Fecal continence outcomes are associated with the type, height, and stage procedure of ileal pouch-anal anastomosis

Purpose This study aims to analyze the quality of life in patients with an ileal pouch-anal anastomosis (IPAA) and to investigate the association between height and type of the anastomosis, the number of stage procedures and age, and the fecal continence outcomes. Methods This is a cross-sectional retrospective study in patients who had undergone IPAA between 1992 and 2016 (N = 133). We sent questionnaires to 102 eligible patients (64% response rate). We used the Wexner score to assess fecal incontinence: 0 = no incontinence to 20 = complete incontinence. We used RAND-36 to measure quality of life. Results Patients who underwent mucosectomy with hand-sewn anastomoses (n = 11, 17%) had significantly higher median Wexner scores than patients with stapled anastomoses (10 versus 3, P = 0.003). Lower anastomoses correlated significantly with increasing Wexner scores (r = - 0.468, P <0.001). Quality of life of incontinent patients was diminished. Patients who were older at the time of IPAA surgery had higher Wexner scores (P = 0.004), while the time between surgery and questionnaire did not influence their Wexner scores (P = 0.810). Considering the stage procedures, multiple linear regression showed that the two-stage procedure without diverting ileostomy was significantly associated with higher Wexner scores (B = 0.815, P = 0.02), adjusted for sex (P = 0.008) and anastomosis type (P = 0.002). The three-stage procedure showed equally low complications and anastomotic leakage rates. Conclusion Mucosectomy with more distal, hand-sewn anastomosis and increasing age at IPAA surgery was associated with poorer fecal continence outcomes. The three-stage procedure appears to give the best fecal continence results without increasing complications. Furthermore, incontinence reduced patient's quality of life

How Should the Low Anterior Resection Syndrome Score Be Interpreted?

BACKGROUND: Bowel dysfunction after low anterior resection is often assessed by determining the low anterior resection syndrome score. What is unknown, however, is whether this syndrome is already present in the general population and which nonsurgical factors are associated. OBJECTIVE: The purpose of this study was to determine the prevalence of minor and major low anterior resection syndrome in the general Dutch population and which other factors are associated with this syndrome. DESIGN: This was a cross-sectional study. SETTINGS: The study was conducted within the general Dutch population. PATIENTS: The Groningen Defecation and Fecal Continence Questionnaire was distributed among a general Dutch population-based sample (N = 1259). MAIN OUTCOME MEASURES: Minor and major low anterior resection syndrome were classified according to the scores obtained. RESULTS: The median, overall score was 16 (range, 0-42). Minor low anterior resection syndrome was more prevalent than the major form (24.3% vs 12.2%; p <0.001). Bowel disorders, including fecal incontinence, constipation, and irritable bowel syndrome were associated with the syndrome, whereas sex, age, BMI, and vaginal delivery were not. Remarkably, patients with diabetes mellitus were significantly more prone to experience minor or major low anterior resection syndrome. The ORs were 2.8 (95% CI, 1.8-4.4) and 3.7 (95% CI, 2.2-6.2). LIMITATIONS: We selected frequent comorbidities and other patient-related factors that possibly influence the syndrome. Additional important factors do exist and require future research. CONCLUSIONS: Minor and major low anterior resection syndrome occur in a large portion of the general Dutch population and even in a healthy subgroup. This implies that the low anterior resection syndrome score can only be used to interpret the functional result of the low anterior resection provided that a baseline measurement of each individual is available. Furthermore, because people with low anterior resection syndrome often experience constipation and/or fecal incontinence, direct examination and diagnosis of these conditions might be a more efficient approach to treating patient bowel dysfunctions

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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A new technique for precisely and accurately measuring lumbar spine bone mineral density in mice using clinical dual energy X-ray absorptiometry (DXA)

Dual Energy X-ray Absorptiometry (DXA) is effective in measuring bone mineral density (BMD) in mice for early detection of osteoporosis. However, scanners designed for use with small animals (i.e. PIXImus) are very expensive. Used human DXA machines are cheaper to obtain, but analysis of scans from these instruments is operator-dependent. Obtaining reliable data depends on having a single operator analyze the scans in a blinded fashion. Scan quality is improved by excising the bone prior to scanning, which does not allow serial measurements. This study describes a novel method of analyzing lumbar spine BMD in mice using whole body DXA. This non-invasive technique has a high degree of precision and reproducibility, with good correlation between multiple observers. Inter-observer variability (0.063 ± 0.00317 g/cm2 [mean ± SD], 5.05 [% coefficient of variation (CV)], repeat scan variability (0.063 ± 0.00364 g/cm2 [mean ± SD], 5.94 [%CV]) were very low compared to variability between different animals (0.063 ± 0.00588 g/cm2 [mean ± SD], 9.64 [%CV]) and variability seen in same animal over time (0.011 ± 0.00885 g/cm2 [mean ± SD], 80.68 [%CV]). The measurement error is thus smaller than the biological variation. Accuracy was determined by comparing average peak BMD from two scans per mouse in-vivo (0.066 g/cm2) versus excised spine (0.065 g/cm2). Furthermore, correlation between bone ash weights and whole body lumbar spine BMD measurements (p < 0.0001) was highly significant. This technique thus shows a high degree of precision and accuracy, even with multiple observers, for measuring BMD in mice using a DXA machine designed for clinical use

The Copper Metabolism MURR1 Domain Protein 1 (COMMD1) Modulates the Aggregation of Misfolded Protein Species in a Client-Specific Manner

The Copper Metabolism MURR1 domain protein 1 (COMMD1) is a protein involved in multiple cellular pathways, including copper homeostasis, NF-kappa B and hypoxia signalling. Acting as a scaffold protein, COMMD1 mediates the levels, stability and proteolysis of its substrates (e.g. the copper-transporters ATP7B and ATP7A, RELA and HIF-1 alpha). Recently, we established an interaction between the Cu/Zn superoxide dismutase 1 (SOD1) and COMMD1, resulting in a decreased maturation and activation of SOD1. Mutations in SOD1, associated with the progressive neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS), cause misfolding and aggregation of the mutant SOD1 (mSOD1) protein. Here, we identify COMMD1 as a novel regulator of misfolded protein aggregation as it enhances the formation of mSOD1 aggregates upon binding. Interestingly, COMMD1 co-localizes to the sites of mSOD1 inclusions and forms high molecular weight complexes in the presence of mSOD1. The effect of COMMD1 on protein aggregation is client-specific as, in contrast to mSOD1, COMMD1 decreases the abundance of mutant Parkin inclusions, associated with Parkinson's disease. Aggregation of a polyglutamine-expanded Huntingtin, causative of Huntington's disease, appears unaltered by COMMD1. Altogether, this study offers new research directions to expand our current knowledge on the mechanisms underlying aggregation disease pathologies.</p

Abdominal Compartment Syndrome and Intra-abdominal Ischemia in Patients with Severe Acute Pancreatitis

Severe acute pancreatitis may be complicated by intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and intestinal ischemia. The aim of this retrospective study is to describe the incidence, treatment, and outcome of patients with severe acute pancreatitis and ACS, in particular the occurrence of intestinal ischemia. The medical records of all patients admitted with severe acute pancreatitis admitted to the ICU of a tertiary referral center were reviewed. The criteria proposed by the World Society of the Abdominal Compartment Syndrome (WSACS) were used to determine whether patients had IAH or ACS. Fifty-nine patients with severe acute pancreatitis were identified. Intra-abdominal pressure (IAP) measurements were performed in 29 patients (49.2 %). IAH was present in all patients (29/29). ACS developed in 13/29 (44.8 %) patients. Ten patients with ACS underwent decompressive laparotomy. A large proportion of patients with ACS had intra-abdominal ischemia upon laparotomy: 8/13 (61.5 %). Mortality was high in both the ACS group and the IAH group. This study confirms that ACS is common in severe acute pancreatitis. Intra-abdominal ischemia occurs in a large proportion of patients with ACS. Swift surgical intervention may be indicated when conservative measures fail in patients with ACS. National and international guidelines need to be updated so that routine IAP measurements become standard of care for patients with severe acute pancreatitis in the ICU

Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of this association for DM2, replication studies in distinct ethic populations are required. We investigated ATF6 for its association with DM2 in Dutch Caucasians. Design/Setting: A genetic association study was conducted at an academic research laboratory. Study Participants: Two independent Dutch cohorts were studied. Cohort 1 (n = 154) was used to evaluate genetic variation in the ATF6 gene in relation to glucose homeostasis in the general population. Cohort 2 (n = 798) consisted of patients with DM2, impaired glucose tolerance, impaired fasting glucose, and normoglycemic control subjects, and was used to investigate ATF6 polymorphisms for their contribution to disturbed glucose homeostasis and DM2. Main Outcome Measures: There were 16 tag single nucleotide polymorphisms genotyped in all subjects of both cohorts. Those single nucleotide polymorphisms included three nonsynonymous coding variants and captured all common allelic variation of ATF6. Results: Our data show that common ATF6 variants are associated with elevated glucose levels in the general population (cohort 1, P = 0.005-0.05). Furthermore, the majority of these variants, and haplotypes thereof, were significantly associated with impaired fasting glucose, impaired glucose tolerance, and DM2 ( cohort 2, P = 0.006-0.05). Associated variants differ from those identified in Pima Indians. Conclusions: Our results strengthen the evidence that one or more variants in ATF6 are associated with disturbed glucose homeostasis and DM2

Exchange of Best Practices Within the European Union:Surgery Standardization of Abdominal Organ Retrieval

AbstractConsidering the growing organ demand worldwide, it is crucial to optimize organ retrieval and training of surgeons to reduce the risk of injury during the procedure and increase the quality of organs to be transplanted. In the Netherlands, a national complete trajectory from training of surgeons in procurement surgery to the quality assessment of the procured organs was implemented in 2010. This mandatory trajectory comprises training and certification modules: E-learning, training on the job, and a practical session. Thanks to the ACCORD (Achieving Comprehensive Coordination in Organ Donation) Joint Action coordinated by Spain and co-funded under the European Commission Health Programme, 3 twinning activities (led by France) were set to exchange best practices between countries. The Dutch trajectory is being adapted and implemented in Hungary as one of these twinning activities. The E-learning platform was modified, tested by a panel of Hungarian and UK surgeons, and was awarded in July 2013 by the European Accreditation Council for Continuing Medical Education of the European Union of Medical Specialists. As a pilot phase for future national training, 6 Hungarian surgeons from Semmelweis University are being trained; E-learning platform was fulfilled, and practical sessions, training-on-the-job activities, and evaluations of technical skills are ongoing. The first national practical session was recently organized in Budapest, and the new series of nationwide selected candidates completed the E-learning platform before the practical. There is great potential for sharing best practices and for direct transfer of expertise at the European level, and especially to export this standardized training in organ retrieval to other European countries and even broader. The final goal was to not only provide a national training to all countries lacking such a program but also to improve the quality and safety criteria of organs to be transplanted