Abdominoperineal Resection for Rectal Cancer: Is the Pelvic Drain Externalization Site an Independent Risk Factor for Perineal Wound Healing?

Aim. The aim of this paper is to investigate if the insertion of the pelvic drainage tube via the perineal wound could be considered as an independent risk factor for perineal healing disorders, after abdominoperineal resection for rectal malignancy. Patients and Methods. The last two decades, 75 patients underwent elective abdominoperineal resection for malignancy. In 42 patients (56%), the pelvic drain catheter was inserted through the perineal wound (PW group), while in the remaining 33 (44%) through a puncture skin wound of the perineum (SW group). Patients' data with respect to age (P = 0.136), stage (P > 0.05), sex (P = 0.188) and comorbidity (P = 0.128) were similar in both groups. 25 patients (PW versus SW: 8 versus 17, P = 0.0026) underwent neoadjuvant radio/chemotherapy. Results. The overall morbidity rate was 36%, but a significant increase was revealed in PW group (52.4% versus 9%, P = 0.0007). In 33.3% of the patients in the PW group, perineal healing was delayed, while in the SW group, no delay was noted. Perineal healing disorders were revealed as the main source of increased morbidity in this group. Conclusion. The insertion of the pelvic drain tube through the perineal wound should be considered as an independent risk factor predisposing to perineal healing disorders

The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms

The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells

Delayed presentation of an isolated gallbladder rupture following blunt abdominal trauma: a case report

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Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk

Adjustment of Insulin Pump Settings in Type 1 Diabetes Management: Advisor Pro Device Compared to Physicians’ Recommendations

Aims: To compare insulin dose adjustments made by physicians to those made by an artificial intelligence-based decision support system, the Advisor Pro, in people with type 1 diabetes (T1D) using an insulin pump and self-monitoring blood glucose (SMBG). Methods: This was a multinational, non-interventional study surveying 17 physicians from 11 countries. Each physician was asked to provide insulin dose adjustments for the settings of the pump including basal rate, carbohydrate-to-insulin ratios (CRs), and correction factors (CFs) for 15 data sets of pumps and SMBG of people with T1D (mean age 18.4 ± 4.8 years; eight females; mean glycated hemoglobin 8.2% ± 1.4% [66 ± 11mmol/mol]). The recommendations were compared among the physicians and between the physicians and the Advisor Pro. The study endpoint was the percentage of comparison points for which there was an agreement on the direction of insulin dose adjustments. Results: The percentage (mean ± SD) of agreement among the physicians on the direction of insulin pump dose adjustments was 51.8% ± 9.2%, 54.2% ± 6.4%, and 49.8% ± 11.6% for the basal, CR, and CF, respectively. The automated recommendations of the Advisor Pro on the direction of insulin dose adjustments were comparable)49.5% ± 6.4%, 55.3% ± 8.7%, and 47.6% ± 14.4% for the basal rate, CR, and CF, respectively(and noninferior to those provided by physicians. The mean absolute difference in magnitude of change between physicians was 17.1% ± 13.1%, 14.6% ± 8.4%, and 23.9% ± 18.6% for the basal, CR, and CF, respectively, and comparable to the Advisor Pro 11.7% ± 9.7%, 10.1% ± 4.5%, and 25.5% ± 19.5%, respectively, significant for basal and CR. Conclusions: Considerable differences in the recommendations for changes in insulin dosing were observed among physicians. Since automated recommendations by the Advisor Pro were similar to those given by physicians, it could be considered a useful tool to manage T1D

Asymmetry of Early Endosome Distribution in C. elegans Embryos

development, we examined the distribution and dynamics of early endosomes (EEs) in embryos.EEs are primarily found at the cell periphery with an initially uniform distribution after fertilization. Strikingly, we find that during the first cell cycle, EEA-1 positive EEs become enriched at the anterior cortex. In contrast, the Golgi compartment shows no asymmetry in distribution. Asymmetric enrichment of EEs depends on acto-myosin contractility and embryonic PAR polarity. In addition to their localization at the cortex, EEs are also found around the centrosome. These EEs move rapidly (1.3um/s) from the cortex directly to the centrosome, a speed comparable to that of the minus end directed motor dynein.We speculate that the asymmetry of early endosomes might play a role in cell asymmetries or fate decisions

Association of iron overload based quantitative T2* MRI technique and carotid intima-media thickness in patients with beta-thalassemia: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis is that high iron status is associated with increased risk of atherosclerosis. We investigated the potential role of iron as an additional risk factor promoting atherosclerosis among beta-thalassemic patients.</p> <p>Methods</p> <p>In this cross-sectional study, the liver iron load was assessed by quantitative T2* MRI technique and intima-media thickness (IMT) of the common carotid artery by high-resolution ultrasound among 119 patients (62 male, 57 female) with beta-thalassemia (major and intermediate) whose age ranged from 10 to 50 years with a mean of 25.6 years. The patients were divided into three groups according to the severity of iron loading, obtained by T2*MRI technique: group I (normal), group II (mild) and group III (moderate and severe) iron load.</p> <p>For elimination of the effect of age on carotid IMT values, the patients also were divided into four age groups (10-19 y, 20-29 y, 30-39 y and 40-50 y). Mean carotid IMT based on the severity of iron loading were compared at different age groups, using one way ANOVA analysis for assessing the effect of iron loading on carotid IMT. Pearson's coefficient of correlation were used to assess the degree of correlation between studied variables (liver T2*, IMT, age).</p> <p>Results</p> <p>There were significant differences in mean carotid IMT based on the severity of iron loading at different age groups, with P = 0.003 at 20-29 y, P = 0.006 at 30-39 y and p = 0.037 at 40-50 y. Age (p = 0.001) and liver T2*(p = 0.003) had significant correlation with mean carotid IMT independently.</p> <p>At the age group of 10-19 years, there were not significant differences in mean carotid IMT based on the liver iron loading (p = 0.661).</p> <p>No significant differences also are seen in mean carotid IMT between male and female (p = 0.41).</p> <p>Conclusions</p> <p>This study identified a relationship between body iron status and carotid IMT. This relationship support to the hypothesis of a link between body iron load and atherosclerosis.</p

Predictors of complications after endoscopic retrograde cholangiopancreatography: a prognostic model for early discharge

Background: Several studies have evaluated predictors for complications of endoscopic retrograde cholangiopancreatography (ERCP), but their relative importance is unknown. In addition, currently used blood tests to detect post-ERCP pancreatitis are inconsistent. The aim of this study was to determine predictors of post-ERCP complications that could discriminate between patients at highest and lowest risk of post-ERCP complications and to develop a model that is able to identify patients that can safely be discharged shortly after ERCP. Methods: In a single-center, retrospective analysis over the period 2002-2007, predictors of post-ERCP complications were evaluated in a multivariable analysis and compared with those identified from a literature review. A prognostic model was developed based on these risk factors, which was further evaluated in a prospective patient population. Results: From our retrospective analysis and literature review, we selected the eight most important risk factors for post-ERCP pancreatitis and cholangitis. In the prognostic model, the risk factors (precut) sphincterotomy, sphincter of Oddi dysfunction, younger age, female gender, history of pancreatitis, p