Pain and aetiological risk factors determine quality of life in patients with chronic pancreatitis, but a brick in the puzzle is missing.

BACKGROUND AND OBJECTIVES: Chronic pancreatitis (CP) is a debilitating fibro-inflammatory disease with a profound impact on patients' quality of life (QOL). We investigated determinants of QOL in a large cohort of CP patients. METHODS: This was a multicentre study including 517 patients with CP. All patients fulfilled the EORTC QLQ-C30 questionnaire. Questionnaire responses were compared to results obtained from a general reference population (n = 11,343). Demographic characteristics, risk factors (smoking and alcohol consumption), pain symptoms, disease phenotype (complications) and treatments were recorded. A multivariable regression model was used to identify factors independently associated with QOL scores. RESULTS: Included patients had a mean age of 56.3 ± 12.8 years, 355 (69%) were men and 309 (60%) had alcohol aetiology. Compared to the reference population, patients with CP had lower global health status (50.5 vs. 66.1; p < 0.001) as well as reduced scores for all functional scales (all p < 0.001). Additionally, CP patients reported a higher burden for all symptom items, with pain being the most prominent complaint (all p < 0.001). Constant pain (coefficient -11.3; p = 0.02), opioid based pain treatment (coefficient -19.7; p < 0.001) and alcoholic aetiology (coefficient -5.1; p = 0.03) were independently associated with lowered global health status. The final multivariable model explained 18% of the variance in global health status. CONCLUSIONS: Patients with CP have significantly lower QOL compared to a population-based reference population. Factors independently associated with a lowered QOL are constant pain, opioid based pain treatment and alcohol aetiology. However, these factors only explain a fraction of QOL and additional factors need identification.

Perturbations in RhoA signalling cause altered migration and impaired neuritogenesis in human iPSC-derived neural cells with PARK2 mutation.

Mutations in parkin, encoded by the PARK2 gene, causes early-onset familial Parkinson's disease (PD), but dysfunctional parkin has also been implicated in sporadic PD. By combining human isogenic induced pluripotent stem cells (iPSCs) with and without PARK2 knockout (KO) and a novel large-scale mass spectrometry based proteomics and post-translational modification (PTM)-omics approach, we have mapped changes in protein profiles and PTMs caused by parkin deficiency in neurons. Our study identifies changes to several proteins previously shown to be dysregulated in brains of sporadic PD patients. Pathway analysis and subsequent in vitro assays reveal perturbations in migration and neurite outgrowth in the PARK2 KO neurons. We confirm the neurite defects using long-term engraftment of neurons in the striatum of immunosuppressed hemiparkinsonian adult rats. The GTP-binding protein RhoA was identified as a key upstream regulator, and RhoA activity was significantly increased in PARK2 KO neurons. By inhibiting RhoA signalling the migration and neurite outgrowth phenotypes could be rescued. Our study provides new insight into the pathogenesis of PD and demonstrates the broadly applicable potential of proteomics and PTMomics for elucidating the role of disease-causing mutations.

Structural imaging findings are related to clinical complications in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Structural pancreatic changes and complications related to chronic pancreatitis are well described, but little is known about their relationship. We aimed to explore the associations between pancreatic morphology and clinical complications in a large chronic pancreatitis cohort. METHODS: The Scandinavian Baltic Pancreatic Club database collects registrations on patients with definite or probable chronic pancreatitis according to the M-ANNHEIM diagnostic criteria. In this cross-sectional study, we used multivariate logistic regression analyses to evaluate whether imaging-based structural pancreatic changes were associated with common clinical complications. We adjusted for sex, age, disease duration, current alcohol abuse and current smoking. RESULTS: We included 742 patients with a mean age of 55 years. Among these, 68% were males, 69% had pancreatic exocrine insufficiency, 35% had diabetes, 12% were underweighted and 68% reported abdominal pain. Main pancreatic duct obstruction, severe (i.e. more than 14) calcifications, pancreatic atrophy and parenchymal changes throughout the entire pancreas (continuous organ involvement) were positively associated with pancreatic exocrine insufficiency. Continuous organ involvement and pseudocysts were positively and negatively associated with diabetes, respectively. Pancreatic atrophy and severe calcifications were positively associated with underweight, and severe calcifications were negatively associated with pain. CONCLUSIONS: This study shows independent associations between distinct structural changes on pancreatic imaging and clinical complications in chronic pancreatitis. Pancreatic atrophy, severe calcifications and continuous organ involvement may be of particular clinical relevance, and these findings should motivate monitoring of pancreatic function and nutritional status.

Systematic approach for assessment of imaging features in chronic pancreatitis: a feasibility and validation study from the Scandinavian Baltic Pancreatic Club (SBPC) database.

PURPOSE: There is an unmet need for new systems with quantitative pancreatic imaging assessments to support better diagnosis and understand development of chronic pancreatitis (CP). The aims were to present such an approach for assessment of imaging features in CP, to apply this system in a multi-center cohort of CP patients (feasibility study), and to report inter-reader agreement between expert radiologists (validation study). METHODS: The feasibility study included pancreatic computed tomography (CT) or magnetic resonance imaging (MRI) from 496 patients with definitive CP in the Scandinavian Baltic Pancreatic Club (SBPC) database. Images were assessed according to the new SBPC imaging system (quantitative assessments of ductal and parenchymal features). Inter-reader agreement of reported imaging parameters was investigated for 80 CT and 80 MRI examinations by two expert radiologists. RESULTS: Reporting of the imaging features into the imaging system was deemed feasible for > 80% of CT and > 90% of MRI examinations. Quantitative assessments of main pancreatic duct diameters, presence/number/diameter of calcifications, and gland diameters had high levels of inter-reader agreement with κ-values of 0.75-0.87 and intraclass correlation coefficients of 0.74-0.97. The more subjective assessments, e.g., irregular main pancreatic duct and dilated side-ducts, had poor to moderate agreement with κ-values of 0.03-0.44. CONCLUSION: The presented system provides a feasible mean for systematic assessment of CP imaging features. Imaging parameters based on quantitative assessment, as opposed to subjective assessments, have better reproducibility and should be preferred in the development of new grading systems for understanding pathophysiology and disease progression in CP.

[Appropriate use of hospital days in medical wards]. / Hensigtsmaessig anvendelse af sengedage på medicinske afdelinger.

INTRODUCTION: This study evaluated the incidence of inappropriate use of bed days in Danish medical wards using the European Appropriateness Evaluation Protocol (AEP). Several European countries have used the AEP to assess the appropriateness of hospitalisation days. MATERIALS AND METHODS: The study was carried out in four Danish medical wards from October 2004 to January 2005. On pre-selected days a doctor and nurse performed case record analyses of all hospitalised patients with registration of the AEP criteria. To assess activities during the entire day, the screening comprised activities from the previous day. RESULTS: Altogether, 738 patients were reviewed. On average, 32.1% of hospitalisation days on the four wards were assessed as inappropriate (range 19.2-39.2%). Lack of alternative facilities (different outpatient services, rehabilitation, home nursing, etc.) and internal waiting time for diagnostic tests were the most common causes of inappropriate bed use. 6.4% of bed days were considered appropriate from a clinical point of view even though no AEP criteria were met. CONCLUSION: In order to reduce the number of inappropriate hospital days, it is necessary to optimise the cooperation with the primary health care sector and ensure immediate availability of diagnostic tests.

Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003-2005: a population-based study from the Danish Crohn colitis database.

OBJECTIVES: A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City. METHODS: All patients diagnosed with IBD during 2003-2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered. RESULTS: Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/10(5) for CD, 13.4/10(5) for UC, and 1.1/10(5) for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported. CONCLUSIONS: The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

Preoperative endoscopic stent placement before pancreaticoduodenectomy: a meta-analysis of the effect on morbidity and mortality.

BACKGROUND: Pancreaticoduodenectomy is the only potentially curative treatment for peripapillary pancreatic tumors. However, postoperative morbidity and mortality are high, and different approaches have been tried to improve results, such as preoperative biliary drainage in patients with jaundice. This meta-analysis investigated the effect on postoperative outcome of preoperative biliary drainage by endoscopic biliary stent placement in patients who are jaundiced and who have peripapillary pancreatic tumors. METHODS: A Medline search for the period 1985 to 2001 was performed. Eight retrospective studies and 2 prospective randomized controlled trials were included. Selection criteria for the primary analysis were as follows: patients with peripapillary pancreatic cancer, endoscopic stent placement versus no stent, radical surgery, and assessment of postoperative morbidity and mortality. A secondary analysis included both radical and palliative surgery. RESULTS: In the primary analysis, 337 patients underwent preoperative endoscopic biliary stent placement, and 412 patients had no endoscopic biliary stent placement (controls). The overall odds ratio for postoperative complications (stent vs. no stent) is estimated as 0.79: 95% CI [0.36, 1.73] and the estimated odds ratio for postoperative mortality is 0.81: 95% CI [0.33, 1.99]. In the secondary analysis, 1008 patients underwent preoperative EBS versus 720 control patients. The odds ratio for postoperative complications in this analysis was 0.93: 95% CI [0.65, 1.33] and for postoperative mortality is 1.12: 95% CI [0.62, 2.01]. CONCLUSION: No evidence was found of either a positive or adverse effect of preoperative endoscopic biliary stent placement on the outcome of surgery in patients with pancreatic cancer.