Left Ventricular Mechanics Differ in Subtypes of Aortic Stenosis Following Transcatheter Aortic Valve Replacement

BackgroundLeft ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). We hypothesized that there would be differences in myocardial mechanics, measured by global longitudinal strain (GLS) recovery in patients with four subtypes of severe AS after transcatheter aortic valve replacement (TAVR), stratified based upon flow and gradient.MethodsWe retrospectively evaluated 204 patients with severe AS who underwent TAVR and were followed post-TAVR at our institution for clinical outcomes. Speckle-tracking transthoracic echocardiography was performed pre- and post-TAVR. Patients were classified as: (1) normal-flow and high-gradient, (2) normal-flow and high-gradient with reduced LV ejection fraction (LVEF), (3) classical low-flow and low-gradient, or (4) paradoxical low-flow and low-gradient.ResultsBoth GLS (−13.9 ± 4.3 to −14.8 ± 4.3, P < 0.0001) and LVEF (55 ± 15 to 57 ± 14%, P = 0.0001) improved immediately post-TAVR. Patients with low-flow AS had similar improvements in LVEF (+2.6 ± 9%) and aortic valve mean gradient (−23.95 ± 8.34 mmHg) as patients with normal-flow AS. GLS was significantly improved in patients with normal-flow (−0.93 ± 3.10, P = 0.0004) compared to low-flow AS. Across all types of AS, improvement in GLS was associated with a survival benefit, with GLS recovery in alive patients (mean GLS improvement of −1.07 ± 3.10, P < 0.0001).ConclusionsLV mechanics are abnormal in all patients with subtypes of severe AS and improve immediately post-TAVR. Recovery of GLS was associated with a survival benefit. Patients with both types of low-flow AS showed significantly improved, but still impaired, GLS post-TAVR, suggesting underlying myopathy that does not correct post-TAVR.

Early Postoperative Extubation is Associated with Shorter Hospitalization and Improved Short-Term Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant operative time, hospital resources, and morbidity. We examine factors associated with hospital length of stay (LOS) and early overall survival (OS) after CRS/HIPEC. Materials and Methods Patients who underwent CRS/HIPEC were evaluated for factors associated with LOS. Institutional learning curve influence was addressed by comparing early vs late cohorts. Variables with P < .200 after univariate analysis were considered for inclusion in multivariate linear regression modeling. Independent factors associated with OS were evaluated using the Kaplan-Meier method. Results Seventy patients underwent CRS/HIPEC (mean age 52.3 years, 64.3% female, and 68.6% Caucasian). Presence of any surgical complication was found in 26 (37.1%), 28 (40%) remained intubated postoperatively, and the mean Peritoneal Carcinomatosis Index (PCI) score was 14.4 ([Formula: see text]10.4). Mean intensive care unit and hospital LOS were 2.9 days ([Formula: see text]2.3) and 9.6 days ([Formula: see text]3.6), respectively. After adjusting for covariates, only shorter time to postoperative ambulation (regression coefficient .92, P = .001) and early extubation (regression coefficient −1.90, P = .018) were associated with decreased hospital LOS on multivariate analysis. Immediate postoperative extubation conferred an independent early survival benefit on Kaplan-Meier analysis (mean OS 714.8 vs 473.4 days, P = .010). There was no difference in hospital LOS or OS between early and late cohorts. Conclusion Early postoperative extubation and shorter time to ambulation are associated with decreased hospital LOS. Moreover, CRS/HIPEC patients extubated immediately postoperatively have an early survival benefit. Every effort should be made to achieve early postoperative extubation and mobilization in CRS/HIPEC patients.

Hyperthermic Intraperitoneal Chemotherapy in the Treatment Armamentarium of Epithelial Ovarian Cancer: Time to End the Dichotomy

<b><i>Background:</i></b> Advanced epithelial ovarian cancer (EOC) is an incurable disease with over 75% of the patients developing recurrence in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for both first-line therapy and treatment of recurrence. In this article, we review the rationale and current evidence for performing HIPEC and the role of HIPEC in the light of targeted systemic therapies. <b><i>Summary:</i></b> There are few randomized trials and several retrospective studies on the role of HIPEC in the management of EOC. A 12-month-overall survival (OS) benefit of the addition of HIPEC to interval cytoreductive surgery (CRS) was demonstrated in 1 randomized trial following which HIPEC has been included as a treatment option for this indication in several national/international guidelines. One retrospective propensity score-matched analysis showed a 16-month OS benefit of adding HIPEC to primary CRS. One randomized trial showed no benefit of the addition of carboplatin HIPEC to secondary CRS over secondary CRS alone. For patients undergoing primary CRS and secondary CRS for recurrence, the results of ongoing randomized trials are needed to define the role of HIPEC in these situations. All clinical trials have shown that the morbidity of HIPEC performed after CRS is acceptable. Along with the emergence of HIPEC as a promising surgical therapy, targeted therapies like bevacizumab and poly adenosine diphosphate-ribose polymerase inhibitors have been developed that have shown a survival benefit in selected patients. In principle, HIPEC and targeted therapies work in different ways and it is plausible to assume that their benefit could be additive, and their combination should be evaluated in clinical trials. The impact of prognostic factors like the disease extent, pathological response to systemic chemotherapy (SC), the histological subtype and molecular profile on the benefit of HIPEC, and targeted therapies has not been evaluated in clinical trials. <b><i>Key Messages:</i></b> HIPEC is an important therapeutic strategy in the treatment of EOC. While its role in patients undergoing interval CRS has been established, the results of ongoing randomized trials are needed to define its benefit at other time points. The morbidity of HIPEC in addition to CRS is acceptable. More research is needed to define subgroups that benefit most from HIPEC based on the extent of disease, response to SC, histology, and molecular profile. The combination of HIPEC and maintenance therapies should be evaluated in well-designed randomized clinical trials that evaluate not just the survival benefit and morbidity but also the cost-effectiveness of each therapy.

Impact of Lymphadenectomy on the Oncologic Outcome of Patients with Adrenocortical Carcinoma—A Systematic Review and Meta-Analysis

(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III).

An 11-Gene Signature Based on Treatment Responsiveness Predicts Radiation Therapy Survival Benefit Among Breast Cancer Patients

PurposeWe developed a strategy of building prognosis gene signature based on clinical treatment responsiveness to predict radiotherapy survival benefit in breast cancer patients.Methods and MaterialsAnalyzed data came from the public database. PFS was used as an indicator of clinical treatment responsiveness. WGCNA was used to identify the most relevant modules to radiotherapy response. Based on the module genes, Cox regression model was used to build survival prognosis signature to distinguish the benefit group of radiotherapy. An external validation was also performed.ResultsIn the developed dataset, MEbrown module with 534 genes was identified by WGCNA, which was most correlated to the radiotherapy response of patients. A number of 11 hub genes were selected to build the survival prognosis signature. Patients that were divided into radio-sensitivity group and radio-resistant group based on the signature risk score had varied survival benefit. In developed dataset, the 3-, 5-, and 10-year AUC of the signature were 0.814 (CI95%: 0.742–0.905), 0.781 (CI95%: 0.682–0.880), and 0.762 (CI95%: 0.626–0.897), respectively. In validation dataset, the 3- and 5-year AUC of the signature were 0.706 (CI95%: 0.523–0.889) and 0.743 (CI95%: 0.595–0.891). The signature had higher predictive power than clinical factors alone and had more clinical prognosis efficiency. Functional enrichment analysis revealed that the identified genes were mainly enriched in immune-related processes. Further immune estimated analysis showed the difference in distribution of immune micro-environment between radio-sensitivity group and radio-resistant group.ConclusionsThe 11-gene signature may reflect differences in tumor immune micro-environment that underlie the differential response to radiation therapy and could guide clinical-decision making related to radiation in breast cancer patients.

Prevalence of obesity and its association with cardiometabolic risk factors, heart failure phenotype and mortality among patients hospitalized for heart failure in Egypt

Background Obesity is an established risk factor for cardiometabolic disease and heart failure (HF). Nevertheless, the relationship between obesity and HF mortality remains controversial. Results The goal of this study was to describe the prevalence of obesity in patients hospitalized for HF in Egypt and investigate the relationship of obesity to cardiometabolic risk factors, HF phenotype and mortality. Between 2011 and 2014, 1661 patients hospitalized for HF across Egypt were enrolled as part of the European Society of Cardiology HF Long-term Registry. Obese patients, defined by a BMI ≥ 30 kg/m2, were compared to non-obese patients. Factors associated with mortality on univariate analysis were entered into a logistic regression model to identify whether obesity was an independent predictor of mortality during hospitalization and at one-year follow-up. The prevalence of obesity was 46.5% and was higher in females compared to males. Obese as compared to non-obese patients had a higher prevalence of diabetes mellitus (47.0% vs 40.2%, p = 0.031), hypertension (51.3% vs 33.0%, p < 0.001) and history of myocardial infarction (69.2% vs 62.8% p = 0.005). Obese patients as compared to non-obese patient were more likely to have acute coronary syndrome on admission (24.8% vs 14.2%, p < < 0.001). The dominant HF phenotype in obese and non-obese patients was HF with reduced ejection fraction (EF); however, obese patients as compared to non-obese patient had higher prevalence of HF with preserved EF (22.3% vs 12.4%, p < 0.001). Multivariable analysis demonstrated that obesity was associated with an independent survival benefit during hospitalization, (OR for mortality 0.52 [95% CI 0.29–0.92]). Every point increase in BMI was associated with an OR = 0.93 [95% CI 0.89–0.98] for mortality during hospitalization. The survival benefit was not maintained at one-year follow-up. Conclusions Obesity was highly prevalent among the study cohort and was associated with higher prevalence of cardiometabolic risk factors as compared to non-obese patients. Obesity was associated with an independent “protective effect” from in-hospital mortality but was not a predictor of mortality at 1-year follow-up.