Development and Validation of a Machine Learning System to Identify Reflux Events in Esophageal 24-Hour pH/Impedance Studies.

INTRODUCTION: Esophageal 24-hour pH/impedance testing is routinely performed to diagnose gastroesophageal reflux disease. Interpretation of these studies is time-intensive for expert physicians and has high inter-reader variability. There are no commercially available machine learning tools to assist with automated identification of reflux events in these studies. METHODS: A machine learning system to identify reflux events in 24-hour pH/impedance studies was developed, which included an initial signal processing step and a machine learning model. Gold-standard reflux events were defined by a group of expert physicians. Performance metrics were computed to compare the machine learning system, current automated detection software (Reflux Reader v6.1), and an expert physician reader. RESULTS: The study cohort included 45 patients (20/5/20 patients in the training/validation/test sets, respectively). The mean age was 51 (standard deviation 14.5) years, 47% of patients were male, and 78% of studies were performed off proton-pump inhibitor. Comparing the machine learning system vs current automated software vs expert physician reader, area under the curve was 0.87 (95% confidence interval [CI] 0.85-0.89) vs 0.40 (95% CI 0.37-0.42) vs 0.83 (95% CI 0.81-0.86), respectively; sensitivity was 68.7% vs 61.1% vs 79.4%, respectively; and specificity was 80.8% vs 18.6% vs 87.3%, respectively. DISCUSSION: We trained and validated a novel machine learning system to successfully identify reflux events in 24-hour pH/impedance studies. Our model performance was superior to that of existing software and comparable to that of a human reader. Machine learning tools could significantly improve automated interpretation of pH/impedance studies.

Microbiomic and Metabolomic Analyses Unveil the Protective Effect of Saffron in a Mouse Colitis Model.

Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron's effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron's colitis-mitigating effects. These data demonstrate saffron's therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites.

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts.

Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.

Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer.

The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer.

Protective Effect of Saffron in Mouse Colitis Models Through Immune Modulation.

BACKGROUND: People with inflammatory bowel disease (IBD) including ulcerative colitis are at risk for colorectal cancer. Despite available effective drugs used to treat IBD, many patients fail or lose response over time with some displaying drug-induced adverse events. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD has not been explored extensively. AIM: To establish whether saffron treatment alleviates inflammation in experimental colitis. METHODS: Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron doses (7.5, 15, 20, 25 mg/kg body weight) or vehicle through daily gavage. On day 11, mice were euthanized and analyzed for gross and microscopic inflammation. Distal colon segments were collected for mRNA and protein expression of HO-1 protein and GPX2, (the downstream targets of NRF-2). Nrf-2 translocation from cytosol to nucleus was confirmed by immunofluorescence, and further Nrf-2 protein expression in nuclear and cytosolic fraction of colon was analyzed by immunoblot. Immune cells were isolated from the lamina propria of mouse colon for flow cytometry-based immunophenotyping. Colitis was also induced in C57BL/6 Ahr knockout and wild type mice to explore the involvement of Ahr-dependent pathways in saffron's protective effect(s). The therapeutic effect of saffron was further validated in another TNBS model of colitis. RESULTS: Saffron 20 mg/kg body weight showed improved colon gross and histology features and led to better body weight, colon length, histology score, and reduced disease activity index (DAI). Saffron significantly decreased pro-inflammatory macrophages (M1), while increasing anti-inflammatory macrophages (M2) and IL10 + dendritic cells. Saffron treatment also enhanced CD3 + T and CD3 + CD8 + T cells followed by increase in different CD3 + CD4 + T cells subsets like CD25 + T cells, FoxP3 + CD25 + regulatory T cells, and CD4 + FOXP3 + CD25-regulatory T cells. Immunoblot analysis showed a significant increase in HO-1/GPX2 protein expression. With saffron treatment, Nrf-2 translocation into nucleus from cytosol also supports the involvement of Nrf-2 and its downstream targets in the protective effect of saffron. Further, we demonstrated that saffron in part exert anti-inflammatory effect through activation of aryl hydrocarbon receptor (AhR)-nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways. CONCLUSION: These data demonstrate saffron's therapeutic potential and its protective role in part via Ahr/Nrf-2 pathways and regulatory innate and adaptive immune cells.

Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.

Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin α4ß7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-α4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α4ß7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-ß7) blocks leukocyte trafficking via α4ß7 and cell adhesion via αEß7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α4ß7 IgG2), PN-943 (orally administered and gut-restricted α4ß7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG).

Development and Validation of an Artificial Intelligence System to Optimize Clinician Review of Patient Records.

Importance: Physicians are required to work with rapidly growing amounts of medical data. Approximately 62% of time per patient is devoted to reviewing electronic health records (EHRs), with clinical data review being the most time-consuming portion. Objective: To determine whether an artificial intelligence (AI) system developed to organize and display new patient referral records would improve a clinician's ability to extract patient information compared with the current standard of care. Design, Setting, and Participants: In this prognostic study, an AI system was created to organize patient records and improve data retrieval. To evaluate the system on time and accuracy, a nonblinded, prospective study was conducted at a single academic medical center. Recruitment emails were sent to all physicians in the gastroenterology division, and 12 clinicians agreed to participate. Each of the clinicians participating in the study received 2 referral records: 1 AI-optimized patient record and 1 standard (non-AI-optimized) patient record. For each record, clinicians were asked 22 questions requiring them to search the assigned record for clinically relevant information. Clinicians reviewed records from June 1 to August 30, 2020. Main Outcomes and Measures: The time required to answer each question, along with accuracy, was measured for both records, with and without AI optimization. Participants were asked to assess overall satisfaction with the AI system, their preferred review method (AI-optimized vs standard), and other topics to assess clinical utility. Results: Twelve gastroenterology physicians/fellows completed the study. Compared with standard (non-AI-optimized) patient record review, the AI system saved first-time physician users 18% of the time used to answer the clinical questions (10.5 [95% CI, 8.5-12.6] vs 12.8 [95% CI, 9.4-16.2] minutes; P = .02). There was no significant decrease in accuracy when physicians retrieved important patient information (83.7% [95% CI, 79.3%-88.2%] with the AI-optimized vs 86.0% [95% CI, 81.8%-90.2%] without the AI-optimized record; P = .81). Survey responses from physicians were generally positive across all questions. Eleven of 12 physicians (92%) preferred the AI-optimized record review to standard review. Despite a learning curve pointed out by respondents, 11 of 12 physicians believed that the technology would save them time to assess new patient records and were interested in using this technology in their clinic. Conclusions and Relevance: In this prognostic study, an AI system helped physicians extract relevant patient information in a shorter time while maintaining high accuracy. This finding is particularly germane to the ever-increasing amounts of medical data and increased stressors on clinicians. Increased user familiarity with the AI system, along with further enhancements in the system itself, hold promise to further improve physician data extraction from large quantities of patient health records.

Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray-Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.

Vitamin D Is Associated with α4ß7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4ß7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4ß7 immunophenotypes and risk of vedolizumab [anti-α4ß7] failure in IBD. METHODS: We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizumab-naïve patients with IBD [N = 48]. We analysed whole-genome mucosal gene expression [GSE73661] from GEMINI I and GEMINI long-term safety [LTS] to determine the association between vitamin D receptor [VDR] and integrin alpha-4 [ITGA4] and beta-7 [ITGB7] genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort [N = 252] with logistic regression. RESULTS: Immunophenotyping revealed that higher 25[OH]D was associated with decreased α4ß7+ peripheral blood mononuclear cells [R = -0.400, p <0.01] and α4ß7+ intestinal leukocytes [R = -0.538, p = 0.03]. Serum 25[OH]D was inversely associated with α4ß7+ peripheral B cells and natural killer [NK] cells and α4ß7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25[OH]D <25 ng/mL was associated with increased vedolizumab primary non-response during induction (odds ratio [OR] 26.10, 95% confidence interval [CI] 14.30-48.90, p <0.001) and failure at 1-year follow-up [OR 6.10, 95% CI 3.06-12.17, p <0.001]. CONCLUSIONS: Low serum 25[OH]D is associated with α4ß7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions.

Inflammatory bowel disease (IBD) is a complex and multifaceted disorder of the gastrointestinal tract that is increasing in incidence worldwide and associated with significant morbidity. The rapid accumulation of large datasets from electronic health records, high-definition multi-omics (including genomics, proteomics, transcriptomics, and metagenomics), and imaging modalities (endoscopy and endomicroscopy) have provided powerful tools to unravel novel mechanistic insights and help address unmet clinical needs in IBD. Although the application of artificial intelligence (AI) methods has facilitated the analysis, integration, and interpretation of large datasets in IBD, significant heterogeneity in AI methods, datasets, and clinical outcomes and the need for unbiased prospective validations studies are current barriers to incorporation of AI into clinical practice. The purpose of this review is to summarize the most recent advances in the application of AI and machine learning technologies in the diagnosis and risk prediction, assessment of disease severity, and prediction of clinical outcomes in patients with IBD.

Therapeutic Implications of Diet in Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory Diseases.

Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising clinical trials are currently underway, there is a need for further evidence-based recommendations. As such, we summarize the current evidence on various diets used in the treatment of IBD and also explore the potential applications of dietary data from related immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and psoriasis, to provide additional information to inform IBD providers. To date, there have been multiple diets investigated as adjunctive therapy in IBD, but many associated studies are small, non-randomized, and not controlled. Mediterranean, vegetarian/vegan, and reduced-calorie/fasting diets have been studied and have shown some positive results in other IMIDs, which may suggest potential applicability to those with IBD, but larger, well-designed clinical trials are needed for further guidance. Gluten-free and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diets do not appear to have an impact on IBD disease activity, but low FODMAP may potentially be helpful for those with concurrent functional gastrointestinal symptoms. Specific carbohydrate diets have been mainly assessed in children but show some potential in small adult studies.

Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing acute cholangitis. The majority of patients with PSC have comorbid inflammatory bowel disease, and many take immunosuppressive medications. The epidemiological risks for the development of acute cholangitis in patients with PSC, including the impact of immunosuppressive therapy, are unknown. METHODS: We conducted a 2-center, retrospective cohort study using data from 228 patients at Stanford University Medical Center and Santa Clara Valley Medical Center (CA), a county health care system. Patient demographics, medications, PSC disease severity, and inflammatory bowel disease status were extracted. Using stepwise variable selection, we included demographic and covariate predictors in the multiple logistic regression model assessing risk factors for cholangitis. Time-to-event analysis was performed to evaluate specific immunosuppressive medications and development of cholangitis. RESULTS: Thirty-one percent of patients had at least 1 episode of acute cholangitis (n = 72). Anti-tumor necrosis factor (TNF) therapy was associated with increased odds of acute cholangitis (odds ratio, 7.29; 95% confidence interval, 2.63-12.43), but immunomodulator use was protective against acute cholangitis (odds ratio, 0.23; 95% confidence interval, 0.05-0.76). Anti-TNF therapy was associated with decreased time-to-cholangitis, with a median time of 28.4 months; in contrast, only 11.1% of patients who were prescribed immunomodulators developed cholangitis over the same time period (P < 0.001). CONCLUSIONS: Our observations suggest that classes of immunosuppressive medications differentially modify the odds of acute cholangitis. Biologic therapy, ie, anti-TNF therapy, was shown to have significantly higher odds for patients developing acute cholangitis whereas immunomodulator therapy was shown to have a potential protective effect. These findings may help guide physicians in decision-making for determining appropriate immunosuppressive therapy.

Shortening Postoperative Stay after Parathyroidectomy - A District General Hospital Experience

Abstract Introduction Historically, concerns about complications following parathyroid surgery, such as airway compromise, bleeding and hypocalcemia, have precluded its consideration as a short-stay surgical procedure. Recent advancements in perioperative care have resulted in several publications demonstrating that parathyroidectomy can be safely performed as a short-stay procedure. Objectives The aim of the present study was to describe the process of implementing a short-stay protocol focusing on preoperative patient education and postoperative calcium management for those undergoing surgery for primary hyperparathyroidism (PHP). Method A retrospective audit of consecutive parathyroidectomies performed for PHP over the period between 2010 and 2013 was performed. A short-stay protocol (SSP) was introduced focusing on postoperative calcium management. Results were reaudited over the period between 2013 and 2015. Results Consecutive parathyroidectomies in 76 patients were included in the study. A total of 42 patients underwent parathyroidectomy prior to the introduction of the protocol. A total of 26.2% of these patients were symptomatic from hypercalcemia. A total of 40 out of 42 (95.2%) patients had a biochemical cure. A total of 36 out of 42 (85.7%) cases were due to parathyroid adenomas. A total of 34 patients underwent surgery following the introduction of the protocol. A total of 13 out of 34 (38.2%) of the patients had symptomatic hypercalcemia. A total of 33 out of 34 (97.1%) had a biochemical cure. A total of 32 out of 34 (94.1%) cases were due to parathyroid adenomas. The length of stay decreased from a median of 3 days (range 2-9 days; mean 3.32) preprotocol to a median of 2 days (range 2-3 days; mean 2.16) postprotocol (p< 0.0001) with no difference in the 30-day unplanned readmission rate (4.8 versus 2.9%; p= 0.999). Conclusions The postoperative length of stay after parathyroidectomy for PHP can be safely reduced through patient education and by rationalizing postoperative calcium management without adversely affecting outcomes.

Shortening Postoperative Stay after Parathyroidectomy - A District General Hospital Experience.

Introduction Historically, concerns about complications following parathyroid surgery, such as airway compromise, bleeding and hypocalcemia, have precluded its consideration as a short-stay surgical procedure. Recent advancements in perioperative care have resulted in several publications demonstrating that parathyroidectomy can be safely performed as a short-stay procedure. Objectives The aim of the present study was to describe the process of implementing a short-stay protocol focusing on preoperative patient education and postoperative calcium management for those undergoing surgery for primary hyperparathyroidism (PHP). Method A retrospective audit of consecutive parathyroidectomies performed for PHP over the period between 2010 and 2013 was performed. A short-stay protocol (SSP) was introduced focusing on postoperative calcium management. Results were reaudited over the period between 2013 and 2015. Results Consecutive parathyroidectomies in 76 patients were included in the study. A total of 42 patients underwent parathyroidectomy prior to the introduction of the protocol. A total of 26.2% of these patients were symptomatic from hypercalcemia. A total of 40 out of 42 (95.2%) patients had a biochemical cure. A total of 36 out of 42 (85.7%) cases were due to parathyroid adenomas. A total of 34 patients underwent surgery following the introduction of the protocol. A total of 13 out of 34 (38.2%) of the patients had symptomatic hypercalcemia. A total of 33 out of 34 (97.1%) had a biochemical cure. A total of 32 out of 34 (94.1%) cases were due to parathyroid adenomas. The length of stay decreased from a median of 3 days (range 2-9 days; mean 3.32) preprotocol to a median of 2 days (range 2-3 days; mean 2.16) postprotocol ( p < 0.0001) with no difference in the 30-day unplanned readmission rate (4.8 versus 2.9%; p = 0.999). Conclusions The postoperative length of stay after parathyroidectomy for PHP can be safely reduced through patient education and by rationalizing postoperative calcium management without adversely affecting outcomes.

Efficacy of Dietary Supplements in Inflammatory Bowel Disease and Related Autoimmune Diseases.

The microbiome is an important contributor to a variety of fundamental aspects of human health, including host metabolism, infection, and the immune response. Gut dysbiosis has been identified as a contributor to the errant immune response in a variety of immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriatic disease (psoriasis and psoriatic arthritis). Given this, probiotics and prebiotics have been investigated as therapeutic options in these disease states. In our review, we highlight the current evidence on prebiotics and probiotics as well as other supplements (such as fish oils, vitamin D, and curcumin) as therapies for IBD. Recommendations, however, regarding the specific use of such supplements in IBD have been lacking, particularly from professional societies, often due to study limitations related to small sample sizes and design heterogeneity. Hence, we additionally examine the literature on the use of prebiotics, probiotics, and other supplements in related IMIDs, namely RA and psoriasis/psoriatic arthritis, as these diseases share many approved therapeutic options with IBD. Based on these combined findings, we offer additional evidence that may help guide clinicians in their treatment of patients with IBD (and other IMIDs) and provide recommendations on potential next steps in therapeutic research in this area.

Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation.

Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in colectomy-treated patients with ulcerative colitis (UC) versus controls (familial adenomatous polyposis [FAP]). We show that relative to FAP, UC pouches have reduced levels of lithocholic acid and deoxycholic acid (normally the most abundant gut SBAs), genes required to convert PBAs to SBAs, and Ruminococcaceae (one of few taxa known to include SBA-producing bacteria). In three murine colitis models, SBA supplementation reduces intestinal inflammation. This anti-inflammatory effect is in part dependent on the TGR5 bile acid receptor. These data suggest that dysbiosis induces SBA deficiency in inflammatory-prone UC patients, which promotes a pro-inflammatory state within the intestine that may be treated by SBA restoration.

Systematic review of contemporary outcomes of endovascular and open thoracoabdominal aortic aneurysm repair.

OBJECTIVE: The purpose of the study was to provide a systematic review of the literature reporting the contemporary early outcomes after endovascular and open repair of thoracoabdominal aortic aneurysms (TAAAs). METHODS: MEDLINE and Embase were searched for studies from January 2006 to March 2018 that reported either endovascular (using branched or fenestrated endografts) or open repair of TAAA in at least 10 patients. Outcomes of interest included perioperative mortality, spinal cord injury (SCI), renal failure requiring dialysis, and stroke. Pooled proportions were determined using a random-effects model. RESULTS: The analysis included 71 studies, of which 24 and 47 reported outcomes after endovascular and open TAAA repair, respectively. Endovascular cohort patients were older and had higher rates of coronary artery disease, chronic obstructive pulmonary disease, and diabetes. Endovascular repair was associated with higher rates of SCI (13.5%; 95% confidence interval [CI], 10.5%-16.7%) compared with open repair (7.4%; 95% CI, 6.2%-8.7%; P < .01) but similar rates of permanent paralysis (5.2% [95% CI, 3.8%-6.7%] vs 4.4% [95% CI, 3.3%-5.6%]; P = .39), lower rates of postoperative dialysis (6.4% [95% CI, 3.2%-9.5%] vs 12.0% [95% CI, 8.2%-16.3%]; P = .03) but similar rates of being discharged on permanent dialysis (3.7% [95% CI, 2.0%-5.9%] vs 3.8% [95% CI, 2.9%-5.3%]; P = .93), a trend to lower stroke (2.7% [95% CI, 1.9%-3.6%] vs 3.9% [95% CI, 3.0%-4.9%]; P = .06), and similar perioperative mortality (7.4% [95% CI, 5.9%-9.1%] vs 8.9% [95% CI, 7.2%-10.9%]; P = .21). CONCLUSIONS: This systematic review summarizes the contemporary literature results of endovascular and open TAAA repair. Endovascular repair studies included patients with more comorbidities and were associated with higher rates of SCI but similar rates of permanent paraplegia, whereas open repair studies had higher rates of postoperative dialysis but similar rates of being discharged on permanent dialysis. Perioperative mortality rates were similar. Universally adopted reporting standards for patient characteristics, outcomes, and the conduct of contemporary comparative studies will allow better assessment and comparisons of the risks associated with the two surgical treatment options for TAAA.

Outcomes after Transverse-Incision 'Mini' Carotid Endarterectomy and Patch-Plasty.

PURPOSE: Traditional exposure for carotid endarterectomy (CEA) involves making a longitudinal incision parallel to the anterior border of the sternocleidomastoid. Such incisions can be painful, aesthetically displeasing, and associated with a high incidence of cranial nerve injury (CNI). This study describes the outcomes of CEA performed through small (<5 cm long), transversely oriented incisions located directly over the carotid bifurcation, as identified by color-enhanced Duplex ultrasound. MATERIALS AND METHODS: Patient demographics and operative data were collected retrospectively from an in-house database of consecutive vascular patients undergoing CEA with a small transversely oriented incision for both symptomatic and asymptomatic carotid artery stenoses. RESULTS: A total of 52 consecutive patients underwent CEA between 2012 and 2016 (median age, 73.5 years; interquartile range, 67-80.3; male/female ratio, 40:12). CEA was performed under regional/local anesthesia (LA) in 48 (92.3%) patients, with 4 (7.7%) being performed under general anesthesia. One patient under LA experienced neurological dysfunction intraoperatively (manifesting as an inability to count out loud) that resolved with insertion of shunt. One patient experienced a transient neurological event (expressive dysphasia) within the immediate postoperative period, which resolved within 6 hours. No in-hospital death or perioperative major adverse cardiovascular events were noted. No persistent CNIs nor bleeding complications necessitating re-exploration were reported. Follow-up data were available for a median period of 3.1 years and for all patients. Three patients experienced strokes following discharge (2 strokes contralateral to and 1 transient ischemic attack ipsilateral to the operated side). CONCLUSION: Small, transversely orientated incisions, hidden within a neck skin crease can be safely performed in the majority of patients undergoing CEA.

The high resource impact of reformatting requirements for scientific papers.

BACKGROUND: Most research manuscripts are not accepted for publication on first submission. A major part of the resubmission process is reformatting to another journal's specific requirements, a process separate from revising the scientific content. There has been little research to understand the magnitude of the burden imposed by the current resubmission process. METHODS: We analyzed original research article submission requirements from twelve randomly selected journals in each of eight scientific and clinical focus areas from the InCites Journal Citation Reports database. From the 96 journals selected, we randomly identified three recently published manuscripts and sent surveys to those first and/or corresponding authors (288 total) to solicit information on time spent reformatting resubmissions and opinions on the process. FINDINGS: There was significant variation in manuscript submission requirements for journals within the same scientific focus and only 4% of journals offered a fully format-free initial submission. Of 203 authors responding (71.5% response rate), only 11.8% expressed satisfaction with the resubmission process and 91% desired reforming the current system. Time spent on reformatting delays most publications by at least two weeks and by over three months in about 20% of manuscripts. The effort to comply with submission requirements has significant global economic burden, estimated at over $1.1 billion dollars annually when accounting for a research team's time. INTERPRETATION: We demonstrate that there is significant resource utilization associated with resubmitting manuscripts, heretofore not properly quantified. The vast majority of authors are not satisfied with the current process. Addressing these issues by reconciling reformatting requirements among journals or adopting a universal format-free initial submission policy would help resolve a major subject for the scientific research community and provide more efficient dissemination of findings.