Citations

Background Acute kidney injury (AKI) is associated with high morbidity and mortality in critically ill patients. Multicenter analyses describing the epidemiology of AKI in the cardiac intensive care unit (CICU) are scarce. Here, we describe the prevalence, predictors, and outcomes associated with AKI in a contemporary multicenter CICU population. Methods The Critical Care Cardiology Trials Network (CCCTN) is a collaboration of CICUs in North America coordinated by the TIMI Study Group (Boston, MA). We evaluated patient and hospital-level outcomes as a function of creatinine-only Kidney Disease: Improving Global Outcomes (KDIGO) AKI stage within the CCCTN registry. Logistic regression was used to assess associations with in-hospital mortality. Results Among 21 603 admissions, the overall prevalence of AKI was 23.7%, which was composed of KDIGO stage 1: 12.7%, stage 2: 1.7%, and stage 3: 9.2%. A higher prevalence and severity of AKI were seen in patients with baseline kidney disease, hypertension, or diabetes and in admissions with heart failure, cardiogenic shock, and cardiac arrest ( P < .001 for all). There was a stepwise increase in hospital mortality across AKI stages (stage 1: 23%, stage 2: 39%, stage 3: 42%; P < .0001). The increased risk of death associated with progressive AKI stage persisted after multivariate adjustment (adjusted OR: stage 1: 2.1, stage 2: 3.7, stage 3: 3.4). Conclusions AKI occurs in 1 in 4 admissions to the CICU, and a higher AKI stage is incrementally associated with in-hospital mortality, highlighting a need to develop strategies to mitigate AKI and its complications.

Abstract Objectives The study aimed to compare long-term outcomes of the David and Yacoub valve-sparing aortic root replacement (VSARR) procedures in a nationwide, low-volume setting. Methods All patients undergoing elective VSARR in Denmark between January 2010 and April 2022 were identified using the Danish registries. The primary end-point was all-cause death. Secondary end-points included stroke, reoperation, a composite of death or reoperation, and long-term echocardiographic outcomes. Analyses were performed in both crude and propensity score-matched (PSM) populations and compared with outcomes from a control group comprised of all elective composite root replacement procedures performed at the contributing centres in the study period. Results A total of 160 patients underwent VSARR (median age; David vs Yacoub; 49.7 [SD 14.1] years vs 51.5 [SD 14.3] years; P = .42) with the David (n = 92, 57.5%; median follow-up 8.2 [SD 3.6] years) or Yacoub (n = 68, 42.5%; median follow-up 7.1 [SD 2.4] years) procedure. Ten-year all-cause death was similar (David 9.3% [95% CI: 2.3-15.2] vs Yacoub 8.8% [95% CI: 3.6-20.6]; log-rank P = .54). Reoperation rates (log-rank P = .12), stroke incidence (P = .41), and the composite end-point of death or reoperation (log-rank P = .63) were comparable, with consistent findings in the PSM cohort. Long-term echocardiographic follow-up demonstrated no difference in recurrent regurgitation, stenosis, or valve-related complications. Compared to elective composite root replacement (CRR) (n = 486), VSARR demonstrated lower rate of all-cause death (P = .027) and stroke (P = .026), while reoperation rate was higher (13.8% vs 4.3%; P &lt; .001). However, the risk of reoperation was comparable between procedures when accounting for competing risk of death (log-rank P = .17). Conclusions Long-term outcomes following elective VSARR using the David and Yacoub procedure were comparable. VSARR was associated with lower risk of all-cause death and stroke compared to elective CRR, supporting the two VSARR procedures as durable options when performed in experienced centres with careful patient selection, even in low-volume settings.

Objective We investigated potential racial disparities in the effects of audiometric hearing loss and its treatment on dementia and mortality among 3,602 older adults aged 68–89 years, 22% of whom were self-identified Black race. Methods Adjudicated all-cause dementia was determined using neurocognitive test data, proxy reports, and surveillance of hospital records and death certificates. Audiometric hearing loss, defined as the better-ear averaged pure-tone threshold (0.5–4 kHz), was categorized using clinical cutpoints. Multivariable-adjusted Cox proportional hazards models included hearing loss–race interaction terms. Results Dementia risk associated with moderate-to-severe hearing loss did not differ by race [Black participants: hazard ratio (HR): 1.66; 95% confidence interval (CI): 1.05, 2.61; White participants: HR: 1.71; 95% CI: 1.16, 2.51; P -interaction = 0.92]. However, moderate-to-severe hearing loss was associated with a 2.3-fold increase in mortality among Black participants only (95% CI: 1.17, 4.60). Conclusions Our findings emphasize the importance of including minoritized populations in hearing treatment research to build an evidence base for policy development and clinical decision-making. Hearing loss affects the health of both Black and White Americans. Racial disparities in hearing healthcare should be addressed to advance health equity for all older adults.

Abstract Background Recently, a posterior pathway for fluid drainage from the retina to the meningeal lymphatics in the optic nerve (ON) sheath was identified in rodents using intravitreal imaging tracers directly injected into the ocular-globe. Fluid and solute clearance along this pathway may be associated with many diseases. However, intravitreal tracers are rarely used in clinical imaging. As intravenous Gadolinium-based-contrast-agent (GBCA) can enter the globe via the blood-ocular-barriers, it may provide an alternative approach to image this pathway. Purpose To establish a clinically feasible intravenous GBCA-based MRI approach for tracking fluid and solute transport along the posterior lymphatic pathway in the ocular glymphatic system. Materials&Methods This prospective study was conducted from March 2021 to September 2022 in healthy participants. Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed before, immediately and 4 hours after intravenous-GBCA administration to track GBCA distribution in aqueous humor (AH) and cerebrospinal fluid (CSF) in regions-of-interest (ROIs) in the globe (anterior-cavity, vitreous-body), in the intraorbital and extraorbital ON, and in the intracranial CSF space proximal to the ON (chiasmatic-cistern, interpeduncular-cistern). Kruskal–Wallis tests with post-hoc Dunn’s tests were used for group comparisons. Results Sixteen healthy participants (mean age±SD: 51±21 years, 5 men) were recruited. Intravenous-GBCA enhancement was observed in all ROIs immediately after injection. At 4-hour-post-GBCA, the vitreous body showed a trend of smaller enhancement area (55±11% versus 49±11%, P =.14) and lower GBCA-concentration (0.044±0.014 versus 0.028±0.010 mmol/L, P =.07) compared to immediate-post-GBCA. The intraorbital ON showed more widespread enhancement (39±5% versus 59±6%, P =.01) and significantly higher GBCA-concentration (0.023±0.009 versus 0.059±0.015 mmol/L, P <.001) at 4-hour-post-GBCA. Conclusion Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-GBCAs entering the globe via the blood-ocular-barriers using cDSC-MRI. Summary Statement Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-Gadolinium-based-contrast-agents entering ocular-globe via blood-ocular-barriers using dynamic-susceptibility-contrast-in-the-CSF (cDSC)-MRI. Key Results In this prospective study of sixteen participants, Gadolinium-based-contrast-agent (GBCA)-induced signal changes were detected in the aqueous-humor and cerebrospinal fluid immediately following intravenous administration using dynamic-susceptibility-contrast-in-the-CSF (cDSC)-MRI. At 4-hour-post-GBCA, the vitreous-body showed a trend of smaller enhancement area (55±11% versus 49±11%, P =.14) and lower GBCA-concentration (0.044±0.014 versus 0.028±0.010 mmol/L, P =.07) compared to immediate-post-GBCA. The intraorbital-optic-nerve showed more widespread enhancement (39±5% versus 59±6%, P =.01) and higher GBCA-concentration (0.023±0.009 versus 0.059±0.015 mmol/L, P <.001) at 4-hour-post-GBCA.

Abstract INTRODUCTION Anti—amyloid‐β (Aβ) therapies are reshaping Alzheimer's disease (AD) management. Understanding changes in real‐world patterns of diagnostic testing and infusion chair usage is essential for optimizing access to care. METHODS Retrospective analysis of Mayo Clinic enterprise electronic health records (Jan 2019–Mar 2025) assessed trends in AD‐relevant brain imaging, fluid biomarkers, apolipoprotein E (APOE) testing, and lecanemab infusions. Rates of amyloid‐beta (Aβ) positivity by sex and age, APOE genotype frequencies, and lecanemab treatment initiation and discontinuation were evaluated. RESULTS Following national insurance coverage changes, lecanemab infusions grew by 110 infusions per quarter to 605 in Q1 2025. Aβ positron emission tomography scans increased (+22/quarter), cerebrospinal fluid biomarker orders declined (−25/quarter), and plasma p‐tau 217 orders rapidly increased (+238/quarter). Females were more likely to be Aβ positive ( p < 0.006). APOE ‐ε4 homozygotes were less likely to initiate lecanemab (HR = 0.11, p < 0.001). DISCUSSION The adoption of anti‐Aβ therapies coincided with a rapid shift in diagnostic workflows.

ABSTRACT Intrinsic Acinetobacter -derived cephalosporinases (ADCs) in Acinetobacter baumannii are AmpC-type β-lactamases that confer resistance to β-lactam agents, typically through insertion sequence (IS) element-driven overexpression. However, the contribution of ADCs to resistance against advanced β-lactam agents has not been systematically investigated. Given the increasing clinical use of these agents, including cefiderocol, we analyzed the diversity and function of ADC variants in a global collection of carbapenem-resistant A. baumannii (CRAb) isolates. We identified 52 distinct ADC variants in a collection of 428 CRAb clinical isolates from the United States. Among these, variants carrying both a valine substitution at position 292 in the R2 loop and an alanine duplication (ADUP) in the Ω loop consistently conferred stable resistance to cefiderocol. Biochemical and crystallographic analyses demonstrated that ADC-227, which harbors a V292W substitution with an ADUP at position 218a in the Ω loop, exhibits enhanced catalytic efficiencies for ceftazidime and cefiderocol and moderately reduced inhibition by avibactam, leading to resistance not only to cefiderocol but also to ceftazidime–avibactam. Structural studies revealed conformational flexibility of the R2 loop, allowing dynamic accommodation of substrates. Collectively, the findings identify Val292, in combination with an ADUP in the Ω loop, as a mutational “hot spot” for ADCs evolution that may undermine the efficacy of newer β-lactams, including cefiderocol. These results underscore the need for ongoing molecular surveillance of A. baumannii isolates to detect and track the emergence of such variants in clinical settings. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii (CRAb) has been designated as a critical priority pathogen by the World Health Organization (WHO). Cefiderocol has been introduced as a novel therapy against CRAb; however, recent clinical data highlight concerning treatment failures and excess mortality. Understanding resistance mechanisms is therefore essential to preserve the clinical utility of this agent. This study addresses a critical knowledge gap by investigating the role of intrinsic Acinetobacter -derived cephalosporinases (ADCs), which are ubiquitous in A. baumannii and diverse in sequence. By defining specific mutational patterns that endanger cefiderocol activity, this work highlights how chromosomally encoded enzymes can evolve to erode the effectiveness of newer β-lactams such as cefiderocol. These insights underscore the importance of integrating molecular surveillance into clinical practice and antimicrobial stewardship to ensure timely detection of emerging resistance in clinical A. baumannii isolates, ultimately informing treatment strategies and guiding future drug development.

Management of locoregionally advanced human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) can include induction chemotherapy followed by definitive chemoradiation. The standard induction regimen of cisplatin, docetaxel, and 5-fluorouracil (TPF) is associated with high toxicity. Given the chemosensitivity of HPV(+) OPSCC, platinum doublets are frequently used as induction therapy with potentially less toxicity. This retrospective study aimed to compare outcomes between treatment-naive HPV(+) OPSCC patients receiving induction TPF and those receiving an induction platinum doublet. Data collected included tumor characteristics, response after chemoradiation, hospitalization rates, and overall survival (OS). Fifty-five patients (18 TPF and 37 platinum doublet) were included. There was no significant difference in response after completion of definitive chemoradiation (TPF: CR 83.3%, PR 5.6%, progression or metastasis 11.1% vs. platinum doublet: CR 75.7%, PR 16.2%, progression or metastasis 8.1%; p = 0.5241). There were also no differences in hospitalizations for adverse events (38.9% in TPF vs. 40.5% in platinum doublet, p = 0.907) or recurrence (11.1% in TPF vs. 2.7% in platinum doublet, p = 0.198). The 5-year OS was 84.6% in the TPF group and 81.5% in the platinum doublet group (p = 0.581). Induction platinum doublet regimens offer comparable OS, response, and hospitalization rates to TPF in locally advanced HPV(+) OPSCC. Induction with a platinum doublet may be a viable de-escalation strategy for patients who are not candidates for TPF.

Abstract Systemic light chain amyloidosis (AL) arises from monoclonal immunoglobulin light chains, but determinants of progression from precursor states remain poorly defined. In a cross-sectional cohort comprising 1950 systemic AL patients diagnosed 2010-2024, 258 (13.2%) patients with a previously diagnosed plasma cell disorder (PCD) were compared to patients with no prior PCD diagnosis. Patients with monoclonal gammopathy of undetermined signficance (MGUS) and smoldering multiple myeloma (SMM) in the former group had lower difference between involved and uninvolved FLCs (dFLC), higher M-protein, and lower rates of t(11;14) at AL diagnosis. Patients developing AL from SMM had a shorter time to AL (median 34.2 versus 61.3 months) and higher dFLC (median 28.9 versus 11.0 mg/dl) compared to those from MGUS. Patients developing AL after known multiple myeloma (MM) or lymphoplasmacytic lymphoma (LPL) commonly lacked deep hematologic response before AL (≤ very good partial response in 78% of MM, 100% of LPL patients). We additionally studied longitudinally followed cohorts of 3,966 MGUS and 426 (SMM) patients with longitudinal FLC measurements and matched follow-up, in which 1.8% of MGUS and 7.2% of SMM patients developed AL. Those patients who developed AL showed markedly higher dFLC at MGUS/SMM diagnosis and more frequent λ restriction and rates of t(11;14). Higher dFLC was associated with progressively earlier AL development; a 10% cumulative risk occurred at 20 months for patients with a dFLC >80 mg/dL but was not reached if dFLC <10 mg/dL at an estimated median follow-up of 86 months. In multivariable analysis, dFLC >6.4 mg/dL (HR 11.3) and λ isotype (HR 3.6) independently predicted AL, whereas heavy chain secretion was associated with lower risk (HR 0.2 for IgG). These findings indicate that AL risk is primarily driven by cumulative light chain exposure, refining our knowledge of AL pathophysiology and providing guidance for follow-up of patients with elevated dFLC.

Background Psychiatric disorders are increasingly contributing to global disability. Despite advances in conservative management, the prevalence of treatment-resistant cases remains high. Meanwhile, neurosurgery for psychiatric disorders (NPD) remains underused, largely due to strict regulations and historical concerns, particularly those related to neuropsychological side effects (NPSE). Objective To address this issue, we conducted a systematic review with meta-analysis to compare NPSE associated with radiofrequency ablative NPD to those observed in neuro-oncological, neurovascular and epilepsy surgeries. Methods PubMed, Embase and LILACS databases were searched in April 2024 for articles published in English/Spanish from 1990 to 2022, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results A total of 48 articles with 2678 participants were included. The frequency of transient and permanent NPSE in the NPD group ranged from 0.94% to 11.50% and 0.94% to 2.03%, respectively, comparable to the other surgical groups (epilepsy: 0.31–11.70%; vascular: 0.52–22.90%; oncology: 0.94–17.60% for transient NPSE; epilepsy: 0.31–12%; vascular: 0.40–1.96% and oncology: 0.84–1.48% for permanent NPSE). Regarding permanent NPSE, arguably the most critical consideration, the NPD group showed better outcomes in memory, language and social cognition than the epilepsy group, but worse outcomes in executive and perceptual-motor functions. Compared with the vascular group, the NPD group had better executive function but worse complex attention. Finally, the NPD group had fewer permanent deficits than the oncology group in executive function, complex attention and perceptual-motor domains, although language performance was lower. Conclusions Contemporary NPD apparently carries a similar risk of NPSE as other conventional neurosurgical procedures, challenging misconceptions and this unjustified barrier to its broader use.