Citations

Abstract Objectives Carbapenem resistance is a growing public health crisis with regional variability in incidence. We characterized the susceptibility of carbapenem-resistant Gram-negative rods (CR-GNRs) from the Pacific Northwest to five reserve beta-lactam agents including cefiderocol and aztreonam-avibactam. Methods A panel of 162 CR-GNRs from unique patients were tested against cefiderocol, aztreonam-avibactam, ceftazidime-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, with a subset of isolates derived from patients with bacteraemia (n = 55). Whole-genome sequencing (WGS) was performed on representative Stenotrophomonas maltophilia isolates displaying a range of cefiderocol MICs (n = 9). Results Among all isolates, the MIC50 and MIC90 to cefiderocol was 0.25 and 4 mg/L, respectively, compared with 4 and >64 mg/L for aztreonam-avibactam. Overall, 98.3% of S. maltophilia (n = 60), 91.2% of Enterobacterales (n = 34) and 88.5% of Pseudomonas aeruginosa (n = 26) isolates were susceptible to cefiderocol, while 78.6% of other non-fermenters had MICs ≤4 mg/L. Aztreonam-avibactam and cefiderocol exhibited similar activity against Enterobacterales and S. maltophilia, but aztreonam-avibactam was less active against other organisms. WGS of S. maltophilia isolates with elevated cefiderocol MICs identified disruptive mutations in PBP-encoding genes (mrcB/PBP1b and pbpC/PBP1c) that were not observed in highly susceptible isolates. The bacteraemia cohort had many comorbidities and a 29% 30 day all-cause mortality. In this cohort, cefiderocol demonstrated the highest in vitro activity as extrapolated from MICs, followed by ceftazidime-avibactam, aztreonam-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, respectively. Conclusions Cefiderocol exhibited the greatest in vitro activity against various CR-GNRs species in a Pacific Northwest population enriched for severely ill patients. Susceptibility to other agents was more variable among tested organisms.

Abstract Context Limited data are available on quality of life (QoL) and adrenal crises in patients with immune checkpoint inhibitor–induced secondary adrenal insufficiency (ICI-SAI). Objective To (1) characterize the presentation, management, and outcomes of patients with ICI-SAI; (2) compare outcomes of ICI-SAI with other etiologies of secondary adrenal insufficiency (oSAI); and (3) identify variables associated with QoL and adrenal crisis. Methods In this single-center cross-sectional study, adults with ICI-SAI or oSAI (2018-2025) completed questionnaires assessing symptoms, management, adrenal crises, and the Addison’s Disease–Specific QoL survey (AddiQoL); outcomes included AddiQoL score and adrenal crisis events. Results Patients with ICI-SAI (n = 109) were older (median age 66 vs 60 years), more often women (59% vs 43%), and more frequently diagnosed within 1 year of symptom onset (88% vs 42%, P < .001), compared to patients with oSAI (n = 139). Patients with ICI-SAI had higher AddiQoL scores (median 87 vs 85, P = .020). In a multivariable analysis of age, sex, glucocorticoid dose and type, insurance support, and duration of SAI, ICI-SAI remained independently associated with higher AddiQoL (estimate 5.4, P = .010). The prevalence of reported adrenal crises within the prior year was similar between groups (15% vs 14%, P = .782). In a multivariable analysis, higher AddiQoL scores were independently associated with lower odds of adrenal crisis (OR 0.57; 95% CI 0.42-0.76). Conclusion Patients with ICI-SAI report better QoL compared with patients with other causes of SAI, despite similar adrenal crisis rates. These differences may be related to earlier diagnosis and differing clinical contexts, underscoring the importance of timeline recognition and patient-centered management.

Background Documentation burden contributes significantly to psychiatric clinician burnout, with psychiatrists spending an average of three hours per workday on administrative tasks rather than direct patient care. While quantitative studies demonstrate that ambient artificial intelligence (AI) scribes reduce workload and improve documentation quality, the experiential perspectives of clinicians and standardized patients (SPs) remain unexplored, particularly in psychiatry where the therapeutic relationship is central to practice. Our aims were to explore clinician and standardized simulated patient perspectives on ambient AI scribes in psychiatric consultations, examining experiences, concerns, and conditions for successful implementation. Methods This study was part of a cross-sectional quantitative simulation study, where qualitative part was planned a-priori. We conducted focus groups with psychiatrists and SPs following a simulation-based crossover study comparing traditional versus AI-assisted documentation. Data were analyzed using Braun and Clarke’s reflexive thematic analysis framework. Results In this focus group session with eight psychiatrists and four SPs, total six themes were identified: (1) Clinical Presence, whereby reduced documentation barriers were perceived to allow more authentic human connection; (2) Liberation from documentation burden, with clinicians describing cognitive and emotional relief beneficial for their mental health; (3) Clinical Competence Amplified, in which clinicians perceived the AI scribe as enhancing practice through intelligent translation to psychiatric terminology and prompting for missed assessments; (4) Calibrating Trust, where participants navigated initial uncertainty while recognizing the importance of human oversight; (5) Privacy, stigma, and psychiatric exceptionalism, highlighting unique consent and confidentiality considerations for psychiatric populations; and (6) Perceptions of an enhanced standard of care, with both groups expressing strong preference for AI-assisted consultations with conditions for adoption. Conclusion In this exploratory simulation-based qualitative study, AI scribes were perceived as having potential to support more present, patient-centered psychiatric consultations by reducing documentation burden. Implementation should be cautious and requires transparent consent processes, clinician training in behavioral adaptations, robust human oversight, specialty-specific templates, and real-world evaluation with patients receiving psychiatric care.

ABSTRACT Introduction Hairy cell leukemia (HCL) is an uncommon hematopoietic stem cell disease known to have an underlying somatic BRAF V600E driver mutation. Currently, the most accepted treatment is five or seven consecutive days of outpatient infusion of cladribine (e.g., continuous infusion), despite frequent antibiotic use and hospitalization with this regimen. As a result, a few investigators have adopted weekly infusion of cladribine with similar or improved results and fewer side effects. Methods We conducted a retrospective, single‐institution cohort study of 36 treatment‐naïve patients with HCL treated at the University of Colorado Hospital. Eighteen patients received intermittent weekly cladribine (intermittent cladribine [IC]) for 5–7 doses and 18 received standard daily cladribine (continuous cladribine [CC]) over 5–7 days. We report clinical cohort characteristics, response rates, progression‐free survival, overall survival, toxicity, hospitalization rates, and measurable residual disease monitoring in select patients using peripheral blood quantitative BRAF V600E PCR. Results We report here our experience with 18 patients with newly diagnosed BRAF ‐mutated HCL treated with weekly cladribine at a single institution compared to 18 HCL patients who received continuous infusions. Baseline hematologic parameters and overall survival were comparable between groups ( p = 0.1135), but there was a higher rate of complete remission for patients treated with IC (94.4% vs. 61.1%) with significantly improved progression‐free survival ( p < 0.0001). We observed comparable rates of neutropenia, neutropenic fever, antibiotic use, and G‐CSF administration. There were fewer hospitalizations for patients treated with IC (4/18) compared to patients treated with CC (6/18). Rituximab exposure differed between groups, with 72% of patients in the IC cohort receiving rituximab compared with 27.2% in the CC cohort (although treatment status was documented for only 66.7% of patients in the CC cohort). Peripheral blood BRAF V600E allele burden significantly declined and correlated with clinical remission, but this was only performed in select patients who were treated in recent years. Conclusions In this retrospective analysis, IC dosed weekly was associated with improved progression‐free survival and higher rates of complete remission compared to CC with comparable toxicity and fewer hospitalizations. These findings suggest a potential clinical benefit from this regimen. However, interpretation of these findings is limited by the non‐randomized design and differences in rituximab exposure between groups, which may have contributed to the observed outcomes and limited definitive conclusions. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission

ABSTRACT Background Coronary artery (CA) injury from catheter ablation is an uncommon complication, but the risk is under‐recognized. The risk for CA injury significantly increases when a CA is within 3 mm of the site of ablation, but CA imaging to assess for CA proximity to ablation sites is not commonly performed in children prior to ablation. Objective The aim of the study was to assess CA proximity to potential ablation sites. Methods A retrospective review of all coronary computed tomography angiograms (CTAs) in pediatric patients <18 years of age at Mayo Clinic from 2017 through 2023 was conducted. The proximity of CAs to potential ablation sites in the coronary sinus and the appendage bases were measured. Results Seventy‐two CTAs in 67 patients >15 kg and <18 years old were included. Median age was 12 years, and median weight was 41 kg. In right dominant CA circulation, 23/36 (64%) had a CA within 3 mm of the coronary sinus. In left and co‐dominant CA circulation, 26/26 (100%) had a CA within 3 mm of the coronary sinus. The right CA was within 3 mm of the appendage base in 49/69 (71%). The circumflex CA was within 3 mm of the appendage base in 50/68 (74%). Conclusion Most pediatric patients have a CA ≤ 3 mm from potential ablation sites in the coronary sinus and base of the appendages. Precautions should be taken to avoid CA damage before performing catheter ablation in these areas.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly conceptualized as multisystem neurodevelopmental conditions involving behavioral, gastrointestinal, immune, and metabolic alterations. The microbiota–gut–brain axis (MGBA) has been proposed as a key framework linking these systems, although evidence from human studies remains heterogeneous and inconclusive. We conducted a structured narrative review of pediatric human studies investigating the microbiota-gut-brain axis (MGBA) in ASD and ADHD, excluding preclinical and animal studies. PRISMA 2020 principles were used as a transparency framework to support reporting of study identification, screening, and eligibility. Observational, cohort, and interventional studies were synthesized with particular attention to study design, methodology, associations with standardized clinical scales, dietary factors, and therapeutic implications. Across ASD ( n = 90), most studies were observational, predominantly cross-sectional or case-control in designs, reporting consistent associations between ASD symptom severity and gastrointestinal symptoms, intestinal permeability, immune activation, and dietary selectivity. Evidence in ADHD ( n = 21) was substantially more limited and largely observational. Diet emerged as a major modulating and confounding factor in microbiota–behavior associations. Interventional studies involving probiotics, microbiota transfer therapy, and other gut-directed approaches showed more consistent improved gastrointestinal outcomes but showed modest and heterogeneous effects on core ASD symptoms, often limited to subgroups with prominent gastrointestinal comorbidities. To strengthen interpretation of interventional findings, randomized trial reports and non-randomized interventional studies were appraised according to study design, whereas the predominantly heterogeneous observational literature was interpreted narratively. Overall, this review suggests that MGBA alterations may be better conceptualized as modifiers of symptom expression, particularly in ASD and with only emerging relevance in ADHD, rather than as disorder-specific causal mechanisms. This interpretation underscores the need for stratified, longitudinal, and clinically informed research frameworks, in line with the focus of the present research topic.

Background Suicide is the second leading cause of death among children and adolescents, with rates of pediatric suicidal behavior rising substantially over the past two decades. The neurobiology of suicide has been extensively studied in adults, yet pediatric-specific evidence remains limited and the extent to which adult findings can be extrapolated to youth is unclear. This review synthesizes current evidence on the neurobiological correlates of suicidal ideation, suicide attempt, and death by suicide in pediatric and adolescent populations across neurological, genetic, epigenetic, inflammatory, metabolic, and endocrine domains. Methods A literature search was conducted in PubMed, Embase, PsycINFO, and Google Scholar for peer-reviewed, English-language human studies. Priority was given to pediatric and adolescent samples, with adult data included where pediatric evidence was lacking. Studies were grouped by biological domain and by suicidal phenotype. Results Suicidal ideation, suicide attempt, and death by suicide showed partially distinct biological signatures rather than lying on a single continuum of severity. Different markers, most notably cortisol regulation and stress-related DNA methylation, differed in direction between pediatric and adult cohorts, indicating that adult biomarker data cannot be directly extrapolated to youth. Findings converged on a developmental cascade in which genetic liability and early-life adversity influence the hypothalamic-pituitary-adrenal axis, with downstream effects on epigenetic regulation, neuroinflammation, neurochemistry, and frontolimbic circuitry. Conclusions Pediatric suicidal behavior reflects developmentally distinct biological processes that cannot be inferred from adult findings. Advancing the field will require longitudinal, multimodal pediatric studies that disaggregate suicidal phenotypes, span the pubertal transition, and apply age-stratified reference ranges, supporting biologically informed stratification and mechanism-targeted intervention.

Abstract B cell activation and differentiation into antibody-secreting cells require extensive metabolic and epigenetic remodeling, yet the molecular mechanisms that integrate these programs remain incompletely understood. ATP-citrate lyase (ACLY) links glucose metabolism to acetyl-CoA production, supporting lipid biosynthesis and protein acetylation. However, its role in humoral immunity has not been fully defined. Here, using genetic and integrated multi-omics approaches, we show that B cell activation is accompanied by coordinated metabolic, transcriptional, and epigenetic reprograming. Although ACLY is dispensable for B cell development and homeostasis, it is required to establish chromatin accessibility programs in activated B cells, with a more pronounced impact on the epigenetic landscape than on transcriptional output. ACLY-deficient B cells exhibit profound defects in TLR and BCR elicited activation, survival and metabolic fitness ex vivo . In vivo , B cell-intrinsic loss of ACLY results in impaired antigen-specific antibody production, associated with reduced germinal center and plasmablast formation, but normal homeostatic proliferation. Deletion of ACLY after B cell activation reduces plasmablast generation in vivo , indicating a continued requirement for ACLY beyond the initial activation phase. Together, these findings identify ACLY as a central regulator that links metabolism to epigenetic programing that supports B cell activation and humoral immunity.