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Background: Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (MTX-PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD)., Aim: To investigate the relationship between MTX-PGs and methotrexate drug survival, efficacy and toxicity METHODS: In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12 months. Primary outcome was subcutaneous methotrexate discontinuation or requirement for step-up therapy. Secondary outcomes included faecal calprotectin (FCP), Harvey Bradshaw Index (HBI), hepatotoxicity and gastrointestinal intolerance. Erythrocyte MTX-PGs were analysed at weeks 8, 12, 24 and 52 or upon treatment discontinuation., Results: We included 80 patients with CD (mean age 55 ± 13y, 35% male) with a median FCP of 268 μg/g (IQR 73-480). After the 12-month visit, 21 patients (26%) were still on subcutaneous methotrexate monotherapy. Twenty-one patients stopped because of disease activity, 29 because of toxicity, and four for both reasons. Five patients ended study participation or stopped methotrexate for another reason. A higher MTX-PG 3 concentration was associated with a higher rate of methotrexate drug survival (HR 0.86, 95% CI 0.75-0.99), lower FCP (β -3.7, SE 1.3, p < 0.01) and with biochemical response (FCP ≤250 if baseline >250 μg/g; OR 1.1, 95% CI 1.0-1.3). Higher MTX-PGs were associated with less gastrointestinal intolerance. There was no robust association between MTX-PGs and HBI or hepatotoxicity., Conclusions: Higher MTX-PG 3 concentrations are related to better methotrexate drug survival and decreased FCP levels. Therefore, MTX-PG 3 could be used for TDM if a target concentration can be established., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: While some articles describe outcome of pregnancy in autoimmune hepatitis (AIH), there are less data evaluating influence of AIH control on maternal and perinatal outcomes. This study analysed outcomes of pregnancy and related possible risk factors in AIH., Method: A retrospective multicentre cohort study on pregnancy in AIH was performed in 11 hospitals in the Netherlands. Maternal and neonatal outcomes were collected from records and completed by interview. Risk factors-including incomplete response, relapse and cirrhosis-for adverse outcomes were identified using logistic regression analysis., Results: Ninety-seven pregnancies in 50 women resulted in 70 deliveries (72%) with a live birth rate of 98.5%. AIH relapse occurred in 6% during pregnancy, and in 27% of post-partum episodes. Absence of complete biochemical response at conception was identified as risk factor for the occurrence of gestational and post-partum relapses. Relapse of AIH in the year before conception was a risk factor for the occurrence of both gestational relapses and post-partum relapses. No complete biochemical response increased the risk for hypertensive disorders during pregnancy and intrahepatic cholestasis of pregnancy (ICP). Cirrhosis was found to be a risk factor for miscarriages, but not for other outcomes., Conclusion: Pregnancy in AIH is related to an increased incidence of maternal and fetal/neonatal complications; in most cases, outcome is good. Incomplete biochemical response at conception or relapse in the year before conception are risk factors for gestational and post-partum relapses, for hypertensive disorders and for ICP. Cirrhosis was a risk factor for miscarriages., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Increasing burn-out rates among gastroenterologists make it necessary to find ways to prevent burn-out and to stimulate their ability and willingness to continue working (i.e., their employability). Understanding their antecedents might help organizations to prevent burn-out and to enhance employability among this occupational group., Objective: The purpose of this study is to provide insight in the relationship between job characteristics and job crafting behavior on the one hand and job outcomes (burn-out symptoms and employability) on the other hand., Methods: Data from two surveys in 2020 and 2021 were collected in a longitudinal study among 238 Dutch gastroenterologists. The data were analyzed with multiple linear regression analyses and paired-samples t-tests., Results: Job characteristics, specifically job aspects that require sustained physical and/or psychological effort or skills (i.e., job demands), are important predictors of burn-out symptoms among gastroenterologists. Specifically, high quantitative and emotional workload are significantly related to more burn-out symptoms. No strong relationship was found between job crafting and burn-out symptoms. Furthermore, job aspects that reduce the negative impact of these demanding aspects and that help to achieve work goals (i.e., job resources), and job demands to some extent, significantly predict employability. In particular, high job autonomy is related to higher employability, and high quantitative workload is associated with lower employability. Job crafting does not significantly affect employability. Furthermore, levels of burn-out symptoms and employability differed only little across time., Conclusion: In gastroenterologists, a high quantitative workload and emotional workload are associated with a higher burn-out risk, while low job autonomy and high quantitative workload are associated with more negative perceptions of employability. To prevent burn-out and to create positive perceptions of employability, it is important to take these aspects into account., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: The etiology of diverticulosis is still poorly understood. However, in patients with diverticulitis, markers of mucosal inflammation and microbiota alterations have been found. The aim of this study was to evaluate potential differences of the gut microbiota composition and mucosal immunity between patients with asymptomatic diverticulosis and controls., Methods: We performed a prospective study on patients who underwent routine colonoscopy for causes not related to diverticular disease or inflammatory bowel disease. Participants were grouped based on the presence or absence of diverticula. Mucosal biopsies were obtained from the sigmoid and transverse colon. Microbiota composition was analyzed with IS-pro, a 16S-23S based bacterial profiling technique. To predict if patients belonged to the asymptomatic diverticulosis or control group a partial least squares discriminant analysis (PLS-DA) regression model was used. Inflammation was assessed by neutrophil and lymphocyte counts within the taken biopsies., Results: Forty-three patients were enrolled. Intestinal microbiota profiles were highly similar within individuals for all phyla. Between individuals, microbiota profiles differed substantially but regardless of the presence (n = 19) of absence (n = 24) of diverticula. Microbiota diversity in both sigmoid and transverse colon was similar in all participants. We were not able to differentiate between diverticulosis patients and controls with a PLS-DA model. Mucosal lymphocyte counts were comparable among both groups; no neutrophils were detected in any of the studied biopsies., Conclusions: Microbiota composition and inflammatory markers were comparable among asymptomatic diverticulosis patients and controls. This suggests that the gut microbiota and mucosal inflammation do not play a major role in the pathogenesis of diverticula formation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AEB reports personal fees of inBiome B.V. (employee/stock holder). Anat Eck was supported by The Netherlands Organisation for Health Research and Development (ZonMw), grant number 95103009. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Research in professional soccer focusing on the relevance of external and internal load indicators for injury prevention is scarce. This study examined the relationship between load indicators and overuse injuries., Design: Prospective cohort study., Methods: Data were collected from 35 professional male soccer players over two seasons. Following load indicators were examined: total distance covered (TD), distance covered at high speed (THSR; >20kmh -1 ), number of accelerations (ACC eff ; >1ms -2 ), number of decelerations (DEC eff ; <-1ms -2 ), and rating of perceived exertion (RPE) multiplied by duration. Cumulative 1-, 2-, 3-, 4-weekly loads and acute:chronic workload ratios (ACWR) were calculated and split into low, medium and high groups. Only overuse injuries were included in the analysis to focus on their specific relationship with the load indicators. Generalized estimating equations were applied to analyse the relationship between load indicators and overuse injuries in the subsequent week., Results: In total, 64 overuse injuries were registered. For cumulative loads, results indicated an increased injury risk for higher 2- to 4-weekly loads as indicated by TD, DEC eff , and RPE multiplied by duration. For ACWR, a high ratio for THSR (>1.18) resulted in a higher injury risk. In contrast, a lower injury risk was found when comparing medium ratios for ACC eff (0.87-1.12), DEC eff (0.86-1.12), and RPE x duration (0.85-1.12) to low ratios., Conclusions: Findings demonstrate that mainly external load indicators are associated with increased or decreased injury risk. The monitoring of various load indicators is recommended for injury prevention in professional soccer., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time., Methods: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria., Results: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10)., Conclusion: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Objective: To determine the diagnostic accuracy of endoscopic follow-up for gastric ulcers., Methods: All cases of gastric ulcers diagnosed at our teaching hospital between September 2005 and November 2011 were reviewed. The cases were selected by using ENDOBASE, an endoscopy documentation system. The characteristics of the ulcers and their histology were analysed., Results: During the study period 321 cases with a gastric ulcer were diagnosed, including 214 benign ulcers (67 %) and 107 malignant ulcers (33 %). The mean age of the population was 71 years. In 200 patients (62 %) the ulcers were classified as benign appearing at the first endoscopy. However, in five of these patients, the ulcers eventually were malignant. In all of these five patients the index gastroscopy revealed a non-benign histology. Therefore, the sensitivity of a benign appearance of the ulcer in combination with histology at the first endoscopy is 100 % to rule out malignancy. In 121 patients (38 %) the ulcers were explicitly labelled as potentially malignant in the report of the first endoscopy. Of these potentially malignant-appearing ulcers, 102 (84 %) were indeed malignant as confirmed by histology. The other 19 ulcers (16 %) were benign at follow-up. The sensitivity of the three potential malignant characteristics at endoscopy was: dirty base 79 %, elevated border 94 % and irregular border 91 %. The specificity was 93, 82 and 89 %, respectively. The median diameter of the ulcers was significantly higher in the malignant group compared to the benign ulcer group (p < 0.0001). The accuracy of endoscopic malignancy diagnosis was as follows: sensitivity of 0.98 and specificity 0.84, positive predictive value 0.84 and negative predictive value 0.98. In total, 546 gastroscopies were performed in these 321 patients, of which 225 were follow-up endoscopies. By not monitoring ulcers considered benign in both appearance and histology, 173 gastroscopies would not have been performed, resulting in a decline of 77 % of the follow-up endoscopies performed., Conclusion: Endoscopic follow-up of gastric ulcers considered benign by appearance and with benign histology showed no additive value in detecting unsuspected malignancy in this study. This strategy could reduce health costs and save distress to patients.

Background: Intestinal malrotation refers to a spectrum of anomalies of midgut rotation and fixation at various stages during early embryonic development. In adults, malrotation manifests itself mainly in chronic non-specific abdominal complaints and may therefore be easily misdiagnosed beyond infancy., Case Presentation: We present a case of an 82-year-old Caucasian man with vomiting and abdominal pain owing to malrotation complicated by duodenal obstruction and intestinal ischaemia confirmed by radiologic evaluation and autopsy report., Conclusion: Although intestinal malrotation is generally discovered near birth, our case demonstrates that physicians should consider this diagnosis at advanced age as well. In addition, particularly radiologic findings are supportive in diagnosing malrotation., (Copyright © 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background: Improved compliance in active ulcerative colitis (UC) is likely to improve healthcare efficiency by reducing time spent in active mild to moderate UC state. To establish whether once daily (OD) mesalazine offers economic advantages over twice daily (BD) dosing in active UC, we evaluated the outcomes and costs of a recently published randomized study., Methods: A cost-effectiveness model with four week Markov cycles was developed to reflect current treatment practices in the Netherlands with OD and BD mesalazine for active UC. The health service perspective of the Netherlands was reflected in the model and considered a 32week time horizon with 4 weekly Markov cycles. Outcomes evaluated in the model were time spent in active and remission UC and the corresponding health-related quality of life associated with different clinical states. This was then used to derive quality adjusted life-years (QALYs) at each treatment stage., Results: A greater proportion of subjects on 4 g OD achieved remission at weeks 4 and 8 compared with 2g BD. After 32 weeks the average costs per patient with active UC were €3097 and €3548 for those treated with OD and BD mesalazine respectively, with an average saving of €451 per patient treated with OD mesalazine. The average costs per QALY for OD and BD mesalazine were €5433 and €6324 for OD and BD, respectively., Conclusions: Based on the results from a single randomized study, OD dosing resulted in a shorter time spent in active UC which resulted in lower healthcare costs., (© 2013 Elsevier B.V. All rights reserved.)

Background: Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient., Aim: To compare the efficacy and safety of once- (OD) vs. twice- (BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study., Methods: Eligible patients (n = 206) were randomised to 8 weeks of mesalazine (4 g/day), either OD with two sachets of 2 g mesalazine granules in the morning (n = 102) or BD with one 2 g sachet in the morning and one in the evening (n = 104). Patients also received 4 weeks of mesalazine enema 1 g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index (UC-DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8 weeks. Patients recorded stool frequency and rectal bleeding in a daily diary., Results: The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8 weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval -3.4, 24.1; P = 0.14). Improvement of UC-DAI score (92% vs. 79%; P = 0.01) and mucosal healing (87.5% vs. 71.1%; P = 0.007) were significantly better, time to remission significantly shorter (26 vs. 28 days; P = 0.04) and safety similar with OD vs. BD dosing., Conclusions: When combined with mesalazine enema, prolonged-release mesalazine once-daily 4 g is as effective and well tolerated as 2 g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789)., (© 2013 Blackwell Publishing Ltd.)

A 74-year-old woman went to the gastroenterologist because of an altered defaecation pattern. Colonoscopy could not be completed due to sigmoid angulation. A CT-scan of the colon showed that the colon was located in the left side of the abdomen, as a result of embryonic non-rotation of the intestine. In adults this is generally asymptomatic. Non-specific abdominal complaints or volvulus seldom occur. Surgical intervention is rarely necessary.

Aim: Conservative treatment of mild colonic diverticulitis usually consists of observation, restriction of oral intake, intravenous fluids and antibiotics. The beneficiary effect of antibiotics remains unclear. The aim of this study is to evaluate the need for antibiotics in mild colonic diverticulitis., Method: A retrospective case-control study was performed in 272 patients with mild colonic diverticulitis admitted to two hospitals with distinctly different treatment regimes concerning antibiotic use., Results: A total of 191 patients were treated without antibiotics and 81 with antibiotics. Groups were comparable at baseline with respect to age, sex, comorbidity, and use of nonsteroid anti-inflammatory drugs, steroids and aspirin. All patients had imaging-confirmed diverticulitis. C reactive protein and white blood count levels did not differ significantly. In the antibiotics group there were significantly more patients with a temperature of 38.5°C or higher on admission. (8 vs 19%; P=0.014). Treatment failure did not differ between groups (4 vs 6%; P=0.350). The risk of recurrence was higher in the antibiotics group on logistic regression analysis but did not reach statistical significance (odds ratio, 2.04; confidence interval, 0.88-4.75; P=0.880). The only factor that increased the risk of recurrence was nonsteroid anti-inflammatory drug use (odds ratio, 7.25; confidence interval, 1.22-46.88; P=0.037)., Conclusion: Antibiotics can be omitted in selected patients with mild colonic diverticulitis and should be given on indication only., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

Aim: The study aimed to investigate current management strategies for left-sided diverticulitis and compare them with current international guidelines. Differences between surgeons and gastroenterologists and between gastrointestinal and nongastrointestinal surgeons were assessed., Method: A web-based survey of treatment options for uncomplicated and complicated diverticulitis was carried out among surgeons and gastroenterologists in the Netherlands. Only surgeons were asked about surgical strategy., Results: A total of 292 surgeons and 87 gastroenterologists responded, representing 92% of all surgical and 46% of all gastroenterology departments. Ninety per cent of respondents treated mild diverticulitis without antibiotics. About one-fifth (18% gastroenterologists; 19% surgeons) regarded a CT scan as mandatory in the initial assessment. Most surgeons and gastroenterologists used some form of bowel rest, would consider outpatient treatment and would perform a colonoscopy on follow up. For Hinchey Stage 3, 78% of surgeons would consider resection and primary anastomosis and laparoscopic lavage was viewed as a valid alternative by 30% of gastrointestinal and 2% of nongastrointestinal surgeons. For Hinchey stage 4, 46% of gastrointestinal and 72% of nongastrointestinal surgeons would always perform Hartmann's procedure., Conclusion: The treatment of diverticulitis in the Netherlands shows major differences when compared with guidelines for all stages of disease., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

Background: The reported incidence of hepatocellular carcinoma (HCC) among patients with primary biliary cirrhosis (PBC) varies from 0.7-3.8%, whereas in cirrhotic patients the risk is considerably higher. Age, male sex, cirrhosis, and portal hypertension are reported risk factors. It has been suggested that ursodeoxycholic acid (UDCA) may protect against HCC. We aimed to define risk factors for the development of HCC at the time of PBC diagnosis and to identify, among patients treated with UDCA for a long term, a subgroup that could benefit from screening., Methods: Prospective multicenter cohort study of patients with established PBC treated with 13-15 mg/kg/day UDCA. Age, sex, antimitochondrial antibodies, bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, aspartate amino transferase, cirrhosis, portal hypertension, Mayo Risk Score, prognostic class (based on bilirubin and albumin levels), and response to UDCA (normalization of bilirubin and/or albumin levels) were analyzed as potential risk factors in Cox regression analysis., Results: Three hundred and seventy-five patients were included, median follow-up was 9.7 years. HCC occurred in nine patients, corresponding with an annual incidence of 0.2%. The factor significantly associated with the development of HCC was the response to UDCA (P<0.001). The risk for HCC was highest in the group of nonresponders to UDCA: the 10 years incidence of HCC was 9% and the 15 years incidence was 20%. The number needed to screen in this subgroup was 11., Conclusion: In UDCA treated PBC patients the risk of HCC is relatively low. The main risk factor for HCC in this study was the absence of biochemical response to UDCA after 1-year treatment.

Background: Alterations in synthesis and breakdown of extracellular matrix components play a role in acute rejection after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are capable of degrading basement membranes and are involved in the process of tissue remodelling in inflammation and liver fibrosis., Methods: We examined MMP-2 and MMP-9 in serum of 33 patients before and during 1 year after OLT, in 60 controls as well as in some specimens of cirrhotic liver and control liver tissue., Results: Serum MMP-2 levels before OLT were significantly higher compared with controls and decreased approximately 50% after OLT. Also, the MMP-2 content of cirrhotic liver specimens was significantly higher compared with normal liver. MMP-9 in serum and liver tissue of patients were similar to controls, but serum levels showed a peak at 1 week after OLT. At this time-point, total and active/inhibitor-complexed MMP-9 was significantly higher in patients with rejection (n=13) compared with those without rejection (n=20). The relative amount of MMP-9 in the active/inhibitor-complexed form did not differ between each group over time. Immunohistochemical staining at 1 week after OLT showed increased numbers of MMP-9-positive inflammatory cells in the portal triads of patients with rejection., Conclusions: Patients with acute allograft rejection have elevated serum levels of MMP-9 1 week after OLT, which was most likely derived from inflammatory cells. An increased MMP-2 serum level and liver tissue content was found in patients with cirrhosis, which decreased after OLT. These observations indicate active involvement of MMP-2 and -9 in end-stage liver disease and OLT.

Uncontrolled activation of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation, yet little is known about the activation of MMPs during orthotopic liver transplantation (OLT). OLT is associated with increased fibrinolytic activity due to elevated plasmin generation. The serine-protease plasmin not only causes degradation of fibrin clots but is also thought, amongst others, to play a role in the activation of some matrix metalloproteinases. We therefore studied the evolution of MMP-2 and -9 plasma concentrations during OLT and the effect of serine-protease inhibition by aprotinin on the level and activation of these MMPs. In a group of 24 patients who participated in a randomized, double-blind, placebo-controlled study we determined serial MMP-2 and MMP-9 plasma levels during transplantation using ELISA (total MMP), activity assays (activatable MMP) and zymography. In addition, the MMP-inhibitors TIMP-1 and TIMP-2 were assessed by ELISA. The putative regulating factors tumor necrosis factor alpha (TNF-alpha) and tissue-type plasminogen activator (t-PA) were assessed as well. Patients were administered high-dose aprotinin, regular-dose aprotinin or placebo during surgery. Plasma TIMP-1, TIMP-2 and MMP-2 level gradually decreased during transplantation. Approximately two-thirds of total MMP-2 appeared to be in its activatable proMMP form. No release of MMP-2 from the graft could be detected. In contrast, plasma levels of MMP-9 increased sharply during the anhepatic and postreperfusion periods. Peak MMP-9 levels of about eight times above baseline were found at 30 minutes after reperfusion. Most MMP-9 appeared to be in its active/inhibitor-complexed form. No significant differences were observed between the three treatment groups. However, in patients with more severe ischemia/reperfusion (I/R) injury the MMP-9 concentration, particularly of the active/inhibitor-complexed form, remained high at 120 minutes postreperfusion compared to patients with no or mild I/R injury. The decrease in plasma levels of MMP-2, TIMP-1 and TIMP-2 during OLT occurred irrespective of the severity of the I/R injury. There was a significant correlation between MMP-9 and t-PA levels, but not with TNF-alpha. In conclusion, OLT is associated with a sharp increase of MMP-9 during the anhepatic and postreperfusion periods, which coincided with the changes in t-PA. MMP-2, TIMP-1 and TIMP-2 gradually decreased during OLT. The composition of these MMPs was not altered by the use of aprotinin, suggesting that serine-protease/plasmin-independent pathways are responsible for MMP regulation during OLT. In addition, only MMP-9 seems to be involved in I/R injury during human liver transplantation.

Introduction: Ischemia and reperfusion (I/R) injury during orthotopic liver transplantation (OLT) is accompanied by neutrophil infiltration and degradation of extracellular matrix. Matrix metalloproteinases (MMP) play an important role in the turnover of extracellular matrix components. We assessed the changes in level and composition of serum MMP-2 and MMP-9 in relation with I/R injury after human OLT., Methods: Thirty-three patients were separated into two groups according to their peak level of aspartate aminotransferase (AST) after OLT (AST < 1500 IU/L: n = 22; AST > 1500 IU/L: n = 11). Serum MMP-2 and MMP-9 were measured before transplantation as well as 2 days and 1 week after OLT using ELISA (MMP protein) and BIA (enzymatic activity of MMP)., Results: MMP-2 and MMP-9 protein concentrations were comparable before and 2 days after OLT, whereas at 1 week MMP-2 decreased and MMP-9 increased significantly. However, there were no significant differences between patients with high or low peak AST at all time points. Also, the composition of MMP-2 and MMP-9 did not differ over time between the groups of patients., Conclusion: Serum MMP-2 and MMP-9 do not relate to the late phase of hepatic I/R injury after human OLT.

Matrix metalloproteinases (MMPs) have the ability to degrade basement membranes and may thus play an important role in extracellular matrix turnover in liver fibrosis and carcinogenesis. Serum levels of MMPs have been suggested as diagnostic markers in these processes. We measured serum MMP-2 and MMP-9 by ELISA in 91 patients with chronic liver disease, including 25 patients with hepatocellular carcinoma (HCC), and in 60 controls. MMP-2 was significantly higher in patients with chronic liver disease compared to controls, and increased with Child-Pugh class. There was a significant correlation between MMP-2 and liver function (bilirubin, albumin, and prothrombin time), and a strong opposite correlation between MMP-9 and these parameters. MMP-2 levels in patients with HCC were significantly higher than in controls, but comparable to patients with chronic liver disease without this malignancy. MMP-9 yielded no significant differences between patients with or without HCC and controls. Serum MMP-2 and to a lesser extent MMP-9 correlate with the severity of liver disease and may reflect changes in extracellular matrix remodeling. Due to a considerable overlap in patients with chronic liver disease with or without HCC, MMP-2 and MMP-9 can not be used as a diagnostic marker for HCC.

Background: Helicobacter pylori infection is found in almost all patients with an uncomplicated ulcer. Non-steroidal anti-inflammatory drug (NSAID) use is the main risk factor for bleeding peptic ulcer. In the older literature ABO blood groups were mentioned as a risk factor. There is continuing uncertainty about the interaction between these risk factors and the development of peptic ulcer bleeding. We therefore determined the separate and combined effect of NSAIDs, H. pylori infection, and the ABO blood group system in patients with a bleeding peptic ulcer., Methods: The prevalence of NSAID use, H. pylori infection, and blood group O was determined in 227 patients who were admitted with a bleeding gastric or duodenal ulcer between 1990 and 1997. These results were compared with the expected frequency of these risk factors in the Dutch population., Results: NSAID use was reported in 48.2% of the patients with a bleeding peptic ulcer. The H. pylori prevalence was 62.0%, whereas blood group O was present in 49.3% of the patients. NSAID use was the strongest risk factor for hemorrhage caused by a peptic ulcer (relative risk, 8.4), whereas the relative risk associated with H. pylori infection and blood group O was 1.5 and 1.2, respectively. With univariate analysis NSAID use and H. pylori infection seemed to be separate risk factors and did not really potentiate each other's effect. Moreover, blood group O did not potentiate the strong effect of NSAIDs., Conclusion: H. pylori infection may add only a little to the important risk of NSAID use in the development of bleeding peptic ulcers.

We report on three patients with severe Graves' dermopathy who were treated with octreotide despite a negative octreotide scintigraphy. One patient showed a complete recovery while two others had a partial response. In contrast to active Graves' ophthalmopathy, an octreotide scintigraphy appears not to be useful for pretreatment identification of patients with Graves' dermopathy who are likely to respond to octreotide treatment.

Between 1975 and 1990, 70 episodes of prosthetic valve endocarditis (PVE) were diagnosed in 65 patients at Leiden University Hospital. The overall mortality rate was 27%. Antecedent endocarditis attributable to the same micro-organism (mortality 63%, P = 0.02) and Staphylococcus aureus as the causative micro-organism (mortality 100%, P = 0.001) were significant predictors for mortality. Sex, type and position of the valve and therapy had no significant influence on the mortality. All patients infected with S. aureus died, irrespective of whether they received medical treatment alone or in combination with surgery. None of the patients with streption, endocarditis had abscesses at reoperation; the mortality rate for this group was 14%. Abscess formation, especially in aortic valves, was the most important finding at reoperation and corresponded with a mortality rate of 55%. Ring abscesses occurred equally in patients with mechanical and bioprosthetic valves. Seven of the 15 patients (47%) with significant prosthetic valve dehiscence died. In patients with mitral valve endocarditis, localized dehiscence of the valve was observed. In conclusion a previous endocarditis attributable to the same micro-organism and the causative micro-organism (S. aureus) were important risk factors for mortality due to PVE.