Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease.

In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs). Herein, we assessed the immunomodulatory effects of four probiotic strains including Lactobacillus salivarius, Bifidobacterium bifidum, Bacillus coagulans and Bacillus subtilis natto on the expression of co-stimulatory molecules, cytokine production and gene expression of signal-transducing receptors in DCs from IBD patients. Human monocyte-derived DCs from IBD patients and healthy controls were exposed to four probiotic strains. The expression of co-stimulatory molecules was assessed and supernatants were analyzed for anti-inflammatory cytokines. The gene expression of toll-like receptors (TLRs), IL-12p40 and integrin αvß8 were also analyzed. CD80 and CD86 were induced by most probiotic strains in ulcerative colitis (UC) patients whereas only B. bifidum induced CD80 and CD86 expression in Crohn's disease (CD) patients. IL-10 and TGF-ß production was increased in a dose-independent manner while TLR expression was decreased by all probiotic bacteria except B. bifidum in DCs from UC patients. TLR-4 and TLR-9 expression was significantly downregulated while integrin ß8 was significantly increased in the DCs from CD patients. IL-12p40 expression was only significantly downregulated in DCs from CD patients. Our findings point to the general beneficial effects of probiotics in DC immunomodulation and indicate that probiotic bacteria favorably modulate the expression of co-stimulatory molecules, proinflammatory cytokines and TLRs in DCs from IBD patients.

A Rare Case of Emphysematous Gastritis Secondary to Organo-Axial Gastric Volvulus Associated With Sarcina ventriculi.

Gastric volvulus is a potentially life-threatening condition that can compromise the blood supply to the stomach predisposing to ischemia, eventually necrosis and cell death associated with gas-forming bacteria. Sarcina ventriculi has been associated with emphysematous gastritis also. We report a case of emphysematous gastritis associated with S. ventriculi in the setting of organo-axial gastric volvulus.

Upadacitinib in Crohn's disease: real-world experience.

Small molecule therapy in inflammatory bowel disease has recently gained momentum. One such agent that was recently approved for use in Crohn's disease is upadacitinib. Even though clinical trials support the use of this agent and efficacy is impressive, real-world data remains limited and scattered in the current literature. This article aims to summarize the real-world data published so far about using upadacitinib in Crohn's disease.

Non-cirrhotic portal hypertension in inflammatory bowel disease.

With the increasing incidence and prevalence of inflammatory bowel diseases (IBD), its complications and associated morbidity also continue to rise. One of these is non-cirrhotic portal hypertension. There is an increasing need of recognizing and understanding the pathophysiology of this condition in the clinical setting of IBD, especially in long standing cases. Due to multiple potential factors, patients with IBD appear to be at a higher risk of developing portal hypertension even in the absence of liver cirrhosis. Portal hypertension is usually diagnosed when complications (such as ascites, variceal bleeding) develop, especially when patients have already experienced multiple complications of the disease. Hence, a high level of vigilance for the detection of portal hypertension at an early stage is needed. This review discusses the known epidemiology, clinical characteristics, clinical presentation, modalities of diagnosis and the potential treatments of the different forms of non-cirrhotic portal hypertension associated with IBD. The concomitant presence of portal hypertension can significantly impact the overall clinical picture and disease burden in IBD. Hence, increased awareness of this condition at an early stage might help tailor a comprehensive and individualized therapeutic plan of care for these patients.

Uretero-Jejunal Fistula: A Rare Cause of Acute Pyelonephritis.

Penetrating peptic ulcers often lead to severe complications. The development of uretero-enteric fistulas is rare and can be challenging to diagnose and treat. Here, we present the case of a 41-year-old patient who previously underwent gastrojejunostomy for superior mesenteric artery syndrome and developed a peptic jejunal ulcer, leading to a uretero-jejunal fistula and finally causing acute pyelonephritis. The patient was managed with a multidisciplinary approach including medical therapy and endoscopic and radiologic interventions.

Colonic Lymphangiomatosis.

Lymphangiomas are benign malformations of the lymphatic vessels which can be primary or secondary in etiology. Colonic involvement is rare, and the diagnosis is mostly incidental. Sometimes, the initial endoscopic appearance can be misleading. We present a case of colonic lymphangiomatosis presenting with free air under the diaphragm requiring surgical removal of the involved portion of the colon. The diagnosis was confirmed by the pathology of the resected specimen and its correlation with prior clinical information. The patient recovered well with an uneventful postoperative course and follow-up. This case demonstrates a rare complication of colonic lymphangiomatosis prompting definitive treatment by surgical resection.

Metastatic Plasmacytoid Urothelial Carcinoma Masquerading as a Primary Signet Ring Cell Carcinoma of the Duodenum.

Plasmacytoid urothelial carcinoma can histologically mimic gastrointestinal signet ring cell carcinoma, a potential diagnostic pitfall resulting in improper clinical management. We present a rare case of a malignant duodenal ulcer due to metastasis from plasmacytoid urothelial carcinoma. Only by histological and retrospective immunohistochemical comparison with the primary bladder tumor was this revealed as a metastasis from a plasmacytoid urothelial carcinoma. This case report highlights the importance of clinical correlation and comparison with any previous pathology specimens, the limitations of immunohistochemical staining, and the utilization of both old and new immunohistochemical tools when differentiating signet ring cell carcinomas of primary sites versus potential metastases.

Does completing advanced endoscopy fellowship improve outcomes after endoscopic mucosal resection?

BACKGROUND: It was reported that about 60% of the physicians in the USA believed that their Gastroenterology fellowship poorly prepared them for large polyp resection. The aim of this study was to compare endoscopic mucosal resection (EMR) efficacy and complication rates between skilled general gastroenterologists who perform high volume of EMR and advanced endoscopists. METHODS: We identified 140 patients with documented large colonic polyps treated by 4 providers using EMR technique at Carilion Clinic, in Roanoke, Virginia, USA between 01/01/2014-12/31/2017, with follow-up through 10-2018. Information on demographics, clinical and pathological features of high-risk polyps (i.e., size, histology, site, and degree of dysplasia), timing of surveillance endoscopies, tools used during resection, and skills of performing endoscopist's were extracted. The cumulative risks of polyp recurrence after first resection using EMR technique were estimated using Kaplan-Meier curves. RESULTS: One hundred and forty patients were identified (mean age, 64.1±11.2 years; 47.1% males). Fifty-five polyps (39.3%) were removed by 2 skilled gastroenterologists and 85 (60.7%) were removed by advanced endoscopists. Most of the polyps resected were located in the right colon (63.6%) and roughly half of the polyps were removed in piecemeal fashion. At follow-up endoscopy, the advanced endoscopy group had lower polyp recurrence rates. The median recurrence after polypectomy was significantly different between the groups (0.88 and 1.03 years for skilled gastroenterologists who did not complete and completed EMR hands-on workshops; respectively vs. 3.99 years for the advanced endoscopist who did not complete EMR hands-on workshop, P=0.03). CONCLUSIONS: There is a need for additional EMR training since polyp recurrence was significantly different between the groups despite high rates of piecemeal resection in the advanced endoscopy groups.

Multidisciplinary Inflammatory Bowel Disease Conference: The Impact of the Expert Pathologist on Patient Care.

BACKGROUND: Multidisciplinary teams (MDT) aid the diagnosis and management of patients with inflammatory bowel disease (IBD) and improve patient outcomes. The direct impact of a gastrointestinal expert pathologist on MDT care of IBD patients is unknown. METHODS: A retrospective chart review was conducted evaluating all cases (N = 289) discussed at the IBD MDT conference at Carilion Roanoke Memorial Hospital from June 1, 2013, through December 31, 2019. Cases were discussed between 1 and 6 times at the conference. Data collected included demographics, diagnosis before and after conference, reason for diagnostic change, endoscopy findings, medications, surgeries, and clinical follow-up. RESULTS: Approximately 15% to 42% of patients had a change in diagnosis after the first 3 conferences. The majority of diagnostic changes after the first (84%), second (73%), and third (67%) conferences were due to expert pathologist interpretation. Indeterminate colitis was the most frequently changed diagnosis, and Crohn's disease was the most common new diagnosis after conference. Among patients with a diagnostic change, 28.6% to 38.5% of patients had a change in their IBD medication regimen, and 7.7% to 10.9% had a surgical intervention after the first 2 conferences. Approximately 54.2% to 60% of patients reported clinical improvement or remission within 6 months of the first 3 conferences. CONCLUSION: The majority of diagnostic changes made at the multidisciplinary IBD conference were due to histopathologic re-interpretation. A change in diagnosis at times led to significant modifications in medical or surgical management. An expert gastrointestinal pathologist is an essential MDT member for IBD management.

An expert gastrointestinal pathologist plays a critical role in the diagnosis of patients presented at multidisciplinary team inflammatory bowel disease conferences. Their input at these conferences significantly impacts patients' medical and surgical management and clinical outcomes.

Imputation by feature importance (IBFI): A methodology to envelop machine learning method for imputing missing patterns in time series data.

A new methodology, imputation by feature importance (IBFI), is studied that can be applied to any machine learning method to efficiently fill in any missing or irregularly sampled data. It applies to data missing completely at random (MCAR), missing not at random (MNAR), and missing at random (MAR). IBFI utilizes the feature importance and iteratively imputes missing values using any base learning algorithm. For this work, IBFI is tested on soil radon gas concentration (SRGC) data. XGBoost is used as the learning algorithm and missing data are simulated using R for different missingness scenarios. IBFI is based on the physically meaningful assumption that SRGC depends upon environmental parameters such as temperature and relative humidity. This assumption leads to a model obtained from the complete multivariate series where the controls are available by taking the attribute of interest as a response variable. IBFI is tested against other frequently used imputation methods, namely mean, median, mode, predictive mean matching (PMM), and hot-deck procedures. The performance of the different imputation methods was assessed using root mean squared error (RMSE), mean squared log error (MSLE), mean absolute percentage error (MAPE), percent bias (PB), and mean squared error (MSE) statistics. The imputation process requires more attention when multiple variables are missing in different samples, resulting in challenges to machine learning methods because some controls are missing. IBFI appears to have an advantage in such circumstances. For testing IBFI, Radon Time Series Data (RTS) has been used and data was collected from 1st March 2017 to the 11th of May 2018, including 4 seismic activities that have taken place during the data collection time.

Wireless Capsule Endoscopy for Diagnosis and Management of Post-Operative Recurrence of Crohn's Disease.

Despite aggressive medical therapy, many patients with Crohn's disease require surgical intervention over time. After surgical resection, disease recurrence is common. Ileo-colonoscopy and the Rutgeerts score are commonly used for diagnosis and monitoring of post-operative endoscopic recurrence. The latter is the precursor of clinical recurrence and therefore it impacts prognosis and patient management. However, due to the limited length of bowel assessed by ileo-colonoscopy, this procedure can miss out-of-reach, more proximal lesions in the small bowel. This limitation introduces an important uncertainty when evaluating post-operative relapse by ileo-colonoscopy. In addition, the Rutgeerts score 'per se' bears a number of ambiguities. Here we will discuss the pros and cons of ileo-colonoscopy and other imaging studies including wireless capsule endoscopy to diagnose and manage post-operative recurrence of Crohn's disease. A number of studies provide evidence that wireless capsule endoscopy is a potentially more accurate as well as less invasive and less costly alternative to conventional techniques including ileo-colonoscopy.

Simulated Annealing-Based Image Reconstruction for Patients With COVID-19 as a Model for Ultralow-Dose Computed Tomography.

The proposed algorithm of inverse problem of computed tomography (CT), using limited views, is based on stochastic techniques, namely simulated annealing (SA). The selection of an optimal cost function for SA-based image reconstruction is of prime importance. It can reduce annealing time, and also X-ray dose rate accompanying better image quality. In this paper, effectiveness of various cost functions, namely universal image quality index (UIQI), root-mean-squared error (RMSE), structural similarity index measure (SSIM), mean absolute error (MAE), relative squared error (RSE), relative absolute error (RAE), and root-mean-squared logarithmic error (RMSLE), has been critically analyzed and evaluated for ultralow-dose X-ray CT of patients with COVID-19. For sensitivity analysis of this ill-posed problem, the stochastically estimated images of lung phantom have been reconstructed. The cost function analysis in terms of computational and spatial complexity has been performed using image quality measures, namely peak signal-to-noise ratio (PSNR), Euclidean error (EuE), and weighted peak signal-to-noise ratio (WPSNR). It has been generalized for cost functions that RMSLE exhibits WPSNR of 64.33 ± 3.98 dB and 63.41 ± 2.88 dB for 8 × 8 and 16 × 16 lung phantoms, respectively, and it has been applied for actual CT-based image reconstruction of patients with COVID-19. We successfully reconstructed chest CT images of patients with COVID-19 using RMSLE with eighteen projections, a 10-fold reduction in radiation dose exposure. This approach will be suitable for accurate diagnosis of patients with COVID-19 having less immunity and sensitive to radiation dose.

Assessing Presenting Symptoms, Co-Morbidities, and Risk Factors for Mortality in Underserved Patients With Non-Hereditary Early-Onset Colorectal Cancer.

Background The presenting symptoms and co-morbidities contributing to mortality in young patients (age < 50 years old) with colorectal cancer (CRC) are poorly understood. We reviewed these features in our patient population with non-hereditary early-onset CRC (EO-CRC). Study aim This study aimed to assess characteristics of patients with a diagnosis of non-hereditary EO-CRC, including presenting symptoms and metabolic disorders contributing to mortality in underserved areas of southwest Virginia. Methods In this retrospective observational study, we selected patients aged 18-50 years with a diagnosis of non-hereditary EO-CRC from 2008 to 2016 at Carilion Roanoke Memorial Hospital. The electronic medical record was queried to identify demographic data, medical history, histopathology results, lab values, and mortality. The cumulative risks of symptoms and co-morbid metabolic disorders was estimated using Kaplan-Meier curves. Results We identified 139 patients with non-hereditary EO-CRC (mean age 41.6 ± 6.9 years). Almost half of these patients were obese (BMI > 30), 30.9% had a diagnosis of hypertension, 29% had hyperlipidemia (HLD), and 17.35% had diabetes mellitus type 2 (DM2). Diagnosis was delayed by 4.5 months from initial presentation, and 17% had advanced disease (stage III/IV). Also, 68.5% of patients were symptomatic with one to three symptoms, most commonly with rectal bleeding (45.3%). The chronicity of HLD (≥5 years) was associated with reduced survival in our patients with EO-CRC. The survival of females with multiple metabolic disorders was reduced compared to females with a single metabolic disorder. Conclusions Multiple symptoms, chronic HLD, and female gender with multiple metabolic disorders were factors associated with poor outcomes in non-hereditary EO-CRC patients.

Gender-Specific Risk Factors Contributing to Mortality in Patients Hospitalized With Alcoholic Cirrhosis.

Introduction Identification of gender-specific prognostic factors in patients with alcoholic liver cirrhosis (ALC) is integral to understanding disease severity and mortality rates. We gathered data on various widely-used laboratory values and comorbid conditions among male and female patients with ALC after initial hospitalization. These individual risk factors were assessed for their relationship with mortality based on gender. Methods We performed a retrospective observational study of hospitalized patients with either a new or prior diagnosis of ALC from 2008 to 2016 with follow-up through June 2018. The electronic medical record (EMR) was queried for demographics, comorbidities, lab values, and mortality. The cumulative risks of mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared among both genders. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariate Cox proportional hazard analysis to determine risk factors associated with mortality. Results We identified 247 male patients (mean age 54.19 ± 13.14 years) and 78 female patients (mean age 51.10 ± 11.60 years) hospitalized at Carilion Clinic with a diagnosis of ALC. About 70% (male) and 46% (female) endorsed alcohol use at the time of admission, 10% (male) and 13% (female) endorsed illicit drug use, and 56% (male and female) endorsed tobacco use. The one-, three- and five-year cumulative mortality after the first hospitalization was 43.4%, 53.2%, and 61.6%, respectively for males and 24.1%, 59.0%, and 67.2%, respectively for females. Median survival for younger male patients with ALC (age < 40 years old) after the first hospitalization was significantly different compared to the older male patients (age > 40 years) (p=0.0009), but age was not a significant factor for survival of female patients. Multivariate analysis further shows that illicit drug use, creatinine level at the time of admission, and age > 40 years had the highest hazard ratios for risk of mortality in male patients. For female patients, history of hepatic encephalopathy (HE) and blood urea nitrogen (BUN) level at the time of discharge were both associated with increased risk of mortality, with a history of HE being associated with a higher hazard ratio for risk of mortality. Conclusion Age, illicit drug use, and creatinine level were risk factors associated with mortality for male patients with ALC but not female patients. Hepatic encephalopathy and BUN were risk factors associated with mortality for female patients. The mortality for male patients was about twice the mortality of female patients at one year, but three-year and five-year mortality was higher in female patients.

Outcomes of Young Patients With Alcoholic Cirrhosis After First Hospitalization for Cirrhosis: A Carilion Clinic Experience.

Background  Alcoholic cirrhosis though uncommon in young patients is being reported more frequently and related mortality is also increasing.  Study aim  To evaluate risk factors associated with mortality among young patients (<40 years) with alcoholic cirrhosis and older patients (> 40 years old) after their first hospitalization in a tertiary referral academic center.  Methods Carilion clinic's electronic medical record (EPIC) was queried to identify all alcoholic patients hospitalized for the first time with either a new diagnosis of alcoholic cirrhosis or a prior diagnosis of this from 2008 to 2016 with follow-up through June 2018. Information on demographics, comorbidities, lab values, procedures, and mortality was extracted. The cumulative risks of long-term mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared between the two groups; those < 40 years of age and those > 40 years of age. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariable Cox proportional hazard analysis to determine risk factors associated with long-term mortality.  Results We identified 65 young patients out of a total of 325 patients admitted for the first time for alcoholic cirrhosis (mean age: 34.6 ± 4.7 yrs, 72.3% males, 74.4% current alcohol users, 52.3% current smokers, 12.6% current illicit drugs users). The one, three, and five-year cumulative mortality after the first hospitalization was 21.1 %, 31.1%, and 49.7% respectively. The median survival for young patients was longer as compared to the older patients (p<0.001); likely related to high early mortality in older patients who had many other comorbidities. On multivariate Cox proportional hazard analysis, increased age [hazard ratio (HR) 1.03; 95% confidence interval (CI), 1.01-1.05], neutrophils-to-lymphocytes ratio (NLR) at first hospital discharge (HR 1.02; 95% CI, 1.01-1.04), the presence of encephalopathy (HR, 1.93; 95% CI, 1.06-3.55), and initial MELD (model for end-stage liver disease) score (HR, 1.13; 95% CI, 1.08-1.19) were associated with increased risk of mortality. Though the majority of patients endorsed current alcohol and tobacco use before the admission, it was not significantly associated with mortality.  Conclusions  Five-year cumulative mortality for patients < 40 years of age with alcoholic cirrhosis after their first hospitalization is 49.7%. Old age, most recent NLR, hepatic encephalopathy, and MELD score on admission were associated with increased late mortality.

Bleeding Gastric Lipoma Resected by Endoscopic Submucosal Dissection.

Gastric lipomas are slow-growing benign lesions of the stomach that are often detected incidentally. Most cases are asymptomatic but larger lesions may become symptomatic, thereby requiring treatment. Multiple endoscopic modalities have been used for resection in the past. We present the case of a 67-year-old patient who presented with upper GI bleeding secondary to a gastric lipoma, which was successfully resected by endoscopic submucosal dissection.

Outcomes of Gastrointestinal Polyps Resected Using Underwater Endoscopic Mucosal Resection (UEMR) Compared to Conventional Endoscopic Mucosal Resection (CEMR).

Objective Underwater endoscopic mucosal resection (UEMR) is reported to be superior to conventional endoscopic mucosal resection (CMER) for the complete resection of large polyps and may offer increased procedural efficiency. Aims To compare recurrence rates and adverse events between UEMR and CEMR and define risk factors related to recurrence. Also, to assess recurrence rates in piecemeal endoscopic mucosal resection (EMR) based on the number of pieces resected. Methods We identified all patients with large polyps treated using the UEMR technique at Carilion Clinic, Roanoke, VA, USA between January 1, 2014 and December 31, 2017 with follow-up through October of 2018. We matched the UEMR patients with patients treated using the CEMR technique (1:2 matching, respectively). The Kaplan-Meier curve was used to estimate the cumulative risks of polyp recurrence. The Cox proportional hazard analysis was used to assess risk factors for developing polyp recurrence. Results Sixty-eight patients (mean age: 63.4 ± 12.5 years; 52.9% males) with polyps removed using the UEMR technique (Group 1) were matched with 122 patients (mean age: 64.4 ± 10.0 years; 51.6% males) who had polyps removed using CEMR (Group 2). Polyps resected in fewer pieces (≤ 3) had lower recurrence rates compared to the ones resected in >3 pieces. Right colon polyps removed using UEMR had a lower recurrence rate compared to right colon polyps resected using CEMR. Polyp size and a high degree of dysplasia were associated with a high risk of polyp recurrence after resection. Completing advanced endoscopy training was also associated with a lower risk of recurrence. Conclusion UEMR had a lower recurrence rate compared with CEMR for right colon polyps. Factors associated with recurrence included the degree of training, high-grade dysplasia, and polyp size.