Citations

Background: No biomechanical study has established the effect of different graft positions or bone block options on anterior glenohumeral joint stability. Purpose/Hypothesis: The purpose of this study was to compare graft choice (distal clavicular vs coracoid autograft for Latarjet) and position on stability of the bone block for anterior glenohumeral instability. It was hypothesized that both grafts would be comparable if flush with the glenoid but that the sling effect of the Latarjet procedure would lead to greater stability in case of graft medialization. Study Design: Controlled laboratory study. Methods: Eight cadaveric shoulders were included. Defects stabilized using a distal clavicular graft and a coracoid graft were consecutively positioned at 0, 4, and 8 mm medially. The starting position was determined by the humeral head’s being seated at its most medial position on the glenoid surface. Each experiment comprised maximal external rotation and glenohumeral abduction at 60° while applying a constant 50-N medial compressive force to the humerus under all conditions. The conjoint tendon was routed through a split in the subscapularis and loaded with a 5-N weight using a pulley system for all Latarjet trials to simulate the sling effect. Results: Regarding the clavicular graft, the stability ratio significantly decreased versus the intact condition at all medial offsets ( P = .007 for 0 mm, P < .001 for 4 mm, and P < .001 for 8 mm), and it was significantly lower in the 4-mm versus 0-mm position ( P = .008), significantly higher in the 4-mm versus 8-mm position ( P < .001), and significantly lower in the 8-mm versus 0-mm position ( P < .001). Regarding the coracoid graft, the stability ratio was comparable with intact for the 0-mm position ( P = .12), while it was significantly lower in the 4-mm and 8-mm positions ( P < .001 for both). The distal clavicular graft at 0-mm offset was comparable with the coracoid graft at 0-mm offset. Conclusion: In shoulders with anterior glenoid bone loss, the coracoid and distal clavicular autografts were biomechanically comparable when placed flush with the glenoid. The distal clavicle at 0-mm offset did not restore stability compared with the intact specimen, but the Latarjet at 0-mm offset was not significantly different from the intact condition. Clinical Relevance: The Latarjet procedure provides higher stability compared with distal clavicular autograft when medialized.

Abstract Objective: Patients with Opioid Use Disorder (OUD) are prone to Multidrug-Resistant Organism (MDRO) colonization and infections, thus at risk for worse outcomes during critical illness. Understanding the prevalence and predictors of MDRO infections is essential to optimize interventions and treatments. Design: Retrospective cohort study. Methods: The study evaluated the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) between January 1, 2018, and July 31, 2023. It included adults admitted to an ICU with bacterial infections and positive cultures obtained within 48 hours of admission. Demographics, clinical traits, and MDRO isolation rates were analyzed using descriptive statistics, univariate methods, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Results: MDRO isolation occurred in 178 of 790 patients (22.5%), with methicillin-resistant Staphylococcus aureus as the most frequently isolated organism. LASSO regression identified housing insecurity (OR: 1.79, 95% CI 1.09–2.93, P = .022), no receipt of medications for OUD treatment (OR: 1.56, 95% CI 1.06–2.29, P = .023), positive hepatitis C virus (HCV) status (OR: 2.19, 95% CI 1.19–4.03, P = .012), and intravenous antibiotic use in the prior 90 days (OR: 1.04 per 24 h, 95% CI 1.01–1.07, P = .007) as significant predictors of MDRO isolation. Conclusions: The study highlights a high prevalence of MDRO isolation in critically ill OUD patients admitted for infection-related issues with positive cultures obtained within 48 hours of admission, influenced by factors like housing insecurity, no receipt of medications for OUD treatment, HCV status, and prior antibiotic use.

Abstract Chronically elevated circulating excess free fatty acids (ie, lipotoxicity) is a pathological process implicated in several metabolic disorders, including obesity-driven type 2 diabetes (T2D). Lipotoxicity exerts detrimental effects on pancreatic islet β-cells by reducing glucose-stimulated insulin secretion (GSIS), altering β-cell transcriptional identity, and promoting apoptosis. While β-cell-derived small extracellular vesicles (sEV) have been shown to contribute to β-cell failure in T2D, their specific role in lipotoxicity-mediated β-cell failure remains to be elucidated. In this work, we demonstrate that lipotoxicity enhances the release of sEVs from β-cells, which exhibit altered proteomic and lipidomic profiles. These palmitate (PAL)-exposed extracellular vesicles (EVs) induce β-cell dysfunction in healthy mouse and human islets and trigger significant islet transcriptional changes, including the upregulation of genes associated with the TGFβ/Smad3 pathway, as noted by RNA sequencing. Importantly, pharmacological inhibition of the TGFβI/II receptor improved PAL EV-induced β-cell dysfunction, underscoring their involvement in activating the TGFβ/Smad3 pathway during this process. We have comprehensively characterized lipotoxic β-cell sEVs and implicated their role in inducing β-cell functional failure in T2D. These findings highlight potential avenues for therapeutic interventions targeting sEV-mediated pathways to preserve β-cell health in metabolic disorders.

PURPOSE Predictive biomarkers to better tailor therapy for patients with early-stage human epidermal growth factor 2 (HER2)-positive breast cancer are a priority. We hypothesized that HER2 and immune-based biomarkers would be predictive of pathologic complete response (pCR) to preoperative trastuzumab/pertuzumab (HP). MATERIALS AND METHODS Patients with stage II/III, estrogen receptor (ER)-negative, HER2-positive breast cancer received neoadjuvant HP in the TBCRC026 clinical trial. The pCR after receiving HP alone was 22% (18/83). Tumor biopsies were performed at baseline. Secondary correlative objectives were to determine the relationship between HER2-based biomarkers and immune processes with pCR. NanoString code sets BC360 and IO360 were used to compare differential gene expression in baseline tumors that underwent pCR versus no pCR. NanoString GeoMx digital spatial profiling was used to assess immune protein abundance in intraepithelial and stromal segments. Stromal tumor-infiltrating lymphocytes and Ki67 were evaluated by hematoxylin and eosin and immunohistochemistry, respectively. RESULTS Intraepithelial HER2 protein abundance was significantly associated with pCR ( P = .001). Low HER2 abundance tumors were primarily basal-like, and essentially all (19/20) failed to achieve pCR. High HER2 abundance tumors that achieved pCR (14/51) exhibited a high degree of immune cell activity, whereas high HER2 abundance tumors that failed to achieve pCR tumors (37/51) were enriched for M-phase processes and epidermal growth factor receptor signaling. Baseline Ki67 was significantly higher in nonresponders ( P = .04). CONCLUSION ER-negative, HER2-positive breast cancer has unique molecular and immunologic features that may predict pCR after neoadjuvant HP. Validation of these potential biomarkers and composite biomarker analyses may guide design of future clinical trials.

Objectives: Early identification of patients living with cancer at higher risk of death from an infection is critical in infection mortality prevention. We characterize patients living with cancer at the highest risk of dying from an infection. Methods: 7,529,481 US cancer survivors (1992 to 2015) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) and 95% CIs were calculated. Fine-gray survival analysis was performed to calculate hazard ratios by adjusting for the effects of competing risks (eg, deaths due to causes other than infection). Results: Among 7,529,481 patients living with cancer (1992 to 2015), 101,167 (1.3%) died of infection. The rate of infection-specific mortality was 27.19/10,000 person-years, with an SMR of 3.29 (95% CI: 3.26-3.32, P <0.001). Patients who were older, male, black, and unmarried were at a greater risk of fatal infection. Overall, the risk of infection-specific mortality for patients living with cancer is greatest 1 year after diagnosis compared with the general population (SMR: 8.68, 95% CI: 8.53-8.84; P< 0.0001), and this risk decreases with follow-up time (SMR at >10 y after diagnosis: 2.93, 95% CI: 2.87-3.00; P< 0.0001). Among patients with Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Kaposi Sarcoma, 9.2%, 11.5%, and 82.2% of all deaths within the first year after cancer diagnosis occurred due to acute infectious disease. In contrast, for patients with liver cancer, the relative percentage of infection-specific mortality increases with follow-up time from 3.5% at <1 year after cancer diagnosis and 10.4% at 10+ years of follow-up. Conclusion: The results of this study characterize infection mortality in patients living with cancer, which can guide more targeted research and interventions in this population.

Background: Benefits of hospice care, such as improvement in quality of life and reduced costs, depend on duration of enrollment in hospice services, making timely hospice referral essential. Patient-, provider-, and system-level factors associated with hospice referral timing and length of stay (LOS) are unclear. 1 – 6 Objective: To review existing hospice referral patterns to identify patient- and system-level factors associated with hospice LOS. Methods: We performed a retrospective review of all adult patients referred from our institution (located in Rochester, Minnesota, USA) to a nonprofit hospice agency between 2013 and 2017. The primary dependent variable was hospice LOS. Patient-level variables included demographic characteristics, place of residence, and hospice diagnosis. System-level variables included referral setting and provider-specific variables, such as title and gender. Statistical analyses were performed using multivariate logistic regression. Results: A total of 2072 patients were referred to hospice during the study period. Patient-level factors associated with LOS included hospice diagnosis and place of residence. Patients referred for cancer had a higher odds of a long LOS, while patients from long-term care facilities had a higher odds of a short LOS. System-level factors associated with LOS included provider gender and title. Referral by a female provider or by a physician, rather than an advanced practice provider, was associated with a lower odds of a short LOS. Conclusion: Based on a review of hospice referral patterns, the integration of hospice care into subspecialty practices, long-term care facilities, and advanced practice education could be an effective strategy to improve hospice LOS.

SUMMARY Lymph nodes with tuberculous lesions identified by federal meat inspectors were collected from 36 swine carcasses at an abattoir in southeastern Minnesota. Nonchromogenic mycobacteria were isolated by culture from 25. By animal pathogenicity and serologic tests, 24 of the 25 were identified as Mycobacterium avium and 1 was a Battey type. Corynebacterium equi was isolated from 4 lesions with M. avium and from 2 without other bacteria. Lesions with C. equi could not be distinguished from others either grossly or microscopically.

Abstract Postpartum pain management practices have significant variation and are known to be influenced by nonclinical factors. We aimed to examine factors that contribute to clinicians' assessment and management of postpartum pain, including the role of opioids. We conducted a qualitative study of obstetric clinicians providing postpartum care at a single, large, tertiary care center (November 2021–June 2022). Attending and trainee OB/GYN physicians and advanced practice providers (APPs) completed in-depth interviews using a semistructured interview guide. Purposive sampling was employed to ensure a representative sample of each clinician type was included. Participants were asked about factors that influence postpartum pain management. Data were analyzed using the constant comparative method. Of 46 participants, 48% were attending physicians, 32% trainee physicians, and 20% APPs. The analysis demonstrated three key themes related to postpartum assessment and management: influencing factors (knowledge or experiences that influence practice), objective findings, and the role of counseling. While clinicians reported guidelines and patient satisfaction as major influencing factors, several also shared the inherent conflict that may arise between them. Objective findings, specifically the impact of pain on patients achieving functional goals, also influenced clinician decision-making. Conversely, many participants reported the limited utility of the numeric pain scale as an objective metric. Additionally, the role of counseling in shared decision-making and providing anticipatory guidance was emphasized. Finally, clinicians had a range of opinions on the role of opioids in pain management, but many spoke to the value of opioids as second-line treatment and the impact of the opioid epidemic on prescribing practices. The factors that influence clinicians' assessment and management of postpartum pain are occasionally in conflict. Furthermore, objective measures, such as the numeric pain scale, have significant limitations.

SUMMARY Normative values were established for results of tests of blood coagulation and platelet function in swine. In swine that have von Willebrand's disease, bleeding time was prolonged, platelet retention was decreased glass bead column), and factor VIII concentration was low.