Epstein-Barr virus protein EBNA-LP engages YY1 through leucine-rich motifs to promote naïve B cell transformation.

Epstein-Barr Virus (EBV) is associated with numerous cancers including B cell lymphomas. In vitro, EBV transforms primary B cells into immortalized Lymphoblastoid Cell Lines (LCLs) which serves as a model to study the role of viral proteins in EBV malignancies. EBV induced cellular transformation is driven by viral proteins including EBV-Nuclear Antigens (EBNAs). EBNA-LP is important for the transformation of naïve but not memory B cells. While EBNA-LP was thought to promote gene activation by EBNA2, EBNA-LP Knockout (LPKO) virus-infected cells express EBNA2-activated cellular genes efficiently. Therefore, a gap in knowledge exists as to what roles EBNA-LP plays in naïve B cell transformation. We developed a trans-complementation assay wherein transfection with wild-type EBNA-LP rescues the transformation of peripheral blood- and cord blood-derived naïve B cells by LPKO virus. Despite EBNA-LP phosphorylation sites being important in EBNA2 co-activation; neither phospho-mutant nor phospho-mimetic EBNA-LP was defective in rescuing naïve B cell outgrowth. However, we identified conserved leucine-rich motifs in EBNA-LP that were required for transformation of adult naïve and cord blood B cells. Because cellular PPAR-g coactivator (PGC) proteins use leucine-rich motifs to engage transcription factors including YY1, a key regulator of DNA looping and metabolism, we examined the role of EBNA-LP in engaging transcription factors. We found a significant overlap between EBNA-LP and YY1 in ChIP-Seq data. By Cut&Run, YY1 peaks unique to WT compared to LPKO LCLs occur at more highly expressed genes. Moreover, Cas9 knockout of YY1 in primary B cells prior to EBV infection indicated YY1 to be important for EBV-mediated transformation. We confirmed EBNA-LP and YY1 biochemical association in LCLs by endogenous co-immunoprecipitation and found that the EBNA-LP leucine-rich motifs were required for YY1 interaction in LCLs. We propose that EBNA-LP engages YY1 through conserved leucine-rich motifs to promote EBV transformation of naïve B cells.

The anatomy of transcriptionally active chromatin loops in Drosophila primary spermatocytes using super-resolution microscopy.

While the biochemistry of gene transcription has been well studied, our understanding of how this process is organised in 3D within the intact nucleus is less well understood. Here we investigate the structure of actively transcribed chromatin and the architecture of its interaction with active RNA polymerase. For this analysis, we have used super-resolution microscopy to image the Drosophila melanogaster Y loops which represent huge, several megabases long, single transcription units. The Y loops provide a particularly amenable model system for transcriptionally active chromatin. We find that, although these transcribed loops are decondensed they are not organised as extended 10nm fibres, but rather they largely consist of chains of nucleosome clusters. The average width of each cluster is around 50nm. We find that foci of active RNA polymerase are generally located off the main fibre axis on the periphery of the nucleosome clusters. Foci of RNA polymerase and nascent transcripts are distributed around the Y loops rather than being clustered in individual transcription factories. However, as the RNA polymerase foci are considerably less prevalent than the nucleosome clusters, the organisation of this active chromatin into chains of nucleosome clusters is unlikely to be determined by the activity of the polymerases transcribing the Y loops. These results provide a foundation for understanding the topological relationship between chromatin and the process of gene transcription.

Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.

The CRISPR-Cas9 system is widely used to permanently delete genomic regions via dual guide RNAs. Genomic rearrangements induced by CRISPR-Cas9 can occur, but continuous technical developments make it possible to characterize complex on-target effects. We combined an innovative droplet-based target enrichment approach with long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving the allelic co-occurrence of a genomic duplication and inversion of the target region, as well as integrations of exogenous DNA and clustered interchromosomal DNA fragment rearrangements. Furthermore, we found that these genomic alterations led to functional aberrant DNA fragments and can alter cell proliferation. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations, and introduce a data-driven workflow enabling detailed dissection of the on-target sequence content with superior resolution.

Dopamine Modulates Effective Connectivity in Frontal Cortex.

There is increasing evidence that the left lateral frontal cortex is hierarchically organized such that higher-order regions have an asymmetric top-down influence over lower order regions. However, questions remain about the underlying neuroarchitecture of this hierarchical control organization. Within the frontal cortex, dopamine plays an important role in cognitive control functions, and we hypothesized that dopamine may preferentially influence top-down connections within the lateral frontal hierarchy. Using a randomized, double-blind, within-subject design, we analyzed resting-state fMRI data of 66 healthy young participants who were scanned once each after administration of bromocriptine (a dopamine agonist with preferential affinity for D2 receptor), tolcapone (an inhibitor of catechol-O-methyltransferase), and placebo, to determine whether dopaminergic stimulation modulated effective functional connectivity between hierarchically organized frontal regions in the left hemisphere. We found that dopaminergic drugs modulated connections from the caudal middle frontal gyrus and the inferior frontal sulcus to both rostral and caudal frontal areas. In dorsal frontal regions, effectivity connectivity strength was increased, whereas in ventral frontal regions, effective connectivity strength was decreased. These findings suggest that connections within frontal cortex are differentially modulated by dopamine, which may bias the influence that frontal regions exert over each other.

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers.

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women's hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women's health.

The IMPACT Score: Does Sex Matter?

OBJECTIVE: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score is a quantitative risk index that predicts 1-year mortality risk, derived from United Network for Organ Sharing data in which women are underrepresented. The validity of the IMPACT score in 1-year mortality risk after OHT in women is unknown. The objective of this study was to assess differences in score performance by sex. We hypothesized that the IMPACT score is a poor predictor of 1-year mortality risk after orthotopic heart transplantation (OHT) in women. DESIGN: In this external validation study, demographic and clinical characteristics were compared by sex. The IMPACT score was calculated and regression models were constructed for the entire sample and stratified by sex. Model discrimination was assessed with the area under the receiver operating characteristic curve, and calibration was assessed graphically. PARTICIPANTS: Patients 18 years and older who were first-time single OHT recipients from the International Society for Heart and Lung Transplantation registry from 2009 to 2018. MEASUREMENTS AND MAIN RESULTS: For 1-year mortality, the area under the receiver operating characteristic curve (95% confidence interval) for the full sample was 0.59 (0.57-0.60): 0.58 (0.55-0.61) for women and 0.59 (0.58-0.61) for men. The 1-year mortality was 9.4% in the overall cohort, with no difference in mortality by sex (9.0% v 9.6% women v men, p = 0.22). CONCLUSIONS: The IMPACT score exhibited poor discrimination and calibration in the International Society for Heart and Lung Transplantation 2009-2019 cohort, overall and by sex. There was no difference in 1-year mortality between women and men.

Racial disparities in parturient urine drug screening at a Texas level IV maternal care center: a single-center retrospective study.

OBJECTIVE: We hypothesized that Black or African American (hereby referred to as Black) and Hispanic patients would have higher rates of urine drug screening (UDS) during pregnancy compared to White or Caucasian (herby referred to as White) patients at our hospital. METHODS: Patients who delivered at our hospital between 1 December 2020 and 31 May 2021 and between 1 December 2022 and 31 May 2023, and who were Black, Hispanic, or White were included in the final analysis. We performed separate bivariate analyses comparing White patients to either Black patients or Hispanic patients. We performed a multivariate logistic regression including variables of interest designed to predict risk factors for UDS during pregnancy. RESULTS: 457, 813, and 1252 patients identified as Black, Hispanic, and White, respectively. 187 (40.9%) Black patients had UDS during pregnancy compared to 265 (21.2%) White patients (P < 0.001). 258 (31.7%) Hispanic patients had UDS during pregnancy, which was also statistically different compared to White patients (P < 0.001). A multivariate logistic regression found that identification as Black was independently associated with UDS during pregnancy (adjusted odds ratio [aOR] 1.871; 95% CI 1.382, 2.534; P < 0.001); identification as Hispanic was not independently associated (aOR 1.177; 95% CI 0.900, 1.538; P = 0.234); and that patients who delivered after the COVID-19 pandemic were less likely to receive UDS (aOR 0.783; 95% CI 0.621, 0.987; P = 0.039). CONCLUSION: Identification as Black and delivery during the COVID-19 pandemic were independently associated with increased adjusted odds of UDS during pregnancy at our hospital. OBJECTIF: Nous avons émis l'hypothèse que le taux de dépistage toxicologique urinaire (DTU) pendant la grossesse serait plus élevé chez les patientes noires ou afro-américaines (ci-après désignées comme patientes noires) et les patientes hispaniques que chez les patientes blanches ou caucasiennes (ci-après désignées comme patientes blanches) dans notre hôpital. MéTHODES: Les patientes noires, hispaniques ou blanches qui ont accouché dans notre hôpital entre le 1 décembre 2020 et le 31 mai 2021 ou entre le 1 décembre 2022 et le 31 mai 2023 ont été incluses dans l'analyse finale. Nous avons réalisé des analyses bivariées distinctes comparant les patientes blanches aux patientes noires ou hispaniques. Nous avons utilisé la régression logistique multivariée avec des variables d'intérêt pour prédire les facteurs de risque du DTU pendant la grossesse. RéSULTATS: Nous avons répertorié 457, 813 et 1252 patientes noires, hispaniques et blanches, respectivement. Parmi elles, 187 patientes noires et 265 patientes blanches ont subi un DTU pendant la grossesse (40,9 % p r/à 21,2 %; P < 0,001). Quant aux patientes hispaniques, 258 ont subi un DTU pendant la grossesse, pour un taux de 31,7 %, ce qui illustre aussi une différence statistiquement significative par comparaison avec les patientes blanches (P < 0,001). Une analyse de régression logistique multivariée a révélé que l'identification comme patiente noire était associée de manière indépendante au DTU pendant la grossesse (rapport de cotes ajusté [RCa] : 1,871; IC à 95 % : 1,382-2,534; P < 0,001); que l'identification comme patiente hispanique n'était pas associée de manière indépendante au DTU (RCa : 1,177; IC à 95 % : 0,900-1,538; P = 0,234); et que les patientes qui ont accouché après la pandémie de COVID-19 étaient moins susceptibles de subir un DTU (RCa : 0,783; IC à 95 % : 0,621-0,987; P = 0,039). CONCLUSION: Dans notre hôpital, l'identification comme patiente noire et l'accouchement pendant la pandémie de COVID-19 ont été associés de manière indépendante à l'augmentation du risque ajusté de DTU pendant la grossesse.

Variability in Practice and Implementation of Oxygen Target Saturation Policies in United States' Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to describe target oxygen saturation (SpO2) ranges used for premature infants in United States' neonatal intensive care units (NICUs) and to describe if these target SpO2 ranges have changed in recent years. STUDY DESIGN: A 29-question survey focused on target SpO2 practices and policies was distributed via the NICU medical directors listservs for the American Academy of Pediatrics Section of Neonatal-Perinatal Medicine and Pediatrix Medical Group between August and October of 2021. Results were collected via Research Electronic Data Capture (REDCap). RESULTS: We received responses representing 170 unique, levels 2, 3, and 4 NICUs from 36 states. Most NICUs (130, 78%) have recently changed their SpO2 targets in response to target SpO2 clinical trials. Over time, the most commonly reported target SpO2 range has shifted from 88-92% to 90-95. Of NICUs that changed limits, the most common lower SpO2 limits increased from 88 to 90% and the upper SpO2 limits changed from 92 to 95%. The interquartile range for lower SpO2 limit shifted from 85-88% to 88-90% and the IQR for upper SpO2 limit decreased from 92-95 to 94-95%. Most NICUs had designated conditions that would allow for deviations from standard target SpO2 ranges. These most commonly include pulmonary hypertension (152, 95%), severe bronchopulmonary dysplasia (81, 51%), and retinopathy of prematurity (51, 32%). CONCLUSION: Oxygen saturation limits have changed over time with an overall increase in targeted SpO2. However, there remains considerable interunit variation in SpO2 policies. There is a need to achieve consensus to optimize clinical outcomes. KEY POINTS: · What are the SpO2 ranges in United States' NICUs?. · There is a shift in SpO2 ranges for preterm infants in NICUs across United States.. · Variability still persists in SpO2 ranges for preterm infants in United States' NICUs..

Modeling and characterization of gas coupled ultrasonic transducers at low pressures and temperatures and implications for sonic anemometry on Mars.

A sonic anemometer targeted at wind speed measurements on the surface of Mars is described. This environment requires transducer operation in 4-10 mbar CO2 at temperatures between 143 and 293 K (-130 °C and 20 °C, respectively). Over these ranges, transducer pressure and temperature sensitivity could be a source of measurement error. To investigate this, four candidate transducers were tested using transmission mode ultrasonic testing and impedance measurements: two narrowband piezoelectric transducers, a broadband capacitive transducer, and a micromachined capacitive ultrasound transducer. A system model was used for comparison and interpretation, and implications for a sonic anemometer were examined. Variation of transducer characteristics, including diffraction effects, across 2-10 mbar in CO2 and 190-293 K (-83 °C-20 °C) result in ±2.3% error in wind speed measurement and ±1.1% error in speed of sound measurement for the worst case but only ±0.14% error in wind and ±0.07% error in speed of sound for the best transducer operated off resonance. The acoustic conditions on Mars are similar to those in Earth's stratosphere at 30-42 km of altitude. Hence, testing was also conducted in dry air over the same range of pressures and temperatures with relevance to a secondary application of the instrument as a stratospheric anemometer for high altitude balloon missions on Earth.

Epstein-Barr Virus Genome Deletions in Epstein-Barr Virus-Positive T/NK Cell Lymphoproliferative Diseases.

The main target cells for Epstein-Barr virus (EBV) infection and persistence are B lymphocytes, although T and NK cells can also become infected. In this paper, we characterize the EBV present in 21 pediatric and adult patients who were treated in France for a range of diseases that involve infection of T or NK cells. Of these 21 cases, 5 pediatric patients (21%) and 11 adult patients (52%) were of Caucasian origin. In about 30% of the cases, some of the EBV genomes contain a large deletion. The deletions are different in every patient but tend to cluster near the BART region of the viral genome. Detailed investigation of a family in which several members have persistent T or NK cell infection by EBV indicates that the virus genome deletions arise or are selected independently in each individual patient. Genome sequence polymorphisms in the EBV in these T or NK cell diseases reflect the geographic origin of the patient and not a distinct type of EBV (the 21 cases studied included examples of both type 1 and type 2 EBV infection). Using virus produced from type 1 or type 2 EBV genomes cloned in bacterial artificial chromosome (BAC) vectors, we demonstrate infection of T cells in cord blood from healthy donors. Our results are consistent with transient infection of some T cells being part of normal asymptomatic infection by EBV in young children. IMPORTANCE EBV contributes to several types of human cancer. Some cancers and nonmalignant lymphoproliferative diseases involving T or NK cells contain EBV. These diseases are relatively frequent in Japan and China and have been shown sometimes to have deletions in the EBV genome in the disease cells. We identify further examples of deletions within the EBV genome associated with T or NK cell diseases, and we provide evidence that the virus genomes with these deletions are most likely selected in the individual cases, rather than being transmitted between people during infection. We demonstrate EBV infection of cord blood T cells by highly characterized, cloned EBV genomes and suggest that transient infection of T cells may be part of normal asymptomatic infection by EBV in young children.

Antiemetic Administration and Its Association with Race: A Retrospective Cohort Study.

BACKGROUND: Anesthesiologists' contribution to perioperative healthcare disparities remains unclear because patient and surgeon preferences can influence care choices. Postoperative nausea and vomiting is a patient- centered outcome measure and a main driver of unplanned admissions. Antiemetic administration is under the sole domain of anesthesiologists. In a U.S. sample, Medicaid insured versus commercially insured patients and those with lower versus higher median income had reduced antiemetic administration, but not all risk factors were controlled for. This study examined whether a patient's race is associated with perioperative antiemetic administration and hypothesized that Black versus White race is associated with reduced receipt of antiemetics. METHODS: An analysis was performed of 2004 to 2018 Multicenter Perioperative Outcomes Group data. The primary outcome of interest was administration of either ondansetron or dexamethasone; secondary outcomes were administration of each drug individually or both drugs together. The confounder-adjusted analysis included relevant patient demographics (Apfel postoperative nausea and vomiting risk factors: sex, smoking history, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use; as well as age) and included institutions as random effects. RESULTS: The Multicenter Perioperative Outcomes Group data contained 5.1 million anesthetic cases from 39 institutions located in the United States and The Netherlands. Multivariable regression demonstrates that Black patients were less likely to receive antiemetic administration with either ondansetron or dexamethasone than White patients (290,208 of 496,456 [58.5%] vs. 2.24 million of 3.49 million [64.1%]; adjusted odds ratio, 0.82; 95% CI, 0.81 to 0.82; P < 0.001). Black as compared to White patients were less likely to receive any dexamethasone (140,642 of 496,456 [28.3%] vs. 1.29 million of 3.49 million [37.0%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.78; P < 0.001), any ondansetron (262,086 of 496,456 [52.8%] vs. 1.96 million of 3.49 million [56.1%]; adjusted odds ratio, 0.84; 95% CI, 0.84 to 0.85; P < 0.001), and dexamethasone and ondansetron together (112,520 of 496,456 [22.7%] vs. 1.0 million of 3.49 million [28.9%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.79; P < 0.001). CONCLUSIONS: In a perioperative registry data set, Black versus White patient race was associated with less antiemetic administration, after controlling for all accepted postoperative nausea and vomiting risk factors.

Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation.

Characteristics of transformed and tumor cells include increased levels of protein synthesis and elevated expression of RNA polymerase (pol) III products, such as tRNAs and 5S rRNA. However, whether deregulated pol III transcription contributes to transformation has been unclear. Generating cell lines expressing an inducible pol III-specific transcription factor, Brf1, allowed us to raise tRNA and 5S rRNA levels specifically. Brf1 induction caused an increase in cell proliferation and oncogenic transformation, whereas depletion of Brf1 impeded transformation. Among the gene products induced by Brf1 is the tRNA(iMet) that initiates polypeptide synthesis. Overexpression of tRNA(iMet) is sufficient to stimulate cell proliferation and allow immortalized fibroblasts to form foci in culture and tumors in mice. The data indicate that elevated tRNA synthesis can promote cellular transformation.

Biofuel blending reduces particle emissions from aircraft engines at cruise conditions.

Aviation-related aerosol emissions contribute to the formation of contrail cirrus clouds that can alter upper tropospheric radiation and water budgets, and therefore climate. The magnitude of air-traffic-related aerosol-cloud interactions and the ways in which these interactions might change in the future remain uncertain. Modelling studies of the present and future effects of aviation on climate require detailed information about the number of aerosol particles emitted per kilogram of fuel burned and the microphysical properties of those aerosols that are relevant for cloud formation. However, previous observational data at cruise altitudes are sparse for engines burning conventional fuels, and no data have previously been reported for biofuel use in-flight. Here we report observations from research aircraft that sampled the exhaust of engines onboard a NASA DC-8 aircraft as they burned conventional Jet A fuel and a 50:50 (by volume) blend of Jet A fuel and a biofuel derived from Camelina oil. We show that, compared to using conventional fuels, biofuel blending reduces particle number and mass emissions immediately behind the aircraft by 50 to 70 per cent. Our observations quantify the impact of biofuel blending on aerosol emissions at cruise conditions and provide key microphysical parameters, which will be useful to assess the potential of biofuel use in aviation as a viable strategy to mitigate climate change.

Sex Differences in In-Hospital Mortality After Open Cardiac Valve Surgery.

BACKGROUND: Cardiac valvular disease affects millions of people worldwide and is a major cause of morbidity and mortality. Female patients have been shown to experience inferior clinical outcomes after nonvalvular cardiac surgery, but recent data are limited regarding open valve surgical cohorts. The primary objective of our study was to assess whether female sex is associated with increased in-hospital mortality after open cardiac valve operations. METHODS: Utilizing the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), we conducted a retrospective cohort study of patients who underwent open cardiac valve surgery from 2007 to 2018 in Washington, Maryland, Kentucky, and Florida; from 2007 to 2011 in California; and from 2007 to 2016 in New York. The primary objective of this study was to estimate the confounder-adjusted association between sex and in-hospital mortality (as recorded and coded by SID HCUP) after open cardiac valve surgery. We used multilevel multivariable models to account for potential confounders, including intrahospital practice patterns. RESULTS: A total of 272,954 patients (108,443 women; 39.73% of sample population with mean age of 67.6 ± 14.3 years) were included in our analysis. The overall mortality rates were 3.8% for male patients and 5.1% for female patients. The confounder-adjusted odds ratio (OR) for in-hospital mortality for female patients compared to male patients was 1.41 (95% confidence interval [CI], 1.35-1.47; P < .001). When stratifying by surgical type, female patients were also at increased odds of in-hospital mortality ( P < .001) in populations undergoing aortic valve replacement (adjusted OR [aOR], 1.38; 95% CI, 1.25-1.52); multiple valve surgery (aOR, 1.38; 95% CI, 1.22-1.57); mitral valve replacement (aOR, 1.22; 95% CI, 1.12 - 1.34); and valve surgery with coronary artery bypass grafting (aOR, 1.64; 95% CI, 1.54 - 1.74; all P < .001). Female patients did not have increased odds of in-hospital mortality in populations undergoing mitral valve repair (aOR, 1.26; 95% CI, 0.98 - 1.64; P = .075); aortic valve repair (aOR, 0.87; 95% CI, 0.67 - 1.14; P = .32); or any other single valve repair (aOR, 1.10; 95% CI, 0.82 - 1.46; P = .53). CONCLUSIONS: We found an association between female patients and increased confounder-adjusted odds of in-hospital mortality after open cardiac valve surgery. More research is needed to better understand and categorize these important outcome differences. Future research should include observational analysis containing granular and complete patient- and surgery-specific data.

Patient care in rapid-expansion intensive care units during the COVID-19 pandemic crisis.

BACKGROUND: The coronavirus-2019 (COVID-19) pandemic highlighted the unfortunate reality that many hospitals have insufficient intensive care unit (ICU) capacity to meet massive, unanticipated increases in demand. To drastically increase ICU capacity, NewYork-Presbyterian/Weill Cornell Medical Center modified its existing operating rooms and post-anaesthesia care units during the initial expansion phase to accommodate the surge of critically ill patients. METHODS: This retrospective chart review examined patient care in non-standard Expansion ICUs as compared to standard ICUs. We compared clinical data between the two settings to determine whether the expeditious development and deployment of critical care resources during an evolving medical crisis could provide appropriate care. RESULTS: Sixty-six patients were admitted to Expansion ICUs from March 1st to April 30th, 2020 and 343 were admitted to standard ICUs. Most patients were male (70%), White (30%), 45-64 years old (35%), non-smokers (73%), had hypertension (58%), and were hospitalized for a median of 40 days. For patients that died, there was no difference in treatment management, but the Expansion cohort had a higher median ICU length of stay (q = 0.037) and ventilatory length (q = 0.015). The cohorts had similar rates of discharge to home, but the Expansion ICU cohort had higher rates of discharge to a rehabilitation facility and overall lower mortality. CONCLUSIONS: We found no significantly worse outcomes for the Expansion ICU cohort compared to the standard ICU cohort at our institution during the COVID-19 pandemic, which demonstrates the feasibility of providing safe and effective care for patients in an Expansion ICU.

Non-White Race/Ethnicity and Female Sex Are Associated with Increased Allogeneic Red Blood Cell Transfusion in Cardiac Surgery Patients: 2007-2018.

OBJECTIVE: To evaluate racial and/or ethnic and sex disparities in allogeneic and autologous red blood cell (RBC) transfusions in cardiac surgery. DESIGN: A retrospective observational study. SETTING: 2007 to 2018 data from FL, MD, KY, WA, NY, and CA from the State Inpatient Databases (SID), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. PARTICIPANTS: A total of 710,296 inpatients who underwent elective or emergency coronary artery bypass grafting (CABG), cardiac valve surgery,or combination CABG and/or valve surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were cohorted by race and/or ethnicity and sex, as defined by SID-HCUP. Demographic characteristics and comorbidities were compared. Rates and risk-adjusted odds ratios (aOR) were calculated for allogeneic and autologous RBC transfusion (primary outcomes). Additional secondary analyses were conducted for in-hospital mortality, 30-day readmission, 90-day readmission, hospital length of stay, and total charges to examine the effect of RBC transfusion status. Effect modification between race and sex was assessed. When controlling for patient demographics, comorbidities, and hospital characteristics, non-White patients were more likely to receive an allogeneic RBC transfusion during cardiac surgery than White patients (Black: aOR 1.17, 99% CI 1.13-1.20, p < 0.001, Hispanic: aOR 1.22, 99% CI 1.19-1.22, p < 0.001). Women were more likely to receive allogeneic RBC than men (aOR 1.69, 99% CI 1.66-1.72, p < 0.001). In interaction models, non-White women had the highest odds of allogeneic blood transfusion as compared to White men (reference category; Black women: aOR 2.04, 99% CI 1.91-2.17, p < 0.001, Hispanic women: aOR 2.03, 99% CI 1.90-2.16, p < 0.001). CONCLUSION: These findings highlighted the differences in the rates of allogeneic RBC transfusion for non-White and female patients undergoing cardiac surgery, which is a well-established marker of poorer outcomes.

Medicare and Medicaid insurance status is associated with increased allogeneic red blood cell transfusion in cardiac surgery patients: 2007-2018.

BACKGROUND AND AIM: Allogeneic red blood cell (RBC) transfusion and health insurance status are independently associated with perioperative morbidity. The aim of this study was to evaluate the effect of insurance status on allogeneic and autologous transfusion risk in cardiac surgery patients. METHODS: We conducted a retrospective observational study of data spanning 2007-2018 from six states from the State Inpatient Databases. Patients were cohorted by medical insurance type. Rates and risk-adjusted odds ratios (aOR) were calculated for allogenic and autologous RBC transfusions. Interactions between insurance and race/ethnicity were assessed. RESULTS: A total of 710,296 cardiac surgery patients were included. Allogeneic infusions occurred in 34.7% of Medicare patients, 31.9% of Medicaid patients, 24.7% of privately insured patients, and 26.1% of uninsured patients. Autologous rates were 2.3%, 2.5%, 3.4%, and 2.6% for Medicare, Medicaid, privately insured, and uninsured patients, respectively. Medicare and Medicaid patients were more likely to receive allogeneic RBC than privately insured patients (Medicare: aOR: 1.42, 99% confidence interval [CI]: 1.40-1.44, p < .001, Medicaid: aOR: 1.18, 99% CI: 1.14-1.21, p < .001). Nonwhite Medicare patients showed higher odds of allogeneic transfusion compared with White patients with private insurance (Black Medicare: aOR 1.74, 99% CI: 1.65-1.83, p < .001, Hispanic Medicare: aOR 1.92, 99% CI: 1.84-2.00, p < .001). CONCLUSION: Cardiac surgery patients with Medicare and Medicaid insurance demonstrate increased risk of allogeneic RBC transfusion; nonwhite patient groups are particularly vulnerable. Further research is needed to understand the causes and implications of these disparities, and to help ensure equitable care across patient groups.

Enhanced Recovery after Surgery for Cesarean Delivery: A Quality Improvement Initiative.

OBJECTIVE: Enhanced recovery after surgery (ERAS) was developed as a way to standardize clinical care pathways and communication across multidisciplinary teams to improve patient recovery and reduce hospital length of stay (LOS). Our objective was to implement an ERAS protocol for cesarean delivery (ERAS-CD) and evaluate its efficacy in reducing LOS. STUDY DESIGN: An ERAS-CD program was implemented at our institution in October 2018. Patients undergoing scheduled and unscheduled CD were maintained on an ERAS pathway of care, which included preoperative hydration, standardized intraoperative protocols, and postoperative analgesic regimens as well as early feeding, urinary catheter removal, and ambulation. We compared LOS after delivery (calculated from time of delivery to discharge), readmission rates, health care disparities and postoperative opioid prescribing practices before (October 2017-September 2018) and after (November 2018-October 2019) ERAS implementation. We excluded any outliers, defined as a LOS >25 days. Continuous data are expressed as mean ± standard deviation. Student's t-test and Chi-square were used for statistical comparison with p <0.05 considered statistically significant. RESULTS: There were 1,729 patients who had a CD in the pre-ERAS group with a mean LOS after delivery of 3.32 ± 6.19 days. In the post-ERAS group, 1,753 women underwent CD with a mean LOS after delivery of 2.85 ± 5.79 days, a statistically significant difference from the pre-ERAS group (p <0.001). There was no difference in readmission rates between pre- and post-ERAS implementation groups (1.9 vs. 2.2%, p = 0.53). There was a reduction in health care disparities in postoperative LOS, when stratifying by race-ethnicity, and a reduction in opioid prescribing practices after the implementation of the program. CONCLUSION: With the implementation of an ERAS-CD program, we achieved a reduced LOS, without increasing readmission rates, and saw a reduction in health care disparities and opioid dispensing. A shorter LOS could offer an enhanced patient experience, as well as improved and equitable perioperative outcomes. KEY POINTS: · ERAS-CD is associated with a reduction in postoperative hospital length of stay.. · A reduction in health care disparities by race-ethnicity was observed with the implementation of ERAS-CD.. · A reduction in opioid dispensing was observed with the implementation of ERAS-CD..

Disparities in Obstetric Readmissions: A Multistate Analysis, 2007-2014.

OBJECTIVE: Hospital readmissions are generally higher among racial-ethnic minorities and patients of lower socioeconomic status. However, this has not been widely studied in obstetrics. The aim of the study is to determine 30-day postpartum readmission rates by patient-level social determinants of health: race ethnicity, primary insurance payer, and median income, independently and as effect modifiers. STUDY DESIGN: Using state inpatient databases from the health care cost and utilization project from 2007 to 2014, we queried all deliveries. To produce accurate estimates of the effects of parturients' social determinants of health on readmission odds while controlling for confounders, generalized linear mixed models (GLMMs) were used. Additional models were generated with interaction terms to highlight any associations and their effect on the outcome. Adjusted odds ratios (aOR) with 95% confidence intervals are reported. RESULTS: There were 5,129,867 deliveries with 79,260 (1.5%) 30-day readmissions. Of these, 947 (1.2%) were missing race ethnicity. Black and Hispanic patients were more likely to be readmitted within 30 days of delivery, as compared with White patients (p < 0.001 and p < 0.05, respectively). Patients with government insurance were more likely to be readmitted than those with private insurance (p < 0.001). Patients living in the second quartile of median income were also more likely to be readmitted than those living in other quartiles (p < 0.05). Using GLMMs, we observed that Black patients with Medicare were significantly more likely to get readmitted as compared with White patients with private insurance (aOR 2.78, 95% CI 2.50-3.09, p < 0.001). Similarly, Black patients living in the fourth (richest) quartile of median income were more likely to get readmitted, even when compared with White patients living in the first (poorest) quartile of median income (aOR 1.48, 95% CI 1.40-1.57, p < 0.001). CONCLUSION: Significant racial-ethnic disparities in obstetric readmissions were observed, particularly in Black patients with government insurance and even in Black patients living in the richest quartile of median income. KEY POINTS: · Using generalized linear mixed models, we observed significant interactions.. · Government-insured Black patients were 2.78X more likely to be readmitted.. · The wealthiest Black patients were still 1.48X more likely to be readmitted..