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Objectives: Sedentary behaviour (SB) is related to lower worker health-related quality of life (HRQOL), mental health and productivity. However, it is unknown whether reducing SB improves these outcomes. This study assessed whether a 3-month SB reduction intervention improved or was associated with dose-response changes in workplace satisfaction, productivity, mood and HRQOL., Methods: Inactive desk workers with elevated blood pressure were randomised to a 3-month SB reduction intervention (n=135) or control (n=136). The intervention used a sit-stand desk, wrist-worn activity prompter and bi-monthly individual coaching to primarily replace work SB with standing and stepping. SB measured via a thigh-mounted activPAL3 micro, workplace satisfaction, productivity, mood and HRQOL were assessed at baseline and 3 months. Analyses of covariance compared changes in outcomes between groups with adjustment for baseline values. In both groups, associations between changes in work and non-work SB and outcomes were examined using linear regression., Results: Compared with control, reducing SB did not significantly change workplace satisfaction, productivity or HRQOL. Among mood measures, only vigour improved (1.01 vs 0.1 points, p=0.0302). Among all participants, reductions in non-work SB were associated with improvements in workplace satisfaction (+0.15 and +0.27 points/hour of non-work standing and stepping, respectively) and productivity (+0.47 points/hour of non-work stepping), while changes in SB during work were not related., Conclusions: Interventions reducing non-work rather than work SB may be more impactful for improving workplace satisfaction and HRQOL outcomes. Future studies should explore workplace-based SB reduction interventions that are longer and target non-work time to improve similar outcomes., Trial Registration Number: NCT03307343., Competing Interests: Competing interests: JMJ reports participation in the Scientific Advisory Board for Wondr Health, ownership of Healthy Lifestyles Consulting, LLC, and PI of the clinical site for a research study awarded to the University of Kansas Medical Center by Epitomee Medical. The other authors report no relevant conflicts of interest., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objectives: Paradoxical associations between high occupational physical activity (OPA) and cardiovascular disease may be explained by exaggerated cardiovascular responses from high work-related stress or low worker fitness., Methods: OPA, blood pressure (BP), heart rate (HR), and rate-pressure product (RPP; HR × BP) were measured objectively for 24 hours in 19 male workers. Work-related stress was measured using the Stress in General Scale. Fitness was estimated using a submaximal treadmill test. Effect modification by work-related stress and fitness on associations between OPA and cardiovascular responses was examined using mixed models with interactions., Results: Associations between OPA and RPP, HR, and BP were stronger with high stress ( P < 0.05). Associations of work-time moderate and vigorous physical activity and RPP were attenuated with higher fitness ( P < 0.05)., Conclusions: OPA performed under high work-related stress or by workers with low fitness may exaggerate cardiovascular responses to OPA., Competing Interests: Conflict of Interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Objectives: While previous research has utilized remote delivery of yoga interventions, no research has specifically interrogated the effectiveness of remote yoga intervention delivery. In this secondary analysis of weight-maintenance trial data, we examined participant perceptions of essential yoga properties across in-person and remote formats, hypothesizing that perceptions would not differ following remote delivery., Methods: 24 women with overweight or obesity (34.6±4.1 kg/m2, 48.2±9.9 years) received a 12-week Iyengar yoga intervention (2x/week) following a 3-month behavioral weight loss program. Of 23 participants who completed follow-up questionnaires, 12 received the planned in-person intervention and 11 received a remote intervention (delivered live) due to the COVID-19 pandemic. The Essential Properties of Yoga Questionnaire (EPYQ) was completed online by participants and by the instructors to measure the perceptions of the relative emphasis placed on the essential components of the yoga intervention via 14 subscales. Linear regression models were used to compare perceptions of each EPYQ dimension across in-person and remote delivery methods, as well as between participants and instructors, independent of delivery method., Results: 13 of the 14 subscales did not differ between delivery modalities (p>0.05). Participants perceived more individual attention within in-person yoga (p = 0.003). For both delivery methods, instructors perceived breathwork, restorative postures, and body locks to be incorporated to a lesser degree compared to participants (β = -1.28, p = 0.003; β = -1.57, p = 0.019; β = -1.39, p = 0.036; respectively). No other significant differences across the participant and instructor scores were observed., Conclusions: Findings provide preliminary support for the use of live remote delivery of yoga, effectively communicating most essential yoga properties when compared to in-person classes. However, participants perceived more individual attention with in-person versus remote delivery; thus, future remote-based yoga interventions may benefit from providing additional individualized feedback., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Unick is on the Scientific Advisory Board of Medifast. Dr. Sherman is an ambassador for lululemon. All remaining authors have no conflicts of interest to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Sherman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Leisure time physical activity (LTPA) confers cardiovascular health benefits, while occupational physical activity (OPA) may have paradoxically negative health associations. This study tested the explanatory hypothesis that unfavourable cardiac remodelling may result from chronic OPA-induced cardiovascular strain., Methods and Results: Longitudinal associations of OPA and left ventricular (LV) structure and function were examined in 1462 participants {50.0% female, 56.4% White, aged 30.4 ± 3.4 years at baseline [Year 5 exam (1990-91)]} from the Coronary Artery Risk Development in Young Adults study. Left ventricular structure and function were measured as LV mass (LVMi), end-diastolic volume (LVEDVi), end-systolic volume (LVESVi), ejection fraction (LVEF), stroke volume (LVSVi), and e/a-wave ratio (EA ratio) via echocardiography at baseline and 25 years later. Occupational physical activity was reported at seven exams during the study period as months/year with 'vigorous job activities such as lifting, carrying, or digging' for ≥5 h/week. The 25-year OPA patterns were categorized into three trajectories: no OPA (n = 770), medium OPA (n = 410), and high OPA (n = 282). Linear regression estimated associations between OPA trajectories and echocardiogram variables at follow-up after adjusting for baseline values, individual demographic/health characteristics, and LTPA. Twenty-five-year OPA exposure was not significantly associated with LVMi, LVEDVi, LVSVi, or EA ratio (P > 0.05). However, higher LVESVi (β = 1.84, P < 0.05) and lower LVEF (β = -1.94, P < 0.05) were observed at follow-up among those in the high- vs. no-OPA trajectories., Conclusion: The paradoxically adverse association of OPA with cardiovascular health was partially supported by null or adverse associations between high OPA and echocardiogram outcomes. Confirmation is needed using more precise OPA measures., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical activity for any purpose counts toward meeting Physical Activity Guidelines (PAG). However, national surveillance systems traditionally focus on leisure-time physical activity. There is an incomplete understanding of the association between meeting PAG in leisure time and occupation activity level among US workers., Methods: We used cross-sectional 2020 National Health Interview Survey data to examine US adults aged 18-64 years who worked the week before the survey (n = 14,814). We estimated the proportion meeting aerobic and muscle-strengthening PAG in leisure time by occupation activity level (low, intermediate, and high). Using logistic regression, we examined the association between meeting PAG in leisure time and occupation activity level, adjusted for sociodemographic characteristics and stratified by hours worked. We compared the sociodemographic characteristics of adults working ≥40 hours (the previous week) in high-activity occupations to those in low- or intermediate-activity occupations., Results: Adults working in high-activity occupations were less likely to meet PAG in leisure time (26.1% [24.3-28.1]) versus those in low-activity (30.6% [29.1-32.2], P < .01) or intermediate-activity (32.4% [30.8-34.2]) occupations. In stratified, adjusted models, adults working ≥40 hours in low- and intermediate-activity occupations were 13% and 20%, respectively, more likely to meet PAG in leisure time versus those in high-activity occupations. Among those working ≥40 hours, adults in high-activity occupations were more likely to be Hispanic or Latino, male, younger, and have a high school education or lower compared with those in less active occupations., Conclusion: Traditional surveillance may underestimate meeting PAG among people working in high-activity occupations, potentially disproportionately affecting certain groups.

Objectives. Postural imbalance can result from hyperthermia-mediated muscular fatigue and is a major factor contributing to injuries from falling. The objective of this study was to investigate the effect of exercise-induced hyperthermia and the impact of cooling on postural balance while wearing firefighters' protective clothing (FPC) in a hot environment. Methods. A portable force platform measured postural balance characterized by postural sway patterns using center of pressure metrics. Twelve healthy, physically fit males were recruited to stand on the force platform once with eyes open and once with eyes closed before and after treadmill exercise (40% V ˙ O 2 max ) inside an environmental chamber under hot and humid conditions (30 °C and 70% relative humidity) while wearing FPC. Subjects participated in two randomly assigned experimental phases: control and cooling intervention. Results. A significant increase in physiological responses and postural balance metrics was observed after exercising in the heat chamber while wearing FPC. Cooling resulted in a significant effect only on postural sway speed after exercise-induced hyperthermia. Conclusions. Hyperthermia can negatively alter postural balance metrics, which may lead to an increased likelihood of falling. The utilization of body cooling reduced the thermal strain but had limited impact on postural balance stability.

Purpose: Differential effects on fitness are hypothesized to contribute to the opposing health effects of leisure-time physical activity (LTPA) and occupational physical activity (OPA). As such, this study examined cross-sectional and longitudinal associations of fitness with LTPA and OPA., Methods: This study examined fitness associations with LTPA and OPA across 13 yr in the Coronary Artery Risk Development in Young Adults study (years 7 (baseline), 10, 15, and 20 (follow-up) examinations). Fitness was measured at baseline and follow-up via symptom-limited maximal graded exercise test (GXT) duration (in seconds), whereas LTPA and OPA were self-reported during each examination. Baseline and follow-up cross-sectional associations of LTPA (low, medium, high) and OPA (0, 1-6, and ≥6 months with OPA) with fitness were examined using linear regression. Longitudinal linear regression examined associations between 13-yr LTPA (low, medium, or high) and OPA (no, decreasing, or increasing) trajectories with fitness at follow-up, adjusted for baseline values. All models adjusted for center, sex, race, age, education, smoking history, alcohol intake, resting blood pressure, diabetes status, and body mass index. Stratified analyses examined associations by sex (female/male), race (Black/White), and LTPA groups., Results: Compared with low, medium, and high LTPA were positively associated with fitness in all analyses ( P < 0.001). Reporting 1-6 or ≥6 months with OPA was negatively associated with fitness in cross-sectional follow-up models ( β = -15.6 and -15.4, respectively; P ≤ 0.01). Longitudinally, those with increasing OPA had lower follow-up fitness compared with no OPA ( β = -16.41, P < 0.01). Negative associations of OPA with fitness were not meaningfully different across sex and race groups. Significant LTPA-OPA interactions were observed ( P < 001)., Conclusions: Physical activity research and public health promotion should consider domain-specific associations on cardiovascular health., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Psychological stress is recognized as an important modifiable risk factor for cardiovascular disease (CVD). Despite its potential significance, few to no studies have evaluated the association between stress, stress mindset, and CVD risk factors among rural first responders. The objectives of this study were to identify relationships between general stress, stress mindset, and CVD risk factors., Methods: The study sample (n = 148) included those 18 years or older and who currently serve as a first responder, defined as either EMS, firefighter, or law enforcement. Questionnaires captured information on demographics, years of work experience as a first responder, multiple first responder occupations, general stress, stress mindset, and self-reported CVD risk factors. Data were analyzed using regression analyses., Results: Findings suggest that first responders with a stress-is-negative mindset have significantly higher general stress levels (β = 2.20, p = 0.01). Of note, general stress was not a significant predictor of CVD risk factors (AOR = 1.00, 95%CI = 0.93, 1.08) included in our study. However, a negative stress mindset was statistically significant predictor of CVD risk factors (AOR = 2.82, 95%CI = 1.29, 6.41), after adjusting for general stress and other potential confounders., Conclusions: Findings suggest that stress mindset is an independent predictor of stress and CVD risk factors among rural first responders. These results have the potential to inform educational and organization level interventions targeting stress appraisal for this vulnerable sub population of workers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: We assessed sedentary behavior (SB) patterns and examined its associations, by domain, with cardiovascular disease (CVD) risk measures in desk workers ( N = 273)., Methods: Sedentary behavior was measured by activPAL3 and partitioned into occupational and nonoccupational SB. Cardiovascular disease risk measures included blood pressure, pulse wave velocity, heart rate, and heart rate variability. Paired t tests evaluated patterns of SB across domains. Linear regressions estimated associations of occupational and nonoccupational SB with CVD risk measures., Results: Participants spent 69% of their time in SB; higher proportions were accumulated during occupational versus nonoccupational time. Higher all-domain SB was only associated with higher pulse wave velocity. Paradoxically, greater nonoccupational SB unfavorably associated with CVD risk measures, while higher occupational SB favorably correlated to CVD risk measures., Conclusions: Observed paradoxical associations suggest that domain should be considered in efforts to improve cardiovascular health by reducing SB., Competing Interests: Conflict of interest: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Background: Firefighters are at high risk for nonfatal and fatal occupational injuries. While some past research has quantified firefighter injuries using various data sources, Ohio workers' compensation injury claims data largely have not been used., Methods: Public and private firefighter claims, including volunteer and career firefighters, from Ohio's workers' compensation data for 2001-2017 were identified based on occupational classification codes and manual review of the occupation title and injury description. The task during injury (firefighting, patient care, training, other/unknown, etc.) was manually coded based on the injury description. Injury claim counts and proportions were described across claim type (medical-only or lost-time), worker demographics, task during injury, injury events, and principal diagnoses., Results: 33,069 firefighter claims were identified and included. Most claims were medical-only (66.28%, <8 days away from work) and involved males (93.81%) aged 25-54 years (86.54%). While the task during injury could not be categorized for many narratives (45.96%), the largest percentage that could be categorized occurred during firefighting (20.48%) and patient care (17.60%). The most common injury events were overexertion involving outside sources (31.33%) and struck by objects or equipment (12.68%). The most frequent principal diagnoses were back, lower extremity, and upper extremity sprains (16.02%, 14.46%, and 11.98%, respectively)., Conclusions: This study provides a preliminary basis for the development of focused firefighter injury prevention programming and training. Obtaining denominator data, enabling rate calculation, would strengthen the risk characterization. Based on the current data, prevention efforts focusing on the most frequent injury events and diagnoses may be warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 National Safety Council and Elsevier Ltd. All rights reserved.)

Introduction/purpose: Sedentary behavior (SB) is common in desk-based work and prolonged periods of SB are associated with negative health outcomes. This study assessed associations between workplace characteristics and setting and movement patterns during working hours., Methods: This secondary analysis used baseline data from the Reducing Sedentary Behavior to Decrease Blood Pressure (RESET BP) clinical trial which enrolled inactive, desk-based workers with elevated blood pressure ( n =271; mean age: 45.3±11.6 years; body mass index (BMI): 30.66±7.1 kg/m 2 ; 59.4% women). Physical and social workplace characteristics were assessed by a study-developed questionnaire and the Office Environment and Sitting Scale (OFFESS). Participants also wore an activPAL activity monitor for 7 days and reported working hours in a diary to measure SB and physical activity (PA) specifically while working. Linear regression was used to analyze cross-sectional associations between workplace characteristics and SB and PA. A stratified analysis was also conducted to assess associations among home-based and in-office desk workers separately. Analyses were adjusted for age, gender, BMI, and work wear time., Results: Participants spent 77% of working hours in SB. Public vs. private offices, working in-office vs. at home, higher local connectivity, and greater overall connectedness were associated with lower SB and/or greater PA (all p<0.05). Higher frequency of face-to-face interactions, and greater visibility and proximity to co-workers was associated with less SB and more PA (all p<0.05). For example, home-based workers had more total SB (+17.2±8.4 mins/day), more SB bouts ≥30 mins (+39.1±12.8 mins/day), and less steps (695±201 steps/day) than in-office employees. Stratification by office setting revealed differences in associations between SB and PA and workplace characteristics., Conclusions: More public, open spaces with more social interactions and physical walkways could improve SB and PA patterns during work. Home-based workers had more SB, less PA, and unique associations of these activities with workplace characteristics, suggesting a need for tailored interventions.

Background: Studies indicate that patients can be "seeded" with their own cancer cells during oncologic surgery and that the immune response to these circulating cancer cells might influence the risk of cancer recurrence. Preliminary data from animal studies and some retrospective analyses suggest that anesthetic technique might affect the immune response during surgery and hence the risk of cancer recurrence. In 2015, experts called for prospective scientific inquiry into whether anesthetic technique used in cancer resection surgeries affects cancer-related outcomes such as recurrence and mortality. Therefore, we designed a pragmatic phase 3 multicenter randomized controlled trial (RCT) called General Anesthetics in Cancer Resection (GA-CARES)., Methods: After clinical trial registration and institutional review board approval, patients providing written informed consent were enrolled at five sites in New York (NY) State. Eligible patients were adults with known or suspected cancer undergoing one of eight oncologic surgeries having a high risk of cancer recurrence. Exclusion criteria included known or suspected history of malignant hyperthermia or hypersensitivity to either propofol or volatile anesthetic agents. Patients were randomized (1:1) stratified by center and surgery type using REDCap to receive either propofol or volatile agent for maintenance of general anesthesia (GA). This pragmatic trial, which seeks to assess the potential impact of anesthetic type in "real world practice", did not standardize any aspect of patient care. However, potential confounders, e.g., use of neuroaxial anesthesia, were recorded to confirm the balance between study arms. Assuming a 5% absolute difference in 2-year overall survival rates (85% vs 90%) between study arms (primary endpoint, minimum 2-year follow-up), power using a two-sided log-rank test with type I error of 0.05 (no planned interim analyses) was calculated to be 97.4% based on a target enrollment of 1800 subjects. Data sources include the National Death Index (gold standard for vital status in the USA), NY Cancer Registry, and electronic harvesting of data from electronic medical records (EMR), with minimal manual data abstraction/data entry., Discussion: Enrollment has been completed (n = 1804) and the study is in the follow-up phase. This unfunded, pragmatic trial, uses a novel approach for data collection focusing on electronic sources., Trial Registration: Registered (NCT03034096) on January 27, 2017, prior to consent of the first patient on January 31, 2017., (© 2023. The Author(s).)

This study compared exercise performance and comfort while wearing an N95 filtering facepiece respirator (N95), cloth mask, or no intervention control for source control during a maximal graded treadmill exercise test (GXT). Twelve Division 1 athletes (50% female, age = 20.1 ± 1.2, BMI = 23.5 ± 1.6) completed GXTs under three randomized conditions (N95, cloth mask, control). GXT duration, heart rate (HR), respiration rate (RR), transcutaneous oxygen saturation (SpO2), transcutaneous carbon dioxide (TcPCO2), rating of perceived exertion (RPE), and perceived comfort were measured. Participants ran significantly longer in control (26.06 min) versus N95 (24.20 min, p = 0.03) or cloth masks (24.06 min, p = 0.04). No differences occurred in the slope of HR or SpO2 across conditions (p > 0.05). TcPCO2 decreased faster in control (B = −0.89) versus N95 (B = 0.14, p = 0.02) or cloth masks (B = −0.26, p = 0.03). RR increased faster in control (B = 8.32) versus cloth masks (B = 6.20, p = 0.04). RPE increased faster in the N95 (B = 1.91) and cloth masks (B = 1.79) versus control (B = 1.59, p < 0.001 and p = 0.05, respectively). Facial irritation/itching/pinching was higher in the N95 versus cloth masks, but sweat/moisture buildup was lower (p < 0.05 for all). Wearing cloth masks or N95s for source control may impact exercise performance, especially at higher intensities. Significant physiological differences were observed between cloth masks and N95s compared to control, while no physiological differences were found between cloth masks and N95s; however, comfort my differ.

Objectives: Recent evidence suggests that occupational physical activity (OPA) is associated with adverse cardiovascular health, whereas leisure time physical activity is protective. This study explored explanatory physiological mechanisms., Methods: Nineteen males (68% white, age=46.6±7.9 years, body mass index=27.9±5.1 kg/m 2 ) with high self-reported OPA wore activity (ActiGraph and activPAL) and heart rate (HR) monitors for 7 days and an ambulatory blood pressure (BP) monitor on one workday and one non-workday. Mixed effects models compared cardiovascular variables (24-hour, nocturnal, waking and non-work time HR and BP) and nocturnal HR variability (HRV) on workdays versus non-workdays. Additional models examined associations of daily activity (steps, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA)) with cardiovascular variables. Workday by daily activity interactions were examined., Results: 24-hour and waking HR and diastolic BP as well as non-work diastolic BP were significantly higher on workdays versus non-workdays (p<0.05 for all). However, no difference in systolic BP or nocturnal HR or BP was observed between work and non-workdays (p>0.05 for all). Low-frequency and high-frequency power indices of nocturnal HRV were lower on workdays (p<0.05 for both). Daily steps and LPA were positively associated with 24-hour and waking HR on work and non-workdays. Significant interactions suggested MVPA increases HR and lowers nocturnal HRV during workdays, with the opposite effect on non-workdays., Conclusions: Cardiovascular load was higher on workdays versus non-workdays with no compensatory hypotensive response following workdays. Daily MVPA may differentially affect ambulatory cardiovascular load and nocturnal HRV on workdays versus non-workdays, supporting the physical activity health paradox hypothesis., Competing Interests: Competing interests: BBG discloses grant funding from the Agency for Healthcare Quality Research, the American Heart Association, the National Institutes of Health and the Tomayko Fund., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : The physical activity (PA) health paradox hypothesizes that occupational physical activity (OPA) and leisure time PA have differential cardiovascular health effects due to increased cardiovascular load without adequate recovery; however, research describing worker PA lacks high-quality objective OPA measurement. This study aimed to objectively describe PA profiles of men reporting high OPA and make comparisons to aerobic PA and OPA recommendations. Methods : Male food service, material moving, health care, or maintenance workers wore activity (ActiGraph ® and activPAL ® ) and heart rate monitors for 7 days. Participants recorded work, non-work, and sleep times in a diary. PA was operationalized as time spent in sedentary behavior, upright time, light, moderate, vigorous, and moderate-to-vigorous PA during work and non-work hours. PA profiles were described and compared with Centers for Disease Control and Prevention aerobic PA guidelines (≥21.4 minute/day) and OPA recommendations (<30 minute/hour upright and intensity of <30% heart rate reserve). Findings : Nineteen male workers (68% White, age = 46.6±7.9 years) were more active on workdays than non-workdays (sedentary: 492.3 vs. 629.7 minute/day; upright: 462.4 vs. 325.2 minute/day; moderate-to-vigorous PA: 72.4 vs. 41.5 minute/day, respectively; all p < .05). Most participants (17/19) achieved aerobic PA guidelines across all days with more achieving on workdays (19/19) than non-workdays (13/19). OPA often exceeded recommended limits with participants accumulating 39.6±12.2 minutes/work hour upright and 30.3±25.9% of working time >30% heart rate reserve. Conclusions/Application to Practice : Male workers reporting high OPA typically met aerobic PA guidelines but exceeded recommended OPA limits. The long-term health implications of such activity profiles should be investigated.

Background: Research suggests reducing sedentary behavior improves low back pain; however, the impact on presenteeism, health, productivity, and sleep in desk workers with chronic low back pain is not known., Objective: Evaluate the effect of a sedentary behavior intervention on multiple dimensions of workplace health., Methods: 24 participants with chronic low back pain and desk jobs were randomized to either a sedentary behavior reduction intervention group or control. Outcomes included a modified Global Physical Activity Questionnaire (GPAQ), the Stanford Presenteeism Scale (SPS), Profile of Mood States (POMS), Health and Work Questionnaire (HWQ), SF-36 Health Survey (SF-36), and Pittsburgh Sleep Quality Index (PSQI). Six-month changes in outcomes were compared across intervention groups using ANCOVA regression, adjusting for baseline values. Cohen's d effect sizes were calculated for outcomes to explain the magnitude of group differences., Results: The intervention group reported 1.5 hours/day less sitting time (p < 0.001) compared to controls at 6 months. SF-36 subscales of energy/fatigue, social functioning, and pain improved, and sleep disturbance was reduced among intervention participants. Productivity, concentration, and presenteeism were unchanged., Conclusions: A sedentary behavior reduction intervention may improve well-being and workplace health without impacting productivity and concentration in desk workers with chronic low back pain.

Pulmonary complications post-hematopoietic stem cell transplantation (HSCT) such as diffuse alveolar hemorrhage (DAH) can occur in 2% to 14% of HSCT patients and have a mortality greater than 80%. Diffuse alveolar hemorrhage is considered to be an inflammatory response; therefore, HSCT patients are primarily treated with different types of systemic corticosteroids with varying dosages. Other treatments currently reported in the literature in conjunction with corticosteroids include aminocaproic acid, recombinant factor VIIa (rFVIIa), and etanercept. This review highlights appropriate frontline and adjunctive treatment options for HSCT patients with DAH and outcomes for each intervention. To perform the review, the PubMed database was searched from inception through March 19, 2021, to identify potential studies using the search terms DAH and HSCT, DAH and hematopoietic cell transplant (HCT), DAH and stem cell, lung injury and HSCT, and lung injury and HCT. When applicable, references from articles identified in the search were also reviewed for inclusion. Much of the data identified were limited to retrospective cohort studies and case series. Based on the data available, the treatment approach should consist of corticosteroid therapy with a suggested methylprednisolone dose of 250 mg daily followed by a 50% taper every 3 days. Intrapulmonary administration of rFVIIa and intravenous administration of aminocaproic acid could be considered as adjunctive agents in those patients who do not promptly respond to corticosteroid therapy. Due to a lack of data specific to HSCT patients who develop DAH and the risk of infectious complications, etanercept should be avoided. Future studies should be designed as randomized controlled trials and examine the use of adjunctive therapies in the upfront setting for HSCT patients with DAH., (© 2021 Pharmacotherapy Publications, Inc.)

Background: Emerging evidence, predominately from European and Asian countries, describes opposing effects of occupational physical activity (OPA) and leisure-time physical activity (LTPA) on cardiovascular health. This analysis examined cardiovascular disease (CVD) prevalence associated with OPA and LTPA., Methods: This cross-sectional analysis of 2015 National Health Interview Survey data (n=16 974) employed logistic regression to estimate odds (OR) of self-reported CVD (coronary heart disease, heart attack, stroke or angina) with self-reported total occupational activity (TOA), occupational exertion (OE), occupational standing and walking (OSW) and LTPA. OPA was measured using two questions: 'How often does your job involve…' (1) 'repeated lifting, pushing, pulling or bending?' (OE) and (2) 'standing or walking around?' (OSW) with responses on a 5-item Likert scale (0=never, 4=always). TOA was categorised similarly after summing OE and OSW scores. LTPA was defined as 0, 1-149 or ≥150 min/week of moderate-to-vigorous activity. All models adjusted for common socioeconomic variables and additional analyses were stratified by sex, smoking status and LTPA., Results: Odds for CVD were higher when 'always' performing TOA (OR 1.99 95% CI 1.12 to 3.53), OE (OR 2.15, 95% CI 1.45 to 3.19) or OSW (OR 1.84, 95% CI 1.07 to 3.17) compared with 'never'. When restricting to never-smokers, odds for CVD were higher when 'always' performing TOA (OR 3.00, 95% CI 1.38 to 6.51) and OE (OR 3.00, 95% CI 1.80 to 5.02) versus 'never'., Conclusion: Associations of high OPA with CVD were equally apparent across sexes, stronger in lower LTPA levels and stronger in never-smokers. While uncontrolled confounding is still possible, even after extensive adjustment, the seemingly paradoxical adverse associations with OPA and CVD should be investigated further., Competing Interests: Competing interests: BBG discloses grant funding from the Agency for Healthcare Quality Research, the American Heart Association, the National Institutes of Health, and the Tomayko Fund., (© Where applicable, author(s) (or their employer(s)) 2021. Re-use permitted under [CC BY]. Published by BMJ.)

Firefighters' protective clothing (FPC) can limit human thermoregulation due to limited water vapor permeability and insulation. This study investigated the effect of cooling on the physiological responses and probability of hyperthermia in subjects wearing FPC during exercise in a hot environment. Twelve males participated in this study. A maximal graded treadmill exercise test was performed to measure maximal oxygen uptake ( V ̇ O 2max ) and to assess subjects' capacity to perform the assigned exercise. Exercise included treadmill walking at 40% V ̇ O 2max in warm (30 °C) and humid (70% RH) conditions for 40 min while wearing FPC. Subjects participated in two randomly counterbalanced assigned experimental protocols: control (no cooling) and intervention (cooling). The experimental intervention consisted of a cooling garment infused with cooled water (18 °C) through silastic tubing sewn into the fabric and worn underneath FPC. Each subject served as their own control and, therefore, completed both the control and intervention of the protocol. A logistic regression model was used to analyze the interaction effect of cooling on the probability of progression to hyperthermia (T c ≥ 38 °C). Subjects' physiological responses increased during exercise in a warm and humid environment. Active cooling decreased (p < 0.05) the thermal stress thereby reducing the probability of hyperthermia while exercising in hot and humid conditions. The results indicate that when cooling was used each subject, on average, was 91% less likely to reach the lower threshold limit of hyperthermia. Exercise in hot environments while wearing FPC results in significant physiological strain, which may lead to hyperthermia. Utilization of a cooling garment reduced physiological strain and the probability of hyperthermia.

Firefighting is physically and mentally strenuous, requiring rapid, appropriate decision-making in hot environments. Intact cognitive function is imperative to firefighters' effectiveness and safety. The study purpose was to investigate the effect of hyperthermia and the effect of body cooling on sustained attention and response inhibition while wearing firefighters' personal protective ensembles after exercise in a hot environment. Twelve healthy males were recruited to participate in two randomly assigned exercise sessions (walking on a treadmill for 40 min at 40% [Formula: see text] O 2max while wearing firefighter's protective ensemble) in a hot environment: control (no cooling) and intervention (cooling). For intervention sessions, a cooling garment was worn underneath firefighter's protective ensemble and infused with 18 °C water supplied by an external water circulator. Participants performed a computerized Go/No-Go (a measure of cognitive function) test three times at baseline and post-exercise for each experimental session. Participants completed baseline testing while wearing cotton athletic clothing. The exercise continued until the core temperature reached ∼39 °C (for all subjects regardless of cooling or non-cooling experimental sessions). Following hyperthermia, participants' physiological responses were significantly increased after exercise. Subjects' reaction time was significantly reduced (improved) after experiencing thermal strain and reaching hyperthermia. The cooling method had a significant impact on suppressing the physiological load, i.e., body cooling delayed the time to reach a T c of 39 °C (p ≤ 0.05), but not cognitive inhibition and attention (reaction time and accuracy). Unexpectedly, hyperthermia resulted in shorter reaction time following exercise (16.64 ± 5.62; p < 0.03), likely influenced by increased attention/vigilance. Hyperthermia may trigger an acute increase in alertness, causing decreased reaction time.

Purpose: To examine differences in activity patterns across employment and occupational classifications., Design: Cross-sectional., Setting: A 2005-2006 Coronary Artery Risk Development in Young Adults (CARDIA) study., Sample: Participants with valid accelerometry data (n = 2068)., Measures: Uniaxial accelerometry data (ActiGraph 7164), accumulated during waking hours, were summarized as mean activity counts (counts/min) and time spent (min/d) in long-bout sedentary (≥30 minutes, SED ≥30 ), short-bout sedentary (<30 minutes, SED <30 ), light physical activity (LPA), short-bout moderate-to-vigorous physical activity (<10 minutes, MVPA <10 ), and long-bout MVPA (≥10 minutes, MVPA ≥10 ) using Freedson cut-points. Employment status was self-reported as full time, part time, unemployed, keeping house, or raising children. Self-reported job duties were categorized into 23 major groups using the 2010 Standard Occupational Classification., Analysis: Omnibus differences were analyzed using adjusted analysis of covariance and repeated after stratification by race (black/white) and sex (female/male)., Results: SED ≥30 , SED <30 , LPA, and MVPA <10 differed significantly by employment and occupational categories ( P ≤ .05), while MVPA ≥10 did not ( P ≥ .50). SED ≥30 , SED <30 , and LPA differed by occupational classification in men, women, blacks, and whites ( P < .05). Mean activity counts, MVPA <10 , and MVPA ≥10 were significantly different across occupational classifications in whites ( P ≤ .05), but not in blacks ( P > .05). Significant differences in mean activity counts and MVPA <10 across occupational classifications were found in males ( P ≤ .001), but not in females ( P > .05)., Conclusion: Time within activity intensity categories differs across employment and occupational classifications and by race and sex.

Background: Individual social support is positively related to physical activity participation. However, less is known about how neighborhood-level social structures relate to physical activity participation., Methods: We analyzed 2017 National Health Interview Survey data for adult participants who completed all questions on physical activity and neighborhood cohesion (N = 23,006). Each cohesion question was binary coded (cohesion or not) and used as a predictor individually and for a composite score measuring total social cohesion. We used linear regression to estimate minutes of moderate aerobic activity, and we used logistic regression to estimate the odds of meeting aerobic guidelines (≥150 min/wk), strength guidelines (≥2 d/wk of muscle strengthening exercises), or both guidelines, predicted by the 5 definitions of cohesion (composite cohesion and the 4 questions separately). Models were adjusted for sex, age, race/ethnicity, family-income-to-poverty ratio, education, nativity, language, and neighborhood tenure., Results: Respondents who reported having more social cohesion had 45.0 more minutes of aerobic activity and increased odds of meeting aerobic, strength, and combined guidelines (odds ratio [OR] = 1.22, OR = 1.13, and OR = 1.14, respectively; P < .01 for all). Reporting having availability of help when needed, neighbors to count on, trustworthy neighbors, and close-knit neighbors all resulted in increased odds of meeting aerobic guidelines but not increased odds for meeting strength guidelines in the latter 3 components or combined guidelines for the latter 2 components., Conclusions: Having neighborhood social cohesion or select individual components of neighborhood cohesion are positively related to meeting aerobic, strength, and combined guidelines.

The objective of this retrospective analysis was to describe the development and implementation of an anesthesiologist-led multidisciplinary committee to evaluate high-risk surgical patients in order to improve surgical appropriateness. The study was conducted in an anesthesia preoperative evaluation clinic at an academic comprehensive cancer center. One hundred sixty-seven high-risk surgical patients with cancer-related diagnoses were evaluated and discussed at a High-Risk Committee (HRC) meeting to determine surgical appropriateness and optimize perioperative care. The HRC is an anesthesiologist-led model for multidisciplinary review of high-risk patients developed at Roswell Park Comprehensive Cancer Center. The group of high-risk patients in which surgery was not performed had, on average, a greater percentage of hypertension, smoking history, dyspnea, heart failure, chronic obstructive pulmonary disease, diabetes, renal failure, and sleep apnea than the group in whom surgery was performed. Only one of 107 high-risk patients who had surgery died within the first 30 days after surgery. A smaller percentage of patients died in the group that had surgery versus the group in which surgery was canceled. For all patients discussed by the HRC, the mortality was less than 2% within the first 30 days after the HRC., (© 2018 American Society for Health Care Risk Management of the American Hospital Association.)

Shared decision-making (SDM) is essential for high-quality surgical care. Barriers to SDM exist in clinical practice but there is evidence these obstacles can be overcome. SDM requires clinician and patient engagement. Though patients may indicate understanding, deficits in decision making may persist based on language, age, or educational barriers. Multidisciplinary decision-making before surgery is an opportunity for anesthesiologists and other perioperative professionals to improve surgical care. The authors present an example of a successfully implemented pathway for high-risk surgical patients at a tertiary care center, leveraging the preoperative anesthesia evaluation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study aimed to determine if trunk posture during walking is related to increases in rectal temperature (T re ). 24 males treadmill walked in one of four conditions (1): 30 min at 3.0 mph and 0% grade, 20 °C and 50% relative humidity (RH), wearing healthcare worker (HCW) PPE; (2): 30 min at 3.0 mph and 0% grade, 27.5 °C and 60% RH, HCW PPE; (3): 30 min at 3.0 mph and 0% grade, 32.5 °C and 70% RH, HCW PPE; and (4): 40 min at 40% VO 2 max, 30 °C and 70% RH, wearing firefighter PPE. Trunk posture (Zephyr BioHarness 3) and T re were measured continuously. T re was positively related to trunk posture, controlling for covariates (B = 3.49, p < .001). BMI and age moderated this relationship (T re ×age, B = 0.76, p < .001; T re *BMI, B = -1.85, p < .001). Trunk posture measurement may be useful in monitoring fall potential and magnitude of heat stress of workers in hot environments. Practitioner Summary: Occupational hyperthermia increases worker risk for heat illness and injury but is difficult to monitor in the field. This investigation shows that trunk posture is independently and positively related to core temperature. Non-invasive measurement or visual inspection of trunk posture could provide novel insight on individual heat strain level.

Introduction: Elevated ambient temperature and personal protective clothing (PPC) induce physiological strain which may be counteracted by heat acclimation. The purpose of this study was to determine if 5-day heat acclimation training (HAT) improves thermal and perceptual responses while wearing chemical, biological, radiological, and nuclear (CBRN) PPC., Methods: Nine healthy men completed a heat stress test (walking for one hour with CBRN PPC) in 35°C and 50% relative humidity (RH) before and after 5-day HAT. The HAT consisted of five consecutive days of two 45-minute cycling sessions (50% VO2max) wearing athletic clothing separated by a 15 min rest in 45°C and 20% RH. Results of the pre- and post-HAT heat stress tests were compared., Results: Heat acclimation was seen through 5-day HAT; however, thermoregulatory responses did not improve while wearing CBRN PPC. Improvement (p<0.05, day 1 vs. day 5 HAT) in skin temperature (38.0±0.5°C vs. 37.6±0.5°C), body temperature (38.6±0.4°C vs. 38.3±0.4°C), sweat rate (2.26±0.3kg vs. 2.64±0.3kg), RPE (15.8±2.4 vs. 13.9±3.1), and heat perception (5.7±0.6 vs. 4.9±1.0) were noted. However, no physiological or perceptual improvements (p>0.05) were found in the post-HAT heat stress test., Conclusions: Heat acclimation adaptations may be blunted by CBRN PPC, thus requiring differing or extended HAT.

Seo, Yongsuk, Jeremiah Vaughan, Tyler D. Quinn, Brittany Followay, Raymond Roberge, Ellen L. Glickman, and Jung-Hyun Kim. The effect of inspiratory resistance on exercise performance and perception in moderate normobaric hypoxia. High Alt Med Biol. 18:417-424, 2017., Purpose: Respirators are simple and efficient in protecting workers against toxic airborne substances; however, their use may limit the physical performance of workers. The purpose of this study was to determine the effect of inspiratory resistance on physical performance and breathing perception in normobaric hypoxia., Method: Nine healthy men wore a tight-fitting respiratory mask outfitted with one of four different inspiratory resistors (R) (0, 1.5, 4.5, 7.5 cm H 2 O/L/Sec) while exercising at normobaric hypoxia (17% O 2 ) at submaximal exercise workloads of 50, 100, and 150 W on a cycle ergometer for 10 minutes each, followed by a maximal oxygen uptake (VO 2 max) test to exhaustion., Results: Maximal power output at R7.5 was significantly lower than R0 (p = 0.016) and R1.5 (p = 0.035). Respiration rate was significantly reduced at R4.5 (p = 0.011) and R7.5 (p ≤ 0.001) compared with R0. Minute ventilation was significantly decreased in R7.5 compared with R0 (p = 0.003), R1.5 (p = 0.010), and R4.5 (p = 0.016), whereas VO 2 was not significantly changed. Breathing comfort (BC) and breathing effort (BE) were significantly impaired in R7.5 (BC: p = 0.025, BE: p = 0.001) and R4.5 (BC: p = 0.007, BE: p = 0.001) compared with R0, but rating of perceived exertion (RPE) remained unchanged., Conclusions: Added inspiratory resistance limited maximal power output and increased perceptions of BC and BE in normobaric hypoxia. However, low-to-moderate inspiratory resistance did not have a deleterious effect on VO 2 or RPE at submaximal or maximal exercise. Perceptual and physiological characteristics of respirators of varying inspiratory resistances should be considered by manufacturers and end users during design and respirator selection processes.

Objective: Cardiac arrest following neurosurgery is a devastating complication associated with significant postoperative morbidity and mortality. There are no published studies that have used a large and robust multicenter database to specifically examine demographic and surgical risk factors associated with cardiac arrests following craniotomy and spine surgeries, respectively., Patients and Methods: We retrospectively analyzed data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for the period between January 1, 2007 and December 31, 2013, focusing on cardiac arrest associated with craniotomy and spine surgery from the intraoperative period to 30days after surgery. A total of 73,584 neurosurgical patients were analyzed (59,609 spine surgeries and 13,975 craniotomies)., Results: There was an increased risk of cardiac arrest for both craniotomy and spine surgeries in patients with American Society of Anesthesiologists (ASA) Physical Status class 4 or 5, Black and Asian patients compared to White patients and patients totally dependent versus independent based on the ACS-NSQIP risk calculator. The risk of cardiac arrest for craniotomy was 66.5 per 10,000 anesthetics and for spine surgery was 21.3 per 10,000 anesthetics. Cardiac arrest associated with emergent non-traumatic craniotomy was 36.5% and with emergent non-traumatic spine surgery was only 17.3%. We found that 18% of cardiac arrests for craniotomy and 25% of cardiac arrests for spine surgery occurred from the intraoperative period through postoperative day (POD) 0. Both craniotomy and spine surgery patients who had a cardiac arrest were more likely to have acute kidney injury (AKI), failure to wean from the ventilator, postoperative dialysis, myocardial infarction (MI), venous thromboembolism (VTE) and sepsis in the postoperative period. The overall mortality rate for both craniotomy and spine surgeries who had a cardiac arrest from the intraoperative period to 30days postoperative was 61.8% versus 1.2% in the no cardiac arrest control group., Conclusions: Identification of patient and surgery specific characteristics from ACS-NSQIP data associated with cardiac arrest following craniotomy and spine surgery may lead to initiatives to reduce morbidity and mortality in the neurosurgical patient population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Fluid therapy in the perioperative period varies greatly between anesthesia providers and may have a negative impact on surgical outcomes., Methods: We conducted a retrospective analysis of 705 elective colorectal cases consisting of colectomies, ileocolic resections, and low anterior resections at an academic institution from January 1, 2010 to May 29, 2015, collected by our electronic medical record before implementation of Enhanced Recovery After Surgery (ERAS ® ) pathways., Results: The mean for total crystalloid administration was 2578 mL with a standard deviation (SD) that was approximately 50% of the mean value. A combination of both normal saline and lactated Ringer's solution was used in almost all cases without a clear rationale for fluid choice. Fluid administered to patients was disproportional to measured intraoperative fluid losses (estimated blood loss and urine output) by a factor of 10. The average rate of fluid given was 1050 mL/h with an SD of nearly the same amount (951 mL). There was a variability of over 67% in total crystalloid administered based on both ideal body weight and total body weight., Conclusions: We found that a wide variability in the amount and type of fluid therapy administered existed at our institution before implementation of a colorectal ERAS pathway or routine use of goal-directed fluid therapy (GDFT). ERAS pathways with GDFT protocols could lead to more rational and consistent fluid therapy leading to improved outcomes.

Purpose: To investigate factors associated with unplanned postoperative admissions to the intensive care unit (ICU)., Methods: Data from the National Anesthesia Clinical Outcomes Registry (NACOR) were analyzed. We performed univariate and multivariate logistic regression to identify patient- and surgery-specific characteristics associated with unplanned postoperative ICU admission. We also recorded the prevalence of Current Procedural Terminology (CPT) and International Classification of Diseases, ninth revision ( ICD-9) billing codes and outcomes for unplanned postoperative ICU admissions., Results: Of 23 341 130 records in the database, 2 910 738 records met our inclusion criteria. A higher American Society of Anesthesiologists physical status (ASA PS) class, case duration greater than 4 hours, and advanced age were associated with a greater likelihood of unplanned ICU admission. Vascular and thoracic surgery patients were more likely to have an unplanned ICU admission. The most common CPT and ICD-9 codes involved repair of femur/hip fracture, bowel resection, and acute postoperative pain. Large community hospitals were more likely than university hospitals to have unplanned postoperative ICU admissions. Patients in the unplanned postoperative ICU admission group were more likely to have experienced intraoperative cardiac arrest, hemodynamic instability, or respiratory failure and were more likely to die in the immediate perioperative period., Conclusion: Our study is the first diverse analysis of unplanned postoperative ICU admissions in the literature across multiple specialties and practice models. We found an association of advanced age, higher ASA PS class, and duration of procedure with unplanned ICU admission after surgery. Surgical specialties and procedures with the most unplanned ICU admissions could be areas for quality improvement and clinical pathways in the future.

Background: While active transportation has health, economic and environmental benefits, participation within the USA is low. The purpose of this study is to examine relationships of demographic and workplace factors with health-enhancing active transportation and commuting., Methods: Participants in the 2009 National Household Travel Survey reported demographics, workplace factors (time/distance to work, flextime availability, option to work from home and work start time) and active transportation (for any purpose) or commuting (to and from work, workers only) as walking or biking (≥10 min bouts only). Multiple logistic regression examined cross-sectional relationships between demographics and workplace factors with active transportation and commuting., Results: Among 152 573 participants, active transportation was reported by 1.11% by biking and 11.74% by walking. Among 111 808 working participants, active commuting was reported by 0.80% by biking and 2.76% by walking. Increased odds (p<0.05) of active commuting and transportation were associated with younger age, lower income, urban dwelling, and the highest and lowest education categories. Males had greater odds of commuting and transporting by bike but decreased odds of walk transporting. Inconsistent patterns were observed by race, but whites had greater odds of any biking (p<0.05). Odds of active commuting were higher with a flexible schedule (p<0.001), the option to work from home (p<0.05), shorter time and distance to work (both p<0.001), and work arrival time between 11:00 and 15:59 (walking only, p=0.001)., Conclusions: Active transportation differed across demographic and workplace factors. These relationships could inform infrastructure policy decisions and workplace wellness programming targeting increased active transportation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Previous literature on preoperative evaluation focuses on the impact on the day of surgery cancellations and delays; however, the framework of cancellations and delays at the time of the elective outpatient preoperative anesthesia visit has not been categorized. We describe the current model in the preoperative clinic at Brigham and Women's Hospital, examining the pattern of cancellations at the time of this preoperative visit and the framework used for categorizing the issues involved. Looking at this broader framework is important in an era of patient-centered care; we seek to identify targets to modify the preoperative assessment and adequately assess and capture the spectrum of issues involved. Elective cases evaluated in the preoperative clinic were reviewed over 10 months. Characteristics of cancelled and noncancelled cases were compared. In-depth analysis of issues related to cancellation was done; 1-year follow-up was completed. Cancellation patterns included categories encompassing clinical, financial, alignment with patient values and goals, compliance, and social issues. The period of preoperative assessment can therefore be leveraged to review a number of domains that can adversely affect surgical outcomes and improve patient-centered care. Also, our framework allows the institution to benchmark these patterns over time; increases in cancellations at the time of the preoperative anesthesia clinic visit for specific categories can prompt an opportunity to examine and improve preoperative workflow.

We present a rare case of acute postoperative sialadenitis or "anesthesia mumps" necessitating emergent intubation in a 16-year-old girl after biopsy of a brainstem mass under general anesthesia. Postoperative computed tomography of the brain demonstrated extensive right-sided facial swelling, parotid gland enlargement, and pharyngeal edema extending to the parapharyngeal space, soft palate, and uvula with significant narrowing of the airway. To our knowledge, this entity has not been previously described in the radiologic literature.

In a recent study, we reported that interleukin (IL)-4 had a protective role against acetaminophen (APAP)-induced liver injury (AILI), although the mechanism of protection was unclear. Here, we carried out more detailed investigations and have shown that one way IL-4 may control the severity of AILI is by regulating glutathione (GSH) synthesis. In the present studies, the protective role of IL-4 in AILI was established definitively by showing that C57BL/6J mice made deficient in IL-4 genetically (IL-4(-/-)) or by depletion with an antibody, were more susceptible to AILI than mice not depleted of IL-4. The increased susceptibility of IL-4(-/-) mice was not due to elevated levels of hepatic APAP-protein adducts but was associated with a prolonged reduction in hepatic GSH that was attributed to decreased gene expression of γ-glutamylcysteine ligase (γ-GCL). Moreover, administration of recombinant IL-4 to IL-4(-/-) mice postacetaminophen treatment diminished the severity of liver injury and increased γ-GCL and GSH levels. We also report that the prolonged reduction of GSH in APAP-treated IL-4(-/-) mice appeared to contribute toward increased liver injury by causing a sustained activation of c-Jun-N-terminal kinase (JNK) since levels of phosphorylated JNK remained significantly higher in the IL-4(-/-) mice up to 24 h after APAP treatment. Overall, these results show for the first time that IL-4 has a role in regulating the synthesis of GSH in the liver under conditions of cellular stress. This mechanism appears to be responsible at least in part for the protective role of IL-4 against AILI in mice and may have a similar role not only in AILI in humans but also in pathologies of the liver caused by other drugs and etiologies.

Hyperthermic isolated limb perfusion is an established method of treatment for regionally advanced melanoma. Recent studies suggest that exogenously administered cytokines potentiate tumor response in patients with in-transit melanoma. We hypothesized that isolated limb perfusion induces an immunogenic response characterized by increased circulating levels of cytokines in the pump circuit, potentially contributing to the antitumor effect. We obtained blood samples from the perfusion circuit and systemic circulation at various intervals from patients undergoing isolated chemotherapeutic perfusion for melanoma. Samples were analyzed for serum cytokine profiles by enzyme-linked immunosorbent assay. When compared with baseline values, significant increases in serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) occurred within the perfusion circuit during isolated limb perfusion (P < 0.05). In addition, there was a corresponding increase in IL-8 within the systemic circulation at the 60-min interval (P < 0.05), suggesting some degree of leakage from the isolated circuit due to the extremely high levels of IL-8 in the perfusion circuit. A transient but insignificant decrease in circulating levels of neutrophils was also observed during the perfusion process, which may be attributed to margination. Increased levels of cytokines IL-6, IL-8, and TNF occurred within the isolated circuit during hyperthermic limb perfusion and may contribute to tumor response seen in patients treated with isolated limb perfusion.

Interleukin-2 (IL-2) mediates the regression of metastatic cancer, but clinical application is restricted by associated toxicities. Previous studies implicate tumor necrosis factor (TNF) as an important mediator of certain IL-2-induced toxicities. We hypothesized that soluble TNF receptor (sTNFr), a TNF antagonist, would alter lymphocyte trafficking into normal tissues and ameliorate IL-2-induced toxicity. Four groups of C57BL/6 mice were treated for 4 days with intraperitoneal injections of 100,000 IU IL-2 alone, 100,000 IU IL-2 and 30 micrograms sTNFr combined, 30 micrograms sTNFr alone, or equal volumes of saline. Animal activity was graded and blood obtained for SGPT and SGOT. At necropsy, organs were harvested for wet:dry ratios as a measurement of organ edema. The lung, liver, and thymus were examined histologically for lymphocytic infiltration and graded on a scale of 1 to 5. IL-2-treated groups had a statistically significant increase in organ edema, lymphocytic infiltration into the lung and liver, liver enzyme elevation, and pancytopenia when compared with controls. Soluble TNFr significantly suppressed IL-2-induced pulmonary lymphocytic infiltration and associated serum lymphopenia without significant alteration of other IL-2-induced effects. These data implicate TNF as a mediator of the pulmonary lymphocytic infiltration and of lymphopenia that accompanies IL-2 therapy and further suggest that alternative mechanisms are involved in other IL-2-induced deleterious effects.