Idiopathic pancreatitis is a consequence of an altering spectrum of bile nucleation time

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of idiopathic pancreatitis (IP) remains poorly understood. Our hypothesis is that IP is a sequel of micro-crystallization of hepatic bile.</p> <p>Methods</p> <p>A prospective case control study compared 55 patients; symptomatic cholelithiasis - 30 (14 male, median age 36 years; mean BMI - 25.1 kg/m²), gallstone pancreatitis - 9 (3 male, median age 35 years; mean BMI - 24.86 kg/m²) and IP - 16 (9 male, median age 34 years; mean BMI -23.34 kg/m²) with 30 controls (15 male, median age 38 years; mean BMI = 24.5 kg/m²) undergoing laparotomy for conditions not related to the gall bladder and bile duct. Ultrafiltered bile from the common hepatic duct in patients and controls was incubated in anaerobic conditions and examined by polarized light microscopy to assess bile nucleation time (NT). In the analysis, the mean NT of patients with gallstones and gallstone pancreatitis was taken as a cumulative mean NT for those with established gallstone disease (EGD).</p> <p>Results</p> <p>Patients were similar to controls. Mean NT in all groups of patients was significantly shorter than controls (EGD cumulative mean NT, 1.73 +/- 0.2 days vs. controls, 12.74 +/- 0.4 days, P = 0.001 and IP patients mean NT, 3.1 +/- 0.24 days vs. controls, 12.74 +/- 0.4 days, P = 0.001). However, NT in those with IP was longer compared with those with EGD (mean NT in IP, 3.1 +/- 0.24 days vs. cumulative mean in EGD: 1.73 +/- 0.2 days, P = 0.002).</p> <p>Conclusion</p> <p>Nucleation time of bile in patients with IP is abnormal and is intermediate to nucleation time of lithogenic bile at one end of the spectrum of lithogenicity and non-lithogenic bile, at the other end.</p

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The usefulness of microscopic bile examination in the evaluation of patients with upper abdominal pain

Background: Biliary microlithiasis is a collection of cholesterol and calcium bilirubinate crystals and is known to cause biliary colic, acute pancreatitis and acute cholecystitis. In some of these patients biliary microlithiasis has been found. Objectives: To estimate the incidence of biliary microlithiasis in patients with upper abdominal pain and negative imaging tests. Methods: A prospective analysis of bile was studied in 50 patients. A positive result was the identification of cholesterol crystals or calcium bilirubinate clumps. Results: In the 50 patients studied, 7 patients were found to have microlithiasis in bile. Conclusion: Microscopic examination of bile for biliary microlithiasis is a simple and safe technique and must be done in patients with upper abdominal pain who have normal blood tests, negative imaging tests and normal upper gastrointestinal endoscopy. Biliary microlithiasis is the probable cause of upper abdominal pain in some of these patients

Penile metastasis from carcinoma of the rectum: A case report

Penile metastases are extremely uncommon. When they do occur the primary lesion is most often in one of the pelvic organs. Patient may present with a painful nodule, priapisfn and urinary obstruction. Treatment is usually pal-liative. Aggressive surgical approach may benefit care-fully selected patients who have no other clinical metastatic lesions

Aerodynamic and Heat Transfer Studies of HPT Rotor and Stator Blades of GTX-35-VS Engine

The stator and rotor blade hub sections designed for a high pressure turbine stage were studied in detail for their aerodynamic and heat transfer characteristics.The profile sections were tested in the National Aeronautical Laboratory(NAL) cascade tunnels over a range of exit flow Mach numbers.The flow field and heat transfer characteristics of the cascades were analysed,employing the Euler code,the method of singularities and the K- turbulence model.The results indicated that there was scope for improving the blade profile sections for the proposed high Mach number application. In particular,it has been observed that the energy loss coefficients of the stator blade are rather high around the design point.The air swallowing capacity of the rotor blade design appears to be inadequate compared to the design expectations.The predictions of the surface pressure distributions obtained from the Euler code are generally in good agreement with the measured values in the Transonic Cascade Tunnel.The measured distribution of heat transfer coefficients around the blade surfaces give a useful data base for the design of the cooled blades.Prediction of the heat transfer for these transonic blades using the K- model of turbulence appears to be in general,not adequate.Recourse to correlation of the measured data using power-law relations appears to be promising ,at least as a short time measure