Serum Adipokines as Biomarkers for Surveillance of Metabolic Syndrome in Childhood Acute Lymphoblastic Leukemia Survivors in Low Middle-Income Countries.

BACKGROUND: Serum adipokines (leptin and adiponectin) are dysregulated before the onset of metabolic syndrome and hence may be useful biomarkers for screening of cardiometabolic late effects in childhood Acute Lymphoblastic Leukemia (cALL) survivors. METHODS: We compared serum adipokine levels between 40 cALL survivors (aged 10-18 years, >2 years from treatment completion) with similar controls. A multivariable logistic regression analysis was then done to assess the association of metabolic syndrome in cALL survivors with variables including adipokines and other metabolic parameters, demographic and treatment details, and Dual-energy X-ray absorptiometry scan-derived variables. RESULTS: Compared to controls, cALL survivors had a higher prevalence of metabolic syndrome (8/40 vs. 2/40, P = .044) and central obesity (11/40 vs. 4/40, P = 0.042). Median Serum Leptin (7.39 vs. 4.23 ng/ml, P = 0.207) levels and derived Leptin-Adiponectin Ratio (1.44 vs. 0.80, P = 0.598), were higher but not statistically different in our survivors compared to controls; Adiponectin levels were similar (6.07 vs. 5.01 µg/ml, P = 0.283). In the cALL survivors, overweight/obesity (odds ratio [OR] 21.9, P = 0.020) or higher Leptin levels (OR 1.11, P = 0.047), were independently associated with metabolic syndrome. CONCLUSIONS: Serum Leptin, independently predictive of metabolic syndrome in our cALL survivors, may be tested in larger studies to assess its utility in surveillance and initiation of early preventive measures.

Body composition from birth to 6 months in term small-for-gestational-age Indian infants: effect of catch-up growth.

The objective of this prospective observational study was to assess the growth and body composition of term small-for-gestational-age (SGA) infants from birth to 6 months and evaluate the effect of catch-up growth (CUG) on body composition. Term SGA newborns were recruited at birth. Anthropometry and body composition were evaluated at 3 days, 6, 10 and 14 weeks, and 6 months. Fat and fat-free mass (FM and FFM) were compared between infants with and without CUG (increase in weight Z-score by > 0·67) by air displacement plethysmography. Factors that could affect body composition and CUG, including parents' BMI and stature, infants' birth weight, sex and feeding, were evaluated. A total of 143 SGA newborns (sixty-six boys) with birth weight of 2336 (sd 214) g were enrolled; 109 were followed up till 6 months. Median weight Z-score increased from -2·3 at birth to -1·3 at 6 months, with 51·9 % of infants showing CUG. Infants with CUG had higher FM (1796 (sd 491) g v. 1196 (sd 474) g, P < 0·001) but similar FFM (4969 (sd 508) g v. 4870 (sd 622) g, P = 0·380), and consequently higher FM percentage (FM%) (26·5 (sd 5·8) v. 19·7 (sd 6·9), P < 0·001), compared with those without CUG. Lower birth weight, exclusive breast-feeding and higher parental stature were positively associated with CUG. In conclusion, CUG in term SGA infants in the first 6 months of life was almost entirely attributable to greater gain in FM. Follow-up of this cohort will provide insight into the long-term effect of disproportionate gain in FM in early infancy in SGA babies.

Reduced Presentation of Biliary Atresia During the COVID-19 Lockdown: A Population Based Observational Study.

OBJECTIVE: The aim of this study was to assess whether there has been a change in presentations of biliary atresia (BA) in England and Wales during the first and second coronavirus disease 2019 (COVID-19) lockdowns (January-June 2020 and 2021). DESIGN: This population study assessed all confirmed cases of BA, from January 2020 to December 2021 across the 3 UK pediatric liver centers originating from England and Wales. Data was then compared to the incidence of confirmed BA cases from January to December 2017, 2018, and 2019. RESULTS: During January-June 2020 and 2021, there were only 8 and 12 presenting cases of BA in England and Wales, compared to 16, 13, and 18 for the same time periods in 2017, 2018, and 2019, respectively. This difference was significant in a two-sided t test for 2020 ( P = 0.035) but not for 2021 ( P = 0.385). There was no difference in the mean days to Kasai procedure in January-June 2020 and 2021 compared to 2017-2019; however average time to Kasai after the lockdown periods was significantly higher. CONCLUSIONS: There was a significant reduction in the presenting cases of BA during the first COVID-19 lockdown, with an increased time for BA referrals after the pandemic lockdowns were lifted in England and Wales.

Transplantation in paediatric patients with MMA requires multidisciplinary approach for achievement of good clinical outcomes.

BACKGROUND: As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. METHODS: We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. RESULTS: There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient's recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. CONCLUSIONS: Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.

High-altitude population neonatal and maternal phenotypes associated with birthweight protection.

BACKGROUND: States which reduce foetal oxygen delivery are associated with impaired intrauterine growth. Hypoxia results when barometric pressure falls with ascent to altitude, and with it the partial pressure of inspired oxygen ('hypobaric hypoxia'). birthweight is reduced when native lowlanders gestate at such high altitude (HA)-an effect mitigated in native (millennia) HA populations. Studying HA populations offer a route to explore the mechanisms by which hypoxia impacts foetal growth. METHODS: Between February 2017 and January 2019, we prospectively studied 316 pregnant women, in Leh, Ladakh (altitude 3524 m, where oxygen partial pressure is reduced by 1/3) and 101 pregnant women living in Delhi (low altitude, 216 m above sea level). RESULTS: Of Ladakhi HA newborns, 14% were small for gestational age (<10th birthweight centile) vs 19% of newborn at low altitude. At HA, increased maternal body mass index, age, and uterine artery (UtA) diameter were positively associated with growth >10th weight centile. CONCLUSIONS: This study showed that Ladakhi offspring birthweight is relatively spared from the expected adverse HA effects. Furthermore, maternal body composition and greater UtA size may be physiological HA adaptations and warrant further study, as they offer potential mechanisms to overcome hypoxia-related growth issues. IMPACT: Reduced foetal oxygen delivery seen in native lowlanders who gestate at HA causes foetal growth restriction-an effect thought to be mitigated in native HA populations. We found that greater maternal body mass and UtA diameter were associated with increased offspring birthweight in a (Ladakh) HA population. This supports a role for them as physiological mediators of adaptation and provides insights into potential mechanisms that may treat hypoxia-related growth issues.

The Childhood and Adolescent Sleep Evaluation Questionnaire (CASEQ): Development and validation of an ICSD-3-based screening instrument, a community and hospital-based study.

Sleep disorders are common in children and adolescents. Polysomnography is the gold-standard diagnostic method; however, it is a tedious procedure. The objective of the study was to develop a screening questionnaire for sleep problems based on International Classification of Sleep Disorders-3 in children and adolescents, and validate it with clinical evaluation and polysomnography. A questionnaire was developed in English and Hindi with content validation by eight multidisciplinary experts. Respondents were parents of children and adolescents, aged 2-18 years, recruited from a public school and a tertiary care teaching hospital in north India. A subset of these children and adolescents underwent overnight polysomnography and detailed clinical evaluation within 4 weeks of applying the questionnaire. The questionnaire, named Childhood and Adolescent Sleep Evaluation Questionnaire, contains primary questions covering all subgroups of disorders under International Classification of Sleep Disorders-3, and secondary questions on sleep hygiene and comorbidities. The questionnaire was filled by 750 respondents, out of which 100 cases underwent polysomnography and clinical evaluation. The internal consistency in the form of Cronbach's α was 0.8 for the questionnaire. The sensitivity, specificity, positive and negative predictive values for the questionnaire in identifying those with sleep problems compared with detailed clinical and polysomnographic evaluations were 85%, 100%, 100% and 62.5%, respectively. For individual subgroups of disorders, the sensitivity, specificity, positive and negative predictive values varied between 72.7% and 100%, 88.9% and 100%, 62.5% and 100% and 81.6% and 100%, respectively. The Childhood and Adolescent Sleep Evaluation Questionnaire has good psychometric properties, moreover, its simplicity and translatability make it ideal for use at the community and hospital settings.

Social and Educational Outcomes in Patients With Biliary Atresia: A Systematic Review.

OBJECTIVES: To systematically review the social outcomes of patients with biliary atresia (BA), including educational, employment and family outcomes. METHODS: We conducted a systematic review of Medline, EMBASE, Global Health, Maternity and Infant Care Database, supplemented by reference searching. National Heart, Lung and Blood Institute scoring was conducted for quality assessment. The PROSPERO registration ID was CRD42020178846. RESULTS: Fifty-one studies were included (41 cohort, 10 cross-sectional), including 4631 participants across 16 countries. Cohorts were BA post-liver transplant (LT) (18 studies), native liver survivors (NLS) (16 studies), mixed (13 studies) and four other cohorts. Outcomes covered; education (n = 35), employment (n = 16), family outcomes (n = 22), and social functioning (n = 22). BA patients had lower school functioning scores than controls, with no difference between NLS versus post-LT. Between 2% and 48% of children required additional educational support. Between 60% and 100% of adult patients with BA were employed. Pregnancies were described in 17 studies, with small samples, and some noted complications. Social functioning scores were similar to healthy controls in 8 of 11 comparisons. CONCLUSIONS: Despite BA being the primary indication for liver transplantation in childhood, social outcomes for children and adolescents are predominantly reported in non-controlled, single-centre survey-based studies. School functioning is lower compared to peer groups, with no evidence of a difference for those having a liver transplant. We recommend routine psychosocial assessment of these patients during follow-up, alongside multi-centre collaborations, to maximise the quality of evidence for future patients.

A comprehensive yoga programme for weight reduction in children & adolescents with obesity: A randomized controlled trial.

Background & objectives: Obesity is a rising pandemic in childhood. There is scarcity of evidence on the efficacy of yoga in achieving weight loss in overweight/obese children. The objective of this study was to assess the efficacy of family-based comprehensive yoga intervention in the reduction of body mass index (BMI) in overweight/obese children, in comparison to standard dietary and lifestyle counselling and control group. Methods: This was an open-label randomized controlled study. Children aged 8-15 yr who were overweight or had obesity were randomized to one of the three arms for 18 wk; standard weight management (group 1), yoga with dietary modification (group 2) and control (no intervention; group 3). Reduction in BMI and improvement in physiological, biochemical and psychological parameters from baseline to 18 wk was compared between the three arms. Late follow up was also done at 6-12 months. Results: A total of 165 children with mean±standard deviation (SD) age of 11.6±1.8 yr and mean BMI 26.3±4.2 kg/m2 were enrolled. Outcome analysis at 18 wk was performed for 109 children. Improved diet quality and reduced intake were observed in both intervention arms. The median (IQR) reduction in BMI in standard and yoga arms was similar [-1.4 (-3.1, -0.5) kg/m2 and -1.2 (-2.3, -0.6) kg/m2, respectively], while it increased by +0.3 (-0.3, 0.1) in the control arm. In the yoga arm, mean systolic BP reduced from 118 (10) to 114 (8) mmHg, (P=0.019). In the standard arm, significant improvement in psychological scores was noted. In group 3, the mean fasting glucose increased from 93±10 to 102±12 mg/dl (P<0.001). Interpretation & conclusions: The findings of the present study suggest that yoga in conjunction with dietary modification is equally effective as the standard weight management for BMI reduction in the paediatric age group.

Adrenocortical Neoplasms in Children: Treatment and Outcomes.

Background: Adrenocortical tumors are rare tumors in children with a paucity of outcome data, especially in a resource-challenged setting. Materials and Methods: A retrospective study was conducted to evaluate the presentation, management, and outcomes of children with adrenocortical tumors who presented to our institute from January 1992 to December 2019. Results: During the study period, 28 children were included. Adenoma was present in nine children and the remaining 19 children had adrenocortical carcinoma. The median age of presentation was 48 months. Nearly half of the children with carcinomas presented with a mass compared to only 10% adenomas (P = 0.049). Virilization was present in 60% of the patients and in most cases was associated with Cushingoid features. Three children (15.7%) had metastasis at presentation. All children underwent surgical excision with a spill in 6 and gross residue in two patients. Recurrence was observed in five patients after a mean duration of 11.8 months. The 4-year overall survival and event-free survival were 100% in patients with adenomas compared to 75% and 44%, respectively, in carcinoma. Children who underwent complete surgical excision without any spill had a relatively favorable outcome. Conclusion: Adrenocortical tumors are uncommon tumors in children. Adenomas have a favorable outcome. There was no disease-free survival in incompletely resected or metastatic tumors. Tumor spill may also have an adverse outcome in completely resected tumors.

Gut Microbiome: A Potential Modifiable Risk Factor in Biliary Atresia.

ABSTRACT: Biliary atresia (BA) is a fibro-obliterative condition of the biliary tree, presenting in infancy. The bilioenteric conduit formed at Kasai portoenterostomy (KPE), achieves restoration of bile flow in approximately 60% of infants. Even if the operation is successful, cirrhosis and its associated complications are, however, common. BA remains the leading cause for liver transplantation (LT) in children. Antibiotic, choleretic, and steroid therapy post-KPE have not convincingly reduced LT rates. Advances in molecular technology have enabled characterisation of the encoded genes of the gut microbiota (gut microbiome). The gut microbiome plays an important role in host metabolism, nutrition, and immune function, with alterations in its diversity and/or composition, known as dysbiosis, being described in disease states, including liver disease. Liver-gut microbiome exploration in adulthood largely focuses on nonalcoholic liver disease, cirrhosis (mainly alcohol- or viral-based aetiology) and cholestatic liver diseases (eg, primary sclerosing cholangitis), with microbial signatures correlating to disease severity. Investigation of the gut microbiota in BA had been limited to culture-based methodology, but molecular studies are emerging, and although in their infancy, highlight a potential pathogenic role for Enterobacteriaceae and Streptococcus, and a potential beneficial role for Bifidobacteria. Bacterial translocation, and the production of gut microbiome-derived metabolites, are key host-microbiome-mechanistic pathways in liver disease pathogenesis. Microbiome-targeted therapeutics for liver disease are in development, with faecal microbiota transplantation showing promise in cirrhosis. Could the gut microbiome be a novel modifiable risk factor in BA, reducing the need for LT?

Adult Liver Disease Prognostic Modelling for Long-term Outcomes in Biliary Atresia: An Observational Cohort Study.

OBJECTIVES: To assess the utility of prognostic scoring systems for adolescents with biliary atresia (BA) surviving with native liver, for predicting the subsequent requirement for liver transplantation (LT). METHODS: Single-centre retrospective analysis of 397 BA patients who received Kasai Portoenterostomy (KP) 1980-1996 and survived with the native liver at 16 years. Laboratory and clinical variables at 16 years (timepoint 16 years) were used to calculate (i) LT allocation scores; Model for End-Stage Liver Disease [MELD/MELD-sodium (Na)], and UK End-Stage Liver Disease (UKELD); (ii) Mayo Primary Sclerosing Cholangitis risk score (MayoPSC) and (iii) a modified Paediatric End-Stage Liver Disease (PELD) score. Scores were compared between patients requiring LT after 16 years of age (LT > 16 years), and those who survived with native liver, at the latest follow-up. Additional subgroup analysis for patients with data available at 12 years (timepoint 12 years). RESULTS: MELD (area under the receiver operating characteristic [AUROC] 0.847) and UKELD (AUROC: 0.815) at 16 years of age predict the need for LT > 16 years. No advantage for MELD-Na over MELD was demonstrated. MELD >8.5 and UKELD >47 predicted LT > 16 years with 84% and 79% sensitivity and 73% and 73% specificity. PELD had a similar performance to MELD, but superiority to UKELD. MayoPSC revealed predictive accuracy for LT >16 years (AUROC 0.859), with a score of >0.87 predicting LT > 16 years with 85% sensitivity and 82% specificity. At timepoint 12 years, MELD and MayoPSC predicted LT >16 years. Change in MELD, PELD and MayoPSC between 12 and 16 years of age, was associated with LT >16 years. CONCLUSIONS: Adult LT allocation scores may help monitor progress in adolescent BA, but the omission of relevant risk factors limits their utility for listing in this cohort. A BA-specific prognostic score would improve the management of adolescent BA.

Frequency spectrum of rare and clinically relevant markers in multiethnic Indian populations (ClinIndb): A resource for genomic medicine in India.

There have been concerted efforts toward cataloging rare and deleterious variants in different world populations using high-throughput genotyping and sequencing-based methods. The Indian population is underrepresented or its information with respect to clinically relevant variants is sparse in public data sets. The aim of this study was to estimate the burden of monogenic disease-causing variants in Indian populations. Toward this, we have assessed the frequency profile of monogenic phenotype-associated ClinVar variants. The study utilized a genotype data set (global screening array, Illumina) from 2795 individuals (multiple in-house genomics cohorts) representing diverse ethnic and geographically distinct Indian populations. Of the analyzed variants from Global Screening Array, ~9% were found to be informative and were either not known earlier or underrepresented in public databases in terms of their frequencies. These variants were linked to disorders, namely inborn errors of metabolism, monogenic diabetes, hereditary cancers, and various other hereditary conditions. We have also shown that our study cohort is genetically a better representative of the Indian population than its representation in the 1000 Genome Project (South Asians). We have created a database, ClinIndb, linked to the Leiden Open Variation Database, to help clinicians and researchers in diagnosis, counseling, and development of appropriate genetic screening tools relevant to the Indian populations and Indians living abroad.

Prognostic markers at adolescence in patients requiring liver transplantation for biliary atresia in adulthood.

BACKGROUND & AIMS: In patients with biliary atresia (BA), the rate of native liver survival (NLS) to adulthood has been reported as 14-44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. The aim of this study was to identify variables that could predict whether young people with BA would require LT when they are >16 years of age. METHODS: This study was a single-centre retrospective analysis of 397 patients who underwent Kasai portoenterostomy (KP) between 1980-96 in the UK. After KP, 111/397 (28%) demonstrated NLS until 16 years of age. At final follow-up, 67 showed NLS when >16 years old (Group 1) and 22 required LT when >16 years old (Group 2). Laboratory, clinical and radiological parameters were collected for both groups at a median age of 16.06 years (13.6-17.4 years). RESULTS: The need for LT when >16 years old was associated with higher total bilirubin (hazard ratio 1.03, p = 0.019) and lower creatinine (hazard ratio 0.95, p = 0.040), at 16 years, on multivariate analysis. Receiver-operating characteristic curve analysis demonstrated that a total bilirubin level of ≥21 µmol/L at 16 years old (AUROC = 0.848) predicted the need for LT when >16 years old, with 85% sensitivity and 74% specificity. Cholangitis episode(s) during adolescence were associated with a 5-fold increased risk of needing LT when >16 years old. The presence of PHT or gastro-oesophageal varices in patients <16 years old was associated with a 7-fold and 8.6-fold increase in the risk of needing LT, respectively. CONCLUSIONS: BA in adulthood requires specialised management. Adult liver disease scoring models are not appropriate for this cohort. Bilirubin ≥21 µmol/L, PHT or gastro-oesophageal varices at 16 years, and cholangitis in adolescence, can predict the need for future LT in young people with BA. Low creatinine at 16 years also has potential prognostic value. LAY SUMMARY: Patients with biliary atresia commonly require liver transplantation before reaching adulthood. Those who reach adulthood with their own liver are still at risk of needing a transplant. This study aimed to identify tests that could help clinicians predict which patients with biliary atresia who reach the age of 16 without a transplant will require one in later life. The study found that the presence of bilirubin ≥21 µmol/L, lower creatinine levels, and a history of portal hypertension or gastro-oesophageal varices at 16 years, as well as cholangitis in adolescence, could predict the future likelihood of needing a liver transplant for young people with biliary atresia.

Left Lateral Port: Safe Laparoscopic Port Entry in Previous Large Upper Abdomen Laparotomy Scar.

The first port entry in patient who underwent previous abdominal surgery. Palmer's point can be used in patients with suspected periumbilical adhesions, a history of an umbilical hernia, or multiple failed attempts of insufflations at the umbilicus. Palmer's point has its limitations in cases of left upper quadrant surgery, splenomegaly, portal hypertension, and improper nasogastric tube placement giving rise to a bloated stomach. In such cases, a new and safe point for laparoscopic entry is needed. In the present case of a patient who underwent previous upper abdominal surgery with the chevron incision obscuring Palmer's point, laparoscopic entry was made through a novel point that was found to be safe in such cases and can be used in similar cases of previously scarred abdomens.

Prevalence, clinical & biochemical correlates of non-alcoholic fatty liver disease in overweight adolescents.

BACKGROUND & OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) characterized by excessive accumulation of fat in the liver, which can progress to inflammation, and cirrhosis, has emerged as an important complication of obesity in adults as well as children. This study was undertaken to assess the prevalence of NAFLD and its correlation with clinical and biochemical parameters in overweight Indian adolescents. METHODS: In this cross-sectional study, 218 overweight adolescents aged 10 to 16 yr and their parents were included. Measurements included anthropometry, ultrasonography to diagnose NAFLD, fasting glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipids for adolescents and parents, and additional parameters of blood pressure, body fat percentage (BF%), fasting insulin, apolipoprotein C3, tumour necrosis factor-α and adiponectin for adolescents. The variables were compared between adolescents with and without NAFLD, and logistic regression analysis was performed. RESULTS: Mean age and body mass index (BMI)SD score (SDS) were 11.9±1.6 yr and 2.3±1.1, respectively. NAFLD was seen in 62.5 per cent of the adolescents. The prevalence of NAFLD in the parents was similar among the adolescents with and without NAFLD, while BMI and waist circumference SDS, BF per cent, blood pressure (BP), ALT, AST, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in the adolescents with NAFLD. On multiple logistic regression, abdominal obesity, HOMA-IR and BF per cent were independently associated with NAFLD with odds ratios (95% confidence interval) of 2.77 (1.40-5.47), 2.21 (1.16-4.21) and 2.17 (1.12-4.22), respectively. INTERPRETATION & CONCLUSIONS: NAFLD was noted among nearly two-thirds of the overweight adolescents. An independent association was observed between abdominal obesity, HOMA-IR and body fat percentage and NAFLD in overweight adolescents.

Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis.

46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

Extracorporeal Liver Support Systems in Paediatric Liver Failure.

Extracorporeal liver support systems (ELSS), encompassing artificial and bioartificial devices, have been used for decades, with the aim of supporting patients with acute liver failure and acute-on chronic liver failure, as a bridge to recovery (acute liver failure only) or liver transplantation, in an era of organ donation shortage. Although biochemical efficacy has been consistently demonstrated by these devices, translation into clinical and survival benefits has been unclear, due to study limitations and lack of reliable prognostic scoring in liver failure. Consequently, extracorporeal devices are not widely accepted as routine therapy in adult liver failure. Recent large multicentre trials using artificial liver systems have not revealed beneficial outcomes associated with albumin dialysis but plasma exchange practices have shown some potential. In paediatric liver failure, data on extracorporeal systems is scarce, comprising few reports on albumin dialysis (namely, Molecular Adsorbent Recirculating System; MARS) and plasma exchange. When extrapolating data from adult studies differences in disease presentation, aetiology, prognosis and the suitability, and safety of such devices in children must be considered. The aim of this review is to critically appraise current practices of extracorporeal liver support systems to help determine efficacy in paediatric liver failure.

Robotic-Assisted Video Endoscopic Inguinal Lymphadenectomy in Carcinoma Vulva: Our Experiences and Intermediate Results.

OBJECTIVES: To describe the technique of robotic-assisted video endoscopic inguinal lymphadenectomy (R-VEIL) in patients with carcinoma vulva and discuss the advantages of the technique and oncological outcome. METHODS: Twelve patients of squamous cell cancer of vulva underwent 22 R-VEIL procedures from February 2011 to February 2015. Their preoperative, intraoperative, and postoperative data were retrospectively analysed. RESULTS: The mean age of patients was 61 years (range, 32-78 years). The mean operative time was 69.3 minutes (range, 45-95 minutes). The mean blood loss was 30 mL (range, 15-50 mL). No intraoperative complication was observed. The mean drain output was 119 mL (range, 50-250 mL), and the drains were removed at a mean of 13.9 days (range, 8-38 days). The average number of superficial and deep inguinofemoral lymph nodes retrieved was 11 (range, 4-26). Two patients had positive lymph nodes on histopathology (16.67%). Postoperative complications were lymphocele (6 groins), chronic lower limb lymphedema (6 cases), prolonged lymphorrhea (1 groin), and cellulitis (2 groins). Over a follow-up period ranging from 7 to 67 months, 1 patient developed recurrence in the inguinal nodes and died 7 months after the recurrence. CONCLUSIONS: The R-VEIL allows the removal of inguinal lymph nodes within the same limits as the open procedure for inguinal lymph node dissection and has a potential to reduce the surgical morbidity associated with the open procedure. Long-term oncological results are not available though our initial results appear promising. Prospective multi-institutional studies are required to prove its efficacy over open inguinal lymph node dissection.

Clinicopathological Characteristics and Prognostic Factors of Synchronous Endometrial and Ovarian Cancers-A Single-Institute Review of 43 Cases.

OBJECTIVES: The objectives of our study were to demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary cancers of the endometrium and ovary. METHODS: A retrospective analysis of 43 pathologically proven cases of synchronous primary endometrial and ovarian cancers diagnosed between January 2005 and December 2015 was carried out. Patients with uterine sarcomas, carcinosarcomas, borderline tumors, and nonepithelial tumors of the ovary and patients who received neoadjuvant chemotherapy were excluded from the study. Disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis to determine independent prognostic factors was performed using the Cox regression model. RESULTS: Mean age at diagnosis was 48.49 years. The most common presenting symptom was abnormal uterine bleeding in 58.2% of the patients. Nineteen patients (44.2%) were obese, and 13 patients (30.2%) were overweight. Twelve patients (30%) were nulliparous, and 25 (58.2%) were premenopausal; 76.7% of the patients received adjuvant treatment after surgery. Mean follow-up period was 48.9 months. Twelve patients developed recurrence, and 7 patients died of recurrent disease. The 5-year DFS for all patients was 65.13%, and the 5-year OS was 79.75%. The 118-month DFS and 118-month OS were 65.13% and 72.50%, respectively. On multivariate analysis, grade 3 disease for both endometrial and ovarian cancers and presence of lymphovascular space invasion were associated with significantly worse 118-month DFS and OS, respectively. CONCLUSIONS: Women with synchronous primary endometrial and ovarian cancers are young, nulliparous, obese, and premenopausal and have a favorable overall prognosis. Grade 3 disease at both sites and presence of lymphovascular space invasion are independent prognostic factors for recurrence and survival, respectively.

Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia: Experience from a tertiary care centre in India.

BACKGROUND & OBJECTIVES: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with a wide range of clinical manifestations. The disease is attributed to mutations in CYP21A2 gene encoding 21-hydroxylase enzyme. In view of severe phenotype in salt-losing cases, issues related to genital ambiguity in girls and precocity in boys, most families opt for prenatal testing and termination of affected foetus. CAH can be diagnosed in utero through direct molecular analysis of CYP21A2 gene, using DNA extracted from foetal tissues or cells obtained from chorionic villus sampling or amniocentesis. The objective of this study was to evaluate the feasibility and accuracy of prenatal diagnosis (PND) using sequencing and multiplex ligation probe amplification (MLPA) methods in families at risk for CAH. METHODS: Fifteen pregnant women at risk of having an affected offspring with CAH were included in this study. Ten families had previous affected children with salt-wasting/simple virilising form of CAH and five families did not have live children but had a high index of suspicion for CAH in previous children based on history or records. Mutation analysis was carried out by Sanger sequencing and MLPA method. RESULTS: Seven different mutations were identified in 15 families. Deletions and I2g mutation were the most common. Of the 15 foetuses analyzed, nine were unaffected while six were affected. Unaffected foetuses were delivered, they were clinically normal and their genotype was found to be concordant to the prenatal report. All except two families reported in the second trimester. None of the couples opted for prenatal treatment. INTERPRETATION & CONCLUSIONS: Our preliminary findings show that PND by direct mutation analysis along with MLPA is a feasible strategy that can be offered to families at risk.