Correlation Between Serum and Fecal Biomarkers and Patient-Reported Outcomes in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). AIM: The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. METHODS: We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. RESULTS: 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6 years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. CONCLUSION: PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.

Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

Gastrointestinal Hemorrhage and Diffuse Bowel Dilation in Huntington Disease.

Huntington disease (HD) is a neurodegenerative condition associated with pathologic involvement beyond the striatum including involvement of the autonomic nervous system. Bowel dysfunction is found in patients with HD, but the exact mechanism is poorly understood and not well reported. Patients may be affected with problems such as dysphagia, weight loss, nutritional deficiencies, esophagitis, and gastritis. Lower bowel symptoms are more prevalent with longer disease course. We present a case of a patient with late-stage HD who presents with severe esophagitis causing gastrointestinal hemorrhage, significant dysmotility including chronic dysphagia requiring gastrostomy tube, and chronic small bowel and colonic ileus.

The Sigmoid Colon as an Unusual Primary Site of T Cell Lymphoma in a Patient Presenting With Brain Metastasis.

Intestinal T-cell lymphomas are an uncommon type of gastrointestinal malignancy, primarily found in the stomach and small bowel. The liver represents the most common distant organ for metastasis in gastrointestinal malignancies, followed by the lungs. Brain and muscular metastases are rare. We present intestinal T-cell lymphoma with a primary site in the sigmoid colon and metastasis to the brain, meninges, and psoas muscle. Biopsy of the malignant mass confirmed intestinal T-cell lymphoma. To our knowledge, this is the first colon T-cell lymphoma with primary brain and meningeal metastasis with another uncommon site of muscular metastasis.

Factors Associated With Extraintestinal Manifestations of Inflammatory Bowel Disease in SPARC-IBD.

BACKGROUND: Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD, yet predicting who may develop them is difficult. The goal of our study was to better characterize which patients may be at highest risk of developing not only 1 EIM, but also multiple EIMs, across both diseases. METHODS: A retrospective study of participants enrolled in the SPARC IBD (Study of Prospective Adult Research Cohort with IBD) registry was performed, and demographic and clinical data were analyzed. A total of 1211 patients with data available on EIMs were included, and differences among variables with vs without EIMs were assessed. RESULTS: A total of 329 participants with at least 1 EIM were identified, compared with 882 participants without any EIMs. Crohn's disease patients and women were more likely to have 2 or more EIMs (P = .005 and P ≤ .001, respectively). Participants with ocular manifestations were likeliest to have at least 2 EIMs (P ≤ .001). Even when diagnosis was controlled for, involvement of the right colon (P = .021) was predictive of IBD-associated arthritis across both diseases in a multivariate generalized linear model. CONCLUSIONS: This is the first comprehensive large-cohort assessment of how EIMs relate to one another at the individual vs systems levels. Further, our analysis is the first to recognize specific locations of colon involvement associated with EIMs of IBD, regardless of IBD type. These results are important in identifying patients at risk of developing future EIMs and may help with risk stratification when choosing treatments.

Although extraintestinal manifestations frequently complicate inflammatory bowel disease, predicting those at highest risk of developing them is difficult. We found female patients with Crohn's disease, ocular, and dermatologic manifestations are likeliest to develop multiple extraintestinal manifestations. Further, we found right-sided involvement is predictive of inflammatory bowel disease­associated arthritis.

Impact of Holding Immunosuppressive Therapy in Patients with Inflammatory Bowel Disease Around mRNA COVID-19 Vaccine Administration on Humoral Immune Response and Development of COVID-19 Infection.

BACKGROUND AND AIMS: The BNT162b2 and mRNA-1273 COVID-19 vaccines are efficacious in patients with inflammatory bowel disease; but there is a lack of data examining if holding immunosuppressive therapy around vaccination improves immune response. We studied the effect of holding IBD medications around the time of vaccination on antibody response and breakthrough COVID-19 infection. METHODS: Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID is a prospective cohort of individuals with IBD receiving COVID-19 vaccination. Quantitative measurement of anti-receptor binding domain IgG antibodies to SARS-CoV-2 was performed 8 weeks after completing a vaccination series. RESULTS: A total of 1854 patients were included; 59% were on anti-tumour necrosis factor [TNF] [10% of these on combination therapy], 11% on vedolizumab, and 14% on ustekinumab; 11% of participants held therapy before or after vaccine administration for at least 2 weeks. Antibody levels were similar in participants continuing versus holding anti-TNF monotherapy before or after the second vaccine [BNT162b2: 10 µg/mL vs 8.9 µg/mL; mRNA-1273: 17.5 µg/mL vs 14.5 µg/mL]. Comparable results were seen in those on combination therapy. Antibody titres in those on ustekinumab or vedolizumab were higher compared with anti-TNF users, but there was no significant difference if the drug was held or continued [BNT162b2: 22.5 µg/mL vs 23 µg/mL; mRNA-1273: 88 µg/mL vs 51 µg/mL]. Holding therapy was not associated with decreased rate of COVID-19 infection compared with those not holding therapy [BNT162b2: 28% vs 29%; mRNA-1273: 19% vs 31%]. CONCLUSION: We recommend continuing IBD medications while receiving mRNA COVID-19 vaccination without interruption.

Impact of Palliative Care on Interhospital Transfers to the Intensive Care Unit.

Community hospitals will often transfer their most complex, critically ill patients to intensive care units (ICUs) of tertiary care centers for specialized, comprehensive care. This population of patients has high rates of morbidity and mortality. Palliative care involvement in critically ill patients has been demonstrated to reduce over-utilization of resources and hospital length of stays. We hypothesized that transfers from community hospitals had low rates of palliative care involvement and high utilization of ICU resources. In this single-center retrospective cohort study, 848 patients transferred from local community hospitals to the medical ICU (MICU) and cardiac care unit (CCU) at a tertiary care center between 2016-2018 were analyzed for patient disposition, length of stay, hospitalization cost, and time to palliative care consultation. Of the 848 patients, 484 (57.1%) expired, with 117 (13.8%) having expired within 48 hours of transfer. Palliative care consult was placed for 201 (23.7%) patients. Patients with palliative care consult were statistically more likely to be referred to hospice (p<0.001). Over two-thirds of palliative care consults were placed later than 5 days after transfer. Time to palliative care consult was positively correlated with length of hospitalization among MICU patients (r=0.79) and CCU patients (r=0.90). Time to palliative consult was also positively correlated with hospitalization cost among MICU patients (r=0.75) and CCU patients (r=0.86). These results indicate early palliative care consultation in this population may result in timely goals of care discussions and optimization of resources.

Fecal Incontinence in Inflammatory Bowel Disease.

BACKGROUND: Fecal incontinence (FI) is frequently reported in inflammatory bowel disease (IBD). METHODS: We retrospectively reviewed data from the Study of a Prospective Adult Research Cohort with IBD registry. RESULTS: Three hundred forty-seven patients had Crohn disease and 145 had ulcerative colitis. 14.2% of patients reported FI. FI was associated with active disease. FI was not associated with disease location, phenotype, or perianal involvement. Greater than 50 years of age or 15 years of disease increased the odds of FI and remission decreased the odds of FI. CONCLUSIONS: Further research into the mechanism of FI in IBD is needed.

Iron pill induced gastritis causing severe anemia.

Iron supplementation is ubiquitously prescribed and considered a benign means of therapy. However, side effects such as iron pill gastritis can be life threatening prompting discontinuation. We describe a case of a 71-year-old man who presents with severe iron deficiency anemia on oral iron therapy. Esophagogastroduodenoscopy revealed mucosal injury in the fundus, including erythema and ulceration. Biopsy of the area was significant for pill debris. After switching to intravenous iron supplementation, his gastric mucosa healed and anemia improved. This case demonstrates the rare life-threatening side effect of iron pills causing corrosive mucosal damage and significant anemia from gastrointestinal bleeding.