Health and equity implications of individual adaptation to air pollution in a changing climate.

Future climate change can cause more days with poor air quality. This could trigger more alerts telling people to stay inside to protect themselves, with potential consequences for health and health equity. Here, we study the change in US air quality alerts over this century due to fine particulate matter (PM2.5), who they may affect, and how they may respond. We find air quality alerts increase by over 1 mo per year in the eastern United States by 2100 and quadruple on average. They predominantly affect areas with high Black populations and leakier homes, exacerbating existing inequalities and impacting those less able to adapt. Reducing emissions can offer significant annual health benefits ($5,400 per person) by mitigating the effect of climate change on air pollution and its associated risks of early death. Relying on people to adapt, instead, would require them to stay inside, with doors and windows closed, for an extra 142 d per year, at an average cost of $11,000 per person. It appears likelier, however, that people will achieve minimal protection without policy to increase adaptation rates. Boosting adaptation can offer net benefits, even alongside deep emission cuts. New adaptation policies could, for example: reduce adaptation costs; reduce infiltration and improve indoor air quality; increase awareness of alerts and adaptation; and provide measures for those working or living outdoors. Reducing emissions, conversely, lowers everyone's need to adapt, and protects those who cannot adapt. Equitably protecting human health from air pollution under climate change requires both mitigation and adaptation.

BNT162b2 Protection against the Omicron Variant in Children and Adolescents.

BACKGROUND: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. METHODS: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. RESULTS: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). CONCLUSIONS: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.).

Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents.

BACKGROUND: The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age. METHODS: We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative). RESULTS: A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated. CONCLUSIONS: Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).

Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants.

BACKGROUND: Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. METHODS: We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022). RESULTS: A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy. CONCLUSIONS: Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).

Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care.

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020-30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. RESULTS: Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Identification of molecular subphenotypes in two cohorts of paediatric ARDS.

BACKGROUND: Two subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions. METHODS: We performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers. FINDINGS: In two cohorts from the Children's Hospital of Philadelphia (n=333) and from a multicentre study based at the University of California San Francisco (n=293), LCA identified two subphenotypes defined by differential elevation of biomarkers reflecting inflammation and endotheliopathy. In both cohorts, hyperinflammatory subjects had greater illness severity, more sepsis and higher mortality (41% and 28% in hyperinflammatory vs 11% and 7% in hypoinflammatory). Both cohorts demonstrated overlap with adult subphenotypes when assessed using parsimonious classifiers. INTERPRETATION: We identified hypoinflammatory and hyperinflammatory subphenotypes of paediatric ARDS from two separate cohorts with utility for prognostic and potentially predictive, enrichment. Future paediatric ARDS trials should identify and leverage biomarker-defined subphenotypes in their analysis.

Combined action observation and mental imagery versus neuromuscular electrical stimulation as novel therapeutics during short-term knee immobilization.

Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization-induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty-nine healthy, college-aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

Bioequivalence of rimegepant, a small molecule CGRP receptor antagonist, administered as an oral tablet, a sublingual orally disintegrating tablet, and a supralingual orally disintegrating tablet: two phase 1 randomized studies in healthy adults.

BACKGROUND: Rimegepant is an orally administered small molecule calcitonin gene-related peptide receptor antagonist indicated for the acute and preventive treatment of migraine. METHODS: Two single-center, phase 1, open-label, randomized bioequivalence studies were conducted in healthy adult non-smokers, aged 18-55 years. One study compared the rate and extent of absorption of the marketed formulation of rimegepant 75 mg orally disintegrating tablet (ODT) administered sublingually with rimegepant 75 mg oral tablet, an earlier development formulation; the second compared the rate and extent of absorption of 75 mg rimegepant ODT administered supralingually with rimegepant oral tablet. RESULTS: The ln-transformed geometric mean ratios for the area under the curve (AUC) from time 0 to the last available concentration time point (time t) (AUC0-t), AUC from time 0 to infinity (AUC0-inf), and maximum observed concentration (Cmax) of sublingual rimegepant ODT vs. rimegepant tablet were 97, 97, and 105%, respectively, and the 90% confidence intervals (CIs) were all within the predefined range (80-125%) for bioequivalence. The ln-transformed geometric mean ratios for the AUC0-t and AUC0-inf of supralingual rimegepant ODT vs. rimegepant tablet were 98%, the 90% CIs were within the predefined range (80-125%), and the geometric mean ratio for Cmax was 103% with the 95% upper confidence bound for the scaled average bioequivalence criterion of -0.0575 (within-participant coefficient of variation for the reference for Cmax > 30%) for bioequivalence. CONCLUSIONS: Rimegepant 75 mg ODT, administered sublingually or supralingually, and rimegepant 75 mg oral tablet were bioequivalent.

Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

fNIRS is capable of distinguishing laterality of lower body contractions.

The use of functional near-infrared spectroscopy (fNIRS) for brain imaging during human movement continues to increase. This technology measures brain activity non-invasively using near-infrared light, is highly portable, and robust to motion artifact. However, the spatial resolution of fNIRS is lower than that of other imaging modalities. It is unclear whether fNIRS has sufficient spatial resolution to differentiate nearby areas of the cortex, such as the leg areas of the motor cortex. Therefore, the purpose of this study was to determine fNIRS' ability to discern laterality of lower body contractions. Activity in the primary motor cortex was recorded in forty participants (mean = 23.4 years, SD = 4.5, female = 23, male = 17) while performing unilateral lower body contractions. Contractions were performed at 30% of maximal force against a handheld dynamometer. These contractions included knee extension, knee flexion, dorsiflexion, and plantar flexion of the left and right legs. fNIRS signals were recorded and stored for offline processing and analysis. Channels of fNIRS data were grouped into regions of interest, with five tolerance conditions ranging from strict to lenient. Four of five tolerance conditions resulted in significant differences in cortical activation between hemispheres. During right leg contractions, the left hemisphere was more active than the right hemisphere. Similarly, during left leg contractions, the right hemisphere was more active than the left hemisphere. These results suggest that fNIRS has sufficient spatial resolution to distinguish laterality of lower body contractions. This makes fNIRS an attractive technology in research and clinical applications in which laterality of brain activity is required during lower body activity.

Assessment of pharmacokinetic and pharmacodynamic interactions between zavegepant and sumatriptan: A phase 1, randomized, placebo-controlled study in healthy adults.

OBJECTIVE: To evaluate the pharmacodynamic (PD) and pharmacokinetic (PK) interactions between zavegepant and sumatriptan in healthy adults. BACKGROUND: Zavegepant is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist administered as a nasal spray approved in the United States for the acute treatment of migraine. Triptans, including sumatriptan, are a different class of drugs for acute migraine treatment and are associated with a risk of increased blood pressure (BP). Hence, it is important to study the drug-drug interactions between zavegepant and sumatriptan due to potential coadministration in clinical settings. METHODS: This was a Phase 1, single-center, partially blind, randomized, placebo-controlled, single-arm study. Eligible participants were males aged ≥ 18 and ≤ 40 years or females aged ≥ 18 and ≤ 50 years. On Day 1, participants received sumatriptan 2 × 6 mg subcutaneous injections (1 h apart) and were then randomized (6:1 ratio) to receive zavegepant 2 × 10 mg nasal spray (1 in each nostril) or placebo on Days 2 and 3. On Day 4, zavegepant or placebo was coadministered with sumatriptan after the second sumatriptan injection. BP, PK, and safety were evaluated at pre-specified time points. RESULTS: Forty-two participants enrolled in the study received at least one dose of any treatment and were included in the safety analyses. Forty-one participants who completed the study were included in the BP and PK analyses. The mean (standard deviation) time-weighted average (TWA) of mean arterial pressure (MAP [sumatriptan + zavegepant 87.2 (6.8) vs. sumatriptan 86.9 (6.0)]), diastolic BP (DBP [sumatriptan + zavegepant 72.3 (6.8) vs. sumatriptan 72.1 (6.2)]), and systolic BP (SBP [sumatriptan + zavegepant 116.8 (10.2) vs. sumatriptan 116.2 (8.6)]) did not change following zavegepant and sumatriptan coadministration on Day 4 compared to sumatriptan alone on Day 1. Statistical comparisons of the TWA of MAP, DBP, and SBP between sumatriptan and zavegepant coadministration and sumatriptan alone were similar; the differences observed were 0.04 mmHg for MAP (90% confidence interval [CI]: -0.69, 0.77 mmHg), 0.00 mmHg for DBP (90% CI: -0.76, 0.76 mmHg), and 0.33 mmHg for SBP (90% CI: -0.97, 1.63 mmHg). Sumatriptan PK after sumatriptan and zavegepant coadministration versus sumatriptan alone was similar; the comparison ratios were 102.5% (90% CI: 100.7%, 104.2%) for AUC0-inf and 104.1% (90% CI: 98.0%, 110.6%) for Cmax. A small difference in zavegepant PK exposure after sumatriptan and zavegepant coadministration versus zavegepant alone was not considered clinically relevant: the comparison ratios were 112.4% (90% CI: 103.4%, 122.3%) for AUC0-24 and 96.7% (90% CI: 88.9%, 105.2%) for Cmax. Overall, 90% (38/42) of participants experienced ≥ 1 treatment-emergent adverse event that was mild or moderate in severity. All treatments were generally safe and well tolerated. CONCLUSION: Coadministration of zavegepant with sumatriptan was safe and without PD or PK interactions in healthy adults.

Pediatric Hematology and Oncology Patients on Extracorporeal Membrane Oxygenation: Outcomes in a Multicenter, Retrospective Cohort 2009-2021.

OBJECTIVE: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter, retrospective study. SETTING: Sixteen PICUs in the United States and Israel. PATIENTS: We included patients aged younger than 19 years with an oncologic diagnosis or HCT who required ECMO support between 2009 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 149 patients were included in the study cohort. There were 118 patients with an oncologic diagnosis and 31 that received HCT. The indications for ECMO were respiratory failure (46%), combined respiratory and cardiac failure (28%), and cardiac failure (25%). Venovenous (V-V) ECMO was used in 45% of patients, with 53% of patients being placed on venoarterial (V-A) ECMO. For oncologic and HCT groups, survival to ECMO decannulation was 52% (62/118) and 64% (20/31), and survival to hospital discharge was 36% (43/118) and 42% (13/31), respectively. After adjusting for other factors, requiring cardiopulmonary resuscitation was associated with greater odds ratio of mortality (3.0 [95% CI, 1.2-7.7]). CONCLUSIONS: Survival to ECMO decannulation of pediatric oncologic and HCT patients in this study was 52-64%, depending upon diagnosis. However, survival to hospital discharge remains poor. Future research should prioritize understanding factors contributing to this survival gap within these patient populations.

Healthcare Burden and Resource Utilization After Pediatric Acute Respiratory Distress Syndrome: A Secondary Analysis of the Collaborative Pediatric Critical Care Research Network Acute Respiratory Distress Syndrome Study.

OBJECTIVES: To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months. DESIGN: Secondary analysis of a prospective multisite cohort study. SETTING: Eight academic PICUs in the United States (2019-2020). PATIENTS: Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event. INTERVENTIONS: None. METHODS AND MEASUREMENT: We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months. MAIN RESULTS: Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not. CONCLUSIONS: Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.

Acute Effects of Sprint Interval Training and Blood Flow Restriction on Neuromuscular and Muscle Function.

BFR) applied during sprint interval training (SIT) on performance and neuromuscular function. METHODS: Fifteen men completed a randomized bout of SIT with CBFR, IBFR, and without BFR (No-BFR), consisting of 2, 30-s maximal sprints on a cycle ergometer with a resistance of 7.5% of body mass. Concentric peak torque (CPT), maximal voluntary isometric contraction (MVIC) torque, and muscle thickness (MT) were measured before and after SIT, including surface electromyography (sEMG) recorded during the strength assessments. Peak and mean revolutions per minute (RPM) were measured during SIT and power output was examined relative to physical working capacity at the fatigue threshold (PWCFT). RESULTS: CPT and MVIC torque decreased from pre-SIT (220.3±47.6 Nm and 355.1±72.5 Nm, respectively) to post-SIT (147.9±27.7 Nm and 252.2±45.5 Nm, respectively, all P<0.05), while MT increased (1.77±0.31 cm to 1.96±0.30 cm). sEMG mean power frequency decreased during CPT (-12.8±10.5%) and MVIC (-8.7±10.2%) muscle actions. %PWCFT was greater during No-BFR (414.2±121.9%) than CBFR (375.9±121.9%). CONCLUSION: SIT with or without BFR induced comparable alterations in neuromuscular fatigue and sprint performance across all conditions, without affecting neuromuscular function.

Innovations in the Assessment of Skeletal Muscle Health: A Glimpse into the Future.

Skeletal muscle is the largest organ system in the human body and plays critical roles in athletic performance, mobility, and disease pathogenesis. Despite growing recognition of its importance by major health organizations, significant knowledge gaps remain regarding skeletal muscle health and its crosstalk with nearly every physiological system. Relevant public health challenges like pain, injury, obesity, and sarcopenia underscore the need to accurately assess skeletal muscle health and function. Feasible, non-invasive techniques that reliably evaluate metrics including muscle pain, dynamic structure, contractility, circulatory function, body composition, and emerging biomarkers are imperative to unraveling the complexities of skeletal muscle. Our concise review highlights innovative or overlooked approaches for comprehensively assessing skeletal muscle in vivo. We summarize recent advances in leveraging dynamic ultrasound imaging, muscle echogenicity, tensiomyography, blood flow restriction protocols, molecular techniques, body composition, and pain assessments to gain novel insight into muscle physiology from cellular to whole-body perspectives. Continued development of precise, non-invasive tools to investigate skeletal muscle are critical in informing impactful discoveries in exercise and rehabilitation science.

NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.

BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.

Successful Powerlifting in a Unilateral, Transtibial Amputee: A Descriptive Case Series.

ABSTRACT: Beausejour, JP, Guinto, G, Artrip, C, Corvalan, A, Mesa, MF, Lebron, MA, and Stock, MS. Successful powerlifting in a unilateral, transtibial amputee: A descriptive case series. J Strength Cond Res 38(5): e243-e252, 2024-There are no reports in the literature of powerlifting success after amputation. We had the unique opportunity to characterize functional outcomes, strength, muscle contractility and size, and corticospinal excitability in an accomplished, competitive powerlifter (best competition squat = 205.0 kg, deadlift = 262.7 kg) with a unilateral, transtibial amputation relative to amputee controls. Four men (age range = 23-49 years) with unilateral, lower-limb amputation (3 transtibial, 1 transfemoral) participated in 1 laboratory visit. We assessed 10-m gait speed, the timed up and go (TUG) test, 5-time sit-to-stand performance (5TSTS), contractile properties of the vastus lateralis (VL) and medial gastrocnemius by tensiomyography, and VL cross-sectional area (CSA) by ultrasonography. Unilateral assessments for the intact limb included isokinetic knee extension and flexion torque and power and transcranial magnetic stimulation derived corticospinal excitability. An interview with the powerlifter provided contextual perspective. Compared with the control subjects, the powerlifter performed the 5TSTS faster (6.8%), exhibited faster VL contraction times (intact limb = 12.2%; residual limb = 23.9%), and showed larger VL CSA for the intact limb (46.7%). The powerlifter exhibited greater knee extension and flexion peak torque and mean power, particularly at 180°·s -1 , as well as greater corticospinal excitability for the intact VL (65.6%) and tibialis anterior (79.6%). By contrast, the control subjects were faster in the TUG (18.3%) and comfortable (13.0%) and fast (21.4%) in the 10-m walk test. The major themes of our interview included needing to modify lifting mechanics, persistence, and remarkable pain tolerance. Our findings highlight the impressive neuromuscular adaptations that are attainable after lower-limb amputation.

BNT162b2 mRNA Vaccination Against Coronavirus Disease 2019 is Associated With a Decreased Likelihood of Multisystem Inflammatory Syndrome in Children Aged 5-18 Years-United States, July 2021 - April 2022.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. METHODS: In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. RESULTS: We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. CONCLUSIONS: Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.

Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children.

BACKGROUND: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury.

Lung injury after pediatric allogeneic hematopoietic cell transplantation (HCT) is a common and disastrous complication that threatens long-term survival. To develop strategies to prevent lung injury, novel tools are needed to comprehensively assess lung health in HCT candidates. Therefore, this study analyzed biospecimens from 181 pediatric HCT candidates who underwent routine pre-HCT bronchoalveolar lavage (BAL) at the University Medical Center Utrecht between 2005 and 2016. BAL fluid underwent metatranscriptomic sequencing of microbial and human RNA, and unsupervised clustering and generalized linear models were used to associate microbiome gene expression data with the development of post-HCT lung injury. Microbe-gene correlations were validated using a geographically distinct cohort of 18 pediatric HCT candidates. The cumulative incidence of post-HCT lung injury varied significantly according to 4 pre-HCT pulmonary metatranscriptome clusters, with the highest incidence observed in children with pre-HCT viral enrichment and innate immune activation, as well as in children with profound microbial depletion and concomitant natural killer/T-cell activation (P < .001). In contrast, children with pre-HCT pulmonary metatranscriptomes containing diverse oropharyngeal taxa and lacking inflammation rarely developed post-HCT lung injury. In addition, activation of epithelial-epidermal differentiation, mucus production, and cellular adhesion were associated with fatal post-HCT lung injury. In a separate validation cohort, associations among pulmonary respiratory viral load, oropharyngeal taxa, and pulmonary gene expression were recapitulated; the association with post-HCT lung injury needs to be validated in an independent cohort. This analysis suggests that assessment of the pre-HCT BAL fluid may identify high-risk pediatric HCT candidates who may benefit from pathobiology-targeted interventions.