PCSK9 Levels Are Raised in Chronic HCV Patients with Hepatocellular Carcinoma.

Background: Since emerging evidence suggests a protective role of proprotein convertase subtilisin/kexin type 9 (PCSK9) on hepatitis C virus (HCV) infection, the aim of the present study was to evaluate the correlation between PCSK9 and HCV infection in hepatocellular carcinoma (HCC) patients. Methods: In this retrospective study, PCSK9 levels were evaluated by ELISA, in plasma samples from control (n = 24) and 178 patients diagnosed for HCC, cirrhosis, or chronic hepatitis, either positive or negative for HCV. Results: HCV positive patients (HCV+) presented with higher PCSK9 levels compared to HCV negative individuals (HCV-), 325.2 ± 117.7 ng/mL and 256.7 ± 139.5 ng/mL, respectively. This difference was maintained in the presence of HCC, although this disease significantly reduced PCSK9 levels. By univariate analysis, a positive correlation between PCSK9 and HCV viral titer was found, being G2 genotype the most-potent inducer of PCSK9 among other genotypes. This induction was not associated with changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). A negative correlation was also found between PCSK9 levels and liver impairment, assessed by Model for End-Stage Liver Disease (MELD). Finally, a multivariate correlation analysis corrected for age, TC, LDL-C, and sex, demonstrated, in the whole cohort, a positive association between PCSK9 and HCV and a negative with HCC. Conclusions: taken together, our study reveals that HCV raised PCSK9 in both the presence and absence of HCC.

Are cytochrome P4502D6 and apolipoprotein E genotypes associated with long-term cognitive and functional changes in patients treated with donepezil?

AIM: We investigated the associations of the single-nucleotide polymorphism rs1080985 of cytochrome P4502D6 (CYP2D6) and the apolipoprotein E (APOE) genotypes with cognitive and functional changes in patients treated with donepezil. METHODS: Sixty-five outpatients with Alzheimer's disease or mixed dementia being treated with donepezil were assessed at baseline and over 27 months. Changes in cognitive status, assessed with the Mini-Mental State Examination, and in functional status, assessed by the Activities of Daily Living Scale and the Instrumental Activities of Daily Living Scale, were evaluated as a function of CYP2D6 and APOE genotypes by using linear mixed models. Multiplicative interactions between the CYP2D6 and APOE genotypes and time were investigated. RESULTS: Individuals with the mutated CYP2D6 exhibited a slower decline in total Mini-Mental State Examination scores, orientation, registration, and functional status than those with the wild type. A significant interaction between CYP2D6, APOE, and time was found for changes in the Activities of Daily Living Scale; among the ε4 carriers, those with the mutated CYP2D6 exhibited a slower decline on the Activities of Daily Living Scale than those with the wild type. CONCLUSION: The CYP2D6 and APOE genotypes may modulate the effectiveness of donepezil on cognitive and functional status.

Parkinson's disease and the non-motor symptoms: hyposmia, weight loss, osteosarcopenia.

Non-motor symptoms (NMSs) are common in Parkinson's disease (PD) and can precede, sometimes for several years. NMSs include, other than gastrointestinal symptoms like constipation and dysphagia, also hyposmia, weight loss and osteosarcopenia. These three NMSs seem to be inter-related and affect patients' health and quality of life. Unfortunately, patients with these symptoms usually are not initially seen by a neurologist, and by the time they are consulted, nearly ~ 80% of the dopaminergic neurons in the substantia nigra have died. To date, no guidelines exist for screening, assessment and management of NMSs in general. A better understanding of these specific NMSs, likely in the context of others, will make it possible to approach and optimise the treatment of the motor symptoms thereby enhancing the welfare of PD patients. Identifying the NMSs could be very helpful, and among them, hyposmia, weight loss and osteosarcopenia may play an important role in solving the limitations in the diagnosis of PD. A strict collaboration between general practitioners, clinicians, geriatricians and neurologists can be one approach towards the diagnosis of pre-PD. Waiting until the motor symptoms develop and the patient is finally visited by the neurologist could be too late, considering the catastrophic prognosis of the disease.

Dietary strategies for mitigating osteosarcopenia in older adults: a narrative review.

The synchronic loss of bone mineral density and decrease in muscle mass, strength, and function defines the scenario of osteosarcopenia, which is associated with an increased risk of falls and fractures in older adults. An important role in preventing muscle and bone loss is played by nutritional factors, in particular the intake of proteins, calcium, magnesium and vitamin D. This review summarizes the available literature concerning the influence of protein intake and supplementation (vitamin D, Ca, Mg, branched-chain amino acids) on the decline of musculoskeletal integrity in healthy older adults. Furthermore, in this paper, we attempted to give some suggestions to build up adequate nutritional and dietary strategies against the age-related loss of muscle and bone mass.

Influence of serum 25-hydroxyvitamin D levels, fat-free mass, and fat mass on bone density, geometry and strength, in healthy young and elderly adults.

PURPOSE: The association between serum 25-hydroxyvitamin D (25-OHD) levels and cortical/trabecular bone parameters has been explored in the elderly, but less so in younger adults; body composition may also influence bone parameters across the life span. We aimed to investigate, with peripheral quantitative computerized tomography (pQCT), the relationship between serum 25-OHD levels and bone geometry and strength and, at the same time, to explore the influence of fat mass and fat-free mass on bone parameters, for the tibia and radius, in healthy young and elderly adults. METHODS: The study involved 149 healthy adults grouped by age: 65 were under 65 years old, and 84 were older. All participants were assessed in terms of: clinical history; serum 25-OHD levels; fat-free mass (FFM) and fat mass (FM), measured with DXA; total and cortical bone cross-sectional area (CSA, CSAc), and trabecular and cortical bone mineral density (BMDt, BMDc); and fracture load x and y for the tibia and radius, measured with pQCT. RESULTS: In the younger group, the association between 25-OHD levels and bone parameters did not remain as significant for any parameters after multivariate adjustment. In the elderly, 25-OHD correlated with CSAc (partial R2 = 0.33), fracture load x (partial R2 = 0.54), and fracture load y (partial R2 = 0.46) for the radius, and marginally with BMDt (partial R2 = 0.09; B-H adjusted p < 0.05 for all) for the tibia. FFM correlated with all bone parameters in both age groups. In the elderly group alone, FM correlated with BMDt at the tibia (r = 0.25, p < 0.05), with CSA at both sites (radius r = -0.25, p < 0.05; tibia r = -0.32, p < 0.001), and with fracture load y on the radius (r = -0.22, p < 0.05). CONCLUSION: While serum 25-OHD levels correlated only weakly with bone parameters in younger adults, a significant relationship was observed for elderly people. Fat-free mass showed positive simple correlation with pQCT-derived bone parameters in both age groups except with BMDc in the younger group. Further longitudinal studies are needed to clarify these relationships.

Long-term cardiovascular risk and coronary events in morbidly obese patients treated with laparoscopic gastric banding.

BACKGROUND: Long-term studies reporting the effects of bariatric surgery on cardiovascular risk factors and events are scarce. The aim of this study was to analyze reduction of multiple cardiovascular risk factors and rates of coronary events in morbidly obese patients treated with bariatric surgery and with>10 years of follow-up. METHODS: This was a prospective uncontrolled study with laparoscopic adjustable gastric banding. Cardiovascular risk factors (fasting glucose, total cholesterol, HDL-C, triglycerides, blood pressure) have been previously determined both at surgery and 12-18 months after in 650 patients treated with laparoscopic adjustable gastric banding from 1993 to 1999. Cardiovascular risk status was again determined in 2010, and the rate of coronary events during long-term (>10 years) follow-up was collected. RESULTS: A total of 318 patients (58 men and 260 women) were retrieved. Age at surgery was 38.6 ± 10.4 years. Body mass index was 46.7 ± 7.2 kg/m(2). Follow-up was 12.7 ± 1.5 years. Weight loss was 17.6% ± 15.7% of baseline weight at 12-18 months and 17.1% ± 14.8% at 12.7 years. A significant reduction in blood glucose, total cholesterol, triglycerides, and systolic and diastolic blood pressure was observed at the short-term evaluation and confirmed in the long term. HDL-C was unchanged at 12-18 months and significantly increased at 12.7 years. Five coronary events (1.6%) were recorded during long-term follow-up. The rate of observed events was compared with the rate of events expected according to baseline 10-year probability of myocardial infarction calculated with the Prospective Cardiovascular Munster study (PROCAM) score. Observed rate (1.6%) was slightly lower than the expected rate (2.0%± 4.9%). CONCLUSIONS: Stable weight loss and significant improvement of cardiovascular risk profile were observed in morbidly obese patients 10 years after laparoscopic adjustable gastric banding.

The effects of the surgical removal of subcutaneous adipose tissue on energy expenditure and adipocytokine concentrations in obese women.

OBJECTIVE: To analyze the effects of the surgical removal of subcutaneous adipose tissue by ultrasound-assisted megalipoplasty (UAM) on energy expenditure and adipocytokine concentrations in obese women. METHODS: Fifteen premenopausal obese women with BMI 37.5+/-6.3 kg/m(2) (range: 30.7-53.6 kg/m(2)) underwent UAM. Body composition (by DEXA), resting metabolic rate (REE) by indirect calorimetry, insulin resistance (by the HOMA method), leptin, C-reactive protein, interleukin-6, resistin and adiponectin were measured before and 1, 3, 28 and 180 days after the procedure. RESULTS: UAM significantly reduced fat mass at day 3, without further changes in the following days. REE increased at day 3 after UAM, returned to baseline levels at day 28 and significantly declined at day 180. Leptin levels transiently increased after UAM and then declined according to fat mass reduction. C-reactive protein, interleukin-6 and resistin levels acutely increased after UAM and then returned to the baseline levels. Adiponectin levels acutely declined after the procedure and then stabilized to a plasma level slightly lower than at baseline. Insulin resistance deteriorated in the acute post-operative phase and then improved. CONCLUSION: The surgical removal of subcutaneous fat was associated to an acute inflammatory reaction with high REE and insulin-resistance. Later on, the metabolic effects of fat mass removal appeared, with a reduction of leptin levels and REE and an improvement of insulin resistance.

High ghrelin concentration is not a predictor of less weight loss in morbidly obese women treated with laparoscopic adjustable gastric banding.

BACKGROUND: We analyzed the role of high plasma ghrelin concentrations at surgery as a negative predictor of weight loss in morbidly obese patients treated with laparoscopic gastric banding (LAGB). METHODS: Fasting plasma ghrelin concentrations were measured in 113 women before LAGB, and 16 of them were identified as having ghrelin concentrations clearly higher than expected according to the BMI levels. The 2-year postoperative outcome of these 16 patients was compared to the outcome of the remaining subjects. RESULTS: Mean fasting plasma ghrelin concentration in the group with hyperghrelinemia was 82.3+/-23.1 pg/ml and in women with normal ghrelin was 27.1+/-11.3 pg/ml (P<0.001). No differences in age, age at onset of obesity or degree of obesity were observed between the two groups. Women with hyperghrelinemia had a weight gain during the waiting time similar to women with normal ghrelin. The prevalence of comorbidities and eating behavior disturbances was similar in the two groups, but depression was 2.5 fold more prevalent in the hyperghrelinemic women than in the women with normal ghrelin. The %EWL after LAGB surgery was similar in women with high and normal ghrelin concentrations, with no differences in levels of postoperative band filling. No differences in band-related complications or revisional surgery rate were observed between the two groups. CONCLUSION: A high fasting ghrelin concentration at baseline did not significantly affect the outcome after LAGB in morbidly obese women, in terms of weight loss and complications rate.

Total and regional body composition and energy expenditure in multiple symmetric lipomatosis.

AIMS: The aim of the present study was to investigate possible alterations in body composition and resting energy expenditure (REE) in type 1 multiple symmetric lipomatosis (MSL). SUBJECTS AND METHODS: Thirteen men aged from 40 to 78 years affected by type I MSL were compared with 13 healthy control subjects. Fat mass (FM) and fat-free mass (FFM) were determined by DEXA using both standard analysis and specifically for the lipomatous region. REE was measured by indirect calorimetry. RESULTS: FM was higher in MSL subjects at proximal arm level, but significantly lower at distal leg level than in controls (left 1.63+/-0.55 vs. 2.26+/-0.49 kg, P<0.05; right 1.63+/-0.53 vs. 2.40+/-0.54 kg, P<0.01). Arm FFM was similar in the two groups, while distal leg FFM was significantly lower in MSL cases (left: 7.8+/-1.3 vs. 8.7+/-0.8 kg, P<0.05; right: 8.0+/-1.5 vs. 9.2+/-0.9 kg, P<0.05). FFM strongly correlated with REE (r:0.86;P<0.001). REE, expressed as an absolute value and adjusted for FFM (1830+/-215 vs. 1675+/-120 kcal, P<0.05) was higher in MSL patients. CONCLUSION: In conclusion, MSL patients had a marked FFM and FM atrophy in the lower segments of the legs and an altered energy expenditure (hypermetabolism).

Short-term effects of weight loss on the cardiovascular risk factors in morbidly obese patients.

OBJECTIVE: To analyze the short-term effects of weight loss on the cardiovascular risk factors in morbidly obese patients. RESEARCH METHODS AND PROCEDURES: Five metabolic cardiovascular risk factors (blood glucose, blood pressure, total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides) were determined before and 15.3 +/- 2.1 months after laparoscopic gastric banding in 650 morbidly obese patients. Global cardiovascular risk was calculated according to the Prospective Cardiovascular Münster (PROCAM) scoring system. RESULTS: Mean weight loss was 22.7 +/- 20.4 kg. Normalization of the metabolic alteration was observed in 67.3% of patients with diabetes, 38.3% of patients with hypercholesterolemia, 72.5% of patients with low HDL-cholesterol, 72.3% of patients with hypertriglyceridemia, and 46.7% of patients with hypertension. PROCAM score fell from 31.4 +/- 11.6 to 28.0 +/- 12.0 points (p < 0.001). The modifications of total cholesterol and blood pressure were unrelated to percentage weight loss. Percentage weight loss was significantly related to the reductions of fasting blood glucose, triglyceride level, and the PROCAM score and to the increase of HDL-cholesterol concentrations observed after surgery. However, the strength of these four relationships was generally low. The variations of HDL-cholesterol concentrations and blood pressure levels were more influenced by actual energy balance than by the extent of weight loss. DISCUSSION: Weight loss observed in the first 12 to 18 months after gastric banding was associated with a significant improvement of single cardiovascular risk factors and global risk. On the other hand, the extent of weight loss was poorly related to the magnitude of improvement in cardiovascular risk.