Inhaled Pulmonary Vasodilators for the Treatment of Right Ventricular Failure in Cardio-Thoracic Surgery: Is One Better than the Others?

Right ventricular failure (RFV) is a potential complication following cardio-thoracic surgery, with an incidence ranging from 0.1% to 30%. The increase in pulmonary vascular resistance (PVR) is one of the main triggers of perioperative RVF. Inhaled pulmonary vasodilators (IPVs) can reduce PVR and improve right ventricular function with minimal systemic effects. This narrative review aims to assess the efficacy of inhaled nitric oxide and inhaled prostacyclins for the treatment of perioperative RVF. The literature, although statistically limited, supports the clinical similarity between them. However, it failed to demonstrate a clear benefit from the pre-emptive use of inhaled nitric oxide in patients undergoing left ventricular assist device implantation or early administration during heart-lung transplants. Additional concerns are related to cost safety and IPV use in pathologies associated with pulmonary venous congestion. The largest ongoing randomized controlled trial on adults (INSPIRE-FLO) is addressing whether inhaled Epoprostenol and inhaled nitric oxide are similar in preventing RVF after heart transplants and left ventricular assist device placement, and whether they are similar in preventing primary graft dysfunction after lung transplants. The preliminary analysis supports their equivalence. Several key points may be achieved by the present narrative review. When RVF occurs in the setting of elevated PVR, IPV should be the preferred initial treatment and they should be preventively used in patients at high risk of postoperative RVF. If severe refractory postoperative RVF occurs, IPVs should be combined with complementary pharmacology (inotropes and inodilators). If unsuccessful, right ventricular mechanical support should be established

Circadian rhythm and melatonin in liver carcinogenesis: updates on current findings

: Liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, can be devastating if not treated early. The risk factors of liver cancer include alcoholic liver disease, non-alcoholic fatty liver disease, disruption of melatonin levels, and dysregulated circadian rhythm. The circadian rhythm is a 24-hour biological clock that regulates the physiological activities at both central and peripheral levels. Its molecular mechanism exists in every cell in mammals. Disruption of the circadian rhythm has found in liver cancers as an independent risk factor. This review summarized the most recent findings about the molecular mechanisms of circadian rhythm, the crosstalk between core clock genes and melatonin, as well as the role of circadian rhythm and melatonin played in chronic liver diseases and liver cancer. Finally, we discussed the potential clinical application of circadian rhythm and melatonin for the treatment of liver cancer and discussed future perspectives of how understanding the circadian rhythm in liver cancer progression could provide new clinical applications for liver cancer treatment and diagnosis

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider, for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immune-competent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance". However, with regard to HBV and LT, outstanding issues are still on the table: (1) A standard HBV prophylaxis protocol after transplant has not yet been clearly defined; (2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs; and (3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons

The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease

Mast cells are key players in acute immune responses that are evidenced by degranulation leading to a heightened allergic response. Activation of mast cells can trigger a number of different pathways contributing to metabolic conditions and disease progression. Aging results in irreversible physiological changes affecting all organs, including the liver. The liver undergoes senescence, changes in protein expression, and cell signaling phenotypes during aging, which regulate disease progression. Cellular senescence contributes to the age-related changes. Unsurprisingly, mast cells also undergo age-related changes in number, localization, and activation throughout their lifetime, which adversely affects the etiology and progression of many physiological conditions including liver diseases. In this review, we discuss the role of mast cells during aging, including features of aging (e.g., senescence) in the context of biliary diseases such as primary biliary cholangitis and primary sclerosing cholangitis and nonalcoholic fatty liver disease

The Operative management in Bariatric Acute abdomen (OBA) Survey: long-term complications of bariatric surgery and the emergency surgeon's point of view

Background: The number of bariatric procedures is increasing worldwide. No consensus or guidelines about theemergency management of long-term complications following bariatric surgery are currently available. The aim ofthis study is to investigate by a web survey how an emergency surgeon approaches this unique group of patientsin an emergency medical scenario and to report their personal experience. Method: An international web survey was sent to 197 emergency surgeons with the aim to collect data aboutemergency surgeons\u2019experience in the management of patients admitted in the emergency department for acuteabdominal pain after bariatric surgery. The survey was conceived as a questionnaire composed by 26 (multiplechoice and open) questions and approved by a steering committee. Results: One hundred seventeen international emergency surgeons decided to join the project and answered tothe web survey with a response rate of 59.39%. Conclusions: The aim of this WSES web survey was to highlight the current management of patients previouslysubmitted to bariatric surgical procedures by ES.Emergency surgeons must be mindful of postoperative bariatric surgery complications. CT scan with oral intestinalopacification may be useful in making a diagnosis if carefully interpreted by the radiologist and the surgeon.In case of inconclusive clinical and radiological findings, when symptoms fail to improve, surgical exploration forbariatric patients presenting acute abdominal pain, by laparoscopy if expertise is available, is mandatory in the first12\u201324 h, to have good outcomes and decrease morbidity rate

Cidadania mediada : processos de democratização da política municipal no Brasil

This article discusses the notion that the persistence of &ldquo;traditional&rdquo; political practices weakens Brazil&rsquo;s democracy.Drawing on the cases of three Brazilian municipalities administered by the Workers&rsquo; Party (PT), the author examines the space between &ldquo;traditional&rdquo; and &ldquo;modern&rdquo; and argues that successful democratization does not eradicate practices such as clientelism and patronage, but it tends to incorporate and build on these traditional political elements. Moreover, the article maintains that the democratization of municipal politics is inextricably bound up with the eradication of poverty and the construction of a responsive, state-based social safety net.<br /

Feedback Signaling between Cholangiopathies, Ductular Reaction, and Non-Alcoholic Fatty Liver Disease

Fatty liver diseases, such as non-alcoholic fatty liver disease (NAFLD), are global health disparities, particularly in the United States, as a result of cultural eating habits and lifestyle. Pathological studies on NAFLD have been mostly focused on hepatocytes and other inflammatory cell types; however, the impact of other biliary epithelial cells (i.e., cholangiocytes) in the promotion of NAFLD is growing. This review article will discuss how cholestatic injury and cholangiocyte activity/ductular reaction influence NAFLD progression. Furthermore, this review will provide informative details regarding the fundamental properties of cholangiocytes and bile acid signaling that can influence NAFLD. Lastly, studies relating to the pathogenesis of NAFLD, cholangiopathies, and ductular reaction will be analyzed to help gain insight for potential therapies

Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation

Background and Aims: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. Methods: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012–2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam- D'Agostino test was used to evaluate the calibration of the models. Results: GEMA-Na (concordance = .82, 95% CI = .75–. 89), MELD 3.0 (concordance = .81, 95% CI = .74–. 87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74–.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed

Mast cells in liver disease progression: An update on current studies and implications

: Mast cells (MCs) induce the progression of liver diseases including, but not limited to, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), alcoholic and non-alcoholic fatty liver disease (ALD/NAFLD), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The effects of MCs during disease progression includes alterations in ductular reaction, steatosis, hepatic fibrosis and inflammation. In addition, there is significant crosstalk between MCs, MC mediators (histamine, tryptase, chymase) and MC-derived cytokines (transforming growth factor beta, tumor necrosis factor alpha, interleukins). Studies have been performed in rodent models, cultured cells, and human tissues to demonstrate the intracellular signaling implications of MC infiltration during liver disease. Targeting MCs may offer novel therapeutic strategies to treat liver disease. Our concise review will encompass the most recent studies involving MCs, their mediators and liver disease with the overall goal to inform the reader about the diverse role of these inflammatory immune cells in liver damage