Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers: a prospective randomized phase II study.

BACKGROUND: Vonoprazan, potassium-competitive acid blocker, is expected to reduce incidence of delayed bleeding after gastric endoscopic submucosal dissection (ESD); however, preliminary data to design a large-scale comparative study are lacking. This study aimed to assess the efficacy of vonoprazan in preventing delayed bleeding after gastric ESD. METHODS: In this single-center randomized phase II trial, a modified screened selection design was used with a threshold non-bleeding rate of 89% and an expected rate of 97%. In this design, Simon's optimal two-stage design was first applied for each parallel group, and efficacy was evaluated in comparison with the threshold rate using binomial testing. Patients were randomly assigned in a 1:1 ratio to receive either vonoprazan 20 mg (VPZ group) or lansoprazole 30 mg (PPI group) for 8 weeks from the day before gastric ESD. The primary endpoint was the incidence of delayed bleeding, defined as endoscopically confirmed bleeding accompanied by hematemesis, melena, or a decrease in hemoglobin of ≥ 2 g/dl. RESULTS: Delayed bleeding occurred in three of 69 patients (4.3%, 95% CI 0.9-12.2%, p = 0.047) in the VPZ group, and four of 70 (5.7%, 95% CI 1.6-14.0%, p = 0.104) in the PPI group. As only vonoprazan showed significant reduction in delayed bleeding compared with the threshold rate, it was determined to be efficacious treatment. CONCLUSIONS: Vonoprazan efficaciously reduced the delayed bleeding rate in patients with an ESD-induced gastric ulcer. A large-scale, randomized, phase III study is warranted to definitively test the effectiveness of vonoprazan compared with proton pump inhibitors.

Comportamiento de la hemorragia digestiva alta en el quinquenio 2009 a 2013 / Behavior of the high digestive bleeding in the five-year period 2009-2013

Introducción: la hemorragia digestiva alta constituye un problema frecuente de salud en el mundo; así se comporta en Cuba, en la provincia Matanzas y en el hospital de estudio. Actualmente es considerada como causa mayor de morbimortalidad. Objetivo: determinar el comportamiento de la hemorragia digestiva alta en el Hospital Militar de Matanzas. Materiales y Métodos: se realizó una investigación descriptiva, en un periodo de cinco años que incluyó a todos los pacientes ingresados con ese diagnóstico, y los que durante su ingreso por otra causa presentaron episodios de hemorragia. El índice de Rockall permitió evaluar la necesidad de cirugía, recidiva y mortalidad. Resultados: la mayoría de los pacientes pertenecieron al grupo de riesgo intermedio. Los hombres fueron los más afectados, el grupo de tercera edad presentó mayor incidencia. La gastritis hemorrágica fue la primera causa de sangrado. La hipertensión arterial resultó ser el factor de riesgo relevante y el tabaquismo el hábito tóxico más frecuente. Conclusiones: como beneficio relevante se demostró la importancia de la endoscopia precoz para el diagnóstico de la causa, tratamiento y pronóstico de la hemorragia. Se observó una buena correlación entre el pronóstico del paciente al ingreso y su estado al final del tratamiento (AU).

Introduction: the high digestive hemorrhage is a frequent health problem in the world; it behaves the same in Cuba, in the province of Matanzas and in the hospital where the study was carried out. Currently it is considered a major cause of morbi-mortality. Objective: to determine the behavior of the high digestive bleeding in the Military Hospital of Matanzas. Materials and Methods: a descriptive research was carried out in a five-year period. It included all the patients admitted with that diagnosis and those who presented episodes of hemorrhage even if they were admitted by any other cause. The Rockall index allowed to assess the necessity of surgery, the recidivism and mortality. Results: most of the patients belonged to the intermediate risk group. Male patients were the most affected one; the group of elder people showed higher incidence. Hemorrhagic gastritis was the first cause of bleeding. Arterial hypertension was the relevant risk factor and smoking the most frequent toxic habit. Conclusions: as a relevant benefit it was showed the importance of precocious endoscopy for the diagnosis of the hemorrhage cause, treatment and prognosis. It was observed a good correlation between the patient´s prognosis at the admission and his status at the end of the treatment (AU).

Comportamiento de la hemorragia digestiva alta en el quinquenio 2009 a 2013 / Behavior of the high digestive bleeding in the five-year period 2009-2013

Introducción: la hemorragia digestiva alta constituye un problema frecuente de salud en el mundo; así se comporta en Cuba, en la provincia Matanzas y en el hospital de estudio. Actualmente es considerada como causa mayor de morbimortalidad. Objetivo: determinar el comportamiento de la hemorragia digestiva alta en el Hospital Militar de Matanzas. Materiales y Métodos: se realizó una investigación descriptiva, en un periodo de cinco años que incluyó a todos los pacientes ingresados con ese diagnóstico, y los que durante su ingreso por otra causa presentaron episodios de hemorragia. El índice de Rockall permitió evaluar la necesidad de cirugía, recidiva y mortalidad. Resultados: la mayoría de los pacientes pertenecieron al grupo de riesgo intermedio. Los hombres fueron los más afectados, el grupo de tercera edad presentó mayor incidencia. La gastritis hemorrágica fue la primera causa de sangrado. La hipertensión arterial resultó ser el factor de riesgo relevante y el tabaquismo el hábito tóxico más frecuente. Conclusiones: como beneficio relevante se demostró la importancia de la endoscopia precoz para el diagnóstico de la causa, tratamiento y pronóstico de la hemorragia. Se observó una buena correlación entre el pronóstico del paciente al ingreso y su estado al final del tratamiento (AU).

Introduction: the high digestive hemorrhage is a frequent health problem in the world; it behaves the same in Cuba, in the province of Matanzas and in the hospital where the study was carried out. Currently it is considered a major cause of morbi-mortality. Objective: to determine the behavior of the high digestive bleeding in the Military Hospital of Matanzas. Materials and Methods: a descriptive research was carried out in a five-year period. It included all the patients admitted with that diagnosis and those who presented episodes of hemorrhage even if they were admitted by any other cause. The Rockall index allowed to assess the necessity of surgery, the recidivism and mortality. Results: most of the patients belonged to the intermediate risk group. Male patients were the most affected one; the group of elder people showed higher incidence. Hemorrhagic gastritis was the first cause of bleeding. Arterial hypertension was the relevant risk factor and smoking the most frequent toxic habit. Conclusions: as a relevant benefit it was showed the importance of precocious endoscopy for the diagnosis of the hemorrhage cause, treatment and prognosis. It was observed a good correlation between the patient´s prognosis at the admission and his status at the end of the treatment (AU).

Relationship of time to presentation after onset of upper GI bleeding with patient characteristics and outcomes: a prospective study.

BACKGROUND AND AIMS: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. METHODS: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. RESULTS: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). CONCLUSIONS: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation.

Advances and pitfalls in the management of small bowel polyps in Peutz-Jeghers syndrome

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Cholesterol metabolism in acute upper gastrointestinal bleeding, preliminary observations.

Hypocholesterolemia is commonly found in critically ill patients; however, the aetiology of this condition remains unclear. Several clinical studies refer to the possible negative impact of haemodilution on cholesterol (CH) metabolism in acute medical conditions. The aim of this study was to examine the serum CH profile (total CH, LDL and HDL CH) during acute gastrointestinal bleeding which is a life-threatening condition characterised by alterations in lipid metabolism. Serum non-CH sterols (lathosterol, squalene, sitosterol and campesterol) concentrations as markers of CH synthesis and CH absorption were measured at the same time. Twenty-four patients with acute upper gastrointestinal bleeding (UGIB) were measured for these parameters over a 6-day period. The control group was 100 healthy blood donors.We found lower plasma levels of total CH (p < 0.001) and LDL CH (p < 0.05) in patients with UGIB than in the control group. The decreased HDL CH plasma levels in patients were not statistically significant. In addition, patients had significantly lower plasma levels of lathosterol, squalene, campesterol and sitosterol (p < 0.05).Our results showed abnormalities not only in the CH plasma profile, but also in plasma concentrations of non-CH sterols. These findings of alterations in both the CH synthesis and absorption process could be a contributory cause of hypocholesterolemia during acute gastrointestinal bleeding. However, further research is necessary.

Correlación clínica- para-clínica en un escolar con hipertensión porta de etiología a esclarecer / Clinical-paraclinical in a school with portal hypertension to determine

La hipertensión porta (HTP) es el resultado del incremento de la presión dentro del sistema venoso porta. Se presenta con poca frecuencia en el paciente pediátrico pero es una de las mayores causas de morbilidad y mortalidad en el niño con enfermedad hepática. La mayoría de los pacientes con http presentan un estado hiperdinámico, lo cual aumenta el flujo venoso porta y mantiene la hipertensión. Puede ser secundaria a obstrucción a nivel prehepático, intrahepático o extrahehepático.

Portal hypertension (PH) is the result of increased pressure within the portal venous system. It occurs infrequently in the pediatric patient but it is a major cause of morbidity and mortality in children with liver disease. Most patients with PH have a hyperdynamic state, which increases venous flow and portal hypertension remains. May be secondary to obstruction at prehepatic, intrahepatic or extrahehepatic.

"My two-week-old daughter is throwing up blood".

Swallowed maternal blood at the time of delivery or from cracked nipples during breastfeeding is the most common cause of suspected gastrointestinal bleeding in the neonate. In this case, the Apt-Downey test is a useful diagnostic tool. The Apt-Downey test can effectively differentiate neonatal from maternal hemoglobin based on the conversion of oxyhemoglobin to alkaline globin hematin when mixed with alkali.

Ischemic retinitis as a result of acute episodic blood loss.

Acute episodic blood loss leads to a sudden change in the haemodynamics leading to a number of ocular and systemic effects. Occurrence of ischemic retinitis secondary to acute blood loss is of a very rare occurrence. This communication presents a case of infarction of the nerve fibre layer secondary to acute blood loss in a 55-year-old male.

Fibronectin, platelet factor 4 and beta-thromboglobulin in endemic hepatosplenic schistosomiasis: relation to acute hematemesis.

Some platelet alpha-granule contents were assessed in parallel with other markers of hemostatic imbalance in 50 patients with hepatosplenic schistosomiasis (15 patients with compensated hepatosplenomegaly, 15 patients with advanced hepatic fibrosis and ascites and 20 patients during an acute attack of hematemesis from ruptured esophageal varices). Platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), fibronectin (FN), prothrombin fragment 1 + 2, thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP) and D-dimer were assessed in schistosomal patients compared to controls (15 healthy subjects). A significant increase in both thrombin (high TAT and prothrombin fragment 1 + 2 levels) and plasmin (high FbDP and D-dimer levels) generation was detected in decompensated patients establishing the presence of a steady state of low-grade disseminated intravascular coagulation, with and without overt bleeding, in these patients. A decrease in plasma FN concentration was found in diseased groups compared to controls. The reduction in plasma levels of FN paralleled the defective liver function and matched the relative decrease in tissue FN in liver specimens of decompensated patients suggesting that FN levels can be used to evaluate the pathological staging of the disease. A significant increase in beta-TG and PF4 levels was noted in decompensated patients with ascites and/or acute hematemesis compared both to controls and compensated patients reflecting platelet alpha-granule release and consequently increased in vivo platelet activation which may initiate and/or perpetuate the pathophysiological mechanisms of the hemostatic imbalance underlying the hemorrhagic diathesis in hepatosplenic schistosomiasis.

Fibrinolytic parameters during acute haematemesis in endemic hepatosplenomegaly.

Fibrinogen (Fg), plasminogen (Plg), alpha 2-antiplasmin (alpha 2-AP), plasminogen activator (PA), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (DD) and fibrin(ogen) degradation products (FDP) were studied in 60 subjects: 40 patients with endemic hepatosplenomegaly (20 during acute haematemesis from ruptured oesophageal varices, 20 with endemic hepatosplenomegaly assigned to the same grade of oesophageal varices but with no history of haematemesis) and 20 normal controls. All parameters were markedly altered in the disease groups. Reduced levels of Fg, Plg, alpha 2-AP and PAI were associated with increasing levels of PA, t-PA, DD and FDP. Alterations were most marked in the group complicated by acute bleeding. It was concluded that these patients have an enhanced fibrinolytic state. This was probably aggravated in the haematemesis group by an acute haemostatic imbalance that superimposed the low grade chronic DIC reported in cases of hepatosplenic schistosomiasis.

Hemodynamically stable upper gastrointestinal bleeding.

This article is a prospective evaluation of 38 patients presenting to an emergency department (ED) with hematemesis but who were otherwise hemodynamically stable. Four patients were admitted, only one because of the development of hemodynamic instability. Thirty-three patients were discharged; on follow-up there was no evidence of major morbidity or mortality. Two patients were lost to follow-up, one who left against medical advice and one who lived in a county outside the service area of our hospital. Patients with hematemesis can be safely discharged from the ED after observation for 6 hours if they: (1) lack orthostatic vital sign changes; (2) lack associated significant underlying disease; (3) have a hemoglobin concentration greater than 10 gm/dL; (4) are less than 60 years of age; and (5) are thought to be reliable and compliant.

Blood ordering for haematemesis.

The blood ordering practices for acute upper gastrointestinal bleeding were assessed in 162 consecutive patients presenting with haematemesis admitted via the Accident and Emergency Centre. The patients were classified according to their estimated blood loss and haemoglobin level at the time of admission, and the amounts of blood ordered and given in the next 24 h were determined. The crossmatch: transfusion (CT) ratio was very high in one group (14.9), although the overall ratio of 2.4 was acceptable. There were marked variations in the ordering pattern of different medical officers, possibly because of the absence of clear guidelines. From the data obtained, a set of guidelines for ordering blood in this clinical condition was developed. It was estimated that if these guidelines had been used, there would have been a reduction of one-third of all units crossmatched, and that the overall CT ratio would have been reduced to 1.6.

Hepatitis and hematemesis complicating nicotinic acid use.

Nicotinic acid has a proven efficacy in the treatment of hypercholesterolemia. Therapeutic use of this water-soluble B vitamin has resulted in a survival benefit among patients enrolled in the Coronary Drug Project. Conversely, nicotinic acid has been associated with a high side-effect profile when used at therapeutic doses. Nevertheless, there are no previously reported cases of hematemesis temporally associated with nicotinic acid use. The authors report the case of a previously healthy 20-year-old man who developed hematemesis and hepatitis 1 week after self-initiating the daily consumption of 6 g of nicotinic acid. Supportive therapy and discontinuing nicotinic acid resulted in rapid clinical improvement in this patient. The clinical circumstances suggest a possible causal relationship between nicotinic acid consumption and his presenting problems. The use of large doses of nicotinic acid may be rapidly complicated by hematemesis and hepatitis.

Individual neurophysin concentrations in the pituitary and circulation of humans.

Specific, homologous human neurophysin I and II radioimmunoassays were established and used to measure the individual, immunoreactive neurophysin concentrations in human plasma. Circulating levels of human neurophysin I in normal individuals were less than 1 ng/ml and neurophysin II levels were 1-2 ng/ml. During dehydration, there was a significant rise in plasma neurophysin I, together with an increase in neurophysin II. Haemorrhage also was associated with a rise in plasma neurophysin I and II, but the percent increase was greater for I than II. In two subjects in whom nicotine inhalation caused a rise in plasma neurophysin I, there was no detectable increase in plasma neurophysin II. These stimuli which have been reported to release vasopressin from the posterior pituitary also are associated with the differential release of neurophysin I. Plasma neurophysin II levels could more clearly be shown to rise independently of plasma neurophysin I during events thought to be related to oxytocin release. Plasma neurophysin II levels were significantly elevated in women taking oral contraceptives. Similarly during pregnancy there was a progressive rise in plasma neurophysin II concentration which was proportional to the period of gestation. Plasma neurophysin II concentrations in seven of fifteen nursing women rose significantly during suckling. There was no detectable change in plasma neurophysin I concentrations during any of these events. Plasma neurophysin I and II levels were both significantly elevated in fourteen patients with chronic renal failure and rose over haemodialysis, suggesting that the kidney may be the major route of clearance of the neurophysins. In humans the independent release of neurophysin II was associated with stimuli thought to release oxytocin, but neurophysin I showed only a differential release compared to neurophysin II in vasopressin stimulated events.