Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome.

OBJECTIVE: Marfan's syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-ß signaling. TGF-ß is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-ß signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan's syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level. APPROACH AND RESULTS: Immunohistochemical and Western blotting analyses of dilated aortas from Marfan patients showed overexpression of contractile protein markers (α-smooth muscle actin, smoothelin, smooth muscle protein 22 alpha, and calponin-1) and collagen I in comparison with healthy aortas. VSMC explanted from Marfan aortic aneurysms showed increased in vitro expression of these phenotypic markers and also of myocardin, a transcription factor essential for VSMC-specific differentiation. These alterations were generally reduced after pharmacological inhibition of the TGF-ß pathway. Marfan VSMC in culture showed more robust actin stress fibers and enhanced RhoA-GTP levels, which was accompanied by increased focal adhesion components and higher nuclear localization of myosin-related transcription factor A. Marfan VSMC and extracellular matrix measured by atomic force microscopy were both stiffer than their respective controls. CONCLUSIONS: In Marfan VSMC, both in tissue and in culture, there are variable TGF-ß-dependent phenotypic changes affecting contractile proteins and collagen I, leading to greater cellular and extracellular matrix stiffness. Altogether, these alterations may contribute to the known aortic rigidity that precedes or accompanies Marfan's syndrome aneurysm formation.

The role of perioperative cardiorespiratory support in post infarction ventricular septal rupture-related cardiogenic shock.

BACKGROUND: Current guidelines recommend emergency surgical correction in patients with post infarction ventricular septal rupture (PIVSR), but patients with multiorgan failure are commonly managed conservatively because of high surgical risk. We assessed characteristics and outcomes of operated PIVSR patients with or without the use of short-term ventricular assist devices (ST-VADs). We also assessed the impact of a ST-VAD on the performance of surgery. METHODS: We retrospectively analysed all consecutive patients with PIVSR between January 2004 and May 2017. Baseline clinical characteristics, use of ST-VAD and performance of surgery during admission were assessed. The main outcome measured was in-hospital mortality. RESULTS: A total of 28 patients were included. Mean age was 69.2 years. Most patients (20/28, 71.4%) underwent surgical repair. ST-VADs were used in 11/28 patients (39.3%). This percentage progressively increased across the study period, from 22.2% (2/9) in 2004-2011 to 58.3% (7/12) in 2015-2017 (p=0.091). Patients undergoing ST-VAD use had poorer INTERMACS status, higher values of creatinine, lactate and alanine aminotransferase and lower left ventricular ejection fraction as compared with operated patients without support. In-hospital mortality did not differ according to the use of ST-VADs in operated patients (27.3% without ST-VAD vs. 22.2% with ST-VAD, p=0.604). All five patients undergoing early preoperative venoarterial extracorporeal membrane oxygenator support and delayed surgery survived at hospital discharge. CONCLUSIONS: ST-VAD use increased in patients with PIVSR. Despite a higher risk profile in operated patients undergoing ST-VAD use, mortality was not significantly different in these patients. Early preoperative venoarterial extracorporeal membrane oxygenation should be considered for very high risk PIVSR patients.

Emergency operations for nondiverticular perforation of the left colon.

OBJECTIVE: Although diverticulitis is the most common cause of large bowel perforation, other disease may result in left colonic peritonitis. The aim of this study was to evaluate and compare the incidence, management, and outcome of patients with different causes of nondiverticular left colonic perforations. PATIENTS AND METHODS: From January 1992 to September 2000, 212 surgical patients underwent emergency operation for distal colonic peritonitis. Perforations were caused by diverticulitis in 133 patients (63%) and by a nondiverticular process in 79 (37%). Mortality and morbidity in patients with nondiverticular perforation of the distal large bowel its relationship with the general conditions, the grade and the cause of peritonitis were analysed. Four types of surgical procedures were used. Hartmann's procedure was performed in 40 patients (51%); intraoperative colonic lavage, resection, and primary anastomosis (ICL) in 27 patients (34%); colostomy in 7 (9%); and subtotal colectomy in 5 (6%). RESULTS: Perforated neoplasm, the most common cause of peritonitis, was observed in 30 patients, colonic ischemia in 20, iatrogenia in 13, and other causes in 16 patients. One or more complications were observed in 57 patients (72%); among causes of perforation, colonic ischemia was significantly associated with the longest hospital stay and highest mortality. Eighteen patients (23%) died. CONCLUSIONS: Left large bowel perforation by nondiverticular disease is associated with high mortality and morbidity. The prognosis of patients is determined by the development of septic shock and colonic ischemia, as underlying disease, may influence patient survival.