Upper gastrointestinal haemorrhage patients' survival: A causal inference and prediction study.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a common medical emergency. This study aimed to develop models to predict critically ill patients with upper GI bleeding in-hospital and 30-day survival, identify the correlation factor and infer the causality. METHODS: A total of 2898 patients with upper GI bleeding were included from the Medical Information Mart for Intensive Care-IV and eICU-Collaborative Research Database, respectively. To identify the most critical factors contributing to the prognostic model, we used SHAP (SHapley Additive exPlanations) for machine learning interpretability. We performed causal inference using inverse probability weighting for survival-associated prognostic factors. RESULTS: The optimal model using the light GBM (gradient boosting algorithm) algorithm achieved an AUC of .93 for in-hospital survival, .81 for 30-day survival in internal testing and .87 for in-hospital survival in external testing. Important factors for in-hospital survival, according to SHAP, were SOFA (Sequential organ failure assessment score), GCS (Glasgow coma scale) motor score and length of stay in ICU (Intensive critical care). In contrast, essential factors for 30-day survival were SOFA, length of stay in ICU, total bilirubin and GCS verbal score. Our model showed improved performance compared to SOFA alone. CONCLUSIONS: Our interpretable machine learning model for predicting in-hospital and 30-day mortality in critically ill patients with upper gastrointestinal bleeding showed excellent accuracy and high generalizability. This model can assist clinicians in managing these patients to improve the discrimination of high-risk patients.

Endoscopic Management of Bleeding in Altered Anatomy after Upper Gastrointestinal Surgery.

Postoperative non variceal upper gastrointestinal haemorrhage may occur early or late and affect a variable percentage of patients-up to about 2%. Most cases of intraluminal bleeding are an indication for urgent Esophagogastroduodenoscopy (EGD) and require endoscopic haemostatic treatment. In addition to the approach usually adopted in non-variceal upper haemorrhages, these cases may be burdened with difficulties in terms of anastomotic tissue, angled positions, and the risk of further complications. There is also extreme variability related to the type of surgery performed, in the context of oncological disease or bariatric surgery. At the same time, the world of haemostatic devices available in digestive endoscopy is increasing, meeting high efficacy rates and attempting to treat even the most complex cases. Our narrative review summarises the current evidence in terms of different approaches to endoscopic haemostasis in upper bleeding in altered anatomy after surgery, proposing an up-to-date guidance for endoscopic clinicians and at the same time, highlighting areas of future scientific research.

Hemobilia: Historical overview, clinical update, and current practices.

Hemobilia refers to macroscopic blood in the lumen of the biliary tree. It represents an uncommon, but important, cause of gastrointestinal bleeding and can have potentially lethal sequelae if not promptly recognized and treated. The earliest known reports of hemobilia date to the 17th century, but due to the relative rarity and challenges in diagnosis of hemobilia, it has historically not been well-studied. Until recently, most cases of hemobilia were due to trauma, but the majority now occur as a sequela of invasive procedures involving the hepatopancreatobiliary system. A triad (Quincke's) of right upper quadrant pain, jaundice and overt gastrointestinal bleeding has been classically described in hemobilia, but it is present in only a minority of patients. Therefore, prompt diagnosis depends critically on a high index of suspicion based on a patient's clinical presentation and a history of recently undergoing hepatopancreatobiliary intervention or having other predisposing factors. Treatment of hemobilia depends on the suspected source and clinical severity and thus ranges from supportive medical care to urgent advanced endoscopic, interventional radiologic, or surgical intervention. In the present review, we provide a historical perspective, clinical update and overview of current trends and practices pertaining to hemobilia.

The influence of a simple blood transfusion policy on overtransfusion in acute upper gastrointestinal haemorrhage.

Blood transfusion is widely used in the management of acute upper gastrointestinal haemorrhage (AUGIH). Trial data suggests that excessive transfusion may be detrimental, yet overtransfusion remains commonplace. This study reports the impact of introducing a simple cross-match policy in a district general hospital, which resulted in a substantial fall in the prevalence of overtransfusion (odds ratio 0.43; 95% confidence interval 0.19-0.98), with potential patient benefits in terms of rebleeding, and a reduction in the total blood transfused from 162 to 121 units per 100 patients with AUGIH. For the cost of blood alone, this corresponds to projected savings across the NHS in England in excess of £2 million per annum.

Gastrosplenic Fistula: a Systematic Review.

Gastrosplenic fistula is an unusual complication of benign as well as malignant gastric and splenic pathologies. This pathology acquires an important clinical significance due to its rare association with life-threatening upper gastrointestinal haemorrhage. The aim of this article is to review the English-language literature in order to gain a better understanding of etiological factors, diagnostic evaluation, and management of gastrosplenic fistula. The systematic search of the literature was performed on PubMed and MEDLINE from January 1950 to September 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We retrieved 44 articles matching our selection criteria from the search. There were 3 case series, 37 case reports, and 4 review of the literature. In our appraisal of articles published in PUBMED, a total of 36 cases of malignant and 10 cases of benign gastrosplenic fistula could be identified. Gastrosplenic fistula is an exceptional complication of malignancies of the gastrointestinal tract. Lymphomas particularly arising from the spleen are the commonest cause. Gastric adenocarcinoma causing GSF is extremely rare. Most cases occur spontaneously, but at times, it can be secondary to tumour necrosis following chemotherapy.

Synergism interaction between genetic polymorphisms in drug metabolizing enzymes and NSAIDs on upper gastrointestinal haemorrhage: a multicenter case-control study.

BACKGROUND: Interindividual genetic variations contribute to differences in patients' response to drugs as well as to the development of certain disorders. Patients who use non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal disorders, mainly upper gastrointestinal haemorrhage (UGIH). Studies about the interaction between NSAIDs and genetic variations on the risk of UGIH are scarce. Therefore, we investigated the effect of 16 single nucleotide polymorphisms (SNPs) involved in drug metabolism on the risk of NSAIDs-induced UGIH. MATERIALS AND METHODS: We conducted a multicenter case-control study of 326 cases and 748 controls. Participants were sub-grouped into four categories according to NSAID exposure and genetic profile. We estimated odds ratios (ORs) and their 95% confidence intervals (CI) using generalized linear mixed models for dependent binomial variables and then calculated the measures of interaction, synergism index (S), and relative excess risk due to interaction (RERI). We undertook stratified analyses by the type of NSAID (aspirin, non-aspirin). RESULTS: We observed an excess risk of UGIH due to an interaction between any NSAID, non-aspirin NSAIDs or aspirin and carrying certain SNPs. The greatest excess risk was observed for carriers of: rs2180314:C>G [any NSAID: S = 3.30 (95%CI: 1.24-8.80), RERI = 4.39 (95%CI: 0.70-8.07); non-aspirin NSAIDs: S = 3.42 (95%CI: 1.12-10.47), RERI = 3.97 (95%CI: 0.44-7.50)], and rs4809957:A>G [any NSAID: S = 2.11 (95%CI: 0.90-4.97), RERI = 3.46 (95%CI: -0.40-7.31)]. Aspirin use by carriers of rs6664:C>T is also associated with increased risk of UGIH [ORaspirin(+),wild-type: 2.22 (95%CI: 0.69-7.17) vs. ORaspirin(+),genetic-variation: 7.72 (95%CI: 2.75-21.68)], yet larger sample size is needed to confirm this observation. CONCLUSIONS: The joint effect of the SNPs s2180314:C>G and rs4809957:A>G and NSAIDs are more than three times higher than the sum of their individual effects. Personalized prescriptions based on genotyping would permit a better weighing of risks and benefits from NSAID consumption.KEY MESSAGESMulticenter case-control study of the effect of genetic variations involved in drug metabolism on upper gastrointestinal haemorrhage (UGIH) induced by NSAIDs (aspirin and non-aspirin).There is a statistically significant additive synergism interaction between certain genetic polymorphisms and NSAIDs on UGIH: rs2180314:C>G and rs4809957:A>G. The joint effect of each of these single nucleotide polymorphisms and NSAIDs on UGIH is more than three times higher than the sum of their individual effects.Genetic profiling and personalized prescriptions would be useful in managing the risks and benefits associated with NSAIDs.

Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study.

Background: Despite the wide benefits of aspirin and its cost-effectiveness, aspirin prescriptions have been reduced due to idiosyncratic responses in susceptible individuals. Low-dose aspirin and single-nucleotide polymorphisms (SNPs) are independently associated with increased risk of gastrointestinal hemorrhage; however, to-date, no studies investigated the SNP-aspirin interaction effect on upper gastrointestinal hemorrhage (UGIH). Therefore, we aimed to evaluate the role of 25 SNPs in multiple genes involved in platelet activation, angiogenesis and inflammatory response in aspirin-related UGIH. Methods: A multicenter, full case-control study was conducted in patients exposed and unexposed to aspirin. Three hundred twenty-six cases diagnosed with UGIH were matched with 748 controls (1:3) by age, gender, health center, and recruitment date. Only adults of European origin were included. Participants were stratified by aspirin exposure and genotype [(Aspirin(-), wild-type), (Aspirin(+), wild-type), (Aspirin(+), genetic variation), (Aspirin(-), genetic variation)]. For each SNP, the Odds Ratio of UGIH and their 95% confidence intervals were estimated in each subgroup by using the generalized linear mixed models for dependent binomial variables. SNP-aspirin interaction effect was estimated through Relative Excess Risk due to Interaction (RERI) measures. Results: We observed two categories of SNPs that might modify the risk magnitude of UGIH in aspirin consumers. Seven SNPs (rs1387180 A > G, rs2238631 T > C, rs1799964 T > C, rs5050 T > C/T > G, rs689466 T > C, rs1799983 T > A/T > G, and rs7756935 C > A) were "positive modifiers" associated with an excess of risk from aspirin exposure and carrying that genetic variation (1.75 ≤ RERI ≤ 4.95). On the contrary, the following nine SNPs (rs2243086 G > T, rs1131882 G > A, rs4311994 C > T, rs10120688 G > A, rs4251961 T > C, rs3778355 G > C, rs1330344 C > T, rs5275 A > G/A > T, and rs3779647 C > T) were "negative modifiers" and associated with a reduced risk in aspirin users (-2.74 ≤ RERI ≤ -0.95). Conclusion: This preliminary study suggests that polymorphisms in genes involved in platelets activity, angiogenesis and inflammatory response might modify the risk of aspirin-related UGIH. Further studies with larger sample size and in different populations are needed to confirm our findings. If confirmed, this might have great impact on public health, thanks to aspirin's prophylactic properties in diseases of high incidence and severity.

Corrigendum: Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study.

[This corrects the article DOI: 10.3389/fphar.2020.00860.].

International prospective observational study of upper gastrointestinal haemorrhage: Does weekend admission affect outcome?

INTRODUCTION: Out of hours admissions have higher mortality for many conditions but upper gastrointestinal haemorrhage studies have produced variable outcomes. METHODS: Prospective study of 12 months consecutive admissions of upper gastrointestinal haemorrhage from four international high volume centres. Admission period (weekdays, weeknights or weekends), demographics, haemodynamic parameters, laboratory results, endoscopy findings, further procedures and 30-day mortality were recorded. Five upper gastrointestinal haemorrhage risk scores were calculated. RESULTS: 2118 patients, 60% male, median age 66 years were studied. Compared with patients presenting on weekdays, patients presenting at weekends had no significant differences in comorbidity, pulse, systolic BP, risk scores, frequency of peptic ulcers or varices. Those presenting on weekdays had lower haemoglobin (p = 0.007) and were more likely to have a normal endoscopy (p < 0.01). Time to endoscopy was less for weeknight presentation (p = 0.001). Sixty-seven per cent of those presenting on weekdays, 75% on weeknights and 60% at weekends had endoscopy within 24 h. Transfusion requirements, need for endoscopic therapy or surgery/embolization, rebleeding rates (6.1%) and mortality (7.2%) did not differ with presentation time. CONCLUSION: This multi-centre international study in large centres found no difference in demographics, comorbidity or haemodynamic stability and no increase in mortality for patients presenting with upper gastrointestinal haemorrhage out of hours.

AETIOLOGY OF UPPER GASTROINTESTINAL HAEMORRHAGEAN ENDOSCOPIC STUDY.

610 patients of upper gastrointestinal haemorrhage were endoscoped over a period of eleven years from July 1985 to June 1996. Average age of the patients was 39.2 years. 82.6% were males and 17.4% were females. Duodenal ulcer (31.5%), erosive mucosal disease (30.8%), oesophageal varices (31.5%) and gastric ulcer (6.2%) were the major causes. Other causes included Mallory Weiss syndrome (10 patients), gastric polyp (3 patients), stomal ulcer (5 patients) and self-induced bleeding (3 patients). Multiple lesions responsible for bleeding were detectable in 6.6% of patients. Endoscopy was non-contributory in 50 (11.2%) patients. Haemorrhage was the first presentation in 8.5% patients of duodenal ulcer. A known ulcerogenic agent in 21% of duodenal ulcer cases precipitated the bleeding. 77.4% of duodenal ulcer patients responded to conservative management. Erosive gastritis (57.5%) was the commonest finding in the erosive mucosal group. Alcohol and analgesics were the major precipitating factors in these patients. Majority of oesophageal varices were treated by sclerotherapy. Mortality (20%) were highest in the oesophageal varices group.

Anticoagulant-induced intramural duodenal haematoma presenting with upper-gastrointestinal haemorrhage.

Warfarin is an anticoagulant agent known to have a common complication, bleeding. Intramural intestinal haematoma is an uncommon incidence of warfarin-induced haemorrhage. Abdominal pain is its most frequent symptom and presentation with upper-gastrointestinal haemorrhage is rarely seen. Here, we present a 67-year-old male who was admitted to the hospital with active upper-gastrointestinal haemorrhage. In this case, the cause of bleeding has been attributed to duodenal intramural haematoma due to warfarin overuse.

Retrospective Analysis of the Impact of the Adjuvant Huoxuehuayu Drugs on Upper Gastrointestinal Haemorrhage in Patients with Acute Coronary Syndrome / 中国药学杂志

OBJECTIVE: To analyze the usage of the adjuvant huoxuehuayu drugs in patients with acute coronary syndrome(ACS), observe the impact of the drugs on upper gastrointestinal haemorrhage(UGH), and provide a reference for the clinical rational use of the adjuvant huoxuehuayu drugs. METHODS: The ACS patients were enrolled in our hospital during May to July 2016. And the patients were divided into four groups according to whether using the adjuvant huoxuehuayu drugs: not use, used one kind, used two kinds, used ≥three kinds of huoxuehuayu drugs. Then we collected medical history, therapeutic measures and other baseline data, gathered the data of the usage of the adjuvant huoxuehuayu drugs, evaluated CRUSADE bleeding risk and analyzed frequency of occurrence of UGH. RESULTS: Overall 503 ACS patients were enrolled, there was no significant differences among the four groups when the medical history, essential medicines and intervene frequency were compared respectively. On the other hand, the incidence rate of UGH increased significantly with CRUSADE bleeding risk rank increasing incrementally.For very low and low bleeding risk ACS patients, there were no significant differences in UGH incidence rate among the four groups; For moderate and high bleeding risk ACS patients, UGH incidence rate increased significantly in ACS patients using more than one kind of huoxuehuayu drugs compared with other two groups(P<0.05). For very high bleeding risk ACS patients, UGH incidence rate increased significantly in ACS patients using 2 and ≥3 kinds of huoxuehuayu drugs compared with patients using one kind drug, P=0.009, 0.025 respectively. CONCLUSION: For moderate and high bleeding risk ACS patients, UGH incidence rate increase significantly in ACS patients using ≥2 kinds of huoxuehuayu drugs. A significant increase in the incidence rate of UGH with CRUSADE bleeding risk rank increasing, the use of huoxuehuayu drugs shoud be controled strictly, especially for very high bleeding risk ACS patients.

Update on risk scoring systems for patients with upper gastrointestinal haemorrhage.

Upper gastrointestinal haemorrhage (UGIH) remains a common medical emergency worldwide. It is increasingly recognised that early risk assessment is an important part of management, which helps direct appropriate patient care and the timing of endoscopy. Several risk scores have been developed, most of which include endoscopic findings, although a minority do not. These scores were developed to identify various end-points including mortality, rebleeding or clinical intervention in the form of transfusion, endoscopic therapy or surgery. Recent studies have reported accurate identification of a very low risk group on presentation, using scores which require simple clinical or laboratory parameters only. This group may not require admission, but could be managed with early out-patient endoscopy. This article aims to describe the existing pre- and post-endoscopy risk scores for UGIH and assess the published data comparing them in the prediction of outcome. Recent data assessing their use in clinical practice, in particular the early identification of low-risk patients, are also discussed.

Artificial Neural Networks for Early Prediction of Mortality in Patients with Non Variceal Upper GI Bleeding (UGIB).

BACKGROUND: Mortality for non variceal upper gastrointestinal bleeding (UGIB) is clinically relevant in the first 12-24 hours of the onset of haemorrhage and therefore identification of clinical factors predictive of the risk of death before endoscopic examination may allow for early corrective therapeutic intervention. AIM: 1) Identify simple and early clinical variables predictive of the risk of death in patients with non variceal UGIB; 2) assess previsional gain of a predictive model developed with conventional statistics vs. that developed with artificial neural networks (ANNs). METHODS AND RESULTS: Analysis was performed on 807 patients with nonvariceal UGIB (527 males, 280 females), as a part of a multicentre Italian study. The mortality was considered "bleeding-related" if occurred within 30 days from the index bleeding episode. A total of 50 independent variables were analysed, 49 of which clinico-anamnestic, all collected prior to endoscopic examination plus the haemoglobin value measured on admission in the emergency department. Death occurred in 42 (5.2%). Conventional statistical techniques (linear discriminant analysis) were compared with ANNs (Twist® system-Semeion) adopting the same result validation protocol with random allocation of the sample in training and testing subsets and subsequent cross-over. ANNs resulted to be significantly more accurate than LDA with an overall accuracy rate near to 90%. CONCLUSION: Artificial neural networks technology is highly promising in the development of accurate diagnostic tools designed to recognize patients at high risk of death for UGIB.

Analysis of risk factors for upper gastrointestinal haemorrhage in hepatocellular carcinoma with concurrent portal hypertension / 中华肝胆外科杂志

Objective To explore the risk factors for upper gastrointestinal haemorrhage (UGH) in hepatocellular carcinoma (HCC) with portal hypertension (PH). Methods We retrospectively reviewed the medical records of 231 patients with HCC-PH treated in our Department from 1st January 2005 to 1st August 2009. The clinicopathologic factors were evaluated for their possible association with UGH in univariate analysis followed by multivariate analysis using Logistic regression model. The overall survival (OS) was calculated by the Kaplan-Meier method. Receiver operating characteristics (ROC) analysis with calculation of the area under the curve (AUC), sensitivity, and specificity were carried out to assess the predictive ability of the independent risk factors. Results Among 247 patients diagnosed with HCC-PH, 231 patients met the inclusion criteria and were entered into this study. UGH occurred in 28 patients (12.12 %, 28/231). Patients suffering from UGH had a higher 30-and 60-d mortality when compared with the non UGH group (53.57% vs. 4.43%, 96.43%vs. 10.34%, P＜0. 001, 0. 001). The 1-,2-and 3-year overall survival (OS) rates in the non-UGH and the UGH groups were 3. 57% (1/28), 0% (0/28), 0% (0/28) and 21.18% (43/203), 14.29% (29/203), 4.43% (9/203), respectively. There was a trend towards a non-significantly statistical difference in long-term (≥3 yr) survival (P=0. 605). UGH had a dismal prognosis with a median OS of 0. 8 months (0. 10-2. 40 months). Multivariate analysis of the risk factors showed elevated alpha-fetoprotein (AFP) (P = 0. 026) and aspartate aminotransferase (AST) more than twice normal (2N)(P=0. 004) were predictive factors, in particular, AST≥2N. A cutoff value (PI≥7. 242) predicted UGH with an AUC of 0.828 (95%CI, 0.698-0.957), sensitivity of 81.0% and a specificity of 81.0%, as calculated from the ROC. Risk score stratification predicted UGH to show a statistically significant difference (P＜0. 001). Conclusions UGH, as one of the end-stage incidents of HCC-PH,had a dismal prognosis. Patients with elevated AFP levels and AST levels above 2N were associated with high risks for UGH and should be monitored carefully or offered prophylactic treatments. Risk score stratification was useful for prediction of UGH.

Fístula aortoesofágica: hemorragia digestiva alta exanguinante: a propósito de un caso / A case of massive upper gastrointestinal hemorrage as a consequence of an a orto-esophageal fistula

Presentamos el caso de un varón de 70 años que sufrió una hemorragia digestiva alta exanguinante, con resultado final de muerte. Fue diagnosticada una fístula aorto-esofágica mediante escáner como causante de la misma, debida con alta probabilidad a una espina de pescado.

We report a case of a 70 old man, who suffered a severe upper gastrointestinal haemorrhage, with final result of death. A scanner diagnosed an aortoesophageal fistula, due with high probability to a fish thorn.

Studies on the Feasibility of Celiac Axis Ligation / 中国普外基础与临床杂志

Objective To summarize the study on the feasibility of celiac axis ligation. Methods Literatures about celiac axis ligation were reviewed retrospectively. Results Celiac axis branches included common hepatic artery, splenic artery, left gastric artery which had many variation and collateral flow between celiac and mesenteric vessels by gastroduodenal artery and pancreaticoduodenal artery. Celiac axis could be possibly ligated without obvious complications in patients who had celiac axis injuries, celiac artery aneurysms, upper gastrointestinal haemorrhage, excision of carcinoma around the celiac axis and portal hypertension. However, gallbladder necrosis or perforation, focal infarction of the liver even higher mortality had also been reported. Conclusion Celiac axis ligation should not be performed routinely, but it is surgically possible and may be a life saving approach in certain circumstances.