The Toronto IBD Global Endoscopic Reporting [TIGER] Score: A Single, Easy to Use Endoscopic Score for Both Crohn's Disease and Ulcerative Colitis Patients.

BACKGROUND AND AIMS: We constructed the Toronto IBD Global Endoscopic Reporting [TIGER] score for inflammatory bowel disease [IBD]. The aim of our study was to develop and validate the TIGER score against faecal calprotectin [FC], C-reactive protein [CRP], and IBD Disk. METHODS: A cross-sectional study was performed among 113 adult patients (60 Crohn's disease [CD] and 53 ulcerative colitis [UC]). In the development and usability phase, blinded IBD experts reviewed and graded ileocolonoscopy videos. In the validity phase the TIGER score was compared with: [1] the Simple endoscopic Score for CD [SES-CD] and the Mayo endoscopic score in CD and UC, respectively; [2] FC and CRP; and [3] IBD Disk. RESULTS: Inter-observer reliability of the TIGER score per segment between reviewers was excellent: interclass correlation coefficient [ICC] = 0.94 [95% CI: 0.92-0.96]. For CD patients, overall agreement per segment between SES-CD and TIGER was 91% [95% CI: 84-95] with kappa coefficient 0.77 [95% CI: 0.63-0.91]. There was a significant correlation between TIGER and CRP [p <0.0083], and TIGER and FC [p <0.0001]. In addition, there was significant correlation between TIGER and IBD Disk [p <0.0001]. For UC patients, overall agreement per segment between Mayo endoscopic score and TIGER was 84% [95% CI: 74%-90%] and kappa coefficient 0.60 [95% CI: 0.42-0.808]. There was a significant correlation between TIGER and FC [p <0.0001]. There was a significant correlation between TIGER and IBD Disk [p <0.0001]. CONCLUSIONS: The TIGER score is a reliable and simple novel endoscopic score that can be used for both CD and UC patients and captures full endoscopic disease burden.

Ileal pouch-anal anastomosis for ulcerative colitis: a Canadian institution's experience.

BACKGROUND: We aimed to summarize the outcomes of ulcerative colitis (UC) patients receiving an ileal pouch-anal anastamosis (IPAA) over an 11-year period at a high-volume Canadian inflammatory bowel disease (IBD) center. METHODS: A retrospective chart review was performed for subjects with UC who underwent IPAA between 2002 and 2013. Patient charts were reviewed for demographic data, clinical characteristics, preoperative medical treatment, and surgical outcomes. Univariate and multivariate logistic regression modeling were used to determine significant factors in postoperative outcomes. RESULTS: Seven hundred fifty-eight were included from the IBD database. The median age at the time of surgery was 37.1 (±12.1). Mean preoperative disease duration was 8.1 years (±8.7). Three hundred sixty-nine patients (48.7 %) had systemic corticosteroids (>15 mg/day) within 30 days prior to surgery. Of these, 286 patients had high dose (>30 mg/day) corticosteroids within 7 days of their first surgery. One hundred nine (14.0 %) IPAA procedures were performed laparoscopically. Pelvic pouches were created in traditional 2 (n = 460) and 3 (n = 285) stages; the remainder (n = 13) was performed in non-traditional staged operations. Early complications, defined as occurring within the same stay in hospital, consisted of pelvic abscess (n = 135, 17.8 %), small bowel obstruction (n = 134, 17.7 %), wound infection (n = 108, 14.3 %), and deep vein thrombosis (n = 33, 4.4 %). The overall pouch leak rate was 92 (12.1 %). There was one death in our study. The median length of stay was 10.3 days (SD6.0). Late complications, defined as occurring after discharge from hospital, consisted of anal stricture (n = 55, 7.3 %), pouch fistula (n = 26, 3.4 %), and functional pouch failure (n = 7, 0.9 %). CONCLUSIONS: IPAA has been found to be a safe and effective method of surgical management of UC patients in a high-volume IBD center.

A role for TENM1 mutations in congenital general anosmia.

Congenital general anosmia (CGA) is a neurological disorder entailing a complete innate inability to sense odors. While the mechanisms underlying vertebrate olfaction have been studied in detail, there are still gaps in our understanding of the molecular genetic basis of innate olfactory disorders. Applying whole-exome sequencing to a family multiply affected with CGA, we identified three members with a rare X-linked missense mutation in the TENM1 (teneurin 1) gene (ENST00000422452:c.C4829T). In Drosophila melanogaster, TENM1 functions in synaptic-partner-matching between axons of olfactory sensory neurons and target projection neurons and is involved in synapse organization in the olfactory system. We used CRISPR-Cas9 system to generate a Tenm1 disrupted mouse model. Tenm1(-/-) and point-mutated Tenm1(A) (/A) adult mice were shown to have an altered ability to locate a buried food pellet. Tenm1(A) (/A) mice also displayed an altered ability to sense aversive odors. Results of our study, that describes a new Tenm1 mouse, agree with the hypothesis that TENM1 has a role in olfaction. However, additional studies should be done in larger CGA cohorts, to provide statistical evidence that loss-of-function mutations in TENM1 can solely cause the disease in our and other CGA cases.

Higher Adalimumab Drug Levels are Associated with Mucosal Healing in Patients with Crohn's Disease.

BACKGROUND AND AIMS: The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 µg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn's disease (CD). METHODS: A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey-Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay. RESULTS: Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl (p = 6.93×10(-6)). Higher adalimumab trough level was significantly associated with MH (median 14.7 µg/mL in those with MH vs 3.4 µg/mL in those without, p = 6.25×10(-5)). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 µg/mL, p = 5.36×10(-3)). A cut-off of 8.14 µg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively). CONCLUSIONS: Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 µg/mL.

A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.

BACKGROUND: Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy. AIM: To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications. METHODS: A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period. RESULTS: Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients. CONCLUSIONS: A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.

Osteomielitis en niños experiencia en el Hospital Dr. Domingo Luciani / Osteomyelitis in children: experience in the Hospital Dr. Domingo Luciani

En el lapso comprendido entre abril 1988 y octubre 1995, se presentaron 41 casos de osteomielitis en el servicio de Pediatría del Hospital Dr. Domingo Luciani, 35 del sexo masculino (85,4 por ciento) y 6 del sexo femenino (14,6 por ciento), con edades compredidas entre los 0 y 8 años. Los motivos de consulta principales fueron: aumento de volumen y dolor en la zona afectada. El proceso infeccioso se ubicó con mayor frecuencia en huesos largos a predominio de miembros inferiores. El 53,6 por ciento de los pacientes registró como antecedente un traumatismo previo. El Stafilococcus aureus fue aislado en 11 casos (39,3 por ciento), siguiendo en frecuencia la Pseudomona aeruginosa en 3 casos (10,7 por ciento). Los pacientes recibieron tratamiento médico en todos los casos, se realizó limpieza quirúrgica en un 51,2 por ciento