Advances in classification, prognostication and treatment of immunocholangitis

Immullocholangitis is a collective for chronic inflammatory disorders affecting the biliary tree, presumably with an autoimmune-mediated pathogenesis. Destruction and distortion of bile ducts, leading to impaired bile flmv, are key features of immunocholangitis. In general, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are considered to be the main diseases of immunochoiangitis. PBC, a chronic cholestatic liver disease, is one of the most common vanishing bile duct disorders. Gradual loss of interlobular and septal bile ducts, histologically described as chronic non-suppurative destructive cholangitis, leads to chronic cholestasis, fibrosis and biliary cirrhosis which may ultimately cause liver failure, necessitating transplantation. Since 1988, PBC has been the third leading indication for liver transp

Alteration of postantibiotic effect during one dosing interval of tobramycin, simulated in an in vitro pharmacokinetic model

The kinetics of the postantibiotic effect (PAE) during one dosing interval of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was investigated. We determined the PAE at different time points during this dosing interval of 12 h in an in vitro pharmacokinetic model simulating human pharmacokinetics in which the half-life of tobramycin was adjusted to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we determined PAEs in samples extracted from the model at 1, 5, 8, and 12 h, corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the MIC for the test organism. The PAE decreased significantly from 2.5 h at 1 h to 0 h at 12 h. No change in MIC was observed for the strains during the experiments. We conclude that the PAE decreases with decreasing tobramycin concentrations during a 12-h dosing interval and completely disappears after the concentration has reached the MIC for the test organism. On the basis of these observations, the emphasis that is placed on the PAE in discussions about the optimal dosing interval in aminoglycoside therapy is questionable

Clinical outcomes of biliary drainage of malignant biliary obstruction due to colorectal cancer metastases : a systematic review

Background and aims: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC). Biliary drainage is frequently performed to relieve symptoms of jaundice or enable palliative systemic therapy, but effective drainage can be difficult to accomplish. The aim of this study is to summarize literature on clinical outcomes of biliary drainage in mCRC patients with malignant biliary obstruction.& nbsp; Methods: We searched Medline and EMBASE for studies that included patients with malignant biliary obstruction secondary to mCRC, treated with endoscopic and/or percutaneous biliary drainage. We summarized available data on technical success, clinical success, adverse events, systemic therapy administration and survival after biliary drainage.& nbsp; Results: After screening 3584 references and assessing 509 full-text articles, seven cohort studies were included. In these studies, rates of technical success, clinical success and adverse events varied between 63%-94%, 42%81%, and 19%-39%, respectively. Subsequent chemotherapy was administered in 17%-56% of patients. Overall survival varied between 40 and 122 days across studies (278-365 days in patients who received subsequent chemotherapy, 42-61 days in patients who did not).& nbsp; Conclusions: Successful biliary drainage in mCRC patients can be challenging to achieve and is frequently associated with adverse events. Overall survival after biliary drainage is limited, but is significantly longer in patients treated with subsequent systemic therapy. Expected benefits of biliary drainage should be carefully weighed against its risks

Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore

Please open article to read abstractThis work was financially supported by the Department of Science and Technology which awarded an innovation fund to five South African institutions (The Medical Research Council, South African National Biodiversity Institute, Council for Scientific and Industrial Research, University of Cape Town and University of Pretoria) to scientifically validate South African medicinal plants for the treatment of malaria

Performance of EUS-FNA for mediastinal lymphadenopathy: impact on patient management and costs in low-volume EUS centers

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymphadenopathy has been shown to be a valuable diagnostic tool in high-volume EUS centers (≥ 50 mediastinal EUS-FNA/endoscopist/year). Our goal was to assess the diagnostic accuracy of EUS-FNA and its impact on clinical management and costs in low-volume EUS centers ( <50 mediastinal EUS-FNA/endoscopist/year). METHODS: Consecutive patients referred to two Dutch endoscopy centers in the period 2002-2008 for EUS-FNA of mediastinal lymphadenopathy were reviewed. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. The impact of EUS-FNA on clinical management was subdivided into a positive impact by providing (1) adequate cytology that influenced the decision to perform surgery or (2) a diagnosis of a benign inflammatory disorder, and a negative impact which was subdivided into (1) false-negative or inconclusive cytology or (2) an adequate cytological diagnosis that did not influence patient management. Costs of an alternative diagnostic work-up without EUS-FNA, as established by an expert panel, were compared to costs of the actual work-up. RESULTS: In total, 213 patients (71% male, median age= 61 years, range = 23-88 years) underwent EUS-FNA. Sensitivity, specificity, and negative and positive predictive values were 89%, 100%, 80%, and 100%, respectively. EUS-FNA had a positive impact on clinical management in 84% of cases by either influencing the decision to perform surgery (49%) or excluding malignant lymphadenopathy (35%), and a negative impact in 7% of cases because of inadequate (3%) or false-negative (4%) cytology. In 9% of cases, EUS-FNA was performed without an established indication. Two nonfatal perforations occurred (0.9%). Total cost reduction was €100,593, with a mean cost reduction of €472 (SD = €607) per patient. CONCLUSIONS: Mediastinal EUS-FNA can be performed in low-volume EUS centers without compromising diagnostic accuracy. Moreover, EUS-FNA plays an important role in the management of patients with mediastinal lymphadenopathy and reduces total diagnostic cost

Early Lumen-Apposing Metal Stent Dysfunction Complicating Endoscopic Ultrasound-Guided Gastroenterostomy: A Report of Two Cases

Endoscopic ultrasonography-guided gastroenterostomy using a lumen-apposing metal stent has emerged as a novel technique in the palliative treatment of malignant gastric outlet obstruction. Endoscopic ultrasonography-guided gastroenterostomy seems to have the potential to provide long-lasting patency in a minimally invasive manner. Low reintervention rates have been described. We report two cases with early lumen-apposing metal stent dysfunction, compromising patency. One case showed food impaction after three weeks, and hyperplastic tissue overgrowth with a buried distal flange six weeks after stent placement. The latter was successfully treated by argon plasma coagulation, stent removal, and deployment of a larger-diameter lumen-apposing metal stent. The second case showed a narrowed luminal diameter of the stent and jejunal pressure ulcerations after three weeks. The narrowing was successfully treated by balloon dilation. Eight weeks later, hyperplastic tissue overgrowth at the distal flange of the stent and a gastro-colonic fistula were diagnosed, followed by extensive reconstructive surgery

Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study

In a collaborative multicenter case-control study, we investigated the effect of factor V Leiden mutation, prothrombin gene mutation, and inherited deficiencies of protein C, protein S, and antithrombin on the risk of Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). We compared 43 BCS patients and 92 PVT patients with 474 population-based controls. The relative risk of BCS was 11.3 (95% CI 4.8-26.5) for individuals with factor V Leiden mutation, 2.1(95% CI 0.4-9.6) for those with prothrombin gene mutation, and 6.8 (95% CI 1.9-24.4) for those with protein C deficiency. The relative risk of PVT was 2.7 (95% CI 1.1-6.9) for individuals with factor V Leiden mutation, 1.4 (95% CI 0.4-5.2) fo

Еволюція історичних уявлень про Україну в середньовічній Франції до середини ХVІІ ст.

У статті розглянуто стан ознайомлення французької громадськості ХІ-ХVІІ ст. з Україною, проаналізовано причини цікавості французів до цієї країни на тлі історичних взаємин України та Франції. Автор простежує еволюцію французьких історичних досліджень про Україну у Франції.The author considers the state of acquaintance of the French society of the XVII century with Ukraine, analyses the reasons of the interest the French took in this country on the phone of the historical relations between Ukraine and France and traces the evolution of the French historical studies in Ukraine

Treatment of refractory post-esophagectomy anastomotic esophageal strictures using temporary fully covered esophageal metal stenting compared to repeated bougie dilation: results of a randomized controlled trial

Background and study aims Fully covered self-expanding metal stents (FCSEMS) provide an alternative to bougie dilation (BD) for refractory benign esophageal strictures. Controlled studies comparing temporary placement of FCSES to repeated BD are not available. Patients and methods Patients with refractory anastomotic esophageal strictures, dysphagia scores ≥ 2, and two to five prior BD were randomized to 8 weeks of FCSEMS or to repeated BD. The primary endpoint was the number of BD during the 12 months after baseline treatment. Results Eighteen patients were included (male 67 %, median age 66.5; 9 received metal stents, 9 received BD). Technical success rate of stent placement and stent removal was 100 %. Recurrent dysphagia occurred in 13 patients (72 %) during follow-up. No significant difference was found between the stent and BD groups for mean number of BD during follow-up (5.4 vs. 2.4, P = 0.159), time to recurrent dysphagia (median 36 days vs. 33 days, Kaplan-Meier: P = 0.576) and frequency of reinterventions per month (median 0.3 vs. 0.2, P = 0.283). Improvement in quality of life score was greater in the stent group compared to the BD group at month 12 (median 26 % vs. 4 %, P = 0.011). Conclusions The current data did not provide evidence for a statistically significant difference between the two groups in the number of BD during the 12 months after initial treatment. Metal stenting offers greater improvement in quality of life from baseline at 12 months compared to repeated BD for patients with refractory anastomotic esophageal stricture

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaff