Inflammatory markers as prognostic factors of survival in patients affected by hepatocellular carcinoma undergoing transarterial chemoembolization

Transarterial chemoembolization (TACE) is a good choice for hepatocellular carcinoma (HCC) treatment when surgery and liver transplantation are not feasible. Few studies reported the value of prognostic factors influencing survival after chemoembolization. In this study, we evaluated whether preoperative inflammatory factors such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio affected our patient survival when affected by hepatocellular carcinoma. Methods. We retrospectively evaluated a total of 72 patients with hepatocellular carcinoma that underwent TACE. We enrolled patients with different etiopathogeneses of hepatitis and histologically proven HCC not suitable for surgery. The overall study population was dichotomized in two groups according to the median NLR value and was analyzed also according to other prognostic factors. Results. The global median overall survival (OS) was 28 months. The OS in patients with high NLR was statistically significantly shorter than that in patients with low NLR. The following pretreatment variables were significantly associated with the OS in univariate analyses: age, Child-Pugh score, BCLC stage, INR, and NLR. Pretreated high NLR was an independently unfavorable factor for OS. Conclusion. NLR could be considered a good prognostic factor of survival useful to stratify patients that could benefit from TACE treatment

Comparison of Faecal versus Rumen Inocula for the Estimation of NDF Digestibility

Cow faeces have been investigated as alternative inoculum to replace rumen fluid to determine neutral detergent fibre (NDF) digestibility (NDFD). Aims of this study were to estimate: (1) the NDFD (48 h) of feed ingredients using a rumen inoculum in comparison with faecal inocula from cows fed diets with different forage basis; (2) the undigestible NDF (uNDF) at 240 and 360 h with ruminal fluid and faecal inocula from lactating cows fed two different diets. At 48 h incubation, the NDFD was affected both by feed and type of inoculum (p < 0.01) and by their interaction (p = 0.03). Overall, the mean NDFD was higher for rumen inoculum than for faecal inocula (585 vs. 389 g/kg NDF, p < 0.05), and faecal inoculum obtained from cows fed hay-based diets gave lower NDFD than those from cows fed maize silage (367 vs. 440 g/kg, p < 0.05). At long incubation times, the average uNDF was affected by substrate, inoculum and incubation time (p < 0.01), but not by their interactions. For each inoculum, significantly lower values were obtained at 360 than at 240 h. Regressions between uNDF with rumen and with the tested faecal inocula resulted in r2 65 0.98. Despite the differences at 48 h, the uNDF showed that faecal inoculum could replace rumen fluid at longer incubation times

Activity and analysis of costs in a dedicated weaning centre.

AIM: To analyse the diagnosis-related characteristics and the costs of treating patients with difficult/prolonged weaning from mechanical ventilation we have undertaken a retrospective observational study. METHODS: The study has considered all the patients admitted to our weaning unit of a regional Rehabilitation department during 3 consecutive periods since the opening date. Characteristics of the admitted patients and the DRG-related cares delivered have been recorded. A cost analysis has been obtained over time. RESULTS: The number of beds allocated to this unit (from 4 in the 1st period to 6 in the 2nd and 3rd periods) and the number of patients cared for (from 32 to 43 and to 65, respectively) increased over time. In particular, the COPD to non-COPD patient ratio (from 2.2 to 1.3 and to 1.0) and the DRG/patient weight (from 3.0 +/- 0.3 to 3.1 +/- 0.2 and to 3.3 +/- 0.2 point) changed significantly (p < 0.05). The daily reimbursement per patient from the public health care system only slightly increased, whereas the operating margin (reimbursement less costs) per patient significantly improved (from -304, to +17 and +55 Euro/pt/day, respectively, p < 0.05) due to a gradual restriction in the variable costs. Length of stay, mortality rate and weaning rate did not change over time. CONCLUSION: The weaning centre is a hospital area where economic burdens should be carefully evaluated. Given the actual reimbursement received on a national level for these patients, variable costs might be better spread, thus optimising the burdens without losing out on clinical outcomes

Manganite/Alq3 interfaces investigated by impedance spectroscopy technique

With the general objective of studying interfaces between ferromagnetic materials and organic semiconductors, we report ac impedance investigations on La0.7Sr0.3MnO3 (LSMO)/tris(8-hydroxyquinoline)aluminium (Alq3)/Al and Indium Tin Oxide (ITO)/Alq3/Al heterostructures, in the frequency range between 20 Hz and 1 MHz. The comparison of the equivalent circuits deduced to fit the experimental ac responses allows isolating a specific RC contribution which can be attributed to the LSMO/Alq3 interface region. Using the information obtained from our ac measurements, we propose a model which fits the temperature dependence of the magnetoresistance in spin valves combining LSMO electrodes and Alq3 layers

The Unfolded Protein Response in a Murine Model of Alzheimer’s Disease: Looking for Predictors

Alzheimer's disease (AD) represents the most frequent type of dementia worldwide, and aging is the most important risk factor for the sporadic form of the pathology. The endoplasmic reticulum (ER), the main cellular actor involved in proteostasis, appears significantly compromised in AD due to the accumulation of the beta-amyloid (A beta) protein and the phosphorylated Tau protein. Increasing protein misfolding activates a specific cellular response known as Unfolded Protein Response (UPR), which orchestrates the recovery of ER function. The aim of the present study was to investigate the role of UPR in a murine model of AD induced by intracerebroventricular (i.c.v.) injection of A beta 1-42 oligomers at 3 or 18 months. The oligomer injection in aged animals induced memory impairment, oxidative stress, and the depletion of glutathione reserve. Furthermore, the RNA sequencing and the bioinformatic analysis performed showed the enrichment of several pathways involved in neurodegeneration and protein regulations. The analysis highlighted the significant dysregulation of the protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 alpha (IRE1 alpha) and activating transcription factor 6 (ATF-6). In turn, ER stress affected the PI3K/Akt/Gsk3 beta and MAPK/ERK pathways, highlighting Mapkapk5 as a potential marker, whose regulation could lead to the definition of new pharmacological and neuroprotective strategies to counteract AD

Evaluation of the Psychometric Properties of the Revised Piper Fatigue Scale in Patients with Multiple Sclerosis

Background: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS), and has a major impact on their quality of life. Measurement tools that assess the patient’s condition are commonly used in the neurological field, though diagnostic tools are currently unable to distinguish potential alternative causes of fatigue in individual patients. The Revised Piper Fatigue Scale (PFS-R) is a self-administered assessment scale that is internationally used for fatigue measurement. Aim: This study aimed to evaluate the reliability and validity of the Italian version of the PFS-R in patients with MS. Methods: Forty-one individuals were included in this study. Each participant in the study was given a dossier, in paper format, containing the informed consent form, a personal data sheet, the Fatigue Symptoms and Impacts Questionnaire in Relapsing Multiple Sclerosis (FSIQ-RMS), the Fatigue Severity Scale (FSS), and the PFS-R. Results: The PFS-R was found to have strong internal consistency, with a value of α equal to 0.977. Correlations between PFS-R, FSS, and FSIQ-RMS scores were analyzed using the Pearson correlation coefficient, and all scales showed statistically significant correlations. Conclusion: The PFS-R is a new self-administered tool to assess fatigue in patients with MS. It evaluates fatigue characteristics, difficulty in carrying out daily life activities, and how the individual feels as a result of this symptom. This tool was previously validated for use in cancer patients, which also allows us to make a comparison between different pathologies and rehabilitation treatments

Activity and analysis of costs in a dedicated weaning centre

Aim. To analyse the diagnosis-related characteristics and the costs of treating patients with difficult/prolonged weaning from mechanical ventilation we have undertaken a retrospective observational study. Methods. The study has considered all the patients admitted to our weaning unit of a regional Rehabilitation department during 3 consecutive periods since the opening date. Characteristics of the admitted patients and the DRG-related cares delivered have been recorded. A cost analysis has been obtained over time. Results. The number of beds allocated to this unit (from 4 in the 1st period to 6 in the 2nd and 3rd periods) and the number of patients cared for (from 32 to 43 and to 65, respectively) increased over time. In particular, the COPD to non-COPD patient ratio (from 2.2 to 1.3 and to 1.0) and the DRG/patient weight (from 3.0±0.3 to 3.1±0.2 and to 3.3±0.2 point) changed significantly (p<0.05). The daily reimbursement per patient from the public health care system only slightly increased, whereas the operating margin (reimbursement less costs) per patient significantly improved (from -304, to +17 and +55 €/pt/day, respectively, p<0.05) due to a gradual restriction in the variable costs. Length of stay, mortality rate and weaning rate did not change over time. Conclusion. The weaning centre is a hospital area where economic burdens should be carefully evaluated. Given the actual reimbursement received on a national level for these patients, variable costs might be better spread, thus optimising the burdens without losing out on clinical outcomes

GLP-1 Mediates Regulation of Colonic ACE2 Expression by the Bile Acid Receptor GPBAR1 in Inflammation

Background & Aims: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. Methods: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn’s disease (CD) patients and three mouse models of colitis and Gpbar1−/− mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. Results: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. Conclusions: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α-and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2

Differences in cardiac phenotype and natural history of laminopathies with and without neuromuscular onset

Objective: To investigate differences in cardiac manifestations of patients affected by laminopathy, according to the presence or absence of neuromuscular involvement at presentation. Methods: We prospectively analyzed 40 consecutive patients with a diagnosis of laminopathy followed at a single centre between 1998 and 2017. Additionally, reports of clinical evaluations and tests prior to referral at our centre were retrospectively evaluated. Results: Clinical onset was cardiac in 26 cases and neuromuscular in 14. Patients with neuromuscular presentation experienced first symptoms earlier in life (11 vs 39 years; p &lt; 0.0001) and developed atrial fibrillation/flutter (AF) and required pacemaker implantation at a younger age (28 vs 41 years [p = 0.013] and 30 vs 44 years [p = 0.086] respectively), despite a similar overall prevalence of AF (57% vs 65%; p = 0.735) and atrio-ventricular (A-V) block (50% vs 65%; p = 0.500). Those with a neuromuscular presentation developed a cardiomyopathy less frequently (43% vs 73%; p = 0.089) and had a lower rate of sustained ventricular tachyarrhythmias (7% vs 23%; p = 0.387). In patients with neuromuscular onset rhythm disturbances occurred usually before evidence of cardiomyopathy. Despite these differences, the need for heart transplantation and median age at intervention were similar in the two groups (29% vs 23% [p = 0.717] and 43 vs 46 years [p = 0.593] respectively). Conclusions: In patients with laminopathy, the type of disease onset was a marker for a different natural history. Specifically, patients with neuromuscular presentation had an earlier cardiac involvement, characterized by a linear and progressive evolution from rhythm disorders (AF and/or A-V block) to cardiomyopathy