Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020.

INTRODUCTION: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings. METHODS: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences. RESULTS: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals. CONCLUSIONS: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery.

Distinct sets of molecular characteristics define tumor-rejecting neoantigens.

Challenges in identifying tumor-rejecting neoantigens limit the efficacy of neoantigen vaccines to treat cancers, including cutaneous squamous cell carcinoma (cSCC). A minority of human cSCC tumors shared neoantigens, supporting the need for personalized vaccines. Using a UV-induced mouse cSCC model which recapitulated the mutational signature and driver mutations found in human disease, we found that CD8 T cells constrain cSCC. Two MHC class I neoantigens were identified that constrained cSCC growth. Compared to the wild-type peptides, one tumor-rejecting neoantigen exhibited improved MHC binding and the other had increased solvent accessibility of the mutated residue. Across known neoantigens that do not impact MHC binding, structural modeling of the peptide/MHC complexes indicated that increased solvent accessibility, which will facilitate TCR recognition of the neoantigen, distinguished tumor-rejecting from non-immunogenic neoantigens. This work reveals characteristics of tumor-rejecting neoantigens that may be of considerable importance in identifying optimal vaccine candidates in cSCC and other cancers.

Moral Distress and Moral Injury in Military Healthcare Clinicians: A Scoping Review.

Introduction: Healthcare clinicians are often at risk of psychological distress due to the nature of their occupation. Military healthcare providers are at risk for additional psychological suffering related to unique moral and ethical situations encountered in military service. This scoping review identifies key characteristics of moral distress and moral injury and how these concepts relate to the military healthcare clinician who is both a care provider and service member. Methods: A scoping review of moral distress and moral injury literature as relates to the military healthcare clinician was conducted on the basis of the Joanna Briggs Institute scoping review framework. Databases searched included CINAHL, Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), Embase (Ovid), PsycInfo, 2 U.S. Defense Department sources, conference papers index, and dissertation abstracts. Reference lists of all identified reports and articles were searched for additional studies. Results: A total of 573 articles, published between the years 2009 and 2021, were retrieved to include a portion of the COVID-19 pandemic period. One hundred articles met the inclusion criteria for the final full-text review and analysis. Discussion: This scoping review identified moral distress and moral injury literature to examine similarities, differences, and overlaps in the defining characteristics of the concepts and the associated implications for patients, healthcare clinicians, and organizations. This review included the unfolding influence of the COVID-19 pandemic on moral experiences in health care and the blurring of those lines between civilian and military healthcare clinicians. Future directions of moral injury and moral distress research, practice, and care are discussed.

Evaluating Chlamydia trachomatis and Neisseria gonorrhoeae screening and treatment among asymptomatic pregnant women to prevent preterm birth and low birthweight in Gaborone, Botswana: A secondary analysis from a non-randomised, cluster-controlled trial.

OBJECTIVE: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana. DESIGN: Non-randomised, cluster-controlled trial. SETTING: Four antenatal care clinics in Gaborone, Botswana. POPULATION: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible. METHODS: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g). RESULTS: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants. CONCLUSION: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants.

Lack of Dosage Balance and Incomplete Dosage Compensation in the ZZ/ZW Gila Monster (Heloderma suspectum) Revealed by De Novo Genome Assembly.

Reptiles exhibit a variety of modes of sex determination, including both temperature-dependent and genetic mechanisms. Among those species with genetic sex determination, sex chromosomes of varying heterogamety (XX/XY and ZZ/ZW) have been observed with different degrees of differentiation. Karyotype studies have demonstrated that Gila monsters (Heloderma suspectum) have ZZ/ZW sex determination and this system is likely homologous to the ZZ/ZW system in the Komodo dragon (Varanus komodoensis), but little else is known about their sex chromosomes. Here, we report the assembly and analysis of the Gila monster genome. We generated a de novo draft genome assembly for a male using 10X Genomics technology. We further generated and analyzed short-read whole genome sequencing and whole transcriptome sequencing data for three males and three females. By comparing female and male genomic data, we identified four putative Z chromosome scaffolds. These putative Z chromosome scaffolds are homologous to Z-linked scaffolds identified in the Komodo dragon. Further, by analyzing RNAseq data, we observed evidence of incomplete dosage compensation between the Gila monster Z chromosome and autosomes and a lack of balance in Z-linked expression between the sexes. In particular, we observe lower expression of the Z in females (ZW) than males (ZZ) on a global basis, though we find evidence suggesting local gene-by-gene compensation. This pattern has been observed in most other ZZ/ZW systems studied to date and may represent a general pattern for female heterogamety in vertebrates.

A Novel Discriminating Tool for Microcytic Anemia in Childhood.

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability.

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.

It's a trap?! Escape from an ancient, ancestral sex chromosome system and implication of Foxl2 as the putative primary sex-determining gene in a lizard (Anguimorpha; Shinisauridae).

Although sex determination is ubiquitous in vertebrates, mechanisms of sex determination vary from environmentally to genetically influenced. In vertebrates, genetic sex determination is typically accomplished with sex chromosomes. Groups like mammals maintain conserved sex chromosome systems, while sex chromosomes in most vertebrate clades are not conserved across similar evolutionary timescales. One group inferred to have an evolutionarily stable mode of sex determination is Anguimorpha, a clade of charismatic taxa including monitor lizards, Gila monsters, and crocodile lizards. The common ancestor of extant anguimorphs possessed a ZW system that has been retained across the clade. However, the sex chromosome system in the endangered, monotypic family of crocodile lizards (Shinisauridae) has remained elusive. Here, we analyze genomic data to demonstrate that Shinisaurus has replaced the ancestral anguimorph ZW system on LG7 with a novel ZW system on LG3. The linkage group, LG3, corresponds to chromosome 9 in chicken, and this is the first documented use of this syntenic block as a sex chromosome in amniotes. Additionally, this ~1 Mb region harbors approximately 10 genes, including a duplication of the sex-determining transcription factor, Foxl2, critical for the determination and maintenance of sexual differentiation in vertebrates, and thus a putative primary sex-determining gene for Shinisaurus.

Skeletal muscle DNA methylation: Effects of exercise and HIV.

Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline. We identified 983 differentially methylated positions (DMPs) in PWH and controls at baseline and 237 DMPs after training. The influence of HIV serostatus on SkM methylation was more pronounced than that of exercise training. There was little overlap in the genes associated with the probes most significantly differentiated by exercise training within each group. Baseline EAA (mean ± SD) was similar between PWH (-0.4 ± 2.5 years) and controls (0.2 ± 2.6 years), and the exercise effect was not significant (p = 0.79). EAA and physical function at baseline were not significantly correlated (all p ≥ 0.10). This preliminary investigation suggests HIV-specific epigenetic adaptations in SkM with exercise training but confirmation in a larger study that includes transcriptomic analysis is warranted.

Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia.

OBJECTIVES: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. METHODS: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. RESULTS: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (IVL), small proline rich protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. CONCLUSIONS: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

Genomic and demographic processes differentially influence genetic variation across the human X chromosome.

Many forces influence genetic variation across the genome including mutation, recombination, selection, and demography. Increased mutation and recombination both lead to increases in genetic diversity in a region-specific manner, while complex demographic patterns shape patterns of diversity on a more global scale. While these processes act across the entire genome, the X chromosome is particularly interesting because it contains several distinct regions that are subject to different combinations and strengths of these forces: the pseudoautosomal regions (PARs) and the X-transposed region (XTR). The X chromosome thus can serve as a unique model for studying how genetic and demographic forces act in different contexts to shape patterns of observed variation. We therefore sought to explore diversity, divergence, and linkage disequilibrium in each region of the X chromosome using genomic data from 26 human populations. Across populations, we find that both diversity and substitution rate are consistently elevated in PAR1 and the XTR compared to the rest of the X chromosome. In contrast, linkage disequilibrium is lowest in PAR1, consistent with the high recombination rate in this region, and highest in the region of the X chromosome that does not recombine in males. However, linkage disequilibrium in the XTR is intermediate between PAR1 and the autosomes, and much lower than the non-recombining X. Finally, in addition to these global patterns, we also observed variation in ratios of X versus autosomal diversity consistent with population-specific evolutionary history as well. While our results were generally consistent with previous work, two unexpected observations emerged. First, our results suggest that the XTR does not behave like the rest of the recombining X and may need to be evaluated separately in future studies. Second, the different regions of the X chromosome appear to exhibit unique patterns of linked selection across different human populations. Together, our results highlight profound regional differences across the X chromosome, simultaneously making it an ideal system for exploring the action of evolutionary forces as well as necessitating its careful consideration and treatment in genomic analyses.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

Background: People with HIV (PWH) have lower exercise capacity compared to HIV-uninfected peers, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. Methods: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus, and change from baseline to 12 and 24 weeks using mixed effects models. Results: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p=0.067). AHRR was lower among PWH (91 vs 102%; difference 11%, 95% CI 2.5-19.7; p=0.01). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p<0.001) and was sustained at week 24 (+5, 95%CI 1-9; p=0.008) compared to no change among controls (95%CI -4 to 4; p=0.95; pinteraction=0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p=0.70). Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Reliability of Phonemically Loaded Sentences in Spanish for Identifying Laryngeal Dystonia by Non-Spanish Speaking Speech-Language Pathologists.

INTRODUCTION: Laryngeal dystonia (LD) is a focal dystonia affecting the intrinsic laryngeal muscles. Clinical diagnosis requires subjective evaluation by experienced clinicians and is primarily based on auditory-perceptual assessment. Several speech tasks are widely accepted to elicit diagnosis specific auditory-perceptual symptoms of glottal stops in adductor LD or breathy breaks in abductor LD in spoken English. With the growing Spanish speaking population in the US and lack of Spanish speech tasks to assist in identifying LD in Spanish speaking subjects, assessing the reliability of phonemically loaded sentences in Spanish for use by non-Spanish speaking providers is critical. The first aim of this study was to develop and assess the reliability of a set of Spanish language phonemically loaded sentences designed to elicit signs and symptoms of LD. The second aim was to determine the effectiveness of non-Spanish speaking speech-language pathologists (SLPs) in identifying LD in Spanish speaking subjects using these stimuli. METHODS: Phonemically loaded sentences were developed for this study following current guidelines for assessment of LD. Voice samples were obtained from native Spanish speaking individuals. Participant-speakers included 20 people with LD and 20 people without LD who served as controls. All participant-speakers were assessed by a Spanish-speaking laryngologist. Audio samples were presented to non-Spanish speaking SLPs with expertise in working with people with LD who served as raters and classified the samples as either presence or absence of LD. Kappa and the intra-class correlation coefficient were calculated and mixed effects logistic regression was used for prediction. RESULTS: The inter and intra-rater reliability indicated statistically significant agreement. Sensitivity, specificity, and predictive values for the diagnosis of LD by the raters were overall strong. CONCLUSIONS: Findings demonstrate that non-Spanish speaking SLPs with expertise in the assessment and treatment of LD can reliably identify the presence of LD using Spanish language stimuli in Spanish-speaking individuals. This study supports the use of newly developed Spanish language phonemically loaded voiced and voiceless sentences by English speaking clinicians as an effective tool for identifying LD in Spanish speakers, perhaps mitigating diagnostic delays experienced by patients with LD.

Retrospective analysis of the management of pelvic decubitus ulcers and their outcomes.

Background: Many patients with decubitus-related osteomyelitis are ineligible for myocutaneous flapping, and optimal management in this population is unknown. We describe treatments and outcomes of hospitalized patients with decubitus ulcer-related osteomyelitis who did not undergo surgical reconstruction or coverage. Methods: We systematically identified hospitalized patients with diagnoses of pelvic, sacral, or femoral osteomyelitis due to decubitus ulceration between 1 January 2018 and 31 December 2018. Demographics, comorbidities, laboratory data, and outcomes were collected by manual chart review. T-tests or Chi-square tests were used for descriptive statistical comparisons; logistic regressions were used to explore the odds of readmission, osteomyelitis-related readmission, and death. Results: Of 89 patients meeting inclusion criteria, 34 (38%) received surgical debridement and ⩾6 weeks of antibiotics; 55 (62%) received either antibiotics alone or debridement and <6 weeks of antibiotics. Mean age was 55 (standard deviation 18) years, 55% of patients were male, and 69% had spinal cord injury or other form of paralysis. Within 1 year, 56 (63%) patients were readmitted, 38 (44%) patients were readmitted due to complications from osteomyelitis, and 15 (17%) died. We found no significant differences in readmission (OR = 1.33, 95% CI: 0.54-3.21, p = 0.53), readmission related to osteomyelitis (OR = 1.64, 95% CI: 0.69-4.04, p = 0.27), subsequent sepsis (OR = 2.27, 95% CI: 0.83-6.93, p = 0.13), or death (OR = 2.88, 95% CI: 0.83-13.4, p = 0.12) by treatment group. Conclusions: Among patients with decubitus-related osteomyelitis who did not undergo myocutaneous flapping, outcomes were generally poor regardless of treatment, and not significantly improved with prolonged antibiotics. Prospective studies are needed to assess best practice strategies for this challenging patient population.

Chronic kidney disease increases cost of care and readmission risk after shoulder arthroplasty.

BACKGROUND: Chronic kidney disease (CKD) is associated with adverse outcomes and higher costs after lower extremity arthroplasty from higher rates of infection, aseptic loosening, and transfusion and longer hospital length of stay (LOS). The purpose of this study was to compare health care utilization and 90-day encounter charges after shoulder arthroplasty (SA) in patients with and without renal disease. A secondary aim was to define the characteristics of patients with renal disease. METHODS: We conducted a retrospective cohort study of all patients who underwent primary SA from January 2015 to December 2019 by a single surgeon at a single institution. Patients without a baseline glomerular filtration rate (GFR) were excluded. We evaluated results for patients with CKD (GFR ≤59 mL/min/1.73 m2) and without CKD (GFR ≥60 mL/min/1.73 m2). Univariate regression was performed to assess the influence of CKD on health care utilization, including LOS, transfusion, and risk for emergency department (ED) revisit or readmission during the 90-day postoperative period. In addition, 90-day encounter charges, revisit charges, and ED charges for patients with CKD were compared with those for patients with normal renal function. Last, multivariable linear regression models were used to assess the effect of estimated GFR on total 90-day encounter charges. RESULTS: A total of 514 patients met the study inclusion criteria, with 125 having CKD and 389 having normal GFR. Patients with CKD were more likely to require transfusion (odds ratio: 16.2 [confidence interval: 1.9, 139.7], P = .011) despite similar intraoperative estimated blood loss (156.9 ± 132.5 mL vs. 153.8 ± 89.7 mL; P = .768). In addition, patients with CKD had longer LOS (2.8 ± 1.3 days vs. 2.3 ± 1.0 days; P < .001), had higher 90-day readmission rates (P = .001), were more likely to visit the ED within 90 days after SA (P = .018), and had higher total 90-day encounter charges ($37,769 ± $6901 vs. $35,684 ± $5312; P = .001). Each unit increase in eGFR independently reduced total encounter charges by $67 (-$132, -$2; P = .043); dialysis patients incurred higher total 90-day encounter charges compared with patients with less severe renal disease ($42,733 ± $8985 vs. $37,531 ± $6749; P = .002). Also, patients with CKD were older (73.2 ± 8.9 vs. 68.1 ± 9.4 years; P < .001); had a lower preoperative hemoglobin level (12.4 ± 1.5 g/dL vs. 13.4 ± 1.5 g/dL; P < .001), higher American Society of Anesthesiologists score (P < .001), and more preoperative comorbidities (5.9 ± 2.9 vs. 5.0 ± 3.1; P < .001); and were more likely to use opioids preoperatively (P = .043). CONCLUSION: Patients with CKD have a higher risk for blood transfusion, ED visits, and readmission after SA, with higher total 90-day encounter charges. Identifying and optimizing this patient population before surgery can reduce costs and improve outcomes, which benefits patients, physicians, institutions, and payors.

Prognostic Utility of Oculomotor Assessments in Determining Return-to-Learn Time in Acutely Concussed College Student-Athletes: A Pilot Study.

We sought to discover which oculomotor test (King-Devick [KD], near point of convergence [NPC], and accommodative facility [AF]) would best produce a prognostic model for an RTL time frame. An observational cohort design was used to longitudinally track division I and III student-athletes with concussion at a private university in New York State. Measurements included pre-RTL oculomotor testing (NPC, KD, and AF), along with daily text messages and phone calls. Participants were considered returned-to-learn once they had returned to baseline symptoms and had attended 2 days of classes. Our data promote KD score and class attendance as the best-fit prognostic model, with every second accrued on the KD test equating to 5.29 h of RTL time. Further, attending class throughout recovery, versus not, shortened RTL time by a mean 170.50 h, or 7.1 days. Five variables produced a significant attenuating association with concussion symptoms: time post-injury (p = 0.01); caffeine (p = 0.05); alcohol (p = 0.01); music (p = 0.01); and physical activity (p = 0.01). Three variables produced a significant worsening association with concussion symptoms: screen time (p = 0.05); music (p = 0.01); and class attendance (p = 0.01). The findings present a preliminary evidence-based model to prognosticate RTL time. To our knowledge, this is the second longitudinal study, and the first overall, to present objective data for guiding and prognosticating RTL, respectively. Correspondingly, these data should assist clinicians with objectively steering RTL in-clinic.

Refractory pancytopenia upon initiation of asciminib in tyrosine kinase inhibitor-resistant chronic myeloid leukemia.

Asciminib, a "Specifically Targeting the ABL Myristoyl Pocket" inhibitor, is a new drug in the treatment of tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML). Hemocytopenias associated with asciminib are common adverse events documented by clinical trials. We report a case of precipitous-onset pancytopenia with the initiation of asciminib treatment in a patient with TKI-resistant CML. This case had a confounding array of laboratory findings that evidenced a drug-induced hemophagocytic component. We hope that our case stimulates further reporting of similar cases to enhance the understanding of the pathophysiology underlying asciminib-induced hemocytopenias.

Causes of Death Among Medical ICU Patients With Pneumonia Due to COVID-19 in a Safety-Net Hospital.

We sought to identify the primary causes of death of adult patients admitted to the medical ICU with symptomatic COVID-19 who ultimately suffered in-hospital mortality over the span of three major waves of COVID-19: Wild-type, alpha/epsilon, and delta. DESIGN: Retrospective single-center cohort study from March 2020 to December 2021. SETTING: One medical ICU in a 600-bed Tertiary Care Hospital in Los Angeles, CA. PATIENTS: Adult (n = 306) ICU patients admitted with symptomatic COVID-19 who suffered in-hospital mortality. INTERVENTIONS: None. MAIN RESULTS: Of the 306 patients with COVID-19 who died in the hospital, 86.3% were Hispanic/Latino. The leading cause of death was respiratory failure, occurring in 57.8% of patients. There was no significant change in the rate of pulmonary deaths across the three waves of COVID-19 in our study period. The mean time from symptom onset to admission was 6.5 days, with an average hospital length of stay of 18 days. This did not differ between pulmonary and other causes of death. Sepsis was the second most common cause of death at 23.9% with a significant decrease from the wild-type wave to the delta wave. Among patients with sepsis as the cause of death, 22% (n = 16) were associated with fungemia. There was no significant association between steroid administration and cause of death. Lastly, the alpha/epsilon wave from December 2020 to May 2021 had the highest mortality rate when compared with wild-type or delta waves. CONCLUSIONS: We found the primary cause of death in ICU patients with COVID-19 was acute respiratory failure, without significant changes over the span of three waves of COVID-19. This finding contrasts with reported causes of death for patients with non-COVID-19 acute respiratory distress syndrome, in which respiratory failure is an uncommon cause of death. In addition, we identified a subset of patients (5%) who died primarily due to fungemia, providing an area for further investigation.

An approach for prioritizing candidate genes from RNA-seq using preclinical cocaine self-administration datasets as a test case.

RNA-sequencing (RNA-seq) technology has led to a surge of neuroscience research using animal models to probe the complex molecular mechanisms underlying brain function and behavior, including substance use disorders. However, findings from rodent studies often fail to be translated into clinical treatments. Here, we developed a novel pipeline for narrowing candidate genes from preclinical studies by translational potential and demonstrated its utility in 2 RNA-seq studies of rodent self-administration. This pipeline uses evolutionary conservation and preferential expression of genes across brain tissues to prioritize candidate genes, increasing the translational utility of RNA-seq in model organisms. Initially, we demonstrate the utility of our prioritization pipeline using an uncorrected P-value. However, we found no differentially expressed genes in either dataset after correcting for multiple testing with false discovery rate (FDR < 0.05 or <0.1). This is likely due to low statistical power that is common across rodent behavioral studies, and, therefore, we additionally illustrate the use of our pipeline on a third dataset with differentially expressed genes corrected for multiple testing (FDR < 0.05). We also advocate for improved RNA-seq data collection, statistical testing, and metadata reporting that will bolster the field's ability to identify reliable candidate genes and improve the translational value of bioinformatics in rodent research.

It's a Trap?! Escape from an ancient, ancestral sex chromosome system and implication of Foxl2 as the putative primary sex determining gene in a lizard (Anguimorpha; Shinisauridae).

Although sex determination is ubiquitous in vertebrates, mechanisms of sex determination vary from environmentally- to genetically-influenced. In vertebrates, genetic sex determination is typically accomplished with sex chromosomes. Groups like mammals maintain conserved sex chromosome systems, while sex chromosomes in most vertebrate clades aren't conserved across similar evolutionary timescales. One group inferred to have an evolutionarily stable mode of sex determination is Anguimorpha, a clade of charismatic taxa including: monitor lizards, Gila monsters, and crocodile lizards. The common ancestor of extant anguimorphs possessed a ZW system that has been retained across the clade. However, the sex chromosome system in the endangered, monotypic family of crocodile lizards (Shinisauridae) has remained elusive. Here, we analyze genomic data to demonstrate that Shinisaurus has replaced the ancestral anguimorph ZW system on LG7 chromosome with a novel ZW system on LG3. The linkage group LG3 corresponds to chromosome 9 in chicken, and this is the first documented use of this syntenic block as a sex chromosome in amniotes. Additionally, this ~1Mb region harbors approximately 10 genes, including a duplication of the sex-determining transcription factor, Foxl2-critical for the determination and maintenance of sexual differentiation in vertebrates, and thus a putative primary sex determining gene for Shinisaurus.