Abstract Background I’m Cryptococcus neoformans is an opportunistic fungal pathogen that primarily affects immunocompromised individuals, particularly those with advanced HIV/AIDS. However, an increasing number of cases are being identified in non-HIV immunocompromised hosts, including patients receiving B-cell-depleting therapies such as Rituximab. Case presentation A 67-year-old male with marginal B-cell lymphoma developed an isolated cryptococcal bloodstream infection shortly after completing Rituximab therapy. Initially, the patient presented with persistent diarrhea and progressive weakness. Subsequently, acute otitis media developed, and Streptococcus pneumoniae bacteremia was diagnosed. During his hospital course, his repeated blood cultures were cleared of bacteria but revealed Cryptococcus neoformans, confirmed by a positive serum cryptococcal antigen (titer 1:40). Given the patient’s severe coagulopathy, a lumbar puncture was not feasible, necessitating an alternative diagnostic approach. Adhering to IDSA guidelines, he received a 2-week induction phase of amphotericin B and flucytosine, followed by consolidation and maintenance therapy with fluconazole. The patient successfully completed his induction therapy as an inpatient without complications and demonstrated clinical recovery at a subsequent follow-up visit. Conclusion This case study highlights the expanding spectrum of cryptococcosis beyond HIV/AIDS and underscores the paramount importance of early recognition and treatment, adhering to established guidelines, in the context of Rituximab-associated immunosuppression. Further research is needed to refine risk stratification of isolated Cryptococcus bloodstream infection and develop tailored management strategies for this emerging at-risk population.
Neurosurgical patients are at an increased risk of developing agitation and intensive care unit (ICU) delirium due to direct inflammation and oxidative stress associated with neurosurgery. There are limited therapeutic options for the management of agitation and delirium in this population; and neurosurgical patients have been largely underrepresented in previous studies. This study aimed to assess the impact of valproic acid (VPA) on adjunctive agent requirements for the management of agitation in neurosurgical ICU patients. This was a single-center, retrospective, descriptive study evaluating adult neurosurgical patients admitted between 1 April 2016 and 31 August 2023. Patients were included if they were on VPA for at least 3 days for the treatment of agitation. The primary outcome evaluated changes in total daily doses (TDD) of adjunctive sedative agent requirements following VPA initiation. Secondary outcomes included the incidence of positive Richmond Agitation and Sedation Scale (RASS) scores and liberation from physical restraints. Safety outcomes included the occurrence of thrombocytopenia, hyperammonemia, and liver function test (LFT) abnormalities while on VPA. A total of 91 patients were included in the analysis. Significant reductions in TDD of opioids (p = 0.001), benzodiazepines (p = 0.003), and dexmedetomidine (p < 0.001) were seen on day 3 of VPA therapy. Significant reductions in the number of patients with positive RASS scores (p = 0.001) and the number of patients requiring physical restraints (p = 0.001) were also observed from day 1 to day 3 of VPA therapy. Initiation of VPA was associated with a significant decrease in adjunctive sedative agent requirements, positive RASS scores, and number of patients requiring physical restraints. Further prospective studies are needed to determine the optimal role of VPA for the management of agitation in neurosurgical ICU patients.
Streptococcus pneumoniae serotypes 3, 6A, 6B, 9N and 19F often cause severe disease. The pneumococcal conjugate vaccines PCV-20 and PCV-21 cover 10 shared serotypes, along with 10 and 11 additional unique serotypes, respectively. The association between serotype coverage and severity of disease remains poorly understood. Serotype distribution of Streptococcus pneumoniae Among Hospitalized Patients This was a secondary analysis of patients with S. pneumoniae pneumonia. Serotype was determined by Quellung reaction and PCR. Demographics were collected, including vaccination status, as well as time to clinical stability, length of stay, bacteremia (invasive disease), organ failure and mortality. Patients were grouped by serotype and categorized based on PCV-20 or PCV-21 vaccine serotype. Clinical outcomes were compared between each group. For the PCV-20 serotype category, clinical outcomes were also compared by vaccination status. A total of 191 patients were included: 89 (47%) had a serotype covered by the PCV-20 vaccine and 151 (70%) had a serotype covered by the PCV-21 vaccine. Of the 89 patients with PCV-20 serotypes, 13 (15%) were unique to the PCV-20 vaccine, and of the 151 patients with PCV-21 serotypes, 83 (55%) were unique to the PCV-21 vaccine. No significant differences in clinical outcomes were observed between unique serotype categories; however, PCV-20 serotypes tended to result in longer time to stability (5.5 vs. 4 days) and hospital stay (16 vs. 8 days), while PCV-21 serotypes showed a trend toward higher rates of bacteremia (25% vs. 11%), organ failure (69% vs. 67%), and mortality (19% vs. 11%). Among those with any serotype covered by the PCV-20 vaccine, clinical outcomes did not differ significantly by vaccination status, though unvaccinated individuals showed non-significant trends toward worse outcomes—longer time to stability (5 vs. 4 days), length of stay (8 vs. 5 days), and higher mortality (13% vs. 11%). More patients had a serotype covered by a unique serotype of PCV-21 vaccine than PCV-20 vaccine, but clinical severity was comparable. Among the PCV-20 vaccine group, vaccination status did not result in significant improvement in outcomes. However, observed trends suggest potential variations in disease severity that warrant further investigation. Forest W. Arnold, DO, MSc, Gilead Sciences: Grant/Research Support Leslie A. Parrish, Ph.D., Gilead Sciences: Grant/Research Support Subathra Marimuthu, MS, Gilead Sciences: Grant/Research Support Vidyulata Salunkhe, MBBS, MPH, Gilead Sciences: Grant/Research Support Daniya Sheikh, MD, Gilead Sciences: Grant/Research Support Nataly Pazmino, MD, Gilead Sciences: Grant/Research Support Jafir Wakeel, MBBS, Gilead Sciences: Grant/Research Support Girish Madishetty, MD, Gilead Sciences: Grant/Research Support Hamza Mehmood, MD, Gilead Sciences: Grant/Research Support Spozhmai Hewadmai, MD, Gilead Sciences: Grant/Research Support Biplab Adhikari, MD, Gilead Sciences: Grant/Research Support Hassan Cheema, MD, Gilead Sciences: Grant/Research Support Hussnain Cheema, MD, Gilead Sciences: Grant/Research Support Imad Majeed, MD, Gilead Sciences: Grant/Research Support Steven Gootee, MHI, Gilead Sciences: Grant/Research Support T'shura Ali, PhD, MPH, Gilead Sciences: Grant/Research Support
Abstract Rationale Lung cancer remains the leading cause of cancer-related mortality in the United States. Chronic occupational and environmental lung diseases such as asbestosis, other pneumoconiosis, and hypersensitivity pneumonitis can cause progressive fibrosis and inflammation, potentially increasing the risk and severity of lung cancer. Over the past two decades, evolving workplace safety standards, reduced smoking rates, and improved diagnostic approaches may have influenced the mortality patterns of lung cancer associated with these conditions. Tracking the epidemiological trends and geographical variations in lung cancer mortality associated with occupational and environmental lung diseases over time is essential. Methods We analyzed national mortality data from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database between 1999 and 2020. Lung cancer (ICD-10: C34)-related deaths associated with occupational and environmental lung diseases (ICD-10: J60-J70) in adults aged ≥25 years were examined using the year 2000 U.S. standard population for age standardization. Mortality rates were expressed as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to assess trends and calculate the annual percentage change (APC), stratified by year, sex, census region, type of facility, and state. Results Between 1999 and 2020, a total of 27572 lung cancer deaths were associated with occupational and environmental lung diseases. The overall AAMR declined from 0.7 in 1999 to 0.5 in 2011 (APC -3.39; 95% CI, -4.61 to -2.15), remained stable for a period, then showed minor fluctuations, returning to 0.5 in 2020 (APC 1.59; 95% CI, -0.65 to 3.90). Males exhibited higher mortality rates than females throughout the study period (0.9 vs. 0.3). Regional variations in AAMR were also significant, with the highest rate in the Midwest and South (0.6 each). In terms of the location of death, 64.70 % died in a hospital. Geographically, AAMRs ranged from 1.3 in West Virginia to 0.2 in New Mexico. Conclusion From 1999 to 2020, lung cancer mortality associated with occupational and environmental lung diseases showed an overall downward trend across the United States. This decline likely reflects improvements in occupational safety standards, reduced exposure to asbestos and silica, heightened awareness of workplace hazards, and a decrease in smoking prevalence among industrial workers. Nonetheless, persistent sex and regional disparities highlight ongoing vulnerabilities. Continued occupational health surveillance, targeted risk reduction, and region-specific prevention strategies remain essential to further mitigate lung cancer burden in populations with prior environmental or occupational exposures. This abstract is funded by: None
BACKGROUND:Influenza is a major global health burden, causing widespread illness, complications, and high economic costs each year. Current diagnostic methods and traditional auscultation (MPA) are limited by delays, subjectivity, and accessibility challenges. Mobile phone auscultation with computational modeling offers a promising rapid, scalable, and noninvasive alternative for detection. OBJECTIVES:To evaluate the feasibility and preliminary diagnostic performance of MPA in distinguishing influenza A from a heterogeneous group of respiratory conditions and controls. Successful classification would support remote influenza A diagnosis using telehealth audio recordings, expanding access for underserved populations. METHODS:In this prospective cohort study, participants were enrolled into five predefined groups: influenza A, pneumonia, acute bronchitis, other respiratory illness, and controls. Subjects were recruited from three emergency departments. Lung sound recordings were collected using unmodified mobile phones. Computational nonlinear biofluid dynamics techniques were applied to extract features, including Maximal Lyapunov Exponent (MLE) and Correlation Dimension (Dcorr). Train-test sets were created by 80/20 clustered random sampling. Time Series Dynamics models were fitted, and logistic regression classifiers were developed to distinguish influenza A from comparison groups. RESULTS:A total of 294 subjects were enrolled, including 59 with influenza A. Baseline differences between influenza A and comparison cohorts were limited to race. All complete recordings were analyzed. Modeling performed well, generating only one false negative. Sensitivity was 92%, specificity 85%, and area under the curve (AUC) 89%. CONCLUSIONS:MPA demonstrates feasibility and moderate discriminatory ability for identifying influenza A from a heterogeneous set of respiratory conditions and controls. These findings support further investigation of MPA as a potential adjunctive or screening tool, particularly in resource-limited settings. Additional studies are needed to validate performance, define clinical use cases, and determine its role relative to existing diagnostic methods.
