High fat in blood and body and increased risk of clinically diagnosed non-alcoholic fatty liver disease in 105,981 individuals.

BACKGROUND AND AIMS: High caloric diets rich in fat and carbohydrates lead to increased fat accumulation in adipose tissue and blood. This may lead to increased risk of non-alcoholic fatty liver disease. We hypothesized that baseline high nonfasting plasma triglycerides, body mass index (BMI), and waist circumference, individually and combined, associate with increased risk of clinically diagnosed non-alcoholic fatty liver disease during follow-up. METHODS: Cohort of 105,981 white Danish individuals recruited in 2003-2015 with end of follow-up on December 13th, 2018. Mean follow-up was 9.2 years during which time 418 were clinically diagnosed at hospitals with non-alcoholic fatty liver disease. RESULTS: Risk of clinically diagnosed non-alcoholic fatty liver disease increased with higher plasma triglycerides, higher BMI, and with higher waist circumference, continuously and stepwise using multivariable adjusted hazard ratios and cumulative incidences. Combining clinical categories of plasma triglycerides with BMI or waist circumference categories, illustrated an almost additive risk with increasing categories. Compared with plasma triglycerides of <1 mmol/L and BMI <25 kg/m2, the multivariable adjusted hazard ratio was 5.2(95% confidence interval: 1.3-21.6) for individuals with both plasma triglycerides of ≥5 mmol/L and BMI ≥35 kg/m2. The corresponding hazard ratio for individuals with plasma triglycerides ≥5 mmol/L and waist circumference was >88 cm for women and >102 cm for men was 4.8(2.3-9.7). Triglyceride results were more pronounced in women versus men. CONCLUSIONS: High fat in blood and body measured by plasma triglycerides, BMI, and waist circumference, individually and especially combined, are associated with up to a 5-fold increased risk of clinically diagnosed non-alcoholic fatty liver disease.

[Appendicitis in late pregnancy].

Appendicitis in pregnancy is correlated with high morbidity especially for the child. However, the diagnosis is difficult to determine due to subtle signs. This is a case report of a pregnant woman who despite being past due date and having progressive abdominal pain was sent home twice before arriving by ambulance severely affected by a perforated appendix. Abdominal pain and urine leukocytosis were the only early indicators. Foetal asphyxia led to caesarian section disclosing the diagnosis. When pregnant women without signs of ongoing birth have emerging abdominal pains, appendicitis should be considered.

Pharmacokinetics of ingenol mebutate gel under maximum use conditions in large treatment areas.

PURPOSE: Actinic keratoses (AKs) exist on a continuum with squamous cell carcinoma and can occur as sub-clinical and clinically visible lesions in cancerized fields on sun-damaged skin. Ingenol mebutate effectively treats AKs on areas up to 25 cm2, but actinic keratosis can affect larger areas of skin. This trial evaluated systemic exposure and safety of ingenol mebutate gel on larger areas of skin under maximum use conditions. METHODS: Phase I, multicenter, open-label, uncontrolled, non-randomized trial. Patients received ingenol mebutate gel for three consecutive days on approximately 250 cm2 of sun-damaged skin on the full face (0.027%), the scalp (0.027%), or arm (0.06%). RESULTS: Of 61 patients, 10 (face =8; arm =2) had ingenol mebutate in whole blood at subnanomolar levels (0.235-0.462 nM). The assayed metabolites were below the lower limit of quantification. Local skin responses increased during Days 1-4 and declined thereafter, approaching baseline by Day 16. Most adverse events were pain/pruritus of mild or moderate intensity. CONCLUSIONS: Subnanomolar systemic exposure to ingenol mebutate was measured after application of the gel to approximately 250 cm2 on the full face, scalp, or arm under maximum use conditions. No clinically relevant systemic adverse reactions were observed, and local skin responses were manageable.