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Background: Endoscopic treatment guided by Doppler endoscopic probes (DEPs) during index endoscopy may be associated with improved outcome in patients with peptic ulcer bleeding (PUB). As competencies for DEP evaluation are not always available for index endoscopy, we examined the outcome associated with DEP evaluation at second-look endoscopy. Methods: The study was designed as a non-blinded, parallel group, randomised controlled trial. Patients admitted with PUB from Forrest Ia-IIb ulcers, controlled by endoscopic therapy, were randomised (1:1 ratio) to second-look endoscopy <24 h with DEP evaluation of the bleeding ulcer or continued standard treatment. Patients were followed up for 30 days. The primary outcome was rebleeding. Secondary outcomes included the number of transfusions, length of hospital stay, and 30-day mortality. Results: A total of 62 patients were included. At second-look endoscopy, 91% (29/32) of patients had a positive DEP signal at the ulcer base and were treated with contact thermal therapy (n = 29), injection of diluted adrenaline (n = 23), and haemoclips (n = 7). Among the 32 patients treated with DEP evaluation, only one rebled (3%) compared to four patients (13%) in the control group (p = 0.20). There were no differences in the secondary outcomes between groups, and there were no complications related to DEP evaluation. Conclusions: Second-look endoscopy with DEP-guided evaluation and treatment is safe and associated with a very low risk of rebleeding (3%) in patients with PUB. Second-look endoscopy with DEP evaluation may be considered in selected PUB patients at high risk of rebleeding, and may represent an alternative to the use of DEP for index endoscopy. Nevertheless, we did not find that second-look endoscopy with DEP evaluation significantly improved patient outcome compared to standard treatment. [ABSTRACT FROM AUTHOR]

Background and aim: Predicting overt hepatic encephalopathy (OHE) is important because the condition is frequent, often requires hospitalization and is potentially preventable. The risk of OHE is related to pre-existing discrete cognitive defects, and for clinical practice it is recommended to apply two different psychometric tests to detect such deficits. We used the continuous reaction time test (CRT) and the portosystemic encephalopathy (PSE) syndrome test and examined their single and combined value for OHE prediction in cirrhosis patients. Patients and methods: We studied 130 clinically mentally unimpaired cirrhosis patients by the two tests and followed them for an average of 38.5 months. The CRT measures velocity and stability of motor reaction times to 150 repeated auditory signals. The PSE is a five sub-set paper-and-pencil test battery evaluating cognitive and psychomotor processing, speed and vision-motor coordination. We collected data on episodes of OHE during follow-up. The clinical course was analysed in patient groups according to the outcome of each test and of both tests together. No anti-HE treatment was initiated except for cases with OHE. Results: At baseline, the CRT test was abnormal in 74 patients and the PSE in 47. During follow-up 35 patients (27%) experienced 74 OHE events. 23 patients with abnormal CRT experienced OHE (prediction sensitivity 65%). The PSE predicted OHE in 14 patients (prediction sensitivity 40%). One or both tests were abnormal in 87/130 (67%) and this predicted OHE in 27 patients (21%) (prediction sensitivity 77%). Conclusion: The CRT test was clinically useful in identifying two-thirds of clinically mentally unimpaired cirrhosis patients who later experienced OHE, and the use of both the CRT and PSE showed satisfactory prediction by identifying three-fourths of later OHE cases. [ABSTRACT FROM AUTHOR]

Background and aims: Acute cholangitis (AC) is a rare but serious condition, with an incidence of 7.0 per 10,000 people and mortality rates up to 10%. The aim of this study was to describe changes in obstruction etiology, comorbidities, clinical factors, and mortality among AC patients during a 25-year period. Methods: Using a database of 11,563 consecutive ERCP-procedures performed from 1990–2015 at Odense University Hospital, we identified all AC cases during that period. Clinical and epidemiological data were collected from the database and the Danish Patient Registry. Association with 30-day mortality was investigated using multiple logistic regression analysis with adjustment for confounding factors. Results: In total, 775 consecutive and individual cases of AC were included. Among cases, 42% (n = 326) were of malignant etiology, with an increasing incidence over time (regression coefficient [95% CI]: 0.03 [0.01–0.04] per year; p =.01). Mean Charlson Comorbidity Index was 1.4, with an increase over time (regression coefficient [95% CI]: 0.04 [0.03–0.05] per year; p <.01). Malignant obstruction etiology was associated with 30-day mortality (OR [95% CI]: 1.11 [1.04–1.18]; p <.01). Overall 30-day mortality was 12% (n = 91). After adjustment for confounding factors, no significant changes in 30-day mortality were observed over time (OR [95% CI]: 1 [1–1.00]; p =.91 per year). Conclusion: Significant increases in the incidence of malignant obstruction etiology and severity of comorbidities among AC patients were observed during the study period. Despite those findings, 30-day mortality remained unchanged, potentially reflecting a general improvement in the management of AC. [ABSTRACT FROM AUTHOR]

IgG4-related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to mass-forming lesions in different organs. When IgG4-related disease affects the bile ducts, it is called IgG4-related sclerosing cholangitis. A 74-year-old male complained of dysphagia and abdominal pain. Endoscopic retrograde cholangiography and magnetic resonance cholangiography revealed bile duct changes suspicious of a bile duct carcinoma or cholangitis. Liver biopsy showed storiform fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, and a portal-based inflammatory nodule with expansion of a portal tract. Hot spots revealed 339 IgG4-positive cells per high power field (HPF) and an IgG4/IgG ratio of 72%. Eight months earlier, an inguinal lymph node had been removed, showing expanded interfollicular zones and increased plasma cells. Hot spots revealed 593 IgG4-positive cells and an IgG4/IgG ratio of 92%. The serum IgG4 of the patient was elevated nearly 10 times upper limit of normal. The diagnosis of IgG4-related sclerosing cholangitis associated with IgG4-related lymphadenopathy was made. There was good response to treatment with prednisolone and azathioprine. The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult. Liver biopsy only rarely contributes to this setting, but we describe and report in detail a case where liver biopsy showed a portal-based inflammatory nodule with the characteristic features of this disease. [ABSTRACT FROM AUTHOR]

Objective: Upper gastrointestinal bleeding (UGIB) is a frequent medical emergency and several scoring systems are developed to help risk-stratify patients. We aimed to investigate if elevated arterial lactate (AL) was associated with 30-day mortality, need for hospital-based intervention, or rebleeding. Furthermore, we compared the performance of AL with existing scoring systems and examined if incorporation of AL could improve their predictive ability. Materials and methods: Retrospective cohort study of 331 consecutive patients admitted with UGIB during a one-year period. Multivariate analyses were performed to evaluate the association between AL and outcomes. Receiver operating characteristic curves were used to compare AL with existing scoring systems and to test if incorporation of AL could significantly increase their performance. Results: AL was significantly associated with mortality (p = .001), need for hospital-based intervention (p = .005), and rebleeding (p = .031). In predicting mortality and rebleeding, AL performed equally to existing scoring systems, however, inferior to all, in predicting need for intervention. Two of the scoring systems were marginally improved in predicting mortality if AL was included. Conclusions: AL is associated with adverse outcomes in patients with UGIB, but has only similar or inferior ability to predict relevant clinical outcomes compared to existing scoring systems. Although AL could enhance performance of two scorings systems in predicting mortality, it does not have an apparent clinical significance. Thus, our data does not support routine measurement of AL in patients with UGIB. [ABSTRACT FROM AUTHOR]

Background. A number of studies have reported a possible association between use of selective serotonin reuptake inhibitors (SSRIs) and serious upper gastrointestinal bleeding (UGB). We conducted this case--control study to assess if Helicobacter pylori ( H. pylori) potentiates the risk of serious UGB in SSRI users. Material and methods. A population-based case--control study was conducted in the county of Funen, Denmark. Cases were 53 SSRI users with serious UGB whose H. pylori status on their bleeding date could be established. Controls ( n == 723) were selected among subjects who participated in a population H. pylori screening study, and who were users of SSRIs. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by unconditional logistic regression. Results. H. pylori infection increased the risk of serious UGB in patients using SSRI with an adjusted odds ratio (OR) of 2.73 (95% confidence interval (CI), 1.17--6.36). The adjusted OR for serious UGB among users of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) were 3.91 (95% CI, 2.03--7.52) and 3.00 (95% CI, 0.94--9.54), respectively. Conclusion. H. pylori infection increases the risk of SSRI-related serious UGB. [ABSTRACT FROM AUTHOR]

The establishment of a reliable radioimmunoassay for secretin in plasma enabled studies on the physiology of secretin. It was shown that secretin, i.e. the heptacosapeptide isolated by Jorpes and Mutt, is in fact responsible for the phenomena observed by Starling and Bayliss in 1902 when studying the stimulation of pancreatic bicarbonate secretion in response to duodenal acidification. Secretin is released in amounts considerably lower than anticipated, but these amounts are nevertheless sufficient to drive pancreatic and biliary secretion of bicarbonate. Whereas secretin in the fasting state is the most important stimulus to pancreatic secretion of water and bicarbonate, other hormones and nervous factors are essential for the majority of pancreatic postprandial secretion. [ABSTRACT FROM AUTHOR]

Rebleeding is a frequent complication of peptic ulcer bleeding (PUB) and is associated with increased mortality. Blood pressure and heart rate are two easy non-invasive measurements to evaluate the hemodynamics and therefore a standard observation during hospitalization. We aimed to investigate the dynamics of systolic blood pressure and heart rate up to time of peptic ulcer rebleeding. Retrospective matched cohort study. Hemodynamics in patients with peptic ulcer rebleeding was compared to hemodynamics in a matched control group consisting of patients with PUB without rebleeding. Blood pressure and heart rate in the six hours up to diagnosis of rebleeding was compared with baseline in the case cohort as well as with the matched control group. Thirty-eight patients with peptic ulcer rebleeding and 66 controls were included. Mean age was 75 years, 62% were males and 30-day mortality was 23%. Baseline systolic blood pressure in cases was 114 mmHg. Compared to baseline, we found significant decrease in systolic blood pressure two hours before rebleeding (4 mmHg; p = 0.041) and one hour before rebleeding (14 mmHg; p = 0.0002). Mean systolic blood pressure 30 min before rebleeding was 89 mmHg. No significant change was found in heart rate (p = 0.99). In the control group no change was found in systolic blood pressure or heart rate. In patients with peptic ulcer rebleeding, hypotension develops 1–2 h before other symptoms of rebleeding. Thus, close monitoring of blood pressure is needed in order to ensure early identification of rebleeding in high-risk patients. [ABSTRACT FROM AUTHOR]

Rebleeding is a frequent complication of peptic ulcer bleeding (PUB). The associated prognosis remains rather unclear because previous studies generally also included non-ulcer lesions. We aimed to identify predictors for rebleeding; clarify the prognostic consequence of rebleeding; and develop a score for predicting rebleeding. Nationwide cohort study of consecutive patients presenting to hospital with PUB in Denmark from 2006–2014. Logistic regression analyses were used to identify predictors for rebleeding, evaluate the association between rebleeding and 30-day mortality, and develop a score to predict rebleeding. Patients with persistent bleeding were excluded. Among 19,258 patients (mean age 74 years, mean ASA-score 2.4), 10.8% rebled, and 10.2% died. Strongest predictors for rebleeding were endoscopic high-risk stigmata of bleeding (Odds Ratio (OR): 2.12 [95% Confidence Interval (CI): 1.91–2.36]), bleeding from duodenal ulcers (OR: 1.87 [95% CI: 1.69–2.08]), and presentation with hemodynamic instability (OR: 1.55 [95% CI: 1.38–1.73]). Among patients with all three factors (7.9% of total), 24% rebled, 50% with rebleeding failed endoscopic therapy, and 23% died. Rebleeding was associated with increased mortality (OR: 2.04 [95% CI: 1.78–2.32]). We were unable to develop an accurate score to predict rebleeding. Rebleeding occurs in ∼10% of patients with PUB and is overall associated with a two-fold increase in 30-day mortality. Patients with hemodynamic instability, duodenal ulcers, and high-risk endoscopic stigmata are at highest risk of rebleeding. When rebleeding occurs in such patients, consultation with surgery and/or interventional radiology should be obtained prior to repeat endoscopy. [ABSTRACT FROM AUTHOR]

Hypozincemia is a well-known phenomenon in patients with infection caused by the activation of the acute phase response (APR). Zn status is still based upon plasma Zn levels in venous blood samples. Recent trials have questioned the validity of this measurement in infected patients. The aim of this study was to assess plasma levels of Zn, albumin and Zinc-binding capacity in patients during and following infection. Furthermore, to assess if an assay for albumin-corrected Zn could potentially replace or add knowledge to existing tools for assessment of Zinc-status. A prospective clinical observational trial was conducted. Associations between P-Zn, -Albumin, -Albumin-corrected Zn and Zn binding capacity were analyzed. Analyzes were based upon two venous blood samples drawn during and following infection, respectively. Twenty-three patients admitted to a medical ward showing paraclinical signs of infection were included in the study. Significantly lower levels of Zn and albumin were found during infection compared with the levels post-infection. These findings corresponded to the changes found in Zn binding capacity. About 52% of patients were deemed Zn deficient by plasma Zn levels during infection but after applying the correction for P-Albumin, all patients were found to be within normal ranges of Zn levels. Furthermore, we found no statistically significant difference between albumin-corrected Zn during infection and P-Zn post-infection. The new assay was found to accurately estimate the 'true' Zn levels in infected patients. Based on our findings, we propose albumin-corrected P-Zn as a promising new tool, which may result in more precise diagnostics and treatment. [ABSTRACT FROM AUTHOR]

We have established and describe two measurement procedures to diagnose possible zinc (Zn) deficiency; albumin-corrected Zn concentration and available free Zn-binding capacity. Reference intervals for both biomarkers were established in healthy adults from the Danish population. The clinical usefulness of the measurement procedures was investigated in patients with cirrhosis and in patients given parenteral nutrition due to short bowel syndrome. The results of both methods indicate that there is a risk of overdiagnosing Zn deficiency based on low plasma Zn concentrations. Needless Zn supplementation may thus be avoided by using the albumin-corrected Zn concentration or available free Zn-binding capacity. [ABSTRACT FROM AUTHOR]

First‐degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk‐assessment and management of high‐risk individuals. Using a Danish cohort of 27 FPC families, we performed whole‐genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to familial aggregation of PDAC. Statistical analysis was performed using the gnomAD database as external controls. Through analysis of heterozygous premature truncating variants (PTV), we identified cancer‐related genes and cancer‐driver genes harboring multiple germline mutations. Association analysis detected 20 significant genes with false discovery rate, q < 0.05 including: PALD1, LRP1B, COL4A2, CYLC2, ZFYVE9, BRD3, AHDC1, etc. Functional annotation showed that the significant genes were enriched by gene clusters encoding for extracellular matrix and associated proteins. PTV genes were over‐represented by functions related to transport of small molecules, innate immune system, ion channel transport, and stimuli‐sensing channels. In conclusion, FDRs of FPC patients carry rare germline variants related to cancer pathogenesis that may contribute to increased susceptibility to PDAC. The identified variants may potentially be useful for risk prediction of high‐risk individuals in predisposed families. [ABSTRACT FROM AUTHOR]

Objective. Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-β-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol - by activation of the mineralocorticoid receptor - may contribute to the abnormal sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. Methods. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily. Results. Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone - placebo) increased 55.1 (−26.4-168.7) mmol/day (median and range). No statistically significant differences (dexamethasone - placebo) were found in changes in body weight (0.00 (−0.45-2.20) kg/day), diuresis (0.56 (−0.35-1.43) L/day) or mean arterial pressure (8.33 (−16.0-41.3) mmHg) (median and range) in reference to the preceding 24 h basal period. Conclusion. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The prevalence of gastroesophageal reflux symptoms (GERS) in the population is high; however, data on long-term follow-up and incidence of GERS in the population are sparse. This study describes the long-term natural history of GERS, the related health-care use, and quality of life in a population followed up for 5 years.METHODS:A total of 10,000 randomly selected inhabitants, 40–65 years old, received, as a part of a controlled trial of Helicobacter pylori screening and treatment (control group), a mailed questionnaire regarding demographic data, gastrointestinal symptoms (the Gastrointestinal Symptom Rating Scale (GSRS)), and quality of life (the Short-Form 36-Item Health Survey (SF-36)) at inclusion and after 5 years. GERS was defined as a mean score ≥2 in the reflux dimension in the GSRS. Information on use of health-care resources was drawn from the questionnaires and registers.RESULTS:In all, 6,781 individuals answered the first questionnaire and 5-year symptom data were complete for 5,578 (82.3%) of them. The mean age at inclusion was 52.4 years, 48% were men. At inclusion, 22% reported GERS. During follow-up, symptoms resolved in 43%, of whom 10% received acid inhibitory treatment at 5-year follow-up. The incidence of GERS was 2.2% per year. Health-care use during follow-up was significantly higher in individuals with GERS at baseline than in individuals without GERS. Quality of life at 5-year follow-up was lower in individuals with GERS at inclusion than in individuals without GERS at inclusion.CONCLUSIONS:GERS are prevalent, long lasting, and associated with an impaired quality of life and substantial health-care use. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Although symptoms of reflux are common, our knowledge of the epidemiology and natural history of gastroesophageal reflux disease is sparse. The risk of esophageal adenocarcinoma is increased among patients with acid reflux, but the contribution of Barrett's lesions is unknown. METHODS: With the aim to estimate the incidence of diagnosed endoscopic esophagitis lesions and the risk of esophageal adenocarcinoma among patients with previously diagnosed esophagitis, we extracted data on endoscopies, esophagitis diagnoses, and gastroesophageal cancer diagnoses from five population-based databases covering the period from 1974 to 2002, and covering all citizens in Funen County (population 470,000). RESULTS: In 2002, the incidence of esophagitis lesions was 2.4 per 1,000 person-years (95% confidence interval 2.3–2.6), 18.3 per 1,000 persons (17.9–18.7) had previously diagnosed esophagitis. Incidence increased by calendar year and age, was higher among males than among females, and was closely related to rate of endoscopy. Among 11,129 patients with previously diagnosed esophagitis, 15 had esophageal adenocarcinoma during 58,322 person-years of follow-up (26 per 100,000 person-years). The expected number was 2.79 and the standardized incidence ratio was 5.38 (3.01–8.87). Ten of the 15 patients with esophageal adenocarcinoma had previously diagnosed Barrett's esophagus. CONCLUSION: The risk of esophageal adenocarcinoma is increased fivefold in patients with previously diagnosed esophagitis, but most of the adenocarcinomas occurred among patients with Barrett's esophagus. [ABSTRACT FROM AUTHOR]

Familial Pancreatic Cancer (FPC) is responsible for up to 10% of all cases of pancreatic ductal adenocarcinoma (PDAC). Individuals predisposed for FPC have an estimated lifetime risk of 16–39% of developing PDAC. While heritability of PDAC has been estimated to be 36% in a Nordic twin study, no heritability estimate specific on FPC has been reported. A national cohort of Danish families with predisposition for FPC is currently included in a screening program for PDAC at Odense University Hospital. Family members included in the screening program were interviewed for pedigree data including: cases of PDAC among first-degree relatives (FDRs) and number of affected/unaffected siblings. Heritability for FPC in the predisposed families was assessed by doubling the estimated intra-class correlation coefficient (ICC) from a random intercept logistic model fitted to data on FDRs. Among families with predisposition for FPC, 83 cases of PDAC were identified. The median age at diagnosis of PDAC was 66 years, and median time from diagnosis to death was 7.6 months. A total of 359 individuals were found as unaffected FDRs of the 83 PDAC cases. The retrieved FDRs included a total of 247 individuals in sibship and 317 individuals in parent-offspring relatedness. We estimated an ICC of 0.25, corresponding to a narrow sense additive heritability estimate of 0.51 in the FPC family cohort. We have established a nation-wide cohort of FPC families to facilitate clinical and genetic studies on FPC. The estimated heritability of 51% prominently underlines a strong genetic background of FPC. [ABSTRACT FROM AUTHOR]

The prevalence of gastroesophageal reflux symptoms (GERS) and dyspepsia is high. Overlapping of GERS and dyspepsia has been described to affect quality of life. However, studies are few. This long-term population-based study evaluates how GERS, dyspepsia, and overlapping symptoms, affect quality of life, and the use of health care and medication. This study presents data for the control group of the randomised population study, HEP-FYN. At baseline 10,000 individuals, aged 40–65 years, received questionnaires at baseline and after 1, 5 and 13 years. The questionnaire included questions regarding demographics, use of health care resources, gastrointestinal symptoms (the Gastrointestinal Symptom Rating Scale (GSRS)), and the Short-Form 36-Item Health Survey (SF-36) to assess quality of life. Complete data was available for 4.403 individuals at 13-year follow-up. Of these 13.6% reported GERS only, 11.6% dyspepsia only, and 27.1% overlapping symptoms during follow-up. Individuals reporting overlapping symptoms had compared to individuals reporting GERS only or dyspepsia only more visits at general practitioner (last year:16.7% vs. 8.5% vs. 12.3%), more sick leave days (last month: 4.3% vs. 2.9% vs 0.7%), used more ulcer drugs (last month: 30.5% vs 16.4% vs 9.4%). In addition, individuals with overlapping symptoms reported a lower quality of life in all eight dimensions of SF-36 compared to individuals with GERS alone or dyspepsia alone. Overlapping symptoms was associated with lower quality of life scores and substantial use of health-care resources. Having solely GERS affected quality of life and health care use least. [ABSTRACT FROM AUTHOR]

Acute cholangitis (AC) is a condition of bacterial infection in the biliary tract with a high mortality rate of around 10%. Direct association between presence of bacteremia and 30-day mortality among AC patients is sparsely investigated and remains unclear. Our aim was to investigate association between bacteremia and 30-day mortality among patients with AC included over a period of 25 years. All AC patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) at Odense University Hospital, between 1 January 1990 and 31 October 2015, were identified using a prospective ERCP database. Blood culture results from the patients along with antimicrobial resistance patterns were collected from a bacteremia research database. During the study period, 775 consecutive AC patients underwent ERCP and blood cultures were collected from 528 patients. Among these patients 48% (n = 260) had bacteremia. Overall, 30-day mortality in patients with blood cultures performed was 13% (n = 69). In patients with bacteremia, 30-day mortality was 19% (n = 49), compared to 7% (n = 20) in patients without bacteremia (p <.01). Presence of bacteremia was associated with increased 30-day mortality (OR [95% CI]: 3.43 [1.92–6.13]; p <.01) following adjustment for confounding factors. Among the species, bacteremia with Enterobacter cloacae was significantly associated with increased 30-day mortality (OR [95% CI]: 2.97 [1.16–7.62]; p =.02). Our results indicate that presence of bacteremia was associated with a nearly fourfold increase in 30-day mortality among AC patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Helicobacter pylori eradication improves dyspeptic symptoms in 8%‐10%, prevents peptic ulcer and may reduce the risk of gastric cancer. Availability of a high quality diagnostic test and an effective treatment makes population screening and eradication of Helicobacter pylori an attractive option. Aim: To evaluate the cost effectiveness of Helicobacter pylori population screening and eradication. Methods: Cost effectiveness analysis and cost utility analysis alongside randomised controlled trial with 13 years follow‐up. The evaluation has a societal perspective. A random general population sample of 20 011 individuals aged 40‐65 were randomised and invited in 1998‐1999; 12 530 were enrolled and, of these, 8658 have been successfully followed up at 1, 5, and 13 years after intervention. Questionnaires included the quality of life instrument SF‐36. From SF‐36 responses an SF‐6D score was derived and used for calculation of quality‐adjusted life years. Register data on costs, use of health care resources and medication were obtained for all randomised individuals. The intervention was an invitation to Helicobacter pylori screening by in‐office blood test; positive tests were validated by 13C‐urea breath test. Those who tested positive were offered eradication therapy. Main outcome measures were Incremental cost per quality‐adjusted life year and life‐years gained. Results: Helicobacter pylori population screening and eradication with 13 years follow‐up was not effective in regards to quality of life and the cost per screened person was higher than not screening (mean difference 11 269 DKK [95% CI: 3175‐19 362]). The probability of being cost‐effective was 80% at a threshold of 400 000 DKK (approximately 53,800 Euros) of willingness‐to‐pay per life‐year gained. Conclusions: Helicobacter pylori population screening and eradication with 13 years follow‐up was not effective in regards to quality of life and the cost of screening was higher than not screening. [ABSTRACT FROM AUTHOR]

Sodium retention in cirrhosis is associated with changes in the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), and the glomerular filtration rate (GFR). We hypothesized that in cirrhosis the acute reactions of RAAS and SNS to volume expansion are qualitatively intact, but occurring from elevated baseline levels. Acute cardiovascular, neurohumoral and renal responses to central blood volume changes were studied in cirrhotic patients and healthy controls. In patients, baseline plasma renin concentration (PRC) was elevated 5-fold compared to controls (p < .001); it increased during standing (+144%,p < .001) and remained elevated during subsequent sitting (+118%,p < .001). At baseline, plasma angiotensin II (pANGII) was not elevated significantly (14 ± 2 vs. 9 ± 2 pg/mL) in contrast to plasma aldosterone (pAldo, +160%,p < .001). During orthostatic RAAS activation, the rise in pAngII per unit increase in PRC was 0.04 pg AngII/mIU and 0.48 pg AngII/mIU in patients and controls, respectively (p < .001); similarly, the change in pAldo per unit change in pANGII was 3.6 in patients and 14.5 pg/pg in controls (p < .001). Plasma noradrenaline was elevated in the patients, but the dynamic changes were virtually identical to those of controls. During standing, abrupt decreases in renal blood flow (−63%,p < .001) and GFR (−42%p < .04) occurred only in patients. In conclusion, in stable cirrhosis, static and dynamic dysregulation exists within the RAAS; in the supine position pAngII levels are inappropriately low, and the AngII-mediated regulation of aldosterone secretion is severely impeded. In cirrhotic patients, profound reductions in renal blood flow and GFR occur during standing. [ABSTRACT FROM PUBLISHER]

Objective. To investigate whether patients on long-term antisecretory medication need to continue treatment to control symptoms. Methods. A double-blinded randomised placebo-controlled trial in general practices in Denmark. Patients aged 18–90 who were treated with antisecretory drugs on a long-term basis were randomized to esomeprazole 40 mg or identical placebo. Outcome measures were time to discontinuation with trial medication due to failed symptom control analysed as survival data. The proportion of patients stopping trial medication during the one-year follow-up was estimated. Results. A total of 171 patients were included with a median prior duration of antisecretory treatment of four years (range: 0.5 to 14.6 years). 86 patients received esomeprazole 40 mg and 85 patients received placebo. At 12 months, statistically significantly more patients in the placebo group had discontinued (73% (62/85)) compared with the esomeprazole group (21% (18/86); p < 0.001). Conclusions. Long-term users of antisecretory drugs showed a preference for the active drug compared to placebo. However, 27% of patients continued on placebo throughout the study and did not need to reinstitute usual treatment. One in five patients treated with esomeprazole discontinued trial medication due to unsatisfactory symptom control. Discontinuation of antisecretory treatment should be considered in long-term users of antisecretory drugs. This trial is registered with Trial registration ClinicalTrials.gov ID: NCT00120315. [ABSTRACT FROM AUTHOR]

Objective. In 5-10% of patients with peptic ulcer bleeding (PUB) it is impossible to achieve endoscopic hemostasis because of severe bleeding. These patients have traditionally been treated surgically. Transcatheter arterial embolization (TAE) may, however, be associated with a better outcome because of the less-invasive nature of the procedure. The aim of the present study was to identify the treatment of choice in endoscopy-refractory PUB. Materials and methods. A retrospective study. Consecutive patients treated with surgery or TAE for endoscopy-refractory PUB during a period of 16 years at a university hospital were included. Primary hemostasis, rebleeding rate, mortality, and complications were assessed. Mortality was compared between groups after adjustment for age, comorbidity, and anemia using logistic regression analyses. Comorbidity was quantified using the Charlson comorbidity index (CCI). Results. One hundred and eighteen patients were included. Patients treated with TAE had a higher CCI (mean: 2.33 vs 1.42; p = .003), and more severe anemia (mean: 6.8 vs 7.9 g/dl; p = .007) compared with patients treated with surgery. Surgery was associated with a higher rate of primary hemostasis (100% vs 91%; p = .007), lower rate of rebleeding (15% vs 40%; p = .004) but also higher rate of complications (60% vs 38%; p = .02) than TAE. Surgery was associated with an increased mortality (Odds ratio: 3.05; p = .033) when adjusting for confounding factors and excluding patients ( n = 3) who were not candidates for both interventions. Conclusions. We propose use of TAE as first-line therapy in these patients as it may be associated with lower mortality and lower rate of complications compared with surgery. [ABSTRACT FROM AUTHOR]

Objective. Previous studies have concluded that peptic ulcer bleeding (PUB) is associated with increased long-term mortality. The underlying mechanism of this excess mortality is poorly understood. The aim of the present study was to examine if PUB patients have an increased long-term mortality compared to a matched control group when adjusting for comorbidity and socioeconomic status. Additionally, we identified predictive factors for mortality and examined causes of death. Material and methods. We performed an observational study, comparing consecutive patients admitted with PUB with a matched control cohort from the source population. Predictors of mortality were identified using proportional hazards models. Causes of death were retrieved from death certificates. Long-term mortality was analyzed with adjustment for Charlson comorbidity index (CCI) and average income in residence municipality using proportional hazards models. Results. We included 455 PUB cases and 2224 control subjects. Median follow up was 9.7 years, and median survival for the PUB and control cohorts was 7 and 12 years, respectively ( p < 0.001). PUB patients had a higher level of comorbidity (mean CCI: 0.92 vs. 0.49; p < 0.0001). After adjustments, PUB patients had an excess mortality lasting at least 10 years after presentation. Age, comorbidity, male sex, anemia, and smoking were predictors for long-term mortality. The distribution of causes of death was similar in the two cohorts. Conclusion. PUB patients have an increased long-term mortality that is explained by nonspecific comorbidity. [ABSTRACT FROM AUTHOR]

Objective. One of the major challenges in peptic ulcer bleeding (PUB) is rebleeding which is associated with up to a fivefold increase in mortality. We examined if supplementary transcatheter arterial embolization (STAE) performed after achieved endoscopic hemostasis improves outcome in patients with high-risk ulcers. Material and methods. The study was designed as a non-blinded, parallel group, randomized-controlled trial and performed in a university hospital setting. Patients admitted with PUB from Forrest Ia - IIb ulcers controlled by endoscopic therapy were randomized (1:1 ratio) to STAE of the bleeding artery within 24 h or continued standard treatment. Randomization was stratified according to stigmata of hemorrhage. Patients were followed for 30 days. Primary outcome was a composite endpoint where patients were classified into five groups based on transfusion requirement, development of rebleeding, need of hemostatic intervention and mortality. Secondary outcomes were rebleeding, number of blood transfusions received, duration of admission and mortality. Results. Totally 105 patients were included. Of the 49 patients allocated to STAE 31 underwent successful STAE. There was no difference in composite endpoint. Two versus eight patients re-bled in the STAE and control group, respectively (Intention-to-treat analysis; p = .10). After adjustment for possible imbalances a strong trend was noted between STAE and rate of rebleeding ( p = .079). Conclusions. STAE is potentially useful for preventing rebleeding in high-risk PUB. STAE can safely be performed in selected cases with high risk of rebleeding. Further studies are needed in order to confirm these findings; ClincialTrials.gov number, NCT01125852. [ABSTRACT FROM AUTHOR]

Background/aims: Publications on etiology of chronic pancreatitis (CP) are infrequent. Etiologies today encompass genetic disorders. We wanted to describe etiologies of today and identify patients with genetic disorders like hereditary pancreatitis (HP), mutations in Serine Protease Inhibitor Kazal type1 (SPINK1), and the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) among patients formerly considered to have idiopathic CP.Methods: Data on patients diagnosed with first-time CP < 30 years of age in Denmark identified in the Danish National Registry of Patients were retrieved. Patients previously considered to have idiopathic pancreatitis were offered genetic counseling and evaluation for HP, SPINK1, and CFTR mutations.Results: In the period 1980-2004, 580 patients < 30 years of age presented with CP, the standardized prevalence ratio of CP increased from 11.7 per 100,000 person years in 1980-1984 to 17.0 per 100,000 in 2000-2004 (p < 0.001). The odds ratio (OR) having gallstone-related CP increased in the latter time period, especially in women, that of alcohol-induced CP decreased over time. OR having idiopathic CP increased in the latter period; 50% of patients with idiopathic pancreatitis accepted genetic reevaluation; 28 patients had a genetic mutation that totally or partly could explain their pancreatitis, nine of these had two, and 11 patients had HP.Conclusion: The prevalence of CP, especially in women, increased over time. Genetic causes that partly or totally could explain the CP were found in 54.90% (95% CI (40.45-68.62)) of those with idiopathic CP, as a minimum estimation 1.9% (95% CI (1.00-3.47)) of the total cohort had HP. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the indium-111 (111In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. Methods. Fourteen patients and 15 healthy subjects underwent an 111In-transferrin study consisting of abdominal scintigraphy, whole-body counting measurement and determination of plasma activity of 111In during the course of 5 days. Two of the patients went through a subsequent chromium-51-trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. Results. The patients had a mean±SEM whole-body loss of 111In of 10.9±2.9% for 96 h, while the healthy controls lost 1.8±1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0±1.0 h in patients and 12.1±1.5 h in controls (p=0.0007). Scintigraphically, patients had obvious abdominal foci of activity, while the control subjects showed diffuse activity. Anatomic localization of the leaking spot seemed more uncertain. By comparison with the 51Cr trichloride test, the loss of radio-labelled protein appeared to be in the same order of magnitude. Conclusions. Quantification of gastrointestinal protein loss can be done without collecting faeces. Normal subjects have a loss of a few per cent, making the 111In-transferrin method comparable with the former standard using 51CrCl3-trichloride. Plasma measurements of 111In are not predictive of the magnitude of the loss. Scintigraphic localization of the site of the loss needs to be optimized, for instance by serial imaging or image fusion with an anatomical modality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Helicobacter pylori ( H. pylori) screening and eradication may reduce the incidence of gastric cancer, AND AIMS: peptic ulcer, and ulcer complications, and it may reduce symptoms in a small proportion of individuals with functional dyspepsia. This study aimed to assess the effect of community H. pylori screening and treatment on the prevalence of dyspepsia, and as secondary outcomes, the effect on dyspepsia-related health-care consumption and quality of life over 5 yr. METHODS: In 1998–1999, individuals aged 40–65 yr were randomized to H. pylori screening and treatment or to the control group. Five years later, the participants were sent a questionnaire to assess the prevalence of dyspepsia and quality of life. In addition, we obtained information from registers on the use of endoscopies and prescription medication. An economic evaluation was done alongside the randomized trial. RESULTS: Of 12,530 participants attending the study at baseline, 11,065 (88%) were traced and contacted at the 5-yr follow-up. The response rate was 94%. At baseline, 17.5% in the screened group were H. pylori-positive. The absolute reduction in dyspepsia during the first year was 4% in the screened group, whereas no change was observed in the unscreened group; this rate remained constant during the next 4 yr. Quality of life did not change. A small effect was found for dyspepsia-related consultations and sick leave days, but not on the prescription rate of ulcer drugs. A 33% lower ulcer incidence (107 ulcers vs 148 ulcers) was seen in the screened group compared to the unscreened group. CONCLUSION: A population H. pylori screening and treatment program in an H. pylori low-prevalence area had only a modest, but insignificant, effect on the rate of dyspepsia, and a modest, significant effect on the consultation rate and sick leave days for dyspepsia, but resulted in a decreased ulcer incidence. The intervention resulted in an increased cost due to H. pylori screening and treatment. [ABSTRACT FROM AUTHOR]

The article presents information on familial pancreatic cancer (FPC). FPC is inherited as an autosomal dominant disease with involvement of different genes and modifying genes. It is believed that tobacco smoking could be responsible for 14% of all pancreatic cancer cases. Cystic fibrosis gives a 32% higher risk of pancreatic cancer. Chronic pancreatitis is responsible for 5% of the pancreatic cancer cases.

OBJECTIVES: The optimal approach for management of patients with dyspepsia has not been determined. The aim of this study was to compare the efficacy of three strategies for management of dyspepsia: empirical antisecretory therapy, testing for Helicobacter pylori ( H. pylori), or a combination of the two. METHODS: Cluster-randomized trial in general practices. Initial treatment with proton pump inhibitor (PPI) was performed in 222 patients, H. pylori test-and-eradicate in 250 patients, and PPI followed by H. pylori-testing if symptoms improved in 250 patients. Symptoms, quality of life, patient satisfaction, and use of resources were recorded during a 1-yr follow-up. RESULTS: The prevalence of H. pylori infection was 24%. We found no difference among the three strategies ( p= 0.16) in terms of the proportion of days without dyspeptic symptoms. After 1 yr gastrointestinal symptom scores and quality-of-life scores had improved significantly and equally in the three groups ( p < 0.001), but no statistically significant differences were found among the groups. The mean use of endoscopies per patient after 1 yr was higher in the PPI group (0.36 [95% CI 0.30–0.43]) than in the test-and-eradicate group (0.28 [95% CI 0.23–0.34]) and the combination group (0.22 [95% CI 0.17–0.27]), p= 0.02. H. pylori-positive patients given eradication therapy had more days without dyspeptic symptoms ( p < 0.001), used less antisecretory therapy ( p < 0.01), and were more satisfied ( p < 0.001) than H. pylori-negative patients. CONCLUSION: The strategies based on H. pylori test enjoyed similar symptom resolution, but reduced endoscopic workload and lower 1-yr total costs compared with empirical antisecretory therapy. [ABSTRACT FROM AUTHOR]

In the present study, we tested the hypothesis that inhibition of renal phosphodiesterase type 5 (PDE5) in patients with liver cirrhosis and ascites increases sodium excretion. The effect of sildenafil citrate was studied in a randomized double-blind, placebo-controlled crossover study. Diuretics were withdrawn, and a fixed sodium diet (100 mmol/day) was given to the patients for 5 days before both study days: After a 60-min basal period, eight patients received either oral sildenafil (50 mg) or placebo. Glomerular filtration rate (GFR) and renal blood flow (RBF) were determined by 99mTc-diethylenetriamine-pentaacetate and 131I-hippuran clearances. In human nephrectomy specimens, PDE5 mRNA was expressed at similar levels in the cortex (n = 6) and inner medulla (n = 4). Histochemical staining showed PDE5 immunoreactivity in collecting ducts and vascular smooth muscle. At baseline, cirrhotic patients exhibited elevated plasma concentrations of ANP, renin, ANG II, and aldosterone that did not differ on the 2 study days. Basal sodium excretion was similar at the 2 study days (median 17 and 18 mmol, respectively), and patients were in positive sodium balance. Sildenafil increased heart rate, plasma renin activity, plasma ANG II, and aldosterone concentrations significantly after 60 min. Plasma cGMP concentration was increased after 120 and 180 min, and urinary sodium excretion and mean arterial blood pressure were decreased significantly at 120 and 180 min. Plasma ANP concentration, GFR, and RBF did not change after sildenafil. In patients with ascites and cirrhosis, inhibition of PDE5 did not promote natriuresis but led to increased plasma levels of the renin-angiotensin-aldosterone system. [ABSTRACT FROM AUTHOR]

: ObjectivesBased mainly on animal experiments, nitric oxide (NO) has been proposed to account for the peripheral arterial vasodilation and hyperdynamic circulation in liver cirrhosis. The aim of this study was to clarify whether a reduction of NO synthesis would ameliorate the circulatory and renal dysfunction in decompensated cirrhotic patients.: MethodsThe effects of NG-monomethyl-L-arginine-acetate (L-NMMA), an NO synthesis inhibitor, were studied. After a 60-min basal period, a total of 10 patients received increasing doses of L-NMMA, five patients (Low) received 12.5, 25, and 50 μg/kg/min, and five patients (High) received 25, 50, and 100 μg/kg/min as a constant infusion during 3 h, followed by a postinfusion period. Five patients (Placebo) received saline infusions only. Glomerular filtration rate and renal plasma flow were measured by clearance techniques with 99mTc-diethylenetriamine-pentaacetate and 131I-Hippuran.: ResultsL-NMMA infusion resulted in an increased blood pressure, decreased heart rate, and dose-dependent suppression of renin of up to 42.1 ± 7.1% (p < 0.01) and angiotensin II of up to 39.9 ± 9.6%, (p < 0.01) levels. Sodium and water excretion were not improved, most likely because of a reduction in renal blood flow of up to 29.1 ± 8.1% (p < 0.01).: ConclusionDespite a partial correction of the hyperdynamic circulation, inhibition of NO synthesis does not improve sodium and water excretion in decompensated cirrhosis, probably because of an accompanying decrease in renal plasma flow. Intrarenal NO synthesis may be important for maintaining intrarenal hemodynamics in decompensated cirrhotic patients. [Copyright &y& Elsevier]

SummaryBackground: Strategies based on screening for Helicobacter pylori to manage dyspeptic patients in primary care have been proposed, but the clinical consequences are unclear. We did a randomised trial to assess the efficacy and safety of a test-and-eradicate strategy compared with prompt endoscopy in the management of patients with dyspepsia.Methods: 500 patients presenting in primary care with dyspepsia (ƒ 2 weeks of epigastric pain, no alarm symptoms) were assigned H pylori testing plus eradication therapy or endoscopy. Symptoms, quality of life, patients' satisfaction, and use of resources were recorded during 1 year of follow-up.Findings: 250 patients were assigned test-and-eradicate, and 250 prompt endoscopy. The median age was 45 years and 28% were H pylori infected. 1 year follow-up was completed by 447 patients. We found no differences in symptoms between the two groups (median registered days without dyspeptic symptoms=0.63 [IQR 0.27-0.81] in the test-and-eradicate group vs 0.67 [0.36-0.86] in the prompt endoscopy group; mean difference 0.04 [95% CI 20.01-0.10], p=0.12). Nor did we find any difference in quality of life or numbers of sick-leave days, visits to general practitioners, or hospital admissions. In the test-and-eradicate group, 27 (12%) of the patients were dissatisfied with management, compared with eight (4%) in the endoscopy group (p=0.013). After 1 year, the use of endoscopies in the test-and-eradicate group was 0.40 times (95% CI 0.31-0.51) the use in the endoscopy group, the use of H pylori tests increased by a factor of 8.1 (5.7-13.1), the use of eradication treatments increased by a factor of 1.5 (0.9-2.7), and the use of proton-pump inhibitors was 0.89 (0.59-1.33) times the use in the endoscopy group. 43 (91% [80-98%]) of 47 peptic-ulcer patients would have been identified by endoscopy or treated by eradication therapy.Interpretation: A H pylori test-and-eradicate strategy is as efficient and safe as prompt endoscopy for m... [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Høgh et al and Vakil papers. To view these articles, visit https://doi.org/10.1111/apt.15193 and https://doi.org/10.1111/apt.15224. [ABSTRACT FROM AUTHOR]