Pancreatic cancer (PC) is a highly lethal malignancy and lacks effective treatments. Current chemotherapies, including gemcitabine (Gem) in combination treatment regimens, produce dose-limiting toxicity, drug resistance, and ultimately limited improvement in the overall survival of PC patients. Niclosamide (Nic), a clinically safe FDA-approved anthelmintic drug has been shown to have anti-cancer properties; however, its limited bioavailability makes Nic largely ineffective as a therapeutic agent. To address this challenge, we have developed a novel combination therapy of Gem with the repurposed drug, Nic, loaded in biodegradable polyanhydride nanoparticles (NicNp), as an effective treatment option for PC. We synthesized and characterized NicNp in vitro and evaluated their biodistribution and efficacy in xenograft and syngeneic pancreatic tumor models in mice. The biodistribution study indicated that NicNp accumulated in high concentrations in the pancreatic tumors of the mice with Cmax of 138 ± 74.1 µg Nic/g tissue. NicNp treatment, in combination with Gem, worked synergistically to reduce the dose of gemcitabine required to kill pancreatic cancer cells in vitro, two-fold. Additionally, the pancreatic tumor burden in the mouse models was significantly reduced, while survival was significantly increased when mice bearing pancreatic tumors were treated with the combination of NicNp and Gem. This study demonstrates the potential for effective repurposing Nic via nanoformulations in combination with Gem to improve PC treatment efficacy. Pancreatic cancer (PC) ranks among the most lethal types of cancer, with largely ineffective current treatments and toxic side effects in patients. Niclosamide is an FDA-approved anti-parasitic drug with minimal side effects, that has shown some anti-cancer properties. However, it is not effectively absorbed in the body. We produced polymer nanoparticles to deliver niclosamide effectively to treat pancreatic tumors in mice in combination with the chemotherapeutic gemcitabine. This combination treatment led to PC tumor reduction and increased the survival, demonstrating that niclosamide encapsulated in nanoparticles in combination with gemcitabine has the potential to be a more effective treatment for PC.

Introduction:Urinary tract infections (UTIs) are commonly diagnosed in the emergency department (ED). However, an accurate diagnosis requires an appropriate clinical presentation. The objective of this retrospective review of patients admitted to the hospital via the ED was to determine the extent of urinary testing for infection despite no appropriate medical criteria and the associated economic costs. Methods:Adult patients admitted to an academic medical center via the ED in two 1-week periods were reviewed. The medical records were manually reviewed to determine whether the urine was tested for infection and whether this was medically necessary based on generally accepted clinical criteria. The economic cost of the unnecessary testing was determined based on direct laboratory processing costs, staffing costs associated with sample acquisition and processing, and antimicrobials prescribed. Results:There were 401 admissions to the hospital via the ED in the two 1-week timeframes, and 212 (52.87%) had urinalyses on admission. Among them, 133 (62.74%) had no medical necessity for the testing. The total annual cost was extrapolated to a direct cost of $8,490.68 and a total cost of $49,701.01. Conclusions:These results demonstrate the projected annual cost of inappropriate urine testing in patients admitted through the ED. Data such as these may be of value to hospital systems in the design or creation of order sets to focus on appropriate testing. These data would also be helpful for diagnostic stewardship programs to help rein in the ever-increasing cost of healthcare.

ECMO is becoming widely used as a life-saving measure for critically ill patients. However, there is limited data on pharmacokinetics and the dosing of beta-lactam antibiotics in ECMO. In this study, we evaluated the serum concentrations of cefepime in patients on ECMO to determine the impact of ECMO circuitry and to guide therapeutic dosing. Methods: Patients 19 years or older admitted to the ICU, treated with ECMO and beta-lactam antibiotics for presumed or documented infection, were enrolled. Three blood samples (peak, midpoint, trough) were obtained before ECMO (pre-ECMO) and during ECMO (intra-ECMO) at a steady state. Results: Eight patients met inclusion criteria; six received cefepime. All patients were male. Average ± SD age was 45.8 ± 14.7. Four patients received ECMO for severe SARS-CoV-2 infection, and one each for Pneumocystis pneumonia and influenza A infection. Mean ± SD APACHE II and SOFA scores prior to ECMO were 24.6 ± 7.1 and 11.0 ± 3.9, respectively. All but one of the patients received venovenous (VV) ECMO. Cefepime 1 g every 6 h intravenously over 2 min was administered to all patients before and during ECMO. Cefepime concentrations were fit to non-compartment analysis (NCA) and area under the serum concentration–time curve averaged ± SE 211.9 ± 29.6 pre-ECMO and 329.6 ± 32.3 mg*h/L intra-ECMO, p = 0.023. No patients displayed signs of cefepime neurotoxicity. Patients received ECMO for 43.1± 30 days. All patients expired. Cefepime dosed at 1 g every 6 h intravenously appears to achieve therapeutic levels for critically ill patients on ECMO.

Background. Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around eight hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites lead to consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. PubMed, Scopus, Science Direct, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials to systematically identify all relevant studies published up to June 16, 2023. Results. The final analysis included two published retrospective cohort studies; a single site (n = 200) and a multisite study (n = 85) of ‘good’ quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Meta-analysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% CI: 47.6% lower to 6.4 times higher risk, p = 0.342) and inverse-variance method (RR: 1.87, 95% CI: 0.52-6.65, p = 0.336). Conclusions. Dosing metronidazole every 12 hours is as effective as every 8-hour dosing for anaerobic infections. Healthcare systems may consider the adoption of every 12-hour metronidazole dosing with continued evaluation of patient outcomes.

The SARS-CoV-2 pandemic has resulted in a public health emergency with unique complications such as the development of fungal co-infections. The diagnosis of fungal infections can be challenging due to confounding imaging studies and difficulty obtaining histopathology. In this retrospective study, 173 patients with COVID-19 receiving antifungal therapy due to concern for fungal co-infection were evaluated. Patient characteristics, clinical outcomes, and the utility of fungal biomarkers were then evaluated for continuation of antifungal therapy. Data were collected from the electronic health record (EPIC) and analyzed using SPSS (version. 28, IBM, Inc., Armonk, NY, USA) Data are presented as mean ± SD or percentages. A total of 56 COVID-19 patients were diagnosed with fungal co-infection and 117 COVID-19 + patients had no fungal infection. Significantly fewer female patients were in the fungal+ group compared to COVID-19 control patients (29% in fungal+ compared to 51% in controls p = 0.005). Fungal diagnostics were all significantly higher in fungal+ patients. These include 1,4-beta-D-glucan (BDG), fungal culture, and bronchoalveolar lavage galactomannan (BAL GM). Intensive care unit hospitalization, mechanical ventilation, and mortality in fungal+ patients with COVID-19 were significantly higher than in control patients. Finally, significantly more fungal+ patients received voriconazole, isavuconazonium, or amphotericin B therapies, whereas control patients received significantly more short-course fluconazole. COVID-19+ patients with fungal co-infection were significantly more likely to be in the ICU and mechanically ventilated, and they result in higher mortality compared to control COVID-19 patients. The use of fungal diagnostics markers were helpful for diagnosis.

INTRODUCTION: Fungal co-infection in ICU patients hospitalized with COVID-19 pneumonia has been described. Biomarkers such as galactomannan (GM) from serum and bronchoalveolar lavage have low sensitivity. 1,3 Beta-d-glucan (BdG) may have higher sensitivity, but it lacks specificity. In this study, we examined the clinical outcome and utility of fungal biomarkers in the diagnosis of fungal co-infections in ICU COVID-19 patients. METHOD(S): Intensive care Unit (ICU) COVID-19 patients treated for fungal co-infections (COVID+ Fungal co-infection) were compared to ICU COVID-19 patients without fungal co-infections as controls. The primary outcome of this study were to determine the utility of fungal biomarkers in COVID+ Fungal-co-infected patients compared to similar patients without fungal infection (control group). Patients were entered into a spreadsheet and then analyzed using SPSS (ver. 27, IBM, Inc.). Mean (+/- SD) and percentages were reported. RESULT(S): A total of 76 ICU COVID-19+ patients were identified. 54 were COVID+ fungal co-infected, 22 were COVID+ control patients. 53 (69.7%) were male. Most patients were Caucasian (76%), with 7.9% Hispanic and 6% African American. Mean (+/- SD) age was 59.6 +/- 12.0. Eightysix percent of patients received mechanical ventilation, 59% underwent bronchoscopy and expired during hospitalization, respectively. COVID associated pulmonary aspergillosis (CAPA) was diagnosed in 21% of COVID+ Fungal coinfected group. BdG was obtained in 17 (31.5%) COVID+ Fungal+ compared to 4.5% in control patients (p=0.012). Fungal culture was obtained in 40 (74%) COVID+ Fungal+ group compared to 5.4% in control group (p< 0.001). Aspergillus antigen in BAL in 52% COVID+ Fungal+ patients compared to 5.4% in controls (p< 0.001). Similarly, 54 (71%) patients received antifungal therapy (97% with positive fungal culture was treated compared to 41% with negative culture, p< 0.001). Most patients (84%) with positive fungal culture were treated with voriconazole. CONCLUSION(S): Fungal biomarkers including BdG and GM were more likely to be positive in COVID-19+ Fungal-coinfection. Use of the fungal biomarkers (BdG, GM) were used in a minority COVID+ patients for diagnosis. Fungal culture did prompt anti-fungal therapy, mainly voriconazole treatment.

SESSION TITLE: Critical Care Posters 18 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm PURPOSE: Dexmedetomidine (DEX) is a central acting alpha2-adrenergic agonist indicated for the sedation of mechanically ventilated patients. DEX has analgesic, anxiolytic, and sedative properties. Since the mechanism of action is in the locus coeruleus, not the cerebral cortex, there is less risk for over-sedation and respiratory depression. DEX is associated with less delirium than benzodiazepines in clinical trials and has efficacy as an adjunct treatment for severe alcohol withdrawal and in agitated toxicology patients. Although off-label DEX use in non-intubated patients is widespread, there is a paucity of data regarding safety of DEX in these patients. Accordingly, the goal of this study was to evaluate the safety profile of DEX in non-intubated patients admitted to the ICU. Our secondary goal was to generally describe DEX usage (dosage, duration, indication) in the non-intubated ICU patient. METHODS: A multicenter retrospective chart review was conducted on patients who received DEX while hospitalized at five Omaha (Nebraska) metropolitan CHI Health hospital between 1/1/17 and 9/1/20. The study was approved by the Institutional Review Board. Inclusion criteria included age ≥19 years, use of DEX in an ICU for ≥24 hours, and no intubation at the time of DEX initiation. Exclusion criteria included age <19 years, use of DEX for <24 hours, or intubation at the time of DEX initiation. Our primary outcome was any documented adverse effects (AE) associated with DEX infusion. Data were analyzed using SPSS ver 28 (IBM, Inc). Mean ± SD or percentages were reported. RESULTS: Of 1,186 patients receiving DEX, 85 patients met inclusion and exclusion criteria. The cohort was 62.4% male with a mean age of 61.9 years and an average BMI of 27.9. Indications for DEX included respiratory failure (n=44), alcohol abuse (n=25), and agitation/delirium (n=16). Mean duration of DEX use was 60.8±44.3 hours (range 24-217). The DEX infusion dosage range was 0.1-1.5 mcg/kg/hr, with a mean minimal dosage of 0.21±0.06 and maximal dosage of 1.14±0.41. In the cohort, 41 of the patients (48.2%) required non-invasive ventilatory (NIV) support. There were 5 patients (5.9%) requiring intubation after being on DEX for >24 hours: 3 progressive respiratory failure, 1 alcohol withdrawal, and 1 multisystem organ failure due to alcoholic hepatitis. Non-respiratory AEs included bradycardia (n=8, 9.4%) and mild/transient hypotension (n=7, 8.2%). CONCLUSIONS: DEX was safe and effective when used in non-intubated ICU patients. The AE rate in this cohort was comparable to what is described with DEX among intubated patients. The need for intubation was low at ~5% and was attributable to the underlying disease process. CLINICAL IMPLICATIONS: This retrospective descriptive study suggests that DEX can safely be used for prolonged periods (> 24 hours) in non-intubated patients when properly monitored in an ICU. DISCLOSURES: No relevant relationships by Ara Choi No relevant relationships by Jacqueline Chung No relevant relationships by Chris Destache No relevant relationships by Megan Dethlefsen No relevant relationships by Adam Highley No relevant relationships by Erin Kajihiro No relevant relationships by Mark Malesker No relevant relationships by Lee Morrow No relevant relationships by Stephen Toth No relevant relationships by Zachariah Wittenberg

Strongyloidiasis is a helminth infection affecting 613.9 million people annually, mainly in the tropics and subtropics. The reported seroprevalence in the United States is 4% with most of the cases reported in immigrants. Human T-lympho-tropic virus 1 (HTLV-1) infections, hypogammaglobulinemia, immunosuppressant use -particularly steroid use, alcoholism, and malnutrition have been associated with an increased risk of strongyloidiasis. Recently, cases of strongyloidiasis hyperinfection syndrome have been described in coronavirus disease 2019 (COVID-19) patients treated with steroids as well.This brief review discusses the epidemiology, clinical features, management, and prevention of strongyloidiasis including some facts about the infection in pregnancy, transplant recipients, and COVID-19 patients. We conducted an online search using the PubMed, Scopus, and Google Scholar databases. Strongyloidiasis can be asymptomatic or present with mild symptoms.Strongyloides stercoralis is known to cause autoinfection. In immunocompromised individuals, it can present with severe symptoms, hyperinfection, or disseminated disease. Reported mortality in cases of disseminated Strongyloidiasis is 87.1%. Serology and detection of larvae in stool by direct microscopy are the most commonly used methods to diagnose strongyloidiasis. The drug of choice for the treatment is ivermectin. However, the use of ivermectin in human pregnancy is not well studied, and its teratogenic risks are unknown. Proactive screening of strongyloidiasis is necessary in immunocompromised individuals to prevent severe disease.

INTRODUCTION:Coronavirus disease 2019 (COVID-19) can cause multisystem complications, with pulmonary involvement associated with the highest mortality. Pneumothorax (PT) and pneumomediastinum (PM) are uncommon complications of COVID-19 that have been reported to occur in the absence of trauma or mechanical ventilation. This study seeks to determine the incidence of these complications in patients with COVID-19 and evaluate clinical characteristics and outcomes.METHODS:We identified 3375 patients admitted to our health system during March 2020 through November 2020 who tested positive for SARS-CoV-2 with a polymerase chain reaction test. Patients were screened for PT or PM and were matched to COVID-19-positive patients without PT and/or PM. Data compared demographics, clinical characteristics, and laboratory values.RESULTS:Out of a total of 3375 COVID-19 admissions, 33 patients with PT/PM (1%) were compared to 32 matched controls without PT and/or PM. The patients with PT and/or PM demonstrated a significantly higher incidence of concomitant cancer diagnosis than those without PT and/or PM (18% vs 3%, respectively; P = 0.05). Those with PT and/or PM required significantly more invasive mechanical ventilation than those without PT and/or PM (79% vs 47%; P < 0.01). Mortality was significantly higher among those patients with PT and/or PM than those without PT/PM (55% vs 25%; P < 0.05).DISCUSSION:A significant number of COVID-19 patients with PT and/or PM had a concomitant cancer diagnosis, required supplemental oxygen on admission, and invasive mechanical ventilation during hospitalization. Additionally, the COVID patients with PT and/or PM had significantly higher mortality compared to those without PT and/or PM. However, with all retrospective studies, there are limitations.

Background: We evaluated pre-and postimplementation of Virtuo on outcome in patients with gram-negative bacteremia using a quasiexperimental time-in-motion design. Methods: Becton Dickinson BACTECTM 9000 series (Bactec) (2018) and Virtuo system (2020) were utilized in a decentralized and centralized process, respectively. Data collected in August-December in 2018 and 2020 were analyzed with SPSS (ver 28). Results: For 185 patients in each time period, patient age, gender, length of hospitalization were not different. However, blood culture (BC) volume was significantly lower in 2020 (7.1 +/- 2.6 mL) compared to 2018 (8.9 +/- 1.9 mL). Time from BC draw and time from pathogen identification (ID) to treatment change were both significantly faster in 2020 (52.9 +/- 38.3 hours; 15.1 +/- 27.4 hours), compared to 2018 (65.0 +/- 46.3 hours; 23.8 +/- 33.8), respectively. Conclusions: Replacement of decentralized Bactec with centralized Virtuo, resulted in significant improvement in management of patients gram-negative bacteremia. (c) 2023 Elsevier Inc. All rights reserved.

Abstract Background Pseudomonas aeruginosa (PA) bloodstream infection is associated with poor clinical outcomes. The purpose of this study was to evaluate treatment efficacy and patient outcomes from different antimicrobials used for treating PA bacteremia during 2020-2022. Methods This was a retrospective review of 2020-2022 hospitalized patients with PA bacteremias at our health system. Hospitalized patients from January 2020 - July 2022 with culture-positive PA were identified. Data collected included demographics, hospitalization and drug treatment length, SARS-CoV-2 infection, and need for vasopressors. Antibiotics used to treat PA, including dose, interval, and MIC data were evaluated. Finally, admission APACHE II score and hospital mortality were collected. Data were analyzed by SPSS. Data are presented as mean ± SD or percentage. Apriori significance was p ≤ 0.05. Results A total of 111 PA bacteremias occurred in 2020-2022, 65% of patients were male. Mean (± SD) age was 68 ± 13 years and weight were 88.2 ± 25 kg. Hospitalization length and duration of antibiotic therapy averaged 12 ± 13 days and 7.1 ± 5.9 days, respectively. Majority were treated with piperacillin-tazobactam (45%) or cefepime (44%). Median cefepime MIC was 2.0 (range 0.5-8). Thirty-seven (33%) PA-infected patients expired. Significantly more 7 of 17 (41%) cefepime patients died receiving 4G/d (1Gq6h) compared to 1 (9%) of 11 receiving 6G/d (2Gq8h), p< 0.001. Significant correlation between mortality and ICU status or mechanical ventilation (p< 0.001), respectively. No correlation between mortality and renal failure, SARS-CoV-2 co-infection, or vasopressor use. APACHE II score was significantly higher for expired patients (survived 13.9 ± 5.7 compared to 22 ± 8.3 in expired group, p< 0.001). Conclusion ICU status and mechanical ventilation significant reduced survival. Cefepime 4G/d resulted in significantly higher mortality. Disclosures Christopher J. Destache, Pharm. D., BioMerieux, Inc: Advisor/Consultant

SESSION TITLE: Critical Care Posters 16 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm PURPOSE: Quetiapine (Seroquel) is FDA approved for the treatment of bipolar disorder, major depressive disorder, and schizophrenia. A common off label use is treatment of intensive care unit (ICU) delirium or agitation. Pilot data from our institution demonstrated quetiapine is not consistently discontinued once delirium has been resolved or upon transfer from the ICU. The goal of this study was to retrospectively evaluate the discontinuation rate of quetiapine in patients requiring ICU care and to delineate factors correlated with inappropriate continuation of quetiapine. METHODS: This study was approved by the Institutional Review Board. A retrospective chart review was conducted of patients receiving quetiapine for more than 24 hours while requiring ICU care between 6/1/2017 to 12/31/2021. Patients less than 19 years, taking quetiapine prior to admission, undergoing active alcohol withdrawal, having history of neurocognitive disorder, and receiving a continuous paralytic agent were excluded. The primary outcome was to evaluate the discontinuation of quetiapine at ICU and hospital discharge. Secondary outcomes included quetiapine administration (dosage, length of use, safety), variables that predict inappropriate continuation of therapy (ordering service, dose used), and discharge disposition. Statistical analysis was performed with SPSS. Mean (± SD) or percentages are reported. RESULTS: 216 patients met inclusion criteria (131 (61%) males and 85 (39%) females). Mean (± SD) age and weight were 62.5 ± 18.3 years and 88.2 ± 29.4 kg. Majority of quetiapine patients were white (87%) with 9% African American and 3% Hispanic. The frequency of quetiapine discontinuation was higher among patients being discharged from hospital compared to ICU downgrade (53.5% vs 19%, p < 0.001). At time of hospital discharge, patients were significantly more likely to go home if quetiapine was discontinued (19.4% vs.10%, p < 0.001). Patients with quetiapine discontinued at time of hospital discharge received significantly more baseline EKG monitoring (36% vs. 17.5%, p=0.003). CONCLUSIONS: 81% of patients started on quetiapine in the ICU continued to receive this therapy at the time of transfer out of the ICU: 27.5% of patients continued to receive quetiapine at the time of discharge. The hospital discharge rate was nearly twice as high for patients whose quetiapine was discontinued during the hospitalization. CLINICAL IMPLICATIONS: ICU clinicians need to be attentive to appropriate discontinuation of quetiapine; and 2) ongoing quetiapine prescription is associated with a lower rate of discharge to home. DISCLOSURES: No relevant relationships by Jacqueline Chung No relevant relationships by Chris Destache No relevant relationships by Mark Malesker No relevant relationships by Lee Morrow No relevant relationships by Robert Plambeck No relevant relationships by Srishti Singal

Abstract Background The management of patients with chronic hepatitis B (CHB) is complex and involves interdisciplinary care across multiple medical specialties. As a result of this complexity, patients with CHB often do not receive adequate monitoring including HCC surveillance with abdominal ultrasonography (AUS). Previous studies have identified multiple factors associated with decreased HCC surveillance. We aimed to study race and sex disparities in HCC surveillance in patients with CHB during the COVID-19 pandemic. Methods We performed a single center retrospective cohort study of patients treated for CHB between January 2018 and January 2022 in Gastroenterology and Infectious Diseases clinics at our institution. HCC surveillance trends for both sexes were further stratified by 6-month time intervals throughout the study period to compare surveillance during the COVID-19 surge at our region and after the surge. The COVID-19 pandemic surge was defined as time 1/1/2020-6/30/2021. Differences between sex and race were evaluated using the chi-square test, Fisher's exact test, and continuous variables were analyzed using analysis of variance (ANOVA). Results A total of 223 adult patient records between January 2018 and January 2022 were evaluated. In total 37% females were adequately screened for HCC in any of the 6-month time frames compared to 26% for males, p >0.05. During the COVID-19 surge, surveillance rates were reduced in both males and females; however, men had significantly reduced HCC screening compared to women (men 38% compared to women 47%, P = 0.011, Figure 1). When comparing COVID-19 HCC screening, stratified by race, 20% Asians, 34% African Americans, and 22% Caucasians were screened by AUS, P = 0.069(Figure 2). Patient Demographics ID, infectious diseases clinic; GI, gastroenterology clinic; SD, standard deviation Conclusion Males received significantly less HCC surveillance compared to females. These differences continued during the COVID-19 pandemic surge. Obtaining appropriate surveillance is important and identifying disparities enables treating physicians to work on measures to mitigate them. Disclosures All Authors: No reported disclosures

Introduction: Fentanyl (F) has a rapid onset of action and short duration of action and is typically given as a continuous infusion for analgesia and sedation in the ICU. There has been concern that F dosing requirements have increased over the past few years. The goal of this study was to retrospectively evaluate the use of F in the ICU to assess whether doses increased over time. Methods: This IRB approved study included intubated ICU adult patients from 2017 - 2021. We identified all patients with F infusions over 24 hours and then randomly pulled 200 patients (40 in each calendar year) to abstract data on F dosing parameters included total length of therapy, time to max dose, and cumulative dose as primary outcomes. F side effects and concomitant diseases were also collected. Continuous variables were analyzed using ANOVA test and discrete variables were analyzed using Kruskal-Wallis test. Results are presented as mean ± SD or percentages. A significant difference in any variable was determined based on p < 0.05. Results: There were no significant differences among background demographics. The average age of the entire sample was 60.1 ± 16.5, and 52% male. Total length of therapy 102.9 ± 75.4, 111.0 ± 106.8, 139.1 ± 173.6, 101.6 ± 88.9, and 102.7 ± 71.6 hours, p>0.05 for each year. Time to max dose (41.2 ± 59.2, 29.6 ± 67.9, 40.2 ± 69.2, 52.9 ± 64.5, and 35.1 ± 37.6 hours), and cumulative dose (11025 ± 11758.7, 10887.5 ± 12450.7, 16587.5 ± 33974.5, 8912.5 ± 8961.4, and 11912.5 ± 10770.3 mcg) for each year was not different, p>0.05. Respiratory, renal, and psychiatric concomitant conditions were significantly different for all years. Regardless of the year, patients who received concomitant F and ketamine had a significant incidence of hypotension, p=0.006. Conclusions: The results of this retrospective review of intubated ICU patients found no difference in F dosing requirements over a five-year period. A significant higher incidence of hypotension was found when patients received F with ketamine. The data may be limited by the varying presence of comorbidities from year to year.

Background: The management of patients with chronic hepatitis B (CHB) is complex and spans multiple medical specialties. As a result of this complexity, patients with CHB often do not receive adequate monitoring including hepatocellular carcinoma (HCC) surveillance with abdominal ultrasonography. Previous studies have identified multiple factors associated with decreased HCC surveillance. We aimed to identify the impact of race and sex on HCC surveillance in patients with CHB.Methods: We performed a single health system chart review between January 2018 and January 2022. Differences between sex and race were evaluated using the Chi-square test and Fisher's exact test, and continuous variables were analyzed using analysis of variance (ANOVA).Results: A total of 248 patient records between January 2018 and January 2022 were evaluated. In total 37% of females were adequately screened for HCC in any of the 6-month time frames compared to 26% of males. During the coronavirus disease 2019 (COVID-19) surge, surveillance rates were reduced in both men and women. During the first 6 months of the COVID-19 surge, there was a significant difference in screening between men and women (19% vs. 35%, P = 0.026). There was a decrease in HCC screening across all races during the COVID-19 surge; however, no significant difference when comparing races was found.Conclusion: Men received less HCC surveillance compared to women. These differences were more pronounced during the COVID-19 pandemic surge. Obtaining appropriate surveillance is important and retrospective evaluations can help us determine the presence of health-related social needs so that progress can be made toward achieving health equity.

OBJECTIVES:By better understanding the long-term effects of COVID-19 and assessing rehabilitation placement among the patients in our study, we hope to determine the predictors of rehabilitation needs in individuals suffering from the long-term sequelae of COVID-19.METHODS:A retrospective chart review was performed of adult patients with a positive COVID-19 polymerase chain reaction test among multiple hospitals in a regional health system. The main outcomes measured were discharge disposition, total length of hospital stay, and overall all-cause mortality and readmission rates within 30 and 90 days of discharge.RESULTS:Of the 2502 patients included in the study, we found that 65.2% were discharged to home, while the remaining patients were discharged to home healthcare (33.6%), skilled nursing facilities (31.7%), or long-term acute rehabilitation centers (11.6%). The overall all-cause mortality rate at 30 and 90 days were 2.7% and 4.4%, respectively. The overall all-cause 30-day and 90-day readmission rates were 7.0% and 7.6%, respectively.CONCLUSION:Younger age and shorter hospitalization stays were the most important predictors of home discharge. Discharge to home was also significantly associated with lower all-cause mortality rates at 30 and 90 days after discharge.

Different pharmacotherapeutics have been introduced, and then stopped or continued, for the treatment of SARS-CoV-2. We evaluated the risks associated with mortality from SARS-CoV-2 infection. METHODS: Data was concurrently or retrospectively captured on COVID-19 hospitalized patients from 6 regional hospitals within the health system. Demographic details, the source of SARS-CoV-2 infection, concomitant disease status, as well as the therapeutic agents used for treating SARS-CoV-2 (e.g., antimicrobials, dexamethasone, convalescent plasma, tocilizumab, and remdesivir) were recorded. Discrete and continuous variables were analyzed using SPSS (ver. 27). Logistic regression identified variables significantly correlated with mortality. RESULTS: 471 patients (admitted from 1 March 2020 through 15 July 2020) were reviewed. Mean (±SD) age and body weight (kg) were 62.5 ± 17.7 years and 86.3 ± 27.1 kg, respectively. Patients were Caucasian (50%), Hispanic (34%), African-American (10%), or Asian (5%). Females accounted for 52% of patients. Therapeutic modalities used for COVID-19 illness included remdesivir (16%), dexamethasone (35%), convalescent plasma (17.8%), and tocilizumab (5.8%). The majority of patients returned home (62%) or were transferred to a skilled nursing facility (23%). The overall mortality from SARS-CoV-2 was 14%. Logistic regression identified variables significantly correlated with mortality. Intubation, receipt of dexamethasone, African-American or Asian ethnicity, and being a patient from a nursing home were significantly associated with mortality (x2 = 86.36 (13) p < 0.0005). CONCLUSIONS: SARS-CoV-2 infected hospitalized patients had significant mortality risk if they were intubated, received dexamethasone, were of African-American or Asian ethnicity, or occupied a nursing home bed prior to hospital admission.

The C–C motif chemokine receptor-5 (CCR5) expression on the T-cell surface is the prime barrier to HIV/AIDS eradication, as it promotes both active human immunodeficiency virus (HIV)-infection and latency; however, antiretrovirals (ARVs) suppress plasma viral loads to non-detectable levels. Keeping this in mind, we strategically designed a targeted ARVs-loaded nanoformulation that targets CCR5 expressing T-cells (e.g., CD4+ cells). Conceptually, CCR5-blocking and targeted ARV delivery would be a dual protection strategy to prevent HIV infection. For targeting CCR5+ T-cells, the nanoformulation was surface conjugated with anti-CCR5 monoclonal antibodies (CCR5 mAb) and loaded with dolutegravir+tenofovir alafenamide (D+T) ARVs to block HIV replication. The result demonstrated that the targeted-ARV nanoparticle’s multimeric CCR5 binding property improved its antigen-binding affinity, prolonged receptor binding, and ARV intracellular retention. Further, nanoformulation demonstrated high binding affinity to CCR5 expressing CD4+ cells, monocytes, and other CCR5+ T-cells. Finally, the short-term pre-exposure prophylaxis study demonstrated that prolonged CCR5 blockage and ARV presence further induced a “protective immune phenotype” with a boosted T-helper (Th), temporary memory (TM), and effector (E) sub-population. The proof-of-concept study that the targeted-ARV nanoformulation dual-action mechanism could provide a multifactorial solution toward achieving HIV “functional cure.”