Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Rare Cause of Hematochezia in Children: Solitary Rectal Ulcer, Single Center Experience.

Background/Aims: Solitary rectal ulcer syndrome (SRUS) can be overlooked, diagnosed late, or misdiagnosed, particularly in childhood. This study reviewed the 13-year experience of the authors' institution to increase clinicians' awareness of SRUS in the presence of symptoms. This paper reports the endoscopic and histopathological findings in children presenting with hematochezia. Methods: The clinical and laboratory findings of 22 patients diagnosed with biopsy-proven SRUS in the authors' clinic between 2007 and 2020 were evaluated retrospectively. Results: The mean age at diagnosis was 12.5±2.6 years, and 59.1% of the patients were male. The median time of diagnosis was 24 months. A single ulcer lesion was found by colonoscopy in 18 patients (81.8%), two ulcers in two patients (9%), and more than two ulcers in two patients (9%). The pathology reports of all biopsies taken from the lesions were consistent with a solitary rectal ulcer. In the first stage, the treatment was started with toilet training, a high-fiber diet, and laxatives. In 11 patients (50%) who did not respond to the initial treatment, a 5-ASA enema was added. A glucocorticoid enema was added to treatment in five patients (22%) whose complaints did not regress despite this treatment. Clinical remission was achieved in five of the patients (18.1%). The time to diagnosis was significantly shorter in those in remission than those not in remission (p=0.04). Conclusions: This study is the first large series on Turkish children. An increased awareness of SRUS in children will increase the rate of early diagnosis and treatment, allowing remission in more patients.

Peptic ulcer characteristics in oral opium and non-opium user patients with upper gastrointestinal bleeding.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is a frequent medical issue. The primary risk factors for bleeding peptic ulcers are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. The association between acute gastric/duodenal ulcer and opium use has been previously proposed; however, there is no available data on endoscopic findings of patients with acute UGIB who use opium. MATERIALS AND METHODS: In the present descriptive cross-sectional study, endoscopic data of 50 consecutive patients with oral opium use and 50 consecutive patients without any opium use who were admitted for UGIB were recorded. The size (5-10 mm, 11-20 mm, or more than 20 mm), number (single, double, or multiple), and location of the ulcers (esophagus, gastric corpus including the fundus and body, antrum, angulus, or duodenum) were examined by endoscopy in both groups. RESULTS: Three or more ulcers were observed in 46% and 16% of patients with oral opium use and without opium use, respectively (P-value = 0.001). The rate of giant ulcers (> 20 mm) was significantly higher in patients who used oral opium (40% vs. 12%; P-value = 0.007). Esophageal ulcers were also more common in oral opium users (30%) than non-users (8%) with UGIB (P-value = 0.01). Nevertheless, the location of the ulcers between the two groups generally was not statistically different. CONCLUSIONS: This study has demonstrated that multiple, large peptic ulcers in GIB are potential complications of oral opium use. This could aid the needed modifications in the treatment protocol for these patients.

Effects of Psychological Nursing Combined with Comprehensive Nursing on Gastrointestinal Bleeding and Nutritional Status in Cirrhosis.

Objective: Cirrhosis of the upper GIB is a surgical emergency, PN and CN can reduce the risk of gastrointestinal bleeding, but there is a lack of analysis on PN combined with CN in Cirrhotic patients. This work explored the effects of psychological nursing (PN) combined with comprehensive nursing (CN) on gastrointestinal bleeding (GIB) and nutritional status of patients with cirrhosis. Methods: Total 80 patients with GIB and cirrhosis who received emergency treatment in the Affiliated Hospital of Shaoxing University from October 2019 to October 2022 were randomly rolled into two groups. Patients in the control group (Ctrl group) received CN (n = 40 cases), and those in the experimental group (Exp group) received PN combined CN (n = 40 cases). The Model for end-stage liver disease (MELD) score, self-rating anxiety scale (SAS), self-rating depression scale (SDS), SCL-90, complication rate, and nursing satisfaction of patients from different groups were analyzed and compared. MELD score effectively predicts short - and medium-term mortality in end-stage liver disease. SAS consisted of 20 questions related to anxiety symptoms, four-level scoring method was adopted. The SCL-90 scale included four aspects: somatic symptoms, interpersonal relationships, psychological emotions, and psychological needs. Results: The results disclosed that after nursing intervention, SAS, SDS, and MELD scores in the Exp group were remarkably lower than those in the Ctrl group (P < .05). The scores of SCL-90 somatic symptoms, interpersonal relationships, psychological emotion, and psychological needs of participants in the Exp group were much lower than those in the Ctrl group (P < .05). The complication rate was significantly lower in the Exp (30.0%) than in the Ctrl groups (72.5%) (P < .05). The total nursing satisfaction was increased, and it is significan higher in the Exp group (97.5%) than control group (87.5% ) (P < .05). Conclusions: In conclusion, PN combined with CN could effectively reduce the incidence of complications in patients with GIB and cirrhosis and improve nursing satisfaction. Therefore, such a method was worth promoting, which provides a reference for the clinical diagnosis and treatment of patients with GIB and cirrhosis.

A case report of systemic lupus erythematosus and intestinal tuberculosis with lower gastrointestinal bleeding: A treatment approach utilizing parenteral nutrition.

RATIONALE: Limited literatures are available on lower gastrointestinal bleeding in systemic lupus erythematosus (SLE) combined with intestinal tuberculosis. Sharing the treatment experiences of a 26-year-old female patient diagnosed with this complex condition in this report may contribute valuable insights. PATIENT CONCERNS: The patient initially presented with abdominal pain and active gastrointestinal bleeding, leading to admission to the hospital. Over a 2-week period, she experienced persistent bleeding, with daily volumes ranging from 300 mL to 800 mL. DIAGNOSES: Lower gastrointestinal bleeding was diagnosed in this patient with concurrent systemic lupus erythematosus and intestinal tuberculosis. INTERVENTIONS: As her symptoms rapidly progressed, food and water intake had to be completely restricted. The parenteral nutrition was implemented. OUTCOMES: The medical team effectively controlled the bleeding, leading to a notable improvement in the patient's condition. Consequently, she was able to resume oral intake and was discharged from the hospital. LESSONS: This case highlights the significance of using parenteral nutrition in the management of lower gastrointestinal bleeding in patients with concurrent systemic lupus erythematosus and intestinal tuberculosis. Close monitoring and collaborative efforts among healthcare professionals are crucial to achieve successful outcomes in similar cases.

Necrosis esofágica aguda (esófago negro) asociado a neoplasias digestivas / Acute esophageal necrosis (black esophagus) associated with digestive neoplasms

INTRODUCCIÓN. La necrosis esofágica aguda es un síndrome raro que se caracteriza endoscópicamente por una apariencia negra circunferencial irregular o difusa de la mucosa esofágica intratorácica, la afectación es generalmente del esófago distal y la transición abrupta de mucosa normal en la unión gastroesofágica, con extensión proximal variable. CASOS. Se presentan dos casos con diferentes comorbiliades, presentación de signos y síntomas, antecedentes y tratamiento, teniendo en común el diagnóstico a través de endoscopía digestiva alta. RESULTADOS. Caso clínico 1: tratamiento clínico basado en hidratación, suspensión de vía oral, omeprazol intravenoso y sucralfato; mala evolución clínica caracterizada por: disfagia, intolerancia oral y recurrencia del sangrado digestivo alto, se realiza colocación de gastrostomía endoscópica. Caso clínico 2: esófago con mucosa con fibrina y parches de necrosis extensa, se realiza compensación tanto de foco infeccioso pulmonar como hidratación y nutrición, en estudios complementarios se observa masa colónica, con estudio histopatológico confirmatorio de adenocarcinoma de colon en estado avanzado. DISCUSIÓN. La esofagitis necrotizante aguda es una entidad inusual, de baja prevalencia e incidencia, asociada con estados de hipoperfusión sistémica y múltiples comorbilidades que favorezcan un sustrato isquémico. Al revisar los reportes de casos que hay en la literatura médica, los casos que reportamos se correlaciona con las características clínicas, epidemiológicas, endoscópicas y factores de riesgo causales de la enfermedad. La presentación clínica más frecuente es el sangrado digestivo alto, que se debe correlacionar con el hallazgo endoscópico clásico. Nuestro primer caso reportado termina con la colocación de una gastrostomía para poder alimentarse. CONCLUSIÓN. El pronóstico de la necrosis esofágica aguda es malo y se requiere un alto índice de sospecha clínica y conocimiento de esta infrecuente patología para un diagnóstico temprano y un manejo oportuno. Se requiere una evaluación por endoscopia digestiva alta. Es una causa de sangrado gastrointestinal que conlleva tasas altas de mortalidad, principalmente en adultos mayores frágiles. El reconocimiento temprano y la reanimación agresiva son los principios fundamentales para un mejor resultado de la enfermedad.

INTRODUCTION. Acute esophageal necrosis is a rare syndrome that is characterized endoscopically by an irregular or diffuse circumferential black appearance of the intrathoracic esophageal mucosa, the involvement is generally of the distal esophagus and the abrupt transition of normal mucosa at the gastroesophageal junction, with variable proximal extension. CASES. Two cases are presented with different comorbidities, presentation of signs and symptoms, history and treatment, having in common the diagnosis through upper gastrointestinal endoscopy. RESULTS. Clinical case 1: clinical treatment based on hydration, oral suspension, intravenous omeprazole and sucralfate; poor clinical evolution characterized by: dysphagia, oral intolerance and recurrence of upper digestive bleeding, endoscopic gastrostomy placement was performed. Clinical case 2: esophagus with mucosa with fibrin and patches of extensive necrosis, compensation of both the pulmonary infectious focus and hydration and nutrition is performed, in complementary studies a colonic mass is observed, with a confirmatory histopathological study of colon adenocarcinoma in an advanced state. DISCUSSION. Acute necrotizing esophagitis is an unusual entity, with low prevalence and incidence, associated with states of systemic hypoperfusion and multiple comorbidities that favor an ischemic substrate. When reviewing the case reports in the medical literature, the cases we report correlate with the clinical, epidemiological, endoscopic characteristics and causal risk factors of the disease. The most common clinical presentation is upper gastrointestinal bleeding, which must be correlated with the classic endoscopic finding. Our first reported case ends with the placement of a gastrostomy to be able to feed. CONCLUSION. The prognosis of acute esophageal necrosis is poor and a high index of clinical suspicion and knowledge of this rare pathology is required for early diagnosis and timely management. Evaluation by upper gastrointestinal endoscopy is required. It is a cause of gastrointestinal bleeding that carries high mortality rates, mainly in frail older adults. Early recognition and aggressive resuscitation are the fundamental principles for a better outcome of the disease.

Study on the Effectiveness and Value of Evidence-Based Nursing and Predictive Nursing in Emergency Treatment of Upper Gastrointestinal Bleeding.

Objective: To study the effectiveness and value of evidence-based nursing and predictive nursing in emergency treatment of upper gastrointestinal bleeding. Methods: A total of 100 patients with upper gastrointestinal bleeding in our hospital were selected. The period was from January 2020 to June 2022. They were grouped according to the double color ball method, 50 cases in the control group were given routine nursing, and 50 cases in the observation group were given evidence-based nursing combined with predictive nursing. The key points of evidence-based nursing are to identify the evidence-based question, search for relevant literature, identify scientifically effective nursing measures, and develop nursing care plans that are tailored to the patient's specific situation based on evidence and clinical experience. Predictive nursing requires nurses to have a high level of awareness and risk prevention consciousness to provide care for early signs of bleeding and prevent the occurrence of complications. The psychological state scores, clinical-related indicators, clinical efficacy, incidence of complications, nursing satisfaction, and quality of life scores of the two groups were compared. Results: After the intervention, the SAS score (42.25 ± 1.67) and SDS score (43.59 ± 1.86) of the observation group were lower than those of the control group, the bleeding times (2.41 ± 0.45) of the observation group were less than those of the control group, the hemostasis time (30.12 ± 5.38d) and hospitalization time (5.01 ± 1.11d) of the observation group were shorter than those of the control group, and the difference was statistically significant (all P < .05). The total effective rate of hemostasis (96.00%), patient satisfaction (98.00%), and scores of physical health (88.98 ± 5.59), psychological function (91.08 ± 5.11), material life state (90.54 ± 6.46) and social function (89.59 ± 5.78) in GQOLI-74 scores in the observation group were higher than those in the control group. The incidence of complications (6.00%) in the observation group was lower than that in the control group, and the difference was statistically significant (all P < .05). Conclusion: Upper gastrointestinal bleeding is a common emergency in gastroenterology, characterized by rapid onset, severe symptoms, and quick changes. Therefore, in order to expedite the recovery of patients with acute upper gastrointestinal bleeding and ensure their safety, it is necessary to provide effective clinical emergency nursing care. Evidence-based nursing can help nurses take appropriate nursing measures based on the best and latest evidence, to meet the reasonable individualized needs of patients. Predictive nursing is a nursing model that predicts potential nursing risks in advance and takes corresponding preventive measures. It can timely and systematically address risks in nursing and promote improvements in the effectiveness of disease treatment. The combined application of evidence-based nursing and predictive nursing can improve the hemostatic efficiency of patients with upper gastrointestinal bleeding, improve the psychological state and quality of life, reduce the incidence of complications, and obtain higher satisfaction. The combined application of these two nursing models has positive implications for improving nursing efficiency, enhancing patient cooperation during emergency care, improving hemostasis effectiveness, enhancing quality of life, and fostering a harmonious nurse-patient relationship.

Celastrol as an intestinal FXR inhibitor triggers tripolide-induced intestinal bleeding: Underlying mechanism of gastrointestinal injury induced by Tripterygium wilfordii.

BACKGROUND: Tripterygium wilfordii has been widely used for the treatment of rheumatoid arthritis, which is frequently accompanied by severe gastrointestinal damage. The molecular mechanism underlying the gastrointestinal injury of Tripterygium wilfordii are yet to be elucidated. METHODS: Transmission electron microscopy, and pathological and biochemical analyses were applied to assess intestinal bleeding. Metabolic changes in the serum and intestine were determined by metabolomics. In vivo (time-dependent effect and dose-response) and in vitro (double luciferase reporter gene system, DRATs, molecular docking, HepG2 cells and small intestinal organoids) studies were used to identify the inhibitory role of celastrol on intestinal farnesoid X receptor (FXR) signaling. Fxr-knockout mice and FXR inhibitors and agonists were used to evaluate the role of FXR in the intestinal bleeding induced by Tripterygium wilfordii. RESULTS: Co-treatment with triptolide + celastrol (from Tripterygium wilfordii) induced intestinal bleeding in mice. Metabolomic analysis indicated that celastrol suppressed intestinal FXR signaling, and further molecular studies revealed that celastrol was a novel intestinal FXR antagonist. In Fxr-knockout mice or the wild-type mice pre-treated with pharmacological inhibitors of FXR, triptolide alone could activate the duodenal JNK pathway and induce intestinal bleeding, which recapitulated the pathogenic features obtained by co-treatment with triptolide and celastrol. Lastly, intestinal bleeding induced by co-treatment with triptolide and celastrol could be effectively attenuated by the FXR or gut-restricted FXR agonist through downregulation of the duodenal JNK pathway. CONCLUSIONS: The synergistic effect between triptolide and celastrol contributed to the gastrointestinal injury induced by Tripterygium wilfordii via dysregulation of the FXR-JNK axis, suggesting that celastrol should be included in the quality standards system for evaluation of Tripterygium wilfordii preparations. Determining the mechanism of the FXR-JNK axis in intestinal bleeding could aid in the identification of additional therapeutic targets for the treatment of gastrointestinal hemorrhage diseases. This study also provides a new standard for the quality assessment of Tripterygium wilfordii used in the treatment of gastrointestinal disorders.

Comparisons Between Endoscopic Band Ligation, Radiofrequency Ablation and Endoscopic Thermal Therapy for Gastric Antral Vascular Ectasia: A Meta-Analysis.

BACKGROUND: Endoscopic band ligation (EBL) and radiofrequency ablation (RFA) have emerged as alternative therapies of gastric antral vascular ectasia (GAVE) in addition to endoscopic thermal therapy (ETT), but the optimum choice remains inconclusive. AIM: We conducted a meta-analysis in order to compare these three treatments for GAVE. METHODS: We searched the electronic databases of PubMed, Embase and Cochrane Central Register of Controlled Trials without any language restrictions and also performed a manual literature search of bibliographies located in both retrieved articles and published reviews for eligible publications prior to December 8, 2021. We included comparative trials which had evaluated the efficacy and safety of interventions in adults (aged ≥ 18 years) diagnosed with symptomatic GAVE and was confirmed according to clinical backgrounds and upper gastrointestinal endoscopy. We included reports that compared three interventions, ETT, EBL, and RFA. The study was comprised of adults diagnosed with GAVE and focused on overall mortality, bleeding cessation, endoscopic improvement, complications, hospitalization, hemoglobin improvement, number of sessions and transfusion requirements. RESULTS: Twelve studies were performed involving a total of 571 participants for analysis. When compared with ETT, EBL achieved better bleeding cessation (OR 4.48, 95% CI 1.36-14.77, p = 0.01), higher hemoglobin improvement (MD 0.57, 95% CI 0.31-0.83, p < 0.01) and lower number of sessions (MD - 1.44, 95% CI - 2.54 to - 0.34, p = 0.01). Additionally, EBL was superior to ETT in endoscopic improvement (OR 6.00, 95% CI 2.26-15.97, p < 0.01), hospitalization (MD - 1.32, 95% CI - 1.91 to - 0.74, p < 0.01) and transfusion requirement (MD - 2.66, 95% CI - 4.67 to - 0.65, p = 0.01) with statistical significance, with the exception of mortality (OR 0.58, 95% CI 0.19-1.77, p = 0.34) and complication rate (OR 5.33, 95% CI 0.58-48.84, p = 0.14). CONCLUSION: For GAVE, we suggest that EBL be initially recommended, and APC and RFA be used as alternative treatment choices based upon a very low quality of evidence.

Recurrent intestinal ulcer with bloody stool for >10 years in an adolescent boy of 15 years: A case report.

RATIONALE: Infectious diseases, autoimmune diseases and vascular diseases can lead to intestinal ulcers, and inflammatory bowel disease is typically suspected as the underlying cause of ulcer and bleeding from the intestinal ulcers leading to bloody stool, and malnutrition. Here we report a rare case of successfully treated case of intestinal ulcer, bloody stool, and malnutrition by dietary modification and avoidance of long term barbecued spicy food and carbonated drinks. PATIENT CONCERNS: A 15-year-old male patient had repeated symptoms of blood in the stool for >10 years. Treatment for Chron's disease was not successful. An exhaustive investigation failed to confirm the diagnosis. DIAGNOSIS INTERVENTIONS: Through changing diet structure, avoiding spicy food, and supplementing enteral nutrition and recurrent glutamine. OUTCOMES: The patient's symptoms improved significantly, and the intestinal ulcer healed under endoscope. LESSONS: Pay attention to healthy diet in life and avoid long-term consumption of spicy food and carbonated drinks.

[Connotation of distal bleeding based on modern pathophysiological mechanism and application of Huangtu Decoction for acute coronary syndrome complicated with acute upper gastrointestinal hemorrhage in critical care medicine].

Huangtu Decoction, first recorded in Essentials from the Golden Cabinet(Jin Kui Yao Lue) from ZHANG Zhong-jing in Han dynasty, is used to treat distal bleeding. It is mainly treated for the syndrome of failing to control blood with spleen-yang deficiency. The connotation of distal bleeding is more extensive, including not only upper gastrointestinal bleeding in the traditional sense such as peptic ulcer bleeding, gastrointestinal tumors, gastric mucosal lesions, vascular dysplasia, esophagogastric variceal bleeding, and pancreatic and biliary tract injury, but also other anorectal diseases such as part colon and rectal cancer swelling or polyps, hemorrhoids, and anal fissure and other parts of bleeding such as epistaxis, thrombocytopenia, functional uterine bleeding, threatened abortion, and unexplained hematuria. Distal bleeding also involves syndromes of failing to keep part deficient and cold fluids in interior, such as nocturia, enuresis, clear nose, sweating, cold tears, and leucorrhea, and excessive gastrointestinal bleeding caused by anti-plate and anticoagulant drugs, unexplained positive in the fecal occult blood test, and other modern clinical new problems. The indications of Huangtu Decoction include not only lower blood, defecation before blood, distant blood, hematemesis, epistaxis, and other diseases in traditional Chinese medicine, but also three types of clinical manifestations including bleeding, deficiency syndrome, and stagnant heat syndrome. In the clinic, Huangtu Decoction can be used to treat acute upper gastrointestinal bleeding, acute coronary syndrome complicated with acute upper gastrointestinal bleeding, bleeding events caused by excessive antiplatelet and anticoagulant drugs, unexplained positive in the fecal occult blood test, gastrointestinal tumor with bleeding, thrombocytopenia, and other acute and critical diseases. The dosage of Cooking Stove Earthkey, Rehmanniae Radix, and Asini Corii Colla in Huangtu Decoction is the key to hemostasis.

Role of oral iron supplementation for anemia secondary to acute nonvariceal upper gastrointestinal bleeding: a randomized controlled trial.

BACKGROUND AND AIM: Although acute upper gastrointestinal bleeding (UGIB) can lead to anemia, evidence regarding the effects of oral iron supplementation on UGIB-induced anemia following discharge remains lacking. The present study aimed to investigate the effects of oral iron supplementation on hemoglobin response and iron storage in patients with anemia secondary to nonvariceal UGIB. METHODS: This randomized controlled trial included 151 patients with nonvariceal UGIB who had anemia at discharge. Patients were assigned to a 1:1 block in which they were either administered 6 weeks of 600 mg/d oral ferrous fumarate (treatment group, n = 77) or treated without iron supplementation (control group, n = 74). The primary outcome was composite hemoglobin response (hemoglobin elevation greater than 2 g/dL or no anemia at the end of treatment [EOT]). RESULTS: The proportion of patients achieving composite hemoglobin response was greater in the treatment group than in the control group (72.7% vs 45.9%; adjusted risk ratio [RR], 2.980; P = 0.004). At EOT, the percentage change in the hemoglobin level (34.2 ± 24.8% vs 19.4 ± 19.9%; adjusted coefficient, 11.543; P < 0.001) was significantly higher in the treatment group than in the control group; however, the proportions of patients with a serum ferritin level <30 µg/L and a transferrin saturation <16% were lower in the treatment group (all P < 0.05). No significant differences in treatment-associated adverse effects and adherence rates were observed between the groups. CONCLUSION: Oral iron supplementation exerts beneficial effects on anemia and iron storage following nonvariceal UGIB without significantly impacting rates of adverse effects or adherence.

Intravenous ferric carboxymaltose versus oral ferrous sulfate replacement in elderly patients after acute non-variceal gastrointestinal bleeding (FIERCE): protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Acute gastrointestinal bleeding (GIB) is a life-threatening emergency with a critical economic burden. As a result of bleeding, anaemia often requires intravenous or oral iron supplementation. Elderly patients are even more prone to untoward outcomes after hospital discharge if iron supplementation is inefficient. There is a gap in current guidelines on which supplementation route clinicians should choose. We aim to investigate the effect of one dose of intravenous iron therapy versus 3-month oral iron administration on anaemia in an elderly population. METHODS AND ANALYSIS: The FIERCE study is an open-label, randomised controlled, two-armed trial. At least 48 hours after the acute non-variceal GIB treatment, patients will be recruited in participating centres. A random sequence generator will allocate the participants to group A (intravenous ferric carboxymaltose, 1000 mg) or group B (oral ferrous sulfate (FS), ca. 200 mg every day) with an allocation ratio of 1:1 on the day of the planned discharge from the hospital. Randomisation will be stratified for participating centres and the need for transfusion within the same hospitalisation before recruitment to the trial. Quality of life assessment, functional measurement and laboratory tests will be performed at baseline, 1 and 3 months±7 days after enrolment to the trial. The primary endpoint is a composite endpoint, including all-cause mortality, anaemia-associated unplanned emergency visit and anaemia-associated unplanned hospital admission within 3 months of enrolment in the trial. ETHICS AND DISSEMINATION: The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (46395-5/2021/EÜIG). We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov (NCT05060731).

Update in the Treatment of the Complications of Cirrhosis.

Cirrhosis consists of 2 main stages: compensated and decompensated, the latter defined by the development/presence of ascites, variceal hemorrhage, and hepatic encephalopathy. The survival rate is entirely different, depending on the stage. Treatment with nonselective ß-blockers prevents decompensation in patients with clinically significant portal hypertension, changing the previous paradigm based on the presence of varices. In patients with acute variceal hemorrhage at high risk of failure with standard treatment (defined as those with a Child-Pugh score of 10-13 or those with a Child-Pugh score of 8-9 with active bleeding at endoscopy), a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) improves the mortality rate and has become the standard of care in many centers. In patients with bleeding from gastrofundal varices, retrograde transvenous obliteration (in those with a gastrorenal shunt) and/or variceal cyanoacrylate injection have emerged as alternatives to TIPS. In patients with ascites, emerging evidence suggests that TIPS might be used earlier, before strict criteria for refractory ascites are met. Long-term albumin use is under assessment for improving the prognosis of patients with uncomplicated ascites and confirmatory studies are ongoing. Hepatorenal syndrome is the least common cause of acute kidney injury in cirrhosis, and first-line treatment is the combination of terlipressin and albumin. Hepatic encephalopathy has a profound impact on the quality of life of patients with cirrhosis. Lactulose and rifaximin are first- and second-line treatments for hepatic encephalopathy, respectively. Newer therapies such as L-ornithine L-aspartate and albumin require further assessment.

A case of Fukuyama-type congenital muscular dystrophy with acute carnitine deficiency triggered by fever, vomiting, and gastrointestinal bleeding.

BACKGROUND: Carnitine is essential for transporting long-chain fatty acids into mitochondria and promotes energy metabolism via ß-oxidation of long-chain fatty acids. Although carnitine is also present in the peripheral blood, 98% of total carnitine is stored in muscle tissue. Neuromuscular diseases accompanied by muscle atrophy are likely to lead to secondary carnitine deficiency, owing to the reduced amount of total carnitine stored in the body. CASE PRESENTATION: An 8-y-old Japanese boy with Fukuyama-type congenital muscular dystrophy accompanied by severe psychomotor retardation had been constantly bedridden, suffered from dysphagia, and had been fed through a gastrostomy tube since the age of 1 y. Regular oral carnitine supplementation (5 mg/kg/d of levocarnitine) was initiated at the age of 7 y, which increased serum carnitine value to within the normal range (serum total carnitine concentration, 58.5-60.9 µmol/L; acylcarnitine concentration, 45.8-55.0 µmol/L; free carnitine concentration, 5.9-12.7 µmol/L). He developed a fever, vomiting, and gastrointestinal bleeding at the age of 8 y. He fell into a coma and visited an emergency room 12 h later. Hypoglycemia and hypocarnitinemia (serum total carnitine concentration, 3.7 µmol/L; acylcarnitine concentration, 2.9 µmol/L; free carnitine concentration, 0.8 µmol/L; acyl-to-free carnitine ratio, 3.6) were observed, and he was found to be negative for urinary ketone bodies. CONCLUSIONS: Neuromuscular diseases accompanied by muscle atrophy may lead to acute carnitine deficiency, even if the serum carnitine concentration is within the normal range before onset. During sick days, it may be necessary to modify a patient's treatment, such as increasing both oral supplementation and intravenous administration of carnitine.

Reduced dose direct oral anticoagulants compared with warfarin with high time in therapeutic range in nonvalvular atrial fibrillation.

Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78-0.93), intracranial bleeding HR 0.64 (0.51-0.80), hemorrhagic stroke HR 0.68 (0.50-0.92), gastrointestinal bleeding HR 0.81 (0.69-0.96) and all-cause stroke HR 0.87 (0.76-0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63-0.78) and HR 0.80 (0.69-0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59-0.96), with higher major bleeding risk, HR 1.31 (1.15-1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03-1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting.

Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Management of iron-deficiency anemia following acute gastrointestinal hemorrhage: A narrative analysis and review.

Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplementation to treat subsequent iron deficiency (ID) or iron-deficiency anemia (IDA). Guidelines regarding management of these patients are lacking. We aimed to identify areas of unmet need in patients with ID/IDA following acute GIB in terms of patient management and physician guidance. We formed an international working group of gastroenterologists to conduct a narrative review based on PubMed and EMBASE database searches (from January 2000 to February 2021), integrated with observations from our own clinical experience. Published data on this subject are limited and disparate, and those relating to post-discharge outcomes, such as persistent anemia and re-hospitalization, are particularly lacking. Often, there is no post-discharge follow-up of these patients by a gastroenterologist. Acute GIB-related ID/IDA, however, is a prevalent condition both at the time of hospital admission and at hospital discharge and is likely underdiagnosed and undertreated. Despite limited data, there appears to be notable variation in the prescribing of intravenous (IV)/oral iron regimens. There is also some evidence suggesting that, compared with oral iron, IV iron may restore iron levels faster following acute GIB, have a better tolerability profile, and be more beneficial in terms of quality of life. Gaps in patient care exist in the management of acute GIB-related ID/IDA, yet further data from large population-based studies are needed to confirm this. We advocate the formulation of evidence-based guidance on the use of iron therapies in these patients, aiding a more standardized best-practice approach to patient care.