Citations

Abstract Introduction Sickle cell disease (SCD) disproportionately affects African Americans(AA), comprising over 90% of cases. Acute pulmonary embolism (APE) is a serious complication in SCD patients due to increased thromboembolic risk from chronic inflammation, endothelial dysfunction, and hypercoagulability. Although recent studies have demonstrated sex-based differences in APE outcomes, data remain limited for SCD patients. We evaluated sex-based differences in outcomes among AA SCD patients with APE. Methods AA adults with SCD hospitalized for APE were queried from the 2016-2022 National Inpatient Sample. COVID-19 positive patients, patients younger than 18 years, and cases missing data were excluded. Demographics, treatment patterns, and in-hospital outcomes were compared between males and females using appropriate statistical tests with survey-weighted analysis. Results We studied 3635 SCD patients who were treated for APE, consisting of 60.66% (3635)females and 39.34%(2205) males. The overall mean age was 38.40 years, with no differences between the two sexes(mean age of 38.71 in males and 38.20 years in females, p = 0.620). While males reported a higher comorbidity burden with a Charlson Comorbidity Index(CCI) score of 1.03 (vs. 0.92 in females), it was not statistically significant(p = 0.345). In total, 23.43% of males and 22.68% of females had a prior history of PE(p = 0.815). Medicare constituted 31.82% of primary payers among males and 38.36% among females, while Medicaid and private insurance accounted for 32.52% and 24.83% of males, and 32.19% and 25.11% of females, respectively(p = 0.015). After adjusting for confounders, we found that females demonstrated higher odds of receiving transfusion to males. No statistically significant differences were seen for mortality, major cardiovascular complications including cardiac arrest, acute kidney injury, acute liver injury, ventricular tachycardia, or cardiogenic shock. In addition, treatment modalities such as mechanical ventilation, vasopressors or thrombolytic interventions(systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy) were comparable between males and females. We further did not find any differences in sepsis, bleeding events, acute ischemic stroke, or acute myocardial infarction(Table 1). Similarly, although females stayed longer(mean: 5.46 days vs. 4.90 days, p = 0.121), and had higher inflation-adjusted charges($61106 vs. $58810, p = 0.688), they were comparable. Conclusion Our study revealed that sex-based differences in outcome disparities among AA SCD patients admitted for APE are limited, with female transfusion requirements differing significantly, which warrants further investigation. This abstract is funded by: None

Abstract Introduction Chronic Lymphocytic Leukemia(CLL) is the most common leukemia in adults in the United States. CLL patients are at higher risk of bacterial infections, and Pseudomonas aeruginosa is a notable pathogen. Limited data is available comparing the demographics and outcomes of pseudomonas sepsis in CLL. Our study aims to analyze the patient characteristics and mortality between intensive care unit (ICU) and non-ICU admissions for pseudomonas sepsis among CLL patients. Methods Adults with active CLL admitted with a primary diagnosis code of pseudomonas sepsis(ICD-10 code: A41.52) were identified via the National Inpatient Sample(NIS)(2016-2022), excluding COVID-19 cases. Admissions to ICU were estimated if the patients required mechanical ventilation , vasopressors or central venous catheter placement, as per prior NIS-based studies. The predictors of ICU admissions were identified using multivariable regression models, with further analyses focused on estimating the in-hospital mortality. All analysis incorporated adjustments for weight, cluster, and strata, as advised by the data source. Results A total of 1,650 admissions were identified, of which 335 (20.3%) required intensive care. The intensive care cohort was younger (mean age: 73.19 vs. 76.86 years), yet age was not a significant predictor for the need for intensive care. Significant racial disparities were observed, with Black patients demonstrating significantly higher odds of intensive care use than White patients. In contrast, Hispanic patients had comparable odds to White patients. Sex, weekend admission status, private insurance coverage versus Medicare, and income quartiles did not significantly impact intensive care utilization. Among comorbidities, liver cirrhosis and palliative care encounters predicted higher ICU admission rates. Paradoxically, hypertension was associated with lower odds. Other comorbidities showed no significant association with intensive care admission (Table 1). Intensive care patients demonstrated an in-hospital mortality rate of 40.91% versus 8.75% in non-intensive care patients (aOR: 6.690, 95% CI: 2.648-16.906, p < 0.01). Furthermore, intensive care had a substantially greater resource utilization, longer stays (mean: 16.49 vs. 8.83 days, p < 0.01) and markedly higher hospitalization charges (mean: $314,311 vs. $89,614, p < 0.01). Conclusions Our study revealed that black race, comorbidities like liver cirrhosis and palliative care encounters were key predictors for ICU admissions. ICU utilization was associated with higher inpatient mortality, length of stay and hospitalization costs. These findings highlight the disparities and resource burden, and warrants strategic interventions to address them. This abstract is funded by: None

Abstract Introduction Pneumocystis jirovecii pneumonia (PJP) is a significant opportunistic infection in immunocompromised patients. While cancer patients experience significant immunosuppression that increases their susceptibility to PJP, outcomes of this infection stratified by specific tumor types remain poorly characterized. Methods This retrospective study identified adults with PJP and either solid or hematologic malignancies using the National Inpatient Sample (2016-2022). Exclusion criteria included age <18 years, COVID-19 positivity, concurrent solid and hematologic malignancies, HIV positivity, or missing data. Baseline characteristics were compared between the two cancer groups. Multivariable regression analyses, adjusting for potential confounders, were conducted to estimate adjusted odds ratios for adverse events, treatments, and mortality. All analyses accounted for the complex survey design of the dataset. Results We found 11565 admissions involving PCP matching our selection, with 55.6%(6430) liquid and 44.4%(5135) solid cancers. Both groups contained an elderly population (mean age in solid: 64.25 years, vs. mean age in liquid: 63.36 years, p = 0.139), and mostly males( 51.32% of solid and 66.33% of liquid cancers, p < 0.01). The adjusted Deyo Charlson Comorbidity Index Scores were also comparable(1.65 in solid vs. 1.55 in liquid cancers, p = 0.195). Majority of patients in both groups (73.97% of solid and 72.55% of liquid) were Whites(p = 0.155), insured via Medicare(52.98% of solid and 54.60% of liquid,p=0.580), and hospitalized at urban teaching centers(85.69% of solid and 87.17% of liquid, p = 0.341). Among patients with solid tumors, 32.03% were respiratory/thoracic cancers, 11.88% were breast cancers, 11.10% were gastrointestinal cancers. Among patients with hematologic malignancies, the most common diagnoses were lymphoma (48.4%) followed by leukemia (37.2%). Patients with hematologic malignancies recorded reduced rates of acute respiratory failure, mechanical ventilation requirements, and intubation. In contrast, no significant differences were observed between groups for cardiovascular complications including cardiac arrest and septic shock. Acute kidney injury odds were similarly comparable between the two cohorts(Table 1). Our analysis demonstrated significantly lower mortality in hematologic malignancy patients compared to solid tumor patients, but with longer lengths of stay (15.4 days vs 13.2 days) and higher hospital charges ($234,616 vs $188,792). Conclusions Our findings demonstrate that solid malignancies may pose a bigger threat to PJP outcomes as compared to hematological cancers, warranting further investigation to set up appropriate preventive strategies and treatment protocols. This abstract is funded by: None

Abstract Introduction Minimally invasive surgical techniques including Robotic-Assisted thoracoscopic surgery (RATS) have advanced the treatment of lung cancer and enhanced patient outcomes from early recovery to improved quality of life. The “July effect” hypothesizes that morbidity and mortality outcomes worsen during the beginning of academic year when new residents and fellows begin training. We investigated the impact of the same on outcomes of RATS among lung cancer patients. Methods Using the National Inpatient Sample (2016-2019), we identified adults(ages≥18 years) with lung cancer who underwent RATS(lobectomy/sublobar resection) at urban teaching centers(UTC). Patients were stratified by surgical timing: July-September versus other months. Multivariable logistic regression compared perioperative outcomes between groups, adjusting for confounders. Results We analyzed 25,480 RATS procedures, with 25.59% performed during July-September. Baseline characteristics were comparable between groups regarding sex, race (White, Hispanic), insurance type, comorbidity burden, and age; however, fewer Black patients underwent surgery during July-September (Table 1a). Multivariable logistic regression revealed no significant differences in perioperative outcomes between the July-September and other months of the year. Evaluated outcomes included thoracic complications like pneumonia (aOR 0.89, 95% CI 0.62-1.28, p = 0.526), pneumothorax (aOR 1.07, 95% CI 0.85-1.34, p = 0.583), air leak (aOR 0.98, 95% CI 0.79- 1.22, p = 0.873), respiratory failure (aOR 0.9, 95% CI 0.50-1.63, p = 0.729) , atelectasis (aOR 1.12, 95% CI 0.88-1.42, p = 0.372), thromboembolic events like pulmonary embolism (aOR 0.63, 95% CI 0.13-2.97, p = 0.557), deep venous thrombosis (aOR 1.01, 95% CI 0.65-1.57, p = 0.952), bleeding complications like transfusion (aOR 0.95, 95% CI 0.55-1.64, p = 0.866), hemothorax/hemoperitoneum/hematoma (aOR 0.58, 95% CI 0.22-1.52, p = 0.264), renal complications (aOR 1.00, 95% CI 0.32-3.17, p = 0.994), conversion to open surgery (aOR 0.53, 95% CI 0.11-2.47, p = 0.417), extended length of stay (>7 days) (aOR 0.96, 95% CI 0.78-1.17, p = 0.667), and in-hospital mortality (aOR 0.57, 95% CI 0.21-1.50, p = 0.250)(Table 1b). Conclusions Our study suggested no “July effect” in the perioperative outcomes of RATS. This demonstrates the robust hospital support systems ensuring the safe transition of resident classes without affecting the patient care negatively. This abstract is funded by: None

Abstract Purpose This study aimed to analyze mortality trends among patients with pneumonia and chronic kidney disease in the United States from 1999 to 2020. By examining patterns across urbanization levels, racial and ethnic groups, geographic regions, and sex, the study sought to identify significant changes over time and potential disparities in mortality outcomes. Methods Mortality data were extracted from the CDC WONDER database for patients diagnosed with pneumonia (ICD-10: J09-J18) and chronic kidney disease (ICD-10: N18). Trends were analyzed using Annual Percent Change (APC) with 95% confidence intervals (CI). Joinpoint regression was utilized to identify significant shifts in mortality trends over time. The analysis was stratified by urbanization level (Large Central Metro, Large Fringe Metro, Medium Metro, Small Metro, Micropolitan), ethnicity (American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, White), census region (Northeast, Midwest, South, West), Hispanic origin (Hispanic or Latino, Not Hispanic or Latino), and sex (Female, Male). Results From 2018 to 2020, significant increases in mortality were observed across all demographic and geographic categories. Urban areas, particularly Large Central Metro (APC = 39.4026%, p = 0.0008) and Small Metro (APC = 37.0284%, p = 0.0004), experienced the most pronounced rises. Ethnic disparities were evident, with Black or African American (APC = 49.9199%, p < 0.000001) and Hispanic or Latino (APC = 61.5742%, p < 0.000001) populations showing the highest mortality increases. By census region, the Midwest (APC = 35.7843%, p = 0.0004) and South (APC = 34.7972%, p = 0.0016) had the most significant spikes. Both females (APC = 36.0664%, p = 0.0004) and males (APC = 35.1504%, p < 0.000001) experienced substantial mortality increases, with females showing slightly higher rates. Conclusion The findings reveal significant increases in mortality from 2018 to 2020 across all analyzed categories, with notable disparities among racial, ethnic, and geographic groups. These trends highlight the need for further investigation into underlying causes and targeted interventions to address inequities. Clinical implications The results underscore the importance of addressing disparities in healthcare access and outcomes, particularly for Black or African American and Hispanic or Latino populations. Clinicians should focus on early diagnosis, effective management of comorbidities, and equitable resource distribution to mitigate mortality risks in high-risk groups. This abstract is funded by: None

An exhalation delivery system for fluticasone (EDS-FLU) is designed to deposit drug into sinonasal regions above the inferior turbinate, particularly sinus drainage pathways not reached by standard nasal steroid sprays. We evaluated the efficacy and safety of EDS-FLU for chronic rhinosinusitis (CRS). We reviewed four independent randomized controlled trials derived from three published articles identified through searches of PubMed, Embase, SCOPUS, Google Scholar, Web of Science, and the Cochrane Library up to April 2024. Outcomes included 22-item Sinonasal Outcome Test (SNOT-22) scores, nasal symptom scores, nasal polyp scores, patient global impression of change (PGIC), responder and surgical indication rates, and adverse events. Compared with EDS-placebo, EDS-FLU produced greater reductions in nasal polyp scores and SNOT-22 scores over 6 months. At 3 months, nasal congestion, facial pain, rhinorrhea, and olfactory dysfunction improved more with EDS-FLU, and PGIC responder and complete response rates were higher at 3 and 6 months. EDS-FLU reduced surgical indication and increased overall responder rates at 3 months but not at 6 months. Epistaxis and nasal septal erosion or ulceration occurred more frequently with EDS-FLU, whereas rates of headache, nasal congestion, nasopharyngitis, and upper respiratory infection were similar between groups. EDS-FLU provides clinically meaningful improvements in subjective and objective outcomes in CRS but is associated with an increased risk of local nasal adverse events, warranting individualized risk-benefit assessment.

PURPOSE We sought to characterize outcome associations of poly ADP-ribose polymerase inhibitors (PARPi) in patients with ovarian cancer (OVCA) whose cancers contain homozygous loss (deletions) of homologous recombination repair (HRR) pathway genes, an alteration class not uniformly reported on clinical testing and not susceptible to acquired resistance via secondary reversion mutations. METHODS This study used US-based deidentified Flatiron Health-Foundation Medicine OVCA Clinico-Genomic Database. Patients with advanced OVCA and genomic profiling by Foundation Medicine were assembled into cohorts evaluating PARPi monotherapy use, and separately, PARPi maintenance therapy use, with outcomes associated with HRR gene alterations: BRCA1 / 2 , PALB2 , RAD51B/C/D , BARD1 , and BRIP1 . RESULTS 1.5% (82/5,404) had HRR gene homozygous loss, with BRCA1 and BRCA2 loss being most common. Among all OVCAs with BRCA1/2 alterations, 7.5% (63/836) were homozygous losses. Most BRCA1 (34/38, 89%) and BRCA2 (18/25, 72%) homozygous losses were intragenic, with breakpoints not spanning entire gene. Maintenance cohort: 22 patients had HRR gene homozygous loss, with strongly improved progression-free survival (PFS) for PARPi versus no PARPi use (HR, 0.06, 95% CI, 0.01 to 0.37). Monotherapy cohort: patients without HRR alterations (n = 198), HRR mutations or rearrangements (n = 93), and HRR homozygous loss (n = 8) had median PFS of 4.9, 10.6, and 25.4 months, and median overall survival of 18.5, 22.5, and 51.8 months, respectively. CONCLUSION We observe durable PARPi effectiveness for patients with OVCA and HRR gene homozygous loss in routine practice. We demonstrate the importance of detecting and reporting homozygous loss in HRR genes, an aspect not standard to all sequencing assays.

Background: Metabolic-associated fatty liver disease (MAFLD) affects approximately 30% of the global population and is associated with obesity and metabolic syndrome. Anthropometric indices such as body mass index (BMI), waist circumference (WC), and weight are crucial markers for evaluating the progression of MAFLD. Curcumin, a bioactive compound with anti-inflammatory and antioxidant properties, has been investigated for its potential to improve metabolic outcomes. This umbrella review aimed to systematically evaluate the effects of curcumin supplementation on anthropometric indices in patients with MAFLD, considering epidemiological strength and power analysis. Methods: An umbrella review of meta-analyses from randomized controlled trials was conducted. PubMed, Scopus, and Web of Science were searched up to September 2024. Meta-analyses assessing curcumin’s effects on BMI, weight, and WC in MAFLD patients were included. Quality was assessed using the A Measurement Tool to Assess Systematic Reviews version (AMSTAR-2) tool, and heterogeneity was evaluated using the I 2 statistic. Statistical analyses were performed using R and Stata 18 software. Results: Curcumin supplementation had no significant effect on BMI (standardized mean difference [SMD]: −0.01; 95% confidence interval [CI]: −0.24 to 0.21, P = .91) with low power (1-β = 0.03) and a low epidemiological grade according to GRADE criteria. Similarly, curcumin showed no significant effect on WC (SMD: −0.27; 95% CI: −0.57 to 0.04, P = .08) with high power (1-β = 0.96) but low epidemiological strength. However, curcumin significantly reduced weight (SMD: −0.12; 95% CI: −0.19 to −0.04, P < .01) with moderate power (1-β = 0.56) and moderate epidemiological strength. No significant effect of dose or effect of supplementation duration was found. Conclusion: Curcumin supplementation may result in a statistically detectable but clinically modest reduction in body weight in patients with MAFLD, while showing limited or no efficacy on BMI and waist circumference. The epidemiological strength of the evidence varies across outcomes and is of low to moderate quality. Further well-designed, high-quality randomized controlled trials are needed to confirm the clinical relevance of curcumin’s effects on anthropometric indices.

Abstract Rationale Dyspnea is a prominent symptom of fibrotic hypersensitivity pneumonitis (fHP), limiting patients’ activity and impairing their quality of life. The University of California San Diego Shortness of Breath questionnaire (UCSD-SOBQ) is a 24-item instrument used to assess dyspnea severity in patients with various respiratory conditions. Objectives This study aimed to examine the reliability and responsiveness of the UCSD-SOBQ score, its validity as a measure of dyspnea severity, and its prognostic value in a prospective cohort with fHP. Methods We conducted psychometric analyses on UCSD-SOBQ response data and assessed the association between score changes and survival in patients with fHP who completed the UCSD-SOBQ and other HP severity metrics at baseline, 6 and 12 months. We introduce the reliable change index (RCI) and the likely change index (LCI) to assess the statistical significance of within-individual change in UCSD scores. Results At baseline, internal consistency was high (Cronbach’s alpha = 0.97). Significant moderately strong correlations were observed between UCSD-SOBQ scores and percent predicted forced vital capacity (FVC%), r = -0.46, percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%), r = -0.32, and Borg dyspnea scores r = 0.56. UCSD-SOBQ scores were significantly different between the lowest and highest strata of FVC% (64.9 ± 18.9 vs. 36.2 ± 22.9), DLCO% and Borg scores. The threshold for worsening within-individual change in the UCSD-SOBQ score at 95% confidence was 12 points. A 1-point higher baseline UCSD-SOBQ score was associated with a 2% increase in the risk of death or transplant (HR 1.02, 95% CI 1.00, 1.04). Conclusions In fHP, the UCSD-SOBQ score is a reliable and valid measure of dyspnea severity, is responsive to change, discriminates patients with differing severities, and is associated with transplant free survival. Additional qualitative data and psychometric analyses could tailor the UCSD-SOBQ to fHP and may further improve its measurement properties.