Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase and is characterized by external ophthalmoparesis, gastrointestinal dysmotility, leukoencephalopathy, and neuropathy. The availability of new therapeutic options (peritoneal dialysis, allogeneic stem cell transplantation, enzyme replacement) makes it necessary to diagnose the disease early, which is not always achieved due to the difficulty in recognizing this disorder, especially in case of atypical presentation. We describe three MNGIE patients with atypical onset of the disease. In the first patient the main symptoms were long-standing chronic fever, recurrent acute migrant arthritis, and gastrointestinal disorders mimicking autoimmune or inflammatory intestinal diseases; the second patient complained only of exercise intolerance and muscle cramps, and the third patient had a CIDP-like polyneuropathy. This study stresses the insidious heterogeneous clinical onset of some cases of MNGIE, expands the spectrum of the phenotype, and suggests considering MNGIE in the differential diagnosis of enteropathic arthritis, isolated exercise intolerance, and inflammatory polyneuropathies not responsive to the usual treatment. A better understanding of the clinical heterogeneity of MNGIE is necessary in order to diagnose atypical cases and promote early diagnosis, which is now absolutely necessary in view of the new available therapies.

Our data provide the first circumstantial evidence of an association between HMG-CoA reductase inhibitor treatment and reduced prevalence, number and volume of thyroid nodules. This finding may be explained by an antiproliferative and/or pro-apoptotic effect of long-term statin treatment on thyroid cells, in vivo.

The progression of mineral phase deposition in hypertrophic cartilage and periosteal bone matrix was studied in human metacarpals primary ossification centers before vascular invasion began. This study aimed to provide a morphologic/morphometric comparative analysis of the calcification process in cartilage and periosteal osteoid used as models of endochondral ossification. Thin, sequential sections from the same paraffin inclusions of metacarpal anlagen (gestational age between the 20th and 22nd weeks) were examined with light microscopy and scanning electron microscopy, either stained or heat-deproteinated. This process enabled the analysis of corresponding fields using the different methods. From the initial CaPO nucleation in cartilage matrix, calcification progressed increasing the size of focal, globular, randomly distributed deposits (size range 0.5-5 µm), followed by aggregation into polycyclic clusters and finally forming a dense, compact mass of calcified cartilage. At the same time, the early osteoid calcification was characterized by a fine granular pattern (size range 0.1-0.5 µm), which was soon compacted in the layer of the first periosteal lamella. Scanning electron microscopy of heat-deproteinated sections revealed a rod-like hydroxyapatite crystallite pattern, with only size differences between the early globular deposits of the two calcifying matrices. The morphology of the early calcium deposits was similar in both cartilage and osteoid, with variations in size and density only. However, integration of the reported data with the actual hypotheses of the mechanisms of Ca concentration suggested that ion transport was linked to the progression of the chondrocyte maturation cycle (with recall of H O from the matrix) in cartilage, while ions transport was an active process through the cell membrane in osteoid. Other considered factors were the collagen type specificity and the matrix fibrillar texture. Anat Rec, 301:571-580, 2018. © 2017 Wiley Periodicals, Inc.

A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.

In this in-hospital cohort, the use of lipid-lowering agents was mainly driven by patients' clinical history, most notably the presence of clinically overt manifestations of atherosclerosis. Increasing age seems to be associated with lower prescription rates. This might be indicative of cautious behavior towards a potentially toxic treatment regimen.