Impact of genetic and non-genetic factors on phenotypic diversity in NBAS-associated disease.

Biallelic pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause a pleiotropic multisystem disorder. Three clinical subgroups have been defined correlating with the localisation of pathogenic variants in the NBAS gene: variants affecting the C-terminal region of NBAS result in SOPH syndrome (short stature, optic atrophy, Pelger-Huët anomaly), variants affecting the Sec 39 domain are associated with infantile liver failure syndrome type 2 (ILFS2) and variants affecting the ß-propeller domain give rise to a combined phenotype. However, there is still unexplained phenotypic diversity across the three subgroups, challenging the current concept of genotype-phenotype correlations in NBAS-associated disease. Therefore, besides examining the genetic influence, we aim to elucidate the potential impact of pre-symptomatic diagnosis, emergency management and other modifying variables on the clinical phenotype. We investigated genotype-phenotype correlations in individuals sharing the same genotypes (n = 30 individuals), and in those sharing the same missense variants with a loss-of-function variant in trans (n = 38 individuals). Effects of a pre-symptomatic diagnosis and emergency management on the severity of acute liver failure (ALF) episodes also were analysed, comparing liver function tests (ALAT, ASAT, INR) and mortality. A strong genotype-phenotype correlation was demonstrated in individuals sharing the same genotype; this was especially true for the ILFS2 subgroup. Genotype-phenotype correlation in patients sharing only one missense variant was still high, though at a lower level. Pre-symptomatic diagnosis in combination with an emergency management protocol leads to a trend of reduced severity of ALF. High genetic impact on clinical phenotype in NBAS-associated disease facilitates monitoring and management of affected patients sharing the same genotype. Pre-symptomatic diagnosis and an emergency management protocol do not prevent ALF but may reduce its clinical severity.

Swallowing-related quality of life in children with oesophageal atresia: a national cohort study.

Swallowing and feeding disorders are a major concern for children with oesophageal atresia (OA) after primary or staged OA repair. Primary OA repair is associated with higher rates of short-term complications in preterm infants with very low birth weight (VLBW) or extreme low birth weight (ELBW). On the other hand, primary repair may have the benefit of early commencement of oral feedings. We hypothesize that also in the medium-term, swallowing-related quality of life is better after primary oesophageal repair. We conducted a prospective cross-sectional study on swallowing quality in a national cohort of former VLBW and ELBW children with OA, using the structured paediatric swallowing quality of life (pedSWAL-QOL) questionnaire. Results were correlated with surgical approach and baseline clinical data. Principal component analysis of pedSWAL-QOL domains was performed. In total, 44 complete data sets of 78 children were available. The mean age of children was 8.5 years (SD = 7.4), and 23 children (52%) had primary OA repair. The overall median pedSWAL-QOL score was 2 (IQR = 0-3), representing a high swallowing-related quality of life, independent of surgical technique (p = 0.086). Children with a history of intracranial haemorrhage (ICH) (p = 0.002) and those with VACTERL association (p = 0.008) had significantly decreased enjoyment with eating. In addition, children with VACTERL association had problems to find suitable foods (p = 0.04). CONCLUSION: In this national cohort of VLBW and ELBW preterm-born children with OA, swallowing-related quality of life is good, mostly independent of initial surgery. Children with OA and ICH or VACTERL association may require more intense support with feeding. WHAT IS KNOWN: • Dysphagia, resembling feeding and swallowing disorders, is common in children and adults with repaired oesophageal atresia. Nevertheless, dysphagia in children with oesophageal atresia decreases with age. • Parents of younger children suffer from increased anxiety and fear regarding eating and swallowing abilities of their children. WHAT IS NEW: • Swallowing-related quality of life in former preterm children with oesophageal atresia is good, independent of initial surgical approach (primary vs. staged repair), even in very low birth weight or extreme low birth weight infants. • Children suffering from VACTERL association or intracranial haemorrhage show decreased enjoyment with eating.

Abatacept for treatment-refractory pediatric CTLA4-haploinsufficiency.

CTLA4-haploinsufficiency is a complex disease of immune dysregulation presenting with a broad spectrum of clinical manifestations. CTLA4-Fc fusion proteins such as abatacept have been described to alleviate immune dysregulation in several adult cases of CTLA4-haploinsufficiency. However, until now only few cases of pediatric CTLA4-haploinsufficiency treated with abatacept have been described. Here we present two pediatric cases of severe CTLA4-haploinsufficiency refractory to conventional immunosuppressive therapies that responded rapidly to treatment with abatacept. No side effects were observed during a follow-up period of 7-15 months. While one patient has successfully undergone HSCT the second patient continues to receive abatacept. Our cases demonstrate safe medium-term use of abatacept in the pediatric population.

NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency.

PURPOSE: Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. METHODS: Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. RESULTS: Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell-intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. CONCLUSION: In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.

Sarcopenia in Children With End-Stage Liver Disease on the Transplant Waiting List.

Sarcopenia predicts morbidity and mortality in adults with end-stage liver disease (ESLD) and is determined by total psoas muscle area (tPMA) measurement from computed tomography (CT) imaging. Recently developed pediatric age- and sex-specific tPMA growth curves provide the opportunity to ascertain prevalence and impact of sarcopenia in children awaiting liver transplantation (LT). This retrospective single-center study evaluated sarcopenia in children between 1 and 16 years with ESLD and a clinically indicated abdominal CT less than 3 months before first isolated LT. Sarcopenia was defined as tPMA z score less than -2 measured at the intervertebral L4-5 level. Patient demographic, biochemical, and outcome data were recorded. tPMA was compared with other measures of nutritional status using univariate and multivariate logistic analyses. Outcome measures included 1-year morbidity events and mortality after LT. CT images from 25 (64% female) children with median age of 5.50 (interquartile range [IQR], 3.75-11.33) years were reviewed. Ten children (40%) had a tPMA z score less than -2. Sarcopenia was associated with lower z scores for weight (odds ratio [OR], 0.38; P = 0.02), height (OR, 0.32; P = 0.03), and nutritional support before LT (OR, 12.93; P = 0.01). Sarcopenic children had a longer duration of pediatric intensive care unit (PICU) stay (3.50 [IQR, 3.00-6.00] versus 2.00 [IQR, 2.00-3.50] days; P = 0.03). Sarcopenia was prevalent in 40% of children with ESLD awaiting LT, and lower tPMA z score was associated with deficient anthropometrics and need for nutritional support before LT. Post-LT PICU duration was increased in children with sarcopenia, reflecting adverse outcomes associated with muscle loss. Further studies are needed to elucidate the underlying mechanisms of sarcopenia in children with ESLD.

Sarcopenia is a prognostic outcome marker in children with high-risk hepatoblastoma.

BACKGROUND: Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children with HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome. PROCEDURE: Retrospective study of children (1-10 years) with hepatoblastoma treated at a large university children's hospital from 2009 to 2018. tPMA was measured as the sum of the right and left psoas muscle area (PMA) at intervertebral disc levels L3-4 and L4-5. z-Scores were calculated using age- and gender-specific reference values and were compared to anthropometric measurements, clinical variables, and outcomes. Sarcopenia was defined as a tPMA z-score below -2. RESULTS: Thirty-three children were included. Mean tPMA z-score was -2.18 ± 1.08, and 52% were sarcopenic. A poor correlation between tPMA and weight was seen (r = 0.35; confidence interval [CI] 0.01, 0.62; P = .045), and most children had weights within the normal range (mean z-score -0.55 ± 1.39). All children categorized as high risk with relapse (n = 5/12) were sarcopenic before surgery. Relapse was significantly higher in the high-risk sarcopenic group compared to the nonsarcopenic group (P = .008). The change in tPMA z-score 1-4 months after surgery did not improve in patients with relapse, but did improve in 75% of children without relapse. CONCLUSIONS: The majority of children with HB were sarcopenic prior to surgery. Especially in children with high-risk hepatoblastoma, sarcopenia is an additional risk factor for relapse. Large multicenter studies are needed to confirm these preliminary results.

Defining clinical subgroups and genotype-phenotype correlations in NBAS-associated disease across 110 patients.

PURPOSE: Pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause an autosomal recessive disorder with a wide range of symptoms affecting liver, skeletal system, and brain, among others. There is a continuously growing number of patients but a lack of systematic and quantitative analysis. METHODS: Individuals with biallelic variants in NBAS were recruited within an international, multicenter study, including novel and previously published patients. Clinical variables were analyzed with log-linear models and visualized by mosaic plots; facial profiles were investigated via DeepGestalt. The structure of the NBAS protein was predicted using computational methods. RESULTS: One hundred ten individuals from 97 families with biallelic pathogenic NBAS variants were identified, including 26 novel patients with 19 previously unreported variants, giving a total number of 86 variants. Protein modeling redefined the ß-propeller domain of NBAS. Based on the localization of missense variants and in-frame deletions, three clinical subgroups arise that differ significantly regarding main clinical features and are directly related to the affected region of the NBAS protein: ß-propeller (combined phenotype), Sec39 (infantile liver failure syndrome type 2/ILFS2), and C-terminal (short stature, optic atrophy, and Pelger-Huët anomaly/SOPH). CONCLUSION: We define clinical subgroups of NBAS-associated disease that can guide patient management and point to domain-specific functions of NBAS.

Diagnosis, Outcome, and Management of Chylous Ascites Following Pediatric Liver Transplantation.

Data on postoperative chylous ascites (CA) after pediatric liver transplantation (LT) are scarce. This retrospective study was conducted to identify the incidence, risk factors, management, and outcomes of postoperative CA in a large single-center pediatric LT cohort (2000-2016). The study cohort comprised 317 LTs (153 living donors and 164 deceased donors) in 310 recipients with a median age of 2.7 years. The incidence of CA was 5.4% (n = 17), diagnosed after a median time of 10 days after LT. Compared with chylomicron detection in peritoneal fluid (the gold standard), a triglyceride cutoff value of 187 mg/dL in peritoneal fluid showed insufficient sensitivity (31%) for CA diagnosis. In univariate logistic regression analyses, ascites before LT, younger age, and lower weight, height, and height-for-age z score at LT were associated with CA. Symptomatic management of CA included peritoneal drain (100%) and diuretics (76%). Therapeutic interventions included very low-fat or medium-chain triglyceride-rich diets (94%) and intravenous octreotide (6%), leading to CA resolution in all patients. CA was associated with prolonged hospital length of stay (LOS; 40 days in the CA group versus 24 days in the non-CA group; P = 0.001) but not with reduced patient or graft survival rates after a median follow-up time of 14 years. In conclusion, CA in the pediatric LT recipient is a relatively uncommon complication associated with increased hospital LOS and morbidity. Measurement of chylomicrons is recommended in patients with ascites that is more severe or persistent than expected. Dietary interventions are effective in most patients.

Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis.

Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet. After weaning, C57BL/6 mice ( n = 8-15/treatment) were fed ground flaxseed (7 g/100 g diet) with either HF (HF Flx) or RF (RF Flx) diets for 4 wk before infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids, and cecal short-chain fatty acids were compared over a 14-day infection period. The RF diet protected against C. rodentium-induced colitis, whereas the RF Flx diet increased pathogen burden, exacerbated gut inflammation, and promoted gut dysbiosis. When compared with the RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although an RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation. NEW & NOTEWORTHY Our results demonstrate a strong protective effect of a reduced-fat diet against intestinal inflammation, dysbiosis, and pathogen burden during Citrobacter rodentium-induced colitis. However, ground flaxseed supplementation in the setting of a reduced-fat diet exacerbated colitis despite higher levels of intestinal n-3 polyunsaturated fatty acids and cecal short-chain fatty acids.

Frailty in Children with Liver Disease: A Prospective Multicenter Study.

OBJECTIVE: To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool. STUDY DESIGN: We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10. RESULTS: The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P < .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10). CONCLUSIONS: A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease.

Sarcopenia in Children With End-Stage Liver Disease.

BACKGROUND: Sarcopenia, reflected by decreased psoas muscle surface area (PMSA), has been identified as a novel and independent predictor of wait-list mortality and outcomes in adult liver transplantation (LT). We hypothesized that children with end-stage liver disease (ESLD) would have smaller PMSA than healthy controls. METHODS: Computer tomography images of children (ages 0 to 18 years) listed for LT in 2015 and a control group comprised 2:1 age- and gender-matched healthy pediatric trauma victims were reviewed. PMSA was determined at 2 intervertebral disc (L3/4; L4/5) levels. A subset of images was reviewed by 2 radiologists to determine interrater correlation. RESULTS: A total of 23 children with ESLD were included, and the most prevalent diagnosis was biliary atresia (61%). On both lumbar levels, median PMSA was significantly smaller in ESLD subjects compared with the 46 healthy controls (L4/5; median total PMSA (tPMSA) 407 mm (interquartile range 339-537) versus controls 513 mm (interquartile range 437-672); P = 0.004), independent of participants' weight z scores (r = 0.01; P = 0.95). Excellent interrater correlation was seen (intraclass correlation 0.99). CONCLUSIONS: In this retrospective pilot study, PMSA was significantly lower in children with ESLD compared with healthy age- and gender-matched controls. Because this finding was independent of growth in ESLD subjects, PMSA may represent a novel objective nutritional biomarker in children with advanced liver disease.

Pulse wave velocity measurement as a marker of arterial stiffness in pediatric inflammatory bowel disease: a pilot study.

In adults with inflammatory bowel disease (IBD), the incidence of cardiovascular events is increased, leading to long-term morbidity. Arterial stiffness (AS) measured by pulse wave velocity (PWV) is a validated early precursor of cardiovascular disease (CVD), and measurement of PWV was shown to be a feasible test in children. The aim of this study was to assess AS in children with IBD. In this prospective study, we determined PWV between the carotid and femoral artery (PWVcf) in 25 children and adolescents with IBD (11 females, median age 14.1 years, median disease duration 2.8 years). The majority (68%) of the subjects were in clinical remission, and 48% received anti-tumor necrosis factor alpha (TNFα) treatment. AS was not increased in this cohort of children and adolescents with IBD, who did not have signs of cardiovascular disease, such as arterial hypertension. CONCLUSION: PWV seems to be normal in children with IBD in remission or with mild disease activity. Larger studies should assess its potential role as a valid and non-invasive follow-up marker in children with IBD, to avoid cardiovascular complications. What is Known : • Inflammatory bowel disease (IBD) is a risk factor of cardiovascular disease (CVD). • Pulse wave velocity (PWV) measurement is the current gold standard to assess arterial stiffness (AS), which is an early predictor of CVD. What is New: • This is the first study using PWV measurements to determine AS in children with IBD. • In children with IBD in remission or only mild disease activity AS is not increased.

Selective enrichment of commensal gut bacteria protects against Citrobacter rodentium-induced colitis.

The intestinal microbiota plays a key role in shaping the host immune system. Perturbation of gut microbial composition, termed dysbiosis, is associated with an increased susceptibility to intestinal pathogens and is a hallmark of a number of inflammatory, metabolic, and infectious diseases. The prospect of mining the commensal gut microbiota for bacterial strains that can impact immune function represents an attractive strategy to counteract dysbiosis and resulting disease. In this study, we show that selective enrichment of commensal gut lactobacilli protects against the murine pathogen Citrobacter rodentium, a well-characterized model of enteropathogenic and enterohemorrhagic Escherichia coli infection. The lactobacilli-enriched bacterial culture prevented the expansion of Gammaproteobacteria and Actinobacteria and was associated with improved indexes of epithelial barrier function (dextran flux), transmissible crypt hyperplasia, and tissue inflammatory cytokine levels. Moreover, cultivation of gut bacteria from Citrobacter rodentium-infected mice reveals the differential capacity of bacterial subsets to mobilize neutrophil oxidative burst and initiate the formation of weblike neutrophil extracellular traps. Our findings highlight the beneficial effects of a lactobacilli-enriched commensal gut microenvironment and, in the context of an intestinal barrier breach, the ability of neutrophils to immobilize both commensal and pathogenic bacteria.

Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis.

Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) relates to a group of rare, debilitating, liver disorders which typically present in early childhood, but have also been reported in adults. Without early detection and effective treatment, PFIC can result in end-stage liver disease. The aim of the paper was to put forward recommendations that promote standardisation of the management of PFIC in clinical practice. Methods: A committee of six specialists came together to discuss the challenges faced by physicians in the management of PFIC. The committee agreed on two key areas where expert guidance is required to optimise care: (1) how to diagnose and treat patients with a clinical presentation of PFIC in the absence of clear genetic test results/whilst awaiting results, and (2) how to monitor disease progression and response to treatment. A systematic literature review was undertaken to contextualise and inform the recommendations. Results: An algorithm was developed for the diagnosis and treatment of children with suspected PFIC. The algorithm recommends the use of licensed inhibitors of ileal bile acid transporters as the first-line treatment for patients with PFIC and suggests that genetic testing be used to confirm genotype whilst treatment is initiated in patients in whom PFIC is suspected. The authors recommend referring patients to an experienced centre, and ensuring that monitoring includes measurements of pruritus, serum bile acid levels, growth, and quality of life following diagnosis and during treatment. Conclusions: The algorithm presented within this paper offers guidance to optimise the management of paediatric PFIC. The authors hope that these recommendations will help to standardise the management of PFIC in the absence of clear clinical guidelines. Impact and implications: This opinion paper outlines a consistent approach to the contemporaneous diagnosis, monitoring, referral and management of children with progressive familial intrahepatic cholestasis. This should assist physicians given the recent developments in genetic diagnosis and the availability of effective drug therapy. This manuscript will also help to raise awareness of current developments and educate health planners on the place for new drug therapies in progressive familial intrahepatic cholestasis.

Erratum to "Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis" [JHEP Reports 6 (2024) 100949].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100949.].

Children with Localized Crohn's Disease Benefit from Early Ileocecal Resection and Perioperative Anti-Tumor Necrosis Factor Therapy.

INTRODUCTION: In pediatric Crohn's disease ileocecal resection is performed reluctantly as postoperative recurrence is frequent. Anti-tumor necrosis factor (TNF) therapy reduces postoperative recurrence rates but increases the risk for infections. MATERIALS AND METHODS: We retrospectively reviewed pediatric Crohn's disease patients who underwent ileocecal resection in our center. We compared disease activity and z-scores for height, weight, and body mass index of patients, who continuously received perioperative anti-TNF therapy (TNF + ), with those who did not (TNF-). RESULTS: Of 29 patients (48% females), 13 and 16 were grouped to TNF+ and TNF-, respectively. Patients' characteristics did not differ between groups, except a longer follow-up time in TNF-. We saw significant postoperative improvement but no normalization in z-scores for weight (1.78 vs. 0.77, p < 0.001), body mass index (1.08 vs. 0.22, p < 0.001), and height (0.88 vs. 0.66, p < 0.001). Disease activity improved significantly more in patients receiving anti-TNF therapy (moderate improvement in 83% vs. 31%, p = 0.02). Endoscopic recurrence was more frequent in patients without anti-TNF therapy (80% vs. 20%; p = 0.023), but endoscopic follow-up was incomplete. There was no increase of infections under perioperative anti-TNF therapy (1 patient each; p = 1.000). CONCLUSION: In patients with localized Crohn's disease an ileocecal resection leads to short-term postoperative improvement of disease activity, body mass index, weight, and growth. For relevant catch-up growth an earlier intervention is necessary. Continuous perioperative anti-TNF therapy had no increased risk of perioperative infections.

Outcome of Children with Transjugular Intrahepatic Portosystemic Shunt: A Meta-Analysis of Individual Patient Data.

PURPOSE: The purpose of the study was to investigate outcome after pediatric transjugular intrahepatic portosystemic shunt (TIPS) with respect to survival MATERIAL AND METHODS: After searching for studies on TIPS in children in Ovid, Medline, Embase, Scopus and Cochrane published between 2000 and 2022, individual patient data were retrieved from five retrospective cohorts. Overall survival (OS) and transplant-free survival (TFS) were calculated using Kaplan-Meier analysis and log-rank test and compared to the indication (ascites vs. variceal bleeding) as well as to the level of obstruction (pre-hepatic vs. hepatic vs. post-hepatic). Additionally, TIPS patency was analyzed. RESULTS: n = 135 pediatric patients were included in the final analysis. Indication for pediatric TIPS creation was heterogeneous among the included studies. TIPS patency decreased from 6 to 24 months, subsequent pediatric liver transplantation was performed in 22/135 (16.3%) of cases. The presence of ascites was related with poorer TFS (HR 2.3, p = 0.023), while variceal bleeding was not associated with impaired survival. Analysis of the level of obstruction (pre-hepatic, hepatic and post-hepatic) failed to prove significantly reduced OS for post-hepatic obstruction (HR 3.2, p = 0.092) and TFS (HR 1.3, p = 0.057). There was no difference in OS and TFS according to age at time of TIPS placement. CONCLUSIONS: The presence of ascites associates with impaired survival after TIPS in children, with no differences in survival according to the age of the child. Interventional shunt procedures can be considered feasible for all ages. LEVEL OF EVIDENCE: Level 2a.

Sarcopenia in Children with Solid Organ Tumors: An Instrumental Era.

Sarcopenia has recently been studied in both adults and children and was found to be a prognostic marker for adverse outcome in a variety of patient groups. Our research showed that sarcopenia is a relevant marker in predicting outcome in children with solid organ tumors, such as hepatoblastoma and neuroblastoma. This was especially true in very ill, high-risk groups. Children with cancer have a higher likelihood of ongoing loss of skeletal muscle mass due to a mismatch in energy intake and expenditure. Additionally, the effects of cancer therapy, hormonal alterations, chronic inflammation, multi-organ dysfunction, and a hypermetabolic state all contribute to a loss of skeletal muscle mass. Sarcopenia seems to be able to pinpoint this waste to a high degree in a new and objective way, making it an additional tool in predicting and improving outcome in children. This article focuses on the current state of sarcopenia in children with solid organ tumors. It details the pathophysiological mechanisms behind sarcopenia, highlighting the technical features of the available methods for measuring muscle mass, strength, and function, including artificial intelligence (AI)-based techniques. It also reviews the latest research on sarcopenia in children, focusing on children with solid organ tumors.

Severe consumptive hypothyroidism in hepatic hemangioendothelioma.

OBJECTIVES: Consumptive hypothyroidism may occur in hepatic hemangioendothelioma. The altered expression of deiodinases inactivates peripheral thyroid hormones. As a result, serum levels of free triiodothyronine and free thyroxine are reduced to varying degrees. There are no established recommendations for the dosage of sirolimus for this particular indication. We describe for the first time the course of treatment with low-dose sirolimus. CASE PRESENTATION: We present a 5-week-old infant with hepatic hemangioendothelioma and severe consumptive hypothyroidism. Due to hepatic infiltration he showed signs of right heart strain. Therapy of hemangioendothelioma was initiated with propranolol and, in the absence of response, methylprednisolone was added. Treatment was continued with low-dose sirolimus (due to side effects) and propranolol. Hypothyroidism was managed with levothyroxine and liothyronine. CONCLUSIONS: Consumptive hypothyroidism due to cutaneous hemangioma and hepatic hemangioendothelioma can be managed with propranolol and low-dose sirolimus. Treatment of severe hypothyroidism may require a combinational therapy by substitution of both T3 and T4.