Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

BACKGROUND AND AIMS: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era. METHODS: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes. RESULTS: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC. CONCLUSIONS: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

Secondary aorto-duodenal fistula: a diagnostic challenge in a patient with fever and anemia.

A 69-year-old male, three years post-endovascular exclusion for an abdominal aortic aneurysm, presented with asthenia and fever. An abdominal CT scan showed no gastrointestinal tract communications, abscess, or contrast extravasation. Tc-99m-HMPAO-labeled leukocytes scintigraphy with SPECT/CT revealed increased uptake on the posterior surface of the aortic graft, along with air bubbles in its right iliac limb. Upper gastrointestinal endoscopy was performed, revealing a duodenal ulcer in the transition between the second and third portions. The ulcer exhibited yellow graft tissue at its center. The patient underwent in situ reconstruction, involving the replacement of the infected prosthetic graft, and the duodenal defect was addressed through segmental resection and duodenojejunal anastomosis. Secondary aorto-duodenal fistula (SADF), a rare complication of vascular surgery, may arise from factors such as local infection or graft-bowel contact. SADF, often located in the duodenum, poses a high mortality risk, necessitating early diagnosis. Clinical presentation varies from significant upper gastrointestinal bleeding to obscured bleeding.

Blue esophagus as a diagnosis of aortic dissection.

A 76-year-old patient, admitted to the department of cardiac surgery, anticoagulated, started with acute dysphagia. An upper endoscopy revealed a blue mucosa from the upper to distal esophagus, with narrowing of the lumen caused by an extrinsic compression. A computed to¬mography (CT) of the thorax was performed, showing a 85x55 mm mediastinal hematoma causing extrinsic compression of the esophagus. Subsequently, a contrast-enhanced CT scan was performed, confirming a contained rupture of descending thoracic aortic dissection as the cause of the hematoma.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Value of CRP/albumin ratio as a prognostic marker of acute pancreatitis: a retrospective study.

INTRODUCTION: the C-reactive protein (CRP) to albumin ratio is an inflammatory marker that has shown promise in the prognosis of critically ill patients. This study is aimed to assess the value of CRP/albumin ratio to predict severity in acute pancreatitis. METHODS: a retrospective study was performed using a prospectively collected database of patients diagnosed with AP admitted to the Department of Gastroenterology between March 2014 and December 2021. RESULTS: among 722 patients included in the study, 78.67 % had mild, 15.65 % had moderately severe, and 5.67 % had severe acute pancreatitis. The CRP/albumin ratio was significantly associated with severe AP (OR 1.02; 95 % CI: 1.01-1.03; p < 0.001), and each ten-unit increase in the ratio was associated with a 20 % increased likelihood of severe acute pancreatitis. The area under the ROC curve (AUC) value of the CRP/albumin ratio in severe acute pancreatitis was 0.68 (95 % CI: 0.58-0.77), which was higher than that of the Ranson criteria (0.62). The optimal cut-off value for predicting severe acute pancreatitis was 7.51, with a sensitivity of 63.4 % and specificity of 65.6 %. CONCLUSIONS: despite its low sensitivity and specificity, the CRP/albumin ratio could be used as a complementary marker to the current scoring systems for the initial assessment of acute pancreatitis prognosis. It is easily obtainable and can provide additional prognostic information to clinicians.

Esophageal epidermoid metaplasia. An unusual find.

A 62-year-old woman presented with an episode of upper gastrointestinal bleeding. Upper endoscopy revealed white exudates at the middle and lower third of the esophagus. Biopsies proved epidermoid metaplasia of the esophagus with low-grade dysplasia. We discuss the risk factors, preneoplastic potential and available treatments of this entity.

Plasma levels of intestinal fatty-acid binding protein (I-FABP), abdominal distension and hydrogen concentration after lactitol small intestinal bacterial overgrowth (SIBO) test.

Breath tests with glucose, lactulose or lactitol are useful for diagnosis of small intestinal bacterial overgrowth (SIBO). Nevertheless, they have suboptimal sensitivity and specificity and, indeed, are positive in a considerable number of patients with irritable bowel syndrome (IBS). The complexity in the management of patients with functional intestinal disorders and the availability of these tests are leading to frequent diagnoses of SIBO. Intestinal Fatty-Acid Binding protein (I-FABP) is a protein present in the cytosol of intestinal epithelial cells. Its plasmatic levels have been related to different enteropathies and, therefore, could be a marker of early intestinal damage with unconfirmed clinical utility. Hence, we have studied the plasmatic I-FABP level of patients who are requested a lactitol test to confirm SIBO and related it to clinical and laboratory characteristics and SIBO test results.

Influence of enlarged waist circumference and hypertriglyceridemia in the severity of acute pancreatitis: A retrospective study.

INTRODUCTION: Acute pancreatitis is a frequent inflammatory gastrointestinal disorder with high mortality rates in severe forms. An early evaluation of its severity is key to identify high-risk patients. This study assessed the influence of waist circumference together with hypertriglyceridemia on the severity of acute pancreatitis. METHODS: A retrospective study was performed, which included patients admitted with acute pancreatitis from March 2014 to March 2021. Patients were classified into four phenotype groups according to their waist circumference and triglyceride levels: normal waist circumference and normal triglycerides; normal waist circumference and elevated triglycerides; enlarged waist circumference and normal triglycerides; and enlarged waist circumference and triglycerides, namely hypertriglyceridemic waist (HTGW) phenotype. Clinical outcomes were compared among the groups. RESULTS: 407 patients were included. Systemic inflammatory response syndrome (SIRS) and intensive care unit admission were most frequent among patients in the HTGW phenotype group, at 44.9% and 8.2%, respectively. The incidence of local complications was higher in the normal waist circumference with elevated triglycerides group (27%). On multivariable analysis, an enlarged waist circumference was related to an increase of 4% and 2% in the likelihood of developing organ failure and SIRS, respectively. Hypertriglyceridemia was an independent risk factor for both organ failure and local complications. CONCLUSIONS: HTGW phenotype was significant related to developing of SIRS. It seems that an enlarged waist circumference has a greater role than hypertriglyceridemia in the development of SIRS. Obesity and hypertriglyceridemia were both independent risk factors for organ failure. Patients with hypertriglyceridemia were more likely to develop local complications.

Incidence, and natural history of inflammatory bowel disease in Castilla y León: Prospective and multicenter epidemiological study. / Incidencia e historia natural de la enfermedad inflamatoria intestinal en Castilla y León: estudio prospectivo, multicéntrico y poblacional.

INTRODUCTION: The incidence of inflammatory bowel disease (IBD) is increasing worldwide. OBJECTIVES: To evaluate the incidence of IBD in Castilla y León describing clinical characteristics of the patients at diagnosis, the type of treatment received and their clinical course during the first year. MATERIALS AND METHODS: Prospective, multicenter and population-based incidence cohort study. Patients aged >18 years diagnosed during 2017 with IBD (Crohn's disease [CD], ulcerative colitis [UC] and indeterminate colitis [IC]) were included from 8 hospitals in Castilla y León. Epidemiological, clinical, and therapeutic variables were registered. The global incidence and disease incidence were calculated. RESULTS: 290 patients were diagnosed with IBD (54.5% UC, 45.2% CD, and 0.3% IC), with a median follow-up of 9 months (range 8-11). The incidence rate of IBD in Castilla y Leon in 2017 was 16.6 cases per 10,000 inhabitants-year (9/105 UC cases and 7.5/105 CD cases), with a UC/CD ratio of 1.2:1. Use of systemic corticosteroids (47% vs 30%; P=.002), immunomodulatory therapy (81% vs 19%; P=.000), biological therapy (29% vs 8%; P=.000), and surgery (11% vs 2%; p=.000) were significatively higher among patients with CD comparing with those with UC. CONCLUSIONS: The incidence of patients with UC in our population increases while the incidence of patients with CD remains stable. Patients with CD present a worse natural history of the disease (use of corticosteroids, immunomodulatory therapy, biological therapy and surgery) compared to patients with UC in the first year of follow-up.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg).

BACKGROUND: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

2021 Guidelines on Helicobacter pylori. Coincidences and divergences between the Spanish and World Gastroenterology Organisation (WGO) guidelines.

This editorial summarizes and discusses the most relevant aspects of the latest WGO guidelines on Helicobacter pylori infection, while considering the recently reported Spanish consensus on its management.

V Spanish Consensus Conference on Helicobacter pylori infection treatment. / V Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori.

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.

Persistent Villous Atrophy in De Novo Adult Patients With Celiac Disease and Strict Control of Gluten-Free Diet Adherence: A Multicenter Prospective Study (CADER Study).

INTRODUCTION: A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. METHODS: Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. RESULTS: Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 µg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). DISCUSSION: The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg).

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management." METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.

Villous atrophy persistence in celiac disease despite following a gluten-free diet must be clarified.

We read with great interest the article recently published in REED by Shadegi et al. Villous atrophy (VA) persists in 35 % and 23.7 % of celiac disease (CD) patients for six and 24 months, respectively, after following a gluten-free diet (GFD). The authors think that the time following a GFD must be longer than two years in some patients to achieve mucosal healing and we agree with this. Our experience comes from a short series of ten females and three males with CD, diagnosed at an average age of 36 years (15-72) based on serology (anti-TG2 > 10 IU/ml or anti-Em positive) and a duodenal biopsy showing VA. All cases followed a GFD, according to the anamnesis and underwent a second duodenal biopsy and anti-TG2 determination after 42 (10-202) months. Immunogenic peptides of gluten (IPG) in feces were determined in four patients.

Influence of the onset of the SARS-CoV-2 pandemic on the diagnosis and treatment of ulcerative colitis.

We analyzed how the healthcare restrictions that occurred in hospitals in Spain due to the COVID-19 pandemic, mainly in March, April and May 2020, influenced the diagnosis, management and treatment of ulcerative colitis (UC) in our center.

Ischemic skin necrosis secondary to the use of terlipressin.

We present the case of a 45-year-old male with alcoholic liver cirrhosis Child-Pugh C and chronic left lower limb lymphedema, hospitalized because of ascites and renal impairment (Cr 2.33 mg/dl). He received intravenous albumin and terlipressin (1 mg every 4h) for suspected hepatorenal syndrome. After 48 hours, purpuric skin lesions appeared on both lower extremities, scrotum and umbilical hernia. Renal function improved (Cr 0.49 mg/dl). Nevertheless, terlipressin was discontinued as the skin lesions worsened due to epidermal detachment, and oral sildenafil was administered at 50 mg twice per day. The left lower limb was severely affected with extensive skin and soft tissue necrosis, which led to supracondylar amputation. All the other lesions had a satisfactory evolution, with reepithelialization of the damaged areas.

Prevalence and factors associated with poor sleep quality in inflammatory bowel disease outpatients.

INTRODUCTION: sleep disorders are common in the general population and have obvious repercussions on quality of life. Poor sleep quality is associated to inflammatory activity and fatigue in inflammatory bowel disease (IBD) patients. This study aimed to analyze the prevalence of poor sleep quality and the factors associated with it, in IBD outpatients. METHODS: an observational and prospective study was performed in which epidemiological, clinical and laboratory data were collected from clinical records and patients who consecutively attended an outpatient clinic. Pittsburgh Sleep Quality index (PSQI), Hospital Anxiety and Depression Scale (HADS) and International Physical Activity Questionnaire (IPAQ) were used to measure sleep quality, anxiety, depression and physical activity, respectively. Treatment optimizations, hospital admissions or surgery were prospectively verified three months after the baseline visit. RESULTS: one hundred and two patients were included and 54.9 % had poor sleep quality (PSQI score > 5). No association was found between poor sleep quality and IBD-related variables such as type of disease, ulcerative colitis (UC) extent, Crohn's disease (CD) location or behavior, time from diagnosis, treatment, prior admissions or surgery and laboratory values. Rotating night shift job (OR 6.116, 95 % CI: 1.312-28.514), HAD score for depression (OR 1.125, 95 % CI: 1.062-1.490) and frequency (days per week) of vigorous physical activity (OR 0.783, 95 % CI: 0.619-0.991) were independent predictors of poor sleep quality. A Pittsburgh questionnaire score higher than 5 was not significantly associated to treatment optimization in the total patient cohort (15.2 % vs 18.2 %, p = 0.451), in UC patients (18.2 % vs 10.7 %, p = 0.362) or CD patients (12.5 % vs 25.9 %, p = 0.198). CONCLUSIONS: poor sleep quality is present in more than half of IBD patients. Aspects not directly related to IBD are associated to poor sleep quality.

V Spanish Consensus Conference on Helicobacter pylori infection treatment.

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.