Using Wearable Biosensors to Predict Length of Stay for Patients with IBD After Bowel Surgery.

BACKGROUND AND AIMS: It remains unknown whether ambulation or sleep predicts postoperative length of stay for patients with IBD. We aim to identify the utility of wearable biosensors in predicting postoperative length of stay for patients with IBD. METHODS: Associations of postoperative length of stay with step count/sleep duration/sleep efficiency measured by wearable biosensors were examined. The best-fitting multivariable linear regression model predicting length of stay was constructed using stepwise model selection. RESULTS: Final sample included 37 patients. Shorter sleep duration on postoperative day 4 (r = 0.51, p = 0.043) or 5 (r = 0.81, p = 0.0045) or higher sleep efficiency on postoperative day 5 (r = - 0.77, p = 0.0098) was associated with a shorter length of stay. Additionally, a more positive change in sleep efficiency from postoperative day 4-5 was associated with a shorter length of stay (r = - 0.77, p = 0.024). The best-fitting multivariable linear regression model revealed Clavien-Dindo grade 1 (p = 0.045) and interaction between Clavien-Dindo grade 2/3a and mean daily steps (p = 0.00038) are significant predictors of length of stay. The following variables were not significantly associated with length of stay: mean daily steps/sleep duration/sleep efficiency, average rate of change in these three variables, and changes in step count between successive postoperative days 1-5, sleep duration between successive postoperative days 2-5, and sleep efficiency between successive postoperative days 2-4. CONCLUSION: We demonstrated the utility of activity and sleep data from wearable biosensors in predicting length of stay. Patients with more severe complications may benefit more (i.e., reduced postoperative length of stay) from increased ambulation. However, overall, sleep duration/efficiency did not predict length of stay.

Follow-Up of Patients With Ulcerative Colitis and Histological Normalization.

The natural history of ulcerative colitis (UC) follows a relapsing and remitting course of inflammation and is accompanied by associated mucosal injury and historically, microscopic features of chronicity that were the sine qua non for the diagnosis.1 As goals for the management of UC have evolved to include objectively measured endoscopic improvement of the mucosa, there also has been a move to include histological endpoints in assessment of disease activity.2,3 However, there remain a number of unanswered questions about histology in UC and this is not yet a specific treatment goal.4.

Ustekinumab Is Effective for the Treatment of Chronic Antibiotic-Refractory Pouchitis.

BACKGROUND: Chronic antibiotic-refractory pouchitis (CARP) occurs in up to 15% of patients with ulcerative colitis (UC) following proctocolectomy with ileal pouch-anal anastomosis (IPAA). AIM: To investigate the effectiveness of ustekinumab in the treatment of CARP. METHODS: This was a retrospective single-center study of UC patients with an IPAA, who subsequently developed CARP and received ustekinumab with standard Crohn's disease (CD) dosing between 2016 and 2018. Patients with CD of the pouch were excluded. Demographic, clinical, and endoscopic data were collected. Outcomes included a change in the endoscopic subscore of the Pouchitis Disease Activity Index (PDAI), change in the ulcerated surface area, clinical response, and the number of bowel movements per 24 h. RESULTS: Twenty-four patients with CARP were included for analysis. Median follow-up time was 12.9 months (IQR 7.9-16). Twelve patients (50%) had a clinical response with the median number of bowel movements within 24 h decreasing from 8 (IQR, 5-12) to 6 (IQR, 5-8) P = 0.002. Thirteen patients had pouchoscopies available post-ustekinumab treatment. In these patients, the median endoscopic subscore of the PDAI decreased from 5 (IQR, 3-6) to 4 (IQR, 2-5), P = 0.016. Likewise, among these thirteen patients, nine (69%) had an ulcerated surface area > 10% before ustekinumab treatment; after treatment with ustekinumab, only four patients (31%) still had an ulcerated surface area of > 10%. CONCLUSIONS: This is the largest study of ustekinumab treatment for patients with chronic antibiotic-refractory pouchitis. We found that ustekinumab therapy led to the improvement in clinical and endoscopic endpoints.

Real-World Experience with Tofacitinib in IBD at a Tertiary Center.

BACKGROUND AND AIMS: Many inflammatory bowel disease (IBD) patients do not respond to medical therapy. Tofacitinib is a first-in-class, partially selective inhibitor of Janus kinase, recently approved for treating patients with ulcerative colitis (UC). We describe our experience with the use of tofacitinib for treatment of patients with moderate-to-severe IBD. METHODS: This is a retrospective, observational study of the use of tofacitinib in IBD. Patients with medically resistant IBD were treated orally with 5 mg or 10 mg twice daily. Clinical response and adverse events were assessed at 8, 26, and 52 weeks. Objective response was assessed endoscopically, radiologically, and biochemically. RESULTS: 58 patients (53 UC, 4 Crohn's, 1 pouchitis) completed at least 8 weeks of treatment with tofacitinib. 93% of the patients previously failed treatment with anti-TNF. At 8 weeks of treatment, 21 patients (36%) achieved a clinical response, and 19 (33%) achieved clinical remission. Steroid-free remission at 8 weeks was achieved in 15 patients (26%). Of the 48 patients followed for 26 weeks, 21% had clinical, steroid-free remission. Of the 26 patients followed for 12 months, 27% were in clinical, steroid-free remission. Twelve episodes of systemic infections were noted, mostly while on concomitant steroids. One episode of herpes zoster infection was noted during follow-up. CONCLUSIONS: In this cohort of patients with moderate-to-severe, anti-TNF resistant IBD, tofacitinib induced clinical response in 69% of the patients. 27% were in clinical, steroid-free remission by 1 year of treatment. Tofacitinib is an effective therapeutic option for this challenging patient population.

The Association of Metabolic-Associated Fatty Liver Disease with Clinical Outcomes of COVID-19: A Systematic Review and Meta-Analysis.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome (MS). MAFLD patients have a higher prevalence of COVID-19. MAFLD also is associated with worse clinical outcomes of COVID-19, such as disease severity, intensive care unit (ICU) admission rate, and higher mortality rates. However, this evidence has not been well characterized in the literature. This meta-analysis aimed to determine the clinical outcomes of COVID-19 among MAFLD patients compared to the non-MAFLD group. Methods: A comprehensive search was conducted in the Cumulative Index of Nursing and Allied Health (CINAHL), PubMed/Medline, and Embase for studies reporting MAFLD prevalence among COVID-19 patients and comparing clinical outcomes such as severity, ICU admission, and mortality among patients with and without MAFLD. The pooled prevalence of MAFLD among COVID-19 patients and the pooled odds ratios (OR) with 95% confidence intervals (CI) for clinical outcomes of COVID-19 were calculated. Results: Sixteen observational studies met inclusion criteria involving a total of 11,484 overall study participants, including 1,746 MAFLD patients. The prevalence of COVID-19 among MAFLD patients was 0.29 (95% CI: 0.19-0.40). MAFLD was associated with the COVID-19 disease severity OR 3.07 (95% CI: 2.30-4.09). Similarly, MAFLD was associated with an increased risk of ICU admission compared to the non-MAFLD group OR 1.46 (95% CI: 1.12-1.91). Lastly, the association between MAFLD and COVID-19 mortality was not statistically significant OR 1.45 (95% CI: 0.74-2.84). Conclusions: In this study, a high percentage of COVID-19 patients had MAFLD. Moreover, MAFLD patients had an increased risk of COVID-19 disease severity and ICU admission rate.

A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab.

BACKGROUND: Combining vedolizumab with a rapid-onset drug such as cyclosporine is a novel combination treatment for severe steroid-resistant ulcerative colitis (UC). This prospective study describes the efficacy and safety of cyclosporine in conjunction with vedolizumab in patients with severe, steroid-resistant UC with 1 year of follow-up. METHODS: Seventeen steroid-resistant UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks. Clinical and endoscopic response, remission rates, and colectomy-free survival were the primary endpoints. Secondary endpoints included biochemical response and remission with C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin. RESULTS: Fifteen (88%) of 17 patients initially responded to cyclosporine and were started on vedolizumab. By week 10, 11 (73%) of 15 patients had achieved endoscopic remission with a Mayo score of ≤1. At week 26, 14 (93%) of 15 of the patients were in clinical remission and 11 (73%) were in endoscopic remission. At week 52 of follow-up, 10 (71%) of 14 of these patients continued to be in endoscopic remission and 11 (79%) of 14 were in clinical remission. Among the 10 patients in endoscopic remission, 8 (80%) reached histological remission. Colectomy-free survival rate was 82% (n = 14 of 17) at 1 year and mean C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin levels were 3.2 mg/L, 16.1 mm/h, and 168.3 µg/g, respectively. No serious adverse events were reported. CONCLUSIONS: Bridging cyclosporine to vedolizumab in severe, steroid-refractory UC patients is effective and safe at inducing and maintaining clinical, endoscopic, and biochemical response and remission up to 52 weeks of follow-up. Larger prospective studies are warranted.

Spontaneous Bacterial Peritonitis Secondary to Salmonella spp. in a Patient With Decompensated Liver Cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a common and serious complication of cirrhosis, with gram-negative bacteria being the culprit in most cases. SBP secondary to Salmonella spp. is rare. Here, we report a case of Salmonella enterica SBP in a patient with decompensated cirrhosis, diagnosed via paracentesis coupled with ascitic fluid analysis and culture. A high index of suspicion must be maintained for atypical causes of SBP, with prompt initiation of treatment.

An Unusual Case of Urothelial Cell Carcinoma With Metastasis to the Pancreas.

Metastasis to the pancreas is far less common than primary pancreatic tumors. Bladder cancer metastasis involving the pancreas is rarely reported. Here, we report a case of metastasis to the pancreas of urothelial cell origin, diagnosed via upper endoscopic ultrasound-guided fine-needle aspiration and biopsy, and coupled with immunostaining. A high index of suspicion must be maintained for atypical metastatic locations of urothelial cell carcinoma, especially to the pancreas.

Cumulative Histologic Inflammation Predicts Colorectal Neoplasia in Ulcerative Colitis: A Validation Study.

BACKGROUND: Chronic inflammation in ulcerative colitis (UC) is associated with the development of colorectal neoplasia (CRN). A group at St. Mark's Hospital reported a novel cumulative inflammatory index that predicted the development of CRN in UC patients that we validated with an independent, well-described, matched, case-controlled cohort from the University of Chicago. METHODS: Cumulative inflammatory burden (CIB) was calculated by summing each histological inflammatory activity (HIA) score and multiplying it by the length of the surveillance interval. Persistency was defined by the number of surveillance episodes (with a severity score >2) divided by the total number of surveillance procedures. T tests compared the mean and maximum HIA scores, assessing mean and maximum severity, CIB, and persistency. RESULTS: Sixty-two UC patients (26 patients with CRN, 36 control patients without CRN) were analyzed. Fifty-five percent were men, mean disease duration was 20.6 years, and mean age at CRN diagnosis was 43.9. Of the CRN patients, 6 (23%) had colorectal cancer, 16 (62%) had low-grade dysplasia, and 4 (15%) had indefinite dysplasia. Using mean HIA scores, we found CIB to be statistically greater in CRN patients (P = 0.04). Using maximum HIA scores, we found CIB (P = 0.02), mean severity (P = 0.03), and persistency (P = 0.01) to be significantly greater in CRN patients. Maximum severity was numerically greater for mean and maximum HIA scores but did not reach significance. CONCLUSION: Cumulative histologic inflammation is significantly associated with the development of CRN in UC patients. This suggests a management strategy of controlling inflammation to reduce the risk of CRN and may influence the selection of surveillance intervals.

Ciclosporin Therapy After Infliximab Failure in Hospitalized Patients With Acute Severe Colitis is Effective and Safe.

BACKGROUND AND AIMS: Options for medical management of patients with acute severe colitis [ASC] failing intravenous (i.v.) steroids are limited and include rescue therapy with either infliximab or ciclosporin. In patients failing infliximab, second-line rescue therapy with ciclosporin is an alternative. The aim of this study was to investigate the efficacy and safety of ciclosporin in patients with steroid-refractory ASC failing first-line rescue therapy with infliximab. METHODS: This is a retrospective, tertiary centre study undertaken from 2010 to 2017. Included were patients hospitalized for ASC and treated with i.v. ciclosporin after failing i.v. steroids and infliximab within the previous 2 months. Time to colectomy, clinical response, and occurrence of adverse events were analysed. RESULTS: Forty patients with steroid-resistant ASC were included. Patients were followed for a median of 13 months (interquartile range [IQR] 5-32 months). Colectomy-free survival was 65%, 59.4%, and 41.8% at 1 month, 3 months and 1 year, respectively. Sixty percent of patients [24/40] achieved clinical remission at a median of 2 weeks [IQR 1-3 weeks]. Infliximab levels before ciclosporin infusion were available for 26 patients [median level 17.5 mg/mL, IQR 8-34 mg/mL] and were not associated with adverse events. Sixteen patients [40%] experienced adverse events after ciclosporin treatment, but none resulted in drug discontinuation. CONCLUSIONS: In patients with i.v. steroid-refractory ASC who failed infliximab therapy, second-line rescue therapy with ciclosporin was shown to be effective and safe. This is the largest patient cohort to receive ciclosporin as second-line rescue therapy for ASC. We believe that ciclosporin may be offered to selected patients prior to referral for colectomy.

Respecting patient choices: using the 'Go Wish' cards as a teaching tool.

BACKGROUND: Individuals have different values and priorities that can have an important impact on their medical management. Understanding this concept can help physicians provide medical care that is in line with the goals of their patients. Communicating this message effectively to students is challenging. OBJECTIVE: To report our experience with using Go Wish cards in the medical education setting. DESIGN: A thematic analysis of student reflection papers using grounded theory. SETTING/SUBJECTS: Second-year medical students participated in an activity using the Go Wish cards as part of a course module on palliative care. The activity aimed to encourage students to reflect on their own choices at the end of life and to highlight that different people have different priorities. RESULTS: Forty-two students (42%) mentioned the Go Wish activity in their reflections on the module. They reported that the activity demonstrated the different priorities at the end of life, it illustrated the importance of providing personalised care, it promoted self-discovery, it transformed their view of death and dying, and it increased their appreciation of the importance of palliative care. CONCLUSION: Go Wish cards can be used to help illustrate the variability in priorities of patients. They can be used as an effective to teach medical students about the importance of considering patient preferences when illness progresses.

Emerging Therapies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic heterogeneous group of diseases that has undergone major advances in the understanding of its etiology and pathogenesis in recent years. The development of biologics had resulted in better overall management of the disease, including lower rates of surgery and better long-term clinical and patient-reported outcomes. Treatment modalities have either been newly developed or extrapolated from their approved use for a different indication. Modes of action and treatment targets have varied as well. Treatments such as vedolizumab and ustekinumab, as well as second-generation corticosteroids have been approved by the US Food and Drug Administration (FDA) for the treatment of IBD. Other agents are currently being developed at various stages of clinical trials including anti-adhesion agents such as etrolizumab and abrilumab, JAK inhibitors such as tofacitinib, and anti-trafficking molecules. Toll-like receptors and phosphatidylcholine are also new promising emerging targets that are being investigated in phase 3 clinical trials. It is projected that many therapies will become available in the coming years if supported by the results of current clinical trials. This will provide IBD patients with a wide array of options and allow physicians to choose the best therapies for each individual patient.

Electrochemical red-ox therapy of prostate cancer in nude mice.

Minimally invasive therapies are increasingly in demand for organ-confined prostate tumors. Electrochemical therapy (EChT) is attractive, as it relies on locally-induced reduction-oxidation reactions to kill tumor cells. Its efficacy for prostate cancer was assessed in human PC-3 and LNCaP tumor xenografts growing subcutaneously in nude mice (n = 80) by applying 2 Stainless Steel vs. 4 Platinum-Iridium (Pt-Ir) electrodes to deliver current densities of 10 to 35 mA/cm(2) for 30 or 60 min. The procedure was uneventful in 90% of mice. No difference in tumor vs. body temperature was observed. Changes at electrode-tumor junctions were immediate, with dryness and acidity (pH2-3) at the anode and oedema and alkalinity (pH10-12) at the cathode. This was accompanied by cellular alterations, found more pronounced at the cathode. Such acidic and alkaline conditions were cytotoxic in vitro and dissolved cells at pH>10. In mice, tumor destruction was extensive by 24h with almost undetectable blood prostate specific antigen (LNCaP model) and covered the whole tumor surface by 4 days. EChT was most efficient at 25-30 mA/cm(2) for 60 min, yielding the longest recurrence-free survival and higher cure rates, especially with 4 Pt-Ir electrodes. EChT is a promising option to optimize for organ-confined prostate tumors.