Tampa General Hospital

Systolic blood pressure (SBP) variability has been associated with an increase in rates of death or disability in patients with intracerebral hemorrhage (ICH). We analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 trial to determine whether the association between SBP variability and death or disability at 90days is dependent on the time from randomization. The difference between maximum and minimum SBP (hourly SBP range) for the first 24h after enrollment was used to calculate the hourly SBP variability. The effect of hourly SBP variability was evaluated in logistic regression models on: (1) death or disability (modified Rankin scale score of 4-6 at 90days), (2) hematoma expansion (increase of > 33% in volume on the computed tomography scan obtained at 24h) within 24h, (3) neurological deterioration within 24h, and (4) acute kidney injury within 72h after enrollment. We adjusted for age, baseline Glasgow Coma Scale score, intraventricular hemorrhage, hematoma volume, and maximum SBP values for each time window. A total of 961 patients (mean age ± standard deviation [SD], 62 ± 13years; 61.9% were men) who were enrolled at a mean ± SD time of 184 ± 56min from symptom onset were analyzed. The mean ± SD hourly SBP variability was 15.6 ± 16mm Hg. The hourly SBP variability became significantly lower with increasing time intervals from randomization (ranging from 41.8 ± 23.3 at hour 1 to 12.4 ± 14.0 at hour 24, P < 0.0001). SBP variability at five hours (P = 0.014) and six hours (P = 0.014) after enrollment was significantly associated with death or disability at 90days, with positive but not statistically significant associations observed at all other points up to eight hours after randomization. Risk of neurological deterioration within 24h was highly associated with SBP variability, with the largest association observed between one (P < 0.001) and five (P < 0.001) hours following randomization, with significant associations observed up to 22h following randomization. Risk of hematoma expansion was associated with SBP variability between three (P = 0.015) and eight (P = 0.002) hours after randomization. Statistically significant associations between SPB variability and risk of acute kidney injury were not observed. Reduced SBP variability within the first eight hours following randomization appears most impactful on both short-term and long-term outcomes in patients with ICH, and the first eight hours may represent a time window for future interventions directed at reducing SBP variability in patients with ICH.

The lung virome (LV) and its interactions with the host-immune system leading to allograft injury after lung transplantation are not well characterized. Shotgun metagenomics and qPCR was performed on a multicenter BAL/serum cohort from lung transplant recipients (LTRs). Viral constructs from betatorquevirus clade and group 2 TTVs were transfected in primary bronchial epithelial cells (PBECs) or airways of C57BL/6 mice with and without exposure to Influenza A (IAV) or RSV. LV in LTRs was dominated by viruses from the family Anelloviridae. CLAD LV was characterized by the enrichment of betatorquevirus clade (BTV). Validation in an independent cohort confirmed BTV abundance in CLAD BAL, serum and lung tissues. BTV ORF1 protein (kV1) suppressed PBEC IFNα and IFNγ responses by preventing intranuclear STAT translocation. Co-culture of IAV or RSV in kV1 transfected PBECs significantly augmented replication of RSV and IAV and increased cellular injury. Likewise, in-vivo transfection of kV1 increased replication and lung injury associated with IAV. Our work illuminates a novel virus-associated dysregulation of host interferon responses that promote lung injury associated with respiratory viral infections and, in part, explain differential host responses to viral infections after lung transplantation.

Introduction: Fibrinolytic therapy with alteplase or tenecteplase (TNK) within 4.5 hours of symptom onset of acute ischemic stroke (AIS) improves functional outcomes and reduces long-term morbidity and mortality, but with increased risk of major bleeding. We sought to compare the safety and efficacy of alteplase and TNK for AIS. Methods: Retrospective, observational, study of adult AIS patients who received alteplase or TNK from May 2020-June 2024. Patients were included if either fibrinolytic was given within 4.5 hours of symptom onset. Extended/wake-up stroke protocol patients were excluded. Primary outcome was incidence of symptomatic ICH (sICH) (National Institutes of Health Stroke Scale [NIHSS] change ≥ 4 and bleeding on computed tomography [CT] scan). Secondary outcomes were occurrence of major and minor bleeding, change in NIHSS score, hospital length of stay (LOS), and in-hospital mortality. Continuous data were analyzed using Mann Whitney U test and categorical data using Chi squared or Fisher’s Exact tests, as appropriate. Results: A total of 479 patients were included; 224 alteplase (46.8%), 255 TNK (53.2%), median age 72 years (IQR 61-83), 53% male. Most patients had minor strokes (55%; NIHSS < 7) and received fibrinolytic in the emergency room (76%). More patients in the TNK group had a large vessel occlusion (26.8% vs. 36.8%). There were numerically more sICH and other major bleeding events in the TNK group; 4.5% vs. 6.7%, p=0.33 and 14.3% vs. 19.2%, p=0.16, respectively, although not statistically significant. There were no differences in minor bleeding events (3.5% vs. 6.7%), change in NIHSS score from admission to discharge (-4 vs -4), hospital LOS (4 days vs. 3 days), or in-hospital mortality (7.8% vs. 7.1%) between alteplase and TNK, respectively. Conclusions: There were no statistically significant differences in safety or efficacy outcomes between alteplase and TNK use for patients with AIS. These results provide real-world experience in a large, older population, with minor stroke. It is possible type II error may be limiting these findings. Additional research is needed to identify patient or stroke related factors that may increase bleeding occurrence and further evaluate if a statistically significant increased risk of bleeding exists with one agent in the real-world AIS population.

Introduction: Current guidelines for management of agitation/sedation in adult intensive care unit (ICU) patients recommend dexmedetomidine (DEX) as a preferred agent for light sedation in critically ill, ventilated patients. However, prolonged administration of DEX may lead to withdrawal upon cessation. Guanfacine, an alpha-2-adrenergic agonist, is used off-label to facilitate DEX weaning or discontinuation. Limited studies exist regarding the efficacy and safety of guanfacine for this use. This study aims to evaluate whether guanfacine reduced the total duration of DEX therapy in comparison to patients who were on DEX alone. Methods: This retrospective, single-center cohort study included adult patients admitted to an ICU and received DEX alone or in combination with guanfacine for a minimum of 24 hrs from January 2023 to October 2023. The primary outcome was the total duration of DEX therapy. Secondary outcomes included improvements in the Intensive Care Delirium Screening Checklist (ICDSC) score (evaluated 24 hrs pre- and 72 hrs post- guanfacine initiation), hospital and ICU length of stay (LOS), and incidence of adverse events. Results: A total of 120 patients were included, with 60 patients in each group. The mean duration of DEX therapy was significantly longer in the guanfacine group compared to the DEX only group (189 hrs vs 81 hrs, respectively; p< 0.00001). At DEX discontinuation the mean dose of guanfacine was 2.2 mg. DEX was restarted less frequently in the DEX only group (5%) compared to the guanfacine group (11.7%; p=0.32). Mean hospital LOS was 37 days in the guanfacine group versus 31 days in the DEX only group (p=0.07), while ICU LOS averaged 21 days versus 14 days, respectively (p=0.001). The incidence of hypotension was lower in the guanfacine group (47%) than the DEX only group (68%; p=0.02). Bradycardia occurred in 5% of patients in both groups (p=1). Among patients with pre- and post- ICDSC scores, improvement was observed in 55% of the guanfacine group versus 48% of the DEX only group (p=0.55). Conclusions: Our study found that patients who received guanfacine with DEX had statistically significant longer durations of DEX therapy and ICU LOS compared to those who received DEX alone. Further prospective studies are warranted to define guanfacine’s role in sedative weaning.

BackgroundHansen’s disease (HD, leprosy), caused by Mycobacterium leprae and M. lepromatosis, remains endemic in parts of the southeastern United States with increasing incidence in Florida. In 2023, Florida accounted for 23 of 225 U.S. cases. The nine-banded armadillo is a known reservoir for M. leprae with mounting evidence of its role in transmission. M. leprae has also shown viability in soil, prompting examination of environmental exposures. Therefore, we aimed to explore environmental exposures in those with HD versus household contactsTable 1.Demographic Characteristics of Index Cases & ContactsTable 2.Environmental Exposures for Index Cases & ContactsMethodsWe recruited participants from private dermatology clinics in East/Central Florida. Eligible individuals included those diagnosed with HD in the past 10 years and household contacts who lived with them for at least 6 months prior to diagnosis and treatment. Structured questionnaires were administered to collect data on age, sex, residence history, travel, and environmental exposure, including soil and armadillo contact.ResultsWe enrolled 36 individuals: 24 with HD and 12 household contacts without HD. Participants had a median age of 72 (53, 92); 20 (55%) were female. All individuals were U.S. born or were residents for 50+ years. 19 (79%) index cases and 3 (27%). Contacts reported regular soil contact (p=0.003). 16 (67%) index cases and 4 (36%) contacts reported gardening (p=0.07). 5 (21%) index cases and 2 (18%) contacts reported touching armadillos (p=0.6), 3 (13%) index cases and 2 (18%) contacts reported trapping them (p=0.5), and 2 (8.3%) index cases reported hunting them (p=0.4). 1 contact (8.3%) reported travel to a high-risk country for HD (p=0.3).ConclusionThis study showed frequent exposure to soil in those with HD that statistically differed from contacts. Typical risk factors like travel to, foreign residence in, or immigration from risk areas were absent. Armadillo contact did not differ greatly between cases and contacts, suggesting that the environmental route may be important in the epidemiologic triangle between humans and armadillos. Considering the ongoing detection of HD in Florida, particularly in East/Central Florida, future studies should continue to elucidate the role of contact with animal and environmental exposures in transmission.DisclosuresAll Authors: No reported disclosures

Background and Objectives: Type 2 diabetes mellitus (T2DM) affects over 537 million adults worldwide and disproportionately burdens low- and middle-income countries, where diagnostic resources are limited. Predictive models trained in one population often fail to generalize across regions due to shifts in feature distributions and measurement practices, hindering scalable screening efforts. Materials and Methods: We evaluated a few-shot domain adaptation framework using a simple multilayer perceptron with four shared clinical features (age, body mass index, mean arterial pressure, and plasma glucose) across three adult cohorts: Bangladesh (n = 5288), Iraq (n = 662), and the Pima Indian dataset (n = 768). For each of the six source-target pairs, we pre-trained on the source cohort and then fine-tuned on 1, 5, 10, and 20% of the labeled target examples, reserving the remaining for testing; a final 20% few-shot version was compared with threshold tuning. Discrimination and calibration performance metrics were used before and after adaptation. SHAP explainability analyses quantified shifts in feature importance and decision thresholds. Results: Several source → target transfers produced zero true positives under the strict source-only baseline at a fixed 0.5 decision threshold (e.g., Bangladesh → Pima F1 = 0.00, 0/268 diabetics detected). Few-shot fine-tuning restored non-zero recall in all such cases, with F1 improvements up to +0.63 and precision–recall gains in every zero-baseline transfer. In directions with moderate baseline performance (e.g., Bangladesh → Iraq, Iraq → Pima, Pima → Iraq), 20% few-shot adaptation with threshold tuning improved AUROC by +0.01 to +0.14 and accuracy by +4 to +17 percentage points while reducing Brier scores by up to 0.14 and ECE by approximately 30–80% (suggesting improved calibration). All but one transfer (Iraq → Bangladesh) demonstrated statistically significant improvement by McNemar’s test (p < 0.001). SHAP analyses revealed population-specific threshold shifts: glucose inflection points ranged from ~120 mg/dL in Pima to ~150 mg/dL in Iraq, and the importance of BMI rose in Pima-targeted adaptations. Conclusions: Leveraging as few as 5–20% of local labels, few-shot domain adaptation enhances cross-population T2DM risk prediction using only routinely available features. This scalable, interpretable approach can democratize preventive screening in diverse, resource-constrained settings.

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