Impact of geographic distance from transplant center on the risk of severe graft-versus-host disease after allogeneic hematopoietic cell transplantation.
e23055 Background: Geographic distance to care has been associated with outcomes in solid tumors, reflecting differences in access, follow-up, and supportive care. However, its relationship with biologic transplant toxicities such as graft-versus-host disease (GVHD) has not been well characterized. Understanding whether access-related factors are associated with immune-mediated complications is important for systems-level optimization of post-transplant care and survivorship. Methods: We conducted a retrospective cohort study of adult patients undergoing allogeneic hematopoietic cell transplantation using the CIBMTR hs1802 publicly available dataset. Distance from patient residence to the transplant center was categorized as less than 20 miles, 20 to 50 miles, 50 to 150 miles, and greater than 150 miles, with less than 20 miles as the reference group. Primary outcomes were acute GVHD and chronic GVHD within one year after transplantation. Secondary outcomes included overall survival. Multivariable Cox proportional hazards models were used to evaluate associations between distance and outcomes, adjusting for age, sex, race and ethnicity, HCT comorbidity index, conditioning intensity, donor type, GVHD prophylaxis, transplant era, disease type, and total body irradiation use. Results: A total of 5,473 patients were included, with a median follow-up of 60.2 months. Crude rates of acute GVHD increased with greater distance from the transplant center, occurring in 40.2 percent of patients living less than 20 miles away and 45.1 percent of those living more than 150 miles away. In adjusted analyses, residence more than 150 miles from the transplant center was associated with a higher risk of acute GVHD compared with less than 20 miles, with an adjusted hazard ratio of 1.15 and a 95 percent confidence interval of 1.00 to 1.31. No significant differences were observed for intermediate distance categories. For chronic GVHD within one year, patients living more than 150 miles away had a lower recorded risk compared with those living less than 20 miles away, with an adjusted hazard ratio of 0.79 and a 95 percent confidence interval of 0.71 to 0.88. Distance to transplant center was not significantly associated with overall survival. Conclusions: Greater geographic distance from transplant centers is associated with a higher risk of severe GVHD after allo-HCT. These findings suggest that access to specialized post-transplant care and close monitoring may influence immune-mediated outcomes. Strategies to improve follow-up care, including enhanced care coordination and telemedicine, may help mitigate GVHD-related disparities and inform health policy efforts aimed at improving access to specialized transplant services, reimbursement for remote monitoring, and regional models of post-transplant care delivery.
Differential clinical and economic signatures of CAR T-cell therapy in multiple myeloma across demographic and payer strata: A national analysis.
e19537 Background: Chimeric antigen receptor (CAR) T cell therapy is a paradigm shifting modality for relapsed/refractory multiple myeloma (MM). Yet national scale delineation of immune effector toxicities, cardiopulmonary and renal sequelae, and economic burden across demographic and payer strata has not been adequately characterized. Methods: The National Inpatient Sample (2018–2022) was queried to identify adult MM hospitalizations receiving CAR T through ICD-10-PCS codes. Cytokine release syndrome (CRS) [all grades - 2021–2022], immune effector cell–associated neurotoxicity syndrome (ICANS) [all grades – 2022], cardiac events and infections were identified through ICD-10 codes. Age was stratified into 21-40, 41-60, 61-80, >81 years. Payer groups were Medicare, Medicaid, Private and Uninsured. Races were White, African American, Hispanic and others [Pacific Islanders, Native Indians, Asians]. Chi-square analysis was performed and multivariate regression adjusted for demographics, comorbidities and hospital characteristics. Results: Across >7,000 weighted hospitalizations, mortality, any grade CRS and ICANS were statistically similar across age, race, and payer (p>0.05). However, CRS was numerically higher in Hispanic patients (78.6%) than in White (63.2%), African American (68.1%), and other minor races (60.0%) (p=0.339). ICANS grade 4 was numerically higher in Hispanic (5.3%) versus White (0.8%) (p=0.278). Mortality was numerically highest in other minor races (9.5%) versus White (3.6%), Hispanic (2.8%), and African American (0.0%) (p=0.179). Age-stratified analyses showed significant heterogeneity in arrhythmias (22.2% [21–40 years] to 28.6% [≥81 years]; p=0.021), attenuating after adjustment. By race, arrhythmias ranged from 8.3% (Hispanic) to 25.0% (White) (p=0.113). Other cardiac events including myocardial infarction, stroke and cardiogenic shock were similar across groups. Payer stratified pneumonia varied (p=0.010) with uninsured 23.8% versus Private 5.1%, Medicare 7.3%, and Medicaid 6.4%, without persistence in adjusted models. Sepsis and septic shock rates showed no differences. Hispanic patients had higher adjusted costs versus White (Odds ratio [OR] 1.3, 1.04–1.7; p=0.023). Age-stratified costs differed (p=0.032), with elevated cost in ≥81 years (USD 394,617) versus 21–40 (USD 229,862), 41–60 (USD 214,974), and 61–80 (USD 269,844) but it was not significant in adjusted analysis. Conclusions: In this national cohort, CRS, ICANS and mortality were broadly stable across strata, while cardiac events displayed select divergences with elevated rates of arrhythmias among the elderly population suggesting robust cardiac surveillance in these patients. Cost differentials were evident with higher costs among Hispanic and elderly patients warranting validation in larger, prospectively harmonized datasets.
Competing risks of relapse and major organ failure after allogeneic hematopoietic cell transplantation.
e18579 Background: Outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) are often summarized using overall survival (OS) or treatment related mortality (TRM), which may obscure distinct biologic and toxicity driven pathways of failure. Major organ toxicities are important causes of morbidity and mortality but are rarely evaluated as competing events alongside relapse. We sought to characterize relapse and major organ failure as distinct competing pathways after allo-HCT. Methods: We analyzed adult allo-HCT recipients from the CIBMTR RT17-01 publicly available dataset (2008-2016). The primary endpoint was the first post transplant failure pathway, defined as relapse, major organ failure (MOF) requiring dialysis or diagnosed as thrombotic microangiopathy (TMA), veno-occlusive disease (VOD), or idiopathic pneumonia syndrome (IPS), or death without prior relapse or MOF. Competing risk methods estimated cumulative incidence, and cause specific Cox models evaluated associations between conditioning intensity and outcomes, adjusting for clinical and transplant related covariates, with the renal component of the hematopoietic cell transplantation comorbidity index (HCT-CI) removed. Results: The cohort included 13,187 adult recipients with a median age of 58.6 years, of whom 59.3 percent were male. Conditioning intensity was myeloablative (MAC) in 6,134 patients, reduced intensity (RIC) in 4,795, and non myeloablative (NMA) in 2,221. The first failure pathway was relapse in 5,157 patients, MOF in 1,511, and death without relapse or MOF in 2,535. At one year, cumulative incidence was 32.4 percent for relapse, 10.4 percent for MOF, and 13.1 percent for death without either event. IPS and dialysis requiring renal failure were the most frequent MOF events. Compared with MAC, RIC was associated with higher relapse risk (adjusted hazard ratio [aHR] 1.14; 95 percent confidence interval [CI] 1.07-1.23) and lower MOF risk (aHR 0.72; 95 percent CI 0.64-0.82). NMA conditioning showed a further shift toward relapse (aHR 1.42; 95 percent CI 1.30-1.54) with greater reduction in MOF risk (aHR 0.55; 95 percent CI 0.46-0.66). Conclusions: Relapse and MOF represent distinct competing pathways of failure after allo-HCT. Conditioning intensity influences which pathway predominates, with less intensive regimens shifting risk from organ toxicity toward relapse. Pathway based competing risk analyses provide insight beyond traditional survival endpoints and may support more individualized transplant decision making.
Real-world use of fruquintinib in refractory metastatic colorectal cancer in the United States.
e15713 Background: Fruquintinib demonstrated overall survival benefit in heavily pretreated metastatic colorectal cancer (mCRC) in FRESCO and FRESCO-2. The FDA approved fruquintinib on Nov 8, 2023 for adult patients with mCRC after standard chemotherapy plus anti-VEGF therapy, with anti-EGFR therapy when appropriate (e.g., RAS wild-type). Observed geographic variation in post-approval uptake suggests potential disparities in the delivery of evidence-based medicine across U.S. regions. Methods: We conducted a retrospective cohort study using Epic Cosmos, a database of over 300 million patient records from over 1,500 hospitals nationwide. We identified adults with metastatic colorectal cancer (mCRC) with prior standard systemic therapy exposure and recorded fruquintinib exposure following FDA approval beginning Nov 8, 2023. Fruquintinib uptake was analyzed by U.S. Census region and state, expressed as the proportion of eligible mCRC patients receiving fruquintinib within each geography. Results: Among 116,116 pre-treated mCRC patients, 6,722 (5.79%) had recorded fruquintinib exposure during the post-approval period. Uptake varied nearly five-fold across states (2.27%–11.33%) (Table). High-uptake states were disproportionately concentrated in the central U.S./Midwest, whereas multiple low-uptake states were observed in the West and Northeast, suggesting broader regional variation beyond state-to-state differences. Conclusions: In a large national EHR-derived cohort of pre-treated mCRC patients after U.S. approval, fruquintinib uptake demonstrated substantial geographic variation. These findings raise concern for inequities in delivery of evidence-based later-line therapy and highlight the need to identify modifiable system- and site-level drivers (e.g., access, referral patterns, treatment infrastructure) to promote equitable adoption. Fruquintinib uptake among eligible metastatic colorectal cancer patients by U.S. state. Rank Geography Eligible mCRC (N) Fruquintinib uptake (%) Overall Overall 116,116 5.79 Top 1 Oklahoma 1,236 11.33 2 Kansas 1,312 10.75 3 Indiana 2,448 10.70 4 Missouri 1,521 9.47 5 Connecticut 2,208 9.24 Bottom 1 Washington 1,232 2.27 2 Nevada 441 2.72 3 Rhode Island 476 2.73 4 Tennessee 1490 2.82 5 Maine 614 2.93 Fruquintinib uptake is reported as the proportion of eligible pre-treated metastatic colorectal cancer (mCRC) patients with recorded fruquintinib exposure following U.S. FDA approval. States are ranked by uptake percentage.
Differential clinical and economic signatures of CAR T-cell therapy in DLBCL across demographic and payer strata: A national analysis.
7064 Background: Chimeric antigen receptor (CAR) T cell therapy has revolutionized care for relapsed/refractory diffuse large B cell lymphoma (DLBCL), yet granular delineation of real-world immune effector toxicities, organ-specific sequelae and economic burden across demographic and socioeconomic strata requires further exploration. Methods: Using the National Inpatient Sample (2017–2022), we identified adult DLBCL hospitalizations receiving CAR T through ICD-10-PCS codes. Cytokine release syndrome (CRS) [all grades - 2021–2022], immune effector cell–associated neurotoxicity syndrome (ICANS) [all grades – 2022], infections, cardiac events and acute kidney injury (AKI) were identified through ICD-10 codes. Age was stratified into 21-40, 41-60, 61-80 and >81 years. Payer groups were Medicare, Medicaid, Private and Uninsured. Races were White, African American, Hispanic and others [Pacific Islanders, Native Indians, Asians]. Chi-square analysis was performed, and multivariate regression adjusted for demographics, comorbidities, and hospital characteristics. Results: Across >11,000 weighted hospitalizations, inpatient mortality, all-grade CRS and ICANS were comparable across age, race, and payer groups (p>0.05). Inpatient mortality was numerically higher in other minor races (6.6%) vs White (3.3%), African American (3.1%), and Hispanic (0.9%; p=0.230). Any grade CRS was numerically higher in other minor races (72.5%) than in White (62.3%) and African American (60.6%; p=0.614). Any grade ICANS dispersion included 29.5% (White), 39.1% (African American), 22.5% (Hispanic) and 11.1% (Other; p=0.204). A race-specific signal for ICANS grade 5 (p=0.030) was seen, but numbers were small. Among cardiac events, arrhythmias rose from 7.6% (age 21–40 years) to 57.1% ( age ≥81 years) (p<0.001). By payer, arrhythmias were highest in Medicare (31.2%; p<0.001). Other cardiac events including myocardial infarction, stroke and cardiogenic shock were similar across groups. Pneumonia rates varied by payer, peaking in the Uninsured (23.8%; p=0.010). Sepsis and septic shock rates showed no differences. AKI (p=0.007) rates showed differences but attenuated after adjustment. Hispanic and other minor races had lower adjusted costs than White (Odds ratio [OR] 0.9, p=0.046; OR 0.8, p=0.006), while ages 61–80 had higher adjusted costs vs 21–40 (OR 1.2, p=0.023). Conclusions: In this national cohort, CRS, ICANS and mortality were similar across demographic and payer strata, indicating consistent immune effector safety. Cardiac arrhythmia rates were higher among the elderly and Medicare beneficiaries. There were lower expenditures among minor race groups and higher costs in elderly. These findings highlight discrete domains of variability and suggest intensified cardiac surveillance in elderly and equitable resource allocation to optimize outcomes with CAR-T.
Pancreatic cancer incidence and survival in lean and obese adults with type 2 diabetes: A propensity matched analysis.
10576 Background: Type 2 diabetes mellitus (T2DM) and excess adiposity are independent risk factors for pancreatic cancer. Pancreatic cancer risk within T2DM across body-mass index (BMI) strata is heterogeneous in real-world cohorts and lean T2DM individuals may represent a distinct high risk phenotype. We compared pancreatic cancer incidence and post-diagnosis survival across BMI strata. Methods: We performed a retrospective comparative outcomes analysis using the TriNetX network. Adults with T2DM (HbA1c ≥6.5%) were categorized as obese (BMI ≥30 kg/m²) or lean (BMI <25 kg/m²). The lean cohort additionally excluded any patient with prior BMI of >25 kg/m² to control for cancer associated weight loss. The index event was first T2DM diagnosis, and outcomes were evaluated after a 365-day window. Patients with pancreatic cancer prior to the outcome window were excluded. Propensity score matching was done using the following parameters: age, sex, smoking status, pancreatitis, pancreatic cysts, chronic kidney disease, gallstones, family history of pancreatic cancer, and HbA1c. Outcomes assessed were incident pancreatic cancer over 10 years and all-cause mortality among patients with pancreatic cancer and T2DM. Results: Total number of patients in the obese group was 1,759,075 with mean age of 57 ± 13.4 years and in the lean cohort were 205,193 with a mean age of 61.8 ± 16.6 years. After propensity score matching, there were 204,086 patients in each group. Mean HbA1c levels were 7.4 ± 1.8% in the obese group and 7.9 ± 2.2% in the lean BMI group. The incidence of pancreatic cancer was 0.16% (n = 335) in obese patients as compared to 0.23% in lean (n = 478) patients with a risk difference of 0.07% (p <0.001). Obesity was associated with lower pancreatic cancer risk (RR 0.692, 95% CI 0.603–0.797; p < 0.001). In the subgroup analysis of patients diagnosed with pancreatic cancer, obese patients had longer median survival (1,109 vs 651 days) with HR 0.853 (95% CI 0.793 - 0.918; p <0.001). Conclusions: Lean adults with T2DM had a higher incidence of pancreatic cancer and worse post-diagnosis survival than obese patients. These results identify lean T2DM as a distinct high-risk phenotype and demonstrate that pancreatic cancer risk within T2DM is heterogeneous and not solely attributable to excess adiposity. Further investigation is needed to elucidate the biological mechanisms underlying this association and its implications for clinical risk assessment. Pancreatic cancer incidence and associated risk estimates among obese and lean adults with type 2 diabetes mellitus. Cohort Pancreatic cancer incidence RD RR Obese T2DM(n = 204,086) 0.16% (n = 335) 0.07% (95% CI: 0.04 - 0.10), p < 0.001 1.44 (95% CI: 1.25 - 1.66) Lean T2DM(n = 204,086) 0.23% (n = 478) Abbreviations: CI, confidence interval; RD, risk difference; RR, relative risk; T2DM, type 2 diabetes mellitus.
Influence of HIV status, age and ethnicity on survival in patients with burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL): A real-world nationwide database study
Abstract Introduction: BL and DLBCL are the two most common lymphomas associated with HIV infection. Notably, clinical trials often exclude HIV-positive patients and prior retrospective studies often lacked long-term follow-up on overall survival (OS). This has limited our knowledge about the influence of HIV status on survival in BL and DLBCL. Survival outcomes can also vary significantly across ethnic groups, influenced mostly by disparities in healthcare access and socioeconomic status. Additionally, survival rates differ among age groups, which may be attributed to tolerance to intensive chemotherapy and the presence of comorbid medical conditions. Our study primarily focused on comparing OS between HIV-positive and negative patients with DLBCL and BL in the real world. We also examined OS disparities among diverse ethnicities and age groups. Method: Patients diagnosed with DLBCL and BL were identified from the Cerner Health Facts database over five years from 2013 to 2018 using ICD-9 and ICD-10 codes. Within this cohort, individuals with a positive HIV status were identified through specific ICD-9 and ICD-10 codes. Demographic characteristics including age, gender, and ethnicity were collected for all patients, and they were stratified into distinct age groups: <20 years, 20-39 years, 40-59 years, 60-79 years, and 80+ years. OS was calculated for all patients from the time of diagnosis to time of death or hospice discharge. A multivariate cox regression model was employed to adjust for confounding variables. Results: The total number of patients diagnosed with DLBCL and BL was 10,534. Of these patients, 45.3% were female. The ethnic composition included 77% Caucasian, 10.3% African American and 12.7 % from other ethnicities. Among this population, 315 patients were HIV positive. In the cohort of DLBCL patients, 8,275 were HIV negative and 185 were HIV positive. In the cohort of BL patients, 1,944 were HIV negative and 130 were HIV positive. Among patients with DLBCL, HIV positive status had more than two-fold higher mortality rate compared to their HIV negative counterparts (HR=2.1, 95% CI 1.31 to 3.36, p=0.0018). Patients with BL who were HIV positive had no difference in OS in comparison to the HIV negative group (p=0.575). African American patients with DLBCL had almost 40% increased risk of mortality compared to Caucasian patients (HR=1.39, 95% CI 1.05-1.83, p=0.017). African American patients with BL had no difference in OS compared to Caucasian patients (p=0.3). Patients aged 60-79 years were found to have 44% higher risk of mortality compared to 40-59 age group (HR=1.44, 95% CI 1.13-1.83, p=0.0033) and patients aged 80 years or above were found to have more than two-fold higher risk of mortality in the DLBCL cohort (HR=2.16, 95% CI 1.63-2.87, p<0.0001). For patients with BL, those aged 20-39 had half the risk of mortality as compared to the 40-59 age group (HR= 0.50, 95% CI 0.28 - 0.87, p=0.014) whereas patients aged 80 or older had almost three times higher risk of mortality (HR = 2.87, 95% CI 1.81-4.57, p<0.0001). Conclusion: HIV status can significantly influence survival outcomes in patients diagnosed with DLBCL. Early identification of HIV infection, along with the initiation of prompt antiretroviral therapy and the administration of appropriate intensive chemotherapy regimens, is crucial for optimizing treatment outcomes in this patient population. Notably, our study indicates that African American patients exhibit a higher mortality rate compared to their Caucasian counterparts with DLBCL. This could be related to disparities in access to healthcare and treatment resources across different ethnicities. Moreover, it also indicates possible lymphoma biological heterogeneity in various ethnicities. Furthermore, elderly patients demonstrate increased mortality rates likely attributed to a greater prevalence of frailty, indicating the need for innovative less intense regimens for these patients with DLBCL and BL.
Digital Pulmonology Practice with Phonopulmography Leveraging Artificial Intelligence: Future Perspectives Using Dual Microwave Acoustic Sensing and Imaging
Respiratory disorders, being one of the leading causes of disability worldwide, account for constant evolution in management technologies, resulting in the incorporation of artificial intelligence (AI) in the recording and analysis of lung sounds to aid diagnosis in clinical pulmonology practice. Although lung sound auscultation is a common clinical practice, its use in diagnosis is limited due to its high variability and subjectivity. We review the origin of lung sounds, various auscultation and processing methods over the years and their clinical applications to understand the potential for a lung sound auscultation and analysis device. Respiratory sounds result from the intra-pulmonary collision of molecules contained in the air, leading to turbulent flow and subsequent sound production. These sounds have been recorded via an electronic stethoscope and analyzed using back-propagation neural networks, wavelet transform models, Gaussian mixture models and recently with machine learning and deep learning models with possible use in asthma, COVID-19, asbestosis and interstitial lung disease. The purpose of this review was to summarize lung sound physiology, recording technologies and diagnostics methods using AI for digital pulmonology practice. Future research and development in recording and analyzing respiratory sounds in real time could revolutionize clinical practice for both the patients and the healthcare personnel.
Applications of Microwaves in Medicine Leveraging Artificial Intelligence: Future Perspectives
Microwaves are non-ionizing electromagnetic radiation with waves of electrical and magnetic energy transmitted at different frequencies. They are widely used in various industries, including the food industry, telecommunications, weather forecasting, and in the field of medicine. Microwave applications in medicine are relatively a new field of growing interest, with a significant trend in healthcare research and development. The first application of microwaves in medicine dates to the 1980s in the treatment of cancer via ablation therapy; since then, their applications have been expanded. Significant advances have been made in reconstructing microwave data for imaging and sensing applications in the field of healthcare. Artificial intelligence (AI)-enabled microwave systems can be developed to augment healthcare, including clinical decision making, guiding treatment, and increasing resource-efficient facilities. An overview of recent developments in several areas of microwave applications in medicine, namely microwave imaging, dielectric spectroscopy for tissue classification, molecular diagnostics, telemetry, biohazard waste management, diagnostic pathology, biomedical sensor design, drug delivery, ablation treatment, and radiometry, are summarized. In this contribution, we outline the current literature regarding microwave applications and trends across the medical industry and how it sets a platform for creating AI-based microwave solutions for future advancements from both clinical and technical aspects to enhance patient care.