Citations

Background: Cefazolin is a preferred treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Recent studies have suggested a potential impact on clinical outcomes in patients with hypoalbuminemia treated with highly protein-bound antimicrobials. Objective: The purpose of this study was to determine if there are any differences in clinical outcomes between normoalbuminemic and hypoalbuminemic patients treated with cefazolin for bacteremia. Methods: A retrospective, multicentered cohort study of patients hospitalized between 2019 and 2023 with MSSA bacteremia treated with cefazolin for at least 24 hours prior to culture clearance. Patients were divided into hypoalbuminemia (serum albumin ≤2.5 g/dL) or normoalbuminemia groups. The primary outcome was time to culture clearance. Results: Of 69 patients included (50 in normoalbuminemia group and 19 in hypoalbuminemia group), the most common sources of bacteremia were line-related, osteoarticular, and infective endocarditis. Deep-seated infections were present in 24% of the normoalbuminemia group and 58% of the hypoalbuminemia group. Patients with hypoalbuminemia had a significantly longer mean hospital length of stay (12 vs 7 days, P = 0.016). After adjusting for deep-seated infection, hypoalbuminemia was associated with increased time to culture clearance by 1.2 days ( P = 0.039). In-hospital mortality was significantly higher in the hypoalbuminemia group (26% vs 4%, P = 0.015). Conclusion and Relevance: Limited research is available describing the relationship between serum albumin levels and clinical outcomes. Our study suggests patients with hypoalbuminemia treated with cefazolin for MSSA bacteremia have significantly longer time to culture clearance, increased mortality, and longer length of stay.

Background: Recent biomechanical evidence for adjustable suture anchor (ASA)–based posterior medial meniscus root (PMMR) fixation has shown promising results compared with conventional transtibial pull-out repair (TPOR). However, ASA fixation has not been evaluated in human tissue to 100,000 cycles. Hypothesis: ASA repair would lead to increased primary fixation strength and less cyclic displacement than conventional TPORs. Study Design: Controlled laboratory study. Methods: A total of 32 human medial menisci were used, 8 of which were intact specimens and served as native controls. For the others, PMMR tears were created and repaired using 3 different techniques (n = 8 group). Two conventional PMMR repairs were prepared consisting of two No. 2 simple sutures (TSS) and two No. 2 sutures in a Mason-Allen (MA) configuration, all tied over a cortical button. The knotless ASA repair was fixed in MA with repair sutures tensioned at 120 N (MA-120). The repairs’ initial force, stiffness, and relief displacement from the tensioned state toward repair unloading (2 N) were measured after fixation. All repair constructs were loaded for 100,000 cycles, with displacement and stiffness measured, and finally were pulled to failure. Results: The TPORs demonstrated similar primary fixation and cyclic loading behavior except for initial cyclic displacement (cycle 10). The ASA repair provided a higher initial repair load ( P < .001) and stiffness ( P < .001) with relief displacement similar to conventional TPORs. Lower initial cyclic displacement ( P < .011; cycle 10) with overall higher repair stiffness ( P < .011) resulted in significantly lower displacement ( P < .001) throughout testing for ASA repair. Although both TPORs were completely loose after 100,000 cycles, the ASA repair achieved near-native dynamic meniscal stabilization. The TSS repair had lower overall ultimate load ( P < .001) and ultimate stiffness ( P < .023) compared with the ASA repair. All repairs had lower ultimate stiffness and loads than the native meniscus ( P < .001). Conclusion: The ASA repair resulted in improved primary PMMR fixation that was stiffer with less cyclic displacement than conventional TPORs and approached that of the human meniscal function after 100,000 load cycles in a cadaveric model. However, all repair techniques had lower ultimate strength than the native human PMMR. Clinical Relevance: Knotless ASA meniscus root fixation resulted in higher tissue compression and less displacement in a cadaveric model; however, future clinical series with surveillance imaging will define the overall significance of healing rates.

Background Improving safety in healthcare has been paramount for decades, yet despite major attention and investment, improvement has remained incremental. Patient safety is a major concern in US healthcare, leading to significant harm and economic losses annually. Accurately identifying safety events remains difficult due to methodological discrepancies and lack of standardisation. This study evaluated the feasibility of implementing a standardised case-review methodology and safety-event taxonomy across diverse hospital settings to assess opportunities for improvement (OFIs) and compare findings with traditional definitions. Methods This multicentre retrospective cohort study reports data from 103 hospitals across the USA and Canada between 2016 and 2023. A multivariable logistic regression was performed to test case reviews for differences in the presence of one or more OFIs across several hospital types (bed size, academic status, urban setting, trauma level and Centres for Medicare and Medicaid Services overall star rating) and patient characteristics (age, gender, length of stay, admission and discharge code status and mortality). Results 19 181 cases were reviewed across the Learning Health System Collaborative, with a median of 107 reviews per hospital. Mortality was the most common cohort selection, studied by 91 hospitals (88%). At least one OFI was identified in 12 714 cases (66.3%). The logistic regression analysis found that all hospital characteristics and patient age, length of stay, code status and discharge disposition were significantly associated with at least one OFI. Of the 46 444 OFIs identified, 41 439 (89%) were from categories focused on omissions of care. The categories of end-of-life, documentation and treatment/care alone accounted for 25 980 OFIs (56%). Conclusion The highest volumes of safety-related OFIs were associated with omissions of care, as opposed to the traditional definition of patient safety, which primarily includes outcomes from acts of commission.

Increased infiltration of CD3 + and CD8 + T cells into ovarian cancer (OC) is linked to better prognosis, but the specific antigens involved are unclear. Recent reports suggest that HLA class I can present peptides from noncoding genomic regions, known as noncanonical or cryptic peptides, but their immunogenicity is underexplored. To address this, we used immunopeptidomic analysis and RNA sequencing on five metastatic OC samples, which identified 311 cryptic peptides (40 to 83 per patient). Despite comprising less than 1% of total peptides, cryptic peptides from noncoding transcripts emerged as the predominant antigen class when compared to the other major classes of known tumor-specific and tumor-associated antigens in OC samples. Notably, nearly 70% of the prioritized cryptic peptides elicited T cell activation, as evidenced by increased 4-1BB and IFN-γ expression in autologous CD8 + T cells. This study reveals noncoding cryptic peptides as an important class of immunogenic antigens in OC.

Abstract Context Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities. Objective Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact. Design An 8-domain LDS was developed by 8 disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to the Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at 2 different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in 2 cohorts of patients with lipodystrophy treated with metreleptin. Results LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by 1 or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility and high reliability by intraclass correlation coefficients (&gt;0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R = 0.79-0.99, P &lt; .001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P &lt; .001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P = .04). Conclusion The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.

Background: Latinas with mammographic dense breasts are at increased risk of breast cancer. This randomized controlled trial tests the effectiveness of three breast density (BD) educational approaches on adherence to subsequent mammography screening among Latinas receiving care at a Federally Qualified Health Center (FQHC). Measure(s): Adherence was ascertained using electronic health record and survey responses. Kaplan–Meier estimates of the time to subsequent mammogram were used to obtain adherence rates at 1- and 2-years post baseline mammogram. Cox modeling assessed whether adherence differed by patient characteristics or group assignment. Results: This analysis was limited to Latinas enrolled between October 27, 2016, and December 21, 2018 ( n = 946; 66.1% <50 years of age, 53.5% with dense breasts). Adherence rates at 1 year was 24.8% increasing to 51.7% by year 2. Latinas randomized to the Promotora + brochure + letter arm (hazard ratio [HR]: 1.09 [95% confidence interval [95% CI] 0.87 to 1.36]) or brochure + letter (HR: 1.03 [95% CI 0.82 to 1.29]) arm were not more likely to be adherent to subsequent mammography compared to the letter only arm ( p = 0.76) . Adjusting for age and study group, having more prior mammograms, being “extremely likely” to get an annual mammogram, and having more confidence to get an annual mammogram at baseline were significant drivers of subsequent adherence. Conclusion: Informational interventions targeting BD education alone are unlikely to significantly improve adherence to subsequent mammography among Latinas receiving care in FQHCs.

Abstract Purpose: Digital proteomic profiling was performed to identify spatial context in relationship to patient response and survival after anti–PD-1 therapy in metastatic colorectal cancer. Experimental Design: Primary colorectal cancers with deficient mismatch repair from patients treated with anti–PD-1 antibodies were analyzed (N = 30) using digital spatial profiling (GeoMx nCounter). At the invasive margin, 71 proteins were profiled in 10 regions of interest/slide that were segmented into 3 compartments labeled with pan-cytokeratin (epithelia), CD45 (stromal cells), and SYTO13 (nuclei). In an independent cohort (n = 13), digital spatial profiling data and single-cell transcriptomic data were analyzed. Differential protein abundance, after Benjamini–Hochberg correction, was examined by clinical response and progression-free survival (PFS) using multivariable Cox regression. Results: Protein abundance varied significantly between epithelial and stromal compartments. Nonresponders to anti–PD-1 showed higher fibronectin and smooth muscle actin abundance in the epithelial compartment that was associated with significantly shorter PFS (adjusted HR: 6.49 and 4.52, respectively; P &lt; 0.05). In CD45+ stroma, increased expression of proteins related to T cells (CD3 and CD4), NK cells (CD56), antigen presentation (CD40), immune activation (CD27, ICOS), and apoptosis (GZMA) were found in responders (vs nonresponders) to anti–PD-1; each marker was significantly associated with longer patient PFS (0.02 &lt; adjusted HR &lt; 0.17; P &lt; 0.05). In a separate cohort, consistent results by compartment were found for fibronectin and CD56. Gene expression data revealed that fibronectin and smooth muscle actin were primarily derived from cancer-associated fibroblasts. Conclusions: Spatially resolved protein profiles within microenvironments of deficient mismatch repair colorectal cancers can influence patient response and survival after anti–PD-1, highlighting their potential clinical significance.

Background Left ventricular diastolic dysfunction (LVDD) predicts mortality in patients in cardiac intensive care units. An artificial intelligence enhanced ECG (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in cardiac intensive care units. Methods This historical cohort study included consecutive adults admitted to Mayo Clinic cardiac intensive care unit from 2007 to 2018 with an admission AIECG. The AIECG assigned the LVDD grade (0–3). Medial mitral E/e' ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. In‐hospital and 1‐year mortality was evaluated, before and after multivariable adjustment. Results We included 11 868 patients (median age 69.5 years, 37.7% female); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grade was 0 (normal), 33%; 1, 7%; 2, 39%; and 3, 21%. In‐hospital and 1‐year mortality increased in each higher AIECG LVDD grade. After adjustment, each higher AIECG LVDD grade was associated with higher in‐hospital (adjusted odds ratio [OR], 1.22 [95% CI, 1.13–1.32]) and 1‐year mortality (adjusted hazard ratio [HR], 1.23 [95% CI, 1.19–1.29]); this persisted after adjustment for TTE measurements. Patients with grade 2 or 3 LVDD by AIECG and medial mitral E/e' ratio >15 by TTE had the highest in‐hospital (adjusted OR, 2.54 [95% CI, 1.69–3.88]) and 1‐year (adjusted HR, 2.03 [95% CI, 1.65–2.48]) mortality, whereas patients meeting either of these criteria had similar, elevated mortality. Conclusions The AIECG LVDD grade was strongly associated with in‐hospital and 1‐year mortality in patients in cardiac intensive care units, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures were at highest risk.