-steroid hormones and provide a compelling framework to consider for policy decisions to safeguard fairness and inclusion in sports. [ABSTRACT FROM AUTHOR]

What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α2-adrenergic agonist, 10-min loading infusion of 0.225 µg·kg−1; maintenance infusion of 0.1–0.5 µg·kg·h−1) in six healthy individuals (5 females, 27 ± 6 yr). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (liquid chromatography-tandem mass spectrometry) levels at baseline and the dexmedetomidine maintenance infusion. Linear mixed-model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], P = 0.002), total AP clusters (β = 0.90 [0.22], P = 0.005), and AP frequency (β = 0.11 [0.03], P = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], P = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], P = 0.030) and AP frequency (β = 2.66 [0.81], P = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation. NEW & NOTEWORTHY: The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans. [ABSTRACT FROM AUTHOR]

Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance [maximal oxygen consumption (V̇ o 2max), lactate threshold, and running economy (RE)], V̇ o 2max appears to be most affected by age. Although endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-yr-old distance runner who broke the marathon world record for men over 70 yr of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (∼90%) of his V̇ o 2max. However, V̇ o 2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇ o 2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes. NEW & NOTEWORTHY: We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇ o 2max. His max heart rate (HR) changed minimally, but his peak O2 pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O2 difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10–30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal–Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, P > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12–39% larger among patients with PASC than in controls (all, P < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes. NEW & NOTEWORTHY: Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19. [ABSTRACT FROM AUTHOR]

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alcohol consumption is associated with cardiovascular disease, and the sympathetic nervous system is a suspected mediator. The present study investigated sympathetic transduction of muscle sympathetic nerve activity to blood pressure at rest and in response to cold pressor test following evening binge alcohol or fluid control, with the hypothesis that sympathetic transduction would be elevated the morning after binge alcohol consumption. METHODS: Using a randomized, fluid-controlled (FC) crossover design, 26 healthy adults (12 male, 14 female, 25±6 years, 27±4 kg/m2) received an evening binge alcohol dose and a FC. All participants underwent next-morning autonomic-cardiovascular testing consisting of muscle sympathetic nerve activity, beat-to-beat blood pressure, and heart rate during a 10-minute rest period and a 2-minute cold pressor test. Sympathetic transduction was assessed at rest and during the cold pressor test in both experimental conditions. RESULTS: Evening alcohol increased heart rate (FC: 60±9 versus alcohol: 64±9 bpm; P=0.010) but did not alter resting mean arterial pressure (FC: 80±6 versus alcohol: 80±7 mm Hg; P=0.857) or muscle sympathetic nerve activity (FC: 18±9 versus alcohol: 20±8 bursts/min; P=0.283). Sympathetic transduction to mean arterial pressure (timexcondition; P=0.003), diastolic blood pressure (timexcondition; P=0.010), and total vascular conductance (timexcondition; P=0.004) was augmented after alcohol at rest. Sympathetic transduction during the cold pressor test was also elevated after evening binge alcohol consumption (P=0.002). CONCLUSIONS: These findings suggest that evening binge alcohol consumption leads to augmented morning-after sympathetic transduction of muscle sympathetic nerve activity to blood pressure, highlighting a new mechanism whereby chronic or excessive alcohol consumption contributes to cardiovascular disease progression via altered end-organ responsiveness to sympathetic neural outflow. [ABSTRACT FROM AUTHOR]

Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia (S p O 2 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia (P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation. NEW & NOTEWORTHY: This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals. [ABSTRACT FROM AUTHOR]

The present study investigated the impact of central α2‐adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2‐adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg−1; maintenance infusion of 0.1–0.5 µg kg h−1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats−1, P = 0.003) most strongly for medium‐sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats−1; P < 0.001). Dexmedetomidine progressively de‐recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de‐recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats−1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ –0.09 ± 0.07 to Δ –0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium‐sized APs (normalized cluster 2: –6.0 ± 5 to –1.6 ± 2 % mmHg−1; P = 0.008). These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. Key points: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear.This microneurographic study investigated the impact of a dexmedetomidine infusion (α2‐adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns.Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre.Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre.These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. [ABSTRACT FROM AUTHOR]

The objective of this study is to derive mathematical equations that closely describe published data on world record running speed as a function of distance, age, and sex. Running speed declines with increasing distance and age. Over long distances, where aerobic metabolism is dominant, speed declines in proportion to the logarithm of distance. Over short distances, anaerobic metabolism contributes significantly to performance, and speed is increased relative to the trend of the long-distance data. Equations are derived that explicitly represent these effects. The decline in speed with age is represented by an age-dependent multiplicative factor, which exhibits increasing sensitivity to age as age increases. Using these equations, data are analyzed separately for males and females, and close fits to published data are demonstrated, particularly for younger age groups. These equations provide insight into the contributions of aerobic and anaerobic components of metabolism to athletic performance and a framework for comparisons of performance across wide ranges of distance and age. NEW & NOTEWORTHY: World record speeds at different distances for men and women in different age categories are used to develop a model to predict running performance as a function of race distance, age, and sex. This empirical model quantifies the decline in running speed with distance and age in a way that provides insight into the aerobic and anaerobic contributions to running speed and may help with developing training strategies for different age groups at various distances. [ABSTRACT FROM AUTHOR]

The article in the Journal of Applied Physiology explores the effects of carbon monoxide (CO) inhalation on elite athletes' performance, hemoglobin levels, and oxygen uptake. The study found that CO inhalation at moderate altitudes enhanced hematological adaptations and improved cycling performance compared to sea-level training. However, there are safety concerns and ethical implications regarding the use of CO as an ergogenic aid in sports, as well as questions about its potential impact on competitive fairness and doping regulations. The authors suggest that CO inhalation for blood manipulation should be explicitly banned by the World Anti-Doping Agency to ensure fair play in sports. [Extracted from the article]

BACKGROUND. Convalescent plasma is the only antibody-based therapy currently available for patients with coronavlrus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. METHODS. Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma. RESULTS. The incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was CONCLUSION. Given the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19. TRIAL REGISTRATION. ClinicalTrials.gov NCT04338360. FUNDING. Mayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc., Introduction The number of confirmed cases of coronavirus disease 2019 (COVID-19) and the number of deaths attributed to COVID-19 in the US exceed that of any other country in the [...]

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in humans need to complement the elegant short-term laboratory-based human studies of simulated short sleep and shift work etc. with studies in subjects in the general population with these disorders. It is conceivable that chronic adaptations occur, and if so, the mechanisms by which they occur needs to be identified and understood. Particular areas of opportunity that are ready for translation are studies to address whether CPAP treatment of patients with pre-diabetes and obstructive sleep apnea (OSA) prevents or delays the onset of diabetes and whether temporal restricted feeding has the same impact on obesity rates in humans as it does in mice.