Characterizing the accuracy of robotic bronchoscopy in localization & targeting of small pulmonary lesions.

PURPOSE: Considering the recent implementation of lung cancer screening guidelines, it is crucial that small pulmonary nodules are accurately diagnosed. There is a significant need for quick, precise, and minimally invasive biopsy methods, especially for patients with small lung lesions in the outer periphery. Robotic bronchoscopy (RB) has recently emerged as a novel solution. The purpose of this study was to evaluate the accuracy of RB compared to the existing standard, electromagnetic navigational bronchoscopy (EM-NB). METHODS: A prospective, single-blinded, and randomized-controlled study was performed to compare the accuracy of RB to EM-NB in localizing and targeting pulmonary lesions in a porcine lung model. Four operators were tasked with navigating to four pulmonary targets in the outer periphery of a porcine lung, to which they were blinded, using both the RB and EM-NB systems. The dependent variable was accuracy. Accuracy was measured as a rate of success in lesion localization and targeting, the distance from the center of the pulmonary target, and by anatomic location. The independent variable was the navigation system, RB was compared to EM-NB using 1:1 randomization. RESULTS: Of 75 attempts, 72 were successful in lesion localization and 60 were successful in lesion targeting. The success rate for lesion localization was 100% with RB and 91% with EM- NB. The success rate for lesion targeting was 93% with RB and 80% for EM-NB. RB demonstrated superior accuracy in reaching the distance from the center of the lesion, at 0.62 mm compared to EM-NB at 1.28 mm (p = 0.001). Accuracy was improved using RB compared to EM- NB for lesions in the LLL (p = 0.025), LUL (p < 0.001), and RUL (p < 0.001). CONCLUSION: Our findings support RB as a more accurate method of navigating and localizing small peripheral pulmonary targets when compared to standard EM-NB in a porcine lung model. This may be attributed to the ability of RB to reduce substantial tissue displacement seen with standard EM-NB navigation. As the development and application of RB advances, so will the ability to accurately diagnose small peripheral lung cancer nodules, providing patients with early-stage lung cancer the best possible outcomes.

All-cause procedural readmissions following transcatheter aortic valve replacement.

Objective: With expanding eligibility criteria, transcatheter aortic valve replacement is being performed on patients with longer life expectancy, and subsequent procedures after index transcatheter aortic valve replacement are inevitable. This study examines the incidence and outcomes of patients undergoing subsequent procedural readmissions after transcatheter aortic valve replacement. Methods: All patients who underwent index transcatheter aortic valve replacement and were discharged alive from January 2012 to December 2019 at a single institution were evaluated. Study end points were mortality and readmission for procedure with more than 1-day hospital stay. Effect on survival was evaluated by treating procedural readmission as a time-dependent variable by Cox proportional hazard model and competing risk analysis. Results: A total of 1092 patients met inclusion criteria with a median follow-up time of 34 months. A total of 218 patients (20.0%) had 244 subsequent procedural readmissions. During the 244 procedural readmissions, there were 260 procedures; 96 (36.9%) were cardiac (most commonly pacemaker implantation, percutaneous coronary interventions, and surgical aortic valve replacements), and 164 (63.1%) were noncardiac (most commonly orthopedic and gastrointestinal procedures). The overall procedural readmission rates were 32%, 39%, and 42%, and all-cause mortality was 27%, 44%, and 54% at 20, 40, and 60 months, respectively. Procedural readmissions were not associated with a survival penalty in any surgical risk group or on Cox regression (hazard ratio, 1.25; 0.91-1.64, P = .17). Conclusions: After transcatheter aortic valve replacement, procedural interventions are seen frequently, with most procedures occurring within the first year after transcatheter aortic valve replacement. However, subsequent procedural readmissions do not appear to have a survival penalty for patients after transcatheter aortic valve replacement. After transcatheter aortic valve replacement with resolution of aortic stenosis, subsequent procedures can and should be pursued if they are needed.

Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib.

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, largely due to metastasis and drug resistant recurrences. Fifteen percent of ovarian tumors carry mutations in BRCA1 or BRCA2, rendering them vulnerable to treatment with PARP inhibitors such as olaparib. Recent studies have shown that TGFß can induce "BRCAness" in BRCA wild-type cancer cells. Given that TGFß is a known driver of epithelial to mesenchymal transition (EMT), and the connection between EMT and metastatic spread in EOC and other cancers, we asked if TGFß and EMT alter the susceptibility of EOC to PARP inhibition. Epithelial EOC cells were transiently treated with soluble TGFß, and their clonogenic potential, expression, and function of EMT and DNA repair genes, and response to PARP inhibitors compared with untreated controls. A second epithelial cell line was compared to its mesenchymal derivative for EMT and DNA repair gene expression and drug responses. We found that TGFß and EMT resulted in the downregulation of genes responsible for homologous recombination (HR) and sensitized cells to olaparib. HR efficiency was reduced in a dose-dependent manner. Furthermore, mesenchymal cells displayed sensitivity to olaparib, cisplatin, and the DNA-PK inhibitor Nu-7441. Therefore, the treatment of disseminated, mesenchymal tumors may represent an opportunity to expand the clinical utility of PARP inhibitors and similar agents.

Opioid Prescriptions After Hemorrhoidectomy.

BACKGROUND: Hemorrhoids cause more than 4 million ambulatory care visits in the United States annually, and hemorrhoidectomy is associated with significant postoperative pain. There are currently no evidence-based opioid-prescribing guidelines for hemorrhoidectomy patients. OBJECTIVE: The purpose of this study was to investigate patterns of opioid prescribing and to identify factors associated with opioid refill after hemorrhoidectomy. DESIGN: This was a retrospective database review. SETTINGS: The study was conducted using the Department of Defense Military Health System Data Repository (2006-2014). PATIENTS: Opioid-naïve patients aged 18 to 64 years enrolled in TRICARE insurance who underwent surgical hemorrhoidectomy were included in this study. MAIN OUTCOME MEASURES: We measured patterns of opioid prescriptions and predictors of a second opioid prescription within 2 weeks of the end date for the first prescription after hemorrhoidectomy. RESULTS: A total of 6294 patients were included; 5536 (88.0%) filled an initial opioid prescription with a median 5-day supply, and 1820 (32.9%) required an opioid refill. The modeled risk of refill based on initial prescription supply ranged from a high of 39.2% risk with an initial prescription of 1-day supply to an early nadir (26.1% risk of refill) with an initial 10-day supply. A variety of sociodemographic and clinical characteristics influenced the likelihood of opioid refill, including black race (OR = 0.75 (95% CI, 0.62-0.89)), history of substance abuse (OR = 3.26 (95% CI, 1.37-7.34)), and length of index opioid prescription (4-6 d, OR = 0.83 (95% CI, 0.72-0.96) or ≥7 d, OR = 0.67 (95% CI, 0.57-0.78) vs 1-3 d). LIMITATIONS: Variables assessed were limited because of the use of claims-based data. CONCLUSIONS: There is wide variability in the length of prescription opioid use after hemorrhoidectomy. Approximately one third of patients require a second prescription in the immediate postoperative period. The optimal duration appears to be between a 5- and 10-day supply. Clinicians may be able to more efficiently discharge patients with adequate analgesia while minimizing the potential for excess supply. See Video Abstract at http://links.lww.com/DCR/B112. PRESCRIPCIÓN DE MÉDICAMENTOS OPIOIDES DESPUÉS DE HEMORROIDECTOMÍA: Las afecciones hemorroidarias ocasionan anualmente más de cuatro millones de consultas ambulatorias en los Estados Unidos. La hemorroidectomía esta asociada con dolor postoperatorio muy significativo. Actualmente no existen pautas claras para la prescripción de medicamentos opioides después de hemorroidectomía, basada en la evidencia.Investigar los patrones de prescripción de medicamentos opioides e identificar los factores asociados con la acumulación de dichos opioides después de una hemorroidectomía.Revisión retrospectiva de una base de datos.Almacén de datos del Sistema de Salud militar del Departamento de Defensa de los Estados Unidos de América (2006-2014).Todos aquellos sometidos a hemorroidectomía quirúrgica, sin tratamiento opiode previo, comprendiodos entre 18-64 años y beneficiarios de seguro TRICARE.Patrones de prescripción de recetas de opioides, predictores de una segunda receta de opioides dentro las dos semanas posteriores a la fecha de finalización de la primera receta después de la hemorroidectomía.6.294 pacientes fueron incluidos en el estudio. 5.536 (88,0%) completaron una receta inicial de opioides con un suministro promedio de cinco días, y 1.820 (32,9%) pacientes requirieron reabastecerse de opioides. El riesgo modelado de reabastecimiento de opiodes basado en el suministro de la prescripción inicial, varió desde un alto riesgo (39.2%) con una prescripción inicial de suministro por día, hasta un acmé temprano (26.1% de riesgo de reabastecimiento) con un suministro inicial de 10 días. Una gran variedad de características socio-demográficas y clínicas influyeron en la probabilidad del reabastecimeinto de los opioides, incluida la raza negra (OR 0.75, intervalo de confianza (IC) del 95% (0.62, 0.89)), los antecedentes de abuso de substancias (OR 3.26, IC del 95% (1.37, 7.34)) y la duración del índice de la prescripción de opioides (4-6 días (OR 0.83, IC 95% (0.72, 0.96)), o 7 días o más (OR 0.67, IC 95% (0.57, 0,78)) comparados a 1-3 días.Las variables analizadas fueron limitadas debido al uso de datos basados en reclamos.Existe una gran variabilidad en la duración del uso de opioides recetados después de hemorroidectomía. Aproximadamente un tercio de los pacientes requieren una segunda prescripción en el postoperatorio inmediato. La duración óptima parece estar entre un suministro de cinco y 10 días. Los médicos pueden dar de alta de manera más eficiente a los pacientes con analgesia adecuada y minimizar el potencial de exceso de suministro. Consulte Video Resumen en http://links.lww.com/DCR/B112. (Traducción-Dr. Xavier Delgadillo).