Effect of proton pump inhibitors on susceptibility and melanogenesis of Sporothrix species.

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

Review article: Oesophageal disorders in chronic liver disease.

BACKGROUND: Oesophageal disorders and chronic liver disease are common worldwide and significantly impact quality of life. The intricate link between these conditions, including how oesophageal disorders like GERD, Barrett's oesophagus and oesophageal cancer affect and are affected by chronic liver disease, remains poorly understood. AIMS: To review the relationship between oesophageal disorders and chronic liver disease, evaluating epidemiology, pathophysiology and therapeutic factors. METHODS: We reviewed the literature on the relationship between oesophageal disorders and chronic liver disease, including cirrhosis, using the PubMed database RESULTS: Oesophageal disorders such as gastroesophageal reflux disease, Barrett's oesophagus, oesophageal cancer, oesophageal motor disorders and oesophageal candidiasis are prevalent among individuals with cirrhosis, exacerbating the burden of liver disease. These diseases have a multifaceted symptomatology and pathogenic basis, posing a significant challenge in cirrhotic patients that necessitates careful diagnosis and management. Additionally, therapies frequently used for these diseases, such as proton pump inhibitors, require careful consideration in cirrhotic patients due to potential adverse effects and altered pharmacokinetics. Managing oesophageal disorders in cirrhotic patients requires a cautious approach due to possible interactions with medications and the risk of adverse effects. Furthermore, symptoms associated with these conditions are often exacerbated by common interventions in patients with cirrhosis, such as band ligation for oesophageal varices. CONCLUSIONS: Oesophageal disorders are common in cirrhosis and increase the disease burden. These conditions require careful management due to complex symptoms and treatment risks. Proton pump inhibitors and other therapies must be used cautiously, as cirrhosis interventions can worsen symptoms.

Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Antimicrobial susceptibility of clinical Helicobacter pylori isolates and its eradication by standard triple therapy: a study in west central region of Colombia.

The aim of the present study was first to isolate Helicobacter pylori from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. H. pylori positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for H. pylori. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% P = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in Helicobacter pylori has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating H. pylori infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.

Proton Pump Inhibitors and Risk of COVID-19 Infection in Children.

OBJECTIVE: To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children. STUDY DESIGN: This retrospective, case-control study included all children ≤21 years undergoing COVID-19 polymerase chain reaction testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes. RESULTS: 116 209 patients age 8.5 ± 6.2 years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P = .002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P = .77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P = .26]. CONCLUSIONS: We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.

Brief Resolved Unexplained Events Symptoms Frequently Result in Inappropriate Gastrointestinal Diagnoses and Treatment.

OBJECTIVE: To determine associations between presenting symptoms and oropharyngeal dysphagia diagnoses, gastroesophageal reflux disease (GERD) diagnoses, and treatment with acid suppression medication in infants with brief resolved unexplained event (BRUE). STUDY DESIGN: We performed a prospective cohort study of infants with BRUE to review presenting symptoms and their potential impact on testing and treatment. Videofluoroscopic swallow study (VFSS) results and explanatory diagnoses were obtained from medical record review; acid suppression use was determined by parental survey. Binary and multivariable logistic regression models were used to evaluate associations between presenting symptoms and obtaining VFSS, VFSS results, GERD diagnoses, and acid suppression medication. RESULTS: Presenting symptoms were varied in 157 subjects enrolled at 51.0 ± 5.3 days of age, with many symptoms that may be related to GERD or dysphagia. Of these, 28% underwent VFSS with 71% abnormal. Overall, 42% had their BRUE attributed to GERD, and 33% were treated with acid suppression during follow-up. Presenting symptoms were significantly associated with the decision to obtain VFSS but not with abnormal VFSS results. Presenting symptoms were also associated with provision of GERD explanatory diagnoses. Both presenting symptoms and GERD explanatory diagnoses were associated with acid suppression use (aOR 2.3, 95% CI 1.03-5.3, P = .04). CONCLUSIONS: Presenting symptoms may play a role in clinicians' decisions on which BRUE patients undergo VFSS but are unreliable to make a diagnosis of oropharyngeal dysphagia. Presenting symptoms may also influence assignment of GERD explanatory diagnoses that is associated with increased acid suppression medication use.

[Approach to refractory gastroesophageal reflux disease]. / Abordaje de la enfermedad por reflujo gastroesofágico refractaria.

An adequate approach to refractory gastroesophageal reflux disease (rGERD) is essential for achieving therapeutic success. From the precise definition of rGERD to the detailed characterization of its phenotypes, it will pave the way for the customization of optimal therapy for each patient. In this narrative literature review, the aim is to provide an updated synthesis of the utility of various diagnostic tools and explore the wide range of therapeutic options, both medical and invasive, available for this condition.

ACCURACY OF THE EOSINOPHILIC ESOPHAGITIS ENDOSCOPIC REFERENCE SCORE IN CHILDREN.

BACKGROUND: To assess the efficacy of applying the endoscopic reference score for EoE (EREFS) in children with symptoms of esophageal dysfunction naïve to proton pump inhibitor (PPI) therapy. METHODS: An observational cross-sectional study was conducted by reviewing reports and photographs of upper gastrointestinal endoscopies (UGE) and esophageal biopsies of patients with symptoms of esophageal dysfunction. Patients who were treated with PPI or had other conditions that may cause esophageal eosinophilia were excluded. RESULTS: Of the 2,036 patients evaluated, endoscopic findings of EoE were identified in 248 (12.2%) and more than one abnormality was observed in 167 (8.2%). Among all patients, 154 (7.6%) presented esophageal eosinophilia (≥15 eosinophils per high power field) (P<0.01). In this group, 30 patients (19.5%) had normal endoscopy. In patients with EoE, edema (74% vs 6.5%, P<0.01) and furrows (66.2% vs 2.4%, P<0.01) were more prevalent than in the control group. Association of edema and furrows was more frequent in patients with EoE than in the control group (29.2% vs 1.6%, P<0.01, OR=24.7, CI=15.0-40.5). The presence of more than one endoscopic finding had sensitivity of 80.5%, specificity of 93.4%, positive predictive value (PPV) of 50%, negative predictive value (NPV) of 98.3%, and accuracy of 92.4%. CONCLUSION: In conclusion, this study showed that endoscopic features suggestive of EoE had high specificity and NPV for diagnosing EoE in children naïve to PPI therapy. These findings highlight the importance of the EREFS in contributing to early identification of inflammatory and fibrostenosing characteristics of EoE, making it possible to identify and to avoid progression of the disease. BACKGROUND: • The EoE endoscopic reference score (EREFS) was developed and validated in adults and has been demonstrated to be an adequate tool for diagnosing and assessing treatment response in children. BACKGROUND: • The presence of more than one endoscopic finding stronglysuggests EoE. BACKGROUND: • The EoE endoscopic reference score presents high specificity and negative predictive value for diagnosing EoE in children naïve to proton pump inhibitor (PPI) therapy. BACKGROUND: • Endoscopic findings suggestive of EoE in patients naïve to treatment may be useful to characterize disease phenotype and individualize treatment according to the initial clinical presentation.

BEHIND THE PROTON PUMP INHIBITOR PRESCRIPTION: AN INTERNATIONAL SURVEY ON PHYSICIAN PRACTICES AND KNOWLEDGE.

BACKGROUND: Proton pump inhibitors (PPIs) are widely prescribed worldwide, often resulting in their overuse. Consequently, it is essential to identify the likely causes of this overuse to facilitate their appropriate prescription. OBJECTIVE: This study aims to assess physician prescribing patterns, their knowledge of PPIs, and factors affecting their knowledge. METHODS: An online survey was conducted among Latin American and Spanish physicians, collecting the following data: professional information, patterns of PPI usage, familiarity with published evidence, and the management approach in three hypothetical case-scenarios. Participant knowledge was categorized as sufficient or insufficient based on the results of the case scenarios. Subsequently, subgroup analysis was performed based on physician training level, years in practice, specialty, and time since the last PPI literature review. RESULTS: A total of 371 physicians participated in the survey. Thirty-eight percent frequently prescribe PPIs, primarily for prophylactic purposes (57.9%). Eighty percent were unfamiliar with PPI deprescribing strategies, and 54.4% rarely reviewed the ongoing indication of patients taking a PPI. Sixty-four percent demonstrated sufficient knowledge in the case-scenarios. A significant association was observed between specialty type (medical vs surgical: 69.4% vs 46.8%, P<0.001), the timing of the PPI indication literature review (<5 years vs >5 years: 71.4% vs 58.7%, P=0.010), and sufficient knowledge. CONCLUSION: While most participants prescribed PPIs regularly and for prophylaxis purposes, the majority were unfamiliar with deprescribing strategies and rarely reviewed ongoing indications. Sufficient knowledge is correlated with recent literature reviews and medical specialty affiliation. BACKGROUND: • The study aims to evaluate physician prescribing patterns, assess their knowledge of proton pump inhibitors, and identify factors influencing their knowledge. BACKGROUND: • An online survey of Latin American and Spanish physicians assessed proton pump inhibitor usage patterns and case-scenario responses, categorizing knowledge, and conducting subgroup analysis based on training, experience, specialty, and literature review timing. BACKGROUND: • Thirty-eight percent of surveyed physicians commonly prescribed proton pump inhibitors, and among them, 80% were unfamiliar with deprescribing strategies, with 54.4% rarely reviewing ongoing indications. BACKGROUND: • Sufficient knowledge was correlated with recent literature reviews and medical specialty affiliations.

BRAZILIAN CLINICAL GUIDELINE FOR THE THERAPEUTIC MANAGEMENT OF GASTROESOPHAGEAL REFLUX DISEASE (BRAZILIAN FEDERATION OF GASTROENTEROLOGY, FBG).

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a prevalent condition in Brazil, affecting 12% to 20% of the urban population, with significant implications for patient quality of life and potential for complications. OBJECTIVE: This paper focuses on the recent update of the Brazilian guidelines for GERD, a necessary revision due to advancements in knowledge and practice since the last publication over a decade ago. The update pays particular attention to the role and safety of proton pump inhibitors (PPIs), acknowledging the growing concerns about their long-term use, adverse events, and overprescription. METHODS: The methodology of the guideline update involved an extensive literature review in multiple languages (English, French, Italian, Spanish, and Portuguese), drawing from major databases such as Medline, Embase, and SciELO-Lilacs. RESULTS: This comprehensive approach resulted in a carefully curated selection of studies, systematic reviews, and meta-analyses, specifically focusing on PPIs and other therapeutic strategies for GERD. The updated guidelines are presented in a user-friendly question-and-answer format, adhering to the PICO system (Population, Intervention, Comparison, Outcomes) for clarity and ease of interpretation. The recommendations are supported by robust scientific evidence and expert opinions, enhancing their practical applicability in clinical settings. To ensure the reliability and clarity of the recommendations, the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation) was employed. This system categorizes the strength of recommendations as strong, weak, or conditional and classifies evidence quality as high, moderate, low, or very low. These classifications provide insight into the confidence level of each recommendation and the likelihood of future research impacting these guidelines. CONCLUSION: The primary aim of these updated guidelines is to offer practical, evidence-based advice for the management of GERD in Brazil, ensuring that healthcare professionals are equipped with the latest knowledge and tools to deliver optimal patient care. BACKGROUND: •Gastrointestinal specialists rely heavily on guidelines to manage digestive pathologies effectively. The Brazilian clinical guideline for therapeutic management of gastroesophageal reflux disease (GERD) is an invaluable tool for these specialists. BACKGROUND: •It critically analyzes practical aspects of therapy through 12 questions covering a wide range of topics, from behavioral measures to surgical and endoscopic indications. BACKGROUND: •The recommendations in this guideline are justified using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation), and experienced experts provide comments and suggestions at the end of each question.

The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

Proton Pump Inhibitor Use and Complications of Cirrhosis Are Linked With Distinct Gut Microbial Bacteriophage and Eukaryotic Viral-Like Particle Signatures in Cirrhosis.

INTRODUCTION: Proton pump inhibitors (PPIs) modulate the progression of cirrhosis to hepatic encephalopathy (HE) and can affect the bacterial microbiome. However, the impact of PPI on the virome in cirrhosis using viral-like particle (VLP) analysis is unclear. METHODS: We determined the VLP in the stool microbiome in patients with cirrhosis cross-sectionally (ascites, HE, and PPI use analyzed) who were followed up for 6-month hospitalizations and through 2 clinical trials of PPI withdrawal and initiation. RESULTS: In a cross-sectional study, PPI users had greater ascites prevalence and 6-month hospitalizations, but VLP α diversity was similar. Among phages, PPI users had lower Autographviridae and higher Streptococcus phages and Herelleviridae than nonusers, whereas opposite trends were seen in ascites and HE. Trends of eukaryotic viruses (higher Adenoviridae and lower Virgaviridae/Smacoviridae) were similar for PPI, HE, and ascites. Twenty-one percent were hospitalized, mostly due to HE. α Diversity was similar in the hospitalized/nonhospitalized/not groups. Higher Gokushovirinae and lower crAssphages were related to hospitalizations such as HE-related cross-sectional VLP changes. As part of the clinical trial, PPIs were added and withdrawn in 2 different decompensated groups over 14 days. No changes in α diversity were observed. Withdrawal reduced crAssphages, and initiation reduced Gokushovirinae and Bacteroides phages. DISCUSSION: In cirrhosis, PPI use has a gut microbial VLP phage signature that is different from that in HE and ascites, and VLP changes are linked with hospitalizations over 6 months, independent of clinical biomarkers. Eukaryotic viral patterns were consistent across PPI use, HE, and ascites, indicating a relationship with the progression of cirrhosis. PPIs alone showed modest VLP changes with withdrawal or initiation. Distinct phage and eukaryotic viral patterns are associated with the use of PPIs in cirrhosis.

Esofagitis eosinofílica: más allá del tratamiento con inhibidores de bomba de protones (uso de biológicos) / Eosinophilic esophagitis: beyond proton pump inhibitor therapy (Biologic therapies)

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease of the esophagus characterized by symptoms of esophageal dysfunction such as dysphagia, food impaction, and chest pain in adults. It is associated with atopic di- seases such as allergic rhinitis, atopic dermatitis, and asthma. Diagnosis requires symptoms of esophageal dysfunction, eosinophilic inflammation in esophageal biopsies with at least 15 eosinophils per high power field, and exclusion of other causes of local or systemic eosinophilia. EoE is more common in men and has an increasing prevalence, varying globally. The pathophysiology involves TH2-mediated eosinophilic inflammation driven by food antigens, esophageal barrier dysfunction and tissue remodeling. Various therapeutic options aim for clinical and histological remission, including dietary and pharmacological treatments. Dietary therapy, topical corticosteroids and proton pump inhibitors are first-line treatments. Topical corticosteroids achieve high histological remission. Development of new therapies is ongoing. Dupilumab, an antibody against IL-4Rα, shows efficacy in achieving histological and symptomatic remission in patients unresponsive to proton pump inhibitors. Other targeted therapies with clinical trials for EoE include mepolizumab, reslizumab, cendakimab, lirentelimab, and etrasimod with variable clinical and histological results. A subgroup of patients with EoE unresponsive or with bad adherence to first line therapies or patients with multiple comorbid atopic diseases may benefit from biological therapies. This review aims to describe new therapeutic options, detailing their mechanisms, efficacy, and safety profiles.

La esofagitis eosinofílica (EEo) es una enfermedad crónica, inmunomediada del esófago, caracterizada por síntomas de disfunción esofágica como disfagia, impactación y dolor torácico en adultos. Se asocia a otras enfermedades atópicas como rinitis alérgica, dermatitis atópica y asma. El diagnóstico requiere síntomas de disfunción esofágica, inflamación eosinofílica en biopsias de esófago con al menos 15 eosinófilos por campo de aumento mayor, y exclusión de otras causas de eosinofilia local o sistémica. La EEo es más común en hombres y tiene una prevalencia en aumento. La fisiopatología incluye inflamación eosinofílica mediada por una respuesta TH2 gatillada por antígenos alimenticios, además disfunción de barrera esofágica y remodelación de tejido. Varias opciones terapéuticas tienen como objetivo la remisión clínica e histológica, incluyendo terapias dietéticas y tratamientos farmacológicos. La terapia dietética, inhibidores de bomba de protones o corticosteroides tópicos sin terapias de primera línea. Los corticosteroides tópicos alcanzan altas tasas de remisión histológica. El desarrollo de nuevas terapias se está llevando a cabo. Dupilumab, un anticuerpo contra IL-4Rα, muestra eficacia en alcanzar remisión histológica y sintomática en pacientes no responde- dores a inhibidores de bomba de protones. Otras terapias con estudios clínicos para EEo incluyen el mepolizumab, reslizumab, cendakimab, lirentelimab y etrasimod, con resultados variables. Un subgrupo de pacientes con EEo no respondedores o con mala adherencia a terapias de primera línea o con comorbilidades atópicas graves se podrían beneficiar de terapias biológicas como dupilumab. Esta revisión tiene como objetivo describir nuevas opciones tera- péuticas, detallando su mecanismo de acción, eficacia y perfil de seguridad.

EFFICACY AND SAFETY OF GEMIFLOXACIN CONTAINING TREATMENT REGIMEN IN FIRST-LINE TREATMENT OF HELICOBACTER PYLORI.

•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.

Frequency of functional esophageal disorders in patients with refractory reflux symptoms in Lima, Peru.

Gastroesophageal reflux disease (GERD) is a clinical condition in which gastric reflux causes symptoms or damage to the esophageal mucosa. It is managed with proton pump inhibitors, however, up to 45% of patients with suspected GERD are refractory to treatment. It is necessary to establish a true GERD diagnosis by means of a digestive endoscopy, which does not show lesions in approximately 70% of patients. In this scenario, it is necessary to perform an esophageal pH-impedance measurement, a procedure that allows to determine whether exposure to gastric acid is pathological. Of this group, patients with pathological acid exposure are diagnosed as true non-erosive reflux disease (NERD). If, in addition to not presenting esophageal lesions, they have a physiological exposure to gastric acid, they suffer from esophageal hypersensitivity or functional heartburn, which are functional disorders. These require a different approach from that of GERD or NERD, as the symptoms are not due to pathological exposure to gastric acid. The aim was to calculate the frequency of esophageal hypersensitivity and functional heartburn in patients with suspected NERD. This was a cross-sectional study. Data was collected by reviewing pH-impedance and manometry reports, 166 patients were selected. The frequency for functional disorders was 86.15%, being 46.9% for functional heartburn and 39.2% for esophageal hypersensitivity. The frequency of functional disorders was higher than that reported in previous studies. In conclusion, age, psychological conditions, dietary, cultural, ethnic or lifestyle factors inherent to our environment might play important roles in the development of functional disorders.

[Quadruple treatment with doxycycline, furazolidone, bismuth and proton pump inhibitor is still effective against Helicobacter pylori in our population]. / Tratamiento cuádruple con doxiciclina, furazolidona, bismuto e inhibidor de bomba de protones sigue siendo efectivo frente al Helicobacter pylori en nuestra población.

Our objective is to determine the effectiveness of a therapeutic regimen for helicobacter pylori that includes a proton pump inhibitor, doxycycline, furazolidone and bismuth in our location. We carried out a retrospective study, non-randomized, in a private hospital in Lima, Peru. Patients with biopsy and/or rapid urease test proven helicobacter pylori infection after an endoscopy, from January 2017 to October 2022 were included. They received the therapeutic regimen of the study or an alternative triple regimen with a proton pump inhibitor, amoxicillin and levofloxacin and were followed with a urea breath test within 1 to 6 months upon completion of therapy. The quadruple therapy with furazolidone obtained success in 117/122 cases (95.9%) while the triple therapy with levofloxacin only in 5/16 (31.2%) when used for 7 days and 22/38 (57.9%) when used for 10 days, a statistically significant difference with p<0.001. Conclusion: Quadruple therapy with furazolidone reached high effectiveness in our location, while triple therapy with levofloxacin was not an acceptable alternative.

Esofagitis necrotizante aguda / Acute necrotizing esophagitis / Esofagite necrotizante aguda

La esofagitis necrotizante aguda es un trastorno poco común que puede ser causa de hemorragia digestiva alta. Predomina en el sexo masculino en la sexta década de la vida. El diagnóstico es endoscópico y muestra una mucosa esofágica de apariencia negra que afecta al esófago distal en toda su circunferencia y se detiene abruptamente en la unión gastroesofágica. Clínicamente suele presentarse con hematemesis y melenas, shock hipovolémico por sangrado masivo, siendo otras manifestaciones el dolor epigástrico, molestia retroesternal y disfagia. Se vincula a pacientes con antecedentes de enfermedad cardiovascular, alcoholismo, diabetes mellitus, desnutrición, hernia hiatal, estenosis gastroduodenal, cáncer, así como pacientes en shock, traumatizados, sometidos a cirugía mayor e inmunosuprimidos. El tratamiento se basa en fluidoterapia, inhibidores de la bomba de protones y suspensión de la vía oral, siendo controvertido el uso de antibioticoterapia. Su pronóstico es malo y dependerá de la gravedad de la enfermedad esofágica y del terreno del paciente, con una mortalidad de hasta el 36 %. Presentamos el caso clínico de un paciente de 81 años, hipertenso, que presenta hematemesis, confirmándose en la endoscopía una esofagitis necrotizante aguda, que evoluciona favorablemente con tratamiento médico.

Acute necrotizing esophagitis is a rare disorder that can cause upper gastrointestinal bleeding. It predominates in males in the sixth decade of life. The diagnosis is endoscopic and shows a black-appearing esophageal mucosa that affects the entire circumference of the distal esophagus and stops abruptly at the gastroesophageal junction. Usually, patients present with hematemesis and melena, with other manifestations such as epigastric pain, retrosternal discomfort, dysphagia, and hypovolemic shock. Almost all patients reported comorbidities: cardiovascular disease, alcoholism, diabetes mellitus, malnutrition, hiatal hernia, gastroduodenal stenosis, and malignant neoplasia; is related as well to patients with shock, trauma, undergoing major surgery, and immunosuppression. The treatment is based on fluid reposition, proton pump inhibitors and suspension of the oral route, the use of antibiotic therapy being controversial. Its prognosis is poor and will depend on the severity of the esophageal disease and the patient comorbidities, with a mortality rate up to 36 %. Case: A 81-year-old male patient with hypertension, who presented hematemesis, confirmed by endoscopy as acute necrotizing esophagitis, whose evolution was favorable with medical treatment.

A esofagite necrosante aguda é uma doença rara que pode causar hemorragia digestiva alta. Predomina no sexo masculino na sexta década de vida. O diagnóstico é endoscópico e mostra uma mucosa esofágica circunferencial difusa com aspecto preto que envolve quase universalmente o esôfago distal e para abruptamente na junção gastroesofágica. Clinicamente, geralmente se apresenta com hematêmese e melena, com outras manifestações sendo dor epigástrica, desconforto retroesternal, disfagia e choque hipovolêmico. Está relacionado a pacientes com histórico de doenças cardiovasculares, alcoolismo, diabetes mellitus, desnutrição, hérnia hiatal, estenose gastroduodenal e neoplasia maligna, bem como pacientes em choque, trauma, cirurgia de grande porte e imunossupressão. O tratamento é a medicação dietética higiênica baseada em fluidoterapia, inibidores da bomba de prótons e suspensão da via oral, sendo o uso de antibioticoterapia controverso. Seu prognóstico é ruim e dependerá da gravidade da doença esofágica e do terreno do paciente, com mortalidade de até 36 %. Apresentamos o caso clínico de um paciente hipertenso de 81 anos que apresentou hematêmese, confirmada por endoscopia como esofagite necrosante aguda, que evoluiu favoravelmente com tratamento higiênico-dietético e medicamentoso.

Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver.

Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFß downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.

Application of Heterocycles as an Alternative for the Discovery of New Anti-ulcer Compounds: A Mini-Review.

A peptic ulcer is a lesion located in the esophagus, stomach, and upper intestine, caused by an imbalance between acid secretion and the release of protective mucus. This pathology is prevalent in approximately 14% of the world population and is commonly treated with proton pump inhibitors and type 2 histaminergic receptor antagonists, however, these drugs present concerning side effects that may lead to gastric cancer. In this sense, this research aimed to present the main heterocyclics studied in recent years. The screening method for the choice of articles was based on the selection of publications between 2000 and 2021 present in the Science Direct, Web of Science, Capes, and Scielo databases, by using the descriptors ''new derivatives'', "heterocyclics" "antiulcerogenic", "gastroprotective" and "antisecretor". This research showed that the most used rings in the development of anti-ulcer drugs were benzimidazole, quinazoline, thiazole, and thiadiazole. The results also portray several types of modern in silico, in vitro and in vivo assays, as well as the investigation of different mechanisms of action, with emphasis on proton pump inhibition, type 2 histaminergic receptor blockers, potassium competitive acid blockers, type E prostaglandin agonism, anti-secretory activity and anti-oxidant action. Additionally, the review evidenced the presence of the nitrogen atom in the heterocyclic ring as a determinant of the potential of the compound. This research suggests new alternatives for the treatment of gastric lesions, which may be more potent and cause fewer side effects than the currently used, and tend to evolve into more advanced studies in the coming years.