Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA

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Minimally invasive versus open pancreatoduodenectomy (LEOPARD-2): Study protocol for a randomized controlled trial

Background: Data from observational studies suggest that minimally invasive pancreatoduodenectomy (MIPD) is superior to open pancreatoduodenectomy regarding intraoperative blood loss, postoperative morbidity, and length of hospital stay, without increasing total costs. However, several case-matched studies failed to demonstrate superiority of MIPD, and large registry studies from the USA even suggested increased mortality for MIPDs performed in low-volume (< 10 MIPDs annually) centers. Randomized controlled multicenter trials are lacking but clearly required. We hypothesize that time to functional recovery is shorter after MIPD compared with open pancreatoduodenectomy, even in an enhanced recovery setting. Methods/design: LEOPARD-2 is a randomized controlled, parallel-group, patient-blinded, multicenter, phase 2/3, superiority trial in centers that completed the Dutch Pancreatic Cancer Group LAELAPS-2 training program for laparoscopic pancreatoduodenectomy or LAELAPS-3 training program for robot-assisted pancreatoduodenectomy and have performed ≥ 20 MIPDs. A total of 136 patients with symptomatic benign, premalignant, or malignant disease will be randomly assigned to undergo minimally invasive or open pancreatoduodenectomy in an enhan

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): Study protocol for a multicentre randomized controlled trial

Background: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improve

Variations in the slope of the psychometric functions for speech intelligibility: a systematic survey

Although many studies have looked at the effects of different listening conditions on the intelligibility of speech, their analyses have often concentrated on changes to a single value on the psychometric function, namely, the threshold. Far less commonly has the slope of the psychometric function, that is, the rate at which intelligibility changes with level, been considered. The slope of the function is crucial because it is the slope, rather than the threshold, that determines the improvement in intelligibility caused by any given improvement in signal-to-noise ratio by, for instance, a hearing aid. The aim of the current study was to systematically survey and reanalyze the psychometric function data available in the literature in an attempt to quantify the range of slope changes across studies and to identify listening conditions that affect the slope of the psychometric function. The data for 885 individual psychometric functions, taken from 139 different studies, were fitted with a common logistic equation from which the slope was calculated. Large variations in slope across studies were found, with slope values ranging from as shallow as 1% per dB to as steep as 44% per dB (median = 6.6% per dB), suggesting that the perceptual benefit offered by an improvement in signal-to-noise ratio depends greatly on listening environment. The type and number of maskers used were found to be major factors on the value of the slope of the psychometric function while other minor effects of target predictability, target corpus, and target/masker similarity were also found

The association between medication use and gait in adults with intellectual disabilities

Background: Adults with intellectual disabilities (ID) often have polypharmacy and often use antipsychotics. Both polypharmacy and antipsychotics have a negative effect on gait in the general population, but this has not been studied in adults with ID. These negative effects may add to pre-existing gait disturbances in adults with ID and increase the risk for adverse health outcomes in this population. Therefore, the aim of this study is to investigate the difference in gait parameters between adults with ID with and without polypharmacy and between adults with ID using and not using antipsychotics. Method: The gait parameters of 31 participants were collected with the GAITRite walkway, a pressure sensitive walkway measuring spatial and temporal gait parameters, in addition to information about personal characteristics, prescribed medication and presence of polypharmacy. Results: After adjustment for sex and body mass index, participants with polypharmacy had a significantly shorter step length [polypharmacy B (SE) = −0.079 (0.034), P = 0.03], shorter stride length [polypharmacy B (SE) = −0.157 (0.069), P = 0.03] and longer double support time [polypharmacy B (SE) = 0.0004 (0.0001), P = 0.047]. Participants using antipsychotics ha

PIN71 QUALITY OF LIFE (QOL) AND OTHER ENDPOINTS COMPARISON IN THE TREATMENT OF FACIAL LIPOATROPHY WITH INJECTION OF POLY-L-LACTIC ACID

Context: Longitudinal data on bone mineral density(BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. Objective: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMAD(LS)) in children with PWS. Design and Setting: This was a prospective longitudinal study of a Dutch PWS cohort. Participants: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. Intervention: The children received GH treatment, 1 mg/m(2)/day (congruent to 0.035 mg/kg/d). Main Outcome Measures: BMDTB, BMDLS, and BMAD(LS) was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. Results: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMAD(LS)SDS remained stable. During adolescence, BMDTBSDS and BMAD(LS)SDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lowerBMAD(LS)SDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. Conclusions: This long-term GH study demonstrates that BMDTB, BMDLS, and BMAD(LS) remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty

Minimally invasive versus open distal pancreatectomy (LEOPARD): Study protocol for a randomized controlled trial

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. Methods: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. Discussion: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Trial registration: Dutch Trial Register, NTR5188. Registered on 9 April 201

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre

BACKGROUND: Celiac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period. METHODS: To diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient. RESULTS: In our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22-67), 6/8 Crohn's disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn's disease patients are B1, 2/6 Crohn's disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients. CONCLUSIONS: Within our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population

Multidisciplinary decision-making in older patients with cancer, does it differ from younger patients?

Background: In order to tailor treatment to the individual patient, it is important to take the patients context and preferences into account, especially for older patients. We assessed the quality of information used in the decision-making process in different oncological MDTs and compared this for older (>70 years) and younger patients. Patients and methods: Cross-sectional observations of oncological MDTs were performed, using an observation tool in a University Hospital. Primary outcome measures were quality of input of information into the discussion for older and younger patients. Secondary outcomes were the contribution of different team members, discussion time for each case and whether or not a treatment decision was formulated. Results: Five-hundred and three cases were observed. The median patient age was 63 year, 32% were >70. In both age groups quality of patient-centered information (psychosocial information and patient's view) was poor. There was no difference in quality of information between older and younger patients, only for comorbidities the quality of information for older patients was better. There was no significant difference in the contributions by team members, discussion time (median 3.54 min) or number of decision reached (87.5%). Conclusion: For both age groups, we observed a lack of patient-centered information. The only difference between the age groups was for information on comorbidities. There were also no differences in contributions by different team members, case discussion time or number of decisions. Decision-making in the observed oncological MDTs was mostly based on medical technical information. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)