Lancaster General Hospital

To evaluate whether preoperative intravenous tranexamic acid (TXA) reduces postoperative blood transfusion rates in geriatric patients undergoing operative treatment for hip fracture. Design: Prospective, double-blinded, randomized controlled trial terminated early after interim futility analysis. Single-center Level I trauma center. Patients aged ≥65 years who underwent operative treatment for femoral neck (AO/OTA 31-B), intertrochanteric region (AO/OTA 31-A), or subtrochanteric (AO/OTA 32-A/B/C) fractures between June 2019 and June 2022 were included. Procedures included arthroplasty (hemiarthroplasty or total hip arthroplasty), and internal fixation (ORIF) with intramedullary nailing or sliding hip screw fixation. Exclusion criteria were recent thromboembolic events, cancer, hypercoagulable disorders, or TXA allergy. The primary outcome was postoperative transfusion. Secondary outcomes included hospital length of stay (HLOS), 30-day readmission, and 90-day complications and mortality. Statistical comparisons were performed using odds ratios, chi-squared, and t-tests, with significance thresholds adjusted by O'Brien-Fleming criteria. 283 patients were analyzed (TXA: 146 (mean age 84 (range 65-100), 71.9% female; Placebo: 137 (mean age 83.1 (range 65-100), 77.2% female). Baseline characteristics, including BMI and procedure type, were comparable (all p> 0.05). 229 patients (80.9%) required no postoperative transfusion (TXA 81%; Placebo: 81%, p=0.97). No significant differences were observed in 30-day readmission (p = 0.729), 90-day complications (p = 0.183), HLOS (p = 0.783), or 90-day mortality (p = 0.655). Subgroup analysis revealed higher transfusion rates in ORIF versus arthroplasty (ORIF 25%, Arthroplasty 8%, p < 0.05), though no difference between TXA and placebo within subgroups (p=0.38). Preoperative TXA was not associated with reduced transfusion requirements in geriatric hip fracture surgery. No significant differences were observed in complications, mortality, or hospital stay. Surgical procedure may influence transfusion risk more than TXA use. Level I.

Background This study assessed the effectiveness and safety of patisiran in patients with V122I/T60A variant transthyretin (ATTRv) amyloidosis with polyneuropathy. These variants have been under-represented in previous trials of gene-silencing agents. Methods This was a multicenter, phase IV study conducted at 27 sites in the USA. Patients were ≥ 18 years, diagnosed with ATTRv amyloidosis with polyneuropathy and a documented V122I or T60A variant. Patisiran-treated patients were enrolled prospectively, ambispectively, and retrospectively. The primary endpoint was the proportion of patients with a stable or improved polyneuropathy disability (PND) score at 12 months vs. baseline. Safety was monitored throughout the trial. Results Sixty-seven patients were enrolled, of whom 58 received ≥ 1 dose of patisiran. In the efficacy population, 42/45 (93.3%) patients demonstrated stable or improved PND scores from baseline to Month 12. Patients also showed stable or improved quality of life, health status, autonomic symptoms, and cardiac function vs. baseline. Adverse events occurred in 13/42 (31.0%) patients in the prospective and ambispective cohorts; most were mild or moderate. No deaths or cardiac hospitalizations were considered related to patisiran. Conclusions Patisiran demonstrated a consistent positive effect across multiple endpoints in patients with V122I/T60A ATTRv amyloidosis, including polyneuropathy manifestations.

Guided Inquiry Learning with Technology (GILT) is web platform designed to facilitate interactions within student teams and to support instructor-team interactions. This study explored introductory computing student perceptions of GILT and its impact on a variety of pedagogical areas. While overall response to GILT was quite positive, student comfort using GILT was highly correlated with their perceptions of its impact and even on their judgement of the course's value. Implications of these findings are discussed as are future steps for the research.

Major depressive disorder (MDD) is a leading cause of disability worldwide. Risk for MDD is heritable, and the genetic structure of founder populations enables investigation of rare susceptibility alleles with large effect. In an extended Old Order Mennonite family cohort, we identified a rare missense variant in GPR156 (c.1599G>T, p.Glu533Asp) associated with a two-fold increase in the relative risk of MDD. GPR156 is an orphan G protein-coupled receptor localized in the medial habenula, a region implicated in mood regulation. Insertion of a human sequence containing c.1599G>T into the murine Gpr156 locus induced medial habenula hyperactivity and abnormal stress-related behaviors. This work reveals a human variant that is associated with depression, implicates GPR156 as a target for mood regulation, and introduces informative murine models for investigating the pathophysiology and treatment of affective disorders.

Objectives Automatic capture confirmation (ACC) algorithms monitor the pacing capture threshold (PCT) and adjust energy output to deliver a tailored safety margin over the PCT, while providing a high-output backup safety pulse in the event of non-capture. Advantages of these algorithms include increased device longevity, enhanced patient safety, and improved remote monitoring capabilities. While such algorithms have been validated for conventional right ventricular pacing (RVP) locations, there is limited information on their performance for pacing in the increasingly utilized location of the left bundle branch area (LBBA). Our objective was to evaluate the longitudinal performance and stability of the Abbott AutoCapture™ algorithm in patients with left bundle branch area pacing (LBBAP). Methods De-identified remote device data were retrospectively analyzed from consecutive patients in our hospital who received AutoCapture enabled Abbott pacemakers with LBBAP from June 2021 to August 2023. Device stored AutoCapture PCT measurements were then evaluated incrementally over an approximate 2-year period, to evaluate longer-term trends and performance, and also compared with the original, manual PCT at the time of initial implant. Results A total of 619 patients with either single chamber (model 1272, n= 89) or dual-chamber Abbott devices (model 2272, n= 530) were identified. AutoCapture and manually measured PCTs at implant were within 0.25 V in 600/615 (97.6%) patients, with average PCTs of 0.76 V ± 0.28 and 0.80 V ± 0.26 respectively, at a pulse width of 0.5 ms. At 1, 3, 6, 12, and 24-month remote follow-up, average AutoCapture PCTs were 0.67 V ± 0.29 (n=594), 0.66 V ± 0.25 (n=560), 0.71 V ± 0.29 (n=543), 0.77 V ± 0.29 (n=447) and 0.81 V ± 0.28 (n=112), respectively. At the last remote follow-up, lead impedances were 536 ohms ±60, and sensed R-wave amplitude were 11 mV ± 3. AutoCapture was found to be effective in assessing PCT and was activated in the majority of patients (619/644, 97%) without complications related to its activation or usage during the follow-up period. Conclusion The AutoCapture algorithm measured accurate PCTs at implant and showed a stable trend during follow-up out to approximately 2 years in patients with LBBAP.

Introduction: Childhood Opportunity Index (COI) measures access to quality education, safe housing, and healthcare based on zip codes. These scores can influence patient behaviors, such as no-shows (NS), which can affect resource utilization and health outcomes. Objective: To quantify the correlation between COI and NS through odds ratio (OR) in a pediatric cardiology clinic. Methods: Patient data was collected from a single, independent pediatric cardiology practice for all visits between 2019 to 2021. COI was categorized into 3 subdomains; education, health and environment, social and economic according to zipcode from Diversitydatakids. The COI was split into low (&lt;40), moderate (40-60U), and high (&gt;60U). Additional variables included age, insurance type, lead time (time from scheduling to appointment date), and telehealth status. Multiple logistic mixed-effect models, both unadjusted (single predictor) and adjusted (multiple predictors), were used to obtain OR for NS. Results: There were 11,474 total encounters. 92% were completed appointments and 8% were NS. Unadjusted model showed statistical significance (p&lt;.05) with increased odds of NS for low COI education, low COI social and economic, and low COI, compared to high COI as the reference category (Table 1). Adjusted model 2 showed similar significant results for the low COI overall category, while for adjusted models 1 and 3, none of the COI categories were statistically significant. In all 4 models, OR for all age categories, all lead times, and public and mixed insurance types were significant. Conclusion: The unadjusted and adjusted model 2 showed that patients with lower COIs were more likely to NS. Public insurance and longer lead times were indicators of NS while higher ages were indicators for completed appointments. Therefore, efforts need to be made to identify vulnerable patients; younger patients, and those with lower COIs and public insurance; and address barriers such as arranging transport and sending reminders that can help decrease NS. Interestingly, the NS rate was lower than the national average. Future research is needed to assess the impact of NS on patient outcomes.