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Background After an increase of central line–associated bloodstream infections (CLABSIs) at our community hospital in 2021, a case-control study suggested that patients with CLABSIs were 3.0 times more likely to have missed daily chlorhexidine gluconate (CHG) bathing than patients without CLABSIs. Objective To increase the rate of daily CHG bathing in hospitalized patients with central lines and subsequently reduce the number of CLABSIs. Methods Our pre-post intervention was launched on September 2022 and consisted of enhancements to the electronic health record (EHR) to simplify the identification of overdue CHG bathing instances to increase compliance, and therefore decrease the CLABSI rate at our hospital. A workflow was implemented Monday–Friday utilizing these EHR enhancements for active surveillance to engage frontline nursing staff and address gaps in care in real time. Results After the initiative was implemented, adherence to daily CHG bathing increased from 94.9% to 95.3%, with a considerable disparity between weekdays (97.6%) and weekends (89.3%). After weekend data were excluded, the post-intervention increase in the adherence rate was statistically significant ( p = .003). Discussion This initiative underscored the importance of involving health care informatics partners and showed how technology can bridge gaps in health care quality. Outreach and reminders effectively improved CHG bathing adherence by emphasizing the importance of consistent communication and follow-up.

Background: Glioblastoma IDH-wildtype (GBM IDH-wt) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping its tumor microenvironment (TME) regulate tumor progression and treatment response. The aim of this study was to characterize the main immunosuppressive elements of the GBM IDH-wt TME. Methods: Immunohistochemistry for CD3, CD4, CD8, CD163, programmed death ligand 1 (PD-L1) and programmed death 1 (PD1) was performed on surgical tumor specimens from patients diagnosed with GBM IDH-wt, according to the CNS WHO 2021 criteria. The impact of categorical variables on time-dependent outcomes such as overall survival (OS) and progression-free survival (PFS) has been estimated through the Kaplan–Meier method. Results: We included 30 patients (19 males and 11 females), median age of 59.8 years (range 40.2–69.1 years). All patients underwent surgery followed by temozolomide concurrent with and adjuvant to radiotherapy. MGMT was methylated in 14 patients (47%) and unmethylated in 16 patients (53%). The overall absolute percentages of CD4+ lymphocytes, both intratumoral and perivascular, were significantly more represented than CD8+ lymphocytes in the TME (p = 0.02). A low density of CD4+ lymphocytes (≤10%) was found to be a favorable prognostic factor for GBM outcome (p = 0.02). Patients with MGMT methylated and unmethylated tumors exhibited a distinct TME composition, with a significant higher number of perivascular CD8+ lymphocytes (p = 0.002), intratumoral CD8+ lymphocytes (p = 0.0024) and perivascular CD4+ lymphocytes (p = 0.014) in MGMT unmethylated tumors. PD-L1 expression in tumor cell surface was observed in four tumors (13.3%), and PD1 expression in infiltrating T lymphocytes was observed in nine (30%) tumors, with predominantly perivascular distribution. Conclusions: MGMT methylated and unmethylated tumors exhibit different immune profiles, likely reflecting the different biology of these tumors. The expression of PD-L1 in GBM IDH-wt patients is confined to a small subpopulation. While we found a significant association between low CD4+ lymphocyte density (≤10%) and survival, given the small numbers of our cohort, the prognostic value of CD4+ lymphocyte density will need to be validated in large-scale studies.

Abstract INTRODUCTION A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β‐amyloid (Aβ) and tau PET image data across multiple scanners and tracers. METHODS We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B‐PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre‐processing, refacing, magnetic resonance imaging (MRI)/PET co‐registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers. RESULTS Measurements from 10,105 cross‐sectional and longitudinal Aβ and tau PET scans acquired in several studies between 2010 and 2024 can be processed, harmonized, and directly merged across tracers and cohorts. DISCUSSION The B‐PIP developed in ADNI is a scalable image harmonization approach used in several observational studies and clinical trials that facilitates rigorous Aβ and tau PET quantification and data sharing. Highlights Quantitative results from ADNI Aβ and tau PET data are generated using a rigorous, scalable image processing pipeline This pipeline has been applied to PET data from several other large, multisite studies and trials Quantitative outcomes are harmonizable across studies and are shared with the scientific community

Abstract Objective An accurate evaluation of behavioral responsiveness during and after seizures in people with epilepsy is critical for diagnosis and management. Current methods for assessing behavioral responsiveness are characterized by substantial variation, subjectivity, and limited reliability and reproducibility in ambulatory and epilepsy monitoring unit settings. In this study, we aimed to develop and implement a novel mobile platform for deployment of automated responsiveness testing in epilepsy—the ARTiE Watch—to facilitate standardized, objective assessments of behavioral responsiveness during and after seizures. Methods We prospectively recruited patients admitted to the epilepsy monitoring units for diagnostic evaluation and long‐term video‐electroencephalographic monitoring at Mayo Clinic and Yale New Haven Hospital. Participants wore the ARTiE Watch, a smartwatch paired with custom smartphone software integrated with cloud infrastructure allowing for remote activation of standardized assessment on the participants' smartwatches. The assessment consisted of 18 command prompts that test behavioral responsiveness across motor, language, and memory domains. Upon visually identifying an electrographic seizure during EMU monitoring, the BrainRISE platform was used to deploy the ARTiE Watch behavioral testing sequence. Responsiveness scoring was conducted on smartwatch files. Results Eighteen of 56 participants had a total of 39 electrographic seizures assessed with the ARTiE Watch. The 18 subjects with ARTiE Watch‐tested seizures had a total of 67 baseline (interictal) ARTiE Watch tests collected for analysis. The analysis showed distinct ARTiE Watch behavioral responsiveness phenotypes: (1) decreased responsiveness across all ARTiE Watch commands during seizure (ictal–postictal) periods compared (to baseline ( p < .0001), (2) decreased responsiveness in bilateral tonic–clonic seizures compared to baseline ( p < .0001) and compared to focal seizures ( p < .0001), and (3) decreased responsiveness during focal impaired awareness seizures compared to baseline ( p < .0001) and compared to focal aware seizures ( p < .001). Significance ARTiE Watch behavioral testing deployed utilizing a mobile cloud‐based platform is feasible and can provide standardized, objective behavioral responsiveness assessments during seizures.

Abstract Ataxia Telangiectasia–mutated (ATM) inhibitors are being developed as radiosensitizers to improve the antitumor effects of radiotherapy, but ATM inhibition can also radiosensitize normal tissues. Therefore, understanding the elevated risk of normal tissue toxicities is critical for radiosensitizer development. This study focused on modeling the relationship between acute mucosal toxicity, radiation dose, fractionation schedule, and radiosensitizer exposure. The ATM inhibitor WSD0628 was combined with single or fractionated doses of radiation delivered to the oral cavity or esophagus of Friend Leukemia virus B (FVB) mice. The potentiation by WSD0628 was quantified by a sensitizer enhancement ratio (SER), which describes the changes in radiation tolerance for radiation combined with WSD0628 relative to radiation-only regimens. WSD0628 profoundly enhanced radiation-induced acute oral and esophageal toxicities. For oral mucosal toxicity, the enhancement by WSD0628 with 3 fractions of radiation resulted in an SER ranging from 1.3 (0.25 mg/kg) to 3.1 (7.5 mg/kg). For the 7.5 mg/kg combination, the SER increased with increasing number of fractions from 2.2 (1 fraction) to 4.3 (7 fractions) for oral toxicity and from 2.2 (1 fraction) to 3.6 (3 fractions) for esophageal toxicity, which reflects a loss of the normal tissue sparing benefit of fractionated radiation. These findings were used to develop a modified biologically effective dose model to determine alternative radiation schedules with or without WSD0628 that result in similar levels of toxicity. Successful radiosensitizer dose escalation to a maximally effective therapeutic dose will require careful deliberation of tumor site and reduction of radiation dose volume limits for organs at risk.

Background To evaluate the benefit-risk assessment of atogepant and calcitonin gene–related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population. Methods The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab. Results In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1–6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (−1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo. Conclusions Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses.

We report a patient who presented clinically with progressive supranuclear palsy (PSP) but was pathologically diagnosed as having primary lateral sclerosis (PLS) with magnetic resonance imaging (MRI) with a quantitative susceptibility mapping (QSM) protocol. A 70‐year‐old man was clinically diagnosed with PSP due to early falls and unresponsiveness to levodopa therapy. Postmortem pathological examination revealed mild loss of Betz cells, gliosis, and transactive response DNA binding protein of 43 kDa (TDP‐43)‐positive inclusions in the motor cortex, leading to the pathological diagnosis of PLS. To explore methods for differentiating PLS from PSP, ante‐mortem QSM images were visually and quantitatively assessed for abnormal increases in magnetic susceptibility in the motor cortex. Prussian blue and Luxol fast blue combined with periodic acid‐Schiff staining were also performed to understand the source of the susceptibility increases. QSM showed clear hyperintense signals in the motor cortex. Magnetic susceptibility in the motor cortex was higher in the PLS patient (Z = 4.7, p < 0.001) compared to normal controls and pathologically diagnosed PSP patients. Pathological examination of the region showed intracortical myelin loss, as well as iron deposition. Underlying pathological processes for the increased magnetic susceptibility include not only iron deposition but also intracortical myelin. Our case suggests that QSM is a potential tool to differentiate PLS from PSP, providing insights for accurate diagnosis and enhancing clinical decision‐making.

Background A multidisciplinary approach improves guideline‐directed medical therapy in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis is unreported. Methods and Results In a retrospective cohort study, we reviewed 848 patients from our institutional cardiac sarcoidosis clinics, identifying those with a cardiac sarcoidosis diagnosis, HF (left ventricular ejection fraction <50%) at index evaluation, and echocardiograms within 90 days and 11 to 36 months. Patients were stratified by participation in a pharmacist‐led medication therapy management (MTM) program for guideline‐directed medical therapy optimization (MTM versus non‐MTM [NMTM]) without randomization. Demographics, left ventricular ejection fraction, guideline‐directed medical therapy (quantified by Kansas City Medical Optimization score), and immunosuppressive therapy were assessed. Primary outcomes included changes in Kansas City Medical Optimization score, left ventricular ejection fraction, and cardiovascular event–free survival (unplanned HF hospitalization, left ventricular assist device /heart transplant, or death). The final cohort included 111 patients (median age, 57 years; 34% women; 64% New York Heart Association class I–II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean Kansas City Medical Optimization score was similar at index evaluation (MTM, 23.2; NMTM, 29.6; P =0.83). At follow‐up (median, 16 months), the Kansas City Medical Optimization score increased significantly in both groups (MTM, 23.2 to 74.8; P <0.001; NMTM, 29.6 to 58.7; P <0.001) but was higher in MTM ( P =0.001). Mean left ventricular ejection fraction trended toward higher values in MTM (44.4% versus 40.0%, P =0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (hazard ratio, 11.97 [95% CI, 1.58–90.54]; P =0.002). Conclusions In this retrospective cohort study, a pharmacist‐led MTM program was associated with favorable guideline‐directed medical therapy optimization and lower risk of adverse cardiovascular outcomes in patients with cardiac sarcoidosis with HF.

AbstractObjectiveTo describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti‐Hu) autoimmunity.MethodsA retrospective review of patients with ANNA1‐IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP‐Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.ResultsOf 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (p < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (p < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP‐Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240–289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long‐term outcomes.InterpretationYoung adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long‐term outcomes in ANNA1 autoimmunity.

Abstract OBJECTIVES Safety, efficacy and durability are important considerations when selecting a bioprosthesis for aortic valve replacement (AVR). This study assessed 7-year clinical outcomes and haemodynamic performance of the Avalus bioprosthesis. METHODS Patients indicated for surgical AVR were enrolled in this prospective, nonrandomized trial, conducted across 39 sites globally. The primary end-point of this analysis was freedom from surgical explant or percutaneous valve-in-valve reintervention due to structural valve deterioration (SVD) at 7 years of follow-up, determined using Kaplan–Meier (KM) analysis. We also evaluated a composite end-point of SVD and/or severe haemodynamic dysfunction requiring reintervention. Survival, valve-related safety events and haemodynamic performance were assessed. Deaths and safety events were adjudicated by an independent clinical events committee. RESULTS A total of 1132 patients underwent surgical AVR. Mean age was 70 years; 854 patients (75%) were men. The mean STS risk of mortality was 2.0 ± 1.4%, and 659 patients (58%) had a New York Heart Association classification of I/II. One or more concomitant procedures were performed in 577 patients (51%). At 7 years, the Kaplan–Meier rate of freedom from SVD/severe haemodynamic dysfunction requiring reintervention was 1.2% (0.5–2.5%) with no cases adjudicated as SVD. The survival rate was 82.6% (79.5–85.0%). The KM event rate was 5.7% (4.3–7.7%) for reintervention, 6.3% (4.9–8.3%) for endocarditis and 0.4% (0.1–1.1%) for valve thrombosis. Mean aortic gradient, dimensionless velocity index and effective orifice area were 13.8 ± 5.9 mmHg, 0.42 ± 0.09 and 1.99 ± 0.53 cm2, respectively. CONCLUSIONS This analysis demonstrated excellent durability of the Avalus valve with good clinical outcomes and stable haemodynamic performance through 7 years of follow-up.