Common variable immunodeficiency enteropathy is a sprue-like disease, which may manifest as a severe malabsorption syndrome with nutritional deficits and cachexia. The authors report a case of a 33-year-old Afghan man, who presented to the emergency department due to chronic watery diarrhea and severe malnourishment. He had been previously misdiagnosed with celiac disease in his early adulthood; however, this was based on inconclusive findings. After a thorough diagnostic workup, the final diagnosis of common variable immunodeficiency enteropathy with symptomatic norovirus infection of the gut was obtained during his prolonged hospitalization. A slow but progressive improvement was observed with immunoglobulin replacement therapy, corticotherapy, and ribavirin treatment. This is a noteworthy case of a rare malabsorption disorder, and it reviews important aspects concerning the differential diagnosis of small bowel villous atrophy of unknown etiology, as well as gastrointestinal manifestations of common variable immunodeficiency disorder.

Background: sarcopenia, frailty and malnutrition are associated with adverse outcomes in liver cirrhosis. Studies assessing the prognostic value of these conditions in ambulatory patients with cirrhosis are scarce. Methods: a prospective cohort study was performed, with consecutive inclusion of all patients with cirrhosis observed in the Hepatology outpatient clinic of a Portuguese tertiary center. At study enrolment, evaluation of muscle mass (ultrasound quadriceps femoris thickness), muscle strength (handgrip dynamometry) and nutritional status (Patient-Generated Subjective Global Assessment Short Form) were performed. Follow-up ended upon the occurrence of a composite endpoint, comprising of liver decompensation events and liver-related death, or last medical appointment/non-liver related death before the end of the study. The prognostic value of anthropometrical parameters and nutritional status in the composite endpoint was assessed using a multivariate Cox regression analysis, adjusted for several confounders. Results: ninety patients were enrolled (80 % male), with a mean age of 63.5 +/- 10.5 years. The median follow-up was 30 (interquartile range 38) weeks, during which, 12 patients reached the composite endpoint. These patients presented a lower mean handgrip strength (23.1 +/- 6.41 vs 30.3 +/- 10.4 kg, p = 0.04) compared to patients who did not reach the composite endpoint. However, Cox regression multivariate analysis did not find any independent predictors of the composite endpoint, apart from previous decompensation episodes. Conclusion: in this study, muscle strength was lower in the group of patients with cirrhosis who presented a liver-related event. Handgrip strength might be a promising tool in the ambulatory setting to identify patients at risk of liver decompensation and liver-related death in the short term.

Background: Bowel preparation is a major quality criterion for colonoscopies. Models developed to identify patients with inadequate preparation have not been validated in external cohorts. We aim to validate these models and determine their applicability. Methods: Colonoscopies between April and November 2019 were retrospectively included. Boston Bowel Preparation Scale ≥2 per segment was considered adequate. Insufficient data, incomplete colonoscopies, and total colectomies were excluded. Two models were tested: model 1 (tricyclic antidepressants, opioids, diabetes, constipation, abdominal surgery, previous inadequate preparation, inpatient status, and American Society of Anesthesiology [ASA] score ≥3); model 2 (co-morbidities, tricyclic antidepressants, constipation, and abdominal surgery). Results: We included 514 patients (63% males; age 61.7 ± 15.6 years), 441 with adequate preparation. The main indications were inflammatory bowel disease (26.1%) and endoscopic treatment (24.9%). Previous surgery (36.2%) and ASA score ≥3 (23.7%) were the most common comorbidities. An ASA score ≥3 was the only identified predictor for inadequate preparation in this study (p < 0.001, OR 3.28). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of model 1 were 60.3, 64.2, 21.8, and 90.7%, respectively. Model 2 had a sensitivity, specificity, PPV, and NPV of 57.5, 67.4, 22.6, and 90.5%, respectively. The AUC for the ROC curves was 0.62 for model 1, 0.62 for model 2, and 0.65 for the ASA score. Conclusions: Although both models accurately predict adequate bowel preparation, they are still unreliable in predicting inadequate preparation and, as such, new models, or further optimization of current ones, are needed. Utilizing the ASA score might be an appropriate approximation of the risk for inadequate bowel preparation in tertiary hospital populations.

A 55-year-old woman with cirrhosis was admitted for acute decompensation caused by portal vein thrombosis. Ten days later, the patient presented melena. Esophagogastroscopy revealed two gastric polyps, both with bleeding stigmata. One of the polyps was removed with a diathermic loop, after adrenalin injection, while in the other the "ligate and let go" technique was applied, after biopsy. A "metallic tulip-bundle" technique, combining through the scope and over-the-scope clips, was applied for hemostasis. This case underlines how the combination of various endoscopic techniques may be useful to manage upper gastrointestinal bleeding, especially in patients with important comorbidities.

This case demonstrates the utility of the "purse string" to close large defects and shows that optical diagnosis may have pitfalls in evaluating the invasion of neoplastic lesions, particularly large ones.

Background/Aims: In the past, dye-spraying chromoendoscopy was the technique of choice for colonic surveillance in patients with long-standing extensive inflammatory bowel disease. Recent evidence suggests that virtual chromoendoscopy is an equally acceptable technique. Materials and Methods: Eleven gastroenterologists were given a survey with 20 pairs of pictures from inflammatory bowel disease surveillance colonoscopies (10 with nondysplastic lesions, 5 with dysplastic lesions, and 5 with no lesions). Each pair contained the same image captured during colonoscopy using indigo carmine and narrow-band imaging. For each picture, the gastroenterologist assessed the presence/absence of lesion and, when a lesion was identified, assessed the presence/absence of dysplasia and delineated its margins. To compare lesion and dysplasia detection between techniques, sensitivity, specificity, and interobserver agreement were calculated. The chi-square test was used to assess the accuracy of margins delineation. Results: When assessing lesion and dysplasia detection, similar sensitivity and specificity values were obtained for both techniques. Interobserver agreement analysis revealed that dye-spraying chromoendoscopy and virtual chromoendoscopy had a moderate agreement in lesion detection but, for dysplasia detection, dye-spraying chromoendoscopy had a slight agreement [K = 0.11 (0.03-0.18), P <.01] and virtual chromoendoscopy a fair agreement [K = 0.30 (0.22-0.37), P <.01]. Margin delineation was similar between techniques. Conclusion: Sensitivity and specificity for lesion and dysplasia detection, as well as the accuracy of margins delineation, were similar between dye-spraying chromoendoscopy and virtual chromoendoscopy. Interobserver agreement for dysplasia detection was suboptimal in both techniques; however, it was superior when using virtual chromoendoscopy. These findings suggest that virtual chromoendoscopy constitutes a valid alternative for dysplasia screening in inflammatory bowel disease.

Background: Molecular therapy with sorafenib remains the mainstay for advancedstage hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining long-lasting benefits due to the high chemoresistance rate. Objective: To perform, for the first time, an overview of the literature concerning the role of adenosine triphosphate-binding cassette (ABC) transporters in sorafenib therapy for hepatocellular carcinoma. Methods: Three online databases (PubMed, Web of Science, and Scopus) were searched, from inception to October 2020. Study selection, analysis, and data collection were independently performed by two authors. Results: The search yielded 224 results; 29 were selected for inclusion. Most studies were pre-clinical, using HCC cell lines; three used human samples. Studies highlight the effect of sorafenib in decreasing ABC transporters expression. Conversely, it is described the role of ABC transporters, particularly multidrug resistance protein 1 (MDR-1), multidrug resistance-associated proteins 1 and 2 (MRP-1 and MRP-2) and ABC subfamily G member 2 (ABCG2) in sorafenib pharmacokinetics and pharmacodynamics, being key resistance factors. Combination therapy with naturally available or synthetic compounds that modulate ABC transporters may revert sorafenib resistance by increasing absorption and intracellular concentration. Conclusion: A deeper understanding of ABC transporters’ mechanisms may provide guidance for developing innovative approaches for hepatocellular carcinoma. Further studies are warranted to translate the current knowledge into practice and paving the way to individualized therapy.

Aims The best timing for small bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) for the management of obscure gastrointestinal bleeding (OGIB) remains unknown. This meta-analysis aimed to compare, for the first time, diagnostic and therapeutic yields, detection of active bleeding and vascular lesions, rebleeding, and mortality of “early” versus “non-early” SBCE and DAE.

A 41-year-old male with a history of Crohn’s disease (CD) with penetrating phenotype (A2L2B3p, Montreal Classification), who was diagnosed aged 17 years and had started treatment with infliximab monotherapy at 30 years old, had been on clinical, imagiological, and endoscopic remission for the previous 2 years. On follow-up ileocolonoscopy with the purpose of considering stopping biological treatment (per the patient’s wishes), only 2 superficial ulcers in the sigmoid colon and 3 small erosions in the terminal ileum (shown in Fig. 1) were detected. Histological examination of the ileum erosions demonstrated an infiltrate of atypical lymphoepithelial cells, CD20 positive and CD5, CD23, CD10, and cyclinD1 negative, compatible with a marginal zone B-cell lymphoma of the mucosal-associated lymphoid tissue (MALT; shown in Fig. 2). Immunoglobulin deposition was not identified in this tissue. Cervico-thoraco-abdominopelvic computed tomography and magnetic resonance bowel enterography were unremarkable. The histological specimens were analyzed by two different pathologists with expertise in hematopathology. Serum lactate dehydrogenase, β2-microglobulin, and immunoglobulin levels were normal. Hepatitis C virus antibodies and DNA of Campylobacter jejuni on ileum tissue were negative. Staging was complete as a MALTlymphoma Galian stage A and Lugano stage I. A 6-month course of antibiotic therapy with combined metronidazole and ampicillin was proposed after consultation with Hematology. As the patient was in clinical remission and the endoscopic activity was residual, biologic therapy was suspended due to an unfavorable risk/benefit. Unfortunately, CD recurred clinically and endoscopically so vedolizumab was started after endoscopic and histologic documentation of MALT remission (1 year after diagnosis, 6 months after antibiotics). Due to a primary non-response, the patient was swapped to ustekinumab and is currently in clinical remission, with a further endoscopic evaluation at 6–9 months.

Gastrenterology Department, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal Received 7 January 2022 Accepted 22 January 2022 Correspondence to Edgar Afecto, MD, Rua Conceição Fernandes, 4434-502, Vila Nova de Gaia, Portugal, Tel: +351 227865100; fax: +351 227868369; e-mail: [email protected]

Introduction/Aims In capsule endoscopy (CE), small bowel subepithelial lesions (SBSL) are difficult to distinguishing from innocent mucosal protrusions. The SPICE score (smooth, protruding lesions index on CE) and a score that assesses the SBSL protrusion angle were developed. We intend to determine if a composite score is superior to the proposed models. Methods All CE between 01/2010 and 12/2020 were included if a smooth, round protruding lesion was identified. Both scores and a composite score (SPICE>2 and Angle<90º) were calculated after video review. Mucosal protrusions were defined as SBSL if they had a histological/imaging diagnosis and innocent protrusions if otherwise. All patients without at least one appointment and an additional diagnostic exam after CE were excluded. Results A total of 34 CE included, 64.7% men, age 65.4±14.7 years. The most common indication for CE was anemia (52.9%). SBSL were identified in 17 cases, with lipomas (14.7%) being the most frequent diagnosis. Both the SPICE (AUROC 0.90, p<0.001) and protrusion angle scores (AUROC 0.74, p=0.019) accurately distinguished SBSL from innocent protrusions. Applying a 90º cut-off, the protrusion angle has a sensitivity of 52.9% and specificity of 88.2%. Applying a cut-off of >2 points, the SPICE score has a sensitivity of 64.7% and specificity of 94.2%. The composite score had a sensitivity, specificity, positive and negative predictive value of 47.0%, 100%, 100% and 65.4%. Conclusion We propose that in cases where both a SPICE>2 and angle of <90º are obtained, additional follow-up investigation should always be undertaken, as the likelihood of SBSL is high.

The authors describe a case of a rectal mucosa-associated lymphoid tissue lymphoma in a 78-year-old female patient, manifested as rectal bleeding. Despite being commonly diagnosed in the localized form, this patient had supradiaphragmatic involvement on disease staging. Immunochemotherapy was proposed due to the disseminated involvement and poorer prognosis.

Background and Aims: Small-bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) are essential in obscure GI bleeding (OGIB) management. However, the best timing for such procedures remains unknown. This meta-analysis aimed to compare, for the first time, diagnostic and therapeutic yields, detection of active bleeding and vascular lesions, recurrent bleeding, and mortality of "early" versus "nonearly" SBCE and DAE. Methods: MEDLINE, ScienceDirect, and Cochrane Central Register of Controlled Trials were searched to identify studies comparing early versus nonearly SBCE and DAE. Random-effects meta-analysis was performed; reporting quality was assessed. Results: From 1974 records, 39 were included (4825 patients). Time intervals for the early approach varied, within 14 days in SBCE and 72 hours in DAE. The pooled diagnostic and therapeutic yields of early DAE were superior to those of SBCE (7.97% and 20.89%, respectively; P < .05). The odds for active bleeding (odds ratio [OR], 5.09; I-2 = 53%), positive diagnosis (OR, 3.99; I-2 = 45%), and therapeutic intervention (OR, 3.86; I-2 = 67%) were higher in the early group for SBCE and DAE (P < .01). Subgroup effects in diagnostic yield were only identified for the early group sample size. Our study failed to identify differences when studies were classified according to time intervals for early DAE (I-2 < 5%), but the analysis was limited because of a lack of data availability. Lower recurrent bleeding in early SBCE and DAE was observed (OR, .40; P < .01; I-2 = 0%). Conclusions: The role of small-bowel studies in the early evaluation of OGIB is unquestionable, impacting diagnosis, therapeutic intervention, and prognosis. Comparative studies are still needed to identify optimal timing.

BACKGROUND The prevention of severe acute respiratory syndrome corona virus 2 transmission implies several social distancing mea- sures, imposing a change in the protocols of several hospital departments. Capsule endoscopy protocols changes were implemented and evaluated in a Portuguese tertiary center. METHODS The authors compared pre-pandemic and peri-pandemic protocols, the latter favoring social distancing, used in MiroCam (IntroMedic, Seoul, Korea) and PillCam Crohn (Medtronic, Minneapolis, Minn, USA) capsule endoscopy, in a Gastroenterology Department of a tertiary center. All capsule endoscopy performed in outpatients between February 2018 and September 2020 was included. The authors compared significant lesions detection rate, completeness of procedure, adequate bowel preparation, complications rate, and patient satisfaction (through a brief phone call survey) among the protocols. RESULTS This study included 70 MiroCam CE and 43 PillCam Crohn capsule endoscopy. No statistically significant differences concern- ing performance measures and patients satisfaction were found among the pre-pandemic protocol and the peri-pandemic protocol in MiroCam capsule endoscopy. Conversely, in PillCam Crohn capsule endoscopy, the rate of complete exams was significantly inferior in the peri-pandemic protocol (84.8% vs 50.0%, P = .036), with no other statistically significant differences in the remaining parameters. CONCLUSION The performance measures and patient satisfaction were similar among the protocols analyzed for MiroCam capsule endoscopy. Thus, the readjustment of this capsule endoscopy system, which favors a reduction in hospital stay, appears to be a good alternative to the former protocols in this pandemic era. In contrast, the rate of complete exams was significantly inferior in the adapted protocol to the pandemic era for PillCam Crohn capsule endoscopy, disfavoring its maintenance in the clinical practice.

Abstract Background Intravenous steroids (IV-S) remain the cornerstone of treatment of Acute Severe Ulcerative Colitis (ASUC). However, one-third of these patients are refractory to this treatment. Several indices have been developed to predict the failure of IV-S for ASUC, using clinical data at day 3 of treatment. However, indices able to predict IV-S failure based on admission data are lacking. Methods A retrospective analysis of all consecutive hospital admissions due to ASUC, in a Portuguese tertiary centre, between February 2007 and April 2021 was performed. Only patients receiving IV-S for at least 3 consecutive days were included in this study. IV-S non-response was defined as the need for a second-line therapy or surgery. The following clinical data was collected from each patient: age, gender, disease duration, Montreal disease extension, previous ASUC, previous and on admission medical therapies (oral mesalazine, rectal mesalazine, oral steroids, immunosuppressants and monoclonal antibodies), fever on admission and weeks of symptoms’ worsening before admission. The following parameters on admission were also registered: C-reactive protein, albumin level, hemoglobin, leucocytes count, platelets count, Mayo endoscopic subscore and presence of transverse colonic dilatation on abdominal X-ray ≥5.5 cm. Univariate analysis was used to identify predictive factors of IV-S failure. Results 68 patients (64.7% female), with a mean age of 40.4 (±16.2) years, were included in this study. 9 patients (13.2%) did not respond to IV-S therapy. On univariate analysis, only transverse colonic distension on X-ray was more frequent in IV-S non-responders (33.3% vs 6.8%, p=0.04). Conclusion Clinical data on admission, including previous medication, analytical parameters and endoscopic activity were not predictive of IV-S refractoriness in this population. However, abdominal X-ray showed to be useful to predict the need for a rescue therapy. These findings highlight, in one hand, the need of larger studies to identify on admission predictors of IV-S refractoriness and, in other hand, the importance of abdominal X-ray, in patients admitted due to ASUC.

BACKGROUND:Recently, Lyon consensus and ROME IV were published as there was a need to create a more objective evaluation for gastroesophageal reflux disease (GERD) in order to better predict treatment outcomes. However, with classical pH-impedance measures, some patients would still have diagnostic uncertainty, and new metrics, such as mean nocturnal basal impedance (MNBI), have emerged to corroborate with GERD diagnosis. The aim of the present study was to describe the prevalence of GERD, functional heartburn (FH), reflux hypersensitivity (RH), and undetermined diagnosis using current consensuses and to evaluate if MNBI could be considered a supportive measure for the diagnosis of GERD.METHODS:Patients who underwent pH-multichannel intraluminal impedance (MII-pH) for suspected GERD between 2013 and 2018 were included. Subjects with previous diagnosis of GERD (e.g., esophagitis grade C or D according to Los Angeles classification, Barrett's esophagus, or peptic stricture), atypical symptoms, major esophageal motor disorder, eosinophilic esophagitis, or under proton pump inhibitor were excluded from the analysis.RESULTS:We included 75 patients. The prevalence of GERD, FH, RH and undetermined diagnosis was 44%, 14.7%, 12%, and 29.3%, respectively. MNBI was lower in patients with GERD (GERD: 1,307.5 ± 817.9 Ω vs. FH: 3,039.6 ± 1,040.8 Ω, RH: 2,617.1 ± 1,342.2 Ω, undetermined: 2,351.9 ± 1,018.2, p < 0.001), although it was similar between patients with FH and RH (p = 0.44) or between undetermined diagnosis and FH/RH (p = 0.15). More patients with a GERD diagnosis had a MNBI under 2,292 Ω (GERD: 93.9% vs. non-GERD: 31.7%, p < 0.001).CONCLUSION:In our study, using MII-pH criteria, less than half of the patients had a GERD diagnosis. MNBI showed additional value as another metric for the diagnosis of GERD.

Introduction: This study aimed to evaluate the effect of small-bowel angioectasia on survival, given the hypothesis that angioectasia might be an independent risk factor of frailty and poor outcomes. Methods: In this retrospective cohort study, all patients undergoing small-bowel capsule endoscopy between 2010 and 2013 for obscure gastrointestinal bleeding from a Portuguese tertiary centre were included. Follow-up started after capsule endoscopy and ended upon death or end of the study (November 2020). Survival analysis was performed using a Cox proportional-hazards model, in order to analyse the effect of small-bowel angioectasia on survival as well as potentially confounding factors (age, vascular diseases and chronic kidney disease). Results: A total of 176 patients were included in this study (50.6% male), with a median age of 68.5 years (IQR 24). The median follow-up was 7 years (IQR 4), during which 67 (38.1%) patients died. Seventy-three (41.5%) patients had at least one small-bowel angioectasia on capsule endoscopy. On multivariate Cox regression analysis, only age, peripheral arterial disease, history of previous mesenteric ischaemia and chronic kidney disease were independent risk factors of death. The presence of small-bowel angioectasia did not affect survival in this analysis (HR 1.30; 95% CI 0.75–2.23; p = 0.35). Conclusion: In this retrospective cohort study, some comorbidities and age were independent predictors of poor survival. The presence of small-bowel angioectasia per se did not affect survival.

Evidence for an urgent approach to ongoing overt suspected small-bowel bleeding (SSBB) is scarce. We aimed to analyze our series of urgent small-bowel capsule endoscopies (SBCEs) for ongoing overt SSBB and to identify factors associated with positive findings and outcomes. A retrospective study of all SBCEs performed in the first 48 h after admission for overt SSBB between January 2006 and February 2022 was performed. Descriptive and inferential analyses (univariate and multivariable) were performed. Eighty-three urgent SBCEs were performed for overt SSBB. Patients were mostly men (69.2%, median age 68) and were followed for a median of 58.2 months (range 5–176). The diagnostic yield was 80.7%; in 60.2%, blood was detected in the small bowel (SB), while in 50.6%, a bleeding lesion was identified, mostly angioectasia. Patients with diabetes mellitus or taking NSAIDs were more prone to present SB findings, yet the explanatory power was low. Endoscopic or surgical treatments were performed in 28.9% and 19.3%, respectively, with the “non-conservative” therapeutic yield being 56.6%. Rebleeding occurred in 20.5% and was associated in the multivariable analysis with the female gender and anticoagulants use. This cohort of urgent SBCE, the largest from a European center, reinforces the usefulness of SBCE for ongoing overt SSBB management. This prompt performance of this procedure is highly effective, regardless of patients’ features.