Citations

Abstract Background Invasive listeriosis remains a leading cause of foodborne infection–related mortality in the United States and is associated with substantial case fatality despite appropriate antimicrobial therapy. Owing to the relative rarity of invasive disease, contemporary data evaluating clinical characteristics, optimal antimicrobial strategies, and predictors of mortality remain limited. Methods We conducted a retrospective cohort study of adults with laboratory-confirmed invasive Listeria monocytogenes infection at Mayo Clinic Health System sites from 1980 to 2024. Clinical syndromes were categorized into four mutually exclusive categories, namely bloodstream infection, central nervous system infection, pregnancy-associated infection, and other focal infections. The primary outcome was 1-year all-cause mortality. Secondary outcomes included 90-day mortality and residual neurological deficits among patients with neurolisteriosis. Results Fifty patients were included (median age, 72 years; 56% immunocompromised). The most common clinical presentations were bacteremia (44%) and neurolisteriosis (36%), followed by endovascular infection (12%) and peritonitis (6%). Most patients received a beta-lactam–based regimen, 46% aminopenicillin monotherapy, and 30% received combination therapy with gentamicin. Thirty-day, 90-day, and 1-year mortality were 10%, 12%, and 20%, respectively. Immunocompromised status and intensive care unit admission were associated with an increased risk of 1-year mortality, whereas adjunctive gentamicin therapy was not associated with improved survival. Conclusion Invasive listeriosis is associated with substantial morbidity and mortality, particularly among immunocompromised hosts. Host factors and severity of illness at presentation appear to be key drivers of unfavorable outcomes. Larger multicenter studies are needed to define optimal management strategies.

Background: Ceftriaxone and cefepime resistance among Enterobacterales continues to increase globally, partly due to the rising prevalence of extended-spectrum β-lactamase (ESBL) producing organisms. Surveillance of both resistance patterns and antimicrobial utilization is essential to inform empiric prescribing practices and stewardship strategies. Since carbapenems are frequently used to treat cephalosporin-nonsusceptible Enterobacterales infections, we evaluated trends in ceftriaxone and cefepime susceptibility among Escherichia coli and Klebsiella pneumoniae from 2012–2024 and institutional carbapenem utilization during overlapping years (2019–2025), following outcomes from the MERINO trial for management of ceftriaxone-resistant Enterobacterales infections. Methods: We conducted a retrospective review of annual cumulative inpatient antibiogram data for E. coli and K. pneumonia isolates for 2012-2024. Percent susceptibility to ceftriaxone and cefepime was assessed using Clinical and Laboratory Standards Institute (CLSI) breakpoints among a median of 1,532 E. coli isolates/year and 561 K. pneumoniae isolates/year. (Table 1). Institutional carbapenem utilization (combined meropenem and ertapenem use) was measured as days of therapy (DOT) per 1000 patient-days during 2019–2025 (not specifically representing treatment of E. coli or K. pneumoniae), following implementation of electronic medical record (EMR)–based antimicrobial utilization dashboards. Temporal trends were visualized using line plots. Pearson correlation coefficients (r) were calculated to assess percent susceptibility trends and carbapenem utilization during 2019–2024. Analyses are descriptive; no causal inference was made. Result: During 2012–2024, ceftriaxone susceptibility declined from 89% to 83% among E. coli and from 93% to 82% for K. pneumoniae, while cefepime susceptibility declined from 95% to 88% and 97% to 85% respectively (Figure 1). During the overlapping years 2019–2024, Pearson correlation showed modest downward susceptibility trends for ceftriaxone (E. coli r = −0.900, p = 0.014; K. pneumoniae r = −0.840, p = 0.036) and cefepime (E. coli r = −0.780, p = 0.067; K. pneumoniae r = −0.850, p = 0.033). Institutional carbapenem use increased from 15.2 to 19.3 DOT per 1,000 patient days between 2019 and 2025 (r = 0.79, p = 0.035) (Figure 2). Upon review, carbapenem use was substantially higher in hematology-oncology services (23.7–25.9 DOT/1000 patient-days, during 2022–2025) compared with overall institutional use (15.2–19.3 DOT/1000 patient-days). Conclusion: Ceftriaxone and cefepime susceptibility among Enterobacterales declined over the past decade, coinciding with a modest increase in institutional carbapenem use without a corresponding increase in carbapenem resistance during 2019-2024. Local susceptibility patterns and antimicrobial utilization data provide critical context for stewardship prioritization, especially in high-risk hematology-oncology populations.

Abstract Healthcare personnel (HCP) are at risk for occupational exposure to tuberculosis. Current guidelines for managing exposed HCP are broad and resource intensive. Based on review of our internal data, we propose a risk-based stratification approach to streamline exposure follow-up testing and optimize resource utilization.

Abstract Background Good syndrome (GS) is an under-recognized adult-onset immunodeficiency characterized by the coexistence of thymoma and hypogammaglobulinemia. It is marked by recurrent infections, combined B- and T-cell immunodeficiency, and frequent autoimmune manifestations. Its rarity, unclear pathogenesis, and often delayed diagnosis contribute to its clinical complexity.Distribution of Infections by pathogen type in patients with Good Syndrome: the microbiological spectrumDemographics, clinical characteristics, thymoma classification with staging and management Methods We conducted a retrospective review of adults diagnosed with good syndrome at Mayo Clinic up until 2024. We assessed baseline characteristics, clinical features with a particular focus on infectious complications, immunological lab parameters, thymoma histopathology with staging, and management. Descriptive statistics were utilized for analysis.Immunological lab parameters and management of Good syndrome Results During the study period, Good syndrome was diagnosed in 32 patients; 78% were male, with a median age at diagnosis of 62 years (Table 1). All patients had thymoma, the majority of which were stage I (localized), and most underwent thymectomy as part of management. The median delay in GS diagnosis following thymoma diagnosis was 1,486 days (interquartile range IQR: 406.75–1,992.75). Infectious complications were observed in 30 of 32 patients (97%), most commonly sinopulmonary infections (87%) (Figure 1). Bacterial infections were documented in 29 patients (94%), viral in 14 (45%), fungal in 13 (42%), and mycobacterial in 3 (10%) (Figure 2). Immunologic data were available for 22 patients. Reduced CD4+ T-cell counts and severe B-cell lymphopenia were observed in 77%. IgM and IgG deficiencies were the most prevalent, present in 82% of cases. Most patients received monthly immunoglobulin replacement; additionally, 59% were prescribed oral antimicrobial prophylaxis due to their elevated risk of infections. All-cause mortality was 31% (n=10); among these, 3 deaths (10%) were directly attributable to complications of Good syndrome. Conclusion We observed a significant delay (Median of 4.07 years) in the diagnosis of Good syndrome following thymoma detection. Given the high risk of infectious complications and associated mortality, clinicians should maintain a high index of suspicion and consider early immunologic evaluation in adults with recurrent or opportunistic infections, particularly in the context of a known thymoma. Disclosures All Authors: No reported disclosures

Abstract Background Despite advancements in vaccination, mortality from Pneumococcal blood stream infections remains high (∼20%). Risk factors include host comorbidities (e.g., immunosuppression, kidney disease, alcohol use, smoking) and certain serotypes. While intensive care unit (ICU) admission and septic shock are associated with poor outcomes, predictors of severe disease remain underexplored. Characteristics of patients with ICU admission within 24 hours of invasive pneumococcal disease diagnosis Epidemiology, clinical characteristics, metastatic complications and management of invasive pneumococcal disease (IPD) Methods We conducted a retrospective review of hospitalized adults with Streptococcus pneumoniae bacteremia between 2013-2023. Clinical comorbidities, laboratory values, vaccination status, microbiologic data, and treatment strategies were collected. Descriptive statistics and univariate logistic regression were used to assess predictors of ICU admission using R Studio v4.4.3 Univariate logistic regression analysis for predictors of ICU admission within 24 hours of diagnosis of streptococcus pneumoniae blood stream infection Rates of streptococcus pneumoniae blood cultures over the years- seasonality trends Results A total of 185 patients were included; the majority were male (60%) with a median age of 64 years (Table 1). Immunocompromising conditions were present in 60%, and only 43% were up to date with pneumococcal vaccination. Metastatic infection was identified in 28% of cases, most commonly meningoencephalitis (74%), musculoskeletal involvement (28%), and endocarditis (12%). ICU admission within 24 hours of presentation was required in 55% of patients (Tables 2 and 3). Predictors of ICU admission included active smoking (OR 2.20), substance use within the past five years (OR 3.45), presence of metastatic foci (OR 2.39), and neurologic complications (OR 6.10). Up-to-date pneumococcal vaccination demonstrated a trend toward a protective effect. 30-day and 90-day mortality rates were 18.9% and 25.4%, respectively. Other predictors of 30-day mortality included smoking history, higher Charlson comorbidity index (CCI), hemodynamic shock at admission, and lab abnormalities such as hypoalbuminemia and elevated liver enzymes. Among the 69 isolates with available serotype data, serogroups 22 and 15 were most frequently identified. Conclusion Pneumococcal bloodstream infections are associated with substantial mortality, particularly among patients requiring ICU admission. Smoking, recent substance use, and the presence of metastatic complications were significantly associated with severe disease and ICU admission. Up-to-date pneumococcal vaccination demonstrated a protective effect. Disclosures All Authors: No reported disclosures

Abstract Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially the underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity as well and the issue should be addressed in conjunction with each other. Methods: Food and Drug Administration (FDA) drug approvals from 7/2007-6/2019 were reviewed to identify oncology approvals, and trials with age details were selected. The primary outcome was the weighted mean difference in age between the clinical trial population and realworld population for various cancers. The secondary outcomes were the prevalence of race reporting and association of age and race reporting with each other. Group comparisons for proportions were performed using the χ2 test while continuous variables were compared using multiple analysis of variance (MANOVA) test or students t-test as appropriate. P values < .05 were considered significant. Results: Of the 261 trials, the race was reported in 223 (85.4%) of the trials while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time – 29 (85.3%) in 2007-2010 vs. 49 (80.3%) in 2011-2014 vs. 145 (85.4%) during 2015-2019 (p-value=0.41). No significant association between type of cancer and race reporting was noted – 147 (86.5%) of solid cancer trials vs. 76 (83.5%) of hematological cancer trials reported race (p-value=0.52). Age discrepancy between the clinical trial population and the real-world population was present for several cancer types. The discrepancy was higher for studies that did not report race, mean difference - 8.8 years 4 (95% CI -12.6 to -5.0 years) vs. studies that did report the race, mean difference -5.1 years, (95% CI -6.4 to -3.7 years), p-value=0.04. Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations. In the meantime, reporting these characteristics for these crucial trials should be mandated. Citation Format: Thejus Jayakrishnan, Sonikpreet Aulakh, Mizba Baksh, Kianna Nguyen, Meghna Ailawadhi, Ayesha Samreen, Ricardo Parrondo, Taimur Sher, Vivek Roy, Rami Manochakian, Aneel Paulus, Asher Chanan-Khan, Sikander Ailawadhi. Disparity in race and age reporting in landmark cancer clinical trials: Underrepresentation of the traditionally underserved U.S. population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-104.

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

We describe the phenotype of a patient with extensive aortic, carotid, and abdominal dissections. The proband was found to have a heterozygous deletion of exons 21–34 inMYLK, which is a rare finding, as deletions in this gene have been infrequently reported. We describe this finding following detection in a proband with an extensive history of aortic, carotid, and abdominal dissections. Neoteric molecular modeling techniques to help determine the impact of this deletion on protein function indicated loss of function due to lack of any kinase domain. We also provide the electrostatics calculations from the wild type and mutant variant. Through a combined multiomic approach of clinical, functional, and protein informatics, we arrive at a data fusion for determination of pathogenicity embedded within the genetic code for this particular genetic variant, which, as a platform, continues to broaden its scope across the field of variants of uncertain significance classification.

Background. The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death. Methods. A newly characterized and suspected pathogenic variant in ABCD1 was analyzed using our protein informatics platform (PIP). Personalized protein-level molecular studies were completed on genetic testing data, complementing the analysis and clinical study. Results. A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 variant are presented. The unique ABCD1 protein is discussed, and the proband’s case is compared to existing reports of AMN. Conclusions. Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient’s disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity.