Deactivation of LVAD Support for Myocardial Recovery - Surgical Perspectives.

Left ventricular assist devices (LVAD) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective to the practical and technical issues surrounding LVAD deactivation.

Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions.

PURPOSE OF REVIEW: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery. RECENT FINDINGS: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels. SUMMARY: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

Contemporary utilization of the axillary artery in cardiac surgery.

INTRODUCTION: The axillary artery is a reliable inflow vessel when addressing pathology of the aortic root and aortic arch that may preclude standard central cannulation strategies. This narrative review examines the use of the axillary artery in cardiac surgery. Anatomy, indications for use, cannulation strategies, and potential complications will be discussed. METHODS: A comprehensive review of the current literature was performed using PubMed, Cochrane Review, and authoritative committee guidelines. A narrative review incorporating current available evidence was undertaken. COMMENT: Use of the axillary artery in select cardiac surgical cases is reliable, reproducible, and may be preferable in certain cases involving ascending aortic pathology, reoperative surgery, porcelain aorta, access for transcatheter valve therapies, and peripheral mechanical circulatory support.

Successful Lung Transplantation for Severe Post-COVID-19 Pulmonary Fibrosis.

Lung transplantation has been well described for patients with coronavirus disease 2019 (COVID-19) in the acute setting, but less so for the resulting pulmonary sequelae. This report describes a case of lung transplantation for post-COVID-19 pulmonary fibrosis. A 52-year-old woman contracted COVID-19 in July 2020 and mounted a partial recovery, but she went on to have declining function over the ensuing 3 months, with development of fibrocystic lung changes. She underwent bilateral lung transplantation and recovered rapidly, was discharged home on postoperative day 14, and has done well in follow-up. This case report demonstrates that lung transplantation is an acceptable therapy for post-COVID-19 pulmonary fibrosis.

High-quality results of cytoreductive surgery and heated intraperitoneal chemotherapy perfusion for carcinomatosis at a low volume institution.

BACKGROUND AND OBJECTIVES: Maximal cytoreductive surgery (CS) with heated intraperitoneal chemotherapy perfusion (HIPEC) for peritoneal carcinomatosis can improve oncologic outcomes, but is associated with significant morbidity. Whether low-volume experience with CS/HIPEC results in acceptable outcomes is unknown. METHODS: A retrospective review of all patients undergoing CS/HIPEC by a single surgeon. Experience was divided into first versus second 50 cases, and patient characteristics, operative details, and outcomes were compared. RESULTS: Ninety patients underwent 100 CS/HIPEC procedures (mean age 57 years, 68% female). -Compared to the initial experience, the second 50 cases included more high grade tumors (68 vs. 52%) and greater disease burden (PCI 14.2 vs. 12.4). Operative times remained unchanged and mean blood loss decreased (978 vs. 684 ml). Hospital stay (mean 18.1 vs. 12.6 days), major complications (24 vs. 16%), and perioperative mortality (8 vs. 2%) declined. Overall median survival was 18 months and was longer with low grade tumors (26 vs. 16 months, P = 0.03). CONCLUSIONS: Patients experienced reduced EBL, fewer major complications, and shorter hospital stay, despite having higher disease burden and higher grade tumors. This suggests that even low-volume experience with CS/HIPEC can lead to a trend in reduction of adverse perioperative events with acceptable oncologic outcomes.

Testosterone regulates thyroid cancer progression by modifying tumor suppressor genes and tumor immunity.

Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castration led to lower rates of cancer in females and less advanced cancer in males. Mechanistically, less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1 macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell growth and increased chemokine secretion (Ccl5) that activates immune cells. Our data demonstrate that testosterone regulates thyroid cancer progression by reducing tumor suppressor gene expression and tumor immunity.

RTN4IP1 is down-regulated in thyroid cancer and has tumor-suppressive function.

CONTEXT: Previously we identified RTN4IP1 to be differentially expressed in thyroid cancer by sex and the gene is located on chromosome 6q21, a chromosomal region frequently deleted or with loss of heterozygosity in a variety of human malignancies including thyroid cancer. OBJECTIVE: Because the expression and function of this gene is unknown, we sought to characterize its expression in normal, hyperplastic, and benign and malignant thyroid tissue samples and to evaluate its function in cancer cells. DESIGN: RTN4IP1 expression was analyzed in normal and hyperplastic thyroid tissue and benign and malignant thyroid tissue samples. In 3 thyroid cancer cell lines (TPC1 from a papillary thyroid cancer, FTC133 from a follicular thyroid cancer, XTC1 from a Hürthle cell carcinoma), small interfering RNA knockdown of RTN4IP1 was used to determine its role in regulating the hallmarks of malignant cell phenotype (cellular proliferation, migration, apoptosis, invasion, tumor spheroid formation, anchorage independent growth). RESULTS: We found RTN4IP1 mRNA expression was significantly down-regulated in follicular and papillary thyroid cancer as compared with normal, hyperplastic, and benign thyroid neoplasms (P < .05). Moreover, RTN4IP1 mRNA expression was significantly lower in larger papillary thyroid cancers (P < .05). Small interfering RNA knockdown of RTN4IP1 expression increased cellular proliferation (2- to 4-fold) in all 3 of the cell lines tested and increased cellular invasion (1.5- to 3-fold) and migration (2- to 7.5-fold), colony formation (3- to 6-fold), and tumor spheroid formation (P < .05) in 2 of the 3 cell lines tested (FTC-133 and XTC1). CONCLUSIONS: This is the first study to characterize the expression and function of RTN4IP1 in cancer. Our results demonstrate RTN4IP1 is down-regulated in thyroid cancer and is associated with larger papillary thyroid cancer and that it regulates malignant cell phenotype. These findings, taken together, suggest that RTN4IP1 has a tumor-suppressive function and may regulate thyroid cancer progression.

Identification of a WD40 repeat-containing isoform of PHIP as a novel regulator of beta-cell growth and survival.

The pleckstrin homology domain-interacting protein (PHIP) was originally identified as a 902-amino-acid (aa) protein that regulates insulin receptor-stimulated GLUT4 translocation in skeletal-muscle cells. Immunoblotting and immunohistological analyses of pancreatic beta-cells reveal prominent expression of a 206-kDa PHIP isoform restricted to the nucleus. Herein, we report the cloning of this larger, 1,821-aa isoform of PHIP (PHIP1), which represents a novel WD40 repeat-containing protein. We demonstrate that PHIP1 overexpression stimulates insulin-like growth factor 1-dependent and -independent proliferation of beta-cells, an event which correlates with transcriptional upregulation of the cyclin D2 promoter and the accumulation of cyclin D2 protein. RNA interference knockdown of PHIP1 in INS-1 cells abrogates insulin receptor substrate 2 (IRS2)-mediated DNA synthesis, providing for a specific role for PHIP1 in the enhancement of IRS2-dependent signaling responses leading to beta-cell growth. Finally, we provide evidence that PHIP1 overexpression blocks free fatty acid-induced apoptosis in INS-1 cells, which is accompanied by marked activation of phosphoprotein kinase B (PKB)/AKT and the concomitant inhibition of caspase-9 and caspase-3 cleavage. Our finding that the restorative effect of PHIP1 on beta-cell lipotoxicity can be attenuated by the overexpression of dominant-negative PKB suggests a key role for PKB in PHIP1-mediated cytoprotection. Taken together, these findings provide strong support for PHIP1 as a novel positive regulator of beta-cell function. We suggest that PHIP1 may be involved in the induction of long-term gene expression programs to promote beta-cell mitogenesis and survival.