Esophageal food bolus impaction in pediatric age.

OBJECTIVES: Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific data on the prevalence and causes of EFI in children is lacking. The aim of this study was to provide further insights into EFI episodes in children. METHODS: We have prospectively enrolled all children admitted for a first episode of EFI between March 2018 and March 2023. A fluoroscopic contrast study was performed in all patients to confirm the boluses and assess their position. Boluses were extracted by esophagogastroduodenoscopies, and esophageal biopsies were routinely obtained for histologic evaluation. RESULTS: Over the study period, 41 children were admitted for a first episode of food impaction. Drooling was the most commonly reported symptom. Half children experiencing a first episode of food bolus were diagnosed with EoE (20/41, 48.8%). Almost a fourth of the episodes subtended a different condition, such as esophageal anastomotic, peptic or congenital strictures, stricturing caustic esophagitis, esophageal duplication, and achalasia. In the last fourth of patients the cause of EFI was not identified and thus probably related to quick eating and inadequate chewing of food. DISCUSSION: Our study represents the largest known series of pediatric patients evaluated for food bolus impaction. Our main finding is the high frequency of EoE, which accounts for a half of EFI episodes in pediatric age, especially in older children. This finding highlights the importance of obtaining esophageal biopsies after the endoscopic bolus removal in children with EFI to provide a complete diagnostic evaluation.

Sharp-Pointed Foreign Body Ingestion in Pediatric Age.

OBJECTIVES: To assess the clinical complications reported after the ingestion of sharp/pointed foreign bodies (FBs) in pediatric age, their incidence among all FB ingestions, and the features and clinical presentation of children. STUDY DESIGN: We have recruited all consecutive patients aged 0-14 years, admitted for sharp/pointed FB ingestion. Clinical data until hospital discharge were accurately recorded, including both children with esophagogastric FB retention who underwent endoscopic removal and children who were radiologically followed-up till spontaneous FB expulsion. Clinical outcomes were recorded for each patient, with special reference to possible prolonged retention and wall perforation during the intestinal passage. RESULTS: We have enrolled 580 children (males/females: 292/288; age range: 11-180 months; mean age ± standard deviation: 50.5 ± 42 months). Sharp/pointed FBs mainly included fragments of metal 270 of 580 (46.55%) and glass 180 of 580 (31%). FBs were endoscopically removed in 79 of 580 (13.6%) children whereas the remaining FBs passed through the gastrointestinal tract over an overall mean time of 29 hours. No cases of intestinal perforation nor prolonged retention were observed. In 3 of 65 (4.6%) procedures the endoscopist faced an uncomfortable endoscopic removal due to the shape and size of the FB which hampered the retrograde passage through the esophageal sphincters. CONCLUSIONS: Our original and extensive data emphasize that accidental ingestion of sharp/pointed FB ingestion is a current issue in pediatric age, especially in toddlers. Metal and glass objects are the most involved FBs and their endoscopic retrieval may not be easy in about 5% of cases. Fortunately, in our pediatric sample no surgical intervention was needed.

Derivation and validation of Re.Co.De death score risk in patients with acute nonvariceal upper GI bleeding.

BACKGROUND AND AIMS: Scores in upper GI bleeding (UGIB) are used to stratify death risk and need for hospitalization at admission, but a tool that incorporates dynamic changes during the hospital stay is lacking. We aimed to develop a death risk score that considers changes in clinical status during hospitalization and compare its performance with existing ones. METHODS: A multicenter cohort study enrolling patients with UGIB in 50 Italian hospitals from January 2014 to December 2015 was conducted. Data were collected and used to develop a risk score using logistic regression analyses. Performance curves (area under the receiver-operating characteristic [AUROC] curves), sensitivities, specificities, positive and negative predictive values, and outcomes classified as low, intermediate, and high death risk were calculated. The score's performance was externally validated and then compared with other scores. RESULTS: We included 1852 patients with nonvariceal UGIB in the development cohort and 912 in the validation cohorts. The new score, which we named the Re.Co.De (rebleeding-comorbidities-deteriorating) score, included 10 variables depicting the changes in clinical conditions while in the hospital. The mortality AUROC curves were .93 (95% confidence interval, .91-.96) in the derivation cohort and .94 (95% confidence interval, .91-.98) in validation cohort. In a comparison of AUROC curves with other scores, the new score showed a significant performance compared with pre- and postendoscopy scores. Patients with low and high scores had 30-day mortality rates of .001% and 48.2%, respectively. CONCLUSIONS: The Re.Co.De score has a higher performance for predicting mortality in patients with UGIB compared with other scores, correctly identifying patients at low and high death risk while in the hospital through a dynamic re-evaluation of clinical status.

Comparison of assessment tools in acute upper gastrointestinal bleeding: which one for which decision.

BACKGROUND: Upper GI bleeding (UGIB) remains a common emergency with significant mortality. Scores help triage patients, but it is still unclear which score should be used in the different decision-making moments to identify patients at high or low death risk. We aimed to compare the overall performances of the most validated scores and their cut-off performance to identify patients at low and high death risk. The secondary outcome was to compare the scores' performance for predicting therapeutic endoscopy, the need for transfusion(s), rebleeding, and surgery/interventional radiology. METHODS: We conducted a prospective multicenter cohort study, including consecutive UGIB patients admitted to 50 Italian hospitals. We collected information to calculate the Rockall, the Progetto Nazionale Endoscopia Digestiva (PNED), the AIMS65, the Glasgow-Blatchford (GBS), and the Age, Blood tests, Comorbidities (ABC) scores, together with demographic figures, clinical data, and outcomes. RESULTS: We obtained complete data of 2307 outpatients, including 1887 non-variceal and 420 variceal bleeders. Our cohort's mean age was 67.5 years, with a prevalence of male gender (69%). The GBS has the best overall performance (ROC 0.74) compared to the other scores in identifying low-risk patients (p < .001). At the cut-off 0-1, both GBS and ABC scores provide the highest PPV (100%) for low-risk patients. ABC and PNED scores are the most useful ones (for AUC >80) to assess the high-risk patients for mortality. CONCLUSIONS: At admission, GBS and ABC scores identify low-risk patients suitable for outpatient management, while PNED and ABC scores identify high-risk patients. During hospitalization, the PNED score should be used to re-assess the mortality risk if a modification of clinical status occurs.

Disc battery ingestion in paediatric age.

AIM: The aim of the present study was to analyse clinical data of children referred for disc battery ingestion in order to assess short- and long-term reported injuries and to identify outcome predictors and trends, define the urgency of intervention and refine treatment guidelines. METHODS: The records of all children admitted to Santobono-Pausilipon Children's Hospital, Naples, Italy for disc battery ingestion from January 2016 to December 2020 were retrospectively reviewed. Odds ratio were computed to assess the association between the different study variables and the rate of complications. RESULTS: We enrolled 118 children. Mild to major complications related to the ingested disc batteries were reported in 12/118 (10.2%) patients. Disc battery oesophageal retention, disc battery diameter >20 mm, together with age below 1 year and symptomatic presentation were the most important factors associated with poor clinical outcome. CONCLUSION: Our data confirm that ingested disc batteries are a serious health hazard and require a timely and qualified medical evaluation. We have identified three predictors of outcome severity: oesophageal retention, large-diameter cells and symptom onset. Disc batteries lodged beyond the oesophagus appear substantially harmless and we may support a more conservative approach.

Clinical outcomes in cirrhotics with variceal or nonvariceal gastrointestinal bleeding: A prospective, multicenter cohort study.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is associated with a distinct mortality in cirrhotics. We evaluated whether the rate of mortality and other outcomes differs between variceal and nonvariceal UGIB. METHODS: This was a prospective, multicenter, cohort study on UGIB cirrhotics observed in 50 hospitals. Variceal or nonvariceal UGIB were diagnosed at endoscopy. The 6-week mortality rate, need of blood transfusion, intensive care unit (ICU) admission, radiologic or surgical intervention, rebleeding rate, and length of stay in hospital were the main clinical outcomes compared. Data were analyzed at univariate and multivariate analysis, and odds ratio (OR) with their 95% confidence interval (CI) was calculated. RESULTS: The study enrolled 706 cirrhotics, including 516 (73%) variceal and 190 (27%) nonvariceal UGIB. There were 78 (11%; 95% CI = 8.7-13.4) deceases, without any difference between variceal (11.0%) and nonvariceal (11.0%) groups. Child-Pugh score C (OR: 6.99; 95% CI = 2.58-18.95), and development of either hepatorenal syndrome (OR: 16.5; 95% CI = 7.02-38.9) or hepatic encephalopathy (OR: 2.38; 95% CI = 1.25-4.5) were independent predictors of mortality. Transfusions and onset of hepatic encephalopathy were significantly more frequent in variceal, whereas ICU admission rate was higher in nonvariceal bleedings. Overall, antibiotic prophylaxis was eventually administered in only 392 (55.5%) patients. CONCLUSIONS: Data found that the overall mortality rate in cirrhotics with UGIB seems to be reducing and that the value did not differ between variceal and nonvariceal types. Prevention of both hepatorenal syndrome and hepatic encephalopathy and implementation of antibiotic prophylaxis could improve survival in these patients.

Diagnostic Accuracy of 3-Dimensional Endoanal Ultrasound in Identifying Perianal Crohn's Fistulas.

BACKGROUND: Perianal fistulizing Crohn's disease is a challenging clinical situation that requires proper management. Some features seen on the endoanal ultrasound can be helpful in discriminating between cryptoglandular and Crohn's disease fistulas. OBJECTIVE: The aim of this study was to define the diagnostic accuracy of 3-dimensional endoanal ultrasound in differentiating between Crohn's disease and cryptogenic fistulas. DESIGN: This was a prospective observational study. SETTINGS: The study was conducted in the colorectal unit of an IBD referral center. PATIENTS: Consecutive patients referred for suspected perianal sepsis from September 2015 to December 2016 were included. INTERVENTIONS: Three-dimensional endoanal ultrasonography was the studied intervention. MAIN OUTCOMES MEASURES: Sensitivity, specificity, and positive and negative likelihood ratios of 4 ultrasonographic features (Crohn's ultrasound fistula sign, the presence of a double track, debris or an abscess within the fistula track, and the maximum width of the track) in discriminating between cryptoglandular and Crohn's disease fistulas were calculated. The interobserver agreement for each feature was quantified. RESULTS: In this study, 158 patients, of whom 33 had a diagnosis of Crohn's disease, were included. The interobserver agreement was good for all of the ultrasonographic features. All of these features were more frequent in cases of Crohn's disease fistulas (p = 0.0001). The maximum width of the fistula track was highly accurate for discriminating between cryptogenic and Crohn's disease fistulas (area under the receiver operating characteristic curve = 0.922). The simultaneous presence of 2 features was suggestive of Crohn's disease fistula. In particular, the presence of a track width >4 mm in conjunction with either a double track or the Crohn's ultrasound fistula sign showed very high specificity (1.00). Conversely, a fistula track width ≤3 mm had high sensitivity (0.97). LIMITATIONS: Patients included in the cryptogenic group might be diagnosed as having Crohn's disease at follow-up. CONCLUSIONS: The combination of specific endoanal ultrasonographic features allows for highly accurate discrimination between Crohn's disease and cryptogenic fistulas. See Video Abstract at http://links.lww.com/DCR/A619.

Alterations in Diets of Patients With Nonceliac Gluten Sensitivity Compared With Healthy Individuals.

BACKGROUND & AIMS: There is evidence that food components beyond gluten cause symptoms in patients with gluten sensitivity without celiac disease (nonceliac gluten sensitivity [NCGS]). We investigated the diets and nutritional characteristics of patients with NCGS. METHODS: We performed a prospective observational study of 29 patients with NCGS seen at the outpatient clinic for celiac disease and other food intolerances of the University of Salerno in Italy from September 2015 through April 2016. Our study also included 37 control subjects. An experienced dietitian administered a validated food frequency questionnaire (from the European Prospective Investigation into Cancer and Nutrition) to collect information on amounts of common foods consumed. Patients and control subjects also completed the Eating Attitudes Test for diet-related disorders. Patients with NCGS completed the Minnesota Multiphasic Personality Inventory 2-I questionnaire. Differences in frequencies between patients and control subjects were calculated using chi-square test, whereas differences between continuous variables were calculated using Student t test. All tests were 2-tailed with significance level set at P < .05. RESULTS: Comparing the mean value of food daily eaten, we found that patients with NCGS ate smaller amounts of bread, rice, pasta, and cheese than control subjects. The patients ingested lower mean amounts of carbohydrates (P < .001), proteins (P = .001), fiber (P = .002), and polyunsaturated fatty acids (P = .01). More patients with NCGS than control subjects reported avoiding fruit, vegetables, milk, and dairy products, as well as snacks and mixed spices that are traditionally considered unsafe for people with gastrointestinal symptoms. Seven patients and 3 control subjects with scores ≥20 on the Eating Attitudes Test were invited for a psychological consultation; it did not confirm the presence of altered eating behaviors. Patients with NCGS had scores >65 from the Minnesota Multiphasic Personality Inventory, indicating a high level of concern for their health. CONCLUSIONS: In an observational study, we found that patients with NCGS eat different foods than healthy individuals; patients consume lower levels of proteins, carbohydrates, fiber, and polyunsaturated fatty acids. Their diets should be routinely analyzed and possibly corrected to avoid nutritional deficiencies.

Ileostomy reversal with handsewn techniques. Short-term outcomes in a teaching hospital.

INTRODUCTION: Fecal diversion is considered an effective procedure to protect bowel anastomosis at high risk for leak. Some concerns exist regarding the risk for a significant morbidity associated to ileostomy creation itself and moreover to its closure. Surgical expertise and closure techniques are considered potential factors influencing morbidity. Aim of the study is to present a single-institution experience with ileostomy closures, in a teaching hospital, whereas ileostomy reversal is mainly performed by young residents. METHODS: A prospective database was investigated to extract data of patients who underwent loop ileostomy closure between January 2005 and December 2014. Ileostomy reversion was always realized in a handsewn fashion, performing either a direct closure (DC) or a resection plus end-to-end anastomosis (EEA). Postoperative morbidity was graded according to Clavien-Dindo classification. Outcomes after DC and EEA were compared by Fisher's exact test and Wilcoxon rank-sum test. RESULTS: Two hundred ninety-eight patients were included. Ileostomy reversal was performed by EEA in 236 patients (79.19 %) and by DC in 62 patients (20.81 %). Surgery was performed with a peristomal access in 296 cases (99.33 %). Incidence of anastomotic leak was 0.67 % (2/298). Overall reoperation rate was 0.34 % (1/298). Short-term overall morbidity rate was 20.47 %; but major complications (≥ grade III) occurred in only one patient (0.34 %). Mortality was nil. No significant differences in postoperative morbidity were found between the DC and EEA group. CONCLUSION: Loop ileostomy reversal is a safe procedure, associated to a low major morbidity and excellent results, even if performed with a handsewn technique by supervised trainee surgeons.

Coeliac disease in the elderly in a tertiary centre.

INTRODUCTION AND AIMS: Coeliac disease (CD) was believed to be a childhood disease while it can affect any age. AIM: to evaluate the prevalence of CD in elderly population, recording the main clinical features of this group respect to young patients. METHODS: We retrospectively analysed the prevalence of CD in an elderly population from 1970 to 2015. We divided patients into three age-groups (group A: 18-34 years; group B: 35-64 years; group C: ≥65 years) and compared them regarding baseline anthropometric and serological variables, clinical features at diagnosis, diagnostic mode, associated autoimmune diseases, and CD-related neoplastic complications. RESULTS: We made 2812 CD diagnoses in adults: 2.5% of them were ≥65 years at diagnosis. When comparing the three groups, we found no differences in sex, haemoglobin, serum iron, albumin, and anti-tissue transglutaminase (anti-tTG) (p = NS) while as expected, we found higher values of cholesterol, glycaemia, and triglycerides in older patients (p < 0.0001). Elderly had a higher risk of being diagnosed with malabsorption symptoms compared to younger patients (OR 2.20, 95%CI 1.3-3.74). No difference in the risk of autoimmune CD-related diseases was seen among groups. Furthermore, we observed 16 neoplastic complications, 13 of them happened in the patients diagnosed with CD aged 35-64 years. The number of CD diagnoses increased over time, particularly in elderly. CONCLUSION: CD diagnosis in elderly population is quite uncommon although not rare. Elderly CD patients have a higher risk of being diagnosed with malabsorption symptoms than younger patients but without increased risk of autoimmune and neoplastic complications.

Optimal bowel cleansing for colonoscopy: split the dose! A series of meta-analyses of controlled studies.

BACKGROUND: Colonoscopy is considered the criterion standard for detecting colorectal cancer; adequate preparation is crucial for an effective colonoscopy, but definitive data on the optimal preparation are lacking. OBJECTIVE: Our aim was to assess the efficacy of split-dose versus non-split-dose preparations, the rate of adequate preparation according to type and dose of laxatives, the role of "runway time" (the interval time between the last drink of purgative and the beginning of colonoscopy), and to evaluate compliance as an additive risk factor for colon cleansing. DESIGN: A series of meta-analyses of controlled studies. SETTING: Randomized clinical trial of split dose regimen versus entire dose taken on the day preceding colonoscopy. PATIENTS: Published trials (1960-2013) comparing split-dose versus non-split-dose preparations in adults undergoing colonoscopy were selected by using MEDLINE, the Cochrane Central Register of Controlled Trials, clinicaltrial.gov, ISI Web of Science, and Scopus. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Rate difference of the degree of colon cleansing between split dose and whole dose was the primary measure of treatment effect. RESULTS: We included 29 studies. Overall, an adequate preparation was obtained in 85% of patients in the split-dose group and in 63% of the non-split-dose group (rate difference 22%). The heterogeneity was caused by 5 factors: the runway time (the longer, the worse the cleansing), type of diet, male sex, use of polyethylene glycol 4 L, and the Jadad score. Compliance was significantly higher in the split-dose group. LIMITATIONS: Average quality of the included studies and publication bias. CONCLUSION: We provided further evidence of the superiority of a split-dose regimen over a non-split-dose regimen and showed that, regardless of type and dose, the superiority of split-dose regimens remains valid if the "golden 5 hours" rule is preserved.

The interaction of patients' physical status and time to endoscopy on mortality risk in patients with upper gastrointestinal bleeding: A national prospective cohort study.

BACKGROUND AND AIM: The correct time to perform an upper endoscopy is decisive in acutely GI bleeding patients. However, patients' physical status may affect mortality. We speculated that the physical status and procedural time could be the principal factors accountable for death-risk. The primary aim was to verify the interaction between physical status and time to endoscopy on mortality; the secondary aim was to verify the interaction of the physical status and time to endoscopy on the length of stay (LOS). METHODS: Consecutive patients admitted to 50 Italian hospitals were included. Clinical and endoscopic data were recorded. A multiple logistic regression analysis was performed and the interaction of adjusted clinical physical status and time to endoscopy on mortality was calculated. RESULTS: Complete data were available for 3.190 patients. The time frames did not interfere with outcomes but influenced LOS. Conversely, the ASA score correlated with mortality, LOS, need for transfusions and rebleeding risk. CONCLUSION: Endoscopy time should be tailored to the patient's physical. In our experience, ASA 1-2-3 patients can be safely submitted to endoscopy to reduce the LOS; on the contrary, keen attention should be paid to ASA4 patients, following the 'not too early-not too late' rule (12-24 h from admission).

'Favourable' IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype 3a infection and do not predict a sustained virological response after 24 weeks of therapy.

IL28B host genetic make-up is known to play a critical role in the outcome of genotype 1 hepatitis C virus (HCV) infection in the context of both primary infection and therapy. However, the role of IL28B in subtype 3a infection remains unclear, and has not yet been assessed in the UK population where subtype 3a is dominant. In this study, we evaluated the role of the IL28B single-nucleotide polymorphism rs8099917 in 201 patients recruited from two well-defined cohorts (from Nottingham and Oxford), treated with the standard-of-care therapy of pegylated interferon and ribavirin for 24 weeks. We showed that the 'favourable' IL28B gene was associated with a rapid virological response to therapy at 4 weeks (P<0.0001), but not with a sustained virological response to therapy. The median viral load at baseline, before therapy, was markedly increased in people with the 'favourable' IL28B genotype [median viral load for the TT allele, 925,961 IU ml(-1) (range 2200-21,116,965 IU ml(-1)), and for the GT or GG allele, 260,284 IU ml(-1) (range 740-7,560,000 IU ml(-1)); P = 0.0010]. Our results suggest that the host genetic response plays an important role in early viral clearance of subtype 3a virus from the blood. However, significant reservoirs of infection must persist, as viral relapse is common, even in those with the favourable host genotype.

Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.

BACKGROUND & AIMS: Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin. METHODS: Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy. Patients were considered to have NCGS based on their symptoms and the current definition of the disorder. Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34). Duodenal biopsy samples collected during endoscopy were incubated with gliadin peptides, and levels of inflammatory markers were assessed. Peripheral blood basophils were extracted and incubated with gliadin peptides or a mix of wheat proteins; activation was assessed based on levels of CD203c, CD63, and CD45. RESULTS: Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers). There were no significant increases in the levels of CD63 and CD203c in NCGS patients. CONCLUSIONS: Unlike the duodenal mucosa from patients with celiac disease, upon incubation with gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin. The in vitro gliadin challenge therefore should not be used to diagnose NCGS.

Comparison of assessment tools in acute upper gastrointestinal bleeding: Which one at which time point?

BACKGROUND: Decisions on managing bleeders remain a critical issue due to the high death risk. The Glasgow-Blatchford score (GBS) correctly identifies low-risk patients but none of the existing scores precisely assess the high risk patients. AIMS: To evaluate bleeding scores' prognostic performances in predicting mortality risk. SECONDARY OUTCOMES: To compare the scores in low and high-risk patients and identify the "best performing cut-off" (if different from the standard one) in discriminating survivors from deceased. METHODS: prospective multicenter cohort study including consecutive UGIB patients admitted to 50 Italian hospitals. We collected information to calculate Rockall, PNED, AIMS65, GB, and ABC scores, together with demographic and clinical data, and outcomes. RESULTS: for low-risk patients, the GB and the ABC are the best performing scores; for high-risk patients, all scores showed weak results, with the PNED score having the higher PPV. Searching for the "best performing cut-off", we found different points that determined a relevant numerical gain in terms of patients correctly assessed. CONCLUSIONS: we suggest using the GBS and the ABC score at admission, while the PNED appears to be more useful for high-risk. We also suggest using a new decisional cut-offs that, if validated, may increase the accuracy of current scores.

Defining Time in Acute Upper Gastrointestinal Bleeding: When Should We Start the Clock?

INTRODUCTION: The execution of upper endoscopy at the proper time is key to correctly managing patients with upper gastrointestinal bleeding (UGIB). Nonetheless, the definition of "time" for endoscopic examinations in UGIB patients is imprecise. The primary aim of this study was to verify whether the different definitions of "time" (i.e., the symptoms-to-endoscopy and presentation-to-endoscopy timeframes) impact mortality. The secondary purpose of this study was to evaluate the similarity between the two timeframes. METHODS: A post-hoc analysis was performed on a prospective multicenter cohort study, which included UGIB patients admitted to 50 Italian hospitals. We collected the timings from symptoms and presentation to endoscopy, together with other demographic, organizational and clinical data and outcomes. RESULTS: Out of the 3324 patients in the cohort, complete time data were available for 3166 patients. A significant difference of 9.2 h (p < 0.001) was found between the symptoms-to-endoscopy vs. presentation-to-endoscopy timeframes. The symptoms-to-endoscopy timeframe demonstrated (1) a different death risk profile and (2) a statistically significant improvement in the prediction of mortality risk compared to the presentation-to-endoscopy timeframe (p < 0.0002). The similarity between the two different timeframes was moderate (K = 0.42 ± 0.01; p < 0.001). CONCLUSIONS: The symptoms-to-endoscopy and presentation-to-endoscopy timeframes referred to different timings during the management of upper endoscopy in bleeding patients, with the former being more accurate in correctly identifying the mortality risk of these patients. We suggest that further studies be conducted to validate our observations, and, if confirmed, a different definition of time should be adopted in endoscopy.

Case Report: Add-on treatment with odevixibat in a new subtype of progressive familial intrahepatic cholestasis broadens the therapeutic horizon of genetic cholestasis.

Odevixibat, an ileal bile acid transporter (IBAT) inhibitor, is effective for the treatment of pruritus in children diagnosed with progressive familial intrahepatic cholestasis (PFIC) type 1 and 2. There are no studies showing the efficacy of Odevixibat in children with different subtypes of PFIC. We describe the case of a 6-year-old girl with chronic cholestatic jaundice. In the last 12 months laboratory data showed high serum levels of bilirubin (total bilirubin x 2.5 ULN; direct bilirubin x 1.7 ULN) and bile acids (sBA x 70 ULN), elevated transaminases (x 3-4 ULN), and preserved synthetic liver function. Genetic testing showed homozygous mutation in ZFYVE19 gene, which is not included among the classic causative genes of PFIC and determined a new non-syndromic phenotype recently classified as PFIC9 (OMIM # 619849). Due to the persistent intensity of itching [score of 5 (very severe) at the Caregiver Global Impression of Severity (CaGIS)] and sleep disturbances not responsive to rifampicin and ursodeoxycholic acid (UDCA), Odevixibat treatment was started. After treatment with odevixibat we observed: (i) reduction in sBA from 458 to 71 µmol/L (absolute change from baseline: -387 µmol/L), (ii) reduction in CaGIS from 5 to 1, and (iii) resolution of sleep disturbances. The BMI z-score progressively increased from -0.98 to +0.56 after 3 months of treatment. No adverse drug events were recorded. Treatment with IBAT inhibitor was effective and safe in our patient suggesting that Odevixibat may be potentially considered for the treatment of cholestatic pruritus also in children with rare subtypes of PFIC. Further studies on a larger scale could lead to the increasing of patients eligible for this treatment.