De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids.

Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe the tissue engineering of human thymus organoids from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus-engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses on T cell receptor engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings indicate that hu mice engrafted with iPSC-thymus can serve as a new animal model to study human T cell-mediated immunity and accelerate the translation of findings from animal studies into the clinic.

Helicobacter pylori World Gastroenterology Organization Global Guideline.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Saccharomyces boulardii CNCM I-745 supplementation modifies the fecal resistome during Helicobacter pylori eradication therapy.

BACKGROUND: The gut microbiota is a significant reservoir of antimicrobial resistance genes (ARGs). The use and misuse of antimicrobials can select multi-resistant bacteria and modify the repertoire of ARGs in the gut. Developing effective interventions to manipulate the intestinal resistome would allow us to modify the antimicrobial resistance risk. MATERIALS AND METHODS: Applying shotgun metagenomics, we compared the composition of fecal resistome from individuals treated with triple therapy for Helicobacter pylori plus Saccharomyces boulardii CNCM-I 745 (Sb) versus triple antibiotherapy without S. boulardii (control) before, after, and one month after treatments. DNA samples were sequenced on an Illumina NovaSeq 6000 platform. Reads were trimmed and filtered for quality, and the reads classified as host genome were removed from further analysis. We used the ResFinder database for resistome analysis and the web-based tool ResistoXplorer and RStudio for graphical representation and statistical analysis. RESULTS: We identified 641 unique ARGs in all fecal samples, conferring resistance to 18 classes of antibiotics. The most prevalent ARGs found in at least 90% of the samples before the treatments were against tetracyclines, MLS-B (macrolide, lincosamide, and streptogramin B), beta-lactams, and aminoglycosides. Differential abundance analysis allowed the identification of ARGs significantly different between treatment groups. Thus, immediately after the treatments, the abundance of ARGs that confer resistance to lincosamides, tetracyclines, MLS-B, and two genes in the beta-lactam class (cfxA2 and cfxA3) was significantly lower in the group that received Sb than in the control group (edgeR, FDR <0.05). CONCLUSION: Our study demonstrated that the addition of S. boulardii CNCM-I 745 to the conventional antibiotic eradication therapy for H. pylori reduced the abundance of ARGs, particularly those genes that confer resistance to lincosamides, tetracyclines, MLS-B, and a few genes in the beta-lactams class.

Effect of Saccharomyces boulardii CNCM I-745 as complementary treatment of Helicobacter pylori infection on gut microbiome.

Conventional therapy for H. pylori infection includes the combination of antibiotics and a proton-pump inhibitor. Addition of probiotics as adjuvants for H. pylori antibiotic treatment can increase eradication rate and decrease treatment side effects. Although many studies show the benefits of S. boulardii CNCM I-745 in the treatment of H. pylori infection, the mechanism by which those benefits are achieved is unknown. Here, we report clinical characteristics and fecal microbiota changes comparing conventional anti-H. pylori therapy versus conventional therapy supplemented with S. boulardii CNCM I-745. A total of 74 patients were included in the current study; patients positive for H. pylori (n = 63) were randomly assigned to 2 groups: 34 patients received conventional therapy and 29 antibiotic therapy plus 750 mg of S. boulardii CNCM I-745 daily, for 2 weeks. Eleven patients negative for H. pylori infection were also studied. Patients provided 3 fecal samples: before initiating the antibiotic treatment, upon its completion, and 1 month after treatment. Patients were contacted every 72 h to inquire about side effects and compliance. DNA was extracted, and 16S rRNA was amplified and sequenced on Illumina MiSeq. Bioinformatic analysis was performed using QIIME2. Patients who received the probiotic had a significantly lower frequency of associated gastrointestinal symptoms (P = 0.028); higher number of bacterial diversity evenness (P = 0.0156); higher abundance of Enterobacteria; and lower abundance of Bacteroides and Clostridia upon treatment completion. Addition of S. boulardii CNCM I-745 induced a lower frequency of gastrointestinal symptoms that could be related to changes in gut microbiota.

Duodenal microbiome in patients with or without Helicobacter pylori infection.

BACKGROUND: Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type-2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection. MATERIALS AND METHODS: Thirty-eight biopsies from the proximal duodenum of uninfected and 37 from H pylori-infected individuals were analyzed. Microbiota composition was assessed by PCR amplification and sequencing of 16S rRNA and ITS genes; sequences were analyzed with QIIME2. RESULTS AND CONCLUSIONS: At the phyla level, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Fusobacteria were predominant in the mucosal associated duodenal microbiota (MAM); at the genera level, we observed the predominance of Ralstonia, Streptococcus, Pseudomonas, Haemophilus, Herbaspirillum, Neisseria, and Veillonella. Microbiota α-diversity was higher in H pylori-infected individuals than in non-infected ones. In terms of ß-diversity metrics, there was a statistically significant difference between groups. Also, relative abundance of Haemophilus, Neisseria, Prevotella pallens, Prevotella 7, and Streptococcus was greater in H pylori-infected patients. In infected patients, several types of H pylori were present in duodenal MAM. Finally, the majority of duodenal samples had fungi sequences; the most common taxa observed were Recurvomyces followed by Ascomycota and Basidiomycota.

"It ain't over till it's over!" Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic.

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health-care needs of COVID-19 patients. During the adaptation phase, GI services are calibrated towards a "new normal," and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long-term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence-based decision-making during the adaptation and consolidation phases.

Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines.

BACKGROUND: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. OBJECTIVE: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. MATERIALS AND METHODS: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. RESULTS: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. A significant negative correlation between the mental component of QoL and IL-6 and IL12/23p40 levels was found, but not with IL-8. CONCLUSION: Higher levels of inflammatory cytokines were found in CD patients with IBS than in either those without IBS or controls, indicating that IBS symptoms are associated with an increase in the inflammatory response and a decrease in quality of life of CD patients. These differences in cytokine levels were not related to CD antibodies status suggesting that IBS, in CD, is related to a different inflammatory process than that which is relevant to CD.

The role of the microbiome and the use of probiotics in gastrointestinal disorders in adults in the Asia-Pacific region - background and recommendations of a regional consensus meeting.

The Asia-Pacific region is diverse, with regard to ethnicity, culture, and economic development incorporating some of the world's least and most developed nations. Gastrointestinal diseases are common in the Asia-Pacific region, and their prevalence, presentation, and management vary considerably within the region. There is growing evidence for an important role for the human gut microbiota in gastrointestinal health. As a consequence, geographic variations in the composition of the gut microbiota may contribute to variations in both the prevalence and response to therapy of specific diseases. Probiotics have been proposed as a valuable option in the prevention and treatment of a number of gastrointestinal illnesses, but the quality of available evidence to support their efficacy is variable. A meeting of international experts in adult and pediatric gastroenterology was held at the Sorbonne University, Paris, France, on April 11 and 12, 2016, to discuss current evidence supporting the use of probiotics in gastrointestinal disorders in the Asia-Pacific region. This article provides an overview of the discussions held at this meeting and recommends the formation of an Asia-Pacific Consortium on Gut Microbiota similar to those established in Europe and North America.

Clinical Practice Guideline: Safe Medication Use in the ICU.

OBJECTIVE: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015. STUDY SELECTION: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed. DATA EXTRACTION: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation. DATA SYNTHESIS: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations. CONCLUSIONS: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients.

An optimized clarithromycin-free 14-day triple therapy for Helicobacter pylori eradication achieves high cure rates in Uruguay.

BACKGROUND: Strong acid inhibition increases cure rates with triple therapy and 14-day are more effective than 7-day treatments. The combination of amoxicillin plus metronidazole at full doses has been shown to overcome metronidazole resistance and to achieve good eradication rates even in patients harboring resistant strains. No previous studies have been reported in Latin-America with this optimized triple-therapy scheme. AIMS: The aim of the present study was to assess the eradication rate and tolerance of a new first-line treatment regimen associating strong acid inhibition, amoxicillin and metronidazole. METHODS: Patients from the Clínica de Gastroenterología of the Hospital de Clínicas (Montevideo, Uruguay) were included. Hp status was mainly assessed by at least one of the following: histologyor urea breath test (UBT). A 14-day treatment was prescribed comprising esomeprazole 40mg twice a day plus amoxicillin 1g and metronidazole 500mg, both three times a day. H. pylori cure was assessed by UBT. RESULTS: Forty-one patients were enrolled. Mean age was 53.3±13 years and 17.1% of patients were male. Main indications for treatment were: functional dyspepsia (27.5%), gastritis (45%), gastric or duodenal erosions (20%), gastric ulcer (5%) and intestinal metaplasia (2.5%). H. pylori eradication was achieved in 33 of the 37 patients who returned for follow-up. Eradication rates were 80.5% (95% CI: 68.4-92.6) by intention-to-treat (ITT) analysis and 89.2% (95% CI; 79.2-99.2) per protocol (PP). No major side effects were reported; 26 patients (65.8%) complained of mild side effects (nausea, diarrhea and headache). CONCLUSIONS: Cure rates of this triple therapy including esomeprazole, amoxicillin and metronidazole were 81% per ITT and the treatment was well tolerated. These optimal results with a simple clarithromycin-free triple therapy are better than described for standard triple therapy but there is still room for improvement to reach the desired target of 90% per ITT.

Implementing Psychopharmacology Rounds in a Nursing Facility to Improve Antipsychotic Usage.

OBJECTIVES: Evaluate whether implementing of pharmacy-led psychopharmacology rounds in a nursing facility will improve the rate of antipsychotic use. DESIGN: Single-center, prospective; medication use evaluation (MUE). SETTING: Rutland Nursing Home, Brooklyn, New York. PARTICIPANTS: Nursing facility residents, excluding the pediatric unit. INTERVENTIONS: Weekly interdisciplinary psychopharmacology rounds that include: clinical pharmacists, nurse managers, medical director, social workers, and administration. Antipsychotics were analyzed for all residents for appropriateness of use, proper documentation, and adequate monitoring. MAIN OUTCOME MEASURE: Assess the overall rate of reduction of antipsychotic use after implementation of psychopharmacology rounds. Secondary outcomes assessed improvements in monitoring and documentation for residents on antipsychotics. RESULTS: A total of 81 residents were evaluated over the six-month MUE. Of those residents, 20 had their antipsychotics discontinued, and 11 had their antipsychotics tapered. The overall use of antipsychotics decreased from 14.6% (62/422) to 12.2% (50/411) (P = 0.285). Compliance with indications generally approved by the Centers for Medicare & Medicaid Services improved from 65% (37/57) to 85% (46/54) (P = 0.008). Matching indications on the psychiatry consult and the medication order improved from 58% (33/57) to 80% (43/54) (P = 0.015). Metabolic laboratory monitoring improved from 58% (33/57) to 83% (45/54) (P = 0.003). Improvements in timeliness of psychiatry and ophthalmology consults were not statistically significant. CONCLUSION: Implementing interdisciplinary psycho-pharmacology rounds in a nursing facility resulted in a reduction of inappropriate antipsychotic use and improved monitoring and documentation.

Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment.

BACKGROUND: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies. OBJECTIVES: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis. METHODS: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates. RESULTS: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies. CONCLUSIONS: PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.

Probable Tapentadol-Associated Serotonin Syndrome After Overdose.

PURPOSE: Drug-induced serotonin syndrome is a potentially life-threatening condition. An Ovid MEDLINE, and PubMed search from 1950 to October 2015 revealed one published case report of suspected tapentadol-induced serotonin syndrome. We report a probable case of tapentadol-induced serotonin syndrome after overdose. CASE SUMMARY: A 48-year-old male was found unresponsive after a witnessed overdose of medications including tapentadol. After administration of naloxone by emergency medical services, the patient became combative and presented with altered mental status. He was managed with physical and pharmacologic restraints in the emergency department. Other medications that could be implicated in the patient's presentation include duloxetine and amitriptyline. It was suspected that the opioid properties of tapentadol were masking the patient's signs and symptoms of serotonin syndrome. The patient was admitted to the medical intensive care unit, remained stable, and was discharged 2 days later. Currently, there is one published case report of suspected tapentadol-induced serotonin syndrome after an overdose. The manufacturer of tapentadol reported no cases of serotonin syndrome during clinical trials, but there have been postmarketing cases reported with co-administration of other serotonergic drugs. CONCLUSION: We report a probable case of tapentadol-induced serotonin syndrome after overdose. Further research is needed to better understand the pharmacology and incidence behind this adverse event.

Impact of a Pharmacist-Initiated Vancomycin Monitoring Program.

OBJECTIVES: Evaluate the clinical impact of pharmacist-initiated vancomycin monitoring and dosing in a long-term care setting. DESIGN: Single-center, pretest, post-test design. SETTING: Rutland Nursing Home, Brooklyn, New York. PARTICIPANTS: Nursing facility residents treated with intravenous vancomycin (N = 198). OUTCOME MEASURES: The primary objective is to determine the incidence of acute kidney injury (AKI) a year before and a year after implementation of a pharmacist-initiated vancomycin-monitoring protocol. The secondary objectives are percentage of serum drug levels in therapeutic range and compliance with laboratory testing for monitoring of nephrotoxicity. RESULTS: The overall incidence of AKI decreased from 16.3% (8/49) to 4.7% (7/149) (P = 0.013). Compliance with weekly monitoring for nephrotoxicity via serum creatinine and blood urea nitrogen improved from 76% (37/49) to 95% (141/149) (P ≤ 0.001). Compliance with weekly vancomycin level monitoring improved from 71% (35/49) to 85% (126/149) (P = 0.041). Percentage of vancomycin trough levels in the therapeutic range of 10-20 mcg/mL were shown to have no difference between two groups, but vancomycin levels > 20 mcg/mL decreased from 31% (15/49) to 17% (26/149) (P = 0.048). CONCLUSION: Implementation of pharmacist-driven vancomycin monitoring significantly improved monitoring compliance of vancomycin serum levels and kidney function as well as reduced the incidence of AKI in the long-term care setting.

Off-label use of gastrointestinal medications in the intensive care unit.

PURPOSE: Determine the level of evidence supporting off-label gastrointestinal (GI) medication use and identify the medication class and indication whereby off-label use was most common. MATERIALS AND METHODS: This prospective, multicentered observational study evaluated all medication orders written in 37 intensive care units (ICUs) in the United States, over a 24-hour period. All medications classified as "GI" according to a national reference were identified. The class and indication whereby off-label use was most prominent were determined and the level of evidence was described. RESULTS: There were 774 orders from 363 patients and 63% (489 of 774) were considered off-label. Proton pump inhibitors (PPIs) accounted for most of the off-label usage (55% [271 of 489]), followed by laxatives (16% [77 of 489]) and histamine-2-receptor antagonists (H2RAs; 15% [71 of 489]). When prescribed, 99% (271 of 274) of PPIs, 99% (71 of 72) of H2RAs, and 79% (30 of 38) of promotility agents were off-label. Stress ulcer prophylaxis (100% [309 of 309]), GI bleeding (100% [18 of 18]), and gastric motility (88% [30 of 34]) were the most common off-label indications. The most common strength of recommendation and level of evidence for off-label use was indeterminate (58% [282 of 489]) and none (57% [280 of 489]), respectively. CONCLUSION: The PPIs are the most widely used off-label medications in the ICU. Stress ulcer prophylaxis is the most common indication. The level of evidence supporting off-label GI medication use is poor.

[Intracranial sinus venous thrombosis in ulcerative colitis. Report of one case]. / Trombosis de senos venosos intracraneales: una complicación infrecuente y grave de la colitis ulcerosa. Primera comunicación de un caso en Uruguay.

Intracranial sinus venous thrombosis (ICSVT) is a rare complication of ulcerative colitis that affects from 1.7 to 7.5% of patients. We report a 22 year-old male with ulcerative colitis in treatment with mesalazine and prednisone presenting with headache and speech disturbances. A magnetic resonance imaging of the brain showed a left temporal hemorrhagic infarct with thrombosis of the ispilateral superficial vein and sigmoid venous sinus. No cause of thrombophilia was detected. Anticoagulation with heparin was started which was changed to oral anticoagulation with warfarin. The patient was discharged ten days after admission.

Radiation exposure in gastroenterology: improving patient and staff protection.

Medical imaging involving the use of ionizing radiation has brought enormous benefits to society and patients. In the past several decades, exposure to medical radiation has increased markedly, driven primarily by the use of computed tomography. Ionizing radiation has been linked to carcinogenesis. Whether low-dose medical radiation exposure will result in the development of malignancy is uncertain. This paper reviews the current evidence for such risk, and aims to inform the gastroenterologist of dosages of radiation associated with commonly ordered procedures and diagnostic tests in clinical practice. The use of medical radiation must always be justified and must enable patients to be exposed at the lowest reasonable dose. Recommendations provided herein for minimizing radiation exposure are based on currently available evidence and Working Party expert consensus.

Management of early-stage esophageal neoplasia (MESEN) consensus.

BACKGROUND: Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett's esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario. METHODS: Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article. RESULTS: There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett's length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates. CONCLUSION: Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.

[Implementation and evaluation of a blended learning course on gastroesophageal reflux disease for physicians in Latin America]. / Implementación y evaluación de un curso semipresencial sobre enfermedad por reflujo gastroesofágico para médicos de América Latina.

Integrating evidence-based clinical practice guidelines on gastroesophageal reflux disease into medical practice is of prime importance in Latin America, given its high prevalence in this region. The aim of this project was to implement and assess an educational intervention on gastroesophageal reflux disease, aimed at primary care physicians in Latin America, with contents based on current clinical guidelines. The course included initial activities, whether face-to-face or through distance learning, and a 2-month period of Internet study and interaction. A pilot test was carried out in Uruguay, which was then repeated in 5 countries (Mexico, Colombia, Venezuela, Argentina and again in Uruguay). A global template was designed, which was then adapted to each of the countries: this was done with the participation of local institutions and leaders. Local credits were given for recertification. Participation was free. Of 3,110 physicians invited to participate, 1,143 (36.8%) started the course. Of these, 587 (51.4%) accessed at least half the contents of the course and 785 (68.7%) took part in the clinical discussions. A total of 338 (29.6%) completed all the requirements of the course and received a certificate. Among physicians who took both the pre- and post-intervention knowledge tests, scores improved from 60 to 80% (P<.001). Ninety-two percent of planned changes in clinical practice were related to the pedagogic aims of the course. In conclusion, a multifaceted, 2-phase continuing education course was successfully imparted in Latin America, with an overall design that was adapted to each country. Determination of specific needs and the participation of national experts were fundamental to the success of the course.