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Therapeutic Hypothermia in Low-Risk Nonpumped Brain-Dead Kidney Donors: A Randomized Clinical Trial

JAMA Netw Open. 2024 Feb 5;7(2):e2353785. doi: 10.1001/jamanetworkopen.2023.53785.


IMPORTANCE: Delayed graft function in kidney-transplant recipients is associated with increased financial cost and patient burden. In donors with high Kidney Donor Profile Index whose kidneys are not pumped, therapeutic hypothermia has been shown to confer a protective benefit against delayed graft function.

OBJECTIVE: To determine whether hypothermia is superior to normothermia in preventing delayed graft function in low-risk nonpumped kidney donors after brain death.

DESIGN, SETTING, AND PARTICIPANTS: In a multicenter randomized clinical trial, brain-dead kidney donors deemed to be low risk and not requiring machine perfusion per Organ Procurement Organization protocol were prospectively randomized to hypothermia (34.0-35 °C) or normothermia (36.5-37.5 °C) between August 10, 2017, and May 21, 2020, across 4 Organ Procurement Organizations in the US (Arizona, Upper Midwest, Pacific Northwest, and Texas). The final analysis report is dated June 15, 2022, based on the data set received from the United Network for Organ Sharing on June 2, 2021. A total of 509 donors (normothermia: n = 245 and hypothermia: n = 236; 1017 kidneys) met inclusion criteria over the study period.

INTERVENTION: Donor hypothermia (34.0-35.0 °C) or normothermia (36.5-37.5 °C).

MAIN OUTCOMES AND MEASURES: The primary outcome was delayed graft function in the kidney recipients, defined as the need for dialysis within the first week following kidney transplant. The primary analysis follows the intent-to-treat principle.

RESULTS: A total of 934 kidneys were transplanted from 481 donors, of which 474 were randomized to the normothermia group and 460 to the hypothermia group. Donor characteristics were similar between the groups, with overall mean (SD) donor age 34.2 (11.1) years, and the mean donor creatinine level at enrollment of 1.03 (0.53) mg/dL. There was a predominance of Standard Criteria Donors (98% in each treatment arm) with similar low mean (SD) Kidney Donor Profile Index (normothermia: 28.99 [20.46] vs hypothermia: 28.32 [21.9]). Cold ischemia time was similar in the normothermia and hypothermia groups (15.99 [7.9] vs 15.45 [7.63] hours). Delayed graft function developed in 87 of the recipients (18%) in the normothermia group vs 79 (17%) in the hypothermia group (adjusted odds ratio, 0.92; 95% CI, 0.64-1.33; P = .66).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that, in low-risk non-pumped kidneys from brain-dead kidney donors, therapeutic hypothermia compared with normothermia does not appear to prevent delayed graft function in kidney transplant recipients.

TRIAL REGISTRATION: Identifier: NCT02525510.

PMID:38416500 | DOI:10.1001/jamanetworkopen.2023.53785

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Resident Burnout, Wellness, Professional Development, and Engagement Before and After New Training Schedule Implementation

JAMA Netw Open. 2024 Feb 5;7(2):e240037. doi: 10.1001/jamanetworkopen.2024.0037.


IMPORTANCE: Burnout is a work-related syndrome of depersonalization (DP), emotional exhaustion (EE), and low personal achievement (PA) that is prevalent among internal medicine resident trainees. Prior interventions have had modest effects on resident burnout. The association of a new 4 + 4 block schedule (4 inpatient weeks plus 4 outpatient weeks) with resident burnout has not previously been evaluated.

OBJECTIVE: To evaluate the association of a 4 + 4 block schedule, compared with a 4 + 1 schedule, with burnout, wellness, and self-reported professional engagement and clinical preparedness among resident physicians.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized preintervention and postintervention survey study was conducted in a single academic-based internal medicine residency program from June 2019 to June 2021. The study included residents in the categorical, hospitalist, and primary care tracks in postgraduate years 1 and 2 (PGY1 and PGY2). Data analysis was conducted from October to December 2022.

INTERVENTION: In the 4 + 4 structure, resident schedules alternated between 4-week inpatient call-based rotations and 4-week ambulatory non-call-based rotations.

MAIN OUTCOMES AND MEASURES: The primary outcome was burnout, assessed using the Maslach Burnout Inventory subcategories of EE (range, 0-54), DP (range, 0-30), and PA (range, 0-48), adjusted for sex and PGY. Secondary outcomes included In-Training Examination (ITE) scores and a questionnaire on professional, educational, and health outcomes. Multivariable logistic regression was used to assess the primary outcome, 1-way analysis of variance was used to compare ITE percentiles, and a Bonferroni-adjusted Kruskal Wallis test was used for the remaining secondary outcomes. The findings were reexamined with several sensitivity analyses, and Cohen’s D was used to estimate standardized mean differences (SMDs).

RESULTS: Of the 313 eligible residents, 216 completed the surveys. A total of 107 respondents (49.5%) were women and 109 (50.5%) were men; 119 (55.1%) were PGY1 residents. The survey response rates were 78.0% (85 of 109) in the preintervention cohort and 60.6% (63 of 104) and 68.0% (68 of 100) in the 2 postintervention cohorts. The PGY1 residents had higher response rates than the PGY2 residents (119 of 152 [78.2%] vs 97 of 161 [60.2%]; P < .001). Adjusted EE scores (mean difference [MD], -6.78 [95% CI, -9.24 to -4.32]) and adjusted DP scores (MD, -3.81 [95% CI, -5.29 to -2.34]) were lower in the combined postintervention cohort. The change in PA scores was not statistically significant (MD, 1.4 [95% CI, -0.49 to 3.29]). Of the 15 items exploring professional, educational, and health outcomes, a large positive association was observed for 11 items (SMDs >1.0). No statistically significant change in ITE percentile ranks was noted.

CONCLUSIONS AND RELEVANCE: In this survey study of internal medicine resident physicians, a positive association was observed between a 4 + 4 block training schedule and internal medicine resident burnout scores and improved self-reported professional, educational, and health outcomes. These results suggest that specific 4 + 4 block combinations may better improve resident burnout than a 4 + 1 combination used previously.

PMID:38416498 | DOI:10.1001/jamanetworkopen.2024.0037

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Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium

JAMA Netw Open. 2024 Feb 5;7(2):e240535. doi: 10.1001/jamanetworkopen.2024.0535.


IMPORTANCE: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors.

OBJECTIVE: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included children enrolled in cohorts participating in the Children’s Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother’s education, parental asthma, smoking during pregnancy, child’s race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023.

EXPOSURE: Early-life exposures to PM2.5 and NO2 according to participants’ birth address.

MAIN OUTCOMES AND MEASURES: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood.

RESULTS: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 μg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 μg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]).

CONCLUSIONS AND RELEVANCE: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

PMID:38416497 | DOI:10.1001/jamanetworkopen.2024.0535

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Morbidity and Length of Stay After Injury Among People Experiencing Homelessness in North America

JAMA Netw Open. 2024 Feb 5;7(2):e240795. doi: 10.1001/jamanetworkopen.2024.0795.


IMPORTANCE: Traumatic injury is a leading cause of hospitalization among people experiencing homelessness. However, hospital course among this population is unknown.

OBJECTIVE: To evaluate whether homelessness was associated with increased morbidity and length of stay (LOS) after hospitalization for traumatic injury and whether associations between homelessness and LOS were moderated by age and/or Injury Severity Score (ISS).

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of the American College of Surgeons Trauma Quality Programs (TQP) included patients 18 years or older who were hospitalized after an injury and discharged alive from 787 hospitals in North America from January 1, 2017, to December 31, 2018. People experiencing homelessness were propensity matched to housed patients for hospital, sex, insurance type, comorbidity, injury mechanism type, injury body region, and Glasgow Coma Scale score. Data were analyzed from February 1, 2022, to May 31, 2023.

EXPOSURES: People experiencing homelessness were identified using the TQP’s alternate home residence variable.

MAIN OUTCOMES AND MEASURES: Morbidity, hemorrhage control surgery, and intensive care unit (ICU) admission were assessed. Associations between homelessness and LOS (in days) were tested with hierarchical multivariable negative bionomial regression. Moderation effects of age and ISS on the association between homelessness and LOS were evaluated with interaction terms.

RESULTS: Of 1 441 982 patients (mean [SD] age, 55.1 [21.1] years; (822 491 [57.0%] men, 619 337 [43.0%] women, and 154 [0.01%] missing), 9065 (0.6%) were people experiencing homelessness. Unmatched people experiencing homelessness demonstrated higher rates of morbidity (221 [2.4%] vs 25 134 [1.8%]; P < .001), hemorrhage control surgery (289 [3.2%] vs 20 331 [1.4%]; P < .001), and ICU admission (2353 [26.0%] vs 307 714 [21.5%]; P < .001) compared with housed patients. The matched cohort comprised 8665 pairs at 378 hospitals. Differences in rates of morbidity, hemorrhage control surgery, and ICU admission between people experiencing homelessness and matched housed patients were not statistically significant. The median unadjusted LOS was 5 (IQR, 3-10) days among people experiencing homelessness and 4 (IQR, 2-8) days among matched housed patients (P < .001). People experiencing homelessness experienced a 22.1% longer adjusted LOS (incident rate ratio [IRR], 1.22 [95% CI, 1.19-1.25]). The greatest increase in adjusted LOS was observed among people experiencing homelessness who were 65 years or older (IRR, 1.42 [95% CI, 1.32-1.54]). People experiencing homelessness with minor injury (ISS, 1-8) had the greatest relative increase in adjusted LOS (IRR, 1.30 [95% CI, 1.25-1.35]) compared with people experiencing homelessness with severe injury (ISS ≥16; IRR, 1.14 [95% CI, 1.09-1.20]).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that challenges in providing safe discharge to people experiencing homelessness after injury may lead to prolonged LOS. These findings underscore the need to reduce disparities in trauma outcomes and improve hospital resource use among people experiencing homelessness.

PMID:38416488 | DOI:10.1001/jamanetworkopen.2024.0795

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“Knees Out” or “Knees In”? Volitional Lateral vs. Medial Hip Rotation During Barbell Squats

J Strength Cond Res. 2024 Mar 1;38(3):435-443. doi: 10.1519/JSC.0000000000004655. Epub 2023 Dec 13.


Chiu, LZF. “Knees out” or “Knees in”? Volitional lateral versus medial hip rotation during barbell squats. J Strength Cond Res 38(3): 435-443, 2024-Medial or lateral hip rotation may be present during barbell squats, which could affect the hip frontal and transverse plane moments. Male (n = 14) and female (n = 18) subjects performed squats using their normal technique and with volitional medial and lateral hip rotation. Hip net joint moments (NJM) were calculated from 3-dimensional motion capture and force platform measurements. Statistical significance was set for omnibus tests (α = 0.05) and Bonferroni’s corrected for pairwise comparisons (αt-test = 0.0056). Normal squats required hip extensor, adductor, and lateral rotator NJM. Lateral rotation squats had smaller hip extensor (p = 0.002) and lateral rotator (p < 0.001) NJM and larger hip adductor (p < 0.001) NJM than normal squats. Medial rotation squats had smaller hip extensor (p = 0.002) and adductor (p < 0.001) NJM and larger hip lateral rotator (p < 0.001) NJM than normal squats. These differences exceeded the minimum effects worth detecting. As gluteus maximus exerts hip extensor and lateral rotator moments, and the adductor magnus exerts hip extensor and adductor moments, these muscles combined would be required to meet these hip demands, supporting previous research that has established these muscles as the primary contributors to the hip extensor NJM. Lateral rotation squats reduce hip lateral rotator and increase hip adductor NJM, which may be hypothesized as preferentially loading adductor magnus. Medial rotation squats increase hip lateral rotator and decrease hip adductor NJM; therefore, this variant may shift loading to the gluteus maximus.

PMID:38416444 | DOI:10.1519/JSC.0000000000004655

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Cognition and Memory after Covid-19 in a Large Community Sample

N Engl J Med. 2024 Feb 29;390(9):806-818. doi: 10.1056/NEJMoa2311330.


BACKGROUND: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

METHODS: We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (“brain fog”).

RESULTS: Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

CONCLUSIONS: Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).

PMID:38416429 | DOI:10.1056/NEJMoa2311330

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Evaluation of the Status of Patients with Autoimmune Bullous Diseases (Pemphigus and Bullous Pemphigoids) in Dermatology Clinics of Mashhad University of Medical Sciences During the COVID-19 Pandemic Using Telemedicine

Telemed J E Health. 2024 Feb 27. doi: 10.1089/tmj.2023.0395. Online ahead of print.


Background: The COVID-19 pandemic impacted the growth of telemedicine. The challenge was in the way of dermatologists, who needed a comprehensive examination of the lesions. Here, we tried a tele-management of patients with autoimmune bullous diseases. Methods: This cross-sectional study was conducted on confirmed bullous disorder cases. Demographic data and the status of COVID-19 infection were assessed in the patients. Some of the cases were provided online, and some with office visits. Drug and treatment plan changes were compared between these two groups. All statistical analysis was conducted using SPSS version 20. Result: Totally, 100 patients, including 46 males (46.0%) and 54 females (54.0%), 48.15 ± 11.11 years old, were studied. Among them, 73 were pemphigus vulgaris (73.0%), 11 were bullous pemphigoid (11.0%), 10 were pemphigus foliaceus (10.0%), and the other 6 (6.0%) were categorized as other autoimmune bullous diseases. During the pandemic, 38 cases (38.0%) had COVID-19 infection. 72 patients had office and 28 had online visits. Treatment plans after visits during the pandemic (p = 0.588) and drug dose change (p = 0.297) showed no significant difference between office and online visits. Conclusion: Our patients tended to plan office visits more than online; however, we found no differences regarding the plan or treatment changes. Online visit has good efficacy, but further investigation in case of provision of a suitable platform and getting the attention of the patients is needed.

PMID:38416427 | DOI:10.1089/tmj.2023.0395

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New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis

Arch Pharm Res. 2024 Feb 28. doi: 10.1007/s12272-024-01486-1. Online ahead of print.


Gymnopilus orientispectabilis, also known as “big laughter mushroom,” is a hallucinogenic poisonous mushroom that causes excessive laughter upon ingestion. From the fruiting bodies of G. orientispectabilis, eight lanostane-type triterpenoids (1-8), including seven novel compounds: gymnojunols A-G (2-8), were isolated. The chemical structures of these new compounds (2-8) were determined by analyzing their 1D and 2D NMR spectra and HR-EISMS, and their absolute configurations were unambiguously assigned by quantum chemical ECD calculations and a computational method coupled with a statistical procedure (DP4+). Upon evaluating autophagic activity, compounds 2, 6, and 7 increased LC3B-II levels in HeLa cells to a similar extent as bafilomycin, an autophagy inhibitor. In contrast, compound 8 decreased the levels of both LC3B-I and LC3B-II, and a similar effect was observed following treatment with rapamycin, an autophagy inducer. Our findings provide experimental evidence for new potential autophagy modulators in the hallucinogenic poisonous mushroom G. orientispectabilis.

PMID:38416389 | DOI:10.1007/s12272-024-01486-1

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Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study

Target Oncol. 2024 Feb 28. doi: 10.1007/s11523-024-01037-0. Online ahead of print.


BACKGROUND: Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce.

OBJECTIVE: This study aimed to compare the safety of different PARPi in patients with EOC.

PATIENTS AND METHODS: Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence.

RESULTS: In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots.

CONCLUSIONS: No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

PMID:38416378 | DOI:10.1007/s11523-024-01037-0

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Brain identification of IBS patients based on GBDT and multiple imaging techniques

Phys Eng Sci Med. 2024 Feb 28. doi: 10.1007/s13246-024-01394-0. Online ahead of print.


The brain biomarker of irritable bowel syndrome (IBS) patients is still lacking. The study aims to explore a new technology studying the brain alterations of IBS patients based on multi-source brain data. In the study, a decision-level fusion method based on gradient boosting decision tree (GBDT) was proposed. Next, 100 healthy subjects were used to validate the effectiveness of the method. Finally, the identification of brain alterations and the pain evaluation in IBS patients were carried out by the fusion method based on the resting-state fMRI and DWI for 46 patients and 46 controls selected randomly from 100 healthy subjects. The results showed that the method can achieve good classification between IBS patients and controls (accuracy = 95%) and pain evaluation of IBS patients (mean absolute error = 0.1977). Moreover, both the gain-based and the permutation-based evaluation instead of statistical analysis showed that left cingulum bundle contributed most significantly to the classification, and right precuneus contributed most significantly to the evaluation of abdominal pain intensity in the IBS patients. The differences seem to suggest a probable but unexplored separation about the central regions between the identification and progression of IBS. This finding may provide one new thought and technology for brain alteration related to IBS.

PMID:38416373 | DOI:10.1007/s13246-024-01394-0