Clinical outcomes at 12 months and risk of inflammatory bowel disease in patients with an intermediate raised fecal calprotectin : a ‘real-world’ view

Objectives: A recent systematic review confirmed the usefulness of fecal calprotectin (FC) in distinguishing organic (inflammatory bowel disease (IBD)) from non-organic gastrointestinal disease (irritable bowel syndrome (IBS)). FC levels 92% to exclude organic gastrointestinal (GI) disease. Levels >250 μg/g correlate with endoscopic IBD disease activity; sensitivity 90%. We aimed to determine clinical outcomes in intermediate raised FC results (50–250 μg/g). Setting: Primary care general practices in Coventry and Warwickshire, and 3 secondary care hospitals. Participants: 443 FC results in adults (>16 years old) were reviewed from July 2012 to October 2013. Clinical data was collected from hospital databases and general practitioners. Long-term clinical data was available in 41 patients (out of 48). Primary and secondary outcome measures: The number of new diagnoses of IBD, IBS and other diagnoses for the intermediate group. The number referred and discharged from secondary care. Results: A new IBD diagnosis was made in 19% (n=8) of intermediate results (1% of normal and 38% of raised results). 5% (n=2) of intermediate results had known IBD in remission. A new IBS diagnosis was made in 27% (n=11) of intermediate results, while 34% (n=14) remained undiagnosed, although 8 of these were not referred to secondary care. Conclusions: FC testing remains useful in aiding diagnosis of organic GI conditions. However, unlike negative and strongly positive FC results, intermediate FC results lead to a mixture of diagnoses. The OR of a new diagnosis of IBD for an intermediate result compared to normal FC result was 26.6, while an intermediate FC result gave an OR of 0.54 for a new IBS diagnosis compared to normal FC. For intermediate FC results, 1 in 3 patients remained in secondary care after 12 months with an OR of 3.6 compared to a normal FC result

The role of nitric oxide in the outgrowth of trophoblast cells on human umbilical vein endothelial cells

AbstractObjectiveEmbryo implantation is a complex process that requires coordinated trophoblast–endometrial interactions. Previous studies demonstrated that the identification of nitric oxide synthase (NOS) in trophoblast cells and the remodeling of the implantation process by nitric oxide (NO) support the important role of NO during implantation. However, the role of NO in trophoblast–endometrial interactions is unclear and is therefore examined in this study.Materials and methodsWe cocultured BeWo trophoblast spheroids with human umbilical vein endothelial cell (HUVEC) monolayers to mimic the trophoblast–endometrial interaction. Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), a competitive inhibitor of NOS, and sodium nitroprusside (SNP), an NO donor, were used to test the role of NO in the trophoblast–endometrial interaction.Resultsl-NAME diminished spheroid expansion on HUVEC monolayers in a concentration-dependent manner (p < 0.05). However, trophoblast spreading on HUVEC-free culture surfaces was unaffected by l-NAME treatment (p > 0.05). Significant suppression of spheroid expansion was found at the higher dose (1mM) of SNP (p < 0.05).ConclusionNO may be needed in the process of implantation, and an adequate but not overly NO-containing environment might be an important factor for successful implantation. This finding is worthy of further investigation

Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

BACKGROUND: We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome. PATIENTS AND METHODS: Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25), PAD (N = 31), VTD (N = 35)]. and received thalidomide maintenance for 2 years post-ASCT. RESULTS: 43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. CONCLUSIONS: These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals

Vancomycin-resistant Enterococcal Bacteremia in a Hematology Unit: Molecular Epidemiology and Analysis of Clinical Course

An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hemato-oncological patients (n=19) in our institution from 2000 through 2001 led us to analyze the molecular epidemiologic patterns and clinical features unique to our cases. The pulsed field gel electrophoresis of the isolates revealed that the bacteremia was not originated from a single clone but rather showed endemic pattern of diverse clones with small clusters. A different DNA pattern of blood and stool isolates from one patient suggested exogenous rather than endogenous route of infection. Enterococcus faecium carrying vanA gene was the causative pathogen in all cases. Patients with VRE bacteremia showed similar clinical courses compared with those with vancomycin-susceptible enterococcal (VSE) bacteremia. Vancomycin resistance did not seem to be a poor prognostic factor because of similar mortality (5/8, 62.5%) noted in VSE bacteremia. Initial disease severity and neutropenic status may be major determinants of prognosis in patients with VRE bacteraemia

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Hierarchical Face Modeling and Fast 3D Facial Expression Synthesis

This paper presents a new hierarchical facial model that conforms to the human anatomy for realistic and fast 3D facial expression synthesis. The facial model has a skin/muscle/skull structure. The deformable skin model uses a kind of nonlinear springs to directly simulate the nonlinear visco-elastic behavior of soft tissue, and a new kind of edge repulsion springs is developed to prevent model collapse. The incorporation of the skull extends the scope of facial motion and facilitates facial muscle construction. The construction of facial muscles is achieved by using an efficient muscle mapping approach that ensures different muscles to be located at the anatomically correct positions. For computational efficiency, we devise an adaptive simulation algorithm which uses either a semi-implicit integration scheme or a quasi-static solver to compute the relaxation by traversing the designed data structures in a breadth-first order. The algorithm runs in real-time and has successfully synthesized realistic facial expressions