losartan-potassium and Gastrointestinal-Hemorrhage

Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development of complications of portal hypertension and liver dysfunction. Advanced chronic liver disease is considered responsible for more than one million deaths annually worldwide. No treatment is available to specifically target fibrosis and cirrhosis; liver transplantation remains the only curative option. Researchers are investigating strategies to restore liver functionality to avoid or slow progression towards end-stage liver disease. Cytokine mobilisation of stem cells from the bone marrow to the liver could improve liver function. Granulocyte colony-stimulating factor (G-CSF) is a 175-amino-acid protein currently available for mobilisation of haematopoietic stem cells from the bone marrow. Multiple courses of G-CSF, with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, might be associated with accelerated hepatic regeneration, improved liver function, and survival.. To evaluate the benefits and harms of G-CSF with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, compared with no intervention or placebo in people with compensated or decompensated advanced chronic liver disease.. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two trial registers (October 2022) together with reference-checking and web-searching to identify additional studies. We applied no restrictions on language and document type.. We only included randomised clinical trials comparing G-CSF, independent of the schedule of administration, as a single treatment or combined with stem or progenitor cell infusion, or with other medical co-interventions, with no intervention or placebo, in adults with chronic compensated or decompensated advanced chronic liver disease or acute-on-chronic liver failure. We included trials irrespective of publication type, publication status, outcomes reported, or language.. We followed standard Cochrane procedures. All-cause mortality, serious adverse events, and health-related quality of life were our primary outcomes, and liver disease-related morbidity, non-serious adverse events, and no improvement of liver function scores were our secondary outcomes. We undertook meta-analyses, based on intention-to-treat, and presented results using risk ratios (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI) and I. We included 20 trials (1419 participants; sample size ranged from 28 to 259), which lasted between 11 and 57 months. Nineteen trials included only participants with decompensated cirrhosis; in one trial, 30% had compensated cirrhosis. The included trials were conducted in Asia (15), Europe (four), and the USA (one). Not all trials provided data for our outcomes. All trials reported data allowing intention-to-treat analyses. The experimental intervention consisted of G-CSF alone or G-CSF plus any of the following: growth hormone, erythropoietin, N-acetyl cysteine, infusion of CD133-positive haemopoietic stem cells, or infusion of autologous bone marrow mononuclear cells. The control group consisted of no intervention in 15 trials and placebo (normal saline) in five trials. Standard medical therapy (antivirals, alcohol abstinence, nutrition, diuretics, β-blockers, selective intestinal decontamination, pentoxifylline, prednisolone, and other supportive measures depending on the clinical status and requirement) was administered equally to the trial groups. Very low-certainty evidence suggested a decrease in mortality with G-CSF, administered alone or in combination with any of the above, versus placebo (RR 0.53, 95% CI 0.38 to 0.72; I. G-CSF, alone or in combination, seems to decrease mortality in people with decompensated advanced chronic liver disease of whatever aetiology and with or without acute-on-chronic liver failure, but the certainty of evidence is very low because of high risk of bias, inconsistency, and imprecision. The results of trials conducted in Asia and Europe were discrepant; this could not be explained by differences in participant selection, intervention, and outcome measurement. Data on serious adverse events and health-related quality of life were few and inconsistently reported. The evidence is also very uncertain regarding the occurrence of one or more liver disease-related complications. We lack high-quality, global randomised clinical trials assessing the effect of G-CSF on clinically relevant outcomes.

Topics: Acute-On-Chronic Liver Failure; Adult; Erythropoietin; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Granulocyte Colony-Stimulating Factor; Growth Hormone; Humans; Intercellular Signaling Peptides and Proteins; Liver Cirrhosis; Quality of Life; Stem Cells

Colorectal cancers are classically revealed by a low digestive bleeding, which can be occult or exteriorized. They commonly present anemia at the diagnosis leading to particular outcomes. Perioperative blood transfusions are frequently indicated for the treatment of localized tumors and for hepatic resection of metastatic lesions but transfusions seem to have a negative impact on prognosis by increasing infections and potentially recurrence. In this context, various strategies aim at limiting the transfusional risk (autologous transfusion, preoperative use of erythropoietin...). Anemia associated with advanced colorectal cancers provides the same interest as for any metastatic tumor, as quality of life of patients is correlated to the hemoglobin's level.

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Colorectal Neoplasms; Erythropoietin; Gastrointestinal Hemorrhage; Humans; Recombinant Proteins; Rectum; Transfusion Reaction

Anaemia caused by acute upper gastrointestinal bleeding is treated with blood transfusion or iron, but patients usually face a two-month recovery period from post-haemorrhage anaemia. This prospective, randomised, open, pilot study was designed to investigate whether recombinant human erythropoietin (Epoetin) therapy accelerate haematocrit increase in the post-bleeding recovery period.. We studied hospitalised patients admitted because of acute ulcer bleeding or haemorrhagic gastritis, who had a haematocrit of 27-33% and did not receive blood transfusions. One day after the endoscopic confirmation of cessation of bleeding, they were randomised either to erythropoietin (20 000 IU Epoetin alfa subcutaneously, on days 0, 4 and 6) plus iron (100 mg im, on days 1- 6, (G(1)) or iron only (G(2)). Haematocrit was measured on days 0, 6, 14, 30, 45, and 60, respectively.. One patient from G(1) and two from G(2) were lost to follow-up. Therefore, 14 and 13 patients from G(1) and G(2) respectively were analysed. Demographic characteristics, serum iron, ferritin, total iron binding capacity, reticulocytes, and haematocrit were not significantly different at entry to the study. Median reticulocyte counts were significantly different between groups on day six (G(1): 4.0, 3.0-6.4 vs G(2): 3.5, 2.1-4.4%, P=0.03) and median haematocrit on day fourteen [G(1): 35.9, 30.7-41.0 vs G(2): 32.5, 29.5-37.0% (median, range), P=0.04].. Erythropoietin administration significantly accelerates correction of anemia after acute ulcer bleeding. The haematocrit gain is equivalent to one unit of transfused blood two weeks after the bleeding episode.

Topics: Acute Disease; Adult; Aged; Anemia; Erythropoietin; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Peptic Ulcer; Pilot Projects; Prospective Studies; Recombinant Proteins; Treatment Outcome

Topics: Erythropoietin; Gastric Antral Vascular Ectasia; Gastrointestinal Hemorrhage; Humans; Renal Insufficiency, Chronic

Topics: Bone Marrow Cells; Erythroblasts; Erythropoiesis; Erythropoietin; Gastrointestinal Hemorrhage; Hematopoietic Stem Cells; Humans; Male; Middle Aged; Myelodysplastic Syndromes

Acute-on-chronic liver failure (ACLF) is characterized by a rapid progression to multiple organ failure and is associated with a very high mortality rate of 50-90%. Novel therapies are being investigated such as Erythropoietin (EPO). The aim of this prospective cohort study was to analyse the value of EPO in predicting prognosis and determine which patients may benefit most from EPO therapy.. According to the EASL-CLIF criteria, 104 consecutive patients were diagnosed with ACLF, and separated into two groups based on the type of insult: bleeding (Group A=31) or non-bleeding (Group B=73). In addition to a complete biochemical work-up and calculation of relevant prognostic scores, levels of EPO were measured on admission and correlated to the type of insult and final outcome.. Fifteen patients from Group A (mean age 60.32+/-9.29 years) had a lethal outcome and higher values of EPO on admission (319.26+/-326.58 mIU/ml) (p<0.005), compared to the 37 patients from Group B (mean age 59.9+/-10.19 years) with EPO levels at admission of 29.88+/-34.6 mIU/mL. In Group B, a cut-off EPO value of 30.65 mIU/mL had a sensitivity of 87.5% and a specificity 57.4% in predicting lethal outcome with an AUROC of 0.823. In Group A, a cut-off value of 229.95 mlU/mL had a sensitivity and specificity of 53.3% and 92.7%, respectively. The AUROC for this cut-off was 0.847.. Erythropoietin is superior to the standard prognostic scores in predicting 28-day mortality. Lower levels of EPO were detected in patients without bleeding as an insult indicating a possible therapeutic benefit in these patients.

Topics: Acute-On-Chronic Liver Failure; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Erythropoietin; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Patient Admission; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; ROC Curve; Time Factors

Iron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1(-/-) mice, which led to increased erythropoietin (EPO) expression, polycythemia, and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1(-/-) mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Diet; Endothelial Cells; Endothelin-1; Erythropoietin; Gastrointestinal Hemorrhage; Gene Deletion; Hematopoiesis, Extramedullary; Hypertension, Pulmonary; Iron; Iron Regulatory Protein 1; Iron Regulatory Protein 2; Longevity; Mice; Models, Biological; Nerve Degeneration; Organ Specificity; Polycythemia; Protein Biosynthesis; Transcriptional Activation

Circulating erythropoietin (EPO) is mainly produced in the kidneys, depending on blood oxygen level. The present study investigated the postmortem serum EPO levels with regard to the cause of death and survival time. Serial medicolegal autopsy cases of postmortem time within 48 h (n = 536) were examined. Serum EPO levels were within the clinical reference range in most cases. Uremic patients with medical administration of an EPO agent (n = 11) showed a markedly high level (140-4,850 mU/ml; median, 1,798 mU/ml). Otherwise, an elevation in serum EPO level (>30 mU/ml) was mainly seen in protracted deaths due to blunt injury and fire fatality, depending on the survival time (r = 0.69, p < 0.0001, and r = 0.45, p < 0.0001, respectively), and in subacute deaths from gastrointestinal bleeding and infectious diseases. However, mildly to moderately elevated serum EPO levels were sporadically found in acute deaths due to mechanical asphyxiation, fire fatality, and acute ischemic heart disease, and in fatal hypothermia cases, especially for elderly subjects. Protracted deaths due to mechanical asphyxiation and ischemic heart disease did not show any survival time-dependent increase in serum EPO level (p > 0.05). EPO was immunohistochemically detected in the tubular epithelia and interstitial cells, showing no evident difference among the causes of death, independent of survival time or serum level. These findings suggest that serum EPO can be used as a marker for investigating anemia and/or hypoxia as a consequence of fatal insult in subacute or prolonged deaths, or a predisposition to traumatic deaths or fatal heart attacks in acute deaths.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asphyxia; Biomarkers; Communicable Diseases; Drowning; Erythropoietin; Female; Fires; Forensic Pathology; Gastrointestinal Hemorrhage; Humans; Hypothermia; Immunohistochemistry; Kidney; Male; Middle Aged; Myocardial Ischemia; Postmortem Changes; Sensitivity and Specificity; Time Factors; Uremia; Wounds, Nonpenetrating; Young Adult

A 3-year-old girl with H. pylori negative duodenal ulcer with hypergastrinemia secondary to chronic renal failure presenting with upper gastrointestinal bleed as the cardinal manifestation is unusual in toddlers and the case is presented for its rarity.

Topics: Anemia, Hypochromic; Anti-Ulcer Agents; Child, Preschool; Drug Therapy, Combination; Duodenal Ulcer; Erythropoietin; Female; Gastric Acid; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Omeprazole; Treatment Outcome

Accumulating studies demonstrate that the expressions of hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) depend on cellular oxygen tension, which is involved in the pathological process of tissue hypoxia and/or ischemia. The present study investigated hypoxia-inducible factor-1alpha (HIF-1alpha), EPO and VEGF mRNA expressions in the kidney with regard to the cause of death in medicolegal autopsy. Relative quantifications of HIF-1alpha, EPO and VEGF mRNAs, based on real-time TaqMan reverse transcription-polymerase chain reaction (RT-PCR), were performed on tissue specimens obtained from consistent sites of the bilateral renal cortices. The cases (total, n=245, 6-48h postmortem) included fatal blunt/sharp instrument injuries (n=53/31), asphyxia (n=28: aspiration, n=8; strangulation/hanging, n=20), drowning (n=27), fire fatality (n=62), acute myocardial infarction/ischemia (AMI, n=39), and gastrointestinal hemorrhage (n=5). Both HIF-1alpha and EPO mRNA levels were significantly lower in drowning cases. More characteristic findings were found for VEGF mRNA: it showed higher expression levels for AMI, acute blunt/sharp instrument injury, and aspiration, whereas it was lower for neck compression (strangulation/hanging), drowning, fire fatality with higher blood carboxyhemoglobin (COHb) levels (>60%), peracute blunt injury, and gastrointestinal hemorrhage. Quantitative assays of renal HIF-1alpha, EPO and VEGF mRNA transcripts are potentially useful for investigating the pathophysiology of death, and VEGF mRNA may be especially useful as an indication of acute circulatory failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asphyxia; Child; Drowning; Erythropoietin; Female; Fires; Forensic Pathology; Gastrointestinal Hemorrhage; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney; Male; Middle Aged; Myocardial Ischemia; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Endothelial Growth Factor A; Wounds, Nonpenetrating; Wounds, Penetrating

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.

Topics: Adenocarcinoma; Aged; Diabetic Nephropathies; Erythropoietin; Gastrectomy; Gastrointestinal Hemorrhage; Hormones, Ectopic; Humans; Male; Paraneoplastic Endocrine Syndromes; Polycythemia; Renal Dialysis; Stomach Neoplasms

Topics: Anemia; Christianity; Erythropoietin; Female; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Refusal

Topics: Administration, Cutaneous; Aged; Angiodysplasia; Erythropoietin; Estradiol; Estrogen Replacement Therapy; Female; Gastrointestinal Hemorrhage; Hepatitis C, Chronic; Humans; Kidney Transplantation; Melena; Recombinant Proteins; Recurrence; Renal Dialysis; Uremia

Topics: Erythropoietin; Gastrointestinal Hemorrhage; Humans; Recombinant Proteins; Transfusion Reaction

Topics: Abdominal Pain; Adult; Analgesics, Non-Narcotic; Anemia, Iron-Deficiency; Appendicitis; Epoetin Alfa; Erythropoietin; Fever; Gastrointestinal Hemorrhage; Glomerulonephritis; Hematinics; Humans; Hypertension; Ibuprofen; Kidney Failure, Chronic; Male; Nursing Diagnosis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Recombinant Proteins; Renal Dialysis

Topics: Aged; Duodenal Diseases; Erythropoietin; Female; Folic Acid; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Male; Recombinant Proteins; Renal Dialysis; Stomach Diseases; Treatment Refusal; Vitamin B 12

The decision to transfuse children in families practicing the Jehovah's Witness faith with human blood products raises medical, legal, and moral questions. Two cases are presented in which recombinant human erythropoietin was used in pediatric patients as an alternative following acute gastrointestinal hemorrhage. The patients demonstrated increased hematocrit levels obviating the need for blood transfusion. Although erythropoietin is not an alternative to hemotransfusion in the unstable patient, it may be an option in the hemodynamically uncompromised Jehovah's Witness patient following acute blood loss.

Topics: Adolescent; Child, Preschool; Christianity; Erythropoietin; Esophageal Stenosis; Gastrointestinal Hemorrhage; Hematocrit; Humans; Male; Recombinant Proteins; Religion and Medicine; Stomach Ulcer

Topics: Aged; Christianity; Erythropoietin; Female; Gastrointestinal Hemorrhage; Hematocrit; Humans; Religion and Medicine

The dependence of the serum erythropoietin (Epo) level on the blood hemoglobin concentration was compared in patients suffering from leukemia and ulcerative colitis. In leukemia, the level of immunoreactive and bioactive Epo was generally much higher than in ulcerative colitis at comparable degrees of anemia. The highest Epo values were found in patients with severe bone marrow insufficiency of erythropoiesis. These findings support the hypothesis that the plasma level of Epo depends not only on the hemoglobin concentration of the blood but is also influenced by the proliferative activity of the erythron.

Topics: Anemia; Animals; Colitis, Ulcerative; Erythropoiesis; Erythropoietin; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Leukemia; Mice; Polycythemia Vera

Topics: Anemia; Bone Marrow Cells; Bone Marrow Transplantation; Child; Diphosphoglyceric Acids; Erythrocyte Aging; Erythropoietin; Gastrointestinal Hemorrhage; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis; Thiourea

Topics: Anemia, Macrocytic; Animals; Erythropoietin; Gastrointestinal Hemorrhage; Mice

Topics: Cerebellar Neoplasms; Cerebral Ventriculography; Erythropoietin; Gastrointestinal Hemorrhage; Hemangiosarcoma; Humans; Male; Middle Aged; Polycystic Kidney Diseases; Polycythemia; Urography