Palliative surgery or metallic stent positioning for advanced gastric cancer: differences in QOL

Background and Objectives: Twenty percent of the patients affected with stage IV antropyloric stomach cancer are hospitalized with a gastric outlet obstruction syndrome (GOOS) requiring its resolution to improve the quality of life (QoL).We present our preliminary short- and mid-term results regarding the influence of endoscopic placement of self-expandable metal stent (SEMS) or open stomach-partitioning gastrojejunostomy in QoL. Materials and Methods: In this prospective randomized longitudinal cohort trial, we randomly assigned 27 patients affected with stage IV antropyloric stomach cancer into two groups: Group 1 (13 patients) who underwent SEMS positioning and Group 2 (14 patients) in whom open stomach-partitioning gastrojejunostomy was performed. The Karnofsky performance scale and QoL assessment using the EQ-5D-5L™ questionnaire was administered before treatment and thereafter at 1, 3, and 6 months. Results: At 1-month, index values showed a statistically significant deterioration of the QoL in patients of Group 2 when compared to those of Group 1 (p = 0.004; CI: 0.04 to 0.21). No differences among the groups were recorded at 3-month; whereas, at 6-month, the index values showed a statistically significant deterioration of the QoL in patients of Group 1 (p = 0.009; CI: -0.25 to -0.043). Conclusions: Early QoL of patients affected with stage IV antropyloric cancer and symptoms of GOOS is significantly better in patients treated with SEMS positioning but at 6-month the QoL significantly decrease in this group of patients. We explained the reasons of this fluctuation with the higher risk of re-hospital admission in the SEMS group

Clinical features of patients with type 2 diabetes with and without Covid-19: a case control study (CoViDiab I)

Aims: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. Methods: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. Results: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59–3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42–9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18–8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13–0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12–0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16–0.93, p = 0.033) were found among cases. Conclusions: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes

Microvascular engineering in perfusion culture: immunohistochemistry and CLSM findings

BACKGROUND: One of the most challenging problems in tissue engineering is the establishment of vascular supply. A possible approach might be the engineering of microvasculature in vitro and the supply by engineered feeder vessels. METHODS: An in vitro model for a small-diameter vessel was developed and made from adipose tissue stromal cells and human umbilical vein endothelial cells in a tube-like gelatine scaffold. The number of "branches" emerging from the central lumen and the morphology of the central lumen of the vessel equivalent were assessed after 16 days of either pulsatile perfusion culture or culture in rotating containers by evaluation of immunohistochemically stained sections (n = 6 pairs of cultures). Intramural capillary network formation was demonstrated in five experiments with confocal laser scanning microscopy. RESULTS: Perfused specimens showed a round or oval lumen lined by a single layer of endothelial cells, whereas following rotation culture the lumen tended to collapse. Confocal laser scanning microscopy showed more extended network formation in perfused specimens as compared to specimens after rotation culture. Partially highly interconected capillary-like networks were imaged which showed orientation around the central lumen. Perfused specimens exhibited significantly more branches emerging from the central lumen. There were, however, hardly any capillary branches crossing the whole vessel wall. CONCLUSION: Pulsatile perfusion supports the development of vascular networks with physiological appearance. Advances in reactor development, acquisition of functional data and imaging procedures are however necessary in order to attain the ultimate goal of a fully functional engineered supplying vessel

Bayesian profiling of molecular signatures to predict event times

BACKGROUND: It is of particular interest to identify cancer-specific molecular signatures for early diagnosis, monitoring effects of treatment and predicting patient survival time. Molecular information about patients is usually generated from high throughput technologies such as microarray and mass spectrometry. Statistically, we are challenged by the large number of candidates but only a small number of patients in the study, and the right-censored clinical data further complicate the analysis. RESULTS: We present a two-stage procedure to profile molecular signatures for survival outcomes. Firstly, we group closely-related molecular features into linkage clusters, each portraying either similar or opposite functions and playing similar roles in prognosis; secondly, a Bayesian approach is developed to rank the centroids of these linkage clusters and provide a list of the main molecular features closely related to the outcome of interest. A simulation study showed the superior performance of our approach. When it was applied to data on diffuse large B-cell lymphoma (DLBCL), we were able to identify some new candidate signatures for disease prognosis. CONCLUSION: This multivariate approach provides researchers with a more reliable list of molecular features profiled in terms of their prognostic relationship to the event times, and generates dependable information for subsequent identification of prognostic molecular signatures through either biological procedures or further data analysis

Cardiometabolic multimorbidity is associated with a worse Covid-19 prognosis than individual cardiometabolic risk factors. A multicentre retrospective study (CoViDiab II)

Background: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. Methods: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. Results: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12-3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37-3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23-5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61-6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90-3.06, adjp = 0.10). Conclusions: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions

The Minimal Autoinhibited Unit of the Guanine Nucleotide Exchange Factor Intersectin

Intersectin-1L is a member of the Dbl homology (DH) domain guanine nucleotide exchange factors (GEF) which control Rho-family GTPase signaling. Intersectin-1L is a GEF that is specific for Cdc42. It plays an important role in endocytosis, and is regulated by several partners including the actin regulator N-WASP. Intact intersectin-1L shows low Cdc42 exchange activity, although the isolated catalytic DH domain shows high activity. This finding suggests that the molecule is autoinhibited. To investigate the mechanism of autoinhibition we have constructed a series of domain deletions. We find that the five SH3 domains of intersectin are important for autoinhibition, with the fifth domain (SH3(E)) being sufficient for the bulk of the autoinhibitory effect. This SH3 domain appears to primarily interact with the DH domain. We have determined the crystal structure of the SH3(E)-DH domain construct, which shows a domain swapped arrangement in which the SH3 from one monomer interacts with the DH domain of the other monomer. Analytical ultracentrifugation and gel filtration, however, show that under biochemical concentrations, the construct is fully monomeric. Thus we propose that the actual autoinhibited structure contains the related intramolecular SH3(E)-DH interaction. We propose a model in which this intramolecular interaction may block or distort the GTPase binding region of the DH domain

Seasonal variation in the incidence of ruptured abdominal aortic aneurysm

In order to determine any possible influence of climatic variables on the incidence of abdominal aortic aneurysm rupture, we reviewed 49,144 autopsies performed in two major hospitals in Rome, Italy, from January 1956 to March 1986. There were 297 subjects who were found to be sufferers of atherosclerotic abdominal aortic aneurysm for a prevalence of 0.6%. The aneurysm was intact in 220 cases (74%) and ruptured in 77 cases (26%). The highest incidence of ruptured aneurysm occurred during the Autumn and in the months May and July. The incidence of ruptured aneurysm was highest in case of significant changes of the atmospheric temperature. There was no correlation between the incidence of ruptured aneurysm and barometric pressure or humidity

Ruptured superior mesenteric artery aneurysm due to fibromuscular dysplasia. A rare vascular presentation in a patient with schizophrenia

Visceral aneurysms are rare entities, with a reported incidence of 0.01-2%. Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory artery disease which may predispose to aneurysmal degeneration. Schizophrenia has been linked to an increased cardiovascular risk because of the influence of traditional and disease specific risk factors. We report the case of a 44-year old male schizophrenic patient presenting with a ruptured giant aneurysm of superior mesenteric artery, managed by mesenteric ligation. The histologic diagnosis was fibromuscular dysplasia. One more other case of visceral aneurysm in schizophrenic patient, with similar histologic features has been previously reported in literature