Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) affects 20-40% of the general population. Despite significant disease burden and mortality associated with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), there is currently no approved medication for NASH. Farnesoid X receptor agonists have been investigated as candidates for the treatment of NASH. Obeticholic acid, approved for the treatment of primary biliary cholangitis, has gained significant attention after showing promising results in patients with NASH and fibrosis. Three trials investigating the effect of obeticholic acid in patients with NASH have been completed and the preliminary results of an ongoing one have also been made public. Generally, treatment with obeticholic acid improved hepatic histology, including inflammation and fibrosis, the latter being the main histological predictor of advanced disease. Nonetheless, there were adverse effects, the most common being pruritus and unfavorable changes in the lipid profile. Pruritus led to discontinuation of treatment in some patients. Obeticholic acid, however, is not the only farnesoid X receptor agonist currently investigated for the treatment of NASH. Another farnesoid X receptor agonist, cilofexor, in combination with firsocostat, an acetyl-CoA carboxylase inhibitor, improved hepatic steatosis, liver stiffness, liver function tests and serum fibrosis markers, without causing pruritus after 12 weeks of treatment. In conclusion, current evidence regarding the effect of farnesoid X receptor agonists on hepatic histology in patients with NASH is promising, but several safety issues need further evaluation.

Obese Children with Metabolic Syndrome Have 3 Times Higher Risk to Have Nonalcoholic Fatty Liver Disease Compared with Those without Metabolic Syndrome.

BACKGROUND: The aim of this study was to investigate the relationship between metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in obese children. One hundred and twenty-five subjects aged 11-12 years old participated in the study. METHODS: Anthropometric and biochemical indices were measured, including lipid and liver profile, blood glucose, serum insulin, and liver ultrasound. RESULTS: Forty-four children (58.6%) were found to have MS. Insulin resistance was present in 78 (62.4%) children. Patients with MS were more likely to have NAFLD (P < 0.001). Children with NAFLD had significantly higher body mass index, waist circumference, triglycerides, fasting insulin, and lower high-density lipoprotein compared to patients with normal livers (P < 0.001). Insulin resistance was significantly higher in children with NAFLD (P < 0.001). Obese children presenting with MS were 3.01 (2.87-3.57, P < 0.002) times more likely to develop NAFLD compared to those without metabolic syndrome after adjustment of cofounders. CONCLUSIONS: Obese children with MS have a higher risk of developing NAFLD. Weight management and early prevention should be the first line of treatment to prevent any possible health issues later on.

Multifocal Epithelioid Hemangioendothelioma of the Foot and Ankle Developing a Postoperative Infection-Long-term Outcome: A Case Report.

A case of rare epithelioid hemangioendothelioma with multiple foot and ankle lytic lesions in a 41-year-old male is reported. The patient presented to our hospital after having received treatment elsewhere and developing a local postoperative infection. After thorough investigations and establishing the diagnosis, we initially treated the local infection and highlighted the potential risk of malignancy. Finally, respecting the patient's wishes, he was treated with consideration mostly of the pending foot and ankle fractures rather than the risk of malignancy. At 9.5 years postoperatively, the patient was clinically well and asymptomatic, without clinical, laboratory, or radiologic signs of malignancy, and the previous infection might have even played a remote role in that outcome. A review of the published data regarding the treatment of this unpredictable neoplasm is also presented.

Associations of Apolipoprotein A, High-Sensitivity C-Reactive Protein and Fasting Plasma Insulin in Obese Children With and Without Family History of Cardiovascular Disease.

BACKGROUND: The worldwide prevalence of childhood obesity has increased from 4.2% to 6.7% during the last two decades. Pediatric obesity is a major health problem, which is dramatically increasing in Greece. A variety of inflammatory variables have been also found to associate with cardiometabolic (CV) risk in obese children. The purpose of this study was to identify and examine the effects of possible CV risk factors in obese and non-obese children with and without family history (FH) of cardiovascular disease (CVD). METHODS: Sixty-eight (68) healthy children and adolescents aged 7 - 13 years participated in the study. Anthropometrical and biochemical indexes were obtained from all children as well as FH of CVD. RESULTS: Systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hsCRP), fasting plasma insulin (FPI) and homeostasis model assessment of insulin resistance (HOMA-IR) levels were found statistically significantly higher in the obese group compared to the non-obese one. High-density lipoprotein (HDL) levels were observed to be statistically significantly lower in the obese children compared to their normal peers. CONCLUSIONS: Apolipoprotein A, hsCRP and FPI levels were significantly higher in the obese children with FH of CVD compared to the ones without FH of CVD. TC and SBP were found to be independently associated with obesity (odds ratio (OR): 1.965, 95% confidence interval (CI): 1.935 - 2.97, P < 0.031 and OR: 1.045, 95% CI: 1.016 - 1.074, P < 0.002, respectively).

Clitoromegaly as first presentation of a neurocutaneous syndrome in a 3-year-old girl.

A rare cause of clitoral hypertrophy in a child is neurofibromatosis type 1 (NF1). Although evaluation, including karyotype and hormonal studies, is necessary to exclude ambiguous genitalia, the diagnosis of neurofibromatosis as a possible cause of clitoromegaly may help avoid lengthy and sometimes invasive interventions.

Multifocal epithelioid hemangioendothelioma of the foot and ankle: a case report.

We report on a 41-year-old man with multiple epithelioid hemangioendothelioma of the left foot and ankle. The patient was treated with curettage and fixation with 2 separate plates, but later developed local infection. Owing to the potential for malignancy, below-knee amputation was suggested, but the patient declined and was treated symptomatically with close monitoring. The patient underwent removal of the plates, excision of the distal fourth of the fibula, intralesional curettage of all lesions, and fusion of the ankle and subtalar joints with a retrograde intramedullary nail. After 5.5 years, the patient had recovered well and had no evidence of malignancy. The tumour was considered definitively benign.

Possible Health Implications and Low Vitamin D Status during Childhood and Adolescence: An Updated Mini Review.

Vitamin D deficiency is common in the developing countries and exists in both childhood and adult life. The great importance of Vitamin D is the moderation of calcium (Ca) and phosphorus (P) homeostasis as well as the absorption of Ca. While insufficiency of vitamin D is a significant contributing factor to risk of rickets in childhood, it is possible that a more marginal deficiency of vitamin D during life span contribute to osteoporosis as well as potentially to the development and various other chronic diseases such as cardiovascular disease, cancer and diabetes. This paper reviews the metabolism, epidemiology, and treatment of vitamin D and calcium insufficiency as well as its relation to various diseases during childhood and adolescence.

Peripheral neuropathy is an early complication of type 2 diabetes in adolescence.

OBJECTIVE: To screen for microvascular complications in adolescents with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: Seven adolescents with T2DM were assessed for early secondary complications. Median duration of diabetes was 1.8 (0.8-3.0) yr. All were assessed as follows: blood pressure, ophthalmologic examination for diabetic retinopathy, renal function, full blood count and vitamin B12 levels (to exclude B12 malabsorption - a side effect of metformin), random urine for microalbuminuria, an electrocardiogram (ECG) rhythm strip and podiatry performed by an experienced podiatrist. Testing for peripheral neuropathy included foot pulse palpation, tendo-Achilles reflexes, plantar callus test, large nerve fibre function (vibration and threshold for light touch/pressure) assessed by a 128-Hz tuning fork, and by the standard 10-g Semmes-Weinstein monofilament test, and small nerve fibre function (pain) assessed by pinprick neurotip. RESULTS: Four adolescents had evidence of peripheral neuropathy on clinical examination, with abnormal large and small nerve fibre function. Six had plantar callus present, and four had weak but palpable posterior tibial pulses. All had normal tendo-Achilles reflex and normal response to vibration. None had diabetic retinopathy or hypertension. Renal function, full blood count (FBC), B12 levels and ECGs were normal. None of 120 adolescents with type 1 diabetes mellitus (T1DM) assessed by the same podiatrist had any signs of peripheral neuropathy. CONCLUSIONS: Unlike T1DM, peripheral neuropathy can be present soon after diagnosis in those with T2DM. Children with T2DM need surveillance for complications from the time of diagnosis.

Discitis in toddlers: a case series and review.

UNLABELLED: Toddlers commonly present to medical services with non-specific symptoms. The presence of refusal to walk and nocturnal waking with crying should alert clinicians to the possibility of discitis. CONCLUSION: Features that may alert clinicians to the diagnosis of discitis in young children are reviewed.

Animal and human bites: evaluation and management.

Animal bites and to a lesser extent human bites are common trauma cases in accident and emergency units and their incidence is rising. Bite wounds are often deeper than they appear to be and they are potentially contaminated with uncommon microorganisms. They need careful assessment, thorough debridement and preferably delayed primary closure. Tetanus cover and, although controversial, prophylactic antibiotics should be considered after individual assessment of each case, as the golden first steps for their management.