Can liquid biopsies for MASH help increase the penetration of metabolic surgery? A narrative review

This narrative review highlights current evidence on non-invasive tests to predict the presence or absence as well as the severity of metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition characterized by fat accumulation in the liver that affects 32 % of the world population. The most severe form of MASLD is MASH in which hepatocyte ballooning and inflammation are present together with steatosis; MASH is often associated with liver fibrosis. MASH diagnosis is determined by invasive liver biopsy. Hence, there is a critical need for non-invasive MASH tests. Plasma biomarkers for MASH diagnosis generally have low sensitivity (62-66 %), and specificity (78-82 %). Monocyte levels of Perilipin2 (PLIN2) predict MASH with an accuracy of 92-93 %, and sensitivity and specificity of 90-95 % and 88-100 %, respectively. This liquid biopsy test can facilitate the study of MASH prevalence in general populations and also monitor the effects of lifestyle, surgical, and pharmacological interventions. Without any FDA-approved MASH therapeutic, and with metabolic surgery markedly surpassing the efficacy of lifestyle modification, an accurate and reliable liquid biopsy could help more people choose surgery as a treatment for MASH

Study of the human hypoglossal nucleus: normal development and morpho-functional alterations in sudden unexplained late fetal and infant death

This study evaluated the development and the involvement in sudden perinatal and infant death of the medullary hypoglossal nucleus, a nucleus that, besides to coordinate swallowing, chewing and vocalization, takes part in inspiration. Through histological, morphometrical and immunohistochemical methods in 65 cases of perinatal and infant victims (29 stillbirths, 7 newborns and 29 infants), who died of both unknown and known cause, the authors observed developmental anomalies of the hypoglossal nucleus (HGN) in high percentage of sudden unexplained fetal and infant deaths. In particular, HGN hypoplasia, hyperplasia, positive expression of somatostatin and absence of interneurons were frequently found particularly in infant deaths, with a significant correlation with maternal smoking

Molecular mechanisms of diabetes reversibility after bariatric surgery

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Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice

Aim: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D)

Cigarette Smoking as a risk factor for coronary artery disease and sudden unexpected death in fetuses and infants

Maternal smoking during pregnancy makes it more likely that the baby will be stillborn or die in the first year of life. Cigarette smoke is the most important risk factor for fetal and infant sudden death (SIDS). The risk of stillbirthor death during the infant's first year of life is directly related to the amount the mother smoked. The present study adds significant evidence on the need to avoid cigarette smoking. The pathogenic mechanism of smoke is referable to different factors. The combustion products of nicotine, in addition to their diffuse toxicity, are heterogeneous and cause specific lesion of the automatic nervous system. Gaseous combustion products, such as carbon oxide, lead to atheosclerotic plaques in the cardiovascular district and in the sino-atrial and atrio-ventricular arteries

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma

Background: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Patients and methods: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. Results: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). Conclusions: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distres

Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02)

Background: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. Patients and methods: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m2 and docetaxel (Taxotere) 75 mg/m2 on days 1 and 22, followed by radiotherapy of 45 Gy (25 × 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m2 and docetaxel 20 mg/m2 weekly for 5 weeks, followed by surgery. Results: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. Conclusions: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigatio

Transient massive hyperlipidaemia in a type 2 diabetic subject

A 50-year-old man, in apparently good health, was referred to the Lipid Center of San Luigi Gonzaga Hospital, Orbassano (Turin, Italy), by his primary care physician (PCP) because clinical tests at the time of blood donation showed milky plasma with serious hypertriglyceridaemia (>5000 mg/dl) and hyperglycaemia (381 mg/dl), diagnostic for diabetes. It was not possible to perform further blood chemical analyses because hypertriglyceridaemia would have provided abnormal results. The patient entered the hospital to prevent acute pancreatitis, which is often associated with severe hypertriglyceridaemi