Citations

Background: We describe an investigation of a cluster of eight Corynebacterium amycolatum sternal surgical site infections (SSIs) that occurred among cardiac surgery patients from February to October 2025. Although C. amycolatum is a member of the skin microbiota, clinically significant infections caused by this organism may occur in cardiac surgery patients. Methods: The investigation included retrospective reviews of SSIs, clinical cultures and medical records, surgical observations, and operating room (OR) assessment. Line lists of surgical case criteria and infection prevention practices were created to assess common factors among cases (e.g., staffing, instrumentation, equipment, skin preparation and antisepsis, nasal decolonization, antibiotic protocols, and closure). Whole genome sequencing of isolates was performed and analyzed using SNIPPY for single-nucleotide polymorphism (SNP)-based phylogenetic analysis. Results: Phylogenetic analysis indicated isolates from five of eight case patients who had cardiac surgeries occurring over a six-week period from February to April 2025 were genetically related (?7 SNPs across the genome), suggesting a common source of infection. These five isolates were ceftriaxone, meropenem, and penicillin resistant. The other three case patient isolates were unrelated (<3181 to <15,000 SNPs); two were ceftriaxone, meropenem and penicillin resistant (one also doxycycline intermediate resistant), and the third penicillin resistant. Use of sternal tape for closure was identified as a recent practice change. Four of five genetically related cases involved the same surgeons and suture tape for sternal closure (wire for all other cases). Sternal tape was discontinued with three cases occurring afterwards. Seven patients completed chlorhexidine gluconate bathing and nasal decolonization. Hair was removed in the OR with reusable surgical clippers. All received the same skin antiseptic, and antibiotic prophylaxis was appropriate. No trends were identified in instrument or equipment use. Broad infection control measures were implemented, including surgical clipper replacement, OR cleaning and ultraviolet light disinfection, headlamp cleaning, and environmental repairs. Leadership was engaged through frequent meetings and audits. Infection control practices such as minimizing OR traffic, double gloving, glove changes, and strict adherence to hand hygiene and attire were reinforced. Two of eight cases occurred after these recommendations were completed but were not genetically related to the primary cluster. Conclusion: We describe a cluster of invasive C. amycolatum sternotomy SSIs. Only two genetically unrelated cases of C. amycolatum occurred following infection control investigation and interventions, underscoring the effectiveness of a comprehensive, multidisciplinary approach. This organism has rarely been reported as a cause of SSIs and may be an emerging pathogen.

Abstract Prediction errors (PEs) drive perceptual learning by updating internal models of the sensory environment, yet it remains unclear how attention reshapes their representation across distributed thalamocortical circuits. Using intracranial stereoelectroencephalography (sEEG) from 17 patients performing a roving auditory oddball task under attended and unattended conditions, we quantified PE encoding using mutual information and co-information to capture redundant and synergistic PE representations. Attention modulated PE encoding in both the thalamus and the temporal cortex, but with distinct informational dynamics. Thalamic encoding showed a stable reduction of PE information during distraction, consistent with state-dependent thalamocortical gating. In contrast, the temporal cortex expressed two opposing learning trajectories during attended listening that converged once attention was diverted, revealing distinct cortical learning regimes rather than a uniform attentional effect. Attention further reorganized the informational content of cortical PE representations by altering the balance between redundant and synergistic information. A biologically constrained neural network showed that attention-dependent changes in inhibition and long-range connectivity reproduced these dynamics through Hebbian learning. Together, these findings suggest that attention regulates predictive learning not simply by changing the strength of PE responses, but by reshaping how distributed thalamocortical circuits represent and integrate sensory evidence over time.

Abstract Aims Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). While CKD is known to give rise to systemic inflammation, its inciting factors remain poorly defined. Oxalate, long implicated in rare genetic kidney disorders, accumulates with decreased kidney function and has emerged as a driver of inflammation and independent risk factor for CVD. Here, we investigate the immunological mechanisms linking oxalate nephropathy to systemic inflammation, cardiac damage and kidney injury. Methods and results Oxalate nephropathy was induced in C57BL6/N mice through an oxalate-enriched diet. Oxalate induced systemic immune activation, renal fibrosis, and adverse cardiac remodelling, including pulmonary congestion with systolic and diastolic dysfunction. Flow cytometry analysis identified interleukin (IL)-17A as a dominant inflammatory effector, with expansion of Th17 and Th17-like Treg in the kidney, intestine, and spleen. Bulk mRNA sequencing confirmed these findings in kidney and heart. In line, plasma IL-17A was increased in oxalate-fed mice. Confirming the oxalate-IL-17A relationship, plasma IL-17A was elevated in patients with primary hyperoxaluria. Gut microbiome analysis by 16S amplicon sequencing showed only mild oxalate-induced alterations in mice. However, soluble oxalate directly enhanced Th17 polarization and disrupted mitochondrial respiration in vitro. In vivo, antibody-mediated IL-17A blockade improved kidney function, cardiac fibrosis, reduced neutrophil infiltration, and partially restored cardiac function in oxalate-fed mice. Conclusion Our study identifies oxalate as a systemic immunometabolic stressor and IL-17A as a central mediator of oxalate-induced cardiorenal injury. These findings establish the oxalate-IL-17A axis as a mechanistic link between CKD and CVD and suggest IL-17A inhibition as a potential therapeutic strategy to reduce cardiovascular damage in CKD.

Importance Tofersen is a disease-modifying antisense oligonucleotide therapeutic for people living with SOD1 –amyotrophic lateral sclerosis ( SOD1 -ALS). Autopsy tissue donors have provided the first opportunity to study the distribution of intrathecally administered tofersen in human central nervous system tissues. Objectives To determine the tissue distribution of tofersen and to provide the first estimates of SOD1 reduction in human somatic motor systems tissues. Design, Setting, and Participants This was a cross-sectional autopsy tissue case series conducted between 2018 and 2026. Autopsies were performed at 3 US academic medical institutions. Tissue samples from 8 deceased patients who lived with SOD1 -ALS, participated in tofersen clinical trials (ClinicalTrials.gov Identifiers NCT02623699 [An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)] and NCT03070119 [Long-Term Evaluation of BIIB067 (Tofersen)]) or the Expanded Access Program, and whose families authorized autopsies were eligible for this study. All autopsy tissue donors known at the time of this study were included (none were excluded). Analyses were conducted between August 2020 and January 2026. Exposures Participants received multiple intrathecal 20- to 100-mg tofersen doses. Main Outcomes and Measures Tofersen tissue concentrations were measured using hybridization enzyme-linked immunosorbent assay (ELISA). SOD1 messenger RNA (mRNA) and protein reduction estimates, defined as percentage SOD1 levels in this study’s recently treated autopsy tissue donors compared to a cohort of samples from tofersen-naive SOD1 -ALS autopsy tissue donors, were measured using quantitative reverse transcription polymerase chain reaction (PCR) and ELISA. Histological localization of tofersen and SOD1 transcripts were studied using immunohistochemistry and in situ hybridization assays. Results In 8 tofersen-treated autopsy tissue donors (5 male and 3 female donors; age range, 42-66 years), spinal cord and motor cortical tissue tofersen concentrations strongly correlated with predictions based on individual dosing histories and a preclinical pharmacokinetic model. For 3 recently treated autopsy tissue donors, reductions in lumbar spinal cord tissue SOD1 mRNA and protein levels ranged from 45% to 84% despite not having been administered 1 to 2 scheduled doses before autopsy. Residual somatic motor neurons demonstrated tofersen transduction and low SOD1 mRNA probe hybridization. Misfolded SOD1 protein inclusions were detected in residual motor neurons of tofersen-naive SOD1- ALS tissue donor controls and tofersen-treated tissue donors. Meningeal and perivascular lymphocytic immune responses were observed in 5 recently treated tissue donors but were not apparent in tissue donors with remote final tofersen doses. Conclusions and Relevance This case series presents the first emerging autopsy tissue data confirming the predicted distribution of tofersen and robust SOD1 protein reduction in human somatic motor systems tissues.

ABSTRACT Blood culture contamination can lead to false-positive blood culture results, potentially contributing to increased costs and unneeded antibiotic utilization. Initial specimen diversion devices (ISDD) have been proposed to reduce blood culture contamination rates. A single-center, observational study conducted at Mayo Clinic Rochester compared blood culture contamination rates using Steripath or Kurin ISDDs versus standard blood culture collection protocols. Over 255 phlebotomists were trained in the use of the ISDDs, with 31,215 blood cultures, 410 of which were contaminated, collected from adults in the emergency department and inpatient wards. Baseline contamination rates were 1.29%–2.53% with standard collection methods. The Steripath ISDD with direct-to-media inoculation of blood culture bottles (Steripath-DTM) reduced blood culture contamination compared to standard practice (0.34% vs. 1.43%, respectively, P < 0.001). Follow-up studies with the alternative Steripath configuration with an integrated syringe (Steripath-syringe), and then the Kurin ISDD with syringe collection (Kurin-syringe), did not meet the primary endpoint of <0.5% contamination (Steripath-syringe: 1.28%; Kurin-syringe: 1.76%). All three ISDD configurations failed to meet our goal of >75% utilization, with an average measured utilization of 26% for the Steripath-DTM, 26.4% for the Steripath ISDD (combined DTM and syringe) in a follow-up study, and 41.5% in the Kurin study. Additionally, a survey of phlebotomists revealed low staff satisfaction with both Steripath ISDD configurations. Staff reported multiple ergonomic barriers limiting the Steripath ISDD’s utility, which precluded implementation of the Steripath-DTM in routine clinical practice. IMPORTANCE We conducted a very large, real-world study of two blood diversion devices to determine whether either would meet goals for reduced blood culture contamination and a high rate of utilization by phlebotomists.

Background: There is growing evidence that social determinants of health (SDOH) are associated with disparities in access to care and hand and upper extremity health. Quality measures represent an opportunity to evaluate disparities in access and outcomes that can inform improvement interventions. We performed a systematic review of evidence regarding health disparities within hand surgery and aimed to develop suitable quality measures that are clinically important, feasible, usable, and scientifically acceptable. Methods: We performed a systematic review including common hand surgery terms to identify health disparities in hand surgery related to SDOH. Candidate quality measures were constructed based upon evidence from the systematic review. A consortium of 11 US-based hand and upper extremity surgeons completed a modified RAND/UCLA Delphi Appropriateness process to evaluate the importance, feasibility, usability, and scientific acceptability of the candidate quality measures. Panelists rated each measure on a scale of 1 ( definitely not important/feasible/usable/scientifically acceptable ) to 9 ( definitely important/feasible/usable/scientifically acceptable ) in 2 voting rounds separated by a face-to-face discussion. Agreement among panelists and validity were assessed using predetermined criteria. Results: Fourteen candidate quality measures addressing health disparities were identified based on evidence from the systematic review, including time to surgery and emergency department use after hand surgery based on insurance type, clinical outcomes based on social deprivation, among others. All 14 measures were accepted. Conclusions: Fourteen candidate quality measures were identified and accepted based upon consensus to address health disparities in hand surgery, although future investigation will be needed to evaluate their effectiveness.

Abstract Introduction Pulmonary fibrosis is characterized by excessive fibroblast activation and alveolar remodeling, leading to progressive lung dysfunction. Osteoglycin (OGN), a small leucine-rich proteoglycan, and its functional fragment MC002 have been identified as regulators of alveolar epithelial regeneration, a process that is impaired in fibrotic lung disease. This study investigates the effects of OGN and MC002 on TGF-β-induced fibrotic responses in lung fibroblasts, organoids, and an in vivo fibrosis model. Methods Human lung fibroblasts (MRC5) were treated with OGN or MC002 for 48 hours, with or without transforming growth factor-beta (TGF-β; 2 ng/mL). Expression of the myofibroblast marker α-smooth muscle actin (ACTA2) and matrix markers collagen 1a1 (COL1A1) and fibronectin (FN1) was assessed by RT-PCR and Western blotting. Global transcriptomic changes were analyzed by RNA sequencing. Myofibroblast differentiation was evaluated by phalloidin staining and quantified using the phalloidin/DAPI ratio. Murine lung organoids were generated by co-culturing epithelial progenitor cells with fibroblasts and treated with TGF-β (2 ng/mL) in the presence or absence of OGN or MC002. Organoid number, size, and alveolar differentiation were quantified after 14 days. In vivo, pulmonary fibrosis was induced in mice using intratracheal bleomycin. MC002 was administered at different doses (6.75 µg or 20.25 µg) every other day starting from day 7 post-bleomycin, and lung weight and pressure-volume (PV) loops were assessed to evaluate fibrotic burden and lung mechanics. Osteoglycin expression in human lung tissue from 13 non-smokers, 11 ex-smokers, and 12 IPF patients was analyzed by immunostaining. Results TGF-β induced pro-fibrotic gene expression in fibroblasts, while OGN and MC002 alone had no pro-fibrotic effects. MC002 fully reversed TGF-β-induced ACTA2, COL1A1, and FN1 expression, whereas OGN selectively attenuated COL1A1. RNA-sequencing revealed broad suppression of fibrosis- and ECM-associated gene programs by MC002. At the protein level, TGF-β-induced ACTA2 expression was reversed by MC002 but not by OGN. Both compounds reduced TGF-β-induced stress fiber formation. In lung organoids, TGF-β impaired organoid formation and alveolar differentiation, effects that were restored by OGN and MC002 in a concentration-dependent manner. In the bleomycin model, MC002 significantly reduced lung weight and improved PV loop profiles, indicating attenuation of fibrotic stiffening and improved lung compliance. Osteoglycin protein expression was significantly diminished in IPF whole lung tissue and parenchyma compared to controls. Conclusion OGN, and particularly MC002, counteract TGF-β-driven fibroblast activation and myofibroblast differentiation while promoting alveolar preservation. The superior efficacy of MC002 supports its potential as a therapeutic candidate for pulmonary fibrosis. This abstract is funded by: Lung Foundation Netherlands 10.1.23.021PPS

PURPOSE Cancer survivors endure costly and time-intensive care throughout treatment and survivorship. Paid sick leave provides employment and financial stability while supporting time off for medical needs. We investigated whether paid sick leave is associated with financial hardship and overall and cancer-specific mortality risk in working adult cancer survivors. METHODS Working adults age 18-64 years with a cancer history were identified from the National Health Interview Survey (NHIS) between 2011 and 2023. Associations of paid sick leave and financial hardship (medical care delays, problems paying medical bills, worry about paying medical bills, and cost-related medication underuse) were examined with 2011-2018 and 2019-2023 data using separate multivariable logistic regressions because of survey redesign in 2019. Linked mortality files from the National Death Index were available for 2011-2018 respondents. The association of paid sick leave and mortality risk was examined with multivariable Cox proportional hazards models. RESULTS A total of 8,091 and 3,919 working cancer survivors were identified from the 2011-2018 and 2019-2023 NHIS, respectively. Paid sick leave was associated with decreased medical care delays because of cost (2011-2018 odds ratio [OR], 0.74 [95% CI, 0.60 to 0.93]; P = .008; 2019-2023 OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) but not consistently with other forms of financial hardship. In adjusted analyses, paid sick leave was associated with significant reductions in risk of overall mortality (hazard ratio [HR], 0.74 [95% CI, 0.61 to 0.9]; P = .003) and cancer mortality (HR, 0.74 [95% CI, 0.61 to 0.91]; P = .003). CONCLUSION In working cancer survivors, paid sick leave is associated with decreased care delays and lower overall and cancer-specific mortality risk, which may be due to maintained employment, household income, and health insurance coverage leading to improvements in treatment access, affordability, and overall survivorship care.