Hydroa vacciniforme lymphoproliferative disorder (HVLPD) is a rare disease related to Epstein-Barr virus (EBV), mainly in children, and is an EBV-associated cutaneous T and natural killer (NK) cell lymphoproliferative disorder. The disorder in some patients may progress to EBV-associated systemic T or NK-cell lymphoma. To summarize the characteristics of HVLPD in Chinese paediatric patients and to examine the risk factors indicating poor prognosis. We performed a retrospective analysis of patients with HVLPD from the Department of Dermatology, Beijing Children\'s Hospital. Based on diagnosis, medical history, examination results, and immunophenotype, we analysed HVLPD in 42 paediatric cases in order to examine the clinical features, prognoses, and risk factors. Forty-two paediatric patients were enrolled, with a median onset age of five years. All patients presented with papulovesicular lesions, and 32 systemic HVLPD (sHVLPD) patients had systemic symptoms, including fever, lymphadenopathy, hepatomegaly, splenomegaly, and liver dysfunction. Of the sHVLPD cases, 13 also had severe mosquito bite allergy (SMBA). Twenty-five cases were T-type, and nine were CD56+-dominant type. Follow-up data showed that 12 patients had complete remission, and three patients died. SMBA is a risk factor for disease progression in patients with HVLPD, and the pathological CD56+-dominant phenotype is associated with poor prognosis.

UNASSIGNED: Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with β-thalassemia major (β-TM) after hematopoietic stem cell transplantation (HSCT).
UNASSIGNED: A model to predict the risk of SFPR in β-TM patients after HSCT was developed.
UNASSIGNED: A retrospective study was used to develop the prediction model.
UNASSIGNED: The clinical data for 218 β-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model.
UNASSIGNED: The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%.
UNASSIGNED: We constructed a nomogram model to predict the risk of SFPR in patients with β-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

Although Ethiopia has more than 78% of leukemia cases and a significant burden of the disease, the survival of leukemia patients in the country is poorly recognized. The purpose of this study was to assess the survival and predictors of acute leukemia patients.
A 5-year retrospective cohort study was conducted including all acute Leukemia patients who visited Tikur Anbessa Specialized Hospital between January 2015 and December 2019. Data were retrieved from patient\'s medical records between March and April 2020. Using SPSS version 25, the Kaplan-Meier curve and Cox regression models were employed to analyze the data.
A total of 119 patients with acute leukemia were retrospectively evaluated for 60 months, having 196 person-years of risk. About 46 deaths (38.7%) were recorded over the follow-up period, giving a mortality incidence rate of 23.5 (95% CL:18-52) per 100 person-years. The median survival time was 35 months (95% CI, 28.3-41.7). At 60 months of follow-up, the predicted overall survival rate after diagnosis for acute leukemia was 21%. The adjusted hazard ratio for acute leukemia subtypes (aHR:4.9, 95% CI:2.3-10.4), history of relapse (aHR:3.9, 95% CI:1.0-7.9), participant age (aHR:1.25, 95% CI:1-1.75), hepatomegaly (aHR:2.7, 95% CI:1.36-5.36), and splenomegaly (aHR:2.29, 95% CI:1.2-4.4).
The 5-year overall survival rate was found to be 21%. The finding was remarkably lower than other published reports. Survival among acute leukemia patients was significantly associated with older age, history of relapse, hepatomegaly, splenomegaly, as well as certain subtypes. Therefore, improving early detection and initiation of treatment for all acute leukemia patients is necessary in order to improve patient\'s survival status.

BACKGROUND: High dose unilobar radioembolization (also termed \'radiation lobectomy\')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant.
METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank.
CONCLUSIONS: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice.
BACKGROUND: Netherlands Trial Register NL8902 , registered on 2020-09-15.

Educational attainment is an essential socio-economic indicator with broad implications for lifestyle behaviour and metabolic health. We aimed to investigate the causal effect of education on chronic liver diseases and the potential mediating pathways.
We applied univariable Mendelian randomization (MR) to assess the causal associations between educational attainment and non-alcoholic fatty liver disease (NAFLD) (cases/controls: 1578/307 576 in FinnGen; 1664/400 055 in UK Biobank), viral hepatitis (1772/307 382; 1215/403 316), hepatomegaly (199/222 728; 297/400 055), chronic hepatitis (699/301 014; 277/403 316), cirrhosis (1362/301 014; 114/400 055) and liver cancer (518/308 636; 344/393 372) using summary statistics of genome-wide association studies from the FinnGen Study and the UK Biobank, respectively. We used two-step MR to evaluate potential mediators and their mediation proportions in the association.
Meta-analysis of inverse variance weighted MR estimates from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was causally associated with decreased risks of NAFLD (OR: 0.48; 95%CI: 0.37-0.62), viral hepatitis (0.54; 0.42-0.69) and chronic hepatitis (0.50; 0.32-0.79), but not hepatomegaly, cirrhosis and liver cancer. Nine, two and three out of 34 modifiable factors were identified as causal mediators in the associations of education with NAFLD, viral hepatitis and chronic hepatitis, respectively, including six adiposity traits (mediation proportion: 16.5%-32.0%), major depression (16.9%), two glucose metabolism-related traits (2.2%-15.8%) and two lipids (9.9%-12.1%).
Our findings supported the causal protective effects of education on chronic liver diseases and outlined mediating pathways to inform prevention and intervention strategies to reduce the burden of liver diseases, especially for individuals with lower education.

OBJECTIVE: To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD) from a metabolomic perspective.
METHODS: We divided 60 rats into 4 groups of 15 rats each according to a random number table, namely the control group, the model group, the Bushen Huoxue Huazhuo Recipe group, and the penicillamine group, and subsequently replicated the WD copper-loaded rat model according to the literature method for a total of 12 weeks. From the 7th week onwards, each intervention group was given an equivalent dose of the corresponding drug, and the control and model groups were given an equal volume of saline gavage until the end of the model replication. We used 1H NMR metabolomics techniques combined with multivariate statistical methods to describe the changes in the striatal metabolic profile of nerve injury in Wilson\'s disease and to analyze the effect of different treatments on their biomarker interventions.
RESULTS: Nerve cell damage was evident in the WD copper-loaded rat model and could be reduced to varying degrees by different methods of intervention in the striatal nerve cells. The content of glycine, serine metabolism, and valine metabolism decreased in WD copper-loaded rat model; aspartate content increased after penicillamine intervention; glycolytic metabolism, valine metabolism, taurine metabolism, and tyrosine metabolism increased in the group of Bushen Huoxue Huazhuo Recipe.
CONCLUSIONS: Different intervention methods of Chinese and Western medicine affect aspartate, glycolysis, taurine, tyrosine, valine, and carbon metabolism in striatal tissues of WD copper-loaded rats, and can regulate the metabolism of small molecules, which in turn have certain repairing effects on nerve damage in WD copper-loaded rats.

To explore the clinical application of shear wave elastography (SWE) in evaluating the degree of liver fibrosis in children.
To explore the value of SWE in assessing liver fibrosis in children, the correlation between elastography values and the METAVIR grade of liver fibrosis in children with biliary system or liver diseases was studied. Children with significant liver enlargement were enrolled, and the fibrosis grade was analyzed to explore the value of SWE in assessing the degree of liver fibrosis in the presence of significant liver enlargement.
A total of 160 children with bile system or liver diseases were recruited. The areas under the receiver operating characteristic curve (AUROCs) for liver biopsy from stage F1 to F4 were 0.990, 0.923, 0.819, and 0.884. According to the degree of liver fibrosis at liver biopsy, there was a high correlation between the SWE value and the degree of liver fibrosis (correlation coefficient 0.74). There was no significant correlation between the Young\'s modulus value of the liver and the degree of liver fibrosis (correlation coefficient 0.16).
Supersonic SWE can generally accurately evaluate the degree of liver fibrosis in children with liver disease. However, When the liver is significantly enlarged, SWE can only evaluate liver stiffness based on Young\'s modulus values, and the degree of liver fibrosis must still be determined by pathologic biopsy.

Lysosomal acid lipase (LAL) is a lysosomal enzyme essential for the degradation of cholesteryl esters through the endocytic pathway. Deficiency of the LAL enzyme encoded by the LIPA gene leads to LAL deficiency (LAL-D) (OMIM 278000), one of the lysosomal storage disorders involving 50-60 genes. Among the two disease subtypes, the severe disease subtype of LAL-D is known as Wolman disease, with typical manifestations involving hepatomegaly, splenomegaly, vomiting, diarrhea, and hematopoietic abnormalities, such as anemia. In contrast, the mild disease subtype of this disorder is known as cholesteryl ester storage disease, with hypercholesterolemia, hypertriglyceridemia, and high-density lipoprotein disappearance. The prevalence of LAL-D is rare, but several treatment options, including enzyme replacement therapy, are available. Accordingly, a number of screening methodologies have been developed for this disorder. This review summarizes the current discussion on LAL-D, covering genetics, screening, and the tertiary structure of human LAL enzyme and preclinical study for the future development of a novel therapy.

To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder.
Patients with genetically confirmed NP-C (NPC1, n = 31; NPC2, n = 3) and liver involvement before age 6 months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining.
At initial evaluation (median age, 17 days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68+ storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6 months of life, including 3 from liver involvement. In patients who survived beyond age 6 months (median follow-up, 6.1 years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients.
Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.

To study clinical, hematological and molecular characteristics of patients of thalassemia and hemoglobinopathies and to correlate the molecular characteristics with clinical and hematological presentations. Material: This observational cross sectional study included 100 patients of age >12 years of all genders with chronic haemolytic anemia and history of multiple blood transfusion. Blood and radiological investigations were done. Clinical, hematological and molecular characteristics were studied. Observation and Clinical: Pallor was present in all cases and icterus in 32% cases. Total 48% of the patients had hepatomegaly and 98% had splenomegaly. Among genotypes, 15% cases had α-thalassemia, 62% had β thalassemia + δβ thalassemia, 7% had HbS hemoglobinopathy, and 16% had HbE hemoglobinopathy. Hematological: Hemoglobin showed significant association with molecular genotypes of thalassemia with lowest being present in β-thalassemia + δβ thalassemia and HbE.MCV showed significant association with molecular genotypes, with HbE having the lowest MCV of 65.5 fl. LDH levels showed a significant association with molecular genotype with highest being in HbS hemoglobinopathy. Molecular Characteristics: Common mutations in compound α-thalassemia were 3.7, 4.2 and 20.5 deletion. As for β-thalassemia and δβ thalassemia, 47 cases had heterozygous type and 15 cases had homozygous types. In β-thalassemia, the homozygous type showed IVS1- 5(G→C),CD 41/42(→CTT) and IVSII-654(G→T) while heterozygous type showed CD16(→G), CD 41/42(→CTT), IVS1-5(G→C), and IVSII-654(G→T) . In δβ thalassemia, the heterozygous type showed δβ inversion mutation.In HbS hemoglobinopathy, heterozygous type showed Codon 6(A→T) and compound heterozygous type showed IVS1- 5(G→C) and Codon 6(A→T). In HbE hemoglobinopathy,the homozygous type showed CD26(G→A) and compound heterozygous type showed IVS1-5(G→C) and IVSII 654(G→T). Conclusion: The common thalassemia genotypes observed in our study were α-thalassemia (15%), β thalassemia + δβ thalassemia, (62%) HbS hemoglobinopathy (7%), and HbE hemoglobinopathy (16%). The patients presented with pallor, icterus, hepatomegaly, and splenomegaly which were comparable among all molecular genotypes of thalassemia and hemoglobinopathies. α-thalassemia had compound α-thalassemia with common mutations being 3.7, 4.2 and 20.5 deletion. As for β-thalassemia and δβ thalassemia, 47 cases had heterozygous type and 15 cases had homozygous types. In δβ thalassemia, the heterozygous type showed δβ inversion mutation in 5 cases. MCH, Retic count, ferritin stores, and peripheral blood smear were similar in all molecular genotypes. Hemoglobin, MCV and LDH showed a significant association with molecular genotypes. Microcytic hypochromic anaemia was commonest among all.The findings of the present study show that the genotypes of thalassemia are characterized by diversity as well as significant genetic heterogeneities.