Sengstaken-Blakemore tube in critical upper gastrointestinal bleeding: Implications for aeromedical retrieval.

Sengstaken-Blakemore tubes (SBTs) are rarely used in Australia, because of improved access to endoscopy and interventional radiology, as well as overall lower rate of variceal haemorrhage from improvements in primary prophylaxis. SBT's use is associated with significant rate of serious complications, such as oesophageal perforation, mucosal necrosis, aspiration pneumonia and respiratory compromise secondary to external compression of the trachea. As such, SBT is currently only recommended for use in life-threatening variceal haemorrhage, where endoscopic, embolization and pharmacologic therapy have been unsuccessful or are unavailable. No data exist for its use in Australasia but one area that it could be indicated is for hemodynamically unstable patients in remote setting, where long transfer times often means delayed access to endoscopy. We present a case of SBT insertion in retrieval medicine and discuss placement in the management of an unstable upper gastrointestinal bleed, complicating factors such as lack of radiology to confirm balloon position, the impact of flight altitude on balloon pressures, the maintenance of traction in flight and logistics of long flight times across the state of Queensland. This is the first case report of SBT use in the Australian aeromedical environment. It is also the first one where SBT has been used for duodenal bleeding, although the source of bleeding was unknown prior to insertion.

Evaluation of a Multidisciplinary Integrated Treatment Approach Versus Standard Model of Care for Functional Gastrointestinal Disorders (FGIDS): A Matched Cohort Study.

BACKGROUND: Functional gastrointestinal disorders (FGID) are linked to a variety of potential causes, and treatments include reassurance, life-style (including diet), psychological, or pharmacologic interventions. AIMS: To assess whether a multidisciplinary integrated treatment approach delivered in a dedicated integrated care clinic (ICC) was superior to the standard model of care in relation to the gastrointestinal symptom burden. METHODS: A matched cohort of 52 consecutive patients with severe manifestation of FGID were matched with 104 control patients based upon diagnosis, gender, age, and symptom severity. Patients in the ICC received structured assessment and 12-weeks integrated treatment sessions provided as required by gastroenterologist and allied health team. Control patients received standard medical care at the same tertiary center with access to allied health services as required but no standardized interprofessional team approach. Primary outcome was reduction in gastrointestinal symptom burden as measured by the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS). Secondary outcome was reduction in anxiety and depressive symptoms as measured by the Hospital Anxiety and Depression Scale (HADS). RESULTS: Mixed models estimated the within ICC change in SAGIS total as -9.7 (95% CI -13.6, -5.8; p < 0.0001), compared with -1.7 (95% CI -4.0, 0.6; p = 0.15) for controls. The difference between groups reached statistical significance, -7.6 (95% CI -11.4, -3.8; p < 0.0001). Total HADS scores in ICC patients were 3.4 points lower post-intervention and reached statistical significance (p = 0.001). CONCLUSION: This matched cohort study demonstrates superior short-term outcomes of FGID patients in a structured multidisciplinary care setting as compared to standard care.

Maladaptive coping, low self-efficacy and disease activity are associated with poorer patient-reported outcomes in inflammatory bowel disease.

BACKGROUND/AIMS: Patient-reported outcomes (PRO) are key aspects in the management of inflammatory bowel disease (IBD). This study aims to evaluate factors associated with adverse PRO, including modifiable social constructs of maladaptive coping and self-efficacy as well as physician-patient concordance on PRO. PATIENTS AND METHODS: This cross-sectional study was performed in patients with Crohn's disease (CD) or ulcerative colitis (UC) from September 2015 to March 2016. Validated questionnaires were used to assess quality of life (Short IBD Questionnaire), disability (IBD disability index), productivity (work productivity and activity impairment questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale), coping strategies [Brief Coping Operations Preference Enquiry (Brief COPE)], and self-efficacy (General Self-Efficacy Scale). Independent physician assessment was used to compare concordance with patients. RESULTS: In all, 207 (CD: 144 and UC: 63) patients, with median age of 39 years, were included, with 42.5% males. Significant proportion of patients reported moderate/severe impairment of disability (30.5%), quality of life (29.4%), productivity (52.4%), anxiety (32.9%) and depression (23.3%). Disease activity and maladaptive coping were independently associated with unfavourable PRO, whereas self-efficacy had a positive effect in multivariate analysis. Physicians could accurately identify the magnitude of PRO impairment in standard clinical settings (r = 0.59-0.65, P < 0.001). CONCLUSION: Disease activity and modifiable psychological constructs are associated with unfavorable PRO in patients with IBD. These factors could assist with identifying high-risk patients, many of whom may benefit from targeted interventions to improve health outcomes.

Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis.

BACKGROUND: Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis. METHODS: Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported. RESULTS: Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels. CONCLUSIONS: In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography.

Background: Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. Methods: We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. Results: A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). Conclusions: NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.

High-Dose Infliximab Rescue Therapy for Hospitalized Acute Severe Ulcerative Colitis Does Not Improve Colectomy-Free Survival.

BACKGROUND AND OBJECTIVE: Optimization strategies with infliximab (IFX) are increasingly used as rescue therapy for steroid refractory acute severe ulcerative colitis (ASUC). We aim to determine if intensified IFX induction improves colectomy rate and identifies outcome predictors. METHODS: Hospitalized adult patients who received IFX for ASUC between 2010 and 2016 were identified. We compared standard inductions (5 mg/kg) vs high-dose induction (10 mg/kg) with 3-month colectomy rate as primary outcome. RESULTS: Seventy-two patients (62.5% male, median age 38.5) were identified. Thirty-seven patients (51.3%) received 5 mg/kg IFX and 35 received 10 mg/kg. Baseline clinical, biochemical and endoscopic parameters were well matched between these two groups. 10 mg/kg was more likely to be used by clinicians from 2014 onwards (p < 0.001). Three-month colectomy rate was 9.7%; which was not significantly different between the standard (5.4%) and high-dose (14.3%) IFX induction (p = 0.205). CRP ≥ 60 (OR 10.9 [95% CI 1.23-96.50], p = 0.032), hemoglobin ≤ 90 g/L (OR 15.6 [95% CI 2.61-92.66], p = 0.036) and albumin < 30 g/L (OR 9.4 [95% CI 1.06-83.13], p = 0.044) were associated with increased risk of colectomy at 3 months in univariate regression analysis. CONCLUSION: Use of high-dose infliximab rescue therapy did not improve 3-month colectomy-free survival in this cohort. Tailored use in high-risk patients may be beneficial although further validation is required.

Management of Paediatric Patients With Medically Refractory Crohn's Disease Using Ustekinumab: A Multi-Centred Cohort Study.

BACKGROUND: Ustekinumab [UST] is effective in the treatment of adults with moderate to severe Crohn's disease [CD]. There is a paucity of data on its use in children. AIM: To evaluate the response to UST in children with moderate to severe CD. METHODS: This multicentre retrospective cohort study identified children under 18 years old with CD, who received open-labelled subcutaneous UST. The primary outcome was changes in mean abbreviated Paediatric Crohn's Disease Activity Index [aPCDAI] between baseline and 3 and 12 months, and rate of clinical remission at 3 and 12 months. Secondary outcomes were clinical response at the same time points, changes in C-reactive protein [CRP] and albumin, improvement in growth parameters, and rate of adverse events. RESULTS: A total of 44 patients who failed at least one biological treatment were identified. Linear mixed model [LMM] analysis revealed a statistically significant effect of UST (χ2[1] = 42.7, p = 1.2 × 10-8) which lowered the aPCDAI scores by about 16 ± 2.7 at 3 months, and 19.6 ± 2.9 at 12 months. At 12 months, 38.6% of the patients achieved clinical remission and 47.8% achieved clinical response. There was a significant increase in mean weight z-score of 0.48 [±0.13] [p <0.001] and in mean body mass index [BMI] z score of 0.66 [±0.16] [p <0.001]. The probability of remaining on UST at 12 months was 76.9%. The rate of adverse events was 12.4 per 1000 patient-months. CONCLUSIONS: Subcutaneous UST should be considered a viable therapeutic option for paediatric patients who are refractory to other biological agents. Prospective randomised trials are needed.

Clinical Parameters Correlate With Endoscopic Activity of Ulcerative Colitis: A Systematic Review.

BACKGROUND & AIMS: Optimal management of patients with ulcerative colitis (UC) requires assessment of disease activity-usually by endoscopy, which is invasive, costly, and not risk free. We performed a systematic review to determine whether clinical symptoms correlate with findings from endoscopy assessments of patients with UC. METHODS: We performed a systematic review of publication databases from January 1980 through July 2018 to identify clinical trials and observational studies reporting correlations among symptoms, disease activity index scores and/or patient reported outcomes (rectal bleeding and/or stool frequency), and endoscopic disease activity. Correlations were ascertained in patients with active vs inactive disease and by disease extent and treatment type. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Because of significant heterogeneity, meta-analysis was not possible. Results were synthesized qualitatively and systematically. RESULTS: Our final analysis included 23 studies (1 randomized trial, 22 observational studies) comprising 3320 patients with UC. The studies used a variety of measures to assess clinical activity, endoscopic activity, and measures of correlation (sensitivity, specificity, correlation coefficients, area under the receiver operator curve). Overall, studies were at moderate-high risk of bias. Composite clinical measures, including rectal bleeding and stool frequency, had moderate to strong correlations with endoscopic disease activity; the absence of rectal bleeding identified patients with inactive disease with higher levels of sensitivity than normalization of stool frequency. In general, symptoms correlated more strongly with endoscopic activity in patients with left-sided colitis than extensive colitis. The effect of different medications on the correlation between clinical and endoscopic activity has not been well studied. CONCLUSIONS: In a systematic review, we found a moderate to strong correlation between clinical activity, particularly the combination of rectal bleeding and stool frequency, and endoscopic activity in patients with UC. Although these clinical assessments could help prioritize patients for endoscopic evaluation in resource-limited settings, challenges associated with treating patients based on symptoms alone preclude adaptation of current management algorithms.

Unsuspected Small-Bowel Crohn's Disease in Elderly Patients Diagnosed by Video Capsule Endoscopy.

BACKGROUND: Video capsule endoscopy (VCE) is increasingly performed among the elderly for obscure bleeding. Our aim was to report on the utility of VCE to uncover unsuspected Crohn's disease (CD) in elderly patients. METHODS: Retrospective review of VCE performed in elderly patients (≥70 y) at a tertiary hospital (2010-2015). All underwent prior negative bidirectional endoscopies. CD diagnosis was based on consistent endoscopic findings, exclusion of other causes, and a Lewis endoscopic score (LS) > 790 (moderate-to-severe inflammation). Those with lower LS (350-790) required histological confirmation. Known IBD cases were excluded. RESULTS: 197 VCE were performed (mean age 78; range 70-93). Main indications were iron deficiency anemia (IDA), occult GI bleeding (OGIB), chronic abdominal pain, or diarrhea. Eight (4.1%) were diagnosed as CD based on the aforementioned criteria. Fecal calprotectin (FCP) was elevated in 7/8 (mean 580 µg/g). Mean LS was 1824. Small-bowel CD detected by VCE led to a change in management in 4/8. One patient had capsule retention secondary to NSAID induced stricture, requiring surgical retrieval. CONCLUSIONS: VCE can be safely performed in the elderly. A proportion of cases may have unsuspected small-bowel CD despite negative endoscopies. FCP was the best screening test. Diagnosis frequently changed management.

Therapeutic Drug Monitoring Guides the Management of Crohn's Patients with Secondary Loss of Response to Adalimumab.

Background: Managing loss of response (LOR) in Crohn's disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Methods: Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed. Primary outcomes were composite remission at 3, 6, and 12 months in those with empiric adjustments versus TDM-guided optimization. Results: There were 104 patients (54.8% men) who were included in the study. Of this group, 81 patients (77.9%) had serum level (SL) ≥5µg/ml at index TDM with a median value of 12µg/ml (IQR 6.1-16.5). There were 10 patients (9.6%) who had undetectable SL with high anti-ADA antibodies and 48 (46.2%) received empiric escalation. TDM led to change in treatment in 58 patients (55.8%). Among them, 28 (48.3%) had discontinued ADA, 12 (21.7%) had addition of immunomodulator or steroid, and 18 (31%) had ADA dose escalation. Empiric dose escalation before TDM-based optimization was not associated with improved outcomes at 3, 6, and 12 months, irrespective of SL levels. Clear SL cutoff associated with composite remission was not identified. Conclusions: Our data do not support empiric dose adjustment beyond that based on the result of the TDM in patients with LOR to ADA. TDM limits unnecessary dose escalation and provides appropriate treatment strategy without compromising clinical outcomes. 10.1093/ibd/izy044_video1izy044.video15768828880001.

Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases.

BACKGROUND: In inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn's disease. METHODS: We examined 9 patients with Crohn's disease (age 26.1±10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge. RESULTS: Following anti-TNFα treatment, ratings of 'fullness' following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings. CONCLUSION: In patients with Crohn's disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.

Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article.

Emerging data have highlighted the co-existence of non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease, largely due to differences in disease definition and diagnostic tools utilised in the studies. Age, obesity, insulin resistance and other metabolic conditions are common risks factors in observational studies. However, other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity, duration, steroid use and prior surgical intervention, in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability, gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity, however no definitive evidence exist linking them to the development of hepatic steatosis, nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification, intervention and improve patient outcomes.

Esophageal perforation, inflammatory mediastinitis and pseudoaneurysm of the thoracic aorta as potential complications of botulinum toxin injection for achalasia.

Primary achalasia is a motility disorder of the esophagus involving impaired relaxation of the esophageal sphincter and, in later stages, dilatation and aperistalsis of the tubular esophagus. Endoscopic botulinum toxin injection to the lower esophageal sphincter is an effective and safe option in the treatment algorithm of achalasia, particularly in high-surgical-risk patients. In the present case report, we describe a rare complication of esophageal perforation following botulinum injection, resulting in associated inflammatory mediastinitis and formation of a pseudoaneurysm in the descending aorta. To the authors' knowledge, this is the first report in the literature of this rare complication of endoscopic botulinum injection. A contributing factor might have been the use of an injecting device with a significantly longer adjustable needle. Endoscopists should remain clinically vigilant to the potential complications associated with this common procedure.

Prospective validation of cerebrospinal fluid bilirubin in suspected subarachnoid haemorrhage.

BACKGROUND: The recommended spectrophotometric scanning for diagnosis of subarachnoid haemorrhage (SAH) is relatively expensive, not fully automated and often requires expert interpretation. Analysis of cerebrospinal fluid (CSF) bilirubin offers an alternative approach and may obviate the need for scanning and, hence, we undertook a prospective validation study. METHODS: CSF bilirubin and spectrophotometric scans were compared from 193 patients in our institution over a two-year period and for this 162 clinical records (83.9%) were reviewed. CSF bilirubin was tested for its ability to predict elevated net bilirubin absorbance by spectrophotometry. Final outcomes were obtained by review of clinical records and contacting the New Zealand Health Information Service. RESULTS: From receiver operating characteristic curve analysis, there was an area under the curve of 0.99 (95% confidence interval: 0.97-1.00). At a cut-off of 359 nmol/L, corresponding to our upper reference interval, CSF bilirubin assay had a sensitivity of 100%, a specificity of 92.2% and a negative predictive value of 100%. There were no outcomes to suggest that SAH had been missed in any case. CONCLUSION: CSF bilirubin is a robust screening test that accurately identifies those samples needing to be scanned and eliminates the need for this to be done in most others.