Prevalence and clinical importance of mesenteric venous thrombosis in the swiss inflammatory bowel disease cohort.

OBJECTIVE. The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS. Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS. The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION. MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Prevalence and clinical importance of mesenteric venous thrombosis in the Swiss Inflammatory Bowel Disease Cohort

OBJECTIVE: The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS: Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS: The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION: MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features.

BACKGROUND: Differences exist between the proximal and distal colon in terms of developmental origin, exposure to patterning genes, environmental mutagens, and gut flora. Little is known on how these differences may affect mechanisms of tumorigenesis, side-specific therapy response or prognosis. We explored systematic differences in pathway activation and their clinical implications. MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis. A subset of 1404 samples had molecular data, including gene expression and DNA copy number profiles for 589 and 199 samples, respectively. In addition, 413 colon adenocarcinoma from TCGA collection were also analyzed. Tumor side-effect on anti-epidermal growth factor receptor (EGFR) therapy was assessed in a cohort of 325 metastatic patients. Outcome variables considered were relapse-free survival and survival after relapse (SAR). RESULTS: Proximal carcinomas were more often mucinous, microsatellite instable (MSI)-high, mutated in key tumorigenic pathways, expressed a B-Raf proto-oncogene, serine/threonine kinase (BRAF)-like and a serrated pathway signature, regardless of histological type. Distal carcinomas were more often chromosome instable and EGFR or human epidermal growth factor receptor 2 (HER2) amplified, and more frequently overexpressed epiregulin. While risk of relapse was not different per side, SAR was much poorer for proximal than for distal stage III carcinomas in a multivariable model including BRAF mutation status [N = 285; HR 1.95, 95% CI (1.6-2.4), P < 0.001]. Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy, in line with the predictions of our pathway enrichment analysis. CONCLUSIONS: Colorectal carcinoma side is associated with differences in key molecular features, some immediately druggable, with important prognostic effects which are maintained in metastatic lesions. Although within side significant molecular heterogeneity remains, our findings justify stratification of patients by side for retrospective and prospective analyses of drug efficacy and prognosis.

Early neurological impairment and severe anemia in a newborn with Pearson syndrome

BACKGROUND: Pearson marrow-pancreas syndrome (PS) is usually a fatal mitochondrial disease, mostly diagnosed during infancy or postmortem. PS is caused by the deletions or duplications of mitochondrial DNA (mtDNA). The tissue distribution and relative proportions of expressed abnormal mtDNA determine the phenotype and the clinical course. MATERIALS AND METHODS: We describe the case of a term baby boy who was diagnosed with PS early in the neonatal period due to severe aregenerative anemia and persistent lactic acidosis. RESULTS: His neurological examination was abnormal since birth. Brain magnetic resonance imaging (MRI) at term was abnormal, indicating that mitochondrial encephalopathy in PS can be already manifested in the neonatal period. To our knowledge, neonatal encephalopathy in PS has not been previously described. CONCLUSION: PS is a rare condition diagnosed in the newborn. It should be suspected in the presence of severe anemia and persistent lactic acidosis, and may manifest with early encephalopathy.

Is spinal stenosis assessment dependent on slice orientation? A magnetic resonance imaging study.

INTRODUCTION: Lumbar spinal stenosis (LSS) treatment is based primarily on the clinical criteria providing that imaging confirms radiological stenosis. The radiological measurement more commonly used is the dural sac cross-sectional area (DSCA). It has been recently shown that grading stenosis based on the morphology of the dural sac as seen on axial T2 MRI images, better reflects severity of stenosis than DSCA and is of prognostic value. This radiological prospective study investigates the variability of surface measurements and morphological grading of stenosis for varying degrees of angulation of the T2 axial images relative to the disc space as observed in clinical practice. MATERIALS AND METHODS: Lumbar spine TSE T2 three-dimensional (3D) MRI sequences were obtained from 32 consecutive patients presenting with either suspected spinal stenosis or low back pain. Axial reconstructions using the OsiriX software at 0°, 10°, 20° and 30° relative to the disc space orientation were obtained for a total of 97 levels. For each level, DSCA was digitally measured and stenosis was graded according to the 4-point (A-D) morphological grading by two observers. RESULTS: A good interobserver agreement was found in grade evaluation of stenosis (k = 0.71). DSCA varied significantly as the slice orientation increased from 0° to +10°, +20° and +30° at each level examined (P < 0.0001) (-15 to +32% at 10°, -24 to +143% at 20° and -29 to +231% at 30° of slice orientation). Stenosis definition based on the surface measurements changed in 39 out of the 97 levels studied, whereas the morphology grade was modified only in two levels (P < 0.01). DISCUSSION: The need to obtain continuous slices using the classical 2D MRI acquisition technique entails often at least a 10° slice inclination relative to one of the studied discs. Even at this low angulation, we found a significantly statistical difference between surface changes and morphological grading change. In clinical practice, given the above findings, it might therefore not be necessary to align the axial cuts to each individual disc level which could be more time-consuming than obtaining a single series of axial cuts perpendicular to the middle of the lumbar spine or to the most stenotic level. In conclusion, morphological grading seems to offer an alternative means of assessing severity of spinal stenosis that is little affected by image acquisition technique.

Prevalence, incidence and indications of hypno-sedative treatments in hospitalized patients aged 75 and older

Introduction Sleep impairment is a common problem in older persons and is associated with adverse health and economic consequences. The most prescribed hypnosedatives in Switzerland are benzodiazepines, benzodiazepine-like hypnosedatives and clomethiazole. In the elderly persons, these medications have been associated with decreased cognitive performance, an increased risk of addiction and an increased risk of falls. The main aim of this study was to determine the prevalence, incidence and indications of hypnosedative prescriptions in older in-patients admitted to a Swiss university hospital. Furthermore, we planned to investigate the possible relationship between hypnosedatives' prescription and patients' falls during the hospital stay and we compared the prevalence of hypnosedative drugs' prescribing between geriatric and non-geriatric clinical wards.Materials & Methods This observational study included all patients aged 75 years or older admitted to a Swiss university hospital for 24 h or more. Prescription-related data were recorded every day for 26 consecutive days in the two geriatric wards, and twice, a week apart, in three non-geriatric wards.Results A total of 204 patients (mean age 84.7 ± 0.7 years, 66% women) were included. The prevalence of hypnosedative drugs prescription was 73% and the incidence was 28% on the two geriatric wards. The most common indications for a prescription on geriatric wards was insomnia (51%), followed by continuation of usual treatment (12%). The most frequently prescribed hypnosedative drug was clomethiazole (64% of the patients), followed by lorazepam (11%). We were not able to demonstrate any significant correlation between the number of hypnosedative drugs prescribed and the number of falls during hospital stay. The prevalence of hypnosedative drugs prescriptions was similar between geriatric and non-geriatric wards. The proportion of patients treated by at least one hypnosedative increased between hospital admission (32%) and discharge (45%).Discussions, Conclusion This study reveals a high prevalence of hypnosedative prescription in medical in-patients aged 75 years or older. Main indication was insomnia and the most frequently prescribed hypnosedative molecule was clomethiazole. Prescription incidence was also very high and the proportion of patients being prescribed a hypnosedative increased during hospital stay. Systematic interventions need to be integrated in order to reduce elderly inpatient exposure to treatments that are associated with adverse health outcomes.Conference information: ESCP 40th International Symposium on Clinical Pharmacy. Clinical Pharmacy: Connecting Care and Outcomes Dublin Ireland, 19-21 October 2011

Cerebral perfusion CT in the evaluation of children with severe head trauma : 12.06

Purpose: To assess the value of cerebral perfusion CT (PCT) in children with traumatic brain injury in prediciting their consecutive clinical outcome. Materials and methods: Twelve paediatric patients with acute traumatic brain injury underwent cerebral CT coupled with PCT during their admission at the emergency room (ER). PCT maps were reviewed for mean transit time (MTT), regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) abnormalities. PCT results were compared to short- and mid-term clinical outcome. Results: 3 patients with low Glasgow Coma Scale (GCS) (98) and bad clinical outcome showed an increased MTT and decreased rCBV and rCBF. 5 patients with low GCS and good clinical outcome showed an increased MTT without abnormalities of rCBV and rCBF. In patients with GCS 08 and good outcome, PCT maps were normal in 2 cases; transient PCT abnormalities were identified in one case with an embedded fracture of the skull and in one case with an epileptic seizure. Conclusion: Cerebral PCT can identify diffuse abnormalities of cerebral perfusion in children with traumatic brain injury showing a low initial GCS and a bad outcome. PCT can be a valuable tool to predict the severity of the prognosis of these patients as soon as they are evaluated by CT-scan during their admission at the ER.

Biological materials in colorectal surgery: current applications and potential for the future.

Biological materials are increasingly used in abdominal surgery for ventral, pelvic and perineal reconstructions, especially in contaminated fields. Future applications are multi-fold and include prevention and one-step closure of infected areas. This includes prevention of abdominal, parastomal and pelvic hernia, but could also include prevention of separation of multiple anastomoses, suture- or staple-lines. Further indications could be a containment of infected and/or inflammatory areas and protection of vital implants such as vascular grafts. Reinforcement patches of high-risk anastomoses or unresectable perforation sites are possibilities at least. Current applications are based mostly on case series and better data is urgently needed. Clinical benefits need to be assessed in prospective studies to provide reliable proof of efficacy with a sufficient follow-up. Only superior results compared with standard treatment will justify the higher costs of these materials. To date, the use of biological materials is not standard and applications should be limited to case-by-case decision.

Does readiness to change predict subsequent alcohol consumption in medical inpatients with unhealthy alcohol use?

We studied whether readiness to change predicts alcohol consumption (drinks per day) 3 months later in 267 medical inpatients with unhealthy alcohol use. We used 3 readiness to change measures: a 1 to 10 visual analog scale (VAS) and two factors of the Stages of Change Readiness and Treatment Eagerness Scale: Perception of Problems (PP) and Taking Action (TA). Subjects with the highest level of VAS-measured readiness consumed significantly fewer drinks 3 months later [Incidence rate ratio (IRR) and 95% confidence interval (CI): 0.57 (0.36, 0.91) highest vs. lowest tertile]. Greater PP was associated with more drinking [IRR (95%CI): 1.94 (1.02, 3.68) third vs. lowest quartile]. Greater TA scores were associated with less drinking [IRR (95%CI): 0.42 (0.23, 0.78) highest vs. lowest quartile]. Perception of Problems' association with more drinking may reflect severity rather than an aspect of readiness associated with ability to change; high levels of Taking Action appear to predict less drinking. Although assessing readiness to change may have clinical utility, assessing the patient's planned actions may have more predictive value for future improvement in alcohol consumption.

A 10-year experience in paediatric spontaneous cerebral hemorrhage: which children with headache need more than a clinical examination?

INTRODUCTION: When a child is seen in a clinic with a headache, stroke is certainly not the first on the list of differential diagnoses. In western countries, stroke is typically associated with adults and the elderly. Although rare, haemorrhagic strokes are not exceptional in the paediatric population, as their incidence is around 1/100 000/year. Prompt diagnosis is essential, since delayed treatment may lead to disastrous prognosis in these children. MATERIALS AND METHODS: This is a retrospective review of paediatric cases with spontaneous cerebral haemorrhage that presented in two university hospitals in the last ten years. The experience of these primary and tertiary referral centres comprises 22 consecutive cases that are analysed according to aetiology, presenting symptoms, treatment and outcome. RESULTS: 77% of the children diagnosed with haemorrhagic stroke presented with headaches. 41% of them had a sudden onset, while 9% developed headaches over a period of hours to weeks. While 9% presented only with headaches, the majority had either subtle (diplopia, balance problems) or obvious (focal deficits, unilateral weakness and decreased level of consciousness) concomitant neurological signs. 55% had an arteriovenous malformation (AVM), 18% had an aneurysm and 14% had a cavernous malformation. In 14% the aetiology could not be determined. The majority of haemorrhages (82%) were supratentorial, while 18% bled into the posterior fossa. All children underwent an emergency cerebral CT scan followed by specific investigations. The treatment was dependent on the aetiology as well as the mass effect of the haematoma. In 23% an emergent evacuation of the haematoma was performed. Two children (9%) died, and 75% had a favourable clinical outcome. CONCLUSION: Headaches in children are a common problem, and a small minority may reveal an intracranial haemorrhage with poor prognosis if not treated promptly. Although characterisation of headaches is more difficult in a paediatric population, sudden, unusual or intense headaches should lead to imaging work-up. Any neurological finding, even one as subtle as hemianopsia or dysmetria, should alarm the physician and should be followed by emergency imaging investigation. If the cerebral CT reveals a haemorrhage, the child should be referred immediately to a neurosurgical referral centre without further investigation. The outcome is grim for children presenting in coma with fixed, dilated pupils. The long-term result overall for children after spontaneous intracranial haemorrhage is not dismal and depends critically on specialised management.

Marginal adaptation in vitro and clinical outcome of Class V restorations

OBJECTIVES: We examined the correlation between the quantitative margin analysis of two laboratory test methods (Berlin, Zurich) and the clinical outcome in Class V restorations. METHODS: Prospective clinical studies with an observation period of at least 18 months were searched in the literature, for which laboratory data were also available. The clinical outcome variables were retention loss, marginal discoloration, detectable margins and secondary caries. Forty-four clinical studies matched the inclusion criteria, including 34 adhesive systems for which laboratory data were also present. For both laboratory test methods and the clinical studies, an index was formulated to better compare the in vitro and in vivo results. Linear mixed models which included a random study effect were calculated. As most clinical data were available for 12 and 24 months, the main analysis was restricted to these recall intervals. RESULTS: The comparative analysis revealed a weak correlation between the clinical index and both in vitro indices. The correlation was statistically significant for the Berlin method but not for the Zurich method and only present if studies were compared which used the same composite in the in vitro and in vivo study. When defining specific cut-off values, the prognosis for the good clinical performance of an adhesive system based on in vitro results was 78% (Berlin) or 100% (Zurich). For poor performance it was 67% and 60%, respectively. No correlation was found between both in vitro methods. SIGNIFICANCE: The surrogate parameter "marginal adaptation" of restorations placed in extracted teeth has a mediocre value to predict the clinical performance of an adhesive system in cervical cavities. The composite is an important factor for a successful prediction. The comparison between in vitro/in vivo is sometimes hampered by the great variability of clinical results on the same adhesive system.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Factors associated with clinical leptospirosis: a population-based case-control study in the Seychelles (Indian Ocean).

BACKGROUND: In Western countries, leptospirosis is uncommon and mainly occurs in farmers and individuals indulging in water-related activities. In tropical countries, leptospirosis can be up to 1000 times more frequent and risk factors for this often severe disease may differ. METHODS: We conducted a one-year population-based matched case-control study to investigate the frequency and associated factors of leptospirosis in the entire population of Seychelles. RESULTS: A total of 75 patients had definite acute leptospirosis based on microagglutination test (MAT) and polymerase chain reaction (PCR) assay (incidence: 101 per 100,000 per year; 95% confidence interval [CI]: 79-126). Among the controls, MAT was positive in 37% (past infection) and PCR assay in 9% (subclinical infection) of men aged 25-64 with manual occupation. Comparing cases and controls with negative MAT and PCR, leptospirosis was associated positively with walking barefoot around the home, washing in streams, gardening, activities in forests, alcohol consumption, rainfall, wet soil around the home, refuse around the home, rats visible around the home during day time, cats in the home, skin wounds and inversely with indoor occupation. The considered factors accounted for as much as 57% of the variance in predicting the disease. CONCLUSION: These data indicate a high incidence of leptospirosis in Seychelles. This suggests that leptospires are likely to be ubiquitous and that effective leptospirosis control in tropical countries needs a multifactorial approach including major behaviour change by large segments of the general public.

Comparability of clinical wear measurements by optical 3D laser scanning in two different centers.

OBJECTIVE: The purpose of this study was to compare the use of different variables to measure the clinical wear of two denture tooth materials in two analysis centers. METHODS: Twelve edentulous patients were provided with full dentures. Two different denture tooth materials (experimental material and control) were placed randomly in accordance with the split-mouth design. For wear measurements, impressions were made after an adjustment phase of 1-2 weeks and after 6, 12, 18, and 24 months. The occlusal wear of the posterior denture teeth of 11 subjects was assessed in two study centers by use of plaster replicas and 3D laser-scanning methods. In both centers sequential scans of the occlusal surfaces were digitized and superimposed. Wear was described by use of four different variables. Statistical analysis was performed after log-transformation of the wear data by use of the Pearson and Lin correlation and by use of a mixed linear model. RESULTS: Mean occlusal vertical wear of the denture teeth after 24 months was between 120μm and 212μm, depending on wear variable and material. For three of the four variables, wear of the experimental material was statistically significantly less than that of the control. Comparison of the two study centers, however, revealed correlation of the wear variables was only moderate whereas strong correlation was observed among the different wear variables evaluated by each center. SIGNIFICANCE: Moderate correlation was observed for clinical wear measurements by optical 3D laser scanning in two different study centers. For the two denture tooth materials, wear measurements limited to the attrition zones led to the same qualitative assessment.