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Objectives: Upper gastrointestinal bleeding (GIB) in patients has been well-characterized in liver cirrhosis but studies on lower GIB are limited. The clinical characteristics, management and outcomes in patients with and without liver cirrhosis was compared to determine the overall features of GIB in patients with liver cirrhosis compared with non-cirrhotics., Methods: A retrospective study on cirrhotics hospitalized for GIB 2010-2021, matched with control group of non-cirrhotics (1:4) for upper vs. lower GIB. Patients with overt bleeding leading to hospitalization were included., Results: Overall, 396 patients had cirrhosis, 267 (67%) men, median age 62, alcoholic etiology 177/396 (45%), median MELD 12 (range 6-32). Overall 102 cirrhotics had GIB, matched with 391 non-cirrhotics. Overall 87 (85%) cirrhotic patients had upper and 15% lower GIB. Compared to non-cirrhotics, the cause of GIB was more commonly acute variceal bleeding (AVB) (42% vs. 1%), hemorrhoids 40% vs. 6% ( p  = 0.002), less commonly gastric ulcer 13% vs. 31% ( p  < 0.001), duodenal ulcer 9% vs. 29% ( p  < 0.001), 5% of cirrhotics used NSAIDs vs. 26% of controls ( p  < 0.001). Rebleeding occurred in 14% of cirrhotics vs. 3% in controls ( p  < 0.001). Only one cirrhotic patient (1%) died from GIB vs. 0.8% of controls within 45 days. Overall mortality 45 days after hospitalization was 10% in cirrhotics vs. 5% in controls ( p  < 0.001)., Conclusions: Bleeding from gastric and duodenal ulcers were less common in cirrhotics than in controls. Bleeding from hemorrhoids was more common in cirrhotics. Mortality due to GIB was low in both groups but overall mortality was significantly higher in cirrhotics.

Background: First-line over-the-scope (OTS) clip treatment has shown higher efficacy than standard endoscopic therapy in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) from different causes. We compared OTS clips with through-the-scope (TTS) clips as first-line mechanical treatment in the specific setting of peptic ulcer bleeding., Methods: We conducted an international, multicenter randomized controlled trial on consecutive patients with suspected NVUGIB. Patients with Forrest Ia-IIb gastroduodenal peptic ulcer were randomized 1:1 to OTS clip or TTS clip treatment. The primary outcome was the rate of 30-day rebleeding after successful initial hemostasis. Secondary outcomes included the rates of successful initial hemostasis and overall clinical success, defined as the composite of successful initial hemostasis and no evidence of 30-day rebleeding., Results: 251 patients were screened and 112 patients were randomized to OTS (n = 61) or TTS (n = 51) clip treatment. The 30-day rebleeding rates were 1.6% (1/61) and 3.9% (2/51) in patients treated with OTS clips and TTS clips, respectively (Kaplan-Meier log-rank, P = 0.46). Successful initial hemostasis rates were 98.4% (60/61) in the OTS clip group and 78.4% (40/51) in the TTS clip group ( P = 0.001). Overall clinical success rates were 96.7% (59/61) with OTS clips and 74.5% (38/51) with TTS clips ( P = 0.001)., Conclusions: Low rates of 30-day rebleeding were observed after first-line endoscopic treatment of acute peptic ulcer bleeding with either OTS or TTS clips. However, OTS clips showed higher efficacy than TTS clips in achieving successful initial hemostasis and overall clinical success., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: The incidence of peptic ulcers has decreased during the last decades; the COVID-19 pandemic may have influenced the peptic ulcer hospitalizations. The study aimed to assess the admissions and mortality for complicated and uncomplicated peptic ulcers and the influence of the pandemic period. Material and Methods: We performed an observational study at a tertiary academic center, including all patients admitted for peptic ulcers between 2017-2021. We evaluated the admissions for complicated and uncomplicated ulcers and risk factors for mortality. Results: 1416 peptic ulcers were admitted, with an equal proportion of gastric and duodenal ulcers; most patients were admitted for bleeding (66.7%), and perforation (17.3%). We noted a decreasing trend for peptic bleeding ulcer (PUB) and uncomplicated ulcer admissions during 2020-2021, while for perforation no significant variation was recorded; a decreasing mortality in PUB was noted from 2017 to 2020. Admissions for bleeding peptic ulcer have decreased by 36.6% during the pandemic period; the mortality rate was similar. Admissions for perforated peptic ulcer have decreased by 14.4%, with a higher mortality rate during the pandemic period (16.83 versus 6.73%). Conclusion: A decreasing trend for PUB admissions but not for perforated ulcers was noted. Admissions for PUB have decreased by more than 1/3 during the pandemic period, with a similar mortality rate. Admissions for perforated peptic ulcers have decreased by 1/7, with significantly higher mortality rates during the pandemic period., (Celsius.)

Multisystem inflammatory syndrome in children (MIS-C) is a known complication of COVID-19. There is still limited knowledge about this condition. Here, we report the case of a previously healthy toddler boy, who presented with acute liver failure and duodenal lesions resulting in severe haematemesis and haemorrhagic shock, requiring intensive care unit care. The patient had persistent transaminitis, a deranged coagulation profile, inflammatory markers were elevated, and laboratory tests were negative for common infectious hepatitis aetiologies as well as COVID-19 Reverse transcription polymerase chain reaction. His COVID-19 antibody was reactive. Upper gastrointestinal endoscopy revealed a Forrest grade III duodenal ulcer. Looking into the constellation of symptoms and laboratory findings a confirmed diagnosis of acute viral hepatitis caused by MIS-C was made. Hence, he was given intravenous methylprednisolone along with intravenous immunoglobulins, after which he improved clinically and transaminitis resolved. The patient was discharged on clinical improvement and was doing fine on follow-up up to 6 months., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Duodenal ulcer perforation in patients undergoing gastric bypass surgery is a rare late complication, occurring in less than 1% of cases. It carries a high mortality risk, particularly in cases of delayed diagnosis. The challenge lies in an unspecific clinical presentation and laboratory findings, as well as a CT scan not very helpful in almost half of cases. These features may lead to the consideration of other differential diagnoses, such as pancreatitis or cholecystitis. A multidisciplinary approach in collaboration with digestive surgeons is essential to enable rapid exploratory laparoscopy in presence of diagnostic uncertainty, and appropriate therapeutic management.

Background and Goals: Peptic ulcer disease is the most frequent cause of upper gastrointestinal bleeding. We sought to establish the epidemiology and hemostasis success rate of the different treatment modalities in this setting., Methods: Retrospective cohort study using the National Inpatient Sample. Non-elective adult admissions with a principal diagnosis of ulcer bleeding were included. The primary outcome was endoscopic, radiologic and surgical hemostasis success rate. Secondary outcomes were patients' demographics, in-hospital mortality and resource utilization. On subgroup analysis, gastric and duodenal ulcers were studied separately. Confounders were adjusted for using multivariate regression analysis., Results: A total of 136,425 admissions (55% gastric and 45% duodenal ulcers) were included. The mean patient age was 67 years. The majority of patients were males, Caucasians, of lower income and high comorbidity burden. The endoscopic, radiological and surgical therapy and hemostasis success rates were 33.6, 1.4, 0.1, and 95.1%, 89.1 and 66.7%, respectively. The in-hospital mortality rate was 1.9% overall, but 2.4% after successful and 11.1% after failed endoscopic hemostasis, respectively. Duodenal ulcers were associated with lower adjusted odds of successful endoscopic hemostasis, but higher odds of early and multiple endoscopies, endoscopic therapy, overall and successful radiological therapy, in-hospital mortality, longer length of stay and higher total hospitalization charges and costs., Conclusions: The ulcer bleeding endoscopic hemostasis success rate is 95.1%. Rescue therapy is associated with lower hemostasis success and more than a ten-fold increase in mortality rate. Duodenal ulcers are associated with worse treatment outcomes and higher resource utilization compared with gastric ulcers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Duodenal ulcer (DU) is the most common gastroscopic manifestation of abdominal Henoch-Schönlein purpura (HSP), which may cause severe bleeding and often requires esophagogastroduodenoscopy (EGD) to confirm the diagnosis. However, the condition of children with HSP changes rapidly; not all children are able to undergo EGD on time, and some hospitals do not have a pediatric EGD unit. Therefore, assessing the risk factors for developing DU in HSP using simple and readily available indicators is essential. Children with HSP at Wuhan Children Hospital from June 2020 to June 2022 were included in the training set and completed EGD. The patients were divided into 2 groups: those with (DU group) and without DU (non-DU group). Data were collected from the 2 groups, and univariate and multivariate logistic regression analyses were used to compare the 2 groups. Children with HSP admitted between July 2022 and June 2023 were included in the validation set. Four indicators, prognostic nutrition index, albumin (ALB), gastrointestinal (GI) bleeding, and duration of onset before EGD, were found in the DU and non-DU groups. GI bleeding and prognostic nutritional index (PNI) ≤ 53.0 have strong predictability for patients with HSP and DU. GI bleeding and PNI ≤ 53.0 may provide new reference evidence for condition assessment and treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We present the case of a 58-year-old female with a history of a bleeding duodenal peptic ulcer. Endoscopic hemostasis was unsuccessful; therefore, a transcatheter arterial embolization of a culprit vessel was performed. She was admitted to the hospital two months later because of obstruction of the common bile duct with cholangitis. Attempts to endoscopically place a biliary stent failed. The treating medical team opted for a surgical choledocho-jejunostomy. After 20 months, she presented with a melena and a severe anemia. Diagnostic work-up revealed portal vein thrombosis with portal cavernoma and bleeding choledocho-jejunostomy varices. The case presents and discusses rare complications of duodenal ulcer disease, as well as possible causes and treatment options., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal cancer, and gastric and duodenal ulcer and a randomly selected subcohort of ~2000 individuals within the China Kadoorie Biobank study of >0.5 million adults. We used a bead-based multiplex serology assay to measure antibodies against 19 pathogens (total 43 antigens) in baseline plasma samples. Associations between pathogens and antigen-specific antibodies with risks of site-specific cancers and ulcers were assessed using Cox regression fitted using the Prentice pseudo-partial likelihood. Seroprevalence varied for different pathogens, from 0.7% for Hepatitis C virus (HCV) to 99.8% for Epstein-Barr virus (EBV) in the subcohort. Compared to participants seronegative for the corresponding pathogen, Helicobacter pylori seropositivity was associated with a higher risk of non-cardia (adjusted hazard ratio [HR] 2.73 [95% CI: 2.09-3.58]) and cardia (1.67 [1.18-2.38]) gastric cancer and duodenal ulcer (2.71 [1.79-4.08]). HCV was associated with a higher risk of duodenal cancer (6.23 [1.52-25.62]) and Hepatitis B virus was associated with higher risk of duodenal ulcer (1.46 [1.04-2.05]). There were some associations of antibodies again some herpesviruses and human papillomaviruses with risks of gastrointestinal cancers and ulcers but these should be interpreted with caution. This first study of multiple pathogens with risk of gastrointestinal cancers and ulcers demonstrated that several pathogens are associated with risks of gastrointestinal cancers and ulcers. This will inform future investigations into the role of infection in the etiology of these diseases., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Abstract: Gastroduodenal perforation commonly due to spontaneous perforation of a pre-existing peptic ulcer is a surgical emergency. On laparotomy, approximately 60%-70% perforations are duodenal and 15%-20% gastric. The most prevalent etiology are Helicobacter pylori infection in 65%-70% and non-steroidal anti-inflammatory drugs (NSAIDS) abuse in 30%-50% cases depending on the prevalence of H. pylori infection. We report here the autopsy findings in a 29-year-old male who collapsed suddenly in the emergency room of our hospital after a bout of massive hematemesis., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Rationale: Retroperitoneal hematomas are relatively common in patients undergoing nephrectomy. Herein, we report an unusual case involving a giant retroperitoneal hematoma and subsequent duodenal ulcerative bleeding following a radical nephrectomy., Patient Concerns: A 77-year-old woman was admitted to our hospital for lower back pain, and she had severe right hydronephrosis and a urinary tract infection., Diagnoses: The patient was diagnosed and confirmed as high-grade urothelial carcinoma., Interventions: After ineffective conservative treatments, a right radical nephrectomy and ureteral stump resection were performed. The patient received proton pump inhibitors to prevent stress ulcer formation and bleeding. On the first day post-surgery, she had normal gastrointestinal (GI) endoscopy findings. On the second day post-surgery, abdominal computed tomography revealed a retroperitoneal hematoma. Notably, 14 days post-surgery, massive GI bleeding occurred, and GI endoscopy identified an almost perforated ulcer in the bulbar and descending duodenum., Outcomes: The patient died on day 15 after surgery., Lessons: Duodenal ulceration and bleeding might occur following a retroperitoneal hematoma in patients treated with nephrectomy. Timely intervention may prevent duodenal ulcers and complications, and thus could be a promising life-saving intercession., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2024. The Author(s).)

Pseudoaneurysms are uncommon but their rupture and bleeding can lead to serious complications and be fatal. We present here a case of a man in his late 70s who was transferred to our hospital with persistent gastrointestinal bleeding. One month prior to his admission, he had undergone surgery for a fracture to his left knee. Endoscopic examination found pulsating blood vessels on a duodenal ulcer, which suddenly ruptured and caused significant bleeding. Immediate endoscopic haemostasis was administered and the bleeding decreased. Considering the high rate of rebleeding that may occur with a pseudoaneurysm, the patient underwent interventional radiology that culminated in a diagnosis of a pseudoaneurysm originating from gastroduodenal artery (GDA); successful embolization was achieved. Tests showed that the patient had Helicobacter pylori infection. We hypothesised that the H. pylori infection had led to the occurrence of the duodenal bulb ulcer, and the patient's left knee fracture and surgery a month previously had contributed to this predisposition for a pseudoaneurysm., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

Objectives: The optimal strategy of Helicobacter pylori eradication in patients with duodenal ulcer is unclear. In this study, we aimed to compare the utility and the ulcer recurrence rate using the empiric treatment versus the test and treat strategies in patients with uncomplicated duodenal ulcer., Methods: A decision-utility analysis was performed using a decision tree. The empiric treatment strategy was compared with the test and treat strategy. The probabilities of recurrent ulcers were determined and utilities of the 2 strategies were compared using the quality-adjusted life-year (QALY). Sensitivity analysis was performed to evaluate for model robustness., Results: The probability of recurrent ulcer with the empiric strategy was 10.5%. The probabilities of recurrent ulcer with the test and treat strategy were 12.6%, 14.7%, 16.8%, and 17.9% based on 95%, 90%, 85%, and 80% sensitivity for histopathology, respectively. At the 95% estimate for the sensitivity of histopathology, the empiric strategy was associated with greater QALY compared with the test and treat strategy, 0.9875 versus 0.9853. The empiric treatment strategy was associated with greater QALY at extreme values for the estimates in our model., Conclusions: The empiric treatment strategy is associated with 2.1% to 7.4% lower recurrence rate for a range of test sensitivity between 95% and 80%, and results in greater QALY compared with the test and treat strategy., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs. Helicobacter pylori (HP)-stratified analysis found an HP-related host genetic locus. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD being enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology., (© 2023. The Author(s).)

BACKGROUND Group G streptococcus (GGS) infection is reported to have invasive pathogenicity similar to that of group A streptococcus (GAS) infection, causing a strong systemic inflammatory response with bacteremia and various complications. Herein, we report a case of posterior reversible encephalopathy syndrome (PRES) as a rare complication of a GGS infection. CASE REPORT An 89-year-old Japanese man presented to our hospital with gastrointestinal bleeding and shoulder pain. Close examination revealed a refractory duodenal ulcer (DU) with disseminated intravascular coagulation and soft tissue infection of the right arm, which was found to be caused by GGS. A hemorrhagic tendency due to disseminated intravascular coagulation made it difficult to achieve hemostasis, leading to repeated blood transfusions. Although remission of both the DU and infection was achieved with treatment, impairment of swallowing function and vision subsequently appeared. Magnetic resonance imaging revealed hyperintense lesions with elevated apparent diffusion coefficient (ADC) values on T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). The patient was diagnosed with PRES, which did not improve even after discharge on day 118. CONCLUSIONS GGS infection developed with refractory duodenal ulcer bleeding, resulting in PRES with irreversible sequelae. The occurrence of PRES, which may be a rare complication of GGS infection, should be considered when central nervous system manifestations are observed in case of invasive streptococcal infection with a systemic inflammatory response.

BACKGROUND Arteriovenous malformation is an unusual cause of gastrointestinal bleeding, particularly in the pancreas. A definitive treatment strategy is not yet established. CASE REPORT We present the case of a 37-year-old man with underlying hypertension and no significant family history who presented with a 3-month history of intermittent epigastric pains and unintentional weight loss of 5 kg in 2 months. The upper endoscopy showed a large duodenal ulcer, which was uncontrolled with a standard dose of proton pump inhibitors. An abdominal computed tomography scan with contrast was indicated and revealed an enhanced mass of 2.5×3.5×4 cm in size, located on the second and third parts of the duodenum and head of the pancreas, indicating an arteriovenous malformation. On day 10 of hospitalization, the patient suddenly had melena and a drop of hemoglobin level to 5.6 g/dL; angiography intervention was successful to control the bleeding. However, gastrointestinal bleeding recurred after 2 weeks, and the patient successfully underwent a Whipple procedure. CONCLUSIONS The diagnosis and therapeutic management of arteriovenous malformations are uniquely challenging; therefore, pancreatic arteriovenous malformations should be listed on the differential diagnosis, particularly in those cases with non-healing and large duodenal ulcers. Otherwise, early imaging modalities should be performed to confirm the diagnosis. In particular, angiography can temporarily control bleeding before proceeding with more definitive therapy.

Rationale: Duodenal ulcer bleeding is a potentially life-threatening condition commonly caused by the erosion of the duodenal arteries., Patient Concerns: A 55-year-old male was referred to our hospital with abdominal pain for the past 3 days. Contrast-enhanced computed tomography of the abdomen revealed wall thickening in the descending part of the duodenum and a cystic lesion (27 × 19 mm) contiguous with the duodenum, with an accumulation of fluid. An esophagogastroduodenoscopy showed the significantly stenotic duodenum, which prevented passage of the endoscope and evaluation of the main lesion. Based on these findings, duodenal ulcer perforation and concomitant abscess formation were suspected. Two days after admission, he had massive hematochezia with bloody drainage from the nasogastric tube., Diagnoses: Emergency angiography revealed duodenal ulcer bleeding from the gastroduodenal artery and the branch artery of the inferior pancreaticoduodenal artery and middle colic artery (MCA)., Interventions: The patient was treated with transcatheter arterial embolization (TAE) of the gastroduodenal artery, the branch vessel of the inferior pancreaticoduodenal artery, and the main trunk of the MCA., Outcomes: Hemostasis was achieved with TAE. The patient recovered uneventfully and undergone a gastro-jejunal bypass surgery for the duodenal stenosis 2 weeks after TAE. He was discharged without any abnormal complaints on postoperative day 12., Lessons: We have experienced a rare case of duodenal ulcer bleeding from a branch of the MCA. In patients with refractory upper gastrointestinal bleeding, careful evaluation of bleeding sites is recommended considering unexpected culprit vessels., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis., Methods: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy., Results: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded., Conclusions: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This study was supported by the National Science and Technology Council, Taiwan (NSTC 111-2622-B-006-002) and National Cheng Kung University Hospital, Taiwan (NCKUH-11103012)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The latest magnet-controlled capsule endoscopy (MCCE) system can examine the water-distended stomach, duodenum, and the small bowel. We assessed the use of MCCE as the first diagnostic tool in patients with acute upper gastrointestinal bleeding (AUGIB)., Methods: This was a prospective cohort study that enrolled patients admitted with AUGIB from two teaching hospitals. Patients underwent MCCE as the initial diagnostic modality. Our primary endpoint was the diagnostic yield of MCCE. The subsequent care of these patients was guided by MCCE findings., Results: Of 100 enrolled patients, 99 (mean age 54 years, 70.7% men) with a median Glasgow-Blatchford score of 6 (IQR 3-9) underwent MCCE. In three patients, MCCE found active bleeding (two duodenal ulcers and Dieulafoy's lesion). The overall diagnostic yield of MCCE was 95.8% (92 lesions in 96 patients); five in the esophagus (Mallory Weiss tears 2, varices 1, and esophagitis 2), 51 in the stomach (gastric erosions 26, gastric ulcers 14, cancer 3, GIST 3, gastric polyps 3, antral vascular ectasia 1,angiodysplasia 1), 32 in the duodenum (ulcers 28, erosions 3, polyp 1), and four in the small bowel (ulcers 2, an erosion with a nonbleeding vessel 1, Meckel's diverticulum 1). Fifty-two (52.5%) patients were discharged without endoscopy. Forty-five (45.5%) patients underwent inpatient esophagogastroduodenoscopy (EGD), which found an antral ulcer and six duodenal ulcers in addition., Conclusions: In stable patients with AUGIB, MCCE can be used as a diagnostic tool. EGD should follow in patients with an inadequate view of the duodenum., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To compare clinical and operative results between laparoscopic primary repair (LPR) alone and LPR with highly selective vagotomy (LPR-HSV) in patients with duodenal ulcer perforation., Methods: Clinical data from patients who underwent either LPR or LPR-HSV by resecting both sides of the neurovascular bundle using an ultrasonic or bipolar electrosurgical device for duodenal ulcer perforations, between 2010 and 2020, were retrospectively collected. Between-group differences in continuous and categorical variables were statistically analysed., Results: Data from 184 patients (mean age, 49.6 years), who underwent either LPR ( n  = 132) or LPR-HSV ( n  = 52) were included. The mean operation time was significantly longer in the LPR-HSV group (116.5 ± 39.8 min) than in the LPR group (91.2 ± 33.3 min). Hospital stay was significantly shorter in the LPR-HSV group (8.6 ± 2.6 days) versus the LPR group (11.3 ± 7.1 days). The mean postoperative day of starting soft fluid diet was also significantly shorter in the LPR-HSV group (4.5 ± 1.4 days) than in the LPR group (5.6 ± 4 days). No between-group difference in morbidity rate was observed. The learning curve of the HSV procedure showed a stable procedure time after 10 operations., Conclusions: LPR with HSV may be a safe and feasible procedure for selective cases who are at high risk for ulcer recurrence., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

A 71-year-old woman underwent endoscopic submucosal dissection for early duodenal cancer at the second portion of the duodenum and developed acute peritonitis due to delayed duodenal perforation. Emergency laparotomy was performed. A huge perforation formed at the descending duodenum without ampulla involvement. Pancreas-sparing partial duodenectomy (PPD) with gastrojejunostomy was performed (250 min operative time) with 50 mL of intraoperative blood loss. She required intensive care for 3 days and was discharged on postoperative day 21 with no severe complications. Emergency treatment for a major duodenal injury or perforation remains challenging because of high morbidity and mortality. An appropriate treatment should be considered according to the nature of the defect. Although PPD is an acceptable procedure for patients with a duodenal neoplasm, its use in emergency surgery is rarely reported. PPD is more reliable than primary repair or anastomosis using a jejunal wall, and less invasive than pancreaticoduodenectomy, for emergency treatment. We performed PPD in this patient because the duodenal perforation was too large to reconstruct and did not involve the ampulla. PPD can be a safe and feasible alternative surgical procedure to pancreaticoduodenectomy for a major duodenal perforation, especially in patients with a duodenal perforation that does not involve the ampulla., (© 2023. Japanese Society of Gastroenterology.)

Background: In the early stages of the coronavirus disease 2019 (COVID-19) outbreak, the most widely recognised symptoms of the disease were fever, cough, shortness of breath, myalgia, and fatigue. However, in addition to these symptoms, COVID-19 can cause systemic symptoms outside the lungs. Older patients with severe COVID-19 often require admission to the intensive care unit (ICU). Acute rectal ulcer bleeding, characterised by painless, profuse haematochezia, caused by solitary or multiple rectal ulcers, is one of the main causes of severe haematochezia in patients with COVID-19 in the ICU. However, recurrent duodenal ulcer bleeding followed by rectal ulcer bleeding has not previously been reported in older patients during ICU treatment for severe COVID-19., Cases Presentation: Herein, we report the case of an 81-year-old woman admitted to the emergency department due to severe COVID-19 and transferred to the ICU 2 days later for treatment. During treatment in the ICU, the patient developed recurrent duodenal ulcer bleeding and underwent endoscopic electrocoagulation haemostasis and gastroduodenal artery embolisation. However, the night after the final haemostatic operation, due to rectal ulcer bleeding, the patient discharged bloody stools intermittently, which was effectively controlled using endoscopic electrocoagulation, topical medication, blood transfusion, and haemostatic drugs., Conclusions: To the best of our knowledge, this is the first report of duodenal ulcer bleeding followed by rectal ulcer bleeding in an older patient with severe COVID-19 infection. This report creates awareness for clinicians about the multiple and complex gastrointestinal symptoms that may occur during COVID-19 treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Most research on duodenal ulcers has focused on bulbar ulcers; details on post-bulbar ulcers remain largely unknown. This study was conducted to determine the characteristics of patients with post-bulbar duodenal ulcers depending on their location., Methods and Materials: We conducted a retrospective study of hospitalized patients newly diagnosed with duodenal ulcers on endoscopy at a tertiary referral center in Japan between April 2004 and March 2019. Five hundred fifty-one patients diagnosed with duodenal ulcers were extracted for analysis., Results: Ulcers were observed only in the bulbus in 383 cases, only in the post-bulbar duodenum in 82 cases, and were co-existing in both areas in 86 cases. The Bulbar group had less comorbidities and was more likely to have atrophic gastritis, while the Post-bulbar and Co-existing groups were more likely to be admitted for non-gastrointestinal conditions. Regular acid suppressant use was more common in the post-bulbar group than in the Bulbar group. Bulbar ulcers were associated with a shorter length of stay relative to post-bulbar and co-existing ulcers, but ulcer location was not an independent predictor of length of stay. Patients with co-existing bulbar and post-bulbar ulcers have characteristics similar to those with post-bulbar ulcers alone., Conclusion: Patients with post-bulbar ulcers and those with co-existing bulbar and post-bulbar ulcers have different characteristics and outcomes relative to patients with bulbar ulcers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Peptic ulcer disease causing perforation is extremely rare in children and primarily affects teenagers. We present a case of a perforated peptic ulcer in a 6-year-old with abdominal pain and emesis with CT findings of moderate pneumoperitoneum and pelvic free fluid without a distinct cause. He was emergently transferred, found to be peritonitic, and taken to the operating room for diagnostic laparoscopy revealing an anterior duodenal ulcer, and underwent laparoscopic Graham patch repair. Postoperatively, the child had positive fecal antigen for H. pylori. He was treated with triple therapy and underwent subsequent testing to confirm eradication. Perforated peptic ulcer is an uncommon pediatric surgical problem, and imaging may not be diagnostic as in the case presented here. Thus, clinicians need to maintain a high index of suspicion when evaluating children with free air and a surgical abdomen in the setting of long-standing abdominal pain.

Background and Aims: Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of standard clips. Data indicate a superiority of OTSCs in hemostasis as first- and second-line therapy. However, the impact of the OTSC designs, in particular the traumatic (-t) or atraumatic (-a) type, in duodenal ulcer bleeding has not been analyzed so far., Methods: This was a retrospective analysis of a prospective collected database from 2009 to 2020 of 6 German endoscopic centers. All patients who underwent emergency endoscopy and were treated using an OTSC for duodenal ulcer bleeding were included. OTSC-t and OTSC-a patients were compared by the Fisher exact test, χ 2 test, or Mann-Whitney U test as appropriate. A propensity score-based 1:1 matching was performed to obtain equal distribution of baseline characteristics in both groups., Results: The entire cohort comprised 173 patients (93 OTSC-a, 80 OTSC-t). Age, gender, anticoagulant therapy, Rockall score, and treatment regimen had similar distributions in the 2 groups. However, the OTSC-t group showed significantly more active bleeding ulcers (Forrest Ia/b). Matching identified 132 patients (66 in both groups) with comparable baseline characteristics. Initial bleeding hemostasis (OTSC-a, 90.9%; OTSC-t, 87.9%; P = .82) and 72-hour mortality (OTSC-a, 4.5%; OTSC-t, 6.0%; P > .99) were not significantly different, but the OTSC-t group revealed a clearly higher rate of recurrent bleeding (34.9% vs 7.6%, P < .001) and necessity of red blood cell transfusions (5.1 ± 3.4 vs 2.5 ± 2.4 concentrates, P < .001)., Conclusions: For OTSC use, the OTSC-a should be the preferred option for duodenal ulcer bleeding., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority of cases despite patients' late presentation. The objective of the study was to determine the frequency of postoperative complications of perforated duodenal ulcer, conducted in the Surgery Department, Jinnah Postgraduate Medical Centre, Karachi, from March 20, 2018 to September 20, 2018. The study was a descriptive case series of 108 patients of both genders with perforated duodenal ulcer > 1 week old with ASA score I & II. Patients with trauma and comorbidities were excluded. The patients underwent laparotomy and peritoneal toilet, and after noting the site of perforation indirect Graham's Omentopexy was performed. Complications like duodenal fistula, peritonitis, and paralytic ileus, and patient's death within 10 days of surgery were noted. Age ranged from 18 to 50 years with mean age of 35.027±5.13 years, mean weight 71.120±12.77 kg, mean height 1.541 ±0.09 metres, mean BMI 29.975±4.99 kg/m2, and the mean duration of complaint was 4.194±1.30 weeks. Male predominance in 75 (69.4%) patients. Duodenal fistula was seen in 10 (9.3%) patients, peritonitis 12 (11.1%), paralytic ileus 14 (13%) and mortality was in 11 (10.2%) patients.

Rationale: Gastric mucosal ulcer caused by drug overdose is very rare in clinical practice, and here is a case of gastric antral ulcer caused by drug overdose., Patient Concerns: A 35-year-old housewife from a mountainous region in China took 48 Ibuprofen Sustained-Release capsules (300 mg/capsule) orally at 1 time. Because of severe tingling in the upper abdomen accompanied by a sharp increase in blood pressure, she came to the doctor 48 hours later., Diagnoses: Gastric antral ulcer (multiple stage A1), duodenococcitis, chronic nonatrophic gastritis, Helicobacter pylori infection, moderate depression, and cognitive impairment., Interventions: Acid suppression, antihypertensive and a series of symptomatic treatments., Outcomes: All somatic symptoms disappeared after a follow-up visit 2 months later., Lessons: This case provides valuable information to the clinic, through the compilation of literature and case analysis, the author found that paying attention to mental health, to women in poor areas and to women from families of low education level are indispensable in medical diagnosis and treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess the value of multiplanar computed tomography (CT) in the diagnosis of nonperforated duodenal bulb ulcer (NPDBU)., Method: We retrospectively analyzed data from 135 patients with NPDBU (ulcer group) and 150 patients with a normal duodenal bulb (control group) who underwent contrast-enhanced abdominal CT and were diagnosed via upper endoscopy from January 2018 to February 2022. The clinical and CT features were compared between the two groups. Independent prognostic factors for diagnosing NPDBU were determined using binary logistic regression analysis. An external validation cohort to determine the model's efficiency comprised 80 patients from another center., Results: Gastrointestinal bleeding was more frequent in patients with NPDBU than in those without (p < 0.001). No significant differences in age and sex were observed between the groups (all p > 0.05). The duodenal bulbar wall was significantly thicker in the ulcer group than in the control group, as determined using CT (p < 0.001). Irregular mucosal surface, layered enhancement, and blurred fat space around the duodenal bulb were more common in the ulcer group than in the control group (all p < 0.001). Binary logistic regression analysis revealed that gastrointestinal bleeding, wall thickness of ≥ 4.85 mm, irregular mucosal surface, and blurred peripheral fat space were the most significant variations associated with NPDBU, with an area under the curve (AUC) of 0.974. The external validation cohort had an AUC of 0.916., Conclusions: Careful multiplanar CT interpretation suggests the underlying presence of NPDBU and allows timely endoscopic verification and appropriate treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: The polymorphisms in the region between 58 and 62 amino acids of the 194-amino acid CagL protein (CagL hypervariable motif) affect the binding affinity of CagL to integrin α5β1 (ITGA5B1) receptor in host epithelial cells and have an effect on the development of various gastrointestinal diseases. We aimed to evaluate the associations of gastroduodenal pathologies, with the polymorphisms of cagL gene of Helicobacter pylori (H. pylori) and also associations between vacA genotypes and cagL polymorphisms., Methods: A total of 19 gastric cancer, 16 duodenal ulcer, and 26 non-ulcer dyspepsia patients were included in this case-control study. All cases had H. pylori. A fragment of 651 bp from gene cagL (hp0539) and cagA, vacA genes was amplified by polymerase chain reaction. Purified polymerase chain reaction products were sequenced by Sanger sequencing, and nucleotide sequences were translated into amino acid sequences., Results: All of the H. pylori strains had cagL and cagA genes. In the 16 (84%) gastric cancer cases, the D58 amino acid polymorphism was significant than the 4 (15.4%) duodenal ulcer cases (P = .029), and the D58/K59 amino acid polymorphism was significant in 12 (63.1%) of the gastric cancer cases than 1 (3.85%) duodenal ulcer case (P = .008). D58/K59 and DKIGQ (n = 10; 52.63%) were the most common polymorphisms in the gastric cancer and were associated with the vacA genotype s1/m2, respectively (P = .022 and P = .008). The D58/K59 amino acid polymorphism was found to have a significant Odds Ratio (OR) value of 8.9 (P = .0017) in multivariate logistic regression analysis., Conclusions: The risk of gastric cancer development is 8.9 times higher with D58/K59 polymorphism.

Rapunzel syndrome is a rare clinical entity in which a trichobezoar is produced by the ingestion of hair at the gastric level, extending in the form of a tail towards the duodenum. It occurs in young patients with trichotillomania and trichophagia. We present the case of a 24-year-old woman with a history of anxiety without treatment, who for 10 years presented trichotillomania and trichophagia, producing a picture of intestinal obstruction that required surgical intervention, evidencing a giant Trichobezoar throughout the gastric cavity and one jejunum associated with diastatic perforation. duodenal.

Aims: Duodenal ulcer perforations are frequently encountered but there is limited literature regarding risk factors for leak after omentopexy., Methodology: The record of 100 patients of duodenal ulcer perforation undergoing omentopexy by open approach was prospectively maintained to identify any significant factors contributing towards leak., Results: Out of 100 patients undergoing omentopexy, 9 (9%) developed leak; when leak occurred, the mortality was very high (44.4%). Patients who developed leak (09) were compared against those who did not (91), and it was seen that seen that duration of symptoms before surgery (> 3 days), amount of intra-abdominal contamination (> 2 L), low body mass index (BMI < 19.35 kg/m 2 ), serum creatinine (> 1.5 mg/dl), and deranged International Normalized Ratio (INR) were found to be significant on univariate analysis; however, multivariate analysis revealed only low BMI and high creatinine to be contributory towards leak., Conclusion: Leak after omentopexy carries a high morbidity and mortality. Identification of risk factors may help in optimizing patients at risk and reduce the incidence of leak and its sequelae., Trial Registration Number: CTRI/2020/03/023798., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: This study aims to summarize our experience in diagnosis and treatment of pediatric duodenal ulcer perforation in a National Center for Children's Health., Methods: Fifty-two children with duodenal perforation hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University from January 2007 to December 2021 were retrospectively collected. According to the inclusion and exclusion criteria, patients with duodenal ulcer perforation were included in the group. They were divided into the surgery group and the conservative group according to whether they received surgery., Results: A total of 45 cases (35 males and 10 females) were included, with a median age of 13.0 (0.3-15.4) years. Forty cases (40/45, 88.9%) were over 6 years old, and 31 (31/45, 68.9%) were over 12 years old. Among the 45 cases, 32 cases (32/45, 71.1%) were examined for Helicobacter pylori (HP), and 25 (25/32, 78.1%) were positive. There were 13 cases in the surgery group and 32 cases in the conservative group, without a significant difference in age between the two groups (P = 0.625). All cases in the surgery group and the conservative group started with abdominal pain. The proportion of history time within 24 h in the two groups was 6/13 and 12/32 (P = 0.739), and the proportion of fever was 11/13 and 21/32 (P = 0.362). The proportion of pneumoperitoneum in the surgery group was higher than that in the conservative group (12/13 vs. 15/32, P = 0.013). The fasting days in the surgery group were shorter than those in the conservative group (7.7 ± 2.92 vs. 10.3 ± 2.78 days, P = 0.014). There was no significant difference in the total hospital stay (13.6 ± 5.60 vs14.8 ± 4.60 days, P = 0.531). The operation methods used in the surgery group were all simple sutures through laparotomy (9 cases) or laparoscopy (4 cases). All patients recovered smoothly after surgery., Conclusion: Duodenal ulcer perforation in children is more common in adolescents, and HP infection is the main cause. Conservative treatment is safe and feasible, but the fasting time is longer than the surgery group. A simple suture is the main management for the surgery group., (© 2023. The Author(s).)

Background: Gastroduodenal perforation stands out as one of the complications in cancer patients. Despite its high mortality, its characteristics are still poorly described. This study aimed to evaluate the characteristics and outcomes of cancer patients who had gastroduodenal perforation, and the influence of chemotherapy (CMT) in these cases., Method: A retrospective analysis of patients who underwent emergency surgery with an intraoperative finding of gastroduodenal perforation. Patients who performed CMT within 60 days before perforation were considered as the CMT group., Results: Among 45 patients included, 16 (35.5%) were classified as the CMT group and the remaining 29 (64.5%) patients as the non-CMT group. There was no difference between the groups regarding sex, age, BMI, comorbidity, and laboratory exams. ECOG 2-3 was significantly more frequent in the CMT group (68.8% vs. 34.5% p = 0.027). Major postoperative complications were similar between both groups (75% vs. 58.6%, p = 0.272). The sepsis of abdominal focus was the main postoperative complication. The 30-day mortality was 55.6%, with no difference between non-CMT and CMT groups (62.5% vs. 51.7%, respectively; p = 0.486). A multivariate analysis of risk factors showed that only an age of ≥65 years was related to 30-day mortality., Conclusions: Patients with gastroduodenal perforation and oncologic treatment present high mortality, regardless of receiving recent CMT.

Background: Duodenal defects are complex clinical situations, and their management is challenging and associated with high mortality. Besides surgery, endoscopic treatment options exist, but the size and location of the perforation can limit their application. We present a retrospective study, demonstrating a successful application of endoscopic vacuum therapy (EVT) for duodenal leaks., Methods: We performed a retrospective study of all patients who underwent EVT for duodenal perforations between 2016 and 2021 at two tertiary centers. We analyzed demographic and clinical patient characteristics, surgical outcomes, leak characteristics, sponge-related complications, and success rate., Results: Indications for treatment with EVT in the duodenum consisted of leak after duodenal suture of a perforated ulcer (n = 4), iatrogenic perforation after endoscopic resection (n = 2), iatrogenic perforation during surgery (n = 2), and anastomotic leak after upper gastrointestinal surgery (n = 2). EVT was used as a first-line treatment in seven patients and as a second-line treatment in three patients. EVT was successfully applied in all interventions (n = 10, 100%). Overall, EVT lead to definitive closure of the defects in eight out of ten patients (80%). No severe EVT-related adverse events occurred., Conclusion: EVT is safe and technically feasible, so it emerges as a promising endoscopic treatment option for duodenal leaks. However, multidisciplinary collaboration and management are important to reduce the occurrence of postoperative complications, and to improve recovery rates., (© 2022. The Author(s).)

Rationale: Owing to the anatomical characteristics of the duodenum, gastroduodenal artery (GDA) pseudoaneurysms can be caused by duodenal ulcers, which may rupture and lead to massive or repeated bleeding. Pseudoaneurysms are usually diagnosed using enhanced computerized tomography or angiography, whereas endoscopic signs have rarely been reported., Patient Concerns: Three patients aged 18 to 83 years with bleeding duodenal ulcers and GDA pseudoaneurysms were treated., Diagnosis: All patients had symptoms of gastrointestinal bleeding, and endoscopy revealed duodenal ulcers with visible vessels or adherent clot pulsations. Angiography confirmed the presence of a GDA pseudoaneurysm, which had an adjacent relationship with the duodenum., Interventions: The GDA pseudoaneurysm was embolized in each patient., Outcomes: Through transcatheter arterial embolization, endoscopic treatment, and traditional treatment, hematemesis or melena was gradually stopped and all patients were discharged., Lessons: The pulsation of visible vessels or adherent clots observed during endoscopy in patients with duodenal ulcer may indicate the formation of a gastroduodenal artery pseudoaneurysm. Therefore, we suggest that such patients receive enhanced computerized tomography or angiography to assess whether they need timely endovascular intervention treatment to avoid bleeding caused by a pseudoaneurysm., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The authors discuss the peculiarities of the terminology of gastric and duodenal ulcers. A clinical, endoscopic and morphological study (determination of the relative area and density of sex hormone receptors in the mucous membrane of the antrum of the stomach) of 760 patients of different ages and genders was carried out. It was found that six clinical parameters (duration of anamnesis, frequency of occurrence of concomitant pathology, epigastric discomfort, belching, heartburn, hereditary predisposition) and two morphological parameters (optical density of estrogen and progesterone receptors) statistically significantly differed in men and women over 60 years old suffering from duodenal ulcer, not gastric localization. The results obtained are consistent with the data of the medical literature, according to which, sexual differences in the pathogenesis of ulceration are more characteristic of ulcers of duodenal localization. Considering that sex differences in the pathogenesis of duodenal ulcers, unlike gastric ulcers, persist until old age, the authors call for a separate study of stomach ulcers and duodenal ulcers, which will probably lead to the need not to combine them two different diseases.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic study in which the duodenum is observed laterally, and the bile duct is instrumented. There are several indications and complications in the procedure., Objective: To determine the incidence of duodenal perforations, using the Stapfer classification in the Hospital Juárez de Mexico over a period of 5 years, as well as the management implemented in such cases., Method: The study was carried out at the Hospital Juárez de Mexico of the Ministry of Health. All patients who underwent ERCP between January 1, 2017, to May 30, 2022 were included., Results: 485 ERCP were performed in the study period. Incidence of 1.6% post-ERCP duodenal perforation. The average age of the subjects 56.37 years. In-hospital stay of post-ERCP perforations averaged 9.37 days. The time of the endoscopic study at the time of the surgical procedure is 10 h on average., Conclusions: Post-ERCP duodenal perforation is a complication that occurs with a low incidence, it tends to increase the number of days of in-hospital stay and increases morbimortality of patients; therefore, it is important to be always alert., (Copyright: © 2023 Permanyer.)