Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Understanding the living-related pediatric liver transplantation donor's decision process: A questionnaire-based retrospective study.

OBJECTIVES: To analyse the donor characteristics and understand the sociocultural and familial aspects of the decision to donate for living donor liver transplant. METHODS: This is a retrospective study done in the Department of Pediatric Gastroenterology and Hepatology of a liver transplant centre. We enrolled the consenting donors of pediatric liver transplantation between January 2020 and January 2022. The study was conducted through an anonymized questionnaire which was drafted in a multiple-choice format. The questionnaire had three domains having questions pertaining to demographic details, donor characteristics and sociofamilial aspects of the decision-making process. RESULTS: The study cohort consisted of 50 donors, 23 males (46%) and 27 females (54%), with the mean age being 31.8 ± 5.6 years. Parent-to-child was the most frequent relationship (n = 39, 78%). More than half of our donors had annual income <2.5 lakh/annum or <3500 USD (n = 27, 54%). Twenty-six (52%) responders had >4 members in their family; 62% were residing in urban areas and 52% of the donors were graduates. The main source of information regarding the feasibility of living donor liver transplantation was primary physicians in 46%. Financial management was the main hurdle in 72%. Majority (74%) denied any effect on their marital relationship and 6% of donors thought that the degree of information provided to them before the transplantation regarding donation was insufficient. CONCLUSION: Our study serves as an essential tool for health professionals to provide sufficient support to the donor. Clinical outcomes and cost must be part of the discussion between caregivers, health professionals and fund contributors.

Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: Expert review on behalf of the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood.

Acute Liver Failure in Dengue: A Common but Overlooked Entity in Pediatric Patients in Tropical Countries.

OBJECTIVE: The objective of the study is to estimate the incidence of acute liver failure (ALF) in dengue infection, understand the demographic and biochemical profiles, and identify prognostic factors associated with mortality. METHODOLOGY: This is a retrospective observational study. We evaluated the data of all pediatric dengue patients admitted over the last 5 years in our hospital to identify patients who fulfilled the criteria for pediatric ALF. Demographic profile, and biochemical and radiological parameters were assessed. Their outcomes and mortality data were analyzed to identify prognostic factors. RESULTS: Thirty children with dengue infection were identified to have developed a during the ALF study period which was 29.1% (30 of 103) of all our ALF admissions. A total of 189 children with dengue infection needed admission during the same period and 15.8% (30 of 189) of them developed ALF. The mean duration of onset of ALF was 5.4 days after fever onset. Twenty-two patients (73%) survived, and 8 patients expired. High creatinine, low albumin level, and multisystemic involvement were identified as poor prognostic markers in those patients who did not survive. CONCLUSION: ALF is common in admitted severe dengue patients. A significant proportion of acute liver patients in endemic countries can be attributed to dengue infection. Low serum albumin, high creatinine, and multi-organ dysfunction during acute illness can be used as prognostic markers in these children. Multicentric prospective studies are needed to validate these results.

Intraoperative portal vein stenting through umbilical vein approach: An innovative salvage procedure for portal vein thrombosis in pediatric liver transplant.

BACKGROUND: IPVS is considered a last resort or a salvage procedure in the event of recurrent PV thrombosis despite multiple attempts at redo PV anastomosis. We employed the opened umbilical vein approach to place the stent in the PV and deliver anticoagulation through a catheter. MATERIALS AND METHODS: From Jan 2017 to Feb 2022, 150 patients underwent pediatric transplantation at department of liver transplant and hepatobiliary surgery unit, Indraprastha Apollo hospitals, New Delhi. Age, weight, PELD Score, diagnosis, portal vein diameter on preoperative CT, Portal flow after stenting, decrease in spleen size after stenting in follow-up CT were collected from a prospectively maintained data base and reviewed. RESULTS: Eight patients underwent IPVS following LDLT (mean age-10.6 ± 2.2 months, mean weight 8.1 ± 1.6, mean PELD score 32.7 ± 7.3). The mean PV diameter on preoperative CT scan was 3.6 mm (range 2.7-5.6 mm). The mean portal flow following stenting was 718.75 cc/min. Percentage reduction in size of the spleen was 26.35% beyond 2nd post-operative week. No patient had recurrent PV thrombosis following IPVS and all maintained an adequate portal flow throughout the immediate postoperative period. Two patients had in-hospital mortality secondary to septic complications. CONCLUSION: Umbilical vein approach is technically feasible, easy to manipulate the stent and catheter placement after stenting helps to deliver anticoagulants locally.

Efficacy of therapeutic plasma exchange in pediatric cases of acute liver failure as an extracorporeal liver support system.

BACKGROUND: Acute liver failure in the pediatric population is often accompanied by deranged metabolism, severe encephalopathy and coagulopathy. A liver transplant is the most viable option for the management of such patients. Therapeutic plasma exchange (TPE) is helpful in improving the liver biochemistry profile, thereby, increasing their likelihood of undergoing a liver transplant METHOD: The study was conducted over a period of 3 years (January 2018 to December 2021). Indications mainly consisted of ALF with hepatic encephalopathy, worsening liver parameters in spite of medical management, and candidacy for undergoing a liver transplant. Plasma exchange was performed daily or alternatively until the patient recovered, succumbed, or was stable enough to undergo a transplant. Biochemical parameters serum bilirubin, ALT, AST serum ammonia serum urea, serum creatinine were recorded before and after TPE sessions. RESULTS: The study group comprised 14 patients of which a total of 28 TPE was performed. There were a total of 5 cases of cryptogenic ALF, 4 of Wilson disease, 2 cases each of infection-related ALF and autoimmune hepatitis, and a single case of drug-induced hepatitis. A total of 5 out of 14 patients underwent a liver transplant and amongst the 9 who did not undergo a transplant, 4 patients expired due to septic shock syndrome; the remaining 5 were discharged in a stable condition following TPE sessions. The disease-free survival was 78.9% and the transplant-free survival was 35.71%. CONCLUSION: TPE plays a crucial role in improving the biochemistry profile of the liver in children with liver failure.

Clinical Profile of Acute Pancreatitis in Children and Adolescents from a Single Center in Northern India.

Introduction: There has been an increase in incidence of pancreatitis in children all over the world; studies in developed countries shown multiple etiological factors such as drugs, infections, trauma, anatomic abnormalities, and/or genetic pancreatitis in children; however, there are sparse data from the developing countries. This study was undertaken to determine the characteristics of Indian children with acute pancreatitis (AP), mainly the clinical features, etiology, complication, association, genetic factors, and outcome and recurrence. Methods: We performed a retrospective study of all patients under the age of 18 years, who had a final diagnosis of pancreatitis admitted at our center between 2017 and 2019. Results: During the 3-year period from 2017 to 2019, 40 patients were admitted at our center with AP. We found a definite etiology in 62.5% cases of patients, which were broadly grouped into seven etiologies: structural, genetic, drug induced, concurrent illness, cholelithiasis related, metabolic, and autoimmune. Recurrence of acute episodes was noted in 13 patients (32.5%). Of these, 11 were found to have a genetic mutation, underlying structural abnormality, or concurrent illness. In our study, we found that 23 patients (57.5%) had mild AP, while 14 patients (35%) had moderately severe pancreatitis; however, 3 patients (7.5%) had severe AP. Discussion: We found that most cases of pancreatitis in children were of mild severity, and the etiology was quite different than adults, and most cases of acute recurrent pancreatitis have a definite etiology of either genetic mutation or structural anomaly.

Complicated Pylephlebitis Secondary to Perforated Appendicitis in an Adolescent.

Septic thrombophlebitis of the portal vein or pylephlebitis is a rare cause of morbidity and mortality in children. The common causes include infective intra-abdominal pathology (acute appendicitis or diverticulitis) or inflammatory conditions (acute pancreatitis and inflammatory bowel disease). Management involves a multidisciplinary team approach for favorable outcome. We present a case report of pylephlebitis secondary to perforated appendicitis with incomplete resolution of thrombosis.

SARS-CoV-2 infection after COVID-19 immunization in healthcare workers: A retrospective, pilot study.

BACKGROUND & OBJECTIVES: COVID-19 pandemic has taken a significant toll on the health of the people across the globe, including India, and is still continuing with its rapidly evolving second wave. Although the COVID-19 vaccines effectively prevent infection, yet some cases of infections have been reported post-vaccination, raising concerns about their efficacy and safety. This study was aimed to investigate the occurrence of SARS-CoV-2 infection among the symptomatic-vaccinated healthcare workers (HCWs) and to analyze the severity of their disease. METHODS: This retrospective study was done at a single multispecialty hospital, on the HCWs who have had COVID-19 vaccination, during the initial period of the vaccination drive (January 16 to April 24, 2021). The symptomatic post-vaccination infections in these HCWs were evaluated. RESULTS: Eighty five of 3235 (2.63%) vaccinated HCWs acquired the SARS-CoV-2 infection after vaccination, during the study period. Of these, 65 (76.5%) were fully vaccinated (FV), and 20 (23.5%) were partially vaccinated (PV) and the protection rate of vaccination was 97.4 per cent [95 % confidence interval (CI)=96.8-97.9]. The odds ratio of acquiring infection among females was higher at 1.84 (95% CI=1.17-2.88; P=0.008) mainly because of their greater involvement in the patient care as nursing personnel. The chances of infections were the highest in the medical and nursing personnel, as compared to paramedical, administrative and supporting staff (P<0.001). Among the HCWs studied, only two required hospitalization (0.06%), none needed an intensive care unit (ICU) admission and there were no deaths. INTERPRETATION & CONCLUSIONS: The COVID-19 infection after vaccination occurred in a smaller subset (2.63%) of HCWs, in both PV and the FV groups. These infections were primarily minor and did not lead to severe disease. Overall, the vaccination with ChAdOx1 nCoV-19 vaccine (recombinant) prevented SARS-CoV-2 severe infection in the HCWs, leading to ICU admission and deaths.

Survey of Impediments to Prevention of Mother-to-infant Transmission of Hepatitis B Virus by International Societies.

OBJECTIVE: Mother-to-infant transmission (MIT) is the leading cause of hepatitis B virus (HBV) infections globally. The aim of this international study was to assess the impediments to prevention of (MIT) of HBV. METHODS: A cross-sectional survey was developed by the Federation of the International Societies for Pediatric Gastroenterology, Hepatology and Nutrition. (FISPGHAN) The survey was sent to HBV experts of the 5-member societies of FISPGHAN, and 63 of 91 countries/regions responded. Main outcome measures include percentage of countries having vaccine programs, timing of the first dose of HBV vaccine, availability of HBV vaccine for outborn neonates, payment of HBV vaccine and hepatitis B immune globulin, screening HBV markers during pregnancy, and antivirals to highly infectious pregnant mothers. RESULTS: Among the participating countries/regions, 11% did not implement infant HBV immunization programs. The first dose of vaccine was given >24 hours in 36% of the total countries and 100% of African countries. The recommended birth dose was unavailable for outborn neonates in 45% of the total countries, including 92% of African and 50% of Latin American countries/regions. During pregnancy, 44% countries do not screen maternal viral markers, and 46% do not provide third trimester antiviral therapy for highly viremic pregnant mothers. CONCLUSIONS: Our study demonstrated multiple obstacles to achieving the goal of preventing MIT of HBV. Comprehensive public health programs to enhance vaccine coverage rate, supply HBV vaccine for out-born neonates, screening maternal HBV markers, treating highly viremic pregnant mothers are proposed to overcome these obstacles and achieve the goal of preventing MIT of HBV.

Time to Detection of Yeast Isolates in Pediatric and Adult Patients with Fungemia and its Relevance to Clinical Profile and Outcome.

CONTEXT: Time to detection (TTD) given by continuous monitoring automated blood culture systems (CMABS) have been found to be a predictor of clinical outcome, drug resistance and type of microorganism in cases of bacteremia but the studies evaluating TTD with respect to fungemia are scarce especially from India. AIMS: To evaluate TTD for yeast isolates in fungal bloodstream infections with respect to the type of yeast isolates, risk factors and outcome and to study yeast susceptibility and distribution of yeast isolates with respect to patient population. MATERIALS AND METHODS: All blood culture specimens were processed in CMABS. The TTD for yeast isolates were recorded. The identification of yeast and susceptibility testing was done by automated methods. A correlation of TTD was done with respect to prior/concurrent yeast isolates, use of antifungal, risk factors and clinical outcome. RESULTS: Out of 80 yeast isolates, the maximum was C. parapsilosis (26.25%) followed by C. albicans (16.25%) and C. tropicalis (13.75%). A statistically significant difference in the occurrence of yeasts with early TTD (TTD < = 48 hours) and late TTD (TTD > 48 hours) was found. TTD of C. glabrata was significantly longer (p = 0.002) while TTD of C. tropicalis was significantly shorter (p = 0.013). There was an observable favorable outcome in shorter TTD (< = 48 hours). C. albicans and C. tropicalis depicted 100% susceptibility for Azoles, Amphotericin B and Echinocandins. CONCLUSION: TTD may be used as both diagnostic and prognostic adjunct in fungal bloodstream infections. This study is a step towards this novel approach. We also emphasize on the importance of speciation of yeast isolates and susceptibility testing. HOW TO CITE THIS ARTICLE: Butta H, Sardana R, Mendiratta L, Sibal A, Gupta V, Chawla R, Jafri AA. Time to Detection of Yeast Isolates in Pediatric and Adult Patients with Fungemia and its Relevance to Clinical Profile and Outcome. Indian Journal of Critical Care Medicine, January 2019;23(1):27-30.

[An approach to improve patient safety and quality beyond accreditation].

Patient safety improvements demand a complex system-wide effort, involving a wide range of actions in performance improvement, environmental safety and risk management, including infection control, safe use of medicines, equipment safety, safe clinical practice and safe environment of care. Healthcare accreditation is one of the major steps towards improving quality and patient safety. Amongst the several accrediting agencies across the world, the Joint Commission International, (JCI) stands out as the gold standard in healthcare accreditation. The patient safety journey for hospitals like the Apollo Group, formally started with Apollo Hospitals, Delhi becoming the first JCI accredited Hospital in India, in 2005. In the years to come, eight hospitals of the Group also became JCI accredited; taking the number of hospitals accredited by JCI to twenty-three in the country. The National Accreditation Board for Hospitals and Healthcare providers (NABH) was formed thereafter and today nearly three hundred hospitals are accredited by NABH across the country. There is more to patient safety and healthcare quality beyond just accreditation. With a view to further improve patient safety; Apollo Hospitals have taken several initiatives.

Experience of 100 solid organ transplants over a five-yr period from the first successful pediatric multi-organ transplant program in India.

To analyze the clinical profile and outcome of pediatric patients who had undergone a liver and/or RT at our center over a five yr period, case records of all the patients who had undergone a liver or RT were analyzed retrospectively. One hundred solid organ transplants were performed at our center between January 2007 and January 2012. These included 50 liver, 44 renal, one sequential liver and renal, and two CLKT. BA was the most common indication for an LT (38%). At a median follow-up of two yr three months, the patient survival was 88%. The most common indication for an RT was chronic glomerulonephritis (54.5%). At a median follow-up of three yr, the survival was 91%. The CLKT were performed for hyperoxaluria. Two yr post LT, a sequential RT was performed for ESRD resulting from transplant associated microangiopathy. All patients received a living related graft. The common post-operative complications were infections, vascular complications, and graft dysfunction. Survival rates for liver and RT at our center are comparable to those in the established centers in the West.

The Apollo Accreditation Program: A web-based Joint Commission International standards compliance management tool.

Creating and implementing processes to deliver quality care in compliance with accreditation standards is a challenging task but even more daunting is sustaining these processes and systems. There is need for frequent monitoring of the gap between the expected level of care and the level of care actually delivered so as to achieve consistent level of care. The Apollo Accreditation Program (AAP) was implemented as a web-based single measurable dashboard to display, measure and compare compliance levels for established standards of care in JCI accredited hospitals every quarter and resulted in an overall 15.5% improvement in compliance levels over one year.

Management of complicated ureteroceles: Different modalities of treatment and long-term outcome.

The presentation and management of ureterocele has been rarely reported from India and is limited to an odd case report. They can be detected antenatally, may have incidental diagnosis or present with consequences of obstructive uropathy. They always present with secondary complications in adulthood, if the diagnosis and treatment is missed in early years of life. The natural history may be particularly disastrous in cases of bilateral obstructing ureterocele. The complications secondary to obstructive ureterocele can be urinary retention, pyonephrosis, urosepsis, stones and even chronic renal failure. Each of these patients needs an individualized treatment plan. In the period 2003-2013, we managed 36 consecutive patients with varied presentation of this entity. All were managed on the basis of a fixed protocol of investigation and operative intervention. Ultrasound, micturating cystourethrogram, isotope renogram were done preoperatively in all the babies. Those with asymptomatic, unobstructed ureteroceles were left without any intervention. Simple or complex intravesical ureteroceles underwent examination under anesthesia and endoscopic deroofing and DJ stenting for 3 weeks. Of a total of 36 children, 6 were presented with acute complications of ureterocele. They have been managed on an individualized optimum management plan. Their management approach with follow-up is being reported as there is no previous reported series on ureterocele in children from our country.

Robotic augmentation ileocystoplasty with bilateral ureteric reimplantation in a young child with neuropathic bladder.

Neuropathic bladder in children is most commonly secondary to spina bifida. The management starts early in life. The modalities of treatment vary depending on the severity of the symptoms. A proportion of children inspite of adequate medical management need augmentation ileocystoplasty later in life. The open surgery has proven safety and success over many decades. Earlier attempts to perform augmentation cystoplasty by the laparoscopic approach were limited by steep learning curve, long operating times, and technical difficulties in intracorporeal anastomosis. The emergence of robotic technology has revived the interest in minimally invasive approach for complex pediatric urological reconstructions. In the recent times, there has been only one reported case report and small series of pediatric robotic augmentation cystoplasty from Chicago. We report the first minimally invasive robotic reconstruction in a child with neuropathic bladder and early renal decompensation despite appropriate medical treatment, from our country.

Trends of Publications and Country Rankings in Pediatrics, Perinatology, and Child Health from Asia: A Bibliometric Study from 1996 to 2022.

There is a need to analyze the trends of country-wise research output in child heath over the past few decades. A total of 7,87,812 global publications in pediatrics, perinatology and child health were found from 1996 to 2022 in SCOPUS, the largest abstract and citation database of peer-reviewed literature, covering over 35,000 journals from diverse disciplines. About 13.4% of these were published from Asia. There was an average growth of global publications of 3.53 times between 1996 and 2022, with China and India showing higher growth than the global average.

Prehabilitation: A proactive approach to enhancing outcomes in joint replacement surgery.

Prehabilitation is an emerging proactive and preventive approach to healthcare that focuses on preparing individuals for upcoming medical interventions or procedures. It aims to optimize physical and mental health before the planned medical and surgical interventions. By integrating exercise, psychological support, and lifestyle modifications, prehabilitation empowers individuals to face medical interventions with increased resilience and a higher likelihood of successful outcomes. Prehabilitation helps patients build strength and endurance, which can enhance their ability to withstand the physical stress of surgery and contribute to faster recovery. It plays a crucial role in optimizing outcomes for patients undergoing joint replacement surgery, by enhancing postoperative recovery, reducing complications, and improving the overall quality of life for patients. As the field of orthopaedics continues to evolve, the integration of prehabilitation into standard care protocols has the potential to redefine the landscape of joint replacement surgeries, ultimately improving patient outcomes, and hence more research is required from diverse population groups from developed and developing countries to collate required data and formulate evidence-based clinical guidelines.

Prolonged Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a type of fatty acid oxidation disorder in which long chain fatty acids cannot be transported into mitochondria for further processing and storage in our body. Typically, the patients present with lethargy, hypoglycemia, and raised serum transaminase levels before 2 years of age. Cholestatic jaundice as manifestation of this deficiency has been reported rarely; here, we report an adolescent male with CPT1A deficiency who developed prolonged cholestatic jaundice following a febrile illness.