Citations

The Omicron variant of SARS-CoV-2 is associated with milder symptoms and lower hospitalization and mortality rates than Delta variants, although the impact of Omicron on immunocompromised patients, especially solid organ transplant (SOT) recipients, is still unclear. This study compares the hospitalization rate and outcomes between immunocompromised, immunocompetent, and SOT patients during the Delta and Omicron periods. We included adult patients who tested positive for SARS-CoV-2 on PCR or nasopharyngeal antigen test between 26 June 2021 to 8 September 2022, at our institution. A total of 12,401 COVID-19 patients were included, of which 11,055 were immunocompetent, and 1346 were immunocompromised (375 SOT recipients). Throughout the Delta and Omicron outbreaks, immunocompromised patients exhibited higher comorbidities and 30-day hospitalizations, but rates of mechanical ventilation and ICU-level care were like immunocompetent patients. During the Omicron wave, immunocompromised patients had higher unadjusted relative risk estimates (RR = 2.37, 95% CI 1.96–2.87, p < 0.05) than Delta (RR = 1.58, 95% CI 1.24–2.01, p < 0.05), with higher adjusted relative risk for hospitalization in Omicron (RR = 1.50, 95% CI 1.10–2.03, p = 0.01). Analyses show increased hospitalization risk in immunocompromised during the Omicron wave compared to the Delta wave, with no significant difference in hospitalization outcomes. The relative risk of hospitalization for SOT patients was higher in both waves.

Vertebral fractures are among the most common skeletal injuries and present significant clinical and biomechanical challenges, particularly in older adults and individuals with low bone density. Accurate prediction of vertebral mechanical response and failure under varying loading conditions is essential for improving understanding of spinal injury mechanisms. This study develops a density-dependent viscoelastic analytical model to predict the stiffness and fracture force of human vertebral specimens subjected to different compression rates. The vertebral body is represented as a composite structure consisting of a cortical shell and a trabecular core. Cortical bone is modeled as a linear elastic material, whereas trabecular bone is described using a Kelvin–Voigt viscoelastic formulation. Density-dependent constitutive relationships are incorporated for the elastic modulus and viscous coefficient of trabecular bone. Unknown material parameters are identified through optimization using the Nelder–Mead algorithm, based on experimental compression data from cadaveric vertebral specimens tested under quasi-static and dynamic loading conditions. The calibrated model reproduced the overall trend of specimen-to-specimen mechanical variation observed experimentally. Predicted stiffness values were in reasonable agreement with measured data. Fracture force predictions showed moderate agreement for dynamically tested specimens (R2 = 0.60), which improved to R2 = 0.88 after exclusion of one statistically identified outlier. Compared with a purely linear elastic formulation, the proposed viscoelastic model demonstrated modest improvement in stiffness prediction and more substantial improvement in fracture force prediction. These findings indicate that incorporating density-dependent viscoelastic effects improves representation of vertebral mechanical behavior, particularly at higher loading rates. Owing to its simplicity and computational efficiency, the proposed model requires only limited imaging input and may be useful for future biomechanical investigations, rapid screening, and injury risk prediction.

Pollen exposure drives allergic disease in millions of Americans, yet no standardized, publicly available national pollen dataset has existed until now. We describe the first nationally standardized and publicly available dataset of pollen season timing and airborne pollen concentrations. The data were derived from the National Allergy Bureau™ (NAB™), the only pollen and mold measuring network in the United States certified by the American Academy of Allergy, Asthma & Immunology (AAAAI), and curated, processed, and disseminated by the U.S. Centers for Disease Control and Prevention (CDC). The 2003–2024 dataset provides standardized measures of (1) taxa-specific historical average main pollen season (MPS) concentrations and timing (e.g., start dates, peak dates, end dates, season length); (2) taxa-specific yearly MPS concentrations and timing; (3) grouped weekly MPS concentrations, levels, and timing; and (4) grouped daily pollen levels and MPS timing. Pollen concentrations are reported as pollen grains per cubic meter (PPCM). MPS timing is computed using a 3-day consecutive method: season start occurs after the first occurrence of three consecutive days with concentrations > 1.0 PPCM; season peak is the day of maximum concentration; and season end occurs after the first occurrence of three consecutive days with concentrations < 1.0 PPCM after the peak. Historical average timing is calculated in a 365-day-of-year format and converted to calendar dates using 2024 as a reference year for display and consistency. By combining long-term data from monitoring sites across the country, this dataset shows how pollen levels vary over time and across geographic locations. This resource supports tracking pollen trends, linking pollen with weather and climate factors, and informing public health action, clinical care, and communication about population exposure and the impact to allergic diseases such as asthma and hay fever.

Background/Objectives: In the United States, HF prevalence is projected to progressively rise by 2030. Prior research suggests a strong association between reduced sleep duration and increased cardiovascular disease and HF risk. This study introduces an alternative parameter, the weekend sleep recovery (WSR), measured by the weekend-to-weekday sleep duration ratio (SDR), to evaluate its association with HF risk. Methods: We conducted a cross-sectional analysis of NHANES (National Health and Nutrition Examination Survey) 2017–2023 to examine self-reported sleep patterns. Participants were classified as WSR (SDR > 1) or non-WSR (SDR ≤ 1). Multivariate logistic regression assessed the association between WSR and HF, adjusting for demographics and comorbidities. Results: Among 8320 participants included in the fully adjusted analysis, WSR was associated with lower odds of HF compared with non-WSR (adjusted OR 0.73, 95% CI 0.55–0.96; p = 0.026). A significant interaction was observed between WSR and weekday sleep duration (P for interaction = 0.003), whereas no interaction was found with weekend sleep duration. In exploratory subgroup analyses, nominally significant associations were observed in several clinical subgroups; however, after correction for multiple comparisons, only participants without dyslipidemia retained statistical significance. No significant effect modification by race/ethnicity was observed (P for interaction = 0.436). Conclusions: Weekend sleep recovery was associated with lower odds of HF in this cross-sectional study. The association varied according to weekday sleep duration but was generally consistent across racial/ethnic groups. Given the observational design, these findings should be interpreted as associative rather than causal and warrant confirmation in prospective studies.

Racial and ethnic survival disparities exist in pediatric and young adult acute lymphoblastic leukemia (ALL), with differential treatment toxicity and setting of care as possible drivers. Whether treatment cost and utilization disparities exist, or how they may contribute to differences in ALL survival, is unknown. Patients with ALL diagnosed between 2000 and 2019 at ages 1 to 24 years were identified using ICD-9/10 codes in the administrative claims data from the OptumLabs Data Warehouse and the Surveillance, Epidemiology, and End Results program. Sex, race and ethnicity, age, year, and subtype of ALL diagnosis were collected. Reimbursed treatment cost and utilization (number of inpatient and outpatient days) were computed over the initial 8 months of treatment. Regression models assessed associations with demographic and clinical characteristics. Survival analyses assessed associations between race and ethnicity and overall survival. Among 374 individuals with ALL, treatment costs were 57% lower for Black patients than for White patients (estimate 0.43, 95% CI: 0.19-0.96; P =0.04). Utilization was similar across groups, though Black patients had 24% fewer outpatient visits (estimate 0.76, 95% CI: 0.58-0.99; P =0.04). No significant differences in survival were detected, but observations are consistent with previous reports. Despite a small sample size, the statistically significantly lower cost and utilization among Black relative to White ALL patients are concerning and warrant further research.

Immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) have improved survival for patients with early-stage NSCLC who are candidates for surgical resection. ICIs enhance antitumor responses and improve a variety of perioperative outcomes when used in the neoadjuvant, adjuvant, or perioperative setting. This review summarizes immunotherapies currently approved for neoadjuvant, adjuvant, and perioperative treatment of resectable NSCLC and the supporting evidence for approval. Gaps in data and future areas of clinical interest of using immunotherapies to maximize survival outcomes are also discussed.

Abstract In human melanoma, tumor cell-specific MHC class II expression is associated with improved response to programmed death 1 and programmed death-ligand 1 blockade; yet the direct effect of melanoma cell-specific MHC class II expression on anti-melanoma T cell responses remains largely unknown. In the clinically relevant Yale University Mouse Melanoma Exposed to Radiation (YUMMER) cell lines, MHC class II expression was IFN-γ-inducible in a subset of cells. Transduction of melanoma cells with CIITA resulted in uniformly high, constitutive expression of MHC class II. YUMMER.G cells transduced with CIITA vector had increased in vivo tumor growth in wild-type mice compared to melanoma cells transduced with empty vector. YUMMER.G cells transduced with empty or CIITA vectors had the same in vivo tumor growth in RAG−/− mice, indicating that the difference in tumor growth between CIITA- and empty-transduced cells was dependent on an intact adaptive immune system. CIITA-transduced YUMMER.G tumors exhibited an increased frequency and infiltration depth of CD4+ T cells, an increased frequency of T regulatory cells, and a decreased frequency and infiltration depth of CD8+ T cells, compared to empty-transduced tumors. Antibody depletion revealed that CIITA- and empty-transduced YUMMER.G tumors were constrained by CD4+ and CD8+ T cells, but only tumor growth of CIITA-transduced cells was decreased by CD25 blockade, which primarily blocks T regulatory cell function. Overall, this work reveals a potential pro-tumorigenic role of melanoma cell-specific overexpression of MHC class II.

Abstract Background Acute hypoxemic and hypercapnic respiratory failure are among the most common reasons for ICU admission and need for invasive mechanical ventilation. Noninvasive respiratory support (NIRS) strategies—including high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP)—may prevent intubation, improve outcomes, and reduce ICU utilization. However, there is uncertainty regarding optimal patient and modality selection, resulting in variable implementation. There are no clinical practice guidelines comprehensively addressing the use of the different noninvasive respiratory support strategies across the spectrum of acute respiratory failure. Objective To update and develop new evidence-based clinical practice recommendations informing noninvasive respiratory support use, including HFNC, NIV and CPAP, in adults with acute respiratory failure. Methods A multidisciplinary panel used the GRADE approach to address four PICO questions related to the use of NIRS for hypoxemic and hypercapnic respiratory failure, preoxygenation for intubation, and post-extubation respiratory support. Recommendations were informed by several systematic reviews and network meta-analyses. Results The panel made a strong recommendation for HFNC and a conditional recommendation for NIV or CPAP for adults with acute hypoxemic respiratory failure with close monitoring for the need for escalation of respiratory support, based primarily on effects on need for intubation. For acute hypercapnic respiratory failure, the panel made a strong recommendation for NIV to reduce mortality and need for invasive mechanical ventilation, and a conditional recommendation for HFNC only in patients with less severe hypercapnia and with mild acidemia (eg, pH &gt; 7.25), provided that close monitoring and prompt escalation to NIV are available. The panel made a strong recommendation for HFNC or NIV for preoxygenation prior to endotracheal intubation to prevent peri-intubation hypoxemia. The panel also issued a risk-based recommendation, suggesting HFNC for low-risk patients and NIV for high-risk patients to reduce the need for re-intubation following extubation after critical illness. Conclusions Noninvasive respiratory support strategies are effective in improving outcomes in a range of clinical scenarios. We provide evidence-based recommendations, which can be further informed by patient risk, institutional capacity, and interface tolerance.

Abstract Macrophages in the tumor microenvironment are known to upregulate PD-L1 expression, thereby suppressing T cells through PD-1 ligation. However, the manner in which PD-L1 expression intrinsically impacts macrophages and their immunomodulatory phenotype is less clear. Clarifying this knowledge gap would yield insight into the mechanisms of immunosuppression within the tumor microenvironment. To characterize the macrophage intrinsic role of PD-L1, we used complementary genetic and pharmacological approaches by analyzing primary murine bone marrow-derived macrophages (BMDMs) with complete genetic PD-L1 deletion and wildtype BMDMs treated with anti-PD-L1 blocking antibodies. Macrophages were evaluated across naïve, pro-inflammatory (M1), and tumor conditioned (TCM) polarization states in vitro. Unlike prior reports, neither genetic deletion nor antibody blockade dramatically altered the expression of macrophage polarization markers or in vitro phagocytic capacity. Both conditions consistently reduced surface levels of the M1-associated costimulatory molecule CD80, prompting further analysis of T cell interacting and antigen presenting proteins, in which we revealed disparate effects of genetic deletion and antibody blockade on the surface levels of MHCI, MHCII, PD-1, and PD-L2. These findings suggest that PD-L1 deletion and antibody-mediated blockade contribute to macrophage immune regulatory profiles in distinct manners. This difference supports a model in which PD-L1 functions in macrophages beyond its canonical role as a ligand for PD-1, influencing antigen presentation and checkpoint molecule levels and playing a broader role in immune regulation in the tumor microenvironment.