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Efficiently Targeting Neuroblastoma With the Combination of Anti-Ror1 Car Nk Cells and N-803 and in Nb Xenografts
No full textThe prognosis for children with recurrent and/or refractory neuroblastoma (NB) is dismal. The receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is highly expressed on the surface of NB cells, provides a potential target for novel immunotherapeutics. Anti-ROR1 chimeric antigen receptor engineered expanded peripheral blood natural killer (anti-ROR1 CAR exPBNK) cells represent this approach. N-803 is an IL-15 superagonist with enhanced biological activity. In this study, we investigated the and anti-tumor effects of anti-ROR1 CAR exPBNK cells with or without N-803 against ROR1 NB models. Compared to mock exPBNK cells, anti-ROR1 CAR exPBNK cells had significantly enhanced cytotoxicity against ROR1 NB cells, and N-803 further increased cytotoxicity. High-dimensional analysis revealed that N-803 enhanced Stat5 phosphorylation and Ki67 levels in both exPBNK and anti-ROR1 CAR exPBNK cells with or without NB cells. anti-ROR1 CAR exPBNK plus N-803 significantly ( \u3c 0.05) enhanced survival in human ROR1 NB xenografted NSG mice compared to anti-ROR1 CAR exPBNK alone. Our results provide the rationale for further development of anti-ROR1 CAR exPBNK cells plus N-803 as a novel combination immunotherapeutic for patients with recurrent and/or refractory ROR1 NB
Impact of Age on Hospital Outcomes After Catheter Ablation for Ventricular Tachycardia
No full textBACKGROUND: The real-world data on the safety profile of ventricular tachycardia (VT) ablation among elderly patients is not well-established. This study aimed to evaluate the procedural outcomes among those aged 18-64 years versus those aged ≥65 years who underwent catheter ablation of VT.
METHOD: Using the Nationwide Readmissions Database, our study included patients aged ≥18 years who underwent VT catheter ablation between 2017 and 2020. We divided the patients into non-elderly (18-64 years old) and elderly age groups (≥65 years old). We then analyzed the in-hospital procedural outcome and 30-day readmission between these two groups.
RESULTS: Our study included 2075 (49.1%) non-elderly patients and 2153 (50.9%) elderly patients who underwent VT ablation. Post-procedurally, elderly patients had significantly higher rates of prolonged index hospitalization (≥7 days; 35.5% vs. 29.3%,
CONCLUSION: Elderly patients have worse in-hospital outcome, early mortality, non-home discharge, and 30-day readmission following catheter ablation for VT. There was no significant difference between elderly and non-elderly groups in the procedural complications
Impact of Left Ventricular Unloading on Outcome of Heart Transplant Bridging With Extracorporeal Membrane Oxygenation Support in New Allocation Policy
No full textBACKGROUND: The new heart allocation policy places veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-supported heart transplant (HT) candidates at the highest priority status. Despite increasing evidence supporting left ventricular (LV) unloading during VA-ECMO, the effect of LV unloading on transplant outcomes following bridging to HT with VA-ECMO remains unknown. METHODS AND RESULTS: From October 18, 2018 to March 21, 2023, 624 patients on VA-ECMO at the time of HT were identified in the United Network for Organ Sharing database and were divided into 2 groups: VA-ECMO alone (N=384) versus VA-ECMO with LV unloading (N=240). Subanalysis was performed in the LV unloading group: Impella (N=106) versus intra-aortic balloon pump (N=134). Recipient age was younger in the VA-ECMO alone group (48 versus 53 years, =0.018), as was donor age (VA-ECMO alone, 29 years versus LV unloading, 32 years, =0.041). One-year survival was comparable between groups (VA-ECMO alone, 88.0±1.8% versus LV unloading, 90.4±2.1%; =0.92). Multivariable Cox hazard model showed LV unloading was not associated with posttransplant mortality after HT (hazard ratio, 0.92; =0.70). Different LV unloading methods had similar 1-year survival (intra-aortic balloon pump, 89.2±3.0% versus Impella, 92.4±2.8%; =0.65). Posttransplant survival was comparable between different Impella versions (Impella 2.5, versus Impella CP, versus Impella 5.0, versus Impella 5.5). CONCLUSIONS: Under the current allocation policy, LV unloading did not impact waitlist outcome and posttransplant survival in patients bridged to HT with VA-ECMO, nor did mode of LV unloading. This highlights the importance of a tailored approach in HT candidates on VA-ECMO, where routine LV unloading may not be universally necessary
The Variation of Chargemaster Price Listings for Urogynecologic Procedures
No full textIMPORTANCE: A 2018 Executive Order calling for price transparency required hospitals to publicly provide chargemasters, which are detailed lists of standard price listings for billable medical procedures. OBJECTIVES: The objective of this study was to evaluate price listing variations in common urogynecology procedures. STUDY DESIGN: This was a cross-sectional study of chargemasters obtained between February and April 2020 from hospitals across 5 states chosen to reflect the diversity of health systems in the United States. Hospital characteristic and quality metric data were obtained from the Homeland Infrastructure Foundation, U.S. Department of Agriculture, and U.S. Centers for Medicare & Medicaid Services websites. Current Procedural Terminology codes and procedure names for 9 urogynecologic procedures were used to search each chargemaster and extract price listings. Price listings were compared with data on quality, population demographics, and hospital characteristics to determine if any significant relationships existed. RESULTS: Eight hundred thirty-four chargemasters were identified. Price listings for most procedures differed significantly across the 5 states, including colpocleisis, cystoscopy with chemodenervation, diagnostic cystoscopy, diverticulectomy, sacral neuromodulation, midurethral sling, and sacrospinous ligament fixation. Price listings were significantly higher in urban hospitals than rural hospitals for 6 procedures. No significant association was seen with price listing and quality measures for most procedures. CONCLUSIONS: Listed prices varied for several urogynecologic procedures. Some of this variation is associated with hospital characteristics such as urban setting. However, notably, price listing was not associated with quality. Further investigation of chargemaster price listings with hospital characteristics and quality metrics and with what is actually paid by patients is imperative for patients to navigate charges
Comparison of Diagnostic Accuracy and Acceptability of Self-Sampling Devices for Human Papillomavirus Detection: A Systematic Review
No full textProject Prevent: A Randomized Controlled Trial of Preoperative Vaginal Metronidazole to Decrease Patient Issues and Infections After Hysterectomy
No full textOBJECTIVES: To evaluate if vaginal metronidazole for 5 days before hysterectomy decreases postoperative infections and patient issues. DESIGN: This randomized trial compared vaginal metronidazole for 5 days before a scheduled hysterectomy to no intervention. Sample size calculation was based on a 20% difference in issues and infection (30% incidence and 10% in the intervention arm) with 80% power and an alpha error of 0.05 and indicated 62 subjects needed in each arm. SETTING: Outpatient gynecology clinics at a single academic institution. PARTICIPANTS: 154 subjects were screened for eligibility between July 2020 and September 2022. 133 underwent hysterectomy including 68 subjects (51.1%) randomized to the metronidazole and 65 (48.9%) controls. Overall, the population was racially and ethnically diverse. There was no significant difference in characteristics between the two groups. INTERVENTIONS: Vaginal metronidazole for 5 days before hysterectomy. MAIN OUTCOME MEASURES: Postoperative patient issues and documented postoperative infections at 4-8 weeks after surgery. RESULTS: There was no difference in the composite rate of patient-reported issues and/or documented postoperative infection (53/133 (39.8%) with no difference between groups (29/68 (42.6%) vs 24/65 (36.9%), p=0.50). There was no difference in patient-reported issues which was 51/133 (38.3%) with no difference between groups (28/68 (41.2%) vs 23/65 (33.8%), p=0.49) or in documented infections with a rate of 25/133 (18.8%) with no significant difference between groups (15/68 (22.0%) vs 10/65 (15.4%), p=0.33). In the intervention arm, the compliance rate was 73.5% for all 5 days of vaginal metronidazole, and a per-protocol analysis was performed which resulted in no significant difference between groups. CONCLUSIONS: There is insufficient evidence to suggest a significant benefit of preoperative vaginal metronidazole to prevent surgical site infections and postoperative patient issues in patients undergoing hysterectomy. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04478617
Baseline Coronary Artery Stenosis Severity is an Independent Predictor of Subsequent Poor Sleep Quality in Patients With Acute Coronary Syndrome
No full textAIM: To investigate the relationship between coronary artery lesion severity determined using the baseline SYNTAX score and sleep problems that might occur after discharge determined using the Pittsburgh Sleep Quality Index (PSQI).
METHODS: This prospective study included patients with first acute coronary syndrome (ACS) who underwent percutaneous coronary angiography between February 2019 and August 2019. The severity of coronary artery stenosis was classified according to coronary angiography and SYNTAX scores. Patients were grouped as those with a SYNTAX score of ≤22 and \u3e22. Sleep quality after discharge was classified according to the PSQI. PSQI ≤5 represented good sleep quality, and PSQI \u3e5 represented poor sleep quality. Univariate and multivariate logistic regression was used to investigate the relationship between sleep quality and coronary artery stenosis severity.
RESULTS: A total of 424 patients were included in the study. Of these, 294 (69.34%) had a SYNTAX score of ≤22 and 130 (30.66%) had a SYNTAX score of \u3e22. The mean age of all patients was 60.37 ± 12.23 years, 59.69 ± 11.85 years in the SYNTAX ≤22 groups and 61.90 ± 12.98 years in the SYNTAX \u3e22 group (P = 0.086). The majority (78.54%) of the patients were male and there was no significant difference between the SYNTAX ≤22 group and the SYNTAX \u3e22 group in terms of sex distribution (P = 0.383). According to the univariate logistic regression analysis, age (P = 0.014), diabetes (P = 0.027), left ventricular ejection fraction (P = 0.001), estimated glomerular filtration rate (P = 0.039), creatine kinase MB (P = 0.040) and SYNTAX scores (P \u3c 0.001) were significantly associated with high PSQI global scores (\u3e5). However, according to the multivariate logistic regression analysis results, high (\u3e22) SYNTAX scores were the only factor independently associated with the high (\u3e5) PSQI global scores [odds ratio, 3.477; 95% confidence interval (CI), (2.190-5.522); P \u3c 0.001]. Complete revascularization group had significantly higher sleep latency and sleep duration time, sleep efficiency and the percentage of patients with PSQI global score of ≤5 than the incomplete revascularization group (P \u3c 0.001 for all).
CONCLUSION: Among patients with ACS, those with high SYNTAX scores should be monitored more carefully for sleep disorders that may occur later
