Racial, Ethnic, Socioeconomic, and Geographic Inequities in Access to Mechanical Circulatory Support.

Background: Hospital admissions for cardiogenic shock have increased in the United States. Temporary mechanical circulatory support (tMCS) can be used to acutely stabilize patients. We sought to evaluate the presence of racial, ethnic, and socioeconomic inequities in access to MCS in the United States among patients with cardiogenic shock. Methods: Medicare data were used to identify patients with cardiogenic shock admitted to hospitals with advanced tMCS (microaxial left ventricular assist device [mLVAD] or extracorporeal membranous oxygenation [ECMO]) capabilities within the 25 largest core-based statistical areas, all major metropolitan areas. We modeled the association between patient race, ethnicity, and socioeconomic status and use of mLVAD or ECMO. Results: After adjusting for age and clinical comorbidities, dual eligibility for Medicaid was associated with a 19.9% (95% CI, 11.5%-27.4%) decrease in odds of receiving mLVAD in a patient with cardiogenic shock (P < .001). After adjusting for age, clinical comorbidities, and dual eligibility for Medicaid, Black race was associated with 36.7% (95% CI, 28.4%-44.2%) lower odds of receiving mLVAD in a patient with cardiogenic shock. Dual eligibility for Medicaid was associated with a 62.0% (95% CI, 60.8%-63.1%) decrease in odds of receiving ECMO in a patient with cardiogenic shock (P < .001). Black race was associated with 36.0% (95% CI, 16.6%-50.9%) lower odds of receiving ECMO in a patient with cardiogenic shock, after adjusting for Medicaid eligibility. Conclusions: We identified large and significant racial, ethnic, and socioeconomic inequities in access to mLVAD and ECMO among patients presenting with cardiogenic shock to metropolitan hospitals with active advanced tMCS programs. These findings highlight systematic inequities in access to potentially lifesaving therapies.

Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.

Several blinding diseases affecting the retina and optic nerve are exacerbated by or caused by dysregulated inflammation and oxidative stress. These diseases include uveitis, age related macular degeneration, diabetic retinopathy and glaucoma. Consequently, despite their divergent symptoms, treatments that reduce oxidative stress and suppress inflammation may be therapeutic. The production of inflammatory cytokines and their activities are regulated by a class of proteins termed Suppressors of Cytokine Signaling (SOCS). SOCS1 and SOCS3 are known to dampen signaling via pathways employing Janus kinases and signal transducer and activator of transcription proteins (JAK/STAT), Toll-like Receptors (TLR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen activated kinase (MAPK) and NLR family pyrin domain containing 3 (NLRP3). We have developed cell-penetrating peptides from the kinase inhibitory region of the SOCS1 and SOCS3 (denoted as R9-SOCS1-KIR and R9-SOCS3-KIR) and tested them in retinal pigment epithelium (RPE) cells and in macrophage cell lines. SOCS-KIR peptides exhibited anti-inflammatory, anti-oxidant and anti-angiogenic properties. In cell culture, both Th1 and Th17 cells were suppressed together with the inhibition of other inflammatory markers. We also observed a decrease in oxidants and a simultaneous rise in neuroprotective and anti-oxidant effectors. In addition, treatment prevented the loss of gap junction proteins and the ensuing drop in transepithelial electrical resistance in RPE cells. When tested in mouse models by eye drop instillation, they showed protection against autoimmune uveitis, as a prophylactic as well as a therapeutic. Mice with endotoxin-induced uveitis were protected by eye drop administration as well. R9-SOCS3-KIR was particularly effective against the pathways acting through STAT3, e.g. IL-6 and VEGF-A mediated responses that lead to macular degeneration. Eye drop administration of R9-SOCS3-KIR stimulated production of antioxidant effectors and reduced clinical symptoms in mouse model of oxidative stress that replicates the RPE injury occurring in AMD. Because these peptides suppress multiple pathogenic stimuli and because they can be delivered topically to the cornea, they are attractive candidates for therapeutics for uveitis, macular degeneration, diabetic retinopathy and glaucoma.

Comparison of Surgical Wait Times and Procedure Length in the Management of Postaxial Polydactyly Using Local or General Anesthesia.

Introduction: For infants with ulnar polydactyly, surgical removal of the supernumerary digit can be performed under general or local anesthetic. This study evaluated the wait times, surgical duration, and sedation times associated with performing the procedure under local versus general anesthetic in infants with ulnar polydactyly. Methods: The databases of three surgeons at our institution were reviewed for children less than 2 years of age who underwent surgery for non-syndromic ulnar polydactyly. Data collection included patient demographics, wait times, duration of surgery and sedation and complications. Results: The study included children (n = 55) who received treatment under local (n = 22) or general (n = 33) anesthesia. The wait times for the local anesthetic group were significantly shorter than the general anesthetic group (p < 0.05) for: referral to first consultation appointment; referral to surgery date, and decision date to surgery date. The duration of surgery (17.9 ± 6.9 vs 36.6 ± 20.2 min) and sedation time (26.3 ± 11.1 vs 74.8 ± 29.1 min) were significantly shorter in the local anaesthetic group (p < 0.05). There were no differences in complication rates between the groups. Conclusion: In this single-institution retrospective analysis, treatment of non-syndromic ulnar polydactyly with local anesthetic and bottle sedation was associated with shorter wait times, and duration of surgery and sedation. Level of Evidence: III, retrospective chart review and quality improvement initiative.

Introduction : Chez les nourrissons présentant une polydactylie cubitale, il est possible de procéder à l'ablation chirurgicale du doigt excédentaire sous anesthésie locale ou générale. La présente étude visait à évaluer les temps d'attente, la durée de l'opération et la durée de la sédation associés à l'intervention lorsqu'elle était effectuée sous anesthésie locale ou générale chez les nourrissons présentant une polydactylie cubitale. méthodes : Les chercheurs ont fouillé les bases de données de trois chirurgiens de leur établissement pour en extraire les cas d'enfants de moins de deux ans ayant subi une opération de la polydactylie cubitale non syndromique. La collecte de données incluait les caractéristiques des patients, les temps d'attente, la durée de l'opération et de la sédation et les complications. Résultats : La présente étude incluait des enfants (n=55) qui avaient été traités sous anesthésie locale (n=22) ou générale (n=33). Le temps d'attente du groupe sous anesthésie locale était beaucoup plus court que celui du groupe sous anesthésie générale (p<0,05) pour ce qui est de la période entre l'orientation et la première consultation, l'orientation et la date de l'opération, ainsi que la date de la décision et la date de l'opération. La durée de l'opération (17,9 ± 6,9 minutes par rapport à 36,6 ± 20,2 minutes) et de la sédation (26,3 ± 11,1 minutes par rapport à 74,8 ± 29,1 minutes) était beaucoup plus courte dans le groupe sous anesthésie locale (p<0,05). Il n'y avait pas de différence entre les groupes à l'égard des taux de complications. Conclusion : Dans cette analyse rétrospective mono-institutionnelle, le traitement de la polydactylie cubitale non syndromique accompagné d'une anesthésie locale et d'une sédation par bonbonne était associé à une diminution du temps d'attente ainsi que de la durée d'opération et de sédation.

Babesiosis in immunosuppressed hosts: pathogenesis, diagnosis and management.

PURPOSE OF REVIEW: This review provides the most recent evidence of the challenges that occur in the management of babesiosis in immunocompromised hosts. RECENT FINDINGS: The epidemiology of babesiosis is affected by climate change leading to increasing numbers of cases as well as increasing areas of endemicity. Immunosuppressed hosts, especially with asplenia or B-cell defects, are at high risk of having severe disease as well as persistent and relapsed infection. Resistance to the primary therapies azithromycin and atovaquone can develop leading to further challenges in treating persistent or relapsed disease in the immunocompromised host. SUMMARY: Babesiosis is likely to become a more frequent infectious complication in immunosuppressed hosts as the areas of endemicity expand. Reduced efficacy of standard therapies is likely to continue emerging so more effort needs to be placed on methods of assessing resistance in vitro and developing more reliable treatments for resistant infections.

Generation of an Armcx1 Conditional Knockout Mouse.

Armadillo repeat-containing X-linked protein-1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 in vivo, we have created a conditional Armcx1 knockout mouse line in which the entire coding region of the Armcx1 gene is flanked by loxP sites. This Armcx1fl line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for ß-actin and Six3, in order to achieve deletion of Armcx1 globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in Armcx1 knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The Armcx1fl mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1-deficient neurons to degeneration in the setting of additional heritable or environmental stressors.

Long-Term Results of Bladder Preservation with Twice-Daily Radiation plus 5-Flourouracil/Cisplatin or Daily Radiation plus Gemcitabine for MIBC - Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.

PURPOSE: 5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. METHODS AND MATERIALS: Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. RESULTS: From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 - 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

Expanding the phenotype of neurofibromatosis type 1 microdeletion syndrome.

Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics. This cohort consists of 57 individuals with NF-1 microdeletion syndrome (28 type-1, 4 type-2, 2 type-3, 9 atypical deletions, and 14 indeterminate). We note 38/56 (67.9%) with describable facial features, 25/57 (43.8%) with plexiform neurofibromas, and 3/57 (5.2%) with malignant peripheral nerve sheath tumors within the observed period. The most reported neurodevelopmental manifestations from school-age or older individuals included 39/49 (79.6%) with developmental delays, 35/49 (71.4%) with expressive and/or receptive speech delays, 33/41 (80.5%) with learning difficulties, and 23/42 (54.8%) with attention-deficit/hyperactivity disorder. Full-scale IQ testing data was available for 22 individuals (range: 50-96). Of the 21 adults in this cohort, 14/21 (66.7%) graduated from high school, and 4/21 (19.0%) had some college experience. Many individuals received academic support (i.e., special education, individual education plan). In this cohort, neurocognitive outcomes in adults varied more than typically reported in the literature.

Cost-effectiveness analysis of health tapestry, a complex primary care program for older adults: a post-hoc analysis.

BACKGROUND: We initially reported on the cost-effectiveness of a 6-month randomized controlled implementation trial which evaluated Health TAPESTRY, a primary care program for older adults, at the McMaster Family Health Team (FHT) site and 5 other FHT sites in Ontario, Canada. While there were no statistically significant between-group differences in outcomes at month 6 post randomization, positive outcomes were observed at the McMaster FHT site, which recruited 40% (204/512) of the participants. The objective of this post-hoc study was to determine the cost-effectiveness of Health TAPESTRY based on data from the McMaster FHT site. METHODS: Costs included the cost to implement Health TAPESTRY at McMaster as well as healthcare resource consumed, which were costed using publicly available sources. Health-related-quality-of-life was evaluated with the EQ-5L-5L at baseline and at month 6 post randomization. Quality-adjusted-life-years (QALYs) were calculated under an-area-under the curve approach. Unadjusted and adjusted regression analyses (two independent regression analyses on costs and QALYs, seemingly unrelated regression [SUR], net benefit regression) as well as difference-in-difference and propensity score matching (PSM) methods, were used to deal with the non-randomized nature of the trial. Sampling uncertainty inherent to the trial data was estimated using non-parametric bootstrapping. The return on investment (ROI) associated with Health TAPESTRY was calculated. All costs were reported in 2021 Canadian dollars. RESULTS: With an intervention cost of $293/patient, Health TAPESTRY was the preferred strategy in the unadjusted and adjusted analyses. The results of our bootstrap analyses indicated that Health TAPESTRY was cost-effective compared to usual care at commonly accepted WTP thresholds. For example, if decision makers were willing to pay $50,000 per QALY gained, the probability of Health TAPESTRY to be cost effective compared to usual care varied from 0.72 (unadjusted analysis) to 0.96 (SUR) when using a WTP of $50,000/QALY gained. The DID and ROI analyses indicated that Health Tapestry generated a positive ROI. CONCLUSION: Health TAPESTRY was the preferred strategy when implemented at the McMaster FHT. We caution care in interpreting the results because of the post-hoc nature of the analyses and limited sample size based on one site.

Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial.

Importance: Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. Objective: To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. Design, Setting, and Participants: This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). Intervention: A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Main Outcomes and Measures: Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. Results: The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Conclusions and Relevance: Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. Trial Registration: ClinicalTrials.gov Identifier NCT04112381.

Sweet syndrome associated with moderate leukocyte adhesion deficiency type I: a case report and review of the literature.

Sweet syndrome is an acute febrile neutrophilic dermatosis characterized by the infiltration of neutrophils into the skin. It may occur idiopathically or be linked to malignancies, inflammatory or autoimmune diseases. Leukocyte adhesion deficiency type I (LAD-I) is an inborn error immunity wherein leukocytes lack adhesion molecules necessary for migration to infection sites due to mutations in the CD18 gene encoding ß2 integrins. We present a case of a 16-month-old female initially diagnosed and treated for Sweet syndrome based on histopathological findings with recurrent flare episodes. Subsequent workup revealed LAD-I, making this case the first documented association between Sweet syndrome and LAD-I. Moreover, we reviewed the pertinent literatures detailing the concurrence of neutrophilic dermatosis and immunodeficiency disorders. This case underscores the significance of comprehensive evaluation for Sweet syndrome patients who are refractory to conventional treatments.

Autoclaving is at least as effective as gamma irradiation for biotic clearing and intentional microbial recolonization of soil.

Sterilization is commonly used to remove or reduce the biotic constraints of a soil to allow recolonization by soil-dwelling organisms, with autoclaving and gamma irradiation being the most frequently used approaches. Many studies have characterized sterilization impacts on soil physicochemical properties, with gamma irradiation often described as the preferred approach, despite the lower cost and higher scalability of autoclaving. However, few studies have compared how sterilization techniques impact soil recolonization by microorganisms. Here, we compared how two sterilization approaches (autoclaving; gamma irradiation) and soil washing impacted microbial recolonization of soil from a diverse soil inoculum. Sterilization method had little impact on microbial alpha diversity across recolonized soils. For sterile soil regrowth microcosms, species richness and diversity were significantly reduced by autoclaving relative to gamma irradiation, particularly for fungi. There was no impact of sterilization method on bacterial composition in recolonized soils and minimal impact on fungal composition (P = 0.05). Washing soils had a greater impact on microbial composition than sterilization method, and sterile soil regrowth had negligible impacts on microbial recolonization. These data suggest that sterilization method has no clear impact on microbial recolonization, at least across the soils tested, indicating that soil autoclaving is an appropriate and economical approach for biotically clearing soils.IMPORTANCESterilized soils represent soil-like environments that act as a medium to study microbial colonization dynamics in more "natural" settings relative to artificial culturing environments. Soil sterilization is often carried out by gamma irradiation or autoclaving, which both alter soil properties, but gamma irradiation is thought to be the gentler technique. Gamma irradiation can be cost prohibitive and does not scale well for larger experiments. We sought to examine how soil sterilization technique can impact microbial colonization, and additionally looked at the impact of soil washing which is believed to remove soil toxins that inhibit soil recolonization. We found that both gamma-irradiated and autoclaved soils showed similar colonization patterns when reintroducing microorganisms. Soil washing, relative to sterilization technique, had a greater impact on which microorganisms were able to recolonize the soil. When allowing sterilized soils to regrow (i.e., persisting microorganisms), gamma irradiation performed worse, suggesting that gamma irradiation does not biotically clear soils as well as autoclaving. These data suggest that both sterilization techniques are comparable, and that autoclaving may be more effective at biotically clearing soil.

Relationships between plasma biomarkers, tau PET, FDG PET, and volumetric MRI in mild to moderate Alzheimer's disease patients.

INTRODUCTION: The "A/T/N" (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimer's disease (AD) diagnosis and can encompass additional changes such as inflammation ("I"). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age. Highlights: Plasma pTau-181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau-181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS-cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate.

Sleep Health and Anxiety Symptoms in Midlife Women: The Study of Women's Health Across the Nation (SWAN).

Purpose: To investigate the associations between anxiety symptoms in midlife women and sleep features later in life, the aim is to test the hypothesis that poor sleep, as measured by each of six individual dimensions (4 objective actigraphy measures, 2 self-reports) of sleep health, is associated with higher levels of anxiety symptoms in midlife women. Participants and Methods: The participants in this longitudinal analysis included women from the SWAN Sleep I Study, a subcohort of the community-dwelling midlife women participating in the core Study of Women's Health Across the Nation (SWAN), which was initiated in 1996. Of the 370 participants enrolled in the Sleep Study, 270 were included in the analytic sample, and 100 who did not meet the inclusion criteria were excluded. Baseline measures of six dimensions of multidimensional sleep health (actigraphy measures: efficiency, duration, mid-sleep timing, regularity; self-report measures: alertness, satisfaction) were obtained between 2003 and 2005, corresponding to SWAN core annual/biennial assessments 5-8. Associations of each dimension with self-reported anxiety symptoms (Generalized Anxiety Disorder - 7-item scale; GAD-7), collected during visits 12 (2009-2011), 13 (2011-2013), and 15 (2015-2017), were examined using mixed models. The GAD-7 outcome was measured both continuously and as a categorical variable due to its skewed distribution. Results: No statistically significant associations were found between any of the six baseline sleep health dimensions and the GAD-7 score after adjustment for covariates. Conclusion: The reasons for the lack of support for our hypothesis, despite previous evidence supporting an association between sleep and anxiety, are unclear. There is considerable overlap between anxiety and sleep symptoms, which may complicate the interpretation of our the findings. Thus, the failure to identify associations is likely multifactorial, and more studies with shorter follow-up intervals are warranted to better understand these relationships.

Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

Disruption of central and peripheral circadian clocks and circadian controlled estrogen receptor rhythms in night shift nurses in working environments.

Chronic disruption of circadian rhythms by night shift work is associated with an increased breast cancer risk. However, little is known about the impact of night shift on peripheral circadian genes (CGs) and circadian-controlled genes (CCGs) associated with breast cancer. Hence, we assessed central clock markers (melatonin and cortisol) in plasma, and peripheral CGs (PER1, PER2, PER3, and BMAL1) and CCGs (ESR1 and ESR2) in peripheral blood mononuclear cells (PBMCs). In day shift nurses (n = 12), 24-h rhythms of cortisol and melatonin were aligned with day shift-oriented light/dark schedules. The mRNA expression of PER2, PER3, BMAL1, and ESR2 showed 24-h rhythms with peak values in the morning. In contrast, night shift nurses (n = 10) lost 24-h rhythmicity of cortisol with a suppressed morning surge but retained normal rhythmic patterns of melatonin, leading to misalignment between cortisol and melatonin. Moreover, night shift nurses showed disruption of rhythmic expressions of PER2, PER3, BMAL1, and ESR2 genes, resulting in an impaired inverse correlation between PER2 and BMAL1 compared to day shift nurses. The observed trends of disrupted circadian markers were recapitulated in additional day (n = 20) and night (n = 19) shift nurses by measurement at early night and midnight time points. Taken together, this study demonstrated the misalignment of cortisol and melatonin, associated disruption of PER2 and ESR2 circadian expressions, and internal misalignment in peripheral circadian network in night shift nurses. Morning plasma cortisol and PER2, BMAL1, and ESR2 expressions in PBMCs may therefore be useful biomarkers of circadian disruption in shift workers.

Co-Morbidity Differences Associated With Long-Term Amputation and Repeat Revascularization Rates After Femoropopliteal Artery Intervention for Intermittent Claudication by Sex, Race, and Ethnicity.

Use of peripheral vascular intervention (PVI) for intermittent claudication (IC) continues to expand, but there is uncertainty whether baseline demographics, procedural techniques and outcomes differ by sex, race, and ethnicity. This study aimed to examine amputation and revascularization rates up to 4 years after femoropopliteal (FP) PVI for IC by sex, race, and ethnicity. Patients who underwent FP PVI for IC between 2016 and 2020 from the PINC AI Healthcare Database were analyzed. The primary outcome was any index limb amputation, assessed by Kaplan-Meier estimate. Secondary outcomes included index limb major amputation, repeat revascularization, and index limb repeat revascularization. Unadjusted and adjusted hazard ratios (HRs) were estimated using Cox proportional hazard regression models. This study included 19,324 patients with IC who underwent FP PVI, with 41.2% women, 15.6% Black patients, and 4.7% Hispanic patients. Women were less likely than men to be treated with atherectomy (45.1% vs 47.8%, p = 0.0003); Black patients were more likely than White patients to receive atherectomy (50.7% vs 44.9%, p <0.001), and Hispanic patients were less likely than non-Hispanic patients to receive atherectomy (41% vs 47%, p = 0.0004). Unadjusted rates of any amputation were similar in men and women (6.4% for each group, log-rank p = 0.842), higher in Black patients than in White patients (7.8% vs 6.1%, log-rank p = 0.007), and higher in Hispanic patients than in non-Hispanic patients (8.8% vs 6.3%, log-rank p = 0.031). After adjustment for baseline characteristics, Black race was associated with higher rates of repeat revascularization (adjusted HR 1.13, 95% confidence interval 1.04 to 1.22) and any FP revascularization (adjusted HR 1.10, 95% confidence interval 1.01 to 1.20). No statistical difference in amputation rate was observed among comparison groups. Women and men with IC had similar crude and adjusted amputation and revascularization outcomes after FP PVI. Black patients had higher repeat revascularization and any FP revascularization rates than did White patients. Black and Hispanic patients had higher crude amputation rates, but these differences were attenuated by adjustment for baseline characteristics. Black patients were more likely to receive atherectomy and had higher rates of any repeat revascularization and specifically FP revascularization. Further study is necessary to determine whether these patterns are related to disease-specific issues or practice-pattern differences among different populations.

Compartmental Differences in the Retinal Ganglion Cell Mitochondrial Proteome.

Among neurons, retinal ganglion cells (RGCs) are uniquely sensitive to mitochondrial dysfunction. The RGC is highly polarized, with a somatodendritic compartment in the inner retina and an axonal compartment projecting to targets in the brain. The drastically dissimilar functions of these compartments implies that mitochondria face different bioenergetic and other physiological demands. We hypothesized that compartmental differences in mitochondrial biology would be reflected by disparities in mitochondrial protein composition. Here, we describe a protocol to isolate intact mitochondria separately from mouse RGC somatodendritic and axonal compartments by immunoprecipitating labeled mitochondria from RGC MitoTag mice. Using mass spectrometry, 471 and 357 proteins were identified in RGC somatodendritic and axonal mitochondrial immunoprecipitates, respectively. We identified 10 mitochondrial proteins exclusively in the somatodendritic compartment and 19 enriched ≥2-fold there, while 3 proteins were exclusively identified and 18 enriched in the axonal compartment. Our observation of compartment-specific enrichment of mitochondrial proteins was validated through immunofluorescence analysis of the localization and relative abundance of superoxide dismutase ( SOD2 ), sideroflexin-3 ( SFXN3 ) and trifunctional enzyme subunit alpha ( HADHA ) in retina and optic nerve specimens. The identified compartmental differences in RGC mitochondrial composition may provide promising leads for uncovering physiologically relevant pathways amenable to therapeutic intervention for optic neuropathies.

Applications of wearable activity monitors for prostate cancer survivors: A systematic scoping review.

BACKGROUND: Wearable technology is used to monitor and motivate physical activity (PA) and provides continuous, objective PA and sleep data outside the clinical setting. We reviewed the literature to understand how wearables are integrated into prostate cancer (PC) investigations in order to identify current practices, gaps, and research opportunities. METHODS: We conducted a literature search for articles using wearables, among PC survivors published between 2012 and 2022. We extracted study details, interventions and outcomes, participant baseline characteristics, and device characteristics and grouped them by study type: randomized control trials (RCTs) and non-randomized studies. RESULTS: Of 354 articles screened, 44 met eligibility criteria (23 RCTs, and 21 non-randomized). 89% used wearables to monitor PA metrics, 11%, sleep metrics, and 6.8%, both. Most studies involved exercise (70% RCTs, 9% non-randomized studies) or lifestyle interventions (30% RCTs, 9% non-randomized studies). Intervention delivery methods included personalized computer-based (48%), in-person (e.g., trainer) (20%), and education web or print-based (20%). Interventions occurred at the participant's home (48%) or at a gym (20%). 57% of the studies evaluated the feasibility and acceptability of the wearable as an activity-measuring device or as part of a remotely delivered computer-based intervention. Studies used wearables to monitor adherence to PA interventions, motivate behavior change, to assess patient outcomes (e.g., patient function, quality of life, mood), or as data collection tools. CONCLUSIONS: Wearables are primarily being used to assess daily activity and monitor adherence to exercise interventions in clinical studies involving PC survivors. Findings suggest that they are feasible for use in this population. More research is needed to understand how to integrate wearables into routine clinical care, expand their use to predict clinical outcomes, or to deliver tailored interventions for PC survivors.