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.

Surgical Treatment of Atrioesophageal Fistula: A Systematic Review.

BACKGROUND: Atrioesophageal fistula is a rare and morbid complication of ablation therapy for atrial fibrillation. Surgery provides increased survival; however, which surgical approach provides the best outcome is unclear. METHODS: We performed a retrospective analysis of cases in the literature and at our institution. We characterized patients by presenting symptoms, diagnostic method, surgical therapy with different approaches, and survival. RESULTS: In total, 219 patients were found, with 216 patients identified from 122 papers in the literature and 3 patients from our institutional database (2000-2022). The most common presenting symptoms included fever/chill (71.8%) and neurologic deficiency (62.9%). The overall survival for this cohort was 47%. Patients who had an operation had significantly improved survival compared with those who did not have an operation (71.9.3% vs 11%, P < .001). Patients who survived after surgical intervention typically underwent right thoracotomy (45.1%), patch repair of the left atrium (61.1%), and primary repair of the esophagus (68.3%) on cardiopulmonary bypass (84.8%) with a flap between the 2 organs (84.6%). Patients who had cardiopulmonary bypass had increased survival (39 of 45 [86.7%]) compared with those who did not have cardiopulmonary bypass (7 of 17 [41.2%], P < .001). CONCLUSIONS: Patients with atrioesophageal fistula should undergo surgical intervention. A patch repair of the left atrium and primary repair of the esophagus with a flap between the organs during cardiopulmonary bypass is the most common successful repair. Cardiopulmonary bypass may allow better débridement and repair of the left atrium, which may provide a survival advantage in the treatment of this rare disease.

Complex Robotic Lung Resection.

Performing robotic thoracic lung resection is becoming an option for patients with complex thoracic disease. The robotic-assisted approach has similar survival with decreased postoperative pain, morbidity, and hospital length of stay compared with the open approach in pneumonectomy, bronchoplasty, and arterioplasty. Appropriate patient selection based on medical and surgical history combined with surgeon experience is imperative for an excellent outcome. This article will discuss the use of the robot in pneumonectomy, arterioplasty, and bronchoplasty to provide information about the technical approach and postoperative management.

Acute mitral valve regurgitation secondary to papillary muscle rupture due to infective endocarditis.

BACKGROUND: Papillary muscle rupture due to infective endocarditis is a rare event and proper management of this condition has not been described in the literature. Our case aims to shed light on treatment strategies for these patients using the current guidelines. CASE PRESENTATION: This case presents a 58-year-old male with acute heart failure secondary to papillary muscle rupture. He underwent an en bloc resection of his mitral valve with a bioprosthetic valve replacement. Specimen pathology later showed necrotic papillary muscle due to infective endocarditis. The patient was further treated with antibiotic therapy. He recovered well post-operatively and continued to do well after discharge. CONCLUSION: In patients who present with papillary muscle rupture secondary to infective endocarditis, clinical symptoms should drive the treatment strategy. Despite the etiology, early mitral valve surgery remains treatment of choice for patients who have papillary muscle rupture leading to acute heart failure. Culture-guided prolonged antibiotic treatment is vital in this category of patients, especially those who have a prosthetic valve implanted.

Lobectomy Provides the Best Survival for Stage I Lung Cancer Patients Despite Advanced Age.

BACKGROUND: The Lung Cancer Study Group has shown that lobectomy provides the best survival in patients with non-small cell lung cancer. However, as patients become older, lobectomy may not provide a survival advantage compared with sublobar resection. METHODS: We analyzed the National Cancer Database for octogenarians with pathologic stage I lung cancer from 2004 to 2016. We then evaluated the patients who underwent lobectomy or sublobar (segmentectomy or wedge) resection for the treatment of cancer. We analyzed the 5-year survival rates of the groups as well as a cubic spline plot to determine age cutoffs where lobectomy does not provide improved survival. RESULTS: Among the octogenarians (227 134), there were 25 362 (26%) who had pathologic stage I lung cancer. There were 6370 (30%) patients who had sublobar resections (segmentectomy [n = 1192] and wedge resection [n = 5178]), whereas 14 594 (70%) patients had a lobectomy. There was significantly improved survival at 5 years with lobectomy compared with sublobar resection (48.5% vs 41.1%; P < .001). The cubic spline plot provided evidence that there was no age at which sublobar resection provided survival better than or equal to lobectomy (P < .001). CONCLUSIONS: In octogenarians with pathologic stage I lung cancer, lobectomy provided better 5-year survival compared with sublobar resection regardless of the age at surgical procedure. Hence, all patients with stage I cancer should be considered for a lobectomy if they are medically able to tolerate such a procedure.

Postoperative bleeding and leaks in sleeve gastrectomy are independent of both staple height and staple line oversewing.

BACKGROUND: Over 100,000 sleeve gastrectomy procedures are performed annually in the USA. Despite technological advances, postoperative bleeding and gastric staple line leak are complications of this procedure. We analyzed patient-specific and perioperative factors to determine their association with these complications. METHODS: We performed a retrospective cohort analysis of patients who underwent sleeve gastrectomy between 2005 and 2019 at our institution. Patient demographics, comorbidities, and procedure details including type of energy device, staple type, staple height, staple line oversewing, and staple line clipping were compared using multiple logistic regression for combined postoperative complications (blood transfusion, bleeding, and staple line leak). Postoperative bleeding was defined by requiring blood transfusion and/or re-operation to control bleeding. Staple line leak was confirmed radiographically. RESULTS: There were 1213 patients who underwent sleeve gastrectomy. Fifty-two high-risk patients were excluded due to cirrhosis, end-stage renal disease, and anticoagulation use for left ventricular assist device. Of the remaining 1161 patients, twenty-five (2.2%) received postoperative blood transfusion, nine (0.8%) had postoperative bleeding, two (0.2%) had staple line leak, and twenty-eight patients (2.4%) had combined postoperative complications. The median age was significantly higher for patients with combined postoperative complications (43 vs 49; p = 0.02). There was no difference in postoperative blood transfusion, bleeding, staple line leak, or combined postoperative complication with different energy devices (p = 0.92), staple types (p = 0.21), staple heights (p = 0.50), or staple line suturing/clipping (p = 0.95). In addition, there was no difference in bleeding when comparing staple line sewing techniques (p = 0.44). Predictably, patients with combined postoperative complications had increased length of stay (3 days vs 1 day; p < 0.001). CONCLUSION: Sleeve gastrectomy procedure has tremendous variability in technique and devices used. We observed no difference in the combined postoperative complications of bleeding or staple line leak with respect to different energy devices, staple height, or oversewing of the gastric staple line. Patient selection is crucial, as patient age and coagulopathic comorbidities were found to lead to higher combined postoperative complications.

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.