Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma.

Background: Circulating tumor DNA has emerging clinical applications in several cancers; however, previous studies have shown low sensitivity in glioma. We investigated if 3 key glioma gene mutations IDH1, TERTp, and EGFRvIII could be reliably detected in plasma by droplet digital polymerase chain reaction (ddPCR) thereby demonstrating the potential of this technique for glioma liquid biopsy. Methods: We analyzed 110 glioma patients from our biobank with a total of 359 plasma samples (median 4 samples per patient). DNA was isolated from plasma and analyzed for IDH1, TERTp, and EGFRvIII mutations using ddPCR. Results: Total cfDNA was significantly associated with tumor grade, tumor volume, and both overall and progression-free survival for all gliomas as well as the grade 4 glioblastoma subgroup, but was not reliably associated with changes in tumor volume/progression during the patients' postoperative time course. IDH1 mutation was detected with 84% overall sensitivity across all plasma samples and 77% in the preoperative samples alone; however, IDH1 mutation plasma levels were not associated with tumor progression or survival. IDH1m plasma levels were not associated with pre- or postsurgery progression or survival. The TERTp C228T mutation was detected in the plasma ctDNA in 88% but the C250T variant in only 49% of samples. The EGFRvIII mutation was detected in plasma in 5 out of 7 patients (71%) with tissue EGFRvIII mutations in tumor tissue. Conclusions: Plasma ctDNA mutations detected with ddPCR provide excellent diagnostic sensitivity for IDH1, TERTp-C228T, and EGFRvIII mutations in glioma patients. Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.

Label-free optical imaging for brain cancer assessment.

Advances in label-free optical imaging offer a promising avenue for brain cancer assessment, providing high-resolution, real-time insights without the need for radiation or exogeneous agents. These cost-effective and intricately detailed techniques overcome the limitations inherent in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scans by offering superior resolution and more readily accessible imaging options. This comprehensive review explores a variety of such methods, including photoacoustic imaging (PAI), optical coherence tomography (OCT), Raman imaging, and IR microscopy. It focuses on their roles in the detection, diagnosis, and management of brain tumors. By highlighting recent advances in these imaging techniques, the review aims to underscore the importance of label-free optical imaging in enhancing early detection and refining therapeutic strategies for brain cancer.

Plasma ctDNA enables early detection of temozolomide resistance mutations in glioma.

Background: Liquid biopsy based on circulating tumor DNA (ctDNA) is a novel tool in clinical oncology, however, its use has been limited in glioma to date, due to low levels of ctDNA. In this study, we aimed to demonstrate that sequencing techniques optimized for liquid biopsy in glioma patients can detect ctDNA in plasma with high sensitivity and with potential clinical utility. Methods: We investigated 10 glioma patients with tumor tissue available from at least 2 surgical operations, who had 49 longitudinally collected plasma samples available for analysis. Plasma samples were sequenced with CAPP-seq (AVENIO) and tissue samples with TSO500. Results: Glioma-derived ctDNA mutations were detected in 93.8% of plasma samples. 25% of all mutations detected were observed in plasma only. Mutations of the mismatch repair (MMR) genes MSH2 and MSH6 were the most frequent circulating gene alterations seen after temozolomide treatment and were frequently observed to appear in plasma prior to their appearance in tumor tissue at the time of surgery for recurrence. Conclusions: This pilot study suggests that plasma ctDNA in glioma is feasible and may provide sensitive and complementary information to tissue biopsy. Furthermore, plasma ctDNA detection of new MMR gene mutations not present in the initial tissue biopsy may provide an early indication of the development of chemotherapy resistance. Additional clinical validation in larger cohorts is needed.

Therapeutic drug monitoring in inflammatory bowel disease patients on vedolizumab.

OBJECTIVE: We aimed to investigate whether vedolizumab (VDZ) levels were associated with inflammatory markers or clinical or endoscopic scoring in inflammatory bowel disease (IBD). METHODS: Besides demographic data, clinical scoring, endoscopic data, and laboratory markers of IBD patients treated with VDZ from 2015 to 2020 who had trough levels drawn on maintenance therapy were collected at baseline and at follow-up (after at least 8 weeks on VDZ therapy or after change in dose frequency). Low drug levels were defined as VDZ trough <20 µg/mL. RESULTS: We identified 89 patients with a mean age of 42.9 years. Of the 90 total trough levels drawn, 61.1% were low. Among patients on every 8 week (Q8 week) VDZ dosing, 81.5% had low troughs. After increasing dosing frequency to Q4 weeks, all patients showed improvement in VDZ levels, but 30.6% remained <20 µg/mL. Higher VDZ levels on Q8 week dosing were associated with higher albumin levels (P = 0.01). While higher VDZ levels on Q4 week dosing were associated with higher albumin (P = 0.02), lower erythrocyte sedimentation rate (P = 0.04) and higher likelihood of having mild disease or endoscopic remission (P = 0.01). No significant association was found between VDZ levels and clinical scoring, body mass index, hemoglobin, vitamin D or platelet levels on either Q8 or Q4 week dosing. CONCLUSIONS: Higher VDZ troughs were associated with higher albumin, mild endoscopic disease or endoscopic remission. Patients who continue to have low VDZ troughs despite Q4 week dosing may require a change in therapy.

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease.

Introduction: The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD). Methods: We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice. Results: Proteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil. Conclusions: Our results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD.

Acute effects of various doses of nitrate-rich beetroot juice on high-intensity interval exercise responses in women: a randomized, double-blinded, placebo-controlled, crossover trial.

BACKGROUND: This study investigated the acute effects of various doses of nitrate-rich beetroot juice on the responses to high-intensity interval exercise in women. METHODS: A double-blinded, randomized, placebo-controlled, crossover trial was conducted with 13 recreationally active young women (age = 23 ± 2 years). All participants performed interval exercise (8 × 1-min bouts of cycling at 85% of peak power output [PPO] interspersed with 1-min active recovery at 20% of PPO) 2.5 h after consumption of the randomly assigned beetroot juice containing 0 mmol (placebo), 6.45 mmol (single-dose), or 12.9 mmol (double-dose) NO3-. The heart rate (HR), blood pressure, blood lactate, blood glucose, oxygen saturation, rating of perceived exertion (RPE), and emotional arousal were assessed. RESULTS: Nitrate supplementation significantly altered the HR and RPE responses across the three trials. The mean HR was lower in the single- and double-dose groups than in the placebo control group during both work intervals and recovery periods, as well as across the overall protocol (all p < .05). The mean RPE was lower in the single- and double-dose groups than in the control group during recovery periods and across the overall protocol (all p < .001). However, there was no significant difference in either HR or RPE between the single- and double-dose groups at any time point. CONCLUSIONS: Acute nitrate ingestion led to significant decreases in the mean HR and RPE during high-intensity interval exercise, but no additional benefit was observed with higher nitrate content. These findings may assist practitioners in implementing more effective nitrate supplementation strategies during high-intensity interval exercise.

A Phase II trial of alternating osimertinib and gefitinib therapy in advanced EGFR-T790M positive non-small cell lung cancer: OSCILLATE.

In this phase II, single arm trial (ACTRN12617000720314), we investigate if alternating osimertinib and gefitinib would delay the development of resistance to osimertinib in advanced, non-small cell lung cancer (NSCLC) with the epidermal growth factor receptor (EGFR) T790M mutation (n = 47) by modulating selective pressure on resistant clones. The primary endpoint is progression free-survival (PFS) rate at 12 months, and secondary endpoints include: feasibility of alternating therapy, overall response rate (ORR), overall survival (OS), and safety. The 12-month PFS rate is 38% (95% CI 27.5-55), not meeting the pre-specified primary endpoint. Serial circulating tumor DNA (ctDNA) analysis reveals decrease and clearance of the original activating EGFR and EGFR-T790M mutations which are prognostic of clinical outcomes. In 73% of participants, loss of T790M ctDNA is observed at progression and no participants have evidence of the EGFR C797S resistance mutation following the alternating regimen. These findings highlight the challenges of treatment strategies designed to modulate clonal evolution and the clinical importance of resistance mechanisms beyond suppression of selected genetic mutations in driving therapeutic escape to highly potent targeted therapies.

CD4+ T cell immunity is dependent on an intrinsic stem-like program.

CD4+ T cells are central to various immune responses, but the molecular programs that drive and maintain CD4+ T cell immunity are not entirely clear. Here we identify a stem-like program that governs the CD4+ T cell response in transplantation models. Single-cell-transcriptomic analysis revealed that naive alloantigen-specific CD4+ T cells develop into TCF1hi effector precursor (TEP) cells and TCF1-CXCR6+ effectors in transplant recipients. The TCF1-CXCR6+CD4+ effectors lose proliferation capacity and do not reject allografts upon adoptive transfer into secondary hosts. By contrast, the TCF1hiCD4+ TEP cells have dual features of self-renewal and effector differentiation potential, and allograft rejection depends on continuous replenishment of TCF1-CXCR6+ effectors from TCF1hiCD4+ TEP cells. Mechanistically, TCF1 sustains the CD4+ TEP cell population, whereas the transcription factor IRF4 and the glycolytic enzyme LDHA govern the effector differentiation potential of CD4+ TEP cells. Deletion of IRF4 or LDHA in T cells induces transplant acceptance. These findings unravel a stem-like program that controls the self-renewal capacity and effector differentiation potential of CD4+ TEP cells and have implications for T cell-related immunotherapies.

Prevalence of Delirium After Abdominal Surgery and Association With Ketamine: A Retrospective, Propensity-Matched Cohort Study.

IMPORTANCE: Delirium is a common postoperative complication for older patients in the ICU. Ketamine, used primarily as an analgesic, has been thought to prevent delirium. OBJECTIVE: Determine the prevalence and association of delirium with low-dose ketamine use in ICU patients after abdominal surgery. DESIGN: Single-center, retrospective, propensity-matched cohort study. SETTING: Eight hospital academic medical center. PATIENTS: Cohort comprising 1836 patients admitted to the ICU after abdominal surgery between June 23, 2018 and September 1, 2022. MAIN OUTCOMES AND MEASURES: Propensity score matching (PSM) with a 3:1 ratio between no-ketamine use and ketamine use was performed through a greedy algorithm (caliper of 0.005). Outcomes of interest included: delirium (assessed by Confusion Assessment Method-ICU), mean pain score (Numeric Pain Scale or Critical Care Pain Observation Tool score as available), mean opioid consumption (morphine milligram equivalents), length of stay (d), and mortality. RESULTS: Prevalence of delirium was 47.71% (95% CI, 45.41-50.03%) in the cohort. Of 1836 patients, 120 (6.54%) used low-dose ketamine infusion. After PSM, the prevalence of delirium was 56.02% (95% CI, 51.05-60.91%) in all abdominal surgery patients. The ketamine group had 41% less odds of delirium (odds ratio [OR] = 0.59; 95% CI, 0.37-0.94; p = 0.026) than patients with no-ketamine use. Patients with ketamine use had higher mean pain scores (3.57 ± 2.86 vs. 2.21 ± 2.09, p < 0.001). In the subgroup analysis, patients in the ketamine-use group 60 years old or younger had 64% less odds of delirium (OR = 0.36; 95% CI, 0.13-0.95; p = 0.039). The mean pain scores were higher in the ketamine group for patients 60 years old or older. There was no significant difference in mortality and opioid consumption. CONCLUSIONS AND RELEVANCE: Low-dose ketamine infusion was associated with lower prevalence of delirium in ICU patients following abdominal surgery. Prospective studies should further evaluate ketamine use and delirium.

Charting Single Cell Lineage Dynamics and Mutation Networks via Homing CRISPR.

Single cell lineage tracing, essential for unraveling cellular dynamics in disease evolution is critical for developing targeted therapies. CRISPR-Cas9, known for inducing permanent and cumulative mutations, is a cornerstone in lineage tracing. The novel homing guide RNA (hgRNA) technology enhances this by enabling dynamic retargeting and facilitating ongoing genetic modifications. Charting these mutations, especially through successive hgRNA edits, poses a significant challenge. Our solution, LINEMAP, is a computational framework designed to trace and map these mutations with precision. LINEMAP meticulously discerns mutation alleles at single-cell resolution and maps their complex interrelationships through a mutation evolution network. By utilizing a Markov Process model, we can predict mutation transition probabilities, revealing potential mutational routes and pathways. Our reconstruction algorithm, anchored in the Markov model's attributes, reconstructs cellular lineage pathways, shedding light on the cell's evolutionary journey to the minutiae of single-cell division. Our findings reveal an intricate network of mutation evolution paired with a predictive Markov model, advancing our capability to reconstruct single-cell lineage via hgRNA. This has substantial implications for advancing our understanding of biological mechanisms and propelling medical research forward.

The effects of physical activity on pediatric eyes: A systematic review and meta-analysis.

INTRODUCTION: Examining the retina represents a non-invasive method to evaluate abnormalities pertaining to the nervous and cardiovascular systems. Evidence indicates that physical activity is a non-pharmacological intervention to enhance the nervous and cardiovascular systems. However, little is unknown about its effects on ocular characteristics in children and adolescents. The purpose of this study was to examine the effects of physical activity interventions on ocular characteristics in children and adolescents. METHOD: The electronic bases Web of Science, Embase, Cochrane Library, PubMed, SPORTDiscus, CINAHL, and ERIC were searched from inception to May 2023. Incorporated were randomized controlled trials or quasi-experimental designs that had implemented acute or chronic physical activity interventions among children and adolescents to evaluate various eye-related attributes via clinical examinations or surveys. Two authors independently performed the data extraction and risk of bias assessment, utilizing the Physiotherapy Evidence Database checklist. RESULTS: A total of 474 articles were identified, of which eight articles underwent a systematic review, and six were chosen for meta-analysis. Chronic physical activity interventions positively impacted central retinal artery equivalent (CRAE) with a small to moderate effect (SMD = 0.21; 95% CI 0.04 to 0.39, p = 0.034, I2 = 0%) and central retinal venular equivalent (CRVE) with a small effect (SMD = 0.098; 95% CI 0.08 to 0.11; p = 0.008, I2 = 0%). Intraocular pressure, kinetic visual acuity, and eye strain also improved significantly after physical activity interventions. DISCUSSION: Participating in chronic physical activity programs appear to impact children and adolescents' eye-related attributes positively.

Effects of intermittent dieting with break periods on body composition and metabolic adaptation: a systematic review and meta-analysis.

CONTEXT: Intermittent dieting incorporated with break periods (INT-B) has recently been promoted as an alternative dietary approach for optimal weight management. OBJECTIVE: This study assessed the effectiveness of INT-B compared with that of conventional continuous energy restriction (CER) for improving body composition and attenuating metabolic adaptation. DATA SOURCES: A systematic search was conducted on 6 databases using all available records until July 2023. DATA EXTRACTION: The extracted data included the lead author, year of publication, population characteristics, intervention protocols, duration, and adherence. DATA ANALYSIS: Random-effects meta-analyses were conducted for within-group and between-group comparisons of anthropometric and metabolic outcomes. Subgroup moderator analysis was performed for the types of INT-B, intervention duration, and population characteristics. RESULTS: Of the 1469 records, 12 randomized trials (with 881 participants) were included. Within-group analyses demonstrated significant improvements in body mass, fat mass, body mass index, body fat percentage, and waist circumference following both INT-B and CER, with no significant group differences. However, resting metabolic rate (RMR) was significantly reduced following CER only. The compensatory reduction in RMR was significantly smaller following INT-B compared with CER, suggesting a lesser degree of metabolic adaptation. INT-B had a more significant effect on RMR retention in individuals with overweight/obesity compared with resistance-trained individuals. CONCLUSION: This review provides up-to-date evidence for INT-B as a viable dietary strategy to improve body composition and attenuate metabolic adaptation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023448959.

TP-0184 inhibits FLT3/ACVR1 to overcome FLT3 inhibitor resistance and hinder AML growth synergistically with venetoclax.

We identified activin A receptor type I (ACVR1), a member of the TGF-ß superfamily, as a factor favoring acute myeloid leukemia (AML) growth and a new potential therapeutic target. ACVR1 is overexpressed in FLT3-mutated AML and inhibition of ACVR1 expression sensitized AML cells to FLT3 inhibitors. We developed a novel ACVR1 inhibitor, TP-0184, which selectively caused growth arrest in FLT3-mutated AML cell lines. Molecular docking and in vitro kinase assays revealed that TP-0184 binds to both ACVR1 and FLT3 with high affinity and inhibits FLT3/ACVR1 downstream signaling. Treatment with TP-0184 or in combination with BCL2 inhibitor, venetoclax dramatically inhibited leukemia growth in FLT3-mutated AML cell lines and patient-derived xenograft models in a dose-dependent manner. These findings suggest that ACVR1 is a novel biomarker and plays a role in AML resistance to FLT3 inhibitors and that FLT3/ACVR1 dual inhibitor TP-0184 is a novel potential therapeutic tool for AML with FLT3 mutations.

Effect of Physical Exercise-Based Rehabilitation on Long COVID: A Systematic Review and Meta-analysis.

PURPOSE: The number of persons living with post-coronavirus disease 2019 (COVID-19) conditions or long COVID continues to rise worldwide; however, the etiology and the treatment of long COVID remain nebulous. Therefore, efficient, feasible, and cost-effective therapeutic strategies for a large population with long COVID remain warranted. Physical exercise-based rehabilitation is a promising strategy for long COVID, although its therapeutic effects remain to be determined. This systematic review and meta-analysis aimed to examine the effects of physical exercise-based rehabilitation on long COVID. METHODS: The electronic databases Medline, Embase, Global Health (Ovid), CINAHL (EBSCO), Web of Science, WHO Global Research Database on COVID-19, LitCovid, and Google Scholar were searched from their inception to November 2022. The identified articles were independently screened by three reviewers, and a random-effects model was used to determine the mean differences in the meta-analysis. RESULTS: Twenty-three studies involving 1579 individuals who had COVID-19 (752 women) were included. Physical exercise-based rehabilitation showed beneficial effects on long COVID-related symptoms characterized by dyspnea, fatigue, and depression, as well as on the 6-min walk test, forced expiratory volume in 1 s/forced vital capacity, and quality of life in people who had COVID-19. CONCLUSIONS: Physical exercise-based rehabilitation is a potential therapeutic strategy against long COVID and can be applied as a routine clinical practice in people who have recovered from COVID-19. However, customized physical exercise-based rehabilitation programs and their effects on specific types of long COVID require future large-scale studies.

Associations of social jetlag with physical activity and sedentary behaviour in children and adolescents: A systematic review and meta-analysis.

Sleep and daytime movement behaviours occur co-dependently with each other within a finite 24 h day. Sleep parameters other than sleep duration, such as social jetlag and chronotype, have been linked to health problems and unhealthy behaviours among children and adolescents. Given the increasing number of studies examining sleep timing/chronotype and weight-related behaviours, including physical activity and sedentary behaviour, in the past decade, this systematic review and meta-analysis collated and evaluated the evidence on the relationships of social jetlag and chronotype with physical activity and sedentary behaviour among children and adolescents aged 3-17 years. Seven databases were searched on 16 March 2022, and 52 studies were identified as eligible for inclusion, 47 of which were suitable for the meta-analysis. A positive association was found between social jetlag and screen media use (r = 0.14, 95% CI: 0.04-0.24; I2 = 96%; p = 0.008). The morning chronotype was associated with a higher level of physical activity and a lower level of sedentary behaviour than the evening chronotype. No relationship was found between social jetlag and physical activity. The magnitude of heterogeneity among the included studies was high. Further experimental studies are urgently required to understand how circadian preference or misalignment affects activity behaviours. Interventions to promote an active lifestyle in young populations should consider their circadian preference, especially among individuals with the evening chronotype.

Automated catheter segmentation and tip detection in cerebral angiography with topology-aware geometric deep learning.

BACKGROUND: Visual perception of catheters and guidewires on x-ray fluoroscopy is essential for neurointervention. Endovascular robots with teleoperation capabilities are being developed, but they cannot 'see' intravascular devices, which precludes artificial intelligence (AI) augmentation that could improve precision and autonomy. Deep learning has not been explored for neurointervention and prior works in cardiovascular scenarios are inadequate as they only segment device tips, while neurointervention requires segmentation of the entire structure due to coaxial devices. Therefore, this study develops an automatic and accurate image-based catheter segmentation method in cerebral angiography using deep learning. METHODS: Catheters and guidewires were manually annotated on 3831 fluoroscopy frames collected prospectively from 40 patients undergoing cerebral angiography. We proposed a topology-aware geometric deep learning method (TAG-DL) and compared it with the state-of-the-art deep learning segmentation models, UNet, nnUNet and TransUNet. All models were trained on frontal view sequences and tested on both frontal and lateral view sequences from unseen patients. Results were assessed with centerline Dice score and tip-distance error. RESULTS: The TAG-DL and nnUNet models outperformed TransUNet and UNet. The best performing model was nnUNet, achieving a mean centerline-Dice score of 0.98 ±0.01 and a median tip-distance error of 0.43 (IQR 0.88) mm. Incorporating digital subtraction masks, with or without contrast, significantly improved performance on unseen patients, further enabling exceptional performance on lateral view fluoroscopy despite not being trained on this view. CONCLUSIONS: These results are the first step towards AI augmentation for robotic neurointervention that could amplify the reach, productivity, and safety of a limited neurointerventional workforce.

A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset. Materials and Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed. Results: The iBRISK model's accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the "low" POM group had malignant lesions, while in the "high" POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million. Conclusion: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs.Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue.

Association of Sedentary Lifestyle with Risk of Acute and Post-Acute COVID-19 Sequelae: A Retrospective Cohort Study.

BACKGROUND: Evidence suggests that coronavirus disease 2019 (COVID-19) survivors could experience COVID-19 sequelae. Although various risk factors for COVID-19 sequelae have been identified, little is known about whether a sedentary lifestyle is an independent risk factor. METHODS: In this retrospective cohort study, 4850 participants self-reported their COVID-19 sequelae symptoms between June and August 2022. A sedentary lifestyle included physical inactivity (<150 min/week of moderate-to-vigorous intensity physical activity) and prolonged sedentary behavior (≥10 h/day) before the fifth COVID-19 wave was recorded. Logistic regression analysis was performed to determine the relationships between sedentary lifestyle and risk of acute and post-acute (lasting ≥2 months) COVID-19 sequelae. RESULTS: A total of 1443 COVID-19 survivors and 2962 non-COVID-19 controls were included. Of the COVID-19 survivors, >80% and >40% self-reported acute and post-acute COVID-19 sequelae, respectively. In the post-acute phase, COVID-19 survivors who were physically inactive had a 37% lower risk of insomnia, whereas those with prolonged sedentary behavior had 25%, 67%, and 117% higher risks of at least one symptom, dizziness, and "pins and needles" sensation, respectively. For the acute phase, prolonged sedentary behavior was associated with a higher risk of fatigue, "brain fog," dyspnea, muscle pain, joint pain, dizziness, and "pins and needles" sensation. Notably, sedentary behavior, rather than physical inactivity, was correlated with a higher risk of severe post-COVID-19 sequelae in both acute and post-acute phases. CONCLUSIONS: Prolonged sedentary behavior was independently associated with a higher risk of both acute and post-acute COVID-19 sequelae, whereas physical inactivity played contradictory roles in COVID-19 sequelae.