Changes in Perioperative Outcomes after Robotic-Assisted Pulmonary Lobectomy during the COVID-19 Era.

Background: The COVID-19 pandemic presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the pandemic affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 721 consecutive patients who underwent RAPL. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as "PreCOVID-19" and 83 patients as "COVID-19-Era" based on surgical date. Demographics, comorbidities, tumor characteristics, intraoperative complications, morbidity, and mortality were analyzed. Variables were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p ≤ 0.05 . Multivariable generalized linear regression was used to investigate predictors of postoperative complication. Results: COVID-19-Era patients had significantly higher preoperative FEV1%, lower cumulative smoking history and higher incidences of preoperative atrial fibrillation, peripheral vascular disease (PVD), and bleeding disorders compared to PreCOVID-19 patients. COVID-19-Era patients had lower intraoperative estimated blood loss (EBL), reduced incidence of new-onset postoperative atrial fibrillation (POAF), but higher incidence of effusion or empyema postoperatively. Overall postoperative complication rates between the groups were similar. Older age, increased EBL, lower preoperative FEV1%, and preoperative COPD are all predictive of an increased risk for postoperative complication. Conclusions: COVID-19-Era patients having lower EBL and less new-onset POAF, despite greater incidences of multiple preoperative comorbidities, demonstrates that RAPL is safe during the COVID-19 era. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Age, preoperative FEV1%, COPD, and EBL should all be considered when planning for complication risk.

Dantrolene inhibits lysophosphatidylcholine-induced valve interstitial cell calcific nodule formation via blockade of the ryanodine receptor.

Calcific aortic valve disease (CAVD), a fibrocalcific thickening of the aortic valve leaflets causing obstruction of the left ventricular outflow tract, affects nearly 10 million people worldwide. For those who reach end-stage CAVD, the only treatment is highly invasive valve replacement. The development of pharmaceutical treatments that can slow or reverse the progression in those affected by CAVD would greatly advance the treatment of this disease. The principal cell type responsible for the fibrocalcific thickening of the valve leaflets in CAVD is valvular interstitial cells (VICs). The cellular processes mediating this calcification are complex, but calcium second messenger signaling, regulated in part by the ryanodine receptor (RyR), has been shown to play a role in a number of other fibrocalcific diseases. We sought to determine if the blockade of calcium signaling in VICs could ameliorate calcification in an in vitro model. We previously found that VICs express RyR isotype 3 and that its modulation could prevent VIC calcific nodule formation in vitro. We sought to expand upon these results by further investigating the effects of calcium signaling blockade on VIC gene expression and behavior using dantrolene, an FDA-approved pan-RyR inhibitor. We found that dantrolene also prevented calcific nodule formation in VICs due to cholesterol-derived lysophosphatidylcholine (LPC). This protective effect corresponded with decreases in intracellular calcium flux, apoptosis, and ACTA2 expression but not reactive oxygen species formation caused by LPC. Interestingly, dantrolene increased the expression of the regulator genes RUNX2 and SOX9, indicating complex gene regulation changes. Further investigation via RNA sequencing revealed that dantrolene induced several cytoprotective genes that are likely also responsible for its attenuation of LPC-induced calcification. These results suggest that RyR3 is a viable therapeutic target for the treatment of CAVD. Further studies of the effects of RyR3 inhibition on CAVD are warranted.

Effects of preoperative pulmonary function on perioperative outcomes after robotic-assisted pulmonary lobectomy.

INTRODUCTION: Effects of pulmonary function test (PFT) results on perioperative outcomes were investigated after robotic-assisted video-thoracoscopic (RAVT) pulmonary lobectomy. METHODS: We retrospectively analyzed 706 consecutive patients who underwent RAVT lobectomy by one surgeon over 10.8 years. Preoperative (preop) forced expiratory volume in 1 s as a percent of predicted (FEV1%) was used to group patients as having normal FEV1% (≥80%) versus reduced FEV1% (<80%). Demographics, preop comorbidities, intraoperative (intraop) and postoperative (postop) complications, perioperative outcomes, and median survival time (MST) were compared across patients with normal vs. reduced FEV1% using Chi-Square (X2), Fisher's Exact test, Student's t-test, Kruskal-Wallis test, or Kaplan-Meier analysis respectively, with significance at p ≤ 0.05. Multivariable analysis was performed for perioperative outcomes to investigate the differences across patients in the FEV1% groups. RESULTS: There were 470 patients with normal FEV1% and 236 patients with reduced FEV1%. The two FEV1% groups did not differ in intraop or postop complication rates, except for higher postop other arrhythmia requiring intervention (p = 0.004), prolonged air leak >5 days (p = 0.002), mucous plug formation (p = 0.009), hypoxia (p < 0.001), and pneumonia (p = 0.002), and total postop complications (p < 0.001) in reduced-FEV1% patients. Reduced FEV1% correlated with increased intraop estimated blood loss (p < 0.0001) and skin-to-skin operative time (p < 0.0001). Median overall survival in patients with normal FEV1% was 93.20 months (95% CI: 76.5-126.0) versus 58.9 months (95% CI: 50.4-68.4) in patients with reduced FEV1% (p = 0.0004). CONCLUSION: Patients should have PFTs conducted before surgery to determine at-risk patients. However, RAVT pulmonary lobectomy is feasible and safe even in patients with reduced FEV1%.

A High Preoperative Blood Urea Nitrogen to Serum Albumin Ratio Does Not Predict Worse Outcomes Following the Robotic-Assisted Pulmonary Lobectomy for Lung Cancer.

BACKGROUND:  The blood urea nitrogen to serum albumin ratio (BAR) is an emerging prognostic parameter of interest. The utility of BAR as a prognostic factor has not been analyzed in lung cancer patients undergoing pulmonary lobectomy. We evaluated the ability of High BAR to predict worse outcomes after robotic-assisted pulmonary lobectomy (RAPL) for lung cancer. METHODS:  We retrospectively analyzed 400 patients who underwent RAPL from September 2010 to March 2022 by one surgeon. Patients were stratified by Low BAR (<6.25 mg/g) and High BAR (≥6.25 mg/g). Patients' demographics, tumor characteristics, comorbidities, surgical complications, outcomes, and survival were collected and compared by High and Low BAR groups. The primary outcome of interest was 30-day mortality. RESULTS:  Receiver operator curves (ROC) confirmed that 6.25 was an optimal threshold for estimating mortality based on Low and High BAR. There were no differences in surgical complications or outcomes between the Low and High BAR groups. The ability of BAR to predict 30-day mortality was evaluated with the area under the curve (AUC) analysis, which showed that higher BAR could not predict mortality (AUC=0.655; 95% CI, 0.435-0.875; p=0.166). Similarly, survival analysis revealed no difference in five-year overall survival between the Low and High BAR groups (p=0.079). CONCLUSION:  High BAR did not predict worse outcomes after RAPL for lung cancer in our study. Further studies are needed to better determine the prognostic ability of BAR in lower-risk populations.

Successful treatment of severe endometriosis in two premenopausal women with an aromatase inhibitor.

OBJECTIVE: To treat severe endometriosis in premenopausal women with an aromatase inhibitor and to document the efficacy and side effects of this new treatment. DESIGN: Case report. SETTING: Clinical practice setting. PATIENT(S): Patients were premenopausal endometriosis cases confirmed by prior laparoscopy. INTERVENTION(S): Oral administration of the aromatase inhibitor anastrozole with the addition of 200-mg oral progesterone (P) capsules once daily, hs, and calcitriol 0.5 microg oral capsules twice daily. All three medications were given daily for 21 days followed by 7 days off, for a 28-day treatment cycle. Additionally, rofecoxib 12.5 mg was administered once a day continuously for the 28-day cycle. The dose could be increased to 25-50 mg daily as needed for increased pain. Six repeat 28-day cycles were planned for the treatment course depending on patient tolerance and response. MAIN OUTCOME MEASURE(S): Reduction of symptoms, elimination of endometrial implants, and improvement in fertility potential in the future. Monitoring for ovarian hyperstimulation as a side effect of aromatase inhibitor therapy. Documentation of potential symptoms or side effects when an aromatase inhibitor is used in menstruating women. RESULT(S): Treatment resulted in a rapid, progressive reduction in symptoms over 3 months with the maintenance of remission of symptoms for over 24 months after treatment in both cases. There was confirmation of absence of disease in one case by follow-up laparoscopy 15 months after treatment. Pregnancy was achieved in both cases after 24 months. CONCLUSION(S): This is the first case report of successful treatment of severe endometriosis in premenopausal women with the aromatase inhibitor anastrozole combined with P, rofecoxib, and calcitriol. Treatment resulted in a rapid elimination of symptoms and was well tolerated in both cases.