"Quality of life is impaired in children with chronic pancreatitis: A multicenter study".

BACKGROUND AND OBJECTIVES: The impact of chronic pancreatitis (CP) on quality of life (QOL) of children is not well established. Our objective was to evaluate the QOL, identify contributing factors, and determine the prevalence of anxiety and depression in children with CP in India. METHODS: Children (8-18y old) with CP were prospectively enrolled across three pediatric gastroenterology centres in India. QOL was assessed using the pediatric QOL inventory (PedsQL 4.0) scale, administered to both children and their parents. Anxiety and depression was studied using the Revised Children's Anxiety and Depression Scale (RCADS 25). Contributing factors were identified using binary logistic regression analysis. The data was compared against published QOL data in healthy Indian children. RESULTS: 121 children with CP (boys-57.9 %, age at QOL-14 ± 3.2years) were enrolled. A majority (82.7 %) had pain and advanced disease (Cambridge grade IV- 63.6 %). Children with CP had poorer QOL compared to controls (total score 74.6 ± 16 vs. 87.5 ± 11.1, p < 0.0001). QOL scores were similar across centres. Older children were similar to younger ones, except for a poorer emotional QOL. Taking QOL < -2 standard deviation (SD) of controls, ∼35 % had poor physical (50.9 ± 11.9) and 20 % had poor psychosocial (PS) QOL score (52.1 ± 7.2). On analysis, presence of pain and lower socio-economic status (SES) adversely affected both physical and PS-QOL. Additionally, girls had poorer PS-QOL than boys (Odds ratio 3.1, 95%CI:1.23-7.31). Anxiety and depression were uncommon (2,1.6 %). CONCLUSIONS: Patients with CP had impaired physical and psycho-social QOL. Presence of pain and lower SES adversely affected QOL. Psychiatric comorbidities were uncommon.

How to suspect the presence of high-risk esophageal varices and when to start endoscopic surveillance in children with biliary atresia?

BACKGROUND AND AIM: Portal hypertension determines the outcome of children with biliary atresia (BA) and is common even after a successful Kasai portoenterostomy (KPE). However, there are no clear-cut guidelines on the age of starting surveillance and the modality (endoscopy vs non-invasive tests [NITs]). In this cohort study, we analyzed our database to find out the utility of NITs in detecting high-risk esophageal varices in BA. METHODS: From June 2010 to May 2022, consecutive children of BA who underwent upper gastrointestinal (UGI) endoscopy were included. Esophageal varices were classified as high-risk (grade II with red-color signs or grade III or IV irrespective of red-color signs. NITs such as splenomegaly (clinical and USG), platelet count, aspartate transaminase to platelet ratio index (APRI), and platelet-to-spleen diameter ratio were compared between cases with high-risk and low-risk varices. RESULTS: A total of 110 children, 75 boys (66 successful KPE and 44 failed/KPE not performed) were enrolled. The median age at KPE was 85 days (IQR 63-98). Thirteen (11.8%) children presented with UGI bleeding. The first endoscopy revealed gastroesophageal varices in 75.4% of cases, and 32% of them had high-risk varices. Multivariate analysis revealed failed KPE, history of UGI bleeding, bigger spleen size (> 3.5 cm), lower platelet count (< 150 000), and higher APRI (> 2) are independent predictors of the presence of high-risk esophageal varices. CONCLUSION: Endoscopy is the best in predicting the presence of high-risk varices that might bleed; hence, early surveillance endoscopy should be started in children with splenomegaly, thrombocytopenia, and high APRI score to prevent variceal bleeding.

Efficacy and Predictors of Pain Response to Combined Antioxidants in Children with Chronic Pancreatitis.

BACKGROUND: Pain is a major problem in 90% of patients with chronic pancreatitis (CP). Studies evaluating response to antioxidants (AO) are conflicting and no pediatric studies are available. AIMS: To evaluate markers of oxidative stress (OS), and efficacy and predictors of response to AO in improving pain in children with CP. METHODS: Antioxidants were given to CP children for 6 months. Subjects were assessed at baseline and post-therapy for pain and markers of OS [serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (S-SOD)] and antioxidant levels [vitamin C, selenium, total antioxidant capacity-ferric reducing ability of plasma (FRAP)]. Matched healthy controls were assessed for OS and antioxidant levels. Good response was defined as ≥ 50% reduction in number of painful days/month. RESULTS: 48 CP children (25 boys, age 13 years) and 14 controls were enrolled. 38/48 cases completed 6 months of therapy. CP cases had higher OS [TBARS (7.8 vs 5.2 nmol/mL; p < 0.001)] and lower antioxidant levels [FRAP (231 vs. 381.3 µmol/L; p = 0.003), vitamin C (0.646 vs. 0.780 mg/dL; p < 0.001)] than controls. Significant reduction in TBARS and S-SOD and increase in FRAP, vitamin C, and selenium occurred after 6 months. 10.5% cases had minor side effects. 26(68%) cases had a good response, with 9(24%) becoming pain-free. Subjects with severe ductal changes had lower median BMI (- 0.73 vs 0.10; p = 0.04) and responded less often than those with mild changes (17/29 vs 9/9; p = 0.036). CONCLUSION: CP children have higher OS than healthy controls. Antioxidant therapy is safe. Pain response is seen in 68% cases, less often in patients with severe ductal changes.

Gastrointestinal bleeding due to pseudoaneurysms in children.

Radiological embolization is the treatment of choice in adults with visceral artery pseudoaneurysm (PSA) and gastrointestinal bleeding, but pediatric data is scanty. We analyzed the etiology, clinical presentation, and outcome of radiological intervention in children with PSA of celiac (CA) or superior mesenteric artery (SMA) branches. Electronic records of children with PSA of CA or SMA branches were reviewed and data on clinical and laboratory profile, radiological intervention, and outcome was recorded. Eleven children with PSA (5 boys, 11 [7-17] years) were studied. Etiology was liver abscess (n 4), abdominal trauma (n 3), pancreatitis (n 3), and indeterminate in 1 case. Ten (91%) patients were symptomatic: abdominal pain (10, 91%), hematemesis/melena (9, 81%), and Quincke's triad (1, 9%). One child with pancreatic pseudocyst was diagnosed incidentally on imaging. Doppler ultrasound identified PSA only in 3 cases, while computed tomography angiography (CTA) picked all cases. Children with liver abscess, trauma, and unknown etiology had PSA from CA (right hepatic artery 7, left hepatic artery 1). Of the 3 pancreatitis cases, 2 had PSA from SMA (inferior pancreatico-duodenal artery and ileal branch) and 1 from CA (left gastric artery). Radiological embolization was done in 9 (81%) cases (coil 6, glue 2, both 1), without any complications or failure. One case resolved spontaneously and 1 died pre-intervention. Nine intervened cases were asymptomatic in follow-up [6 (1-24) months].Conclusion: Liver abscess, trauma, and pancreatitis are causes of PSA of CA and SMA branches in children. A majority present with gastrointestinal bleeding and are identified on CTA. Radiological embolization was safe with 100% success. What is Known: • Pseudoaneurysm of visceral artery is an uncommon cause of gastrointestinal bleeding. • Endoluminal intervention is an established and efficacious treatment modality in adults and preferred over surgery. What is New: • Liver abscess, abdominal trauma and pancreatitis are common causes of celiac artery and superior mesenteric artery branch pseudoaneurysm in children and computed tomography angiography has high sensitivity in identifying these pseudoaneurysms. • Minimally invasive radiological angio-embolization, in the hands of trained radiologists, is a safe and successful modality of treatment in children.

Childhood pancreatic trauma: Clinical presentation, natural history and outcome.

OBJECTIVES: To study the presentation, management strategies and long-term natural history of children with pancreatic trauma. METHODS: Children admitted with pancreatic trauma were analyzed for their presentation, management and outcome. Management included nasojejunal feeds, total parenteral nutrition (TPN), octreotide, drainage (radiological and endoscopic), endoscopic retrograde cholangiopancreatography (ERCP) and surgery. Patients were assessed in follow-up for development of chronic pancreatitis (CP). RESULTS: 36 children [29 boys, age 144 (13-194) months] presented at 30 (3-210) days after trauma. Most common cause of trauma was bicycle handle bar injury [n = 18,50%]. Presenting features were abdominal pain [n = 26,72%], lump [n = 16, 44.4%], ascites [n = 13,36%], pleural effusion [n = 9,25%] and anasarca [n = 3,8.3%]. All presented with sequelae of ductal disruption with pseudocyst, ascites or pleural effusion. Fifteen (41.6%) patients each had Grade III and IV injury, 4 (11%) had grade V, and grading was unavailable in 2. Other organs were injured in 4 (11%) cases. Management consisted of various combinations of nasojejunal feeds [n = 17,47.2%], TPN [n = 5,13.8%], octreotide [n = 13,36%], pseudocyst drainage [radiological (n = 18,50%), endoscopic (n = 3,8.3%)] and ERCP [n = 12,33.3%]. Surgical intervention was done in 2 (5.5%) cases [cystojejunostomy and peritoneal lavage in 1 each]. Two (5.5%) patients died due to sepsis. Of the 32 cases in follow-up, 19 (59.3%) recovered and 13 (40.6%) developed CP, with half (6/13) of them being symptomatic with recurrent pain. CONCLUSION: Multi-disciplinary non-operative management is effective for managing pancreatic trauma in 94.4% of children, with 75% requiring radiological or endoscopic intervention. 40% developed structural changes later but only half were symptomatic.

Efficacy of Single- Versus Split-dose Polyethylene Glycol for Colonic Preparation in Children: A Randomized Control Study.

OBJECTIVES: Polyethylene glycol (PEG) is the most effective colon-cleansing agent but volume-related adverse effects are common. Though split-dose PEG is used in adults, no pediatric study so-far has compared split-dose with single-dose PEG. We aimed at comparing the efficacy and tolerability of split-dose versus single-dose PEG for bowel preparation in children. METHODS: Consecutive children (1-18 years) were randomized into either single-dose or split-dose PEG. Single-dose group received 4000 mL/1.73 m PEG solution day before colonoscopy whereas split-dose group received half dose day before and the remaining half on the day of colonoscopy. Effectiveness of bowel preparation was assessed on Aronchik scale, by the endoscopist who was blinded to the type of preparation. Interobserver variability was analyzed by comparing with independent scoring by the blinded trained endoscopy-nurse. The trial was registered with Clinical Trials Registry of India (Trail number 2017/08/009303). RESULTS: Of the 220 randomized children, 179 completed the study (split-dose: 93, single-dose: 86). The mean age of the study population was 11.51 (4.82) years (72.6% boys). The efficacy of bowel preparation was better with split-dose (satisfactory preparation:76.34% vs 43.02%, P < 0.001) with almost perfect inter-observer agreement (k = 0.803). Nausea, vomiting, and sleep disturbance were significantly less in split-dose than single-dose group (P < 0.05). Split-dose patients were able to drink PEG solution faster (P = 0.002). Total sleep duration and uninterrupted sleep duration was also better in split-dose group as compared with single-dose (P = 0.001). CONCLUSIONS: Split-dose PEG is more effective than single-dose regimen for bowel preparation with better tolerability and improved sleep quality in pediatric population.

Transjugular Versus Percutaneous Liver Biopsy in Children: Indication, Success, Yield, and Complications.

BACKGROUND/OBJECTIVE: Percutaneous biopsy (PB) and transjugular liver biopsy (TJLB) are 2 main ways of obtaining liver tissue. We evaluated the indications, success rate, tissue yield, and complications of TJLB in comparison to PB in children. METHODS: Electronic records of children undergoing liver biopsy (LB) were reviewed. Clinico laboratory data including indication, type of biopsy, complications, and tissue yield (length and number of complete portal tracts [CPT]) were noted. RESULTS: Five hundred forty LB (indication: neonatal cholestasis [42.9%], chronic liver disease [43.7%], liver failure [3.7%], focal lesions [3.3%] and others [6.3%]) were done. Four hundred seventy-three were PB (317 boys, 14 [1--216] months) done by percussion (322 [68%]), real-time ultrasound guidance (125 [26.4%]), or plugged method [26 (5.5%)]. Sixty-seven (12.4%) were TJLB [38 boys, 140 (24--216) months], done in patients with contraindications for PB. Technical success (67/68 vs 473/473; P = 0.7) and complications (4 [6%]; vs 15 [3.3%]; P = 0.2) of TJLB and PB were similar. Major complications (0.5%) included supraventricular tachycardia (n = 1) in TJLB and hemoperitoneum (n = 2) in PB. Tissue yield of TJLB was poorer in terms of length (1.0 [0.2--2.0] vs 1.1 [0.4--2.1] cm; P < 0.001), CPT (4 [0--9] vs 5 [2--17]; P < 0.001) and adequacy for reporting (56/67 vs 459/473; P < 0.001). Biopsy yield of <6 CPT was predicted by cirrhosis at histology and TJLB. No factor identified risk of complications with LB. CONCLUSIONS: LB is a safe procedure and only 12% children require TJLB because of contraindications of PB. Technical success and complications are similar but tissue yield is poorer in TJLB than PB. Presence of cirrhosis and TJLB adversely affected tissue yield.

Clinical Profile, Response to Therapy, and Outcome of Children with Primary Intestinal Lymphangiectasia.

OBJECTIVE: Intestinal lymphangiectasia (IL; primary or secondary) is an important cause of protein-losing enteropathy. We evaluated the clinicolaboratory profile, response to therapy, complications, and outcome of children with primary IL (PIL). METHODS: Consecutive children (≤18 years) diagnosed with PIL (clinical setting, typical small bowel histopathology, and exclusion of secondary causes) from 2007 to 2017 were evaluated. RESULTS: Twenty-eight children with PIL (16 boys, age at symptom onset-12 [1-192] months and at diagnosis 8 [1-18] years) were studied. Pedal edema (93%), chronic diarrhea (78.6%), and recurrent anasarca (64%) were the common presentations. Ascites, pleural, and pericardial effusion were seen in 64 (n-18; chylous-5, non-chylous-13), 18, and 18% cases, respectively. Hypoproteinemia, hypoalbuminemia, hypocalcemia, and lymphopenia were present in 82, 82, 75 and 39% cases, respectively. Duodenal biopsy established the diagnosis in 86% cases, while 14% required distal small bowel biopsies. Dietary therapy was given in all and 6 cases required additional therapy (octreotide-6, tranexamic acid-3, and total parenteral nutrition-1). Lymphedema (3/5 vs. 1/23), pleural effusion (4/5 vs. 1/23), and the need for additional therapy (4/5 vs. 2/23) were significantly more in patients with chylous ascites (n = 5) than those without chylous ascites (n = 23). Twenty-four cases in follow-up (39 [6-120] months) showed improvement; however, 8 required readmission (symptom recurrence-6 [25%], complication-2 [8.3%], Budd Chiari Syndrome-1, and abdominal B cell lymphoma-1). CONCLUSION: Presence of chylous ascites suggests severe disease in children with PIL. Majority of PIL children respond to dietary therapy; only 20% need additional therapy. Long-term follow-up is essential to monitor for symptoms relapse and complications.

Jaundice in a Child with Sickle Cell Anemia: A Case Based Approach.

Sickle cell anemia (SCA) is an autosomal recessive disorder caused by a mutation in beta globin gene. Hepatobiliary system is affected in 10-40% of patients with SCA and has a multifactorial etiology. The authors present a child with SCA and conjugated hyperbilirubinemia due to biliary obstruction. He underwent endoscopic retrograde cholangiopancreatography (ERCP) and biliary stenting, had complications of post sphincterotomy bleed, retroperitoneal hematoma and post laparoscopic cholecystectomy sepsis with acute sickle hepatic crisis. He was managed successfully and is doing well on follow-up. Here authors discuss a stepwise approach in management of jaundice in a patient with SCA. Patients with SCA are prone to develop vaso-occlusive crisis (VOC) during periods of stress. VOC affects the liver as acute sickle hepatic crisis, acute hepatic sequestration or sickle cell intrahepatic cholestasis and is collectively termed as sickle cell hepatopathy. Hemolysis due to sickling results in cholelithiasis with its associated complications. These patients are vulnerable to viral hepatitis and hemochromatosis due to multiple blood transfusions. There may be a concomitant acute viral hepatitis, drug induced liver injury, Budd-Chiari syndrome or other chronic liver diseases. These conditions have considerable clinical overlap and may coexist, making the evaluation more challenging. Detailed history, examination and investigations are required for differentiation of etiology. Periods of stress must be tackled with proper hydration, oxygen supplementation, maintaining hemoglobin >10 g/dL, and a low hemoglobin S fraction. Patients with SCA and conjugated hyperbilirubinemia are "high-risk" and best managed by a multidisciplinary team. Preventive strategies like timely vaccinations, chelation, etc. must be practised.

Biomarker for infection in children with decompensated chronic liver disease: Neutrophilic CD64 or procalcitonin?

OBJECTIVE: Biomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD. METHODS: Consecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines. RESULTS: 107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection. CONCLUSION: nCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD.

Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN).

Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.

Expert management of congenital portosystemic shunts and their complications.

Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up.

Corrigendum to "Expert management of congenital portosystemic shunts and their complications" [JHEP Reports 6 (2024)].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100933.].

Cholestatic Liver Disease in a Child with KIF12 Mutation.

Cholestatic liver diseases in children often have an underlying genetic defect. Genetic testing by next-generation sequencing has become a crucial part of the diagnostic armamentarium in such clinical scenarios. Here, authors report an infant with recurrent cholestasis, pruritus, elevated gamma-glutamyl transpeptidase, patent biliary tract and biliary changes on histology who was detected to have a novel KIF12 mutation, which is crucial for intracellular transport of microtubules and cellular polarity in hepatocytes. The child developed progressive liver dysfunction and decompensation in the form of ascites and coagulopathy over a span of eight years. This case highlights the role of next-generation sequencing in identifying novel mutations, which can help in both diagnosis and prognostication.

MPV17 mutation-related mitochondrial DNA depletion syndrome: A case series in infants.

MPV17 is a mitochondrial inner membrane protein, involved in transporting deoxynucleotides into the mitochondria. Pathogenic MPV17 mutations can cause mitochondrial deoxyribonucleic acid (DNA) depletion syndrome, which has a varied presentation with neurological, muscular and hepatic involvement. Presentation as liver failure is relatively uncommon. Here, we report four infants from four separate families with pathogenic, homozygous MPV17 mutations. All had predominant hepatic involvement with cholestasis, lactic acidosis and hypoketotic hypoglycemia. Three of them had presented with liver failure. Interestingly, one of them showed fluctuating liver functions, which worsened with infection and improved after aggressive treatment with antibiotics and supplements. Two of the four cases died in infancy, while the other two improved on conservative management with medium-chain triglyceride-based diet, vitamin supplements, co-enzyme Q and carnitine. The two surviving children are alive at 12 and 25 months of age with native liver with normal to mildly deranged liver function and no neurological dysfunction. Next-generation sequencing confirmed the diagnosis in all of our cases. One of the detected mutations, c.55delC (p.Gln19ArgfsTer3) is a novel pathogenic frameshift mutation, while another mutation c.388G>C (p.Ala130Pro), which was previously reported in Single Nucleotide Polymorphism Database in heterozygous form, is being predicted as likely pathogenic in our case series. We, therefore, propose mutation testing for MPV17 gene during evaluation of indeterminate infantile liver failure, especially those with hypoglycemia and raised plasma lactate.

Endoscopic Band Ligation in Blue Rubber Bleb Nevus Syndrome: A Report of Two Children.

Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital disorder presenting with multifocal venous malformations of the skin, soft tissues, and gastrointestinal (GI) tract. Patients usually present with chronic anemia resulting from occult GI bleeding and sometimes with massive GI bleeding. We report 2 children with blue rubber bleb nevus syndrome with GI bleeding: 1 with obscure GI bleeding and the other with overt GI bleeding. In both cases, the presence of cutaneous lesions provided useful clues toward diagnosis. Colonoscopy and upper GI endoscopy revealed bluish polypoidal lesions in the GI tract. Capsule endoscopy helped in disease mapping. Both of them were successfully treated with endoscopic band ligation and nonselective beta-blockers, which resulted in an improvement in their hemoglobin levels. Our cases highlight the successful use of endoscopic band ligation of GI lesions as a therapeutic modality. It is important for gastroenterologists to be aware of this rare condition for current diagnosis.

Achalasia cardia sub-types in children: Does it affect the response to therapy?

BACKGROUND: Achalasia sub-types affect treatment response in adults, but there is no similar data in children. We studied the differences in clinico-laboratory features and response to therapy between achalasia sub-types in children. METHODS: Forty-eight children (boys:girls-25:23, 14 [0.9-18] years) with achalasia (clinical, barium, high-resolution manometry [HRM], gastroscopy) were evaluated. The sub-type was determined by Chicago classification at HRM. Pneumatic dilatation (PD) or surgery was the primary therapy. Success was defined as Eckhardt score of ≤ 3. RESULTS: Dysphagia (95.8%) and regurgitation (93.8%) were the most common symptoms. Forty of 48 cases had an adequate HRM study: Type I (n-19), II (n-19) and III (n-2). Types I and II had similar clinical profile. Type II had higher basal lower esophageal sphincter (LES) pressure (30.5 [16.5-46] vs. 22.5 [13-43] mmHg; p = 0.007) and less dilated esophagus on timed barium esophagogram (TBE, 25 [13-57] vs. 34.5 [20-81] mm; p = 0.006) than type I. Both types had similar success (86.6% [13/15] vs. 92.8% [13/14]; p = 1) after first PD and need of post-PD myotomy (5/17 vs. 1/16; p = 0.1) in follow-up. Twenty-three cases had TBE before and after PD; 15 (65.2%) had good clearance. These subjects required myotomy (1/15 vs. 4/8; p = 0.03) and repeat PD (5/15 vs. 4/8; p = 0.08) less often than those with poor clearance on TBE. CONCLUSION: Types I and II achalasia have similar frequency and clinical profile. Type II has higher LES pressure and less dilated esophagus than Type I. Both respond equally well to initial PD. Type I required post-PD myotomy more often, though not significantly. TBE is useful for assessing therapeutic response.

Higher Prevalence of Monogenic Cause Among Very Early Onset Inflammatory Bowel Disease in Children: Experience From a Tertiary Care Center From Northern India.

BACKGROUND: Very early-onset inflammatory bowel disease (VEO-IBD) is generally defined as onset of IBD at <6 years of age. Up to 20% of VEO-IBD may have a monogenic cause; hence, next-generation sequencing is highly recommended for diagnostic accuracy. There remains a paucity of data on VEO-IBD and the proportion of monogeneic causes in South Asia. We analyzed our tertiary care center experience of monogenic VEO-IBD from Northern India and compared them with nonmonogenic VEO-IBD to find out the factors that differentiate monogenic from nonmonogenic VEO-IBD. METHODS: All children (<18 years of age) diagnosed with IBD between January 2010 to July 2021 were analyzed along with the next-generation sequencing data and functional assays when available. Clinical features and outcomes between monogenic and nonmonogenic VEO-IBD were compared. RESULTS: A total of 200 children with a median age of 15.3 (range, 0.17-17) years, 125 of whom were boys, were diagnosed to have IBD during the study period. VEO-IBD was seen in 48 (24%) children. Monogenic IBD was diagnosed in 15 (31%) children with VEO-IBD and 7.5% of all IBD cases. The causes of monogenic VEO-IBD included disorders of the immune system (including interleukin-10 receptor mutations) in 12 and epithelial barrier dysfunction in 3. Features that differentiated monogenic from nonmonogenic VEO-IBD were neonatal IBD, presence of perianal disease, IBD unclassified, history of consanguinity and sibling death, wasting, and stunting (P < .05). There were 6 deaths. CONCLUSIONS: One-third of participants were monogenic among Indian children with VEO-IBD, the highest proportion reported to date in the world. Next-generation (either exome or whole genome) sequencing should be recommended in a subset of VEO-IBD with neonatal onset, perianal disease, history of consanguinity and siblings' death, wasting, stunting, and IBD unclassified phenotype for an early diagnosis and referral to an appropriate center for hematopoietic stem cell transplantation for a better outcome.

Of 200 children with inflammatory bowel disease (IBD), 48 were very early-onset IBD (VEO-IBD) and 15 (32%) of them had monogenic VEO-IBD. Clinical features that differentiated monogenic from nonmonogenic VEO-IBD were neonatal onset, perianal disease, history of consanguinity and sibling death, wasting, stunting, and IBD unclassified phenotype.