MR Brain Screening in ADPKD Patients : To Screen or not to Screen?

BACKGROUND: Adult polycystic kidney disease (ADPKD) still represents a major cause of renal failure and intracranial aneurisms (IA) have a higher prevalence in ADPKD than in the general population. Current guidelines suggest performing brain MRI only in the subjects with a positive familiar history of IAs or subarachnoid hemorrhage (SAH). This is a retrospective case-control analysis to evaluate the usefulness of a MR screening program in ADPKD patients. METHODS: We retrospectively analyzed all ADPKD patients followed in our outpatient clinic between 2016 and 2019 who underwent a brain MRI screening. We evaluated the presence of IAs and others brain abnormalities and compared our results with a non-ADPKD population (n = 300). We performed univariate and multivariate regression analysis to evaluate if general and demographic features, laboratory findings, clinical parameters and genetic test results correlated with IAs or other brain abnormalities presence. RESULTS: Among the patients evaluated 17 out of 156 (13.6%) ADPKD patients had IAs, compared to 16 out of 300 (5.3%) non-ADPKD controls (p < 0.005). Considering ADPKD patients presenting IAs, 12 (70.6%) had no family history for IAs or SAH. Genetic analysis was available for 97 patients: in the sub-population with IAs, 13 (76.5%) presented a PKD1 mutation and none a PKD2 mutation. We found that arachnoid cysts (AC) (p < 0.001) and arterial anatomical variants (p < 0.04) were significantly more frequent in ADPKD patients. CONCLUSION: In our population ADPKD patients showed a higher prevalence of IAs, AC and arterial variants compared to non-ADPKD. Most of the IAs were found in patients presenting a PKD1 mutation. We found a significant number of alterations even in those patients without a family history of IAs or SAH. The practice of submitting only patients with familial IAs or kidney transplantation candidates to MRI scan should be re-evaluated.

Endoscopic management of frontal sinus diseases after frontal craniotomy: a case series and review of the literature.

PURPOSE: To evaluate frontal sinus complications developed after previous external craniotomies requiring frontal sinus reconstruction and their treatment with an endoscopic approach. METHODS: We retrospectively evaluated 22 patients who referred to Sant'Orsola-Malpighi University Hospital and Bellaria Hospital (Bologna, Italy) between 2005 and 2017. All patients presented with frontal sinus disease after frontal craniotomy with sinus reconstruction performed to treat various pathological conditions. We reported our experience in the endoscopic management of such complications and we reviewed the current literature concerning the endoscopic treatment of these conditions. RESULTS: In total, 14 frontal mucoceles, 4 cases of chronic frontal sinusitis, 2 mucopyoceles and 2 fungus ball of the frontal sinus were identified. Endoscopic surgical treatment included 7 DRAF IIa, 1 DRAF IIb, 11 DRAF III and 3 DRAF IIc (modified DRAF III) approaches. The success rate of the surgical procedure was 86% (19/22 patients). Recurrence of the initial pathology occurred in three patients (14%) requiring a conversion of previous frontal sinusotomy into a DRAF III sinusotomy. CONCLUSION: Frontal sinusopathy can be a long-term complication following craniotomies and may lead to potentially severe pathological conditions, such as mucoceles and frontal sinus inflammation. Its management is still debated and requires recovery of the patency of nasal-frontal route. Our study confirms that the endoscopic endonasal approach may offer a valid solution with low morbidity avoiding re-opening of the craniotomic access. For selected cases, endoscopic approach could also be performed simultaneously to craniotomy as a combined surgery to reduce the risk of short- and long-term complications. Long-term follow-up is mandatory in patients with a history of opened and reconstructed frontal sinus and should include imaging and endoscopic outpatient evaluation.

Results and predictors of outcome of endoscopic endonasal surgery in Cushing's disease: 20-year experience of an Italian referral Pituitary Center.

PURPOSE: To assess outcomes and predictors of early and long-term remission in patients with Cushing's disease (CD) due to ACTH-secreting adenomas treated via endoscopic endonasal approach (EEA). METHODS: This is a retrospective study. Consecutive patients operated for CD from 1998 to 2017 in an Italian referral Pituitary Center were enrolled. Clinical, radiological, and histological data at enrollment and follow-up were collected. RESULTS: 151 patients (107 F) were included; 88.7% were naïve for treatment, 11.3% had been treated surgically and 11.2% medically. At pre-operative magnetic resonance imaging (MRI), 35 had a macroadenoma and 80 a microadenoma, while tumor was undetectable in 36 patients. Mean age at surgery was 41.1 ± 16.6 years. Diagnosis was confirmed histologically in 82.4% of the cases. Patients with disease persistence underwent second surgery and/or medical and/or radiation therapy. Mean follow-up was 92.3 ± 12.0 (range 12-237.4) and median 88.2 months. Remission rate was 88.1% after the first surgery and 90.7% at last follow-up. One patient died of pituitary carcinoma. Post-surgical cortisol drop (p = 0.004), tumor detection at MRI (p = 0.03) and size < 1 cm (p = 0.045) increased the chance of disease remission; cavernous sinus invasion was a negative predictor of outcome (p = 0.002). Twenty-seven patients developed diabetes insipidus and 18 hypopituitarism. Surgery repetition increased the risk of hypopituitarism (p = 0.03), but not of other complications, which included epistaxis (N = 2), cerebrospinal fluid leakage (1), pneumonia (3), myocardial infarction (1), and pulmonary embolisms (2). CONCLUSIONS: Selective adenomectomy via EEA performed by experienced surgeons, supported by a multidisciplinary dedicated team, allows long-term remission in the vast majority of CD patients with low complication rate.

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Site and type of craniopharyngiomas impact differently on 24-hour circadian rhythms and surgical outcome. A neurophysiological evaluation.

This study aimed to quantify 24h body core temperature (BcT°) and sleep-wake cycle rhythm alterations in craniopharyngioma (CP) patients and to identify markers related to the postsurgical outcomes. Ten consecutive CP patients underwent neuroradiological, endocrinological and ophthalmological evaluations, 24h BcT° and sleep-wake cycle recordings before and after endoscopic endonasal surgery. The sample included four women and six men. Nocturnal sleep efficiency was pathologically reduced in eight patients before surgery. Seven out of ten patients presented one to three daytime naps. 24h BcT° rhythm was pathological in six out of ten cases. Post-surgery sleep efficiency normalized in four out of eight patients, whereas nine out of ten patients presented with two to six longer daytime naps. Diurnal naps were mainly present in patients showing pre-operative involvement of the third ventricle floor. 24h BcT° remained pathological in only one out of six cases, returned to normal in two and improved in three. 24h BcT° rhythm improved more in papillary CPs than in adamantomatous CPs. Our data confirmed that both CP and surgery frequently disrupt the sleep-wake cycle and BcT° rhythms. Tumour location and histotype may be related to a worse postsurgical outcome. Therefore, in-depth investigation including circadian monitoring is crucial for surgical outcome.

Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

In vivo chronic nicotine exposure differentially and reversibly affects upregulation and stoichiometry of α4ß2 nicotinic receptors in cortex and thalamus.

Studies with heterologous expression systems have shown that the α4ß2 nicotinic acetylcholine receptor (nAChR) subtype can exist in two stoichiometries (with two [(α4)2(ß2)3] or three [(α4)3(ß2)2] copies of the α subunit in the receptor pentamer) which have different pharmacological and functional properties and are differently regulated by chronic nicotine treatment. However, the effects of nicotine treatment in vivo on native α4ß2 nAChR stoichiometry are not well known. We investigated in C57BL/6 mice the in vivo effect of 14-day chronic nicotine treatment and subsequent withdrawal, on the subunit expression and ß2/α4 subunit ratio of (3)H-epibatidine labeled α4ß2*-nAChR in total homogenates of cortex and thalamus. We found that in basal conditions the ratio of the ß2/α4 subunit in the cortex and thalamus is different indicating a higher proportion in receptors with (α4)2(ß2)3 subunit stoichiometry in the thalamus. For cortex exposure to chronic nicotine elicited an increase in receptor density measured by (3)H-epibatidine binding, an increase in the α4 and ß2 protein levels, and an increase in ß2/α4 subunit ratio, that indicates an increased proportion of receptors with the (α4)2(ß2)3 stoichiometry. For thalamus we did not find a significant increase in receptor density, α4 and ß2 protein levels, or changes in ß2/α4 subunit ratio. All the changes elicited by chronic nicotine in cortex were transient and returned to basal levels with an average half-life of 2.8 days following nicotine withdrawal. These data suggest that chronic nicotine exposure in vivo favors increased assembly of α4ß2 nAChR containing three ß2 subunits. A greater change in stoichiometry was observed for cortex (which has relatively low basal expression of (α4)2(ß2)3 nAChR) than in thalamus (which has a relatively high basal expression of (α4)2(ß2)3 nAChR).

Years of life that could be saved from prevention of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥ 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

BACKGROUND: Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. AIM: To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. METHODS: A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. RESULTS: Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. CONCLUSIONS: Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice.

Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks. One hour after the last session, half of the animals were sacrificed for neurochemical analysis, and the others underwent mecamylamine-precipitated or spontaneous withdrawal for the purposes of behavioural analysis. Chronic intermittent non-contingent, second-hand exposure to cigarette smoke or e-cig vapour led to similar brain cotinine and nicotine levels, similar urine cotinine levels and the similar up-regulation of α4ß2 nicotinic acetylcholine receptors in different brain areas, but had different effects on body weight, food intake, and the signs of mecamylamine-precipitated and spontaneous withdrawal episodic memory and emotional responses. The findings of this study demonstrate for the first time that e-cig vapour induces addiction-related neurochemical, physiological and behavioural alterations. The fact that inhaled cigarette smoke and e-cig vapour have partially different dependence-related effects indicates that compounds other than nicotine contribute to tobacco dependence.

Glioneuronal tumors and epilepsy in children: seizure outcome related to lesionectomy.

AIM: Glioneuronal tumors (especially gangliogliomas and dysembryoplastic neuroepithelial tumors) are an increasingly recognised cause of drug-resistant epilepsy in children. The optimal surgical strategy (lesionectomy vs. extended resection of epileptogenic peritumoral areas) to obtain seizure control has not been fully established. Our aim was to analyze the post-surgical seizure outcome in children with epileptogenic glioneuronal tumors related to lesionectomy. METHODS: The clinical data were collected through a database. Video-EEG and MRI were performed in all patients pre-operatively and at the follow-up. RESULTS: Our series included 22 patients. The age range at surgery was 10 months-16 years (mean: 6.5±4.5 years). Epilepsy duration ranged 1-78 months (mean: 11.6±17.0). There were complex partial seizures in 14 cases, simple partial seizures in 6 patients and generalized epilepsy in 2. Gross-total surgical removal was achieved in 15 (68.2%) patients. At the last follow-up (mean 4.7 years), 20 (90.9%) patients were seizure-free (Engel Class I) and two (9.1%) were Engel Class III. Six out of seven (85.7%) patients with subtotal removal were Engel Class I. Statistical analysis failed to detect any difference between seizure outcome (Engel Class) and tumor type (DNT vs. GG; P=1.00) or location (temporal vs. non temporal; P=0.51), and extension of the resection (total vs. subtotal; P=1.00). CONCLUSION: Primary aim of the surgery for epileptogenic glioneuronal tumors is to remove the lesion and to obtain a complete seizure control. However, if a complete tumor resection cannot be carried out, a subtotal removal of the lesion can equally provide satisfactory results.

A comparison of risk factors as predictors of cardiovascular and non-cardiovascular mortality in the elderly people--relevance of N-terminal pro-B-type natriuretic peptide and low systolic blood pressure.

BACKGROUND: Many risk factors are known to predict ischaemic events and mortality in the elderly people, but their ranking of importance remains uncertain. This study was designed to identify and compare the main predictors of total mortality (TM), cardiovascular mortality (CVM) and non-cardiovascular mortality (NCVM) in older adults. METHODS: Nine hundred and seventy-nine community resident adults aged ≥ 65 years, free of previous heart failure and cardiovascular events, participated in the study. The univariate and multivariate (Cox regression) relationships of baseline cardiovascular risk factors, treatments and laboratory data with TM, CVM and NCVM were assessed after a median follow up of 6.7 years. RESULTS: Overall, there were 104 deaths (30 because of CVM and 74 to NCVM). In multivariate analysis, the following factors remained independently associated with mortality: NT pro-B-type natriuretic peptide (NT-proBNP) upper quintile (≥ 237 pg/ml for men, ≥ 280 pg/ml for women): hazard ratio (HR) vs. the rest of the population (95% confidence interval) 2.34 (1.52-3.60), p < 0.001 for TM; HR 5.41 (2.32-12.65), p < 0.001 for CVM; systolic blood pressure lower quintile (≤ 130 mmHg): HR 3.06 (1.80-5.21), p < 0.001 for NCVM; diabetes: HR 2.46 (1.29-4.72), p = 0.007 for NCVM; erythrocyte sedimentation rate (ESR) upper decile (≥ 41 mm/h): HR 2.33 (1.16-4.69), p = 0.02 for NCVM; platelet count lower quintile (≤ 177 × 10(9) /l): HR 2.09 (1.20-3.64), p = 0.009 for NCVM; ever-smoker status: HR 2.08 (1.23-3.52), p = 0.007 for NCVM. CONCLUSIONS: In elderly community dwellers, NT-proBNP was the strongest predictor of TM and CVM, while especially low systolic blood pressure, together with diabetes, ESR, reduced platelet count and ever-smoker status, were the main predictors of NCVM.

Extended endoscopic transplanum-transtuberculum approach for pituitary adenomas.

Few pituitary adenomas require removal through a transcranial route. This may be associated with more significant morbidity and mortality, compared to the transsphenoidal approach. An endoscopic, extended, transplanum-transtuberculum approach (ETTA) in selected pituitary adenomas may offer an alternative to the transcranial route. We describe our technique and experience of ETTA in pituitary adenomas over 10 years. Between 2000 and 2010, we performed 700 endoscopic endonasal procedures for pituitary adenomas. Nineteen patients (13 men; mean age, 48 years; range, 22-76 years) underwent 22 ETTAs. Thirteen patients had non-functioning adenomas. Three tumor groups were identified: (1) tumors developing in or around the pituitary stalk; (2) tumours with sub- frontal extension and (3) tumours with a major extrasellar component. Mean follow-up was 37 months (range 6-72 months). Gross total resection was achieved in 11 procedures (no recurrences), with partial tumour resection in 11 procedures. Of the 12 patients with visual symptoms, ten improved. Of eight patients with hormonal hypersecretion four were cured. Complications included CSF leak (14%), haemorrhage (9%), hemiplegia (5%). There were no mortalities. Experience using the ETTA for pituitary adenomas is limited because it is indicated in highly selected cases (3.1% of our series). An absolute indication is represented by ectopic secreting pituitary stalk/peri-stalk adenomas. ETTA is a useful option in midline frontal adenomas and adenomas with a major extrasellar component, but has a higher morbidity than that seen in the standard transsphenoidal approach. A study comparing ETTA versus transcranial resection is highly desirable.

Impact of evidence-based medicine on the treatment of patients with unresectable hepatocellular carcinoma.

BACKGROUND: A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well-selected patients with unresectable hepatocellular carcinoma (HCC). AIM: To access whether this information has modified the use of TACE in clinical practice. METHODS: From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4-year periods (1999-2002, n = 161 and 2003-2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival. RESULTS: Patients undergoing TACE increased in the 2003-2006 period (from 62% to 73%, P = 0.035), with an increase in of Child-Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999-2002 period, there was no significant difference in survival between TACE-treated and untreated patients, while in the 2003-2006 period, TACE-treated patients survived longer (P < 0.0001). CONCLUSIONS: Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well-compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage.

Splanchnic haemodynamics in non-alcoholic fatty liver disease: effect of a dietary/pharmacological treatment. A pilot study.

BACKGROUND: Previous studies demonstrated that in experimental animals fatty liver is associated with reduced hepatic blood flow and that metformin reverses steatosis, while no data were reported in humans. AIMS: To evaluate the clinical relevance of echo-Doppler measurements and the effects of therapy in non-alcoholic fatty liver disease. PATIENTS: Twenty patients with biopsy proven non-alcoholic fatty liver disease. METHODS: Abdominal echo-Doppler examination was performed at enrolment and, in 11 patients, after 6 months of dietary/pharmacological therapy (metformin 500 mg three times a day). RESULTS: Non-alcoholic fatty liver disease was characterised by hepatomegaly, bright echotexture and posterior attenuation. Mean portal blood velocity and flow were low-normal. Brightness and posterior attenuation significantly correlated with fat score in liver biopsies as well as with the hepatic veins spectrum. After therapy, echotexture improved and liver volume significantly decreased. Portal blood velocity and flow significantly increased, intrahepatic arterial indexes decreased and the spectrum of hepatic veins improved. CONCLUSIONS: Fatty liver is associated with an impaired hepatic blood flow characterised by increased intrahepatic resistances. Vascular changes are reversed by treatment and can be measured by echo-Doppler which may be useful to evaluate the natural course of non-alcoholic fatty liver disease, and to monitor the putative beneficial effects of therapy.

Perception of health-related quality of life and psychological status in oldest hospitalized patients without cognitive impairment.

The most diffuse questionnaires on health-related quality of life (HRQL) and/or psychological status (PS) consider all subjects older than 74 years, for normative reference values, in a single group without any further separation for age decades. Their authors assume that there are no further age-related differences, since older patients had a severely limited autonomy and lose the capacity of grading the severity of the diseases they are affected. Healthy subjects older than 80, without mental impairment (WMI) present an acceptable HRQL, PS and a perception of health status. No data are available on the oldest patients, carrying chronic diseases, admitted to hospital departments for acute health problems.We collected 46 WMI oldest patients (>/= 80 years), admitted for such troubles. They were investigated by the mini mental state examination (MMSE) and, in random order, the Nottingham health profile (NHP) and the psychological general well-being instrument(PGWBI). Clinical data recordings were carried out by the medical personnel, using standardized forms. The value of any individual domain of each patient was compared to the age - (>/=75-year) and sex-matched control group derived from two large Italian population studies, using the Z-score. Charlson's comorbidity index, the index of coexistent disease (ICED), and the cumulative illness rating scale (CIRS) were also calculated. Patients older than 80 did show difference in NHP domains in comparison with normative values only for social isolation, but presented significantly worse Z-scores in all domains ofPGWBI. A relationship was observed between number of daily medications and Z-scores of physical mobility and energy (NHP). Similarly, vitality (PGWBI) correlated with all comorbidity indices, ICED with positive well-being (PGWBI), pain (NHP) with CIRS subscales. Hospitalized WMI oldest subjects maintain a HRQL quite comparable to normative group of subjects older than 74 years. Furthermore, they showed a preserved correct perception of factors/diseases that possibly affect their psychological status and autonomy.

Gallstone disease and related risk factors in a large cohort of diabetic patients.

BACKGROUND AND AIM: The aim of this study of a large cohort of consecutive patients with diabetes mellitus was to investigate the still controversial questions concerning the prevalence and possible risk factors of gallstone disease in diabetics. PATIENTS AND METHODS: We enrolled 1337 consecutive patients (710 males aged 63 +/- 11 years and 627 females aged 65 +/- 11 years), of whom 1235 (92%) had type 2 and 102 (8%) had type 1 diabetes mellitus. The data were statistically analysed using multiple logistic regression analysis. RESULTS: The prevalence of gallstone disease was significantly higher in diabetics than in the general population with comparable characteristics (MICOL study) (332/1337 (24.8%) versus 4083/29684 (13.8%); z = 11.208, P = 0.0001) and this difference maintained its statistical significance even when only the North Italian centers involved in this nation-wide survey were considered (332/1337 (24.8%) versus 2469/18091 (13.6%); z = 11.225, P = 0.0001). A total of 332 diabetics (25%) had gallstone disease: 261 had stone(s) and 71 had previously undergone cholecystectomy for gallstone disease after a diagnosis of diabetes mellitus. The prevalence of gallstone disease was higher in the females (29% versus 22%, P = 0.003), and increased with age (13, 20 and 30% in patients aged < or = 40, 41-65 and > 65 years, respectively; P = 0.001), body mass index (24% in patients with a body mass index of < or = 30 and 30% in those with a body mass index of > 30 kg/m2; P = 0.001) and a positive family history of gallstone disease (31% versus 23%; P = 0.001). Gallstone disease was not significantly related to the type of diabetes, plasma total and HDL cholesterol and triglyceride levels, alcohol intake, smoking habits, physical activity, weight reduction in the last year, the use of oral contraceptives, parity or menopause. At multivariate analysis, increasing age, a higher body mass index and a positive family history maintained their statistical significance. CONCLUSIONS: In patients with type 1 or type 2 diabetes mellitus, the prevalence of gallstone disease was significantly related to age, body mass index and a family history of gallstone disease.

Impaired insulin-mediated amino acid plasma disappearance in non-alcoholic fatty liver disease: a feature of insulin resistance.

BACKGROUND AND AIM: Insulin resistance is a main feature, and possibly a pathogenic factor, of non-alcoholic fatty liver disease. It is usually measured on glucose metabolism; the effects on amino acid regulation have never been assessed. In particular, no data are available on insulin-dependent branched-chain amino acid metabolism, which is under insulin control. MATERIALS AND METHODS: We measured amino acid disappearance from plasma during an euglycemic glucose clamp in 39 biopsy-proven non-alcoholic fatty liver disease patients and in ten control subjects. A primed-constant infusion of insulin (constant rate, 40 mU/m2 per min for 2 h) was used to raise plasma insulin to approximately 100 mU/l. Euglycemia was maintained by a variable glucose infusion, a measure of tissue insulin sensitivity. Plasma amino acids were assayed during the clamp after ninhidrin derivatization. RESULTS: Fasting plasma amino acids were similar in the two groups. Steady-state insulin levels were significantly higher in non-alcoholic fatty liver disease patients, whereas tissue sensitivity to insulin was reduced by 50%. The plasma disappearance of branched-chain amino acids, as well as the disappearance of the sum of glutamine and glutamate and that of serine were significantly reduced in non-alcoholic fatty liver disease. Differences were maintained after adjustment for steady-state insulin, and correlated with reduced tissue sensitivity to glucose. CONCLUSION: Insulin resistance in non-alcoholic fatty liver disease patients also affects amino acid metabolism, especially for amino acids involved in peripheral muscle nitrogen exchange. The metabolic effects of altered protein/amino acid metabolism must be considered.

Reduced quality of life of patients with hepatocellular carcinoma.

BACKGROUND: It has been shown that health-related quality of life is reduced in patients with cirrhosis and with chronic hepatitis in relation to antiviral therapy. No data are available on patients with hepatocellular carcinoma. AIM: To assess health-related quality of life in cirrhotic patients with hepatocellular carcinoma. PATIENTS AND METHODS: Health-related quality of life was assessed in 101 hepatocellular carcinoma patients by means of Short Form-36 and Nottingham Health Profile questionnaires. Final scores of domains for individual patients were compared to age-adjusted normative Italian values, using Z-score and with values obtained in 202 matched patients with cirrhosis, without hepatocellular carcinoma. RESULTS: All Short Form-36 domains and 4 out of 6 Nottingham Health Profile domains were altered. When hepatocellular carcinoma patients were compared with matched cirrhotics, differences were present for Bodily Pain, Role Limitation-Physical, and the Physical Component Summary of Short Form-36, as well as Pain of Nottingham Health Profile. Perceived health status had changed significantly in the year prior to assessment. Health-related quality of life was not primarily related to tumour mass or hepatocellular failure, whereas sleep disorders were selected by logistic regression as strongly associated with poor health-related quality of life. CONCLUSIONS: The present data stress the relevance of pain in poor perceived health status of hepatocellular carcinoma patients, and the importance of minor symptoms, such as sleep disorders.

Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors.

The mesostriatal dopaminergic system influences locomotor activity and the reinforcing properties of many drugs of abuse including nicotine. Here we investigate the role of the alpha4 nicotinic acetylcholine receptor (nAChR) subunit in mediating the effects of nicotine in the mesolimbic dopamine system in mice lacking the alpha4 subunit. We show that there are two distinct populations of receptors in the substantia nigra and striatum by using autoradiographic labelling with 125I alpha-conotoxin MII. These receptors are comprised of the alpha4, beta2 and alpha6 nAChR subunits and non-alpha4, beta2, and alpha6 nAChR subunits. Non-alpha4 subunit-containing nAChRs are located on dopaminergic neurons, are functional and respond to nicotine as demonstrated by patch clamp recordings. In vivo microdialysis performed in awake, freely moving mice reveal that mutant mice have basal striatal dopamine levels which are twice as high as those observed in wild-type mice. Despite the fact that both wild-type and alpha4 null mutant mice show a similar increase in dopamine release in response to intrastriatal KCl perfusion, a nicotine-elicited increase in dopamine levels is not observed in mutant mice. Locomotor activity experiments show that there is no difference between wild-type and mutant mice in basal activity in both habituated and non-habituated environments. Interestingly, mutant mice sustain an increase in cocaine-elicited locomotor activity longer than wild-type mice. In addition, mutant mice recover from depressant locomotor activity in response to nicotine at a faster rate. Our results indicate that alpha4-containing nAChRs exert a tonic control on striatal basal dopamine release, which is mediated by a heterogeneous population of nAChRs.