Introduction

Peptic ulcer is the most common cause of upper gastrointestinal bleeding (UGB), accounting for about 50 percent of cases. Several scoring systems have been developed for the early and accurate assessment of patients with UGB to predict clinical outcomes, assisting in the management of patients. The Glasgow-Blatchford score (GBS) is currently recommended for risk stratification of UGB in the emergency department, helping triage patients to in-hospital or ambulatory management. GBS includes hemoglobin, urea, heart rate, systolic blood pressure, co-morbidity and symptoms like syncope and melena.

Aims & Methods

Aim: To compare GBS in patients with bleeding peptic ulcer (BPU) infected and non-infected by Helicobacter pylori (HP).
Methods: We conducted a prospective observational study from September 2019 to March 2002, 48 patients with BPU were prospectively evaluated in a tertiary hospital. During emergency endoscopy, two gastric mucosal biopsy samples (one from corpus and one from the antrum) were collected for polymerase chain reaction (PCR) and invasive rapid urease test (RUT). Two hours later, all underwent carbon-13 urea breath test (13C-UBT). Patients were considered HP infected when two or more tests were positive. The clinical data were obtained from the patients´s records immediately before the endoscopy. The Qui-square test and Fisher were used to compare the groups. Written informed consent was obtained from all patients. The study protocol was approved by the local ethical committee.

Results

Mean age was 61.7±17.3 years, 25 (52.1%) presented with melena. Gastric ulcers were the major cause of acute bleeding in 39 (81.3%) and duodenal in 9 (18.8%) patients. Data about blood transfusion (BT), Rockall Score (RS) and presence of blood in the stomach are represented in table 1. GBS was significantly lower in HP positive patients (n=19) compared to HP negative (n=25): 9.1±3.3 e 11.5±3.1, p= 0.0441.

Table 1. Comparison between H.pylori negative and positive groups

* BT: blood transfusion, RS: Rockall score, GBS: Glasgow Blatchford score

Conclusion

H pylori positive patients showed less comorbidities and lower GBS in the BPU scenario. HP negative patients need more severe clinical conditions to bleed than those HP positive. HP is a pathogenic factor by itself, suggesting that GBS might be underestimated in this population. A score using HP presence could be better to predict prognostic in the episode of bleeding peptic ulcer.

References

Bibliography:

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2. Jang HJ, Lee D, Kim TH, Kim JS, Lee HJ, Kim JB, Kim JY. Clinical outcomes of gastrointestinal bleeding management during anticoagulation therapy. PLoS One. 2022 Jun 3;17(6):e0269262. doi: 10.1371/journal.pone.0269262. PMID: 35658063; PMCID: PMC9165820.

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Introduction

Pediatric Acute Liver Failure (PALF) presents a considerable threat to children with a high risk of mortality, despite its rarity. However, the exact cause remains unknown in about half of the cases, emphasizing the need for continued investigation and advancements in our understanding of the condition. Recurrent Acute Liver Failure (RALF) represents an even more uncommon phenomenon, defying diagnosis despite thorough examination. The advent of Whole Exome Sequencing offers hope in uncovering its elusive genetic origins, potentially shedding light on specific genetic disorders underlying this condition.

Aims & Methods

This study aimed to report spectrum of Recurrent Acute Liver Failure (RALF) cases and role of Whole Exome Sequencing (WES) in establishing a cause for RALF, during January 2023 – January 2024 in a tertiary care institute.

Results

We report 4 cases of Recurrent Acute Liver Failure (RALF). First case was a 5 year old 1^st born female child of 3^rd degree consanguineous marriage who presented with RALF during febrile episodes at 10 months, 18 months and 5 years. Child had low GGT (19 IU/L) cholestasis initially. Etiological workup for Wilson, infective, metabolic was normal. Provisionally, Fever Associated Infantile Liver Failure (ILFS) was thought. But, Upper GI endoscopy revealed esophageal varices confirming portal hypertension, and liver biopsy revealed- acute on chronic hepatitis with cirrhosis, confirming chronic liver disease, which was in contrast to complete liver function resolution seen in ILFS. Change in gait and expressive language ability was lost from 3 years of age. The child had rigidity, increased deep tendon reflexes, tremor and ataxia on examination. Genetic analysis revealed homozygous (autosomal recessive) likely pathogenic variant of SCYL1 gene mutation leading to Spinocerebellar Ataxia 21.
The second child also presented with RALF at 8 months, 1year and 1.5 years during febrile episodes, with low GGT Cholestasis. WES revealed pathogenic variant of SCYL1 gene mutation leading to Spinocerebellar Ataxia 21. Child died at 1.5years of age.
Third child is a 10 year old girl presented with multiple fever-related RALF since 9 years of age and was asymptomatic in between episodes. As the cause was indeterminate after extensive evaluation, WES was done which revealed novel compound heterozygote mutation in RINT1 gene in exon 8 and 12.
The fourth child is a sibling of third case who succumbed with the first acute liver failure following a febrile episode at 12 years of age.

Conclusion

Understanding the genetic basis of PALF is crucial for accurate diagnosis and management. Genetic testing, including targeted gene sequencing or whole-exome sequencing, can help identify these mutations and provide insights into the underlying causes of PALF in affected individuals. This information is essential for personalized treatment approaches and genetic counseling for families. In addition to metabolic and mitochondrial diseases, mutations in genes related to both cytosolic and mitochondrial pathways—such as NBAS, TRMU, IRAS, MARS, RINT1, and SCYL1—have been implicated in pediatric acute liver failure (PALF).

References

1. Lenz D, Schlieben LD, Shimura M, Bianzano A, Smirnov D, Kopajtich R, Berutti R, Adam R, Aldrian D, Baric I, Baumann U. Genetic landscape of pediatric acute liver failure of indeterminate origin. Hepatology. 2024 May 1;79(5):1075-87.
2. Çakır M, İssi F, Güven B, Yakici N, Karaguzel G, Selimoglu A. Rare Causes of Recurrent Acute Liver Failure In Children: Infantile Liver Failure Syndromes. Klinische Pädiatrie. 2023 Jul;235(04):245-9.
3. Youssef, Mariam et al. “CALFAN (Low γ-Glutamyl Transpeptidase (GGT) Cholestasis, Acute Liver Failure, and Neurodegeneration) Syndrome: A Case Report with 3-Year Follow-Up after Liver Transplantation in Early Adulthood.” Case reports in hepatology vol. 2023 3010131. 31 Jul. 2023, doi:10.1155/2023/3010131

Introduction

Chronic constipation (CC) is a prodromal and severe symptom in up to the 80% of Parkinson's disease (PD) patients (PD/CC) often refractory to standard laxative treatments. The molecular mechanisms underlying PD/CC are still unclear, although changes of enteric nervous system and intestinal epithelial barrier (IEB) have been thought to play a pathogenetic role.

Aims & Methods

In this study, PD/CC and chronic constipated (CCs) patients were functionally characterized, and possible abnormalities to IEB and the key neuromodulator vasoactive intestinal polypeptide (VIP) were investigated. N=12 PD/CCs (2 females; age range: 51-80 yrs), 20 CCs (15 females; 27-78; yrs) and 23 controls (Ctrls; 11 females; 32-74yrs) were enrolled. PD was diagnosed according to the United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria, whereas CC was established following Rome IV criteria. Ctrls were otherwise asymptomatic subjects undergoing screening colonoscopy. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colonic mucosal / submucosal biopsies were obtained in all patients / subjects and tested for gene, protein expression and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1) and zonula occludens-1 (ZO-1) and VIP, by RT-qPCR, immunoblot and immunofluorescence staining.

Results

PD/CCs were clustered in two groups: a) patients with delayed TT and altered AM (60%); b) those with altered AM only (13%). The evaluation of IEB markers on mucosal specimens showed an increase of CLDN4 mRNA in PD/CCs (1.26 ± 0.26) vs. Ctrls (1.00 ± 0.19) and CCs (0.95 ± 0.33), whereas a trend to CLDN4 protein reduction in PD/CCs (0.88 ± 0.33) vs. Ctrls (0.96 ± 0.25) and CCs (1.02 ± 0.51) was observed. Moreover, the OCCL-1 transcript was significantly increased in PD/CCs (1.36 ± 0.36) vs. Ctrls (1.05 ± 0.33) and CCs (0.81 ± 0.18). ZO-1 mRNA relative levels were consistent with those of OCCL-1 showing a significant increase in PD/CCs (1.35 ± 0.38) vs. Ctrls (1.02± 0.27) and CCs (0.85 ± 0.24). Notably, both OCCL-1 and ZO-1 showed a tendency to be reduced in CCs vs. Ctrls. Immunofluorescence highlighted a decrease in OCCL-1 immunoreactivity (IR) in PD/CCs (score= 1.5) vs. CCs and Ctrls (score= 4). Conversely, ZO-1-IR displayed an intense pattern (score=4) in both Ctrls and PD/CCs, but it was decreased in CCs (score= 2). VIP mRNA levels resulted significantly greater in CCs (3.98 ± 3.93, p<0.05) vs. Ctrls (1.52 ± 1.55) and PD/CCs (0.86 ± 1.056), whereas a decreasing trend was observed in PD/CCs vs. Ctrls (p>0.05). Both immunofluorescence and immunoblot confirmed this tendency showing a 15% drop of the VIP protein (PD/CCs 0.86 ± 0.43 vs. Ctrls 1.01 ± 0.56, p>0.05).

Conclusion

Transit and anorectal dysfunctions in PD/CCs are associated with ZO-1, OCCL-1, CLDN-4 and VIP changes, hence suggesting that a leaky IEB contributes to submucosal neurochemical abnormalities underlying PD/CC. These findings suggest that the expression of the IEB markers are subject to both transcriptional and post-translational regulatory mechanisms, presumably distinct in CC and PD/CC.

References

1. Giancola F, Torresan F, Repossi R, Bianco F, Latorre R, Ioannou A, Guarino M, Volta U, Clavenzani P, Mazzoni M, Chiocchetti R, Bazzoli F, Travagli RA, Sternini C, De Giorgio R. Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation. Neurogastroenterol Motil. 2017 May;29(5):10.1111/nmo.12995.
2. Clairembault T, Leclair-Visonneau L, Coron E, Bourreille A, Le Dily S, Vavasseur F, Heymann MF, Neunlist M, Derkinderen P. Structural alterations of the intestinal epithelial barrier in Parkinson's disease. Acta Neuropathol Commun. 2015 Mar 10;3:12.
3. Neunlist M, Toumi F, Oreschkova T, Denis M, Leborgne J, Laboisse CL, Galmiche JP, Jarry A. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G1028

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with increased technical difficulty and can potentially contribute to prolonged procedural duration and excess exposure to ionizing radiation.

Aims & Methods

The purpose of the present study was to present descriptive information about fluoroscopy during ERCP from a large reference center and to investigate possible determinants of the radiation dose or fluoroscopy duration during ERCP. We examined a prospectively collected single-center database of adult patients undergoing ERCP between 09/2021 and 12/2023 in a tertiary greek public hospital. Detailed information concerning patient, endoscopist and procedural parameters including ERCP indication, degree of difficulty of ERCP (defined using the Schutz score), types of interventions and fluoroscopy were recorded retrospectively. Non parametric statistical methods were used (Mann–Whitney U-test and Kruskal–Wallis test) for the analysis.

Results

In total, data of 1051 ERCPs were collected at first, while 1028 ERCPs with complete information for fluoroscopy duration and radiation dose were included (mean patient age 72.20 ±14.02years, 49.1% men) in the analysis. The mean procedure time was 34.22 ± 14.9 minutes, carried out by three different endoscopists (n₁=321, 31.4%, n₂=338, 33%, n₃= 363, 35.6%). The majority of ERCPs were performed for treatment of choledocholithiasis (64.5%) and were classified as of intermediate difficulty according to Schutz scoring system [Schutz score 2 (n=523, 53.4%)]. Fluoroscopy was used in 1010 ERCPs (98.2%) and the median fluoroscopy duration was 2.4 minutes (IQR=2.6 min) and the median radiation dose was 1031.6 μGym²(IQR=1237.5 μGym²). ERCPs performed with an indication of biliary tract neoplasm (e.g. cholangiocarcinoma, liver metastases) were associated with prolonged fluoroscopy duration [5.05min (IQR=6.35 min), p=0.008] and increased radiation dose [2372.75 μGym² (IQR=2462.68 μGym²), p=0.003] in comparison to the rest of the indications including choledocholithiasis, pancreatic neoplasm, obstructive jaundice and other indications.ERCP difficulty was also related with increased radiation; ERCPs with Schutz score ≥3 were associated with increased radiation dose and fluoroscopy duration compared with ERCP procedures evaluated as Schutz sore ≤2 [3.3min (IQR=3.9 min) vs. 2.1min (IQR=2.15 min), p<0.001 and 1280.8 μGym² (IQR=1836.8 μGym²) vs. 937.6 μGym² (IQR=820.25 μGym²),p<0.001 respectively]. There was no significant difference of the fluoroscopy duration (p=0.495) and radiation dose (p=0.950) among the three performing endoscopists.

Conclusion

Increased difficulty of ERCP and the indication of biliary tract neoplasm were related to higher radiation dose and prolonged fluoroscopy duration. These factors could be utilized to predict ERCP procedures related to increased radiation exposure and may contribute to adoption of appropriate radiation reduction methods.