Serotonin transporter deficiency in mice results in an increased susceptibility to HTR2B-dependent pro-fibrotic mechanisms in the cardiac valves and left ventricular myocardium.

Increased serotonin (5HT) concentration and signaling, can lead to pathological remodeling of the cardiac valves. We previously showed that a reduction of the 5HT transporter (SERT) expression in the mitral valve (MV) contributes to the progression of degenerative MV regurgitation (MR). We sought to investigate the myocardial and valvular phenotype of SERT-/- mice in order to identify remodeling mechanisms specific to the MV and left ventricular (LV) remodeling. Using 8- and 16-week-old WT and SERT-/- mice we show that male and female animals deficient of SERT have pathological remodeling of the cardiac valves, myocardial fibrosis, diminished ejection fraction and altered left ventricular dimensions. In the MV and intervalvular area of the aortic valve (AV)-MV, gene expression, including Col1a1 mRNA, was progressively altered with age up until 16 weeks of age. In contrast, in the AV and myocardium, most gene expression changes occurred earlier and plateaued by 8 weeks. To explore basal differences in susceptibility to remodeling stimuli among cardiac valves, valve interstitial cells (VIC) were isolated from AV, MV, tricuspid valve (TV), pulmonary valve (PV) and fibroblasts (Fb) from the myocardial apex from 16 weeks old wild type (WT) mice. After 24h stimulation with 10 µM of 5HT, the gene expression of Col1a1 and Acta2 were upregulated in MVIC to a higher degree than in VIC from other valves and Fb. Treatment with TGFß1 similarly upregulated Cola1 and Acta2 in MVIC and AVIC, while the increase was milder in right heart VIC and Fb. Experiments were also carried out with human VIC. In comparison to mice, human left heart VIC were more sensitive to 5HT and TGFß1, upregulating COL1A1 and ACTA2; TGFß1 upregulated HTR2B expression in all VIC. Our results support the hypothesis that a deleterious cardiac effect of SERT downregulation may be mediated by increased susceptibility to HTR2B-dependent pro-fibrotic mechanisms, which are distinct among VIC populations and cardiac fibroblasts, regardless of SERT activity. Given that HTR2B mechanisms involved in VIC and myocardial remodeling response are due to both 5HT and also to downstream related TGFß1 and TNFα activity, targeting HTR2B could be a therapeutic strategy for dual treatment of MR and LV remodeling.

Walking one hour per day and the derived neutrophil-to-lymphocyte ratio are associated with outcome in palliative second-line immunotherapy for patients with recurrent and/or metastatic squamous cell carcinoma of head and neck.

OBJECTIVES: To determine whether routinary walking activity and the derived neutrophil-to-lymphocyte ratio are associated with outcomes in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. METHODS: This multicenter retrospective cohort study included 64 patients diagnosed with recurrent and/or metastatic squamous cell carcinoma of head and neck and treated with immunotherapy (Programmed Death-1 and Programmed Death-ligand-1 proteins inhibitors) at two tertiary centers. We compared a group that performed uninterrupted physical activity for 1 h per day and controls who performed no activity. The derived neutrophil-to-lymphocyte ratio was calculated as follows: [neutrophils / (leukocytes - neutrophils)]. Progression-free survival and overall survival were evaluated. RESULTS: We included 28 (44%) and 36 (56%) patients in the activity and non-activity groups, respectively. Patient characteristics, treatment details, and tumor Programmed Death-ligand-1 expression were not associated with either progression-free survival or overall survival. Physical activity was an independent beneficial factor for progression-free survival (p < 0.001) and overall survival (p < 0.001). By contrast, a derived neutrophil-to-lymphocyte ratio <3.5 was an independent beneficial factor for overall survival (p = 0.013), but not for progression-free survival (p = 0.328). CONCLUSIONS: Walking one hour per day and having a high proportion of lymphocytes to neutrophiles (expressed as a low derived neutrophil-to-lymphocyte ratio) independently predict a better prognosis in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck treated with immunotherapy. LEVEL OF EVIDENCE: III.

Patient Characteristics and Outcomes Associated with Sentinel Protection Device Use in Patients with Aortic Valve Disease Undergoing TAVR in a "Real-World" Setting.

Background: Transcatheter aortic valve replacement (TAVR) has become the dominant treatment for aortic valve disease. While TAVR safety has improved over time, concern remains over the occurrence of cerebrovascular accidents (CVA) secondary to device placement, which is associated with increased morbidity and mortality. The Sentinel Cerebral Protection System (CPS) was developed to reduce the risk of embolic strokes associated with debris produced during TAVR. Studies evaluating Sentinel CPS efficacy have produced conflicting results, and there is little understanding of which patients are selected for device placement in "real-world" settings. With no existing guidelines on device use, the purpose of this study was to describe and compare the characteristics of patients who receive CPS with those who do not in a "real-world" setting of consecutive TAVR patients and evaluate its impact on postoperative complications, namely stroke. Methods: This was a single-center, retrospective study of all patients undergoing TAVR between July 1, 2019, and December 31, 2020. Patient demographics, baseline, and perioperative characteristics were collected prospectively using the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry and our institution's TAVR database for analysis. Postoperative outcomes were assessed using primary endpoints of in-hospital/30-day stroke and the composite of death, stroke, and bleeding/vascular events at one-year. To adjust for baseline differences, a propensity score was developed including all factors that were different between groups, and Multivariate Cox Regression analysis was used to control for these differences. Patient follow-up was 97% complete at 12 months with 100% echocardiographic follow-up. Results: A total of 242 consecutive patients (57.9% male) were analyzed, with a mean age of 79.9 ± 9 years. Of these patients, 134 (55.4%) received the Sentinel CPS and 108 (44.6%) did not. Sentinel CPS patients were more likely to be male, not on dialysis, without prior CVA or pacemaker, had less severe chronic lung disease, and were lower operative risk compared to concurrent non-CPS patients. CPS patients were also found to have higher hemoglobin and albumin levels, lower creatinine, and were less likely to be on immunosuppressant therapy. The incidence of in-hospital/30-day stroke after TAVR did not differ between CPS and non-CPS patients (0.0% vs. 1.9%; p = 0.198). Unadjusted analyses at one-year showed a lower occurrence of the composite endpoint in CPS patients compared non-CPS patients (8.3% vs. 17.0%; p = 0.034). After adjustment, the hazard ratio (Adj HR) for the CPS group was no longer significantly associated with a lower composite endpoint (Adj HR = 0.609, 95% CI 0.244-1.523; p = 0.289). Both unadjusted (p = 0.233) and adjusted (p = 0.132) analyses showed no difference in the incidence of stroke at one-year. Conclusions: Our study demonstrates that in a "real-world" setting, the Sentinel CPS device is more likely to be used in healthier and less complex patients. In analyses adjusted for illness severity and patient complexity, CPS use did not have a significant effect on the incidence of in-hospital/30-day stroke or the composite endpoint of death, stroke, and bleeding/vascular events at one-year.

Closure of the Peritoneum in Laparoscopic Transabdominal Preperitoneal Inguinal Hernia Repair (TAPP) With Cyanoacrylate Glue in a Microdroplet Device: A Single Surgeon Prospective Comparison vs. Barbed Suture.

Purpose: To describe and compare a peritoneal closure technique using cyanoacrylate glue (Glubran 2®, GEM, Cardiolink SL) with a microdroplet device (Glutack®, GEM, Cardiolink SL) in laparoscopic transabdominal preperitoneal repair (TAPP) of inguinal hernia with the routinely used barbed suture peritoneal closure (V-Lock 3.0, Covidien France). Materials and methods: From January to August 2022, 60 patients undergoing TAPP repair for uni- or bilateral inguinal hernia were randomized into one of two groups. One using as mesh fixation and peritoneal closure the Glutack® device with Glubran 2® cyanoacrylate glue (Glu-close group) and the other using mesh fixation with cyanoacrylate and peritoneal closure with V-lock 3.0 (Sut-close group), with a follow-up of 12 months. Demographic variables, operative time, peritoneal closure time, main surgical findings and main intra- and postoperative complications were analyzed prospectively. Results: 63 patients were included with no losses to follow-up. The mean operative time was 34 min (range 58.25) for the glu-close group and 40 (range 64.25) for the sut-close group, with no conversion (0%) for either group. The mean flap closure time was 1.18 min (SD 24 0.19) for the glu-close group and 3.24 min (SD 0.78) for the sut-close group, with statistically significant differences (p < 0.001). The intraoperative complication rate was 0 for the glu-close group and 0 for the sut-close group, with no significant difference. The median hospital stay was 0.8 days (range, 0-1) for both groups. The median duration of follow-up was 12 months and none had hernia recurrence. The postoperative VAS score at the first and second check-up at 1 month and 3 months was 2.83 (SD 1.341) and 0.60 (SD 0.621) in the sut-close group and 1.03 (0.984) and 0.24 (SD 0.435) in the glue-close group, with significant differences (p < 0.001 and p < 0.012). Conclusion: The data demonstrated by the study are that the glue can be used safely to close the peritoneum and that the method provides a small, statistically significant but not clinically relevant reduction in the time to close the peritoneal flap, as well as in postoperative pain after surgery in short and medium term.

Impact of nondiameter aortic indices on surgical eligibility: Results from the Treatment in Thoracic Aortic Aneurysm: Surgery Versus Surveillance (TITAN: SvS) randomized controlled trial.

OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.

Spatial Profiling of Ovarian Carcinoma and Tumor Microenvironment Evolution under Neoadjuvant Chemotherapy.

PURPOSE: This study investigates changes in CD8+ cells, CD8+/Foxp3 ratio, HLA I expression, and immune coregulator density at diagnosis and upon neoadjuvant chemotherapy (NACT), correlating changes with clinical outcomes. EXPERIMENTAL DESIGN: Multiplexed immune profiling and cell clustering analysis were performed on paired matched ovarian cancer samples to characterize the immune tumor microenvironment (iTME) at diagnosis and under NACT in patients enrolled in the CHIVA trial (NCT01583322). RESULTS: Several immune cell (IC) subsets and immune coregulators were quantified pre/post-NACT. At diagnosis, patients with higher CD8+ T cells and HLA I+-enriched tumors were associated with a better outcome. The CD8+/Foxp3+ ratio increased significantly post-NACT in favor of increased immune surveillance, and the influx of CD8+ T cells predicted better outcomes. Clustering analysis stratified pre-NACT tumors into four subsets: high Binf, enriched in B clusters; high Tinf and low Tinf, according to their CD8+ density; and desert clusters. At baseline, these clusters were not correlated with patient outcomes. Under NACT, tumors were segregated into three clusters: high BinfTinf, low Tinf, and desert. The high BinfTinf, more diverse in IC composition encompassing T, B, and NK cells, correlated with improved survival. PDL1 was rarely expressed, whereas TIM3, LAG3, and IDO1 were more prevalent. CONCLUSIONS: Several iTMEs exist during tumor evolution, and the NACT impact on iTME is heterogeneous. Clustering analysis of patients unravels several IC subsets within ovarian cancer and can guide future personalized approaches. Targeting different checkpoints such as TIM3, LAG3, and IDO1, more prevalent than PDL1, could more effectively harness antitumor immunity in this anti-PDL1-resistant malignancy.

Total Arterial Revascularization: Evaluating the Length of the Radial Artery in a Composite Graft Configuration.

PURPOSE: Reimplanting the radial artery in the left internal thoracic artery as a composite graft allows total arterial revascularization (TAR) without aortic manipulation. The limitation of this strategy is the length of the radial artery required to reach distal right coronary artery (RCA) branches. Our analysis focuses on the feasibility of this strategy. METHODS: A total of 169 patients underwent TAR using the radial artery in a composite grafting configuration. Length of the radial artery, number of sequential anastomoses, heart size, target location, length of the arm, patient height, body surface area, and flow in the composite graft were prospectively collected. RESULTS: The mean length of the radial artery was 18.02 cm. Patients with a mean length of the radial artery of 15.9 cm needed an extension of the radial artery with another conduit to reach the RCA distal branches. When T-configuration is used, the length of the radial artery should be 0.53 cm per sequential anastomosis to reach the RCA distal branches. CONCLUSIONS: Our study shows that an average length of 18.02 cm of radial artery is needed to reach targets on the RCA distal branches in composite grafting. In T-configuration, we need 0.53 cm more length per anastomosis to achieve TAR.

Invasive Management of Hypertrophic Cardiomyopathy With Clinically Important Obstruction: Surgical Myectomy Is Superior, but Only When Accessible.

For patients with hypertrophic cardiomyopathy (HCM), a thickened intraventricular septum and systolic anterior motion of the mitral valve (SAM) can contribute to significant left ventricular outflow tract obstruction (LVOTO), mitral regurgitation, and debilitating symptoms. Current guidelines recommend septal reduction therapy through alcohol septal ablation or surgical septal myectomy for patients whose symptoms persist despite medical therapy. Although alcohol septal ablation is a less invasive treatment option, it is not suitable for patients with septal perforator branch anatomy that is not compatible with the procedure, those with midcavitary obstruction, and patients in whom the mechanism of LVOTO is primarily related to SAM. Septal ablation also has a notably higher rate of atrioventricular block requiring permanent pacemaker insertion, and the need for reintervention has been reported to be 15% or more. In contrast, septal myectomy offers direct visualisation and can address thickened septum and mitral valve (MV) anomalies. It can be used to treat a wider variety of anatomies, with lower rates of reoperation. Aside from the more invasive nature of the procedure, a major limitation of septal myectomy, however, is access, because relatively few surgeons specialise in the procedure. This is important because there is a significant correlation between procedural volumes and outcomes. Patients should be evaluated by a multidisciplinary heart team to ensure that they are aware of all treatment options. In this review, we explore the 2 methods of septal reduction therapy and highlight the need for further training of septal myectomy surgeons to ensure access to optimal septal reduction therapies for Canadian patients with HCM.

Formación en cirugía mayor ambulatoria. Una asignatura pendiente en nuestro país / Training in ambulatory surgery. A pending subject in our country

La implantación y generalización a nivel mundial de la cirugía mayor ambulatoria (CMA) es una realidad patente en la actualidad y se espera un crecimiento progresivo de la misma a corto plazo, pero esta globalización también puede afectar de forma negativa a la docencia y el entrenamiento de los futuros médicos y aquellos que están en formación, si no se estandariza y regula, ya que una parte importante de la gestión de la patología más frecuente subsidiaria de ser realizada en CMA, acaba fuera de los circuitos del hospital donde el médico residente se está formando. (AU)

The implantation and generalization of ambulatory surgery worldwide is currently a clear reality and its progressive growth is expected in the short term, but this globalization can also negatively affect the teaching and training of future doctors and those who are in training, if it is not standardized and regulated, since an important part of the management of the most common pathology that could be performed in ambulatory surgery finish outside the circuits of the hospital where the resident doctor is training. (AU)

CCTA-based CABG SYNTAX Score: a tool to evaluate completeness of coronary segment revascularization after bypass surgery.

To describe the updated coronary computed tomographic angiography (CCTA)-based coronary artery bypass graft (CABG) anatomic SYNTAX Score (aSS) and assess its utility and reproducibility for assessing the completeness of revascularization after CABG. The CCTA-CABG aSS is a visual assessment using CCTA post-CABG which quantifies the failure in effectively grafting stenotic coronary segments, and therefore assesses the completeness of surgical revascularization. It is calculated by subtracting the aSS of successfully anastomosed coronary segments from the aSS of the native coronary tree. The inter-observer reproducibility of the CCTA-CABG aSS was evaluated in 45 consecutive patients with three-vessel disease with or without left main disease who underwent a CCTA 30 days (± 7 days) after CABG. The CCTA-CABG aSS was evaluated in 45 consecutive patients with 117 bypass grafts and 152 anastomoses. The median native coronary aSS was 35.0 [interquartile range (IQR) 27.0-41.0], whilst the median CCTA-CABG aSS was 13.0 (IQR 9.0-20.5). The inter-observer level of agreement for the native coronary aSS and the CCTA-CABG aSS were both substantial with respective Kappas of 0.67 and 0.61. The CCTA-CABG aSS was feasible in all patients who underwent CABG for complex coronary artery disease with substantial inter-observer reproducibility, and therefore can be used to quantify the completeness of revascularization after CABG.