Incidental biliary dilation in the era of the opiate epidemic: High prevalence of biliary dilation in opiate users evaluated in the Emergency Department

BACKGROUNDBiliary dilation is frequently related to obstruction; however, non-obstructive factors such as age and previous cholecystectomy have also been reported. In the past two decades there has been a dramatic increase in opiate use/dependence and utilization of cross-sectional abdominal imaging, with increased detection of biliary dilation, particularly in patients who use opiates.AIMTo evaluate associations between opiate use, age, cholecystectomy status, ethnicity, gender, and body mass index utilizing our institution’s integrated informatics platform. METHODSOne thousand six hundred and eighty-five patients (20% sample) presenting to our Emergency Department for all causes over a 5-year period (2011-2016) who had undergone cross-sectional abdominal imaging and had normal total bilirubin were included and analyzed.RESULTSCommon bile duct (CBD) diameter was significantly higher in opiate users compared to non-opiate users (8.67 mm vs 7.24 mm, P < 0.001) and in patients with a history of cholecystectomy compared to those with an intact gallbladder (8.98 vs 6.72, P < 0.001). For patients with an intact gallbladder who did not use opiates (n = 432), increasing age did not predict CBD diameter (r² = 0.159, P = 0.873). Height weakly predicted CBD diameter (r² = 0.561, P = 0.018), but weight, body mass index, ethnicity and gender did not.CONCLUSIONOpiate use and a history of cholecystectomy are associated with CBD dilation in the absence of an obstructive process. Age alone is not associated with increased CBD diameter. These findings suggest that factors such as opiate use and history of cholecystectomy may underlie the previously-reported association of advancing age with increased CBD diameter. Further prospective study is warranted.     

The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility

National and ethnic mutation databases provide comprehensive information about genetic variations reported in a population or an ethnic group. In this paper, we present the Moroccan Genetic Disease Database (MGDD), a catalogue of genetic data related to diseases identified in the Moroccan population. We used the PubMed, Web of Science and Google Scholar databases to identify available articles published until April 2013. The Database is designed and implemented on a three-tier model using Mysql relational database and the PHP programming language. To date, the database contains 425 mutations and 208 polymorphisms found in 301 genes and 259 diseases. Most Mendelian diseases in the Moroccan population follow autosomal recessive mode of inheritance (74.17%) and affect endocrine, nutritional and metabolic physiology. The MGDD database provides reference information for researchers, clinicians and health professionals through a user-friendly Web interface. Its content should be useful to improve researches in human molecular genetics, disease diagnoses and design of association studies. MGDD can be publicly accessed at http://mgdd.pasteur.ma.     

Proximal Roux-en-y Gastrojejunal Anastomosis with Pyloric Ring Resection Improves Gastric Emptying After Pancreaticoduodenectomy

Background

Delayed gastric emptying (DGE) is a common complication of pancreaticoduodenectomy. We determined the efficiency of a new reconstruction technique, designed to preserve motilin-secreting cells and maximize the utility of their receptors, in reducing the incidence of DGE after pancreaticoduodenectomy.

Methods

From April 2005 to September 2014, 217 consecutive patients underwent pancreaticoduodenectomy at our institution. Nine patients who underwent total pancreatectomy were excluded. We compared outcomes between patients who underwent pancreaticoduodenectomy with resection of the pyloric ring followed by proximal Roux-en-y gastrojejunal anastomosis (group I, n?=?90) and patients who underwent standard pancreaticoduodenectomy with the orthotopic reconstruction technique (group II, n?=?118).

Results

Overall and clinically relevant rates of DGE were significantly lower in group I than in group II (10 and 2.2 % vs. 57 and 24 %, respectively; p?<?0.05). Length of hospital stay as a result of DGE was shorter in group I than in group II. In univariate analysis, older age, comorbidities, ASA grade 4, operative time, preoperative diabetes, standard reconstruction technique, and postoperative complications were significant risk factors for DGE. In multivariate analysis, older age, standard technique, and postoperative complications were independent risk factors for DGE.

Conclusion

Our new reconstruction technique reduces the occurrence of DGE after pancreaticoduodenectomy.

     

Efficacy of zinc oxide nanoparticles in attenuating pancreatic damage in a rat model of streptozotocin-induced diabetes

Zinc oxide nanoparticles (ZnO NPs) therapy is a promising strategy for treatment of several diseases. We aimed to investigate the therapeutic potential of ZnO NPs in ameliorating the histopathological and functional alterations in the pancreas of a rat model of streptozotocin-induced diabetes. Rats were randomized into control, diabetic and ZnO NPs-treated diabetic groups. Biochemical assays of blood glucose and serum insulin were performed. Pancreas specimens were processed for light and electron microscope examinations. ZnO NPs effectively reversed diabetes-induced pancreatic injury, as evidenced by the structural and ultrastructural improvement and confirmed by biochemical normalization of blood glucose and serum insulin.     

Modulation of ATP/ADP Concentration at the Endothelial Surface by Shear Stress: Effect of Flow Recirculation

The extracellular presence of the adenine nucleotides ATP and ADP induces calcium mobilization in vascular endothelial cells (ECs). ATP/ADP concentration at the EC surface is determined by a balance of convective-diffusive transport to and from the EC surface, hydrolysis by ectonucleotidases at the cell surface, and flow-induced ATP release from ECs. Our previous numerical simulations in a parallel plate geometry had demonstrated that flow-induced ATP release has a profound effect on nucleotide concentration at the EC surface. In the present study, we have extended the modeling to probe the impact of flow separation and recirculation downstream of a backward facing step (BFS) on ATP/ADP concentration at the EC surface. The results show that for both steady and pulsatile flow over a wide range of wall shear stresses, the ATP + ADP concentration at the EC surface is considerably lower within the flow recirculation region than in areas of undisturbed flow outside the recirculation zone. Pulsatile flow also leads to sharp temporal gradients in nucleotide concentration. If confirmed experimentally, the present findings suggest that disturbed and undisturbed flow may affect EC calcium mobilization differently. Such differences might, in turn, contribute to the observed endothelial dysfunction in regions of disturbed flow.     

Extended-release naltrexone/bupropion and liver health: Pooled,post hoc analysis from four randomized controlled trials

Sustained weight loss improves liver histology in non-alcoholic fatty liver disease. This post hoc analysis of four phase III, 56-week, randomized controlled trials investigated if extended-release naltrexone and bupropion (NB) affects alanine aminotransferase (ALT) and Fibrosis-4 (FIB-4) index in adults with overweight or obesity. Two thousand and seventy-three subjects (NB = 1310; placebo = 763; 79.0% female; 81.6% Caucasian) had baseline mean weight 101 kg, body mass index 36.2 kg/m², ALT 26.9 IU/L and FIB-4 0.79. At 56 weeks, NB-treated subjects experienced more weight loss than placebo (8.7 vs. 3.2 kg, respectively, P < .0001). Weight loss, independent of treatment, was associated with improved ALT and FIB-4 (P < .0001). There was a significant independent effect of NB on change from baseline for FIB-4 (P < .0001), but not for ALT (P = .54). Categorical ALT response (from above to within normal ranges: 10-40 IU/L for men; 7-35 IU/L for women) and achievement of 25% and 50% reduction in ALT were greater for NB versus placebo, and independently affected by weight loss (P < .0001), but not treatment. NB-associated weight loss may improve liver health by normalizing ALT values for those with high baseline levels.     

Early- and late-onset pancreatic adenocarcinoma: A population-based comparative study

BackgroundPancreatic cancer is projected to become the second leading cause of cancer related death in the US. We aim to investigate the demographics, clinical outcomes and survival outcomes of patients diagnosed with early-onset (<40 years) and late-onset (>40 years) pancreatic adenocarcinoma (PAC).MethodsData on PAC between 1975 and 2016 were extracted from the Surveillance, Epidemiology, and End Results Registry.ResultsWithin the study period, 136,100 patients were identified which included 1181 patients with early-onset PAC and 134,919 patients with late-onset PAC. Both cohorts tend to present with distant metastasis (70.3% vs 57.9%). Both groups also showed an exponential rise in incidence (early-onset 3.69% annual change vs late-onset 6.25% annual change). When stratified by anatomical location, there was a trend of increasing cancer in the head of the pancreas for patients <40 years (3.63% annual change). While late PAC showed increasing cancer in all anatomical locations, the largest increase was observed in the tail of the pancreas (8.62% annual change). Overall, there was a mild difference in survival for early- and late-onset PAC (7 months vs 6 months, respectively, log rank p = 0.004). Both age groups showed the worse prognosis when cancer occurred in the tail of the pancreas (6 months vs 4 months, respectively). On cox proportion analysis, patients with late-onset PAC had twice the risk of mortality compared to early-onset PAC (HR 2.06, CI: 1.788–2.370, P = 0.001).ConclusionsOur study showed that both early- and late-onset PAC are increasing and while prognosis remains poor. Tumor anatomy showed a growing incidence of early-onset PAC in the head of the pancreas while late-onset PAC showed a rising incidence in the body and tail of the pancreas.     

Discovery of Novel Peptidomimetics as Irreversible CHIKV NsP2 Protease Inhibitors Using Quantum Mechanical‐Based Ligand Descriptors

Chikungunya virus (CHIKV) is a mosquito‐borne alphavirus. Recent outbreaks of CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents 3a , 4b, and 5d showing 93–100% maximum inhibition of CHIKV replication in cell‐based assay having EC₉₀ of 8.76–9.57 μg/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics 3a , 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme inactivation via Michael adduct formation between α/β‐unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b satisfied the Lipinski rule of five for drug‐likeness and showed promising intestinal absorption and aqueous solubility via computational admet studies making them promising hits for further optimization.     

In palindromic rheumatism,hand joint involvement and positive anti-CCP antibodies predict RA development after 1 year of follow-up

This study aimed to determine the frequency of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies in a cohort of patients with palindromic rheumatism (PR) and to find determinants for progression to rheumatoid arthritis (RA). All new cases of PR (n?=?90) were included prospectively and followed up for 1 year, and a comparison group of RA cases (n?=?70) was also included. At study entry in all patients in both groups, RF and anti-CCP antibodies were tested, and the findings were compared and correlated. In the PR group at presentation, RF was positive in 30 patients (33.3 %) and, in the RA group, in 45 patients (64.3 %). Anti-CCP antibodies were positive in 35 patients (38.9 %) with PR and in 58 patients (82.9 %) with RA. In the PR group, positive correlations were observed between RF and C-reactive protein (CRP) (p?=?0.036), while anti-CCP positively correlated with disease duration (p?=?0.015) and CRP (p?<?0.001). At 1-year follow-up, 25 cases (27.5 %) had progressed to RA, 3 (3.3 %) cases had developed systemic lupus, 43 cases had responded to hydroxychloroquine with complete remission, five cases had developed other rheumatic diseases, and 14 cases had progressed to undifferentiated arthritis. After regression analysis, the involvement of hand joints and positive anti-CCP were the only predictors that determined progression into RA within a year (p?<?0.001 and p?=?0.02, respectively). Early hand joint involvement and positive anti-CCP at disease onset are good predictors for progression to RA in this domain.