Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study

Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression. This study aims to identify the characteristics and outcomes of patients who underwent LT for OTCD. // We conducted a retrospective study for OTCD patients from 5 UK centres receiving LT in 3 transplantation centres between 2010 and 2022. Patients' demographics, family history, initial presentation, age at LT, graft type and pre- and post-LT clinical, metabolic, and neurocognitive profile were collected from medical records.// A total of 20 OTCD patients (11 males, 9 females) were enrolled in this study. 6/20 had neonatal and 14/20 late-onset presentation. 2/20 patients had positive family history for OTCD and one of them was diagnosed antenatally and received prospective treatment. All patients were managed with standard of care based on protein-restricted diet, ammonia scavengers and supplementation with arginine and/or citrulline before LT. 15/20 patients had neurodevelopmental problems before LT. The indication for LT was presence (or family history) of recurrent metabolic decompensations occurring despite standard medical therapy leading to neurodisability and quality of life impairment. Median age at LT was 10.5 months (6–24) and 66 months (35–156) in neonatal and late onset patients, respectively. 15/20 patients had deceased donor LT (DDLT) and 5/20 had living related donor LT (LDLT). Overall survival was 95% with one patient dying 6 h after LT. 13/20 had complications after LT and 2/20 patients required re-transplantation. All patients discontinued dietary restriction and ammonia scavengers after LT and remained metabolically stable. Patients who had neurodevelopmental problems before LT persisted to have difficulties after LT. 1/5 patients who was reported to have normal neurodevelopment before LT developed behavioural problems after LT, while the remaining 4 maintained their abilities without any reported issues. // LT was found to be effective in correcting the metabolic defect, eliminates the risk of hyperammonemia and prolongs patients' survival

Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A–E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology

ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents.

BACKGROUND:: The diagnosis of pediatric-onset IBD (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. METHODS:: We aimed to revise the original Porto criteria utilizing an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria whilst incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. RESULTS:: The revised criteria depart from existing criteria by defining two categories of ulcerative colitis (UC; typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBDU) is proposed. Specifically, these revised criteria recommend upper GI endoscopy and ileocolonscopy for all suspected PIBD patients, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography (MRE) or wireless capsule endoscopy. CONCLUSIONS:: These revised Porto criteria for the diagnosis of PIBD have been developed to meet current challenges and developments in PIBD and provide up to date guidelines for the definition and diagnosis of the IBD spectrum

Genetic landscape of pediatric acute liver failure of indeterminate origin.

BACKGROUND AIMS Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, main causes are viral infections (12-16%) and inherited metabolic diseases (14-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. METHODS With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF (RALF). WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (46%), and in children with RALF (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8) and DGUOK (n=7) were the most frequent findings. When categorizing, most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%) and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplants. CONCLUSION This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

LiHiSTO: a comprehensive list of Hindi stopwords

Acknowledgements: The author would like to thank the journal reviewers for their valuable suggestions contributing to the improvement of this paper.A preliminary preprocessing step in text analytics is the removal of words with no semantic meaning, otherwise known as stopwords. English stopwords are very easily accessible and created due to the broad usability of the English language. However, a standard list of Hindi stopwords is still missing. This paper proposes an exhaustive list of generic Hindi stopwords and a Python package for easy distribution and usage. The methodology uses a dual mechanism for creating a list of Hindi stopwords. First, the famous English stopwords are collected and translated into meaningful Hindi words (group 1). Second, unique Hindi stopwords from multiple sources are fetched (group 2). Finally, the respective Hindi stopwords from groups 1 and 2 are combined, which resulted in a significantly large set of 820 Hindi stopwords. Additionally, the list of Hindi stopwords is made openly available for use at the Python Package Index (PyPI) repository as a Python package, which is named LiHiSTO. With the help of illustrative implementations, it is shown that LiHiSTO provides abstract and easy access to the list of stopwords for users to perform Hindi text analytics

LiHiSTO: A Comprehensive List of Hindi Stopwords

A preliminary preprocessing step in text analytics is the removal of words with no semantic meaning, otherwise known as stopwords. English stopwords are very easily accessible and created due to the broad usability of the English language. However, a standard list of Hindi stopwords is still missing. This paper proposes an exhaustive list of generic Hindi stopwords and a Python package for easy distribution and usage. The methodology uses a dual mechanism for creating a list of Hindi stopwords. First, the famous English stopwords are collected and translated into meaningful Hindi words (group 1). Second, unique Hindi stopwords from multiple sources are fetched (group 2). Finally, the respective Hindi stopwords from groups 1 and 2 are combined, which resulted in a significantly large set of 820 Hindi stopwords. Additionally, the list of Hindi stopwords is made openly available for use at the Python Package Index (PyPI) repository as a Python package, which is named LiHiSTO. With the help of illustrative implementations, it is shown that LiHiSTO provides abstract and easy access to the list of stopwords for users to perform Hindi text analytics.No funding

STUDY OF METABOLIC SYNDROME IN INDIAN POPULATION WITH COMPARISON OF TWO DEFINITIONS

Objectives: Metabolic syndrome (MetS) is described as the collection of risk factors for cardiovascular disease such as hypertension, hyperglycemia/ insulin resistance, abdominal obesity, and dyslipidemia. In developed countries, MetS is highly prevalent among adults and is an emerging health problem in developing countries. In this study, we used the International Diabetes Federation (IDF) and National Cholesterol Education Program- Adult Treatment Panel-III (NCEP-ATP III) to define the Mets. The aim of this research was to evaluate the prevalence of MetS, its components, and its major risk factors among adults ≥20 in Jammu and Kashmir according to IDF and the NCEP ATP III criteria. Methods: The project was conducted in the Department of Biochemistry, Laboratory Medicine, Shri Mata Vaishno Devi Narayana Superspeciality Hospital, Katra, and Jammu and Kashmir in 100 subjects between the age groups of 20 and 80 years old attending the OPD from 2 January to 30 April 2017. Results: MetS was diagnosed in 57% and 55%, gender-wise distribution came out to be 45.6% and 52.7% in men, and in women, we found 54.3% and 47.3%, according to IDF and the NCEP ATP III definition, respectively. Conclusion: In our study, IDF criteria were better for the early diagnosis of MetS. On the basis of gender prevalence in all parameters in IDF, females are at risk, and in NCEP ATP III, males are more at risk. According to the IDF, central obesity is the only the risk for women