Abstract
Background
Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy. Complete BBS without visible parts of the inner bumper is a challenge for endoscopic ...treatment.
Methods and Aims
Data base analysis of all procedures performed at our tertiary university endoscopy center between 2000 and 2015 was conducted. Our aim was to improve the success rates of endoscopic treatment using a standardized approach and a pull-modification of the papillotome-based extraction technique in a prospective cohort.
Results
Retrospectively, 55 patients were identified (37 men; age 54 ± 16 years). The prospective series comprised 11 patients (8 men; age 63 ± 27 years). Patients with partial BBS were effectively treated by endoscopy in both cohorts (24/25 and 4/4 patients, respectively). For complete BBS (Cyrany grade 3), success rates of endoscopic therapy differed significantly between the cohorts (P = 0.017). In the retrospective cohort, only 38% of patients (9/24 patients) were successfully treated. In the prospective cohort, all six patients (deep-type in five cases) were managed without complications. Patients with extra-gastric tubes underwent primary surgery in both cohorts (six and one patients, respectively).
Conclusion
A structured approach improved success rates of endoscopic treatment. All patients with an internal bumper verified to lie within the gastric wall can be treated by an experienced investigator using a papillotome-based technique.
Poor adherence to medication leads to worsening of the disease, increased mortality and substantial rise in health care costs.
It was our aim to evaluate drug adherence and influencing factors in a ...cohort of non-selected adult pharmacy customers with various chronic diseases and following long-term treatment.
We conducted an 8 week anonymized survey in 152 German pharmacies using the Morisky Medication Adherence Scale to measure medication adherence and a questionnaire comprising questions on multiple factors with potential impact on adherence. Depression was assessed applying the Patient Health Questionnaire-9.
In total, 1192 patients were included showing an overall adherence rate of 59.1%. A positive association to drug adherence was found in univariate analysis for non-smoking status, retirement, less disease related complaints, positive belief in drug effects, comprehensive knowledge about the disease and high quality of care by the physician and pharmacist. Multivariate regression analysis revealed that no or minimal depression (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.7-3.0), higher patient age (>63 years) (OR 2.2, CI 1.7-2.8), high perceived importance of the medication (OR 2.0, CI 1.5-2.6), good tolerability of the medication (OR 2.0, CI 1.2-3.5) and drug effect as expected or better (OR 1.6, CI 1.1-2.3) were positively correlated with adherence.
Suboptimal adherence to medication is common in pharmacy customers with chronic diseases. The determined factors influencing adherence may help to identify patients at risk for nonadherence and support the need of improvement in physicians' communication with patients to achieve adequate adherence rates.
The purpose of this study was to assess the changes in duodenal composition in three nutritional states: fasted, fed, and fat-enriched fed state. Two isocaloric meals were administered to healthy ...subjects on nonconsecutive days. Subsequently, duodenal samples were collected every 30min after which they were characterized with respect to pH, lipolytic products, bile salts, phospholipids, osmolality, and surface tension. The resulting time profiles displayed fluctuating patterns, which reflect high inter- and intrasubject variability. Duodenal composition was not altered by the higher fat percentage of the fat-enriched liquid meal. Monoglycerides, amounting from 5% to 88% of total lipids, were the dominant lipolytic species, followed by free fatty acids. Within 30min after meal administration, individual intraduodenal concentrations of lipid products were 0.0–5.5, 1.0–14.9, and 3.1–22.4mg/mL in fasted, fed, and fat-enriched fed state, respectively. The corresponding values for bile salts were 2.0–9.0, 6.9–9.3, and 4.4–30.3mM and for phospholipids 0.06–2.4, 2.6–5.7, and 1.4–9.3mM, respectively. Specific trends though, were not detected. This study illustrates the variable intraluminal conditions that can result after food intake. As intraduodenal events (e.g., intraduodenal dissolution) affect absorption of poorly water soluble and/or highly lipophilic drugs, this variability may possibly contribute to the highly variable drug plasma-time profiles often observed.
Abstract Background Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line ...gemcitabine plus sorafenib in a double-blind phase II study. Patients and methods 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0–2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks + 1-week rest followed by once 3-weeks + 1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity. Tumour samples were prospectively stained for sorafenib targets and potential biomarkers. Serum samples (first two cycles) were measured for vascular endothelial growth factors (VEGFs), vascular endothelial growth factor receptor 2 (VEGFR-2) and stromal cell-derived factor 1 (SDF1)α by enzyme-linked immunosorbent assay (ELISA). Results Gemcitabine plus sorafenib was generally well tolerated. Four and three patients achieved partial responses in the sorafenib and placebo groups, respectively. There was no difference in the primary end-point, median progression-free survival (PFS) for gemcitabine plus sorafenib versus gemcitabine plus placebo (3.0 versus 4.9 months, P = 0.859), and no difference for median overall survival (OS) (8.4 versus 11.2 months, P = 0.775). Patients with liver metastasis after resection of primary BTC survived longer with sorafenib ( P = 0.019) compared to placebo. Patients who developed hand-foot syndrome (HFS) showed longer PFS and OS than patients without HFS. Two sorafenib targets, VEGFR-2 and c-kit, were not expressed in BTC samples. VEGFR-3 and Hif1α were associated with lymph node metastases and T stage. Absence of PDGFRβ expression correlated with longer PFS. Conclusion The addition of sorafenib to gemcitabine did not demonstrate improved efficacy in advanced BTC patients. Biomarker subgroup analysis suggested that some patients might benefit from combined treatment.
Summary
Background
Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The ...automated low‐flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.
Aim
To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.
Methods
Fifty‐six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.
Results
At the time of this analysis, 3 patients completed the 24‐month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty‐three pump‐related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow‐up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.
Conclusions
The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions.
https://clinicaltrials.gov/ct2/show/NCT01532427
Linked ContentThis article is linked to Macdonald and Jalan and Stirnimann and De Gottardi papers and Weil et al papers. To view these articles visit https://doi.org/10.1111/apt.14390, https://doi.org/10.1111/apt.14415, https://doi.org.10.1111/apt.14440 and https://doi.org.10.1111/apt.14500.
In response to the COVID-19 pandemic, endoscopic societies initially recommended reduction of endoscopic procedures. In particular non-urgent endoscopies should be postponed. However, this might lead ...to unnecessary delay in diagnosing gastrointestinal conditions.
Retrospectively we analysed the gastrointestinal endoscopies performed at the Central Endoscopy Unit of Saarland University Medical Center during seven weeks from 23 March to 10 May 2020 and present our real-world single-centre experience with an individualized rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy. We also present our experience with this strategy in 2021.
Altogether 359 gastrointestinal endoscopies were performed in the initial period. The testing strategy enabled us to conservatively handle endoscopy programme reduction (44% reduction as compared 2019) during the first wave of the COVID-19 pandemic. The results of COVID-19 rtPCR from nasopharyngeal swabs were available in 89% of patients prior to endoscopies. Apart from six patients with known COVID-19, all other tested patients were negative. The frequencies of endoscopic therapies and clinically significant findings did not differ between patients with or without SARS-CoV-2 tests. In 2021 we were able to unrestrictedly perform all requested endoscopic procedures (> 5000 procedures) by applying the rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy, regardless of next waves of COVID-19. Only two out-patients (1893 out-patient procedures) were tested positive in the year 2021.
A structured pre-endoscopy SARS-CoV-2 testing strategy is feasible in the clinical routine of an endoscopy unit. rtPCR-based pre-endoscopy SARS-CoV-2 testing safely allowed unrestricted continuation of endoscopic procedures even in the presence of high incidence rates of COVID-19. Given the low frequency of positive tests, the absolute effect of pre-endoscopy testing on viral transmission may be low when FFP-2 masks are regularly used.
Intrahepatic cholestasis of pregnancy (ICP) has a complex aetiology with a significant genetic component. ABCB11 encodes the bile salt export pump (BSEP); mutations cause a spectrum of cholestatic ...disease, and are implicated in the aetiology of ICP.
ABCB11 variation in ICP was investigated by screening for five mutant alleles (E297G, D482G, N591S, D676Y and G855R) and the V444A polymorphism (c.1331T>C, rs2287622) in two ICP cohorts (n = 333 UK, n = 158 continental Europe), and controls (n = 261) for V444A. PCR primers were used to amplify and sequence patient and control DNA. The molecular basis for the observed phenotypes was investigated in silico by analysing the equivalent residues in the structure of the homologous bacterial transporter Sav1866.
E297G was observed four times and D482G once. N591S was present in two patients; D676Y and G855R were not observed. The V444A polymorphism was associated with ICP (allelic analysis for C vs T: OR 1.7 (95% CI 1.4 to 2.1, p<0.001)). In addition, CC homozygotes were more likely to have ICP than TT homozygotes: OR 2.8 (95% CI 1.7 to 4.4 p<0.0001). Structural analyses suggest that E297G and D482G destabilize the protein fold of BSEP. The molecular basis of V444A and N591S was not apparent from the Sav1866 structure.
Heterozygosity for the common ABCB11 mutations accounts for 1% of European ICP cases; these two mutants probably reduce the folding efficiency of BSEP. N591S is a recurrent mutation; however, the mechanism may be independent of protein stability or function. The V444A polymorphism is a significant risk factor for ICP in this population.
Summary Large-scale whole-genome sequencing of the Icelandic population identified an association between several mutations of ABCB4 encoding the hepatobiliary phosphatiylcholine floppase with liver ...diseases and function in the general population. Whereas rare mutations of this transporter were known to cause progressive familial intrahepatic cholestasis, the genome-wide association studies in Iceland find the common ABCB4 variant c.711A>T to be a general risk factor for elevated aminotransferases and higher impact variants to be potential determinants of early-onset gallstone disease, cholestasis of pregnancy, liver cirrhosis, and hepatobiliary cancer.
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