Isolated fetal ascites caused by Wolman disease.

Wolman disease is a rare autosomal-recessive disorder caused by reduced levels of lysosomal acid lipase. It occurs in infancy and is fatal in most cases before the age of 1 year. Affected infants show signs of lipid storage in most tissues, including hepatosplenomegaly, abdominal distension, vomiting, steatorrhea, failure to thrive, and adrenal calcifications. We present a case of isolated fetal ascites diagnosed at 32 weeks of gestation, with negative work-up for immune and non-immune hydrops fetalis and congenital infections and malformations. After delivery, the diagnosis of Wolman disease was established. Although rare, storage diseases such as Wolman disease should be considered in cases of isolated fetal ascites.     

Importance of reciprocal ST segment depression in leads V5 and V6 as an indicator of disease of the left anterior descending coronary artery in acute inferior wall myocardial infarction

The purpose of this study was to determine the coronary angiographic correlations (specifically disease of the left anterior descending coronary artery) of reciprocal ST segment depression appearing during inferior acute myocardial infarction. Forty six patients (41 men and five women; mean age 56 years) were allocated into two groups based on the extent of precordial ST segment depression: widespread (V1-V6) ST depression v localised (V1-V4) ST depression. Patients with no reciprocal ST depression or patients with ST depression in V1-V4 but with ST elevation in V5 and V6 (inferolateral acute myocardial infarction) were excluded. All patients were catheterised during hospital admission for infarction. Twenty four of the 28 patients with ST depression in V1-V6 had significant lesions in the left anterior descending coronary artery whereas 16 of the 18 patients with ST depression in V1-V4 had insignificant or no lesions in the left anterior descending artery. The sensitivity, specificity, and positive and negative predictive values of widespread ST depression in predicting disease in the left anterior descending coronary artery were 92%, 80%, and 86% and 89% respectively. In patients with inferior acute myocardial infarction and precordial ST depression, the extent of ST depression is of clinical significance. Widespread (V1-V6) ST depression suggests disease of the left anterior descending coronary artery, whereas localised ST depression (V1-V4) indicates its absence.     

Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice

Although genetic revolution of recent years has vastly expanded a list of genes implicated in epilepsies, complex architecture of epilepsy genetics is still largely unknown, consequently, universally accepted workflows for epilepsy genetic testing in a clinical practice are missing. We present a comprehensive NGS‐based diagnostic approach addressing both the clinical and genetic heterogeneity of disorders involving epilepsy or seizures. A bioinformatic panel of 862 epilepsy‐ or seizure‐associated genes was applied to Mendeliome (4813 genes) or whole‐exome sequencing data as a first stage, while the second stage included untargeted variant interpretation. Eighty‐six consecutive patients with epilepsy or seizures associated with neurodevelopmental disorders and/or congenital malformations were investigated. Of the 86 probands, 42 harbored pathogenic and likely pathogenic variants, giving a diagnostic yield of 49%. Two patients were diagnosed with pathogenic copy number variations and 2 had causative mitochondrial DNA variants. Eleven patients (13%) were diagnosed with diseases with specific treatments. Besides, genomic approach in diagnostics had multiple additional benefits due to mostly non‐specific, overlapping, not full‐blown phenotypes and abilities to diagnose novel and ultra rare epilepsy‐associated diseases. Likely pathogenic variants were identified in SOX5 gene, not previously associated with epilepsy, and UBA5, a recently associated with epilepsy gene.     

Conception after early IVF pregnancy loss: should we wait?

Research questionIs the interval length between an early pregnancy loss and the following treatment cycle a predictor for achieving clinical pregnancy among IVF patients?DesignThis retrospective cohort study of 257 women who reinitiated treatment after first-trimester IVF pregnancy loss was conducted at a tertiary, university-affiliated medical centre between 1 January 2014 to 1 January 2018. Women aged 18–40 years, with normal uterine cavity, who experienced first-trimester pregnancy loss at less than 14 weeks after IVF, were included. Miscarriages were classified as spontaneous, biochemical, medical or surgical.ResultsAmong 257 women, interval to subsequent IVF treatment was not associated with achieving pregnancy. Patients after biochemical pregnancy (72.7 ± 56.4, median 60 days) or spontaneous miscarriage (97.7 ± 93.1, median 66 days) had shorter intervals to next cycle, compared with medical (111.9 ± 103.2, median 65 days) or surgical (123.4 ± 111.1, median 84 days) (Kaplan–Meier, P = 0.03) miscarriages.Logistic regression analysis showed that the chance of subsequent pregnancy was affected by the number of embryos transferred (P = 0.009) and the type of miscarriage. Medical (P = 0.005) and surgical (P = 0.017) miscarriages were related to lower likelihood of pregnancy compared with biochemical pregnancy (reference group).When pregnancy was achieved in the first post-miscarriage cycle, the chance of live birth increased with shorter intervals (median 57.5 days), whereas second miscarriage was related to longer intervals (median 82.5 days) between miscarriage and subsequent IVF cycle (P = 0.03).ConclusionOn the basis of this cohort, IVF should not be postponed after pregnancy loss, as shorter intervals were associated with greater likelihood of live birth.     

A mutation in the peroxisome proliferator-activated receptor γ-binding site in the gene for the cytosolic form of phosphoenolpyruvate carboxykinase reduces adipose tissue size and fat content in mice

Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis in adipose tissue was assessed in mice by specifically eliminating the expression of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role in the pathway. To accomplish this, we mutated the binding site for the peroxisome proliferator-activated receptor gamma (PPAR gamma) called the peroxisome proliferator-activated receptor element (PPARE), in the 5' flanking region of the PEPCK-C gene in the mouse by homologous recombination. The mutation abolished expression of the gene in white adipose tissue and considerably reduced its expression in brown adipose tissue, whereas the level of PEPCK-C mRNA in liver and kidney remained normal. Epididymal white adipose tissue from these mice had a reduced triglyceride deposition, with 25% of the animals displaying lipodystrophy. There was also a greatly reduced level of lipid accumulation in brown adipose tissue. A strong correlation between the hepatic content of triglycerides and the size of the epididymal fat pad in PPARE(-/-) mice suggests that hepatic triglyceride synthesis predominantly utilizes free fatty acids derived from the adipose tissue. Unlike other models, PPARE(-/-) mice with lipodystrophy did not exhibit the lipodystrophy-associated features of diabetes and displayed only moderate hyperglycemia. These studies establish the importance of the PPARE site for PEPCK-C gene expression in adipose tissue and the role of PEPCK-C in the regulation of glyceroneogenesis, a pathway critical for maintaining the deposition of triglycerides in adipose tissue.     

Differing proliferative responses in proximal and distal colons of growing rats fed food eaten by adenoma patients

Animal dietary studies related to human colorectal carcinogenesis are usually based on AIN-76A diet, which is dissimilar to human food in source, preparation, and content. Our aim was to examine colonic epithelial proliferation in rats fed a diet based on the mean daily food intake of adenoma patients. Foods were prepared as reported by the adenoma patients and dehydrated; 64 Sprague-Dawley rats were fed either “human adenoma” or AIN-76A diet and every eight weeks, eight from each group were sacrificed. Both groups gained weight equally, had no colonic histological changes, but during the study showed progressive lengthening of colonic crypts (P<0.01) and decreased proliferation (P<0.05) in distal colons. Compared to controls, rats fed human adenoma diet had significantly longer crypts (P<0.01) and more labeled cells (P<0.05) at 32 weeks; overall they had increased proliferation (P<0.01), most significantly in the distal colon. Thus, food eaten by adenoma patients induced hyperproliferative changes in the rat colon during growth and maturity, especially the distal colon, as found in humans at risk for neoplasia.     

Continuous glucose monitoring for treatment adjustment in diabetic pregnancies--a pilot study.

AIMS: To examine the efficacy of a continuous glucose monitoring (CGM) system for treatment adjustment in patients with diabetic pregnancy treated with insulin. METHODS: The study sample consisted of eight women with diabetic pregnancy, six with pre-pregnancy Type 1 diabetes mellitus and two with gestational diabetes (GDM), all being treated with multiple daily insulin injections. Gestational age ranged from 24 to 32 weeks. Data derived from the Continuous Glucose Monitoring System (MiniMed) for 72 h were compared with fingerstick glucose measurements (six to eight times a day), and treatment was adjusted on the basis of the findings. Two to four weeks later, the patients were re-evaluated with CGM. RESULTS: In the first part of the study, an average of 744+/-33 glucose measurements was recorded for each patient with CGM. The mean total time of hyperglycaemia (glucose level >7.7 mmol/l) undetected by the fingerstick method was 152+/-33 min/day. Nocturnal hypoglycaemic events (glucose level <2.7 mmol/l) were recorded in seven patients. Based on the additional information obtained by continuous monitoring, the insulin regimen was changed in all patients. CGM re-evaluation after treatment adjustment showed a reduction in undetected hyperglycaemia to 89+/-17 min/day and in nocturnal hypoglycaemic events, which were recorded in only one patient. CONCLUSIONS: Continuous glucose monitoring may diagnose high blood glucose levels and nocturnal hypoglycaemic events that are unrecognized by intermittent blood glucose monitoring and could serve as a useful tool for the long-term management of diabetic pregnancies. A large prospective study is needed to determine the clinical implications of this new monitoring technique.