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1.
Eat Weight Disord ; 26(7): 2421-2426, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33201394

ABSTRACT

Androgen Insensitivity Syndrome represents a disorder due to partial (PAIS), mild (MAIS) or complete (CAIS) resistance to androgens caused by X-linked mutations of androgen receptor gene. CAIS is characterized by a female phenotype and XY karyotype. Cases of patients with CAIS and associated obesity have been reported, while to date, there are no reports about the onset of an Eating Disorder (ED) in the carriers of this condition. We describe the case of a patient affected by CAIS and Anorexia Nervosa (AN) restricting type later shifted to Bulimia Nervosa (BN). A previous overweight was present since childhood, contributing to severe Body Dissatisfaction (BD) and consequent restrictive behaviour in adolescence. Beyond its peculiarity, this case highlights also the importance of diagnosing and monitoring the overweight and BD in CAIS patients to avoid the onset of an ED.Level of Evidence: V, descriptive study.


Subject(s)
Androgen-Insensitivity Syndrome , Feeding and Eating Disorders , Androgen-Insensitivity Syndrome/diagnosis , Child , Female , Humans , Male , Mutation , Receptors, Androgen/genetics
2.
Nutr Metab Cardiovasc Dis ; 29(1): 4-8, 2019 01.
Article in English | MEDLINE | ID: mdl-30503707

ABSTRACT

AIMS: To review the formation, catabolism, and the possible atherogenic properties of Lp-X. DATA SYNTHESIS: The conversion of cholesterol to bile acids is regulated by several mechanisms including cholesterol 7 alpha hydroxylase, fibroblast growth factor 19, and farnesoid X receptors. During cholestasis these mechanisms are altered and there is an accumulation of bile acids and cholesterol in plasma. The hypercholesterolemia observed in cholestasis is due to the presence of an anomalous lipoprotein called lipoprotein-X (Lp-X). Lp-X is a lipoprotein rich in phospholipid and free cholesterol present in plasma of patients with cholestasis and, with some variations, in patients with lecithin-cholesterol-acyl-transferase deficiency (LCAT), and after lipid infusion. Lp-X is formed from a bile lipoprotein moving to the blood vessels where it incorporates small quantities of triglycerides, apo-C and esterified cholesterol and becomes a "mature" Lp-X. The activity of the phosphatidilcholine canalicular transporter Mdr2 P-glycoprotein (homologous to the human ABCB4) is essential for LpX appearance, since its suppression abolishes Lp-X formation. However, the concentration of Lp-X in plasma is determined also by the degree of the cholestasis, the residual liver function, and the LCAT deficiency. The Lp-X catabolism seems to be mediated by the reticuloendothelial system and possibly the kidney. CONCLUSIONS: Lp-X might be considered a defense mechanism against the toxic effect of free cholesterol in cholestasis. The frequency of cardiovascular events in patients affected by primary biliary cholangitis, in whom the Lp-X is present in high concentration, are not increased. Further studies could now clarify the remaining open questions on the role of Lp-X in the dyslipidemia of cholestasis.


Subject(s)
Cholestasis/blood , Hypercholesterolemia/blood , Lipoprotein-X/blood , Liver/metabolism , Animals , Biological Transport , Cholestasis/epidemiology , Cholestasis/history , History, 20th Century , History, 21st Century , Humans , Hypercholesterolemia/epidemiology , Hypercholesterolemia/history , Lecithin Cholesterol Acyltransferase Deficiency/blood , Lecithin Cholesterol Acyltransferase Deficiency/epidemiology , Lipoprotein-X/history , Prognosis , Risk Factors
3.
Rhinology ; 56(4): 351-357, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-29938715

ABSTRACT

BACKGROUND: The etiology of age-related olfactory loss is still unclear, but it has been claimed that polypharmacotherapy may contribute to olfactory dysfunction, particularly in the elderly, who are more likely to need multiple drugs. The present pilot study investigated the relationship between smell and the number and type of drugs taken in a group of elderly. METHODOLOGY: 50 elderly volunteers (over 64 years old) who were healthy from the sinonasal standpoint (SNOT-22 under 1) and had no cognitive impairments [Mini Mental State Examination (MMSE over 18) were administered the Screening 12 test and tested on their n-butanol olfactory threshold. Their olfactory performance was then connected with the number and type of drugs participants used. RESULTS: The mean age of the included volunteers was 74 plus/minus 7 years. No association emerged between odor identification and number of drugs taken. The number of drugs taken correlated directly with a worse olfactory threshold and with a worse MMSE score, meaning a worse cognitive status. Odor identification significantly worsened with age. Comparing those volunteers taking only one drug known to not influence olfaction with another sub-group of volunteers taking five or more drugs, it was evident that subjects taking only one drug scored significantly better in olfactory threshold test and MMSE, and marginally better in olfactory identification test. For what concerns the difference between male and female volunteers, no difference in olfactory test result was shown, both for threshold and identification. Univariate analysis showed a direct correlation between the consumption of calcium channel blockers, beta-blockers, acetylsalicylic acid and olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also correlated inversely with odor identification, meaning again a worse sense of smell, and so did potassium-sparing diuretics. Multivariate analysis showed that MMSE scores correlated with a better sense of smell, that is a lower olfactory threshold, and that beta-blockers and acetylsalicylic acid negatively affected olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also correlated inversely with odor identification, meaning again a worse sense of smell. CONCLUSIONS: The number of drugs taken demonstrated to be significantly correlated with a worse olfactory threshold and worse MMSE. Larger studies on elderly volunteers are needed to confirm these preliminary findings.


Subject(s)
Olfaction Disorders/chemically induced , Polypharmacy , Sensory Thresholds/drug effects , Aged , Female , Humans , Italy , Male , Odorants , Surveys and Questionnaires
4.
Bone ; 113: 89-94, 2018 08.
Article in English | MEDLINE | ID: mdl-29753150

ABSTRACT

PURPOSE: Vertebral fractures are associated with persistent pain, disability and mortality. However, around two thirds of women with vertebral fractures are unaware of them. We aimed to analyze which factors could mostly be associated to the presence of vertebral fractures in post-menopausal women, and evaluate the effectiveness of current screening criteria for the detection of vertebral fractures in an outpatient setting. METHODS: We evaluated 1132 post-menopausal women referred to the osteoporosis outpatient clinic of the Geriatrics Department of Padova. For each participant we assessed: anthropometric data, femoral and lumbar bone mineral density (BMD), dorso-lumbar X-rays, bone metabolism markers. Current recommendations for X-ray examinations by SIOMMMS (Società Italiana di Osteoporosi, Metabolismo Minerale e Malattie dello Scheletro) and ISCD (International Society of Clinical Densitometry) versus routine X-ray examinations were considered, and fracture risk was assessed through the derived FRAX (DeFRA) tool. RESULTS: Of the women included in our study, 28% presented vertebral fractures, most of these previously unknown (82.8%). Lumbar BMD did not differ between patients with and without vertebral fractures. According to SIOMMMS guidelines, 50% of patients <60 years with unknown vertebral fractures would have been excluded from spinal X-ray examination. According to ISCD recommendations, the number of patients excluded reached 94.6% in the <60 age-group and 84.9% in the 60-70 age-group. The under-identification of vertebral fractures led to the 10-year risk of fractures computed by DeFRA being underestimated by around 15%. CONCLUSIONS: BMD, particularly in the lumbar site, may not properly predict the presence of vertebral fractures in post-menopausal women. Improvement of the current recommendations for spinal X-ray examination may lead to early identification and better management of patients with vertebral fractures.


Subject(s)
Osteoporotic Fractures/diagnostic imaging , Spinal Fractures/diagnostic imaging , Aged , Bone Density/physiology , Female , Frailty/complications , Frailty/diagnostic imaging , Humans , Lumbar Vertebrae , Middle Aged , Radiography , Retrospective Studies
5.
Article in English | MEDLINE | ID: mdl-27726223

ABSTRACT

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. SETTINGS: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.


Subject(s)
Geriatric Assessment/methods , Neoplasms/mortality , Severity of Illness Index , Aged , Aged, 80 and over , Female , Humans , Italy/epidemiology , Male , Prognosis , Prospective Studies , ROC Curve
6.
Aging Clin Exp Res ; 30(2): 133-138, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28534301

ABSTRACT

A long history of diabetes mellitus and increasing age are associated with the onset of diabetic neuropathy, a painful and highly disabling complication with a prevalence peaking at 50% among elderly diabetic patients. Acetyl-L-carnitine (ALC) is a molecule derived from the acetylation of carnitine in the mitochondria that has an essential role in energy production. It has recently been proposed as a therapy to improve the symptoms of diabetic neuropathy. ALC is widely distributed in mammalian tissues, including the brain, blood-brain barrier, brain neurons, and astrocytes. Aside from its metabolic activity, ALC has demonstrated cytoprotective, antioxidant, and antiapoptotic effects in the nervous system. It exerts an analgesic action by reducing the concentration of glutamate in the synapses. It facilitates nerve regeneration and damage repair after primary trauma: its positive effects on metabolism promote the synthesis, fluidity, and functionality of neuronal membranes, increase protein synthesis, and improve the axonal transport of neurofilament proteins and tubulin. It also amplifies nerve growth factor responsiveness, an effect that is believed to enhance overall neurite growth. ALC has been proposed for the treatment of various neurological and psychiatric diseases, such as mood disorders and depression, dementias, Alzheimer's disease, and Parkinson's disease, because synaptic energy states and mitochondrial dysfunction are core factors in their pathogenesis.


Subject(s)
Acetylcarnitine/therapeutic use , Analgesics/therapeutic use , Diabetic Neuropathies/drug therapy , Pain/drug therapy , Acetylcarnitine/pharmacology , Aged , Alzheimer Disease/drug therapy , Analgesics/pharmacology , Humans , Mitochondria/metabolism
7.
J Nutr Health Aging ; 21(2): 131-135, 2017.
Article in English | MEDLINE | ID: mdl-28112766

ABSTRACT

OBJECTIVE: Older women have frequently low serum 25-hydroxivitamin D (25[OH]D) concentrations, high parathormone (PTH) levels and low bone mineral density (BMD) values. Endogenous synthesis, dietary habits, sunlight exposure and fat-mass-mediated storage may influence 25(OH)D levels and bone metabolism, but the relevance of these factors in the elderly has yet to be fully elucidated. We aimed to investigate the influence of dietary vitamin D intake and fat mass on serum 25(OH)D levels and bone metabolism in older women. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: 218 fit older women attending a biweekly mild fitness program. MEASUREMENTS: Dietary habits was investigated through a 3-day record questionnaire. Serum 25(OH)D and intact parathormone (PTH) concentrations were measured by radioimmunoassay and by a 2-step immunoradiometric assay, respectively. BMD and body composition were estimated using dual-energy X-ray absorptiometry with fan-beam technology. RESULTS: Only fat mass showed a significant negative association with 25(OH)D (ß=-3.76, p<0.001), and positive associations with whole body, lumbar, femoral neck and total hip BMD. Binary logistic analysis revealed a protective effect of adiposity on secondary hyperparathyroidism (OR=0.42, 95%CI:0.19-0.92, p=0.03). Dietary vitamin D intake was not associated to any of these outcomes. CONCLUSION: Fat mass has a greater influence on serum 25(OH)D than dietary vitamin D intake.


Subject(s)
Bone Density/drug effects , Diet , Vitamin D/blood , Absorptiometry, Photon , Adiposity , Aged , Aged, 80 and over , Body Mass Index , Cross-Sectional Studies , Female , Humans , Linear Models , Logistic Models , Parathyroid Hormone/blood , White People
9.
Lung ; 194(6): 897-904, 2016 12.
Article in English | MEDLINE | ID: mdl-27699476

ABSTRACT

PURPOSE: As studies examining the association between bone mineral density (BMD) and airflow limitation (AL) have produced conflicting results, the current one set out to analyze if and to what degree there are any correlations between these variables in a population of fit elderly women. METHODS: One hundred and twenty-one non-smoking, fit and healthy women (age ≥ 65 years) underwent anthropometric assessment, laboratory testing (serum 25-hydroxy vitamin D, parathormone, and cytokine levels), pulmonary function testing (PFT), and dual-energy X-ray absorptiometry to evaluate BMD values of the lumbar and femoral regions. RESULTS: A significant positive association was found between FEV1/FVC ratio (Tiffeneau index), a sensitive index of AL, and lumbar and femoral BMD; a 10 % increase in the FEV1/FVC ratio resulted in a significant increase of 0.025 g/cm2 in the total hip (p = 0.05), 0.027 g/cm2 in the femoral neck (p = 0.02), 0.028 g/cm2 in the femoral trochanter (p = 0.01), and 0.047 g/cm2 in the lumbar (p = 0.03) BMDs. Binary logistic analyses demonstrated more than a threefold higher risk of low BMD values for the lowest FEV1/FVC quartile in the lumbar (OR 4.62, 95 % CI 1.48-14.40, p = 0.008), total hip (OR 4.09, 95 % CI 1.28-13.05, p = 0.02 for the second quartile), and femoral trochanter regions (OR 3.90, 95 % CI 1.25-12.20, p = 0.02 for the third quartile). CONCLUSIONS: AL was associated with a higher risk of reduced BMD in healthy, fit elderly women.


Subject(s)
Bone Density , Femur Neck/diagnostic imaging , Forced Expiratory Volume , Lumbar Vertebrae/diagnostic imaging , Physical Fitness/physiology , Vital Capacity , Absorptiometry, Photon , Aged , Female , Healthy Volunteers , Humans
10.
Eur J Clin Nutr ; 70(12): 1354-1359, 2016 12.
Article in English | MEDLINE | ID: mdl-27530471

ABSTRACT

Although higher dietary intakes of magnesium (Mg) seem to correspond to lower diabetes incidence, research concerning Mg supplementation in people with or at risk of diabetes is limited. Thus, we aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes compared with placebo. A literature search in PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov without language restriction, was undertaken. Eligible studies were randomized controlled trials (RCTs) investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or at high risk of diabetes. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used for summarizing outcomes with at least two studies; other outcomes were summarized descriptively. Eighteen RCTs (12 in people with diabetes and 6 in people at high risk of diabetes) were included. Compared with placebo (n=334), Mg treatment (n=336) reduced fasting plasma glucose (studies=9; SMD=-0.40; 95% CI: -0.80 to -0.00; I2=77%) in people with diabetes. In conditions in people at high risk of diabetes (Mg: 226; placebo=227 participants), Mg supplementation significantly improved plasma glucose levels after a 2 h oral glucose tolerance test (three studies; SMD=-0.35; 95% CI: -0.62 to -0.07; I2=0%) and demonstrated trend level reductions in HOMA-IR (homeostatic model assessment-insulin resistance; five studies; SMD=-0.57; 95% CI: -1.17 to 0.03; I2=88%). Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes and also improves insulin-sensitivity parameters in those at high risk of diabetes.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/therapy , Dietary Supplements , Magnesium/therapeutic use , Adult , Aged , Blood Glucose/analysis , Diabetes Mellitus/blood , Diabetes Mellitus/etiology , Double-Blind Method , Fasting/blood , Female , Glucose Tolerance Test , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic
11.
J Thromb Haemost ; 14(11): 2124-2131, 2016 11.
Article in English | MEDLINE | ID: mdl-27471198

ABSTRACT

Essentials Anticoagulation in the elderly is still a challenge and suspension of warfarin is common. This is an observational study reporting reasons and consequences of warfarin suspension. Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension. After suspension for bleeding or frailty, patients remain at high-risk of death or complications. SUMMARY: Background Anticoagulation in elderly patients with non-valvular atrial fibrillation (NVAF) is still a challenge, and discontinuation of warfarin is common. The aim of this study was to analyze the aspects related to warfarin discontinuation in a real-world population. Methods This was an observational cohort study on very elderly NVAF patients naive to warfarin therapy (VENPAF). The included subjects were aged at least 80 years, and started using warfarin after a diagnosis of NVAF. Warfarin discontinuation was assessed, and the reason reported for discontinuation, the person who decided to stop treatment, subsequent antithrombotic therapy and mortality, ischemic and bleeding events were collected. Results Over a period of 5 years, warfarin was discontinued in 148 of 798 patients. Despite similar CHA2 DS2 -VASc scores, the frequencies of thromboembolic and major bleeding events were significantly higher (P = 0.01 and P = 0.001, respectively) and the time in therapeutic range (TTR) was significantly lower (P < 0.001) in patients who discontinued warfarin. Independent risk factors for warfarin discontinuation were vascular disease (hazard ratio [HR] 2.5, P < 0.001), age ≥ 85 years (HR 1.4, P = 0.04), TTR < 60% (HR 1.8, P = 0.001), and bleeding events (HR 2.3, P < 0.001). The main reasons for warfarin discontinuation were physician-perceived frailty or low life-expectancy (45.9%), bleeding complications (19.6%), and sinus rhythm restoration (16.9%). Event and death rates were very high, especially in frail patients and in those with bleeding complications. Conclusions Warfarin discontinuation is frequent in very elderly patients, and is associated with increased risks of death and adverse events. Identification of elderly patients who are at high risk of bleeding and the poor quality of anticoagulation during warfarin are still unsolved clinical problems.


Subject(s)
Atrial Fibrillation/drug therapy , Vitamin K/antagonists & inhibitors , Warfarin/therapeutic use , Aged, 80 and over , Anticoagulants/therapeutic use , Blood Coagulation , Female , Fibrinolytic Agents/therapeutic use , Follow-Up Studies , Hemorrhage , Humans , Male , Multivariate Analysis , Proportional Hazards Models , Risk Factors , Stroke/etiology , Thromboembolism/mortality , Thromboembolism/therapy , Treatment Outcome , Vascular Diseases/blood
12.
Eur J Clin Nutr ; 70(9): 1080-2, 2016 09.
Article in English | MEDLINE | ID: mdl-27245210

ABSTRACT

Prospective studies have suggested that hypovitaminosis D can predict the onset of obesity, but they relied mainly on body mass index, which could be scarcely reliable in older people. We investigated whether baseline hypovitaminosis D could predict higher fat mass (FM) levels using dual-energy X-ray absorptiometry in a sample of 116 fit and healthy older subjects. Although no significant differences in FM estimates emerged between subjects with and without hypovitaminosis D at the baseline, abdominal FM was found significantly higher in the former group (with hypovitaminosis D at the baseline) than in the latter after 3 years of follow-up. Adjusted logistic regression analysis confirmed these findings: hypovitaminosis D coincided with an approximately sixfold higher risk of subjects having higher abdominal FM levels at the follow-up. In conclusion, hypovitaminosis D predicts higher abdominal FM levels in the elderly.


Subject(s)
Abdominal Fat/metabolism , Body Composition , Obesity, Abdominal/etiology , Vitamin D Deficiency/complications , Vitamin D/analogs & derivatives , Absorptiometry, Photon , Body Mass Index , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity, Abdominal/blood , Prospective Studies , Vitamin D/blood , Vitamin D Deficiency/blood
13.
Osteoporos Int ; 27(11): 3155-3164, 2016 11.
Article in English | MEDLINE | ID: mdl-27289533

ABSTRACT

Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. INTRODUCTION: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). METHODS: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and HCs. Standardized mean differences (SMDs), 95 % confidence intervals (CIs) were calculated for BMD parameters; in addition odds (ORs) for case-control and adjusted hazard ratios (HRs) in longitudinal studies for categorical variables were calculated. RESULTS: From 1816 initial hits, 28 studies were included. A meta-analysis of case-control studies including 1595 patients with nephrolithiasis (mean age 41.1 years) versus 3402 HCs (mean age 40.2 years) was conducted. Patients with nephrolithiasis showed significant lower T-scores values for the spine (seven studies; SMD = -0.69; 95 % CI = -0.86 to -0.52; I 2 = 0 %), total hip (seven studies; SMD = -0.82; 95 % CI = -1.11 to -0.52; I 2 = 72 %), and femoral neck (six studies; SMD = -0.67; 95 % CI = --1.00 to -0.34; I 2 = 69 %). A meta-analysis of the case-controlled studies suggests that people with nephrolithiasis are at increased risk of fractures (OR = 1.15, 95 % CI = 1.12-1.17, p < 0.0001, studies = 4), while the risk of fractures in two longitudinal studies demonstrated trend level significance (HR = 1.31, 95 % CI = 0.95-1.62). People with nephrolithiasis were four times more likely to have osteoporosis than HCs (OR = 4.12, p < 0.0001). CONCLUSIONS: Nephrolithiasis is associated with lower BMD, an increased risk of osteoporosis, and possibly, fractures. Future screening/preventative interventions targeting bone health might be indicated.


Subject(s)
Bone Density , Fractures, Bone/complications , Nephrolithiasis/complications , Osteoporosis/complications , Adult , Humans , Risk Factors
15.
Eur J Surg Oncol ; 42(7): 919-25, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27005805

ABSTRACT

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Lymph Node Excision , Sentinel Lymph Node/pathology , Sentinel Lymph Node/surgery , Breast Neoplasms/surgery , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Sentinel Lymph Node Biopsy , Survival Analysis
16.
Eur J Clin Pharmacol ; 72(6): 711-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26952092

ABSTRACT

PURPOSE: The purpose of the study is to evaluate whether donepezil (D) plasma concentrations and activity of CYP2D6 and CYP3A4 are associated with the therapeutic response of patients with mild to moderate Alzheimer's disease (AD). METHODS: This study comprised 54 patients affected by probable AD in therapy with D 10 mg/daily for at least 3 months. Plasma concentrations of D and its three main metabolites (6DD, 5DD, DNox) were assayed with a novel high performance liquid chromatography (HPLC) technique. Cognitive progression was assessed at baseline and at 9 months of follow-up with the mini mental state examination (MMSE). The activities of the two cytochromes involved in D metabolism-CYP2D6 and CYP3A4-were evaluated according to their metabolic ratios in plasma or urine, after test doses of probe drugs (dextromethorphan and omeprazole). RESULTS: A significant correlation was found between plasma levels of D and variations in MMSE scores after 9 months of therapy (r (2) = 0.14; p = 0.006). Neither the concentrations of D metabolites nor the metabolic ratios of CYP2D6 and CYP3A4 showed any correlations with cognitive variations. Low CYP2D6 activity and advanced age were associated with high D concentrations. Patients who were treated with CYP2D6 and P-glycoprotein (P-gp) inhibitors also had higher D plasma levels (mean difference = 19.6 ng/mL; p = 0.01) than those who were not. CONCLUSIONS: D plasma concentrations, but not cytochrome phenotyping, are associated with cognitive outcomes in AD patients.


Subject(s)
Alzheimer Disease , Cholinesterase Inhibitors/blood , Cognition , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP3A/metabolism , Indans/blood , Piperidines/blood , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Aged , Aged, 80 and over , Alzheimer Disease/blood , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Cholinesterase Inhibitors/pharmacokinetics , Cholinesterase Inhibitors/therapeutic use , Cytochrome P-450 CYP2D6 Inhibitors/pharmacology , Donepezil , Drug Interactions , Female , Humans , Indans/pharmacokinetics , Indans/therapeutic use , Male , Phenotype , Piperidines/pharmacokinetics , Piperidines/therapeutic use
18.
Ann Oncol ; 27(1): 42-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26483050

ABSTRACT

BACKGROUND: The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer. MATERIALS AND METHODS: Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with colorectal cancer, comparing participants with the presence of ENE (ENE+) versus only intranodal extension (ENE-) were eligible. Data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) together with 95% confidence intervals (CIs) for time-dependent risk related to ENE+, adjusted for potential confounders. RESULTS: Thirteen studies including 1336 patients were identified with a median follow-up of 4.7 years. ENE was associated with a higher T stage and tumor grading. In addition, ENE was associated with a significantly increased risk of all-cause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I(2) = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I(2) = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I(2) = 47%; HR = 2.31, 95% CI 1.54-3.44, P < 0.0001, I(2) = 48%). CONCLUSIONS: Based of these results, in colorectal cancer, ENE should be considered from the gross sampling to the pathology report, as well as in future oncologic staging systems.


Subject(s)
Colorectal Neoplasms/pathology , Lymph Nodes/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Humans , Lymphatic Metastasis , Neoplasm Recurrence, Local , Prognosis , Proportional Hazards Models , Regression Analysis , Treatment Outcome
19.
Nutr Metab Cardiovasc Dis ; 26(1): 27-35, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26643208

ABSTRACT

BACKGROUND AND AIMS: Serum uric acid (SUA) is the end-product of purine metabolism in humans, and its levels often increase in subjects with metabolic syndrome (MetS). Despite several studies demonstrating a relationship between increased SUA levels and the prevalence of MetS, prospective data on SUA as a predictor of the incidence of MetS in the elderly are limited. Our aim was to conduct a prospective study on the association between SUA concentrations and the onset of MetS in an elderly Italian cohort. METHODS AND RESULTS: This is a cohort study (Progetto Veneto Anziani; Pro.V.A.) involving community-dwelling subjects aged ≥65 years and followed up for a mean 4.4 years. We included 1128 participants (aged 74.7 ± 7.1 years) without MetS at the baseline. Gender-specific SUA groups according to the standard deviation (SD) from the mean were considered, taking the incidence of MetS as the main outcome. The mean SUA level was significantly higher in men than in women (5.4 ± 1.2 vs. 4.5 ± 1.2 mg/dl; p < 0.0001). Over the 4.4-year follow-up, 496 individuals developed MetS. After adjusting for potential confounders, Cox's regression analysis revealed no relationship between higher baseline SUA concentrations and the incidence of MetS in men or in the sample as whole, while women with SUA levels more than 1 SD above the mean (≥5.7 mg/dl) carried a 58% higher risk (95%CI: 1.03-2.40; p = 0.03) of being newly diagnosed with MetS during the follow-up. CONCLUSION: High SUA levels significantly and independently predicted MetS in older women, but not in men, over a 4.4-year follow-up.


Subject(s)
Hyperuricemia/epidemiology , Metabolic Syndrome/epidemiology , Uric Acid/blood , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Female , Follow-Up Studies , Humans , Hyperuricemia/blood , Hyperuricemia/diagnosis , Incidence , Italy/epidemiology , Linear Models , Logistic Models , Longitudinal Studies , Male , Metabolic Syndrome/diagnosis , Proportional Hazards Models , Prospective Studies , Risk Assessment , Sex Factors , Time Factors , Up-Regulation
20.
Obes Rev ; 16(11): 1001-15, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26252230

ABSTRACT

Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI = 1.26-1.58) for underweight, 0.85 (95% CI = 0.73-0.99) for overweight and 0.74 (95% CI = 0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 [95% CI = 1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.


Subject(s)
Body Mass Index , Frail Elderly/statistics & numerical data , Homes for the Aged/statistics & numerical data , Nursing Homes/statistics & numerical data , Overweight/mortality , Thinness/mortality , Aged , Aged, 80 and over , Female , Humans , Male , Nutritional Physiological Phenomena , Risk Factors
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