Pediatric nonalcoholic fatty liver disease.

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Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD

The impact of nonalcoholic fatty liver disease on renal function in children with overweight/obesity

The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction >= 5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m(2). Abnormal albuminuria was defined as urinary excretion of >= 30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16-5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease

Pediatric nonalcoholic fatty liver disease.

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Immune dysregulation in Kabuki syndrome. a case report of Evans syndrome and hypogammaglobulinemia

Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient’s case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Thyroid function in childhood obesity and metabolic comorbidity

Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Elevated TSH concentrations in association with normal or slightly elevated free T4 and/or free T3 levels have been consistently found in obese subjects, but the mechanisms underlying these thyroid hormonal changes are still unclear. Whether higher TSH in childhood obesity is adaptive, increasing metabolic rate in an attempt to reduce further weight gain, or indicates subclinical hypothyroidism or resistance and thereby contributes to lipid and/or glucose dysmetabolism, remains controversial. This review highlights current evidence on thyroid involvement in obese children and discusses the current controversy regarding the relationship between thyroid hormonal derangements and obesity-related metabolic changes (hypertension, dyslipidemia, hyperglycemia and insulin resistance, nonalcoholic fatty liver disease) in such population. Moreover, the possible mechanisms linking thyroid dysfunction and pediatric obesity are reviewed. Finally, the potential role of lifestyle intervention as well as of therapy with thyroid hormone in the treatment of thyroid abnormalities in childhood obesity is discussed. (C) 2011 Elsevier B.V. All rights reserved

Effective compression bandage for repair of a complicated radial artery pseudoaneurysm

We describe a 10-week-old hemophilic infant who developed a large-sized pseudoaneurysm of the radial artery after arterial puncture. Based on our previous experience, compression bandage was elected as first-line treatment. The clinical course was complicated by skin ulceration. However, compression bandage was continued, and complete thrombosis of the pseudoaneurysm occurred after 4 weeks of treatment, preserving arterial patency. Bedside clot evacuation and enzymatic debridement promoted rapid wound healing with negligible scar formation. Compression bandage is a safe and valuable measure for repair of radial artery pseudoaneurysm, even in patients with clotting disorders. Professionals are encouraged to consider the benefit of such an artery-sparing treatment option. © 2014 Elsevier Inc. All rights reserved