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We discuss the case of a rare and often unrecognized neurologic syndrome, called Acquired Hepatocerebral Degeneration (AHD), observed in patients with advanced liver disease and portosystemic shunts. The clinical manifestations can be very heterogeneous and in our case included a combination of cerebellar and extrapyramidal signs, arisen in a period of few days. Brain Magnetic Resonance Imaging (MRI) showed, in T1-weighted images, diffuse bilateral hyper intensities in basal ganglia and biemispheric brain and cerebellar cortices, resembling paramagnetic deposits. No other neurological impairments, like stroke, infection or neoplasia, were found. It was excluded an episode of acute hepatic encephalopathy. We also ruled out Wilsonian degeneration, iron overload and autoimmune encephalitis and we lastly found high manganese levels as the possible cause of the brain paramagnetic deposits. Even though either serum Mn determination or its accumulation in the brain are not specific for AHD, however the chronic and progressively worsening of the neurological manifestations advocated a degenerative condition, possibly AHD. We finally opted for the early restoration of liver function by OLT, and we observed complete clinical symptoms' resolution and partial MRI reversal after a follow up of 6 months. [ABSTRACT FROM AUTHOR]

Reports the case of cutaneous hypersensitivity to human insulin that was successfully treated with the human insulin analog aspart. Information on the insulin analog aspart; Details on the subject; Significance of the results of the skin prick tests.

Mutations in the transcription factors encoded by PHOX2B or LBX1 correlate with congenital central hypoventilation disorders. These conditions are typically characterized by pronounced hypoventilation, central apnea, and diminished chemoreflexes, particularly to abnormally high levels of arterial PCO 2 . The dysfunctional neurons causing these respiratory disorders are largely unknown. Here, we show that distinct, and previously undescribed, sets of medullary neurons coexpressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in congenital hypoventilation. By combining intersectional chemogenetics, intersectional labeling, lineage tracing, and conditional mutagenesis, we uncovered subgroups of dB2 neurons with key functions in (i) respiratory tidal volumes, (ii) the hypercarbic reflex, (iii) neonatal respiratory stability, and (iv) neonatal survival. These data provide functional evidence for the critical role of distinct medullary dB2 neurons in neonatal respiratory physiology. In summary, our work identifies distinct subgroups of dB2 neurons regulating breathing homeostasis, dysfunction of which causes respiratory phenotypes associated with congenital hypoventilation.

Background and Aims: Patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are at high risk of hepatic fibrosis. To prospectively evaluate changes in fibrosis in diabetic patients with NAFLD, predisposing factors and sodium glucose cotransporter 2 inhibitors (SGLT2i) influence., Methods: 237 T2DM outpatients (mean age 67 ± 9 years, 54% male) were enrolled and re-evaluated after 52 ± 10 months. At baseline and follow-up NAFLD and liver fibrosis (LSM) were detected by ultrasonography and Fibroscan®., Results: During follow-up an increase in LSM (6.0 ± 2.8 vs 5.8 ± 2.7 kPa, p = 0.02) and in the prescription of SGLT2i (20% vs 6%, p<0.001) was registered, despite stability of diabetic control. LSM worsened in 133(56%) subjects, 92 (39%) with worsening >10% from baseline. Patients with worsening versus non worsening of LSM had higher prevalence of increase in BMI during follow-up (45% vs 32%, p = 0.06) and lower SGLT2i prescription (15% vs 27%, p = 0.034). In multivariate analysis use of SGLT2-inhibitors at follow-up reduced the risk of LSM worsening (HR 0.34, 95% CI 0.13-0.88), even when considered>10% from baseline., Conclusions: A high prevalence of fibrosis progression was observed in diabetic subjects with NAFLD over a nearly 5-years follow up and SGLT2-inhibitors seem to reduce the risk of worsening of liver stiffness., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

We demonstrate in 351 diabetic patients with steatosis that NAFLD fibrosis score (NFS), a rapid and affordable score to diagnose hepatic fibrosis, identifies patients at higher risk of advanced fibrosis and vascular diabetic complications (especially peripheral neuropathy), pointing NFS as a first-line vascular and hepatic screening in diabetic patients., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely associated, and liver fibrosis has been related to macrovascular complications. We examined whether liver fibrosis, diagnosed by FibroScan ® , correlates with chronic vascular complications in a cohort of T2DM., Methods: We recruited 394 outpatients with T2DM attending five Italian diabetes centres who underwent liver ultrasonography (US), FibroScan ® and extensive evaluation of macrovascular and microvascular diabetic complications., Results: Steatosis by US was present in 89%. Almost all patients (96%) were on hypoglycaemic drugs, 58% had at least one chronic vascular complication, 19% a macrovascular complication (prior myocardial infarction and/or ischaemic stroke) and 33% a microvascular one (26% chronic kidney disease [CKD]; 16% retinopathy; 6% neuropathy). In all, 171 (72%) patients had CAP ≥ 248dB/m (ie hepatic steatosis), whereas 83 (21%) patients had LSM ≥ 7.0/6.2 kPa (M/XL probes) (significant liver fibrosis). CAP was not associated with any macro/microvascular complications, whereas LSM ≥ 7.0/6.2 kPa was independently associated with prior cardiovascular disease (adjusted OR 3.3, 95%CI 1.2-8.8; P = .02) and presence of microvascular complications (adjusted OR 4.2, 95%CI 1.5-11.4; P = .005), mainly CKD (adjusted OR 3.6, 95%CI 1.3-10.1; P = .01) and retinopathy (adjusted OR 3.7, CI 95% 1.2-11.9; P = .02). Neither diabetes duration nor haemoglobin A1c differed according to CAP or LSM values., Conclusion: Significant fibrosis, detected by FibroScan ® , is independently associated with increased prevalence of macrovascular and microvascular complications, thus opening a new scenario in the use of this tool for a comprehensive evaluation of hepatic and vascular complications in patients with T2DM., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Available studies on metabolic syndrome (MS) after hematopoietic stem cell transplantation (HSCT) are retrospective with heterogeneous inclusion criteria, and little is known about the early post-transplant phase. In our prospective study, clinical and laboratory data were collected in 100 HSCT recipients, 48 allogeneic and 52 autologous, at baseline, at + 30, + 100 and + 360 days. At baseline, MS was observed in 24 patients, significantly associated with insulin resistance and leptin on multivariate analysis. At + 30, the diagnosis of MS was confirmed in 43 patients, significantly related to insulin resistance and allogeneic transplants. If the whole series was considered, patients with MS had significantly higher mortality from any cause. The baseline presence of any MS feature was a predictor of + 30 MS. Isolated occurrences of MS features were related to hyperleptinemia and hyperinsulinemia, except in the case of low HDL cholesterol, linked to adiponectin and resistin. Our data confirm that patients undergoing HSCT have a high prevalence of MS, with hyperleptinemia playing a major role. The early peak of new MS cases is primarily attributable to insulin resistance, notably but not exclusively immunosuppression-induced; the subsequent long-term increase in MS cases may be an effect of persistent adipokine imbalance.

Background and Aims: Non-alcoholic fatty liver disease is recognized not only as part of the metabolic syndrome but also as an independent predictor of cardiovascular disease., Methods: In this study, NMR spectroscopy method, together with perfusion techniques, was used to detect subclinical brain vascular damage in subjects with NAFLD without overt atherosclerosis risk factors (i.e. hypertension, diabetes, hypercholesterolemia, obesity)., Results: The results suggest that subjects with histologically proven NAFLD have a reduced cerebral perfusion (CBFr) confined to limited brain areas, i.e., left semioval center and posterior cingulate cortex. No statistically significant differences in CBFr values were found, dividing the NAFLD cohort into subgroups, considering NAS score, presence/absence of NASH/fibrosis, and degree of steatosis., Conclusions: Our data suggest that NAFLD per se may be involved in cerebral atherosclerotic disease. It will be interesting to draw longitudinal studies to determine whether these changes could evolve in more serious cerebral injury., (Copyright © 2017 Elsevier B.V. All rights reserved.)