University of Wisconsin Hospital and Clinics

Flea-borne typhus (FBT) is an infection caused by the bacteria Rickettsia typhi. It is usually an acute undifferentiated febrile illness; however, approximately one-quarter of patients suffer from organ-specific complications. In the present report, the case of a 51-year-old woman who originally presented to the clinic with a febrile illness is described. After being given supportive care with intravenous fluids and antiemetics for presumed viral infection, she returned to the emergency department the next day in a hypotensive state and experiencing respiratory distress, requiring emergent intubation in the context of developing severe acute respiratory distress syndrome (ARDS). An initial chest computed tomography scan revealed diffuse ground-glass opacities with interlobular septal thickening. Bronchoalveolar lavage was performed, revealing acellular eosinophilic aggregates consistent with pulmonary alveolar proteinosis (PAP). The clinical context of her serology strongly supported the diagnosis of FBT. This case illustrates the critical care complexities associated with FBT, in addition to a previously undescribed finding, PAP, in rickettsial infections. The patient's rapid progression of life-threatening ARDS and multiorgan dysfunction highlights the need for the timely diagnosis and treatment of FBT.

Abstract Meningiomas are the most common primary brain tumors in adults. Although local control is often achievable with surgical resection and radiation therapy, patients with recurrent disease treated with prior radiotherapy (RT) have few options for salvage treatment. We investigate retrospectively whether pulsed-reduced dose rate RT (PRDR) is effective and well-tolerated in a cohort with recurrent meningioma treated with prior radiotherapy. We retrospectively identified 26 patients with recurrent meningioma treated with PRDR from 2003 to 2025 at a single institution. Acute and late toxicities were graded based on CTCAE 5.0. Radiographic progression was assessed using RECIST criteria. Cumulative incidence method with death as a competing risk was used to analyze local recurrence. The Kaplan-Meier method and Cox proportional hazards models were used for progression free survival (PFS), overall survival (OS), univariate, and multivariate analyses. Median time between RT courses was 7.5 years. Median age and Karnofsky Performance Status at the time of PRDR were 68 years old and 90, respectively. Median PRDR dose was 54 Gy in 27 fractions (range 37.5-64 Gy, 15-33 fractions). Median planning treatment volume was 207.4 cm3. Seven patients (27%) received a boost of 4 to 6.6 Gy to gross disease. PFS at 6 months was 77% and median PFS was 20.5 months. Eleven patients (42%) had in-field failure with a median follow up of 18 months. Eleven patients (42%) were still alive at last follow up. Median OS was 33 months. Four patients (15%) experienced grade ≥ 3 acute or late toxicities. PRDR resulted in a manageable toxicity profile and achieved PFS for a cohort of patients with meningioma previously treated with RT. Notably, the median PFS observed in this study compares favorably to a recent phase II trial evaluating radiopharmaceutical therapy for refractory meningioma.

Ambient artificial intelligence (AI) offers the potential to reduce documentation burden and improve efficiency through clinical note generation. Widespread adoption, however, remains limited due to challenges in electronic health record (EHR) integration, coding compliance, and real-world evaluation. This study introduces a framework and protocols to design, monitor, and deploy ambient AI within routine care. We launched an implementation phase to build technical workflows, establish governance, and inform a pragmatic randomized trial. A bidirectional governance model linked operations and research through multidisciplinary workgroups that incorporated the Systems Engineering Initiative for Patient Safety (SEIPS) framework. Integration into the EHR used Fast Healthcare Interoperability Resources (FHIR), and a real-time dashboard tracked utilization and documentation accuracy. To monitor drift, a difference-in-differences analysis was applied to three process metrics: time in notes, work outside work, and utilization. Audits of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) compliance were performed using an internally developed large language model (LLM), the validity of which was assessed through correlation with certified professional coders. Ambient AI utilization, measured as the proportion of eligible clinical notes completed using the system, had a weighted median of 65.4% (interquartile range, 50.6 to 84.0%). Iterative improvement cycles targeted task-specific adoption. A brief workflow issue related to a note template change initially reduced ICD-10 documentation accuracy from 79% (95% confidence interval [CI], 72 to 86%) to 35% (95% CI, 28 to 42%); accuracy returned to baseline after note template redesign and user training. The internally developed LLM coder achieved a strong correlation with professional coders (Pearson's r=0.97). The trial enrolled 66 providers across eight specialties, powered at 90% for the primary outcome of provider well-being. We provide a publicly available framework and protocols to help safely implement ambient AI in health care. Innovations include an embedded pragmatic trial design, human factors engineering, compliance-driven feedback loops, and real-time monitoring to support deployment, ensuring fidelity before initiation of the clinical trial. (Funded by the University of Wisconsin Hospital and Clinics and the National Institutes of Health Clinical and Translational Science Award; NIH/ NCATS UL1TR002737; ClinicalTrials.gov number, NCT06517082.).

BK polyomavirus (BKPyV) poses a significant threat to kidney transplant recipients (KTR). Current management primarily involves reducing immunosuppression, which increases the risk of rejection. Cell-based immunotherapy with virus-specific T cells (VST) has emerged as an alternative approach for treating BKPyV in KTRs. This single-center phase I, open-label trial enrolled KTRs with persistent BKPyV-DNAemia and BKPyV nephropathy (BKPyVAN) (NCT05042076) despite being on lower immunosuppression. BK-specific T cells were isolated from leukapheresis products from compatible donors. Patients were treated with VST therapy and followed for 52 weeks. Safety and tolerability were the primary focus of this trial. Three patients completed the trial. No grade III or IV adverse events, acute rejections, or graft versus host disease were reported. All patients tolerated the therapy well, with no significant safety concerns observed during the follow-up period. BK-VST demonstrated promising safety and tolerability profiles in this small cohort of kidney transplant recipients with severe BK infections. These findings suggest that VST therapy may offer a safe adjunctive treatment option for BKPyV infections post-transplantation. Larger studies are needed to confirm these preliminary results and assess long-term efficacy in treating BKPyV infections and preserving graft function in kidney transplant recipients.

BackgroundThe COVID-19 pandemic stressed antimicrobial stewardship (AMS) programs with increased workloads and lack of guidance on the treatment of COVID-19. Throughout the pandemic, COVID-19 patients have received antibiotics for this viral illness despite reported low rates of confirmed bacterial co-infections. The purpose of this study was to identify challenges to and strategies for successful antibiotic stewardship for COVID-19 inpatients.Part 1 of Table 1MethodsWe utilized the Premier Healthcare Database to identify hospitals with appropriate antibiotic prescribing before and maintained during the pandemic while facing significant COVID-19 patient burden. We conducted semi-structured interviews with pharmacists, physicians, and quality leaders involved in AMS during the pandemic. Interview guides were developed according to participants’ roles using the Systems Engineering Initiative for Patient Safety (SEIPS) framework. Interviews were recorded, transcribed, and analyzed iteratively using directed content analysis guided by the SEIPS model.Part 2 of Table 1ResultsWe conducted 30 interviews from 19 different high-performing health care systems across the country. We interviewed 17 pharmacists, 12 physicians and 1 nurse. The main challenges participants identified included lack of knowledge and formal guidance on how to treat COVID-19, feelings of helplessness, and diagnostic uncertainty. Strong, clear leadership from hospital leaders or infectious disease groups, organizational and national guidelines and clinical experience caring for COVID-19 helped providers overcome lack of knowledge, and guidelines on how to treat COVID-19 assuaged feelings of helplessness. Diagnostic tools including host response biomarkers (e.g. procalcitonin) and chest imaging were utilized and incorporated into workflows to help overcome diagnostic uncertainty and guide antibiotic prescribing.Part 3 of Table 1ConclusionSuccessful strategies for COVID-19 antibiotic stewardship included overcoming knowledge gaps with clear leadership from infectious disease teams and implementation of structured COVID-19 diagnostic and treatment guidelines.DisclosuresAll Authors: No reported disclosures

BackgroundTricuspid atresia (TA) is the second most common form of functionally univentricular heart. For patients with TA and normally related great arteries (Type I), left ventricular outflow tract obstruction (LVOTO) is rare.MethodsFrom the Congenital Heart Surgeons' Society multi-institutional cohort of 445 patients with Type I TA enrolled from 1999 to 2024 from 42 sites, 14 infants (3%) had interventions for associated LVOTO, either at presentation or after their first TA-related intervention.ResultsOf seven infants initially undergoing Norwood/Damus-Kaye-Stansel (DKS), six survived to Stage II, of whom five survived with one developing pulmonary hypertension and four achieving Fontan. An additional seven infants who were first managed with pulmonary artery band placement subsequently had bidirectional superior cavopulmonary anastomosis (BCPA) and a DKS procedure; there were six survivors, all achieving Fontan. All ten survivors who underwent the Fontan procedure had normal left ventricular and mitral valve function at the latest follow-up. The overall Kaplan-Meier survival estimate at 20 years for these 14 patients was 79% (70% CI, 66%-88%), and the median follow-up was 8.3 years (0.24-21.5).ConclusionsWhile infants with TA and transposition of the great arteries are more likely to have LVOTO, this can also occur in the setting of normally related great arteries. Infants with Type I TA and LVOTO can be managed in the neonatal period with the Norwood procedure ensuring complete arch relief with acceptable outcomes. If LVOTO becomes evident after initial pulmonary artery band placement, a subsequent DKS procedure facilitates satisfactory success to Fontan.