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Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

Objectives Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. Design/Setting/Participants/Interventions This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors’ center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. Measurements and Main Results The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. Conclusion Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

OBJECTIVES The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year. METHODS A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan–Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days. RESULTS A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P CONCLUSIONS A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.

BACKGROUND Surgical site infections (SSIs) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. METHODS This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin, or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30-day and 1-year postimplantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. RESULTS Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs. 12.8%, p = .290) and 1 year (16.9% vs. 25.6%, p = .435). Comparing narrow to broad prophylaxis, the risk of mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.15-1.35, logrank p = .14), and composite of mortality and infection was reduced (HR = 0.92, 95% CI = 0.45-1.88, logrank p = .83), but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p = 1.00) and mortality (p = .33) by device type. CONCLUSIONS The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected (Δ) albumin was −0.08 g/dL/day (95% CI −0.11 to −0.04; p70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems.

Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.

Background: Heart failure with preserved ejection fraction (HFpEF) patients often have other comorbidities, including obesity, dyslipidemia, hypertension, and diabetes, comprising the metabolic syndrome. The impacts of hemodynamic monitoring via CardioMEMS on these co-morbidities remain unknown. Methods: A retrospective analysis of 29 patients with HFpEF (EF 45% or greater) and CardioMEMS was performed at a single center. Weight, body mass index (BMI), systolic blood pressures (SBP), high-density lipoprotein (HDL), triglycerides (TGL), hemoglobin A1C (HbA1c), and pulmonary artery diastolic pressures (PADP) were assessed at baseline and six months post-implant. Paired t-tests and the Wilcoxon signed-rank test were used, as appropriate, to test differences between time points. Results: These patients were 69% female, with a mean age of 73 years, and 62% had non-ischaemic cardiomyopathies (NICM). At the time of CardioMEMS implantation, average PADP was 20.1 mmHg ± 5.7, weight was 102.6 kg ± 22.7, BMI was 38.0 kg/m2 ± 8.3, SBP was 135 mmHg ± 19, HDL was 42.4 mg/dL ± 11.3, and median TGL was 130 mg/dL (100, 180). At six months we witnessed a decrease by 20.9% in PADP to 15.9 mmHg ± 5.8, (p < 0.001). In addition, the following was noted: weight decreased by 2.5% to 100.0 kg ± 23.2, (p = 0.006), BMI reduced by 2.6% to 37.0 ± 8.2, (p = 0.002), SBP decreased by 6.7% to 126 mmHg ± 16 (p < 0.001), HDL increased by 10.8% to 47 mg/dL ± 11.9 (p < 0.001), and TGL decreased by 15.4% to 110 mg/dL (105, 135) (p = 0.001). 62% of patients were diabetic with no significant improvements in HbA1C values at the 6-month follow-up. Conclusion: The utilization of CardioMEMS to optimize PADP results in an improvement in the comorbidities associated with the metabolic syndrome. Further studies are warranted to validate these findings and delineate clinical significance.

ObjectivesAnimal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3–4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB).MethodsA series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen.ResultsUsing linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13–0.23) versus 0.15 (95% credible interval=0.08–0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13–0.18) versus 0.11 (95% credible interval=0.09–0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1–41.34) and 72.30% (95% credible interval=71.41–73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18–94.13) at 6 months for standard therapy.ConclusionsThe kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.

This article examines the effect of shared group membership on civilian attitudes regarding insurgent forces during an armed conflict. We rely on the original survey conducted in eight towns of Donetsk and Luhansk oblasts in May–June 2015. Based on the bivariate and multivariate analysis of the survey results, this article finds that a sense of shared identity with rebel forces at the start of the armed conflict in Donbas had a strong independent effect on civilian views of insurgents. Those respondents who identified themselves as residents of the region were more likely to attribute ideational motives to insurgents, report no knowledge of civilian victimization caused by rebel forces, and feel secure in their presence. By contrast, respondents identifying themselves as Ukrainian citizens were more likely to attribute material motives to insurgents, indicate their responsibility for attacks against civilians, and feel intimidated during direct encounters with rebels. These findings point to broader significance of identity cleavages in explaining the Donbas conflict.

Objective To determine whether the apparent excess incidence of pneumothorax and pneumomediastinum in patients with coronavirus disease 2019 (COVID-19) is explained adequately by iatrogenic causes vs reflecting sequelae of severe acute respiratory syndrome coronavirus 2 infection. Patients and Methods We retrospectively reviewed patients within our health care system from March 15, 2020, through May 31, 2020, who had a diagnosis of pneumothorax or pneumomediastinum during hospitalization for confirmed COVID-19 infection with attention to timing of pneumothorax and pneumomediastinum; presence, laterality, and placement, or attempts at central lines; and presence of mechanical ventilation before the event. Results We report clinical data and outcomes from 9 hospitalized patients with COVID-19 who developed pneumothorax and/or pneumomediastinum among more than 1200 hospitalized patients admitted within our hospital system early in the pandemic. Many events were inexplicable by iatrogenic needle injury, including 1 spontaneous case without central line access or mechanical ventilation. One occurred before central line placement, 2 in patients with only a peripherally inserted central line, and 1 contralateral to a classic central line. Three of these 9 patients died of complications of COVID-19 during their hospital stay. Conclusion With COVID-19 affecting the peripheral lung pneumocytes, patients are vulnerable to develop pneumothorax or pneumomediastinum irrespective of their central line access site. We hypothesize that COVID-19 hyperinflammation, coupled with the viral tropism that includes avid involvement of peripheral lung pneumocytes, induces a predisposition to peripheral bronchoalveolar communication and consequent viral hyperinflammatory-triggered pneumothorax and pneumomediastinum.

Background In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. Methods In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. Results The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 - 63.4] vs 13.8 [9.5 - 40.3] kPa, p = 0.049). Moreover, the risk of composite outcome was highest in the 3rd tertile (>39.8 kPa compared to 1st and 2nd combined, HR 2.83, 95% CI 1.20- 6.67, p = 0.02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = 0.01). Conclusions LSM may serve as a novel noninvasive tool to determine LVAD, HT or death in patients with ADHF. This article is protected by copyright. All rights reserved.

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid, is a highly effective immunosuppressive agent in heart transplant therapy. While the FDA approved dose is 1500 mg twice daily, dosing is often reduced due to dose-dependent adverse effects. However, empiric MMF dose reductions may lead to sub-therapeutic dosing and impair clinical outcomes. Our single center protocolized a risk-stratified approach based on age and weight to dose 500 mg twice daily or 1000 mg twice daily to patients after heart transplantation. This retrospective single-center study analyzed 140 consecutive heart transplant patients who were initiated on our risk-stratified MMF protocol post-transplant. The analysis revealed that the composite rate of biopsy-proven rejection, graft loss, or mortality at 1-year post-transplantation was similar between the two groups. Incidence of neutropenia, thrombocytopenia, infection, cardiac allograft vasculopathy, or acute kidney injury by 1-year also showed similar results between the two groups. Risk-stratification of MMF dosing appears to be a safe and effective strategy after heart transplantation.

Surgical site infections (SSI) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30 days and 1 year post-implantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs 12.8%, p = 0.290) and 1 year (16.9% vs 25.6%, p = 0.435). Comparing narrow to broad prophylaxis, the risk of mortality [HR (95% CI): 0.44 (0.15. 1.35), logrank P = 0.14], and composite of mortality and infection was reduced [HR (95% CI): 0.92 (0.45, 1.88), logrank P = 0.83], but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p=1.00) and mortality (p=0.33) by device type. The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.

Background Radial artery (RA) catheterization is the access of choice over femoral artery access for most interventional vascular procedures given its safety and faster patient recovery. There has been growing interest in distal radial artery (dRA) access as an alternative to the conventional proximal radial artery (pRA) access. Preserving the RA is important which serves as a potential conduit for future coronary artery bypass surgery, dialysis conduit or preserve the artery for future cardiovascular procedures . The dRA runs in close proximity to the radial nerve , which raises the concern of potential detrimental effects on hand function. Study design The Distal versus Proximal Radial Artery Access for cardiac catheterization and intervention (DIPRA) trial is a prospective, randomized, parallel-controlled, open-label, single center study evaluating the outcomes of hand function and effectiveness of dRA compared to pRA access in patients undergoing cardiac catheterization. The eligible subjects will be randomized to dRA and pRA access in a (1:1) fashion. The primary end point is an evaluation of hand function at one and twelve months follow-up. Secondary end points include rates of access site hematoma, access site bleeding, other vascular access complications, arterial access success rate, and RA occlusion at one and twelve months follow up. Conclusion Effects of dRA on hand function remains unknown and it's use questionable in the presence of a widely accepted pRA. DIPRA trial is designed to determine the safety and effectiveness of dRA for diagnostic and interventional cardiovascular procedures compared to the standard of care pRA.

Background: Ceftazidime-avibactam is an effective agent for the treatment of tuberculosis (TB) but requires frequent administration because of a short half-life. Due to a longer half-life, ceftriaxone could allow intermittent dosing. Methods: First, we identified the MIC of ceftriaxone with 15 mg/L avibactam in 30 clinical Mycobacterium tuberculosis isolates. Next, 2 ceftriaxone exposure-effect studies in the intracellular hollow fiber model of TB (HFS-TB) that mimics disseminated disease in young children, were performed. Ceftriaxone was administered once or twice daily for 28 days to explore percentage of time that the concentration persisted above MIC (%TMIC) ranging from 0 to 100%. In a third HFS-TB experiment, the “double cephalosporin” regimen of ceftazidime-ceftriaxone-avibactam was examined and analyzed using Bliss Independence. Conclusion: The MIC99 of the clinical strains was 32 mg/L, in the presence of 15 mg/L avibactam. Ceftriaxone %TMIC 54% demonstrated a 4.1 log10 colony-forming units per milliliter M. tuberculosis kill, while %TMIC mediating Emax was 68%. The “double cephalosporin” combination was highly synergistic. Monte Carlo experiments of 10,000 subjects identified the optimal ceftriaxone dose as 100 mg/kg twice a day. Conclusion: The combination of ceftriaxone-avibactam at 100 mg/kg could achieve Emax in >90% of children. The ceftriaxone potent activity M. tuberculosis could potentially shorten therapy in children with disseminated TB.

In patients who underwent transcatheter aortic valve implantation (TAVI), vascular disease is associated with increased risk of mortality. Thoracic aortic calcification (TAC), an objective surrogate of vascular disease, could be a predictor of mortality after TAVI. We aimed to analyze the association between TAC burden and 1-year all-cause mortality in patients who underwent TAVI in a US population. From July 2015 through July 2017, a retrospective review of TAVI procedures was performed at Baylor Scott & White-The Heart Hospital, Plano, Texas. Patients were analyzed for comorbidities, cardiac risk factors, and 30-day and 1-year all-cause mortality. Restricted cubic splines analysis was used to define low, moderate, and high TAC categories. The association between TAC and survival was evaluated using unadjusted and adjusted Cox models. A total of 431 TAVI procedures were performed, of which TAC was measured in 374 (81%) patients. Median (interquartile range) age was 82 (77, 87) years, and 51% were male. Median (interquartile range) STS PROM was 5.6 (4.1, 8.2) %. Overall 30-day and 1-year all-cause mortality was 1% and 10%, respectively. TAC was categorized as low ( 2.9 cm3). At 1 year, all-cause mortality was 16% in patients with high TAC compared with 6% in the low and moderate TAC categories (p = 0.008). Unadjusted and adjusted Cox regression analysis showed a significant increase in mortality for patients with high TAC compared with low TAC (hazard ratio 2.98, 95% confidence interval [1.34-6.63]), but not significant compared with moderate TAC group. TAC is a predictor of late mortality after TAVI. In conclusion, adding TAC to preoperative evaluation may provide an objective, reproducible, and potentially widely available tool that can help in shared decision-making.

Drug-resistant tuberculosis represents a global emergency, requiring new drugs. We found that minocycline was highly potent in laboratory strains of Mycobacterium tuberculosis and that 30 drug-susceptible and multidrug/extensively drug-resistant clinical strains were susceptible to clinically achievable concentrations. In the hollow fiber system model, lung concentration-time profiles of 7 mg/kg/day human-equivalent minocycline dose achieved bacterial kill rates equivalent to those of first-line antituberculosis agents. Minocycline killed extracellular bacilli directly. Minocycline also killed intracellular bacilli indirectly, via concentration-dependent granzyme A-driven apoptosis. Moreover, minocycline demonstrated dose-dependent antiinflammatory activity and downregulation of extracellular matrix-based remodeling pathways and, thus, could protect patients from tuberculosis immunopathology. In RNA sequencing of repetitive samples from the hollow fiber system and in independent protein abundance experiments, minocycline demonstrated dose-dependent inhibition of sonic hedgehog-patched-gli signaling. These findings have implications for improved lung remodeling and for dual immunomodulation and direct microbial kill-based treatment shortening regimens for drug-susceptible and drug-resistant latent and active M. tuberculosis infection.

A problem that often arises from dose-control studies is that of determining differences in the K > 2 treatment arms (increasing dose amounts) when adjusting for covariate effects. Recent results for a covariate adjusted Jonckhere Trend Test (JT) provides a useful means for modeling this problem. In this article, we present a multiple comparison for the K treatment arms that controls the family-wise error rate. The new method is compared with two existing rank-based nonparametric multiple comparison procedures using simulated data, an example from one of the existing methods, and several examples as motivated by problems found in clinical settings.

A semiparametric regression model for the area under the ROC curve (AUC) is adapted to test of hypotheses for which the Jonckheere trend test (JTS) is appropriate. Since a nonparametric estimate of the AUC and the JTS depend upon the Mann-Whitney statistic, one can exploit this fact to develop a JTS that accounts for discrete covariates. The new method is illustrated with a simulation study and using real and simulated data motivated by three clinical studies.

We are delighted to see a letter to the editor1 essentially agreeing with the message conveyed through our retrospective observation: that a dynamic, accelerated fall of albumin levels in patients admitted with severe COVID-19 predicts progression to critical COVID-19.2 Our express intent was to spur further clinical investigation. Our conclusion remains unchanged after accounting for pre-existing liver disease. COVID-19 frequently causes a self-limited transaminitis in patients without liver disease. Liver function measured at hospital admission using alanine aminotransferase and aspartate aminotransferase for the patients in our study who progressed to critical disease, compared with those who did not progress, was similar (table …

Background Surgical site infections (SSI) for implantation of left ventricular assist devices (LVADs) are associated with high mortality. Updated guidance from the International Society for Heart and Lung Transplant recommends that SSI prophylaxis regimens target Staphylococcus spp and recommend against broad regimens targeting gram-negatives and fungi. The purpose of this study was to compare outcomes between patients that received broad or narrow antimicrobial prophylaxis regimens after a change in institutional protocol. Methods This single center retrospective study included adult patients who underwent LVAD implantation between January 2015 and September 2019. Patients were excluded if post-surgical care was managed at an outside facility, were treated for an active infection at the time of implantation, or underwent re-implantation within 90 days. The narrow spectrum group consisted of patients that received cefazolin, vancomycin or both, while the broad spectrum group consisted of patients that received an anti-pseudomonal beta-lactam plus vancomycin ± other antibiotics. Data was compared using t-test or Wilcoxon rank sum test, Chi-Square test, or Fisher’s Exact. Cox-proportional hazards models and log-rank tests were used for survival analysis. Results A total of 104 patients were included, with 39 and 65 patients receiving narrow and broad spectrum prophylaxis, respectively. There was no difference in the primary outcome of SSI rate between the narrow and broad antimicrobial prophylaxis groups at 30 days (7.7% vs 7.7%, p=1.00) and 1 year (18.0% vs 18.5%, p=1.00) respectively. Secondary outcomes of time to mortality (HR 0.45, 95% CI 0.15-1.36, logrank P=0.15), time to first infection (HR 0.68, 95% CI 0.26-1.8, logrank P=0.44), or the composite outcome of mortality or infection (HR 0.55, 95% CI 0.24-1.23, logrank P=0.14) were not different between the groups. The majority of infections were due to gram-positive bacteria (73%), most commonly methicillin susceptible S. aureus (36%). Time to Mortality Time to First Infection Composite Outcome (Time to First Infection or Death) Conclusion This study supports the use of narrow spectrum antimicrobial prophylaxis in LVAD implantation. These results highlight an opportunity to improve antibiotic use in LVAD implantation. Disclosures All Authors: No reported disclosures

For the case where all multivariate normal parameters are known, we derive a new linear dimension reduction (LDR) method to determine a low-dimensional subspace that preserves or nearly preserves the original feature-space separation of the individual populations and the Bayes probability of misclassification. We also give necessary and sufficient conditions which provide the smallest reduced dimension that essentially retains the Bayes probability of misclassification from the original full-dimensional space in the reduced space. Moreover, our new LDR procedure requires no computationally expensive optimization procedure. Finally, for the case where parameters are unknown, we devise a LDR method based on our new theorem and compare our LDR method with three competing LDR methods using Monte Carlo simulations and a parametric bootstrap based on real data.