Mortality index is more accurate than volume in predicting outcome and failure to rescue in Medicare beneficiaries undergoing robotic right upper lobectomy.

Background: Surgical volume is known to influence failure to rescue (FTR), defined as death following a complication. Robotic lung surgery continues to expand and there is variability in outcomes among hospitals. We sought to estimate the contribution of hospital-based factors on outcomes and FTR following robotic right upper lobectomy (RRUL). Methods: Using the Centers for Medicare and Medicaid Services inpatient claims database, we evaluated all patients age ≥65 years with a diagnosis of lung cancer who underwent RRUL between January 2018 and December 2020. We excluded patients who had undergone segmentectomy, sublobar, wedge, or bronchoplastic resection; had metastatic or nonmalignant disease; or had a history of neoadjuvant chemotherapy. Primary outcomes included FTR rate, length of stay (LOS), readmissions, conversion to open surgery, complications, and costs. We analyzed hospitals by tertiles of volume and Medicare Mortality Index (MMI). Defined as the institutional number of deaths per number of survivors, MMI is a marker of overall hospital performance and quality. Propensity score models were adjusted for confounding using goodness of fit. Results: Data for 4317 patients who underwent robotic right upper lobectomy were analyzed. Hospitals were categorized by volume of cases (low, <9; medium, 9-20; high, >20) and MMI (low, <0.04; medium, 0.04-0.13; high, >0.13). After propensity score balancing, patients from tertiles of lowest volume and highest MMI had higher costs ($34,222 vs $30,316; P = .006), as well as higher mortality (odds ratio, 7.46; 95% confidence interval, 2.67-28.2; P < .001). Compared to high-volume centers, low-volume centers had higher rates of conversion to open surgery, respiratory failure, hemorrhagic anemia, and death; longer LOS; and greater cost (P < .001 for all). The C-statistic for volume as a predictor of overall mortality was 0.6, and the FTR was 0.8. Hospitals in the highest tertile of MMI had the highest rates of conversion to open surgery (P = .01), pneumothorax (P = .02), and respiratory failure (P < .001). They also had the highest mortality and rate of readmission, longest LOS, and greatest costs (P < .001 for all) and the shortest survival (P < .001). The C-statistic for MMI as a predictor of overall mortality was 0.8, and FTR was 0.9. Conclusions: The MMI incorporates hospital-based factors in the adjudication of outcomes and is a more sensitive predictor of FTR rates than volume alone. Combining MMI and volume may provide a metric that can guide quality improvement and cost-effectiveness measures in hospitals seeking to implement robotic lung surgery programs.

Intersection of Race, Rurality, and Income in Defining Access to Minimally Invasive Lung Surgery.

BACKGROUND: Race is a potent influencer of health care access. Geography and income may exert equal or greater influence on patient outcomes. We sought to define the intersection of race, rurality, and income and their influence on access to minimally invasive lung surgery in Medicare beneficiaries. METHODS: Centers for Medicare and Medicaid Services data were used to evaluate patients with lung cancer who underwent right upper lobectomy, by open, robotic-assisted thoracic surgery (RATS), or video-assisted thoracic surgery (VATS) between 2018 and 2020. International Classification of Diseases, 10th Edition, was used to define diagnoses and procedures. We excluded sublobar, segmental, wedge, bronchoplasty, or reoperative patients with nonmalignant or metastatic disease or a history of neoadjuvant chemotherapy. Risk adjustment was performed using inverse probability of treatment weighting (IPTW) propensity scores with generalized linear models and Cox proportional hazards models. RESULTS: The cohort comprised 13,404 patients, 4291 open (32.1%), 4317 RATS (32.2%), and 4796 VATS (35.8%). Black/urban patients had significantly higher RATS and VATS rates (P < .001), longer long-term survival (P = .007), fewer open resections (P < .001), and lower overall mortality (P = .007). Low-income Black/urban patients had higher RATS (P = .002), VATS (P < .001), longer long-term survival (P = .005), fewer open resections (P < .001), and lower overall mortality compared with rural White patients (P = .005). CONCLUSIONS: Rural White populations living close to the federal poverty line may suffer a burden of disparity traditionally observed among poor Black people. This suggests a need for health policies that extend services to impoverished, rural areas to mitigate social determinants of health.

Predictors of Occlusion after Carotid Stenting.

BACKGROUND: Carotid artery stent (CAS) occlusion is a rare complication not well studied. We used a national dataset to assess real world CAS experience to determine the rate of stent occlusion. The purpose of this study was to 1) Identify risk factors associated with CAS occlusion on long-term follow-up (LTFU) and 2) Determine the adjusted odds of death/transient ischemic attack (TIA)/stroke (cerebrovascular accident (CVA)) in patients with occlusion. METHODS: The national Vascular Quality Initiative CAS dataset (2016-2021) comprised the sample. The primary endpoint was occlusion on LTFU (9-21 months postoperatively as defined by the Vascular Quality Initiative LTFU dataset) with secondary endpoint examining a composite of death/TIA/CVA. Descriptive analyses used chi-square and Wilcoxon tests for categorical and continuous variables respectively. Adjustment variables were selected a priori based on clinical expertise and univariate analyses. Multivariable logistic regression was used to model the odds of occlusion and the odds of death/TIA/CVA. Generalized estimating equations accounted for center level variation. RESULTS: During the study period, 109 occlusions occurred in 12,143 cases (0.9%). On univariate analyses, symptomatic indication, prior stroke, prior neck radiation, lesion calcification (>50%), stenosis (>80%), distal embolic protection device (compared to flow reversal), balloon size, >1 stent and current smoking at time of LTFU were predictive for occlusion. Age ≥ 65, coronary artery disease (CAD), elective status, preoperative statin, preoperative and discharge P2Y12 inhibitor, use of any protection device intraoperatively and protamine were protective. On multivariable analyses, age ≥ 65, CAD, elective status and P2Y12 inhibitor on discharge were protective for occlusion, while patients with prior radiation and those taking P2Y12 inhibitor on LTFU were at increased odds. The adjusted odds of death/TIA/CVA in patients with occlusion on LTFU were 6.05; 95% confidence interval: 3.61-10.11, P < 0.0001. CONCLUSIONS: This study provides an in-depth analysis of predictors for CAS occlusion on LTFU. On univariate analyses, variables related to disease severity (urgency, degree of stenosis, nature of lesion) and intraoperative details (balloon diameter, >1 stent) were predictive for occlusion. These variables were not statistically significant after risk adjustment. On multivariable analyses, prior neck radiation was strongly predictive of occlusion. Elective status, patient age ≥ 65, CAD, and P2Y12 inhibitor upon discharge (but not on LTFU) were protective for occlusion. Additionally, patients who developed occlusion had high odds for death/TIA/CVA. These findings provide important data to guide clinical decision-making for carotid disease management, particularly identifying high-risk features for CAS occlusion. Closer postoperative follow-up and aggressive risk factor modification in these patients may be merited.

Comparison of direct oral anticoagulants and warfarin in chronic limb-threatening ischemia.

OBJECTIVE: The role of direct oral anticoagulants (DOACs) in chronic limb-threatening ischemia after revascularization is unknown. Current evidence-based guidelines do not provide clear guidance on the role of anticoagulation or the selection of anticoagulant. Current practice is highly varied and based on provider and patient preference. The purpose of this study was to measure the impact of different anticoagulants on the incidence of major adverse limb events (MALEs) after revascularization for chronic limb-threatening ischemia, major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for major bleeding events. METHODS: This was a single-center, observational, retrospective cohort study. Subjects were eligible if they were 18 years or older; underwent endovascular or open revascularization for chronic limb-threatening ischemia, rest pain, or tissue loss; and were subsequently prescribed apixaban, rivaroxaban, or warfarin. The primary end point was the incidence of MALEs, including above-ankle amputation or major index-limb reintervention, within 1 year of index event. Secondary end points included the rate of all-cause mortality, MACEs, and incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding. RESULTS: From January 1, 2017, to September 20, 2022, 141 patients met the inclusion and exclusion criteria and were reviewed. The median age was 67 years, with 92 patients prescribed apixaban or rivaroxaban and 49 patients prescribed warfarin. Of these, 42 patients were prescribed triple antithrombotic therapy, 88 dual antithrombotic therapy, and 13 anticoagulant monotherapy. The primary outcome of 1-year MALEs occurred in 36.7% of the warfarin group and 33.7% of the DOAC group (relative risk [RR], 1.09; 95% CI, 0.53-2.25; P = .72). Secondary outcomes of 1-year MACEs (10.2% vs 4.3%; RR, 2.35; 95% CI, 0.60-9.18; P = .18) and 1-year all-cause mortality (26.5% vs 16.3%; RR, 1.63; 95% CI, 0.70-3.78; P = .15) did not differ between the groups. The secondary safety outcome of 1-year ISTH major bleeding occurred in 16.3% of the warfarin group and 4.3% of the DOAC group (RR, 3.76; 95% CI, 1.07-13.19; P = .015). CONCLUSIONS: In patients with chronic limb-threatening ischemia who were revascularized and prescribed anticoagulation with apixaban, rivaroxaban, or warfarin on discharge, no difference in MALEs, MACEs, or all-cause mortality was found. However, 1-year admissions for ISTH major bleeding were significantly higher among patients prescribed warfarin. A randomized trial may confirm these findings.

Factors during training which predict future use of minimally invasive thoracic surgery.

BACKGROUND: While minimally invasive thoracic surgery (MIS) has increased nationwide over the years, most patients undergoing lung and esophageal resections still undergo an open approach. We performed a national survey to analyze factors associated with a propensity to perform MIS after completing a cardiothoracic training program. MATERIALS AND METHODS: Cardiothoracic surgery trainees in 2 or 3-year programs from 2010 to 2016 were sent an online survey regarding the numbers and types of cases performed during training and current practice patterns as attending surgeons. Comfort level with MIS was also assessed. Responses were recorded and analyzed using SPSS. RESULTS: One hundred thirty-six trainees responded, with a mean of 121 lobectomies (30-250) and 40 esophagectomies (8-110) performed during training. Mean minimally invasive lobectomy and esophagectomy rates during training were 53% and 30% respectively. A greater ratio of MIS procedures performed during training correlated with a higher rate performed as an attending (lobectomies, p = 0.04; esophagectomies, p = 0.01) and a greater comfort level with performing these procedures (lobectomies, p = 0.01 and esophagectomies, p < 0.01). CONCLUSIONS: Based on these results, performing a greater ratio of minimally invasive lobectomies and esophagectomies during fellowship training increases the likelihood of performing them as an attending.

Absolute oral bioavailability and pharmacokinetics of canagliflozin: A microdose study in healthy participants.

Absolute oral bioavailability of canagliflozin was assessed by simultaneous oral administration with intravenous [(14) C]-canagliflozin microdose infusion in nine healthy men. Pharmacokinetics of canagliflozin, [(14) C]-canagliflozin, and total radioactivity, and safety and tolerability were assessed at prespecified timepoints. On day 1, single-dose oral canagliflozin (300 mg) followed 105 minutes later by intravenous [(14) C]-canagliflozin (10 µg, 200 nCi) was administered. After oral administration, the mean (SD) Cmax of canagliflozin was 2504 (482) ng/mL at 1.5 hours, AUC∞ 17,375 (3555) ng.h/mL, and t1/2 11.6 (0.70) hours. After intravenous administration, the mean (SD) Cmax of unchanged [(14) C]-canagliflozin was 17,605 (6901) ng/mL, AUC∞ 27,100 (10,778) ng.h/mL, Vdss 83.5 (29.2) L, Vdz 119 (41.6) L, and CL 12.2 (3.79) L/h. Unchanged [(14) C]-canagliflozin and metabolites accounted for about 57% and 43% of the plasma total [(14) C] radioactivity AUC∞ , respectively. For total [(14) C] radioactivity, the mean (SD) Cmax was 15,981 (2721) ng-eq/mL, and AUC∞ 53,755 (15,587) ng-eq.h/mL. Renal (34.5% in urine) and biliary (34.1% in feces) excretions were the major elimination pathways for total [(14) C] radioactivity. The absolute oral bioavailability of canagliflozin was 65% (90% confidence interval: 55.41; 76.07). Overall, oral canagliflozin 300 mg coadministered with intravenous [(14) C]-canagliflozin (10 µg) was generally well-tolerated in healthy men, with no treatment-emergent adverse events.

Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on the pharmacokinetics of oral contraceptives, warfarin, and digoxin in healthy participants.

OBJECTIVE: Drug-drug interactions between canagliflozin, a sodium glucose co-transporter 2 inhibitor approved for the management of type-2 diabetes mellitus, and an oral contraceptive (OC), warfarin, and digoxin were evaluated in three phase 1 studies in healthy participants. METHODS: All studies were open-label; study 1 included a fixed-sequence design, and studies 2 and 3 used a crossover design. Regimens were: study 1: OC (levonorgestrel (150 µg) + ethinyl estradiol (30 µg))/day (day 1), canagliflozin 200 mg/day (days 4 - 8), and canagliflozin with OC (day 9); study 2: canagliflozin 300 mg/day (days 1 - 12) with warfarin 30 mg/day (day 6) in period 1, and only warfarin 30 mg/day (day 1) in period 2, or vice versa; study 3: digoxin alone (0.5 mg/day (day 1) + 0.25 mg/day (days 2 - 7)) in period 1, and with canagliflozin 300 mg/day (days 1 - 7) in period 2, or vice versa. Pharmacokinetics (PK) were assessed at prespecified intervals; OC: days 1 and 9, canagliflozin: days 8 - 9 (study 1); warfarin: days 6 (period 1) and 1 (period 2) (study 2); and digoxin: days 5 - 7 (periods 1 and 2) (study 3). Warfarin's pharmacodynamics (PD; International Normalized Ratio (INR)) was assessed on days 6 (period 1) and 1 (period 2). RESULTS: Canagliflozin increased the plasma exposure of OC (maximum plasma concentration (Cmax): 22%, area under the curve (AUC): 6%) and digoxin (Cmax: 36%, AUC: 20%); but did not alter warfarin'€™s PK and PD. No clinically relevant safety findings (including hypoglycemia) were noted. CONCLUSION: Canagliflozin can be coadministered with OC, warfarin, or digoxin without dose adjustments. All treatments were well-tolerated.

Usability of telepresence in a level 1 trauma center.

OBJECTIVES: Limited resources and the diminishing physician workforce in trauma require unique and innovative solutions. Our hypothesis is that telepresence by a remote physician is an appropriate application in an urban trauma setting. The purpose of this study is to assess user satisfaction and usability of a mobile telemedicine robot in trauma care. MATERIALS AND METHODS: A usability study of trauma patient assessments utilizing the Remote Presence-7 (RP-7) robot (InTouch Health, Santa Barbara, CA) with real-time, two-way communication between remote and local physicians was conducted at a Level 1 trauma center. Usability and acceptability was measured using survey questionnaires, open-ended feedback, and general observations. Comparisons were made between remote and local physician responses. RESULTS: One hundred fourteen patient encounters utilizing telepresence were performed. Remote and local physicians expressed a high level of satisfaction with the mobility (92% and 79%, respectively), communication (97% and 90%, respectively), and visual abilities (91% and 97%, respectively) of the RP-7 robot for remote consultation purposes. On average, 89% of remote and local physician participants rated their overall telemedicine experience as "excellent" or "above average." CONCLUSIONS: This study suggests that telepresence of a remote trauma surgeon may be a useful and functional adjunct in the trauma setting. Further development of these technologies could mitigate current and future concerns about gaps in rural and urban trauma care and critical care staffing shortages and during mass casualty or disaster scenarios.

Whole-body biodistribution and radiation dosimetry of the human cannabinoid type-1 receptor ligand 18F-MK-9470 in healthy subjects.

UNLABELLED: The cannabinoid type-1 (CB1) receptor is one of the most abundant G-coupled protein receptors in the human body and is responsible for signal transduction of both endogenous and exogenous cannabinoids. The endocannabinoid system is strongly implicated in regulation of homeostasis and several neuropsychiatric disorders, obesity, and associated comorbidities, such as dyslipidemia and metabolic syndrome. We have used whole-body PET/CT to characterize the biodistribution and dosimetry of a novel high-affinity, subtype-selective radioligand, (18)F-MK-9470, in healthy male and female subjects. METHODS: Eight nonobese subjects (5 men, 3 women; age, 22-54 y) underwent serial whole-body PET/CT for 6 h after a bolus injection of 251 +/- 25 MBq (18)F-MK-9470 (N-[2-(3-cyano-phenyl)-3-(4-(2-(18)F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide). Source organs were delineated 3-dimensionally using the combined morphologic and functional data. Residence times were derived from time-activity profiles using both the trapezoid rule and curve fitting. Individual organ doses and effective doses were determined using the OLINDA software package, with different approaches for gastrointestinal and urinary excretion modeling. RESULTS: (18)F-MK-9470 is taken up slowly in the brain, reaching a plateau at approximately 90-120 min after bolus injection and is excreted predominantly through the hepatobiliary system. The gallbladder, upper large intestine, small intestine, and liver are the organs with the highest absorbed dose (average: 159, 98, 87, and 86 microGy/MBq, respectively). The mean effective dose (ED) was 22.8 +/- 4.3 microSv/MBq, indicating relatively low intersubject variability and a mean value in the range of many commercially available (18)F-labeled radiopharmaceuticals. Brain uptake was relatively high compared with that of existing central nervous system ligands for other receptors, between 3.2% and 4.9% of the injected dose. CONCLUSION: The estimated radiation burden of (18)F-MK-9470 for PET CB1 receptor imaging shows relatively low variability between subjects and has an acceptable ED, which allows multiple serial cerebral scans of good image quality, while remaining within the risk category class II-b defined by the World Health Organization and the International Commission for Radiation Protection for a standard injected activity (185-370 MBq).