Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Accertamento e valutazione medico legale della sofferenza morale

Nel mese di aprile 2018 un Gruppo di Esperti Specialisti Medico Legali Nazionali identificati dalla Societ\ue0 Italiana di Medicina Legale (SIMLA) si \ue8 riunito a Padova al fine di confrontarsi, alla luce dei contenuti della legge 4.8.17, n. 124, della dottrina medico legale e della recente giurisprudenza di merito, circa gli ambiti di competenza medico legale nell\u2019accertamento e nella valutazione del \u201cDanno non patrimoniale\u201d alla persona ed ha contestualmente esteso un documento di sintesi con particolare riferimento alla sofferenza morale, successivamente approvato dal Direttivo della predetta Societ\ue0, al fine della diffusione su tutto il territorio nazionale

Correction to: Homicide and concealment of the corpse. Autopsy case series and review of the literature

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Homicide and concealment of the corpse. Autopsy case series and review of the literature

The concealment of the body following a homicide undermines different moments of the forensic and medico-legal investigations. The aim of the present study is to provide an overview of the literature and the forensic casuistry of the Institute of Legal Medicine of Padova for analyzing and discussing diverse methodological approaches for the forensic pathologist dealing with covered-up homicides

Outcomes of congenital cytomegalovirus disease following maternal primary and non-primary infection

BACKGROUND: Natural history and long term prognosis of congenital cytomegalovirus (CMV) disease according to maternal primary versus non-primary infection are not clearly documented. OBJECTIVE: To investigate clinical, laboratory and neuroimaging features at onset and long term outcome of congenitally CMV-infected patients born to mothers with non-primary infection compared with a group of patients born to mothers with primary infection. STUDY DESIGN: Consecutive neonates born from 2002 to 2015 were considered eligible for the study. Patients underwent clinical, laboratory and instrumental investigation, and audiologic and neurodevelopmental evaluation at diagnosis and during the follow up. RESULTS: A cohort of 158 congenitally infected children was analyzed. Ninety-three were born to mothers with primary CMV infection (Group 1) and 65 to mothers with a non-primary infection (Group 2). Eighty-eight infants had a symptomatic congenital CMV disease: 49 (46.2%) in Group 1 and 39 (60%) in Group 2. Maternal and demographic characteristics of patients of Group 1 and Group 2 were comparable, with the exception of prematurity and a 1-min Apgar score less than 7, which were more frequent in Group 2 compared to Group 1. Prevalence of neuroimaging findings did not significantly differ between the two groups. An impaired neurodevelopmental outcome was observed in 23.7% of patients of Group 1 and in 24.6% cases of Group 2. Similarly, the frequency of hearing loss did not differ between the two groups (25.8% versus 26.2%, respectively). CONCLUSIONS: Neurodevelopmental and hearing sequelae are not affected by the type of maternal CMV infection. Preventing strategies should be developed for both primary and non-primary infections

Characterization of AR-CGD female patient with a novel homozygous deletion in CYBC1 gene presenting with unusual clinical phenotype

chronic granulomatous disease (CGD) is a human IEI caused by mutations in genes encoding the NADPH oxidase subunits, the enzyme responsible for the respiratory burst. CGD patients have severe life-threatening infections, hyperinflammation and immune dysregulation. recently, an additional autosomal recessive AR-CGD (type 5) caused by mutations in CYBC1/EROS gene was identified.We report a AR-CGD5 patient with a novel loss of function (LOF) homozygous deletion c.8_7del in the CYBC1 gene including the initiation ATG codon that leads to failure of CYBC1/EROS protein expression and presenting with an unusual clinical manifestation of childhood-onset sarcoidosis-like disease requiring multiple immuno-suppressive therapies. we described an abnormal gp91phox protein expression/function in the patient's neu-trophils and monocytes (about 50%) and a severely compromised B cell subset (gp91phox < 15%; DHR+ < 4%). our case-report emphasized the importance of considering a diagnosis of AR-CGD5 deficiency even in absence of typical clinical and laboratory findings

Eosinophilic esophagitis in children: clinical findings and diagnostic approach

Eosinophilic esophagitis (EoE) is an emerging chronic immune and antigen-mediated clinicopathologic disease. During the last 2 decades, the incidence of this condition in children has increased significantly, thanks to practitioners for creating the awareness and higher use of diagnostic endoscopy. We have analysed paediatric literature on EoE focusing on the epidemiology, pathophysiology, clinical findings and diagnostic approach. EoE is pathogenically related to a Th2 inflammation characterized by a mixed IgE and non-IgEmediated reaction to food and/or environmental agents. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. EoE can be presented with several range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infants and toddlers, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnostic suspicion is based on the presence of chronic symptoms of esophgeal dysfunction and esophageal eosinophilia characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field). In this review, we will provide an update on clinical presentation and diagnostic approach to EoE in children. We emphasized on the relevant aspects of the new clinical condition termed “PPI responsive esophageal eosinophilia”, as entities distinct from EoE and the role of PPI trial in the diagnostic workup, therefore we proposed a new diagnostic algorithm

Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS)

Adherence to the Mediterranean diet (MedDiet) leads to reduction of mortality from all causes, especially in subjects with cardiovascular disease, obesity, and diabetes. Numerous scores have been proposed to evaluate the adherence to MedDiet, mainly focused on eating habits. In this study, we verified whether existing validated MedDiet scores, namely, MEDI-LITE and the Mediterranean Diet Score (MDS), could be associated with visceral adiposity. Failing to find a significant association with adiposity, we proposed the validation of a new, easy-to-use adherence questionnaire, the Chrono Med-Diet score (CMDS). CMDS contains eleven food categories, including chronobiology of dietary habits and physical activity. Compared to the MEDI-LITE score and MDS, low values of CMDS are linked to increased waist circumference (WC) and dysmetabolic conditions. CMDS was also inversely correlated with cardiovascular risk (CVR), as well as Fatty Liver Index (FLI). In conclusion, the CMDS is a novel questionnaire to study the adherence to the MedDiet that, focusing on type and timing of carbohydrates intake, has the peculiar capability of capturing subjects with abdominal obesity, thus being an easy-to-use instrument of personalized medicine