The SPLIT Research Agenda 2013

This review focuses on active clinical research in pediatric liver transplantation with special emphasis on areas that could benefit from studies utilizing the SPLIT infrastructure and data repository. Ideas were solicited by members of the SPLIT Research Committee and sections were drafted by members of the committee with expertise in those given areas. This review is intended to highlight priorities for clinical research that could successfully be conducted through the SPLIT collaborative and would have significant impact in pediatric liver transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98814/1/petr12090.pd

Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis

Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse. Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to 50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose. Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to 25% drop in haemoglobin to <70 g/L. Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events. PROSPERO registration number CRD42022313730

Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study

Objectives: The aim of the study was to determine the frequency and natural history of infantile idiopathic cholestasis (IC) in a large, prospective, multicenter cohort of infants. Methods: We studied 94 cholestatic infants enrolled up to 6 months of age in the NIDDK ChiLDReN (Childhood Liver Disease Research Network) "PROBE" protocol with a final diagnosis of IC; they were followed up to 30 months of age. Results: Male sex (66/94; 70%), preterm birth (22/90 with data; 24% born at 1 mg/dL and/or ALT > 35 U/L; n = 7), and exited healthy (resolved disease per study site report but without documented biochemical resolution; n = 34). Biochemical resolution occurred at median of 9 months of age. GGT was <100 U/L at baseline in 34 of 83 participants (41%). Conclusions: Frequency of IC and of death or liver transplant was less common in this cohort than in previously published cohorts, likely because of recent discovery and diagnosis of genetic etiologies of severe/persistent cholestasis that previously were labeled as idiopathic. Preterm birth and other factors associated with increased vulnerability in neonates are relatively frequent and may contribute to IC. Overall outcome in IC is excellent. Low/normal GGT was common, possibly indicating a role for variants in genes associated with low-GGT cholestasis-this warrants further study

Utility of non-invasive haemoglobin monitoring in oncosurgery patients

Background and Aims: Oncosurgeries may incur massive blood loss demanding frequent blood sampling to assess blood loss and the need for intraoperative blood transfusions. Accuracy of non-invasive spectrophotometric haemoglobin (hereafter to be referred as SpHb) monitoring has been studied in various perioperative settings. The intraoperative use of Radical-7®, Masimo Corp., (Radical-7®) for SpHb monitoring may be useful during cancer surgery. The aim of this study is to evaluate the intraoperative utility of SpHb monitoring by the Radical-7® to guide intraoperative transfusion in oncosurgeries. Methods: Fifty adult patients, undergoing oncosurgery with anticipated blood loss of more than 20% of blood volume, were selected. Continuous SpHb monitoring was performed intraoperatively and blood transfusion was based on SpHb values. Simultaneous laboratory haemoglobin (LabHb) samples were taken for validation. The accuracy of intraoperative blood transfusions based on SpHb was analysed using Error Grid Analysis. Paired measurements of SpHb and LabHb were compared using Bland–Altman plot analysis. Results: There were 66 paired data points for blood transfusion from fifty patients with a correlation of 73% (P < 0.001) between SpHb and LabHb. In the Bland–Altman analysis, the bias was − 0.313 g/dl with ~ 95% of values within the limits of agreement of 1.81 g/dl to −2.44 g/dl. In the Error Grid Analysis, most data points were in the least error zone (Zone A). Conclusion: The Radical-7® has the advantage of providing SpHb value continuously to take prompt decision regarding blood transfusion intraoperatively

KAP Study on Sexually Transmitted Infections/Reproductive Tract Infections (STIs/RTIs) among married women in rural Haryana

Context: About 490 million cases of curable Reproductive Tract Infections (RTI) occur throughout the world, of which 79 million cases occur in India annually. Sexually Transmitted Infections/Reproductive Tract Infections (STI/RTI) confers a huge economic burden on the individual and the health system. Complications of RTI/STI are many, ranging from chronic pain syndrome to infertility. Most of these complications can be prevented by early diagnosis and treatment. Aims: To assess knowledge, attitude and practices on STI/RTIs among married women aged 15-45 years in rural Haryana. Setting and Design: Cross-sectional study, conducted in selected villages under the primary health centre Mandi, Sonepat, Haryana. Subjects and Methods: Systematic sampling was used to cover 10 villages. In each village, every tenth house was sampled, taking first house from the center of the village. Face-to-face interview was conducted using pretested questionnaire. Statistical Analysis Used: Descriptive statistics and results were described in percentages. Results: A total of 344 women were interviewed. About 44% women had never heard of STI/RTI. The prevalence of self-reported symptoms of STI/RTI was very high (60%). Only 40% of them opted for treatment and most common cause for not opting for treatment was that they considered it as a minor problem. Advice for use of condom during the treatment was received by only 20% of patients and only 26.5% of their husbands also received treatment. Conclusions: Overall knowledge, attitude and practices relating to STI/RTI among married women in rural Haryana was poor. The prevalence of self-reported STI/RTI was found to be high and treatment seeking behavior was poor

Soluble PD1 levels are increased with disease activity in paediatric onset autoimmune hepatitis and inflammatory bowel disease

Introduction: Immune mediated liver diseases entail a broad category which are associated with increased morbidity and mortality amongst the paediatric population. Programmed Death 1 (PD1) is an inhibitory receptor mainly expressed by T cells, and when activated shed into plasma as soluble PD1(sPD1). The AIM of this study was to evaluate sPD1 levels in plasma of paediatric patients with Autoimmune Hepatitis (AIH), Primary Sclerosing Cholangitis (PSC), AIH and PSC overlap, Inflammatory Bowel Disease (IBD) alone, and concurrent PSC/IBD and AIH/IBD in order to identify a biomarker to response or predict relapse verses remission. Methods: Plasma samples were collected from 41 paediatric patients. AIH patients were further categorized into active, incomplete responders and responders, based on response to standard therapy. sPD1 levels were measured and compared between PSC, PSC/AIH, IBD alone, PSC/IBD and AIH/IBD patients and between active AIH, incomplete responders and responders. Flow cytometry was performed to further analyze CD45RA+, CD3CD4, CD8, CCR7, CXCR3, CD38 and PD1. Results: In the AIH group, those with active disease demonstrated a significantly higher sPD1 levels in comparison to responders (*p > .001). However, the incomplete responders didn’t show a reduction in sPD1 in comparison to active AIH and patients with IBD alone. Interestingly, patients with PSC showed significantly lower level of sPD1 compared to active AIH (*p < .002), whereas, patients with PSC in conjunction with AIH (*p < .006) or IBD (*p < .02) demonstrated a significant increase in sPD1. In addition, we have observed increased levels of circulating CD4 and CD8 bound PD1 in active AIH but not in PSC or responders suggesting T cells activation. CD4+ PD1 double positive cells demonstrated increased expression of CXCR3. Thus, suggesting the activation of PD1 + T cells is mediating through CXCR3 in Autoimmune hepatitis. Conclusions: Our study demonstrates that sPD1 levels correlate with active disease state of AIH and IBD. sPD1 levels did not correlate with PSC. However, PSC in conjunction with AIH or IBD showed higher levels of sPD1. This suggests that T cell activation plays a critical role in active AIH and IBD but not in PSC. Soluble PDI levels could be used as a clinical biomarker to assess response in patients with AIH and for prospectively monitoring PSC patients for development of IBD or AIH

Factors associated with improved patient and graft survival beyond 1 year in pediatric liver transplantation

With advances in surgical techniques, medical management, and more equitable allocation systems, children who receive a liver transplantation (LT) today can expect remarkable outcomes early after LT. However, beyond 1 year after transplant, attrition rates have not improved. We reviewed two separate eras (Era 1: January 1995-June 2004 vs. Era 2: July 2004-March 2018) of the Society of Pediatric Liver Transplant registry to explore the evolution and associated factors contributing to late graft loss (LGL) and late mortality (LM). The fraction of long-term pediatric LT recipients surviving after 1 year with their first graft significantly improved (81.5% in Era 1 vs. 85.7% in Era 2; p < 0.0001). This improvement occurred despite significant changes in patient selection toward higher risk populations (p < 0.001) and without notable improvement in perioperative complications such as hepatic artery thrombosis (p = 0.24) and early posttransplant reoperation (p = 0.94) that have historically contributed to poor late-allograft outcomes. Improved outcomes were associated with changes in patient characteristics and perioperative practices, which subsequently impacted both early post-LT complications as well as other sequalae known to contribute to adverse events in long-term pediatric LT recipients. In conclusion, despite significant changes in patient selection toward higher risk populations, and without notable improvement in several perioperative complications known to contribute to poor late-allograft outcomes, significant improvements in LGL and a trend toward improvement in LM was seen in a more contemporary cohort of children receiving an LT