Post-operative morbidity in Crohn's disease: what is the impact of patient-, disease- and surgery-related factors?

PURPOSE: Over 50% of patients suffering from Crohn's disease (CD) require surgery in their lifetime. Predictors/risk factors of post-operative morbidity and mortality in CD are poorly investigated. We aimed to assess the risk factors of post-operative morbidity/mortality in CD. METHODS: We performed a retrospective cohort study in which all CD patients operated and followed up at our tertiary Inflammatory Bowel Disease Centre from 2014 to 2019 were enrolled. For each patient, we evaluated patient-dependent, disease-dependent and surgery-dependent variables. All patients underwent small bowel and/or colic resections. RESULTS: Of the 165 operated patients, forty-two (25.5%) developed post-operative complications (major complication rate = 9.8%) including wound infection (12.1%), respiratory complications (4.8%), prolonged ileum (4.2%), anastomotic leak (3.6%), urinary infections (3%), abdominal abscess (2.4%), anastomotic bleeding (3.6%), abdominal bleeding (1.2%) and obstruction (0.6%). Two subjects (1.2%) required re-operation within 30 days, and one died. A surgery duration < 141 min was predictive of a better post-operative outcome (sensitivity 80.9%, specificity 43.1%, PPV 32.7%, NPV 86.9%). The multivariable analysis showed stricturing/fistulizing behaviour (OR 3.7, 95% CI 1.6-6.4, p = 0.02), need for total parenteral nutrition (OR 4.1, 95% CI 2.4-9.2, p = 0.01), pre-operative bowel cleansing (OR 0.6, 95% CI 0.41-0.83, p = 0.01) and surgery duration < 141 min (OR 0.2, 95% CI 0.08-0.7, p = 0.03) as the only risk factors associated with post-operative morbidities. CONCLUSIONS: About 25% of CD patients develop post-operative complications. Several patient-related, disease-related and surgery-related factors should be considered risk factors for post-operative morbidity. The recognition of these factors, as well as a multidisciplinary approach to the pre-operative management of CD, could reduce post-operative complications.

Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial.

The polyphenol resveratrol is considered to exert many beneficial actions, such as antioxidant, anti-inflammatory, insulin-sensitizer and anticancer effects. Its benefits in patients with type 2 diabetes mellitus (T2DM) are controversial. Our aims were to determine whether resveratrol supplementation at two different dosages (500 and 40mg/day) for 6 months i) reduced the concentrations of C-reactive-protein (CRP) and ii) ameliorated the metabolic pattern of T2DM patients. In the present double-blind, randomized, placebo-controlled trial, 192 T2DM patients were randomized to receive resveratrol 500mg/day (Resv500arm), resveratrol 40mg/day (Resv40arm) or placebo for 6-months. At baseline and at the trial end, CRP values, anthropometric, metabolic and liver parameters were determined. No serious adverse event occurred. A dose-dependent, though not significant, CRP decrease of 5.6% (Resv40arm) and 15.9% (Resv500arm) was observed vs placebo. We failed to detect significant differences in weight, BMI, waist circumference, and values of arterial blood pressure, fasting glucose, glycated hemoglobin, insulin, C-peptide, free fatty acids, liver transaminases, uric acid, adiponectin, interleukin-6, in both the Resv500 and Resv40 arms vs placebo. Total cholesterol and triglycerides slightly increased in the Resv500arm. Subgroup analyses revealed that lower diabetes duration (in both Resv500 and Resv40arms), and, in the Resv500arm, younger age, aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo. The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations, nor improve the metabolic pattern of T2DM patients.

The lipid theory in the pathogenesis of calcific aortic stenosis.

AIMS: Biologically active phenomena, triggered by atherogenesis and inflammation, lead to aortic valve (AV) calcification. Lipids play an important role in activating the cell signaling leading to AV bone deposition. This review, based on evidence from animal and human studies, mainly focused on the involvement of lipids and atherogenic phenomena in the pathogenesis of calcific aortic stenosis (AS). DATA SYNTHESIS: The role of elevated low density lipoproteins for the risk of both vascular atherosclerosis and AS has been elucidated. Lipid disorders act synergistically with other risk factors to increase prevalence of calcific AS. Atherosclerosis is also involved in the pathogenesis of bone demineralization, a typical hallmark of aging, which is associated with ectopic calcification at vascular and valvular levels. Animal studies have recently contributed to demonstrate that lipids play an important role in AS pathogenesis through the activation of molecular cell signalings, such as Wnt/Lrp5 and RANK/RANKL/Osteprotegerin, which induce the transition of valvular myofibroblasts toward an osteogenic phenotype with consequent valvular bone deposition. Although all these evidence strongly support the lipid theory in AS pathogenesis, lipids lowering therapies failed to demonstrate in controlled trials a significant efficacy to slow AS progression. Encouraging results from animal studies indicate that physical activity may counteract the biological processes inducing AV degeneration. CONCLUSIONS: This review indicates a robust interplay between lipids, inflammation, and calcific AS. This new pathophysiological scenario of such an emerging valvular disease paves the way to the next challenge of cardiovascular research: "prevent and care aortic valve stenosis".

Strongly Interacting Gas of Two-Electron Fermions at an Orbital Feshbach Resonance.

We report on the experimental observation of a strongly interacting gas of ultracold two-electron fermions with an orbital degree of freedom and magnetically tunable interactions. This realization has been enabled by the demonstration of a novel kind of Feshbach resonance occurring in the scattering of two (173)Yb atoms in different nuclear and electronic states. The strongly interacting regime at resonance is evidenced by the observation of anisotropic hydrodynamic expansion of the two-orbital Fermi gas. These results pave the way towards the realization of new quantum states of matter with strongly correlated fermions with an orbital degree of freedom.

Optimizing design and fabrication of microfluidic devices for cell cultures: An effective approach to control cell microenvironment in three dimensions.

The effects of gradients of bioactive molecules on the cell microenvironment are crucial in several biological processes, such as chemotaxis, angiogenesis, and tumor progression. The elucidation of the basic mechanisms regulating cell responses to gradients requires a tight control of the spatio-temporal features of such gradients. Microfluidics integrating 3D gels are useful tools to fulfill this requirement. However, even tiny flaws in the design or in the fabrication process may severely impair microenvironmental control, thus leading to inconsistent results. Here, we report a sequence of actions aimed at the design and fabrication of a reliable and robust microfluidic device integrated with collagen gel for cell culturing in 3D, subjected to a predetermined gradient of biomolecular signals. In particular, we developed a simple and effective solution to the frequently occurring technical problems of gas bubble formation and 3D matrix collapsing or detaching from the walls. The device here proposed, in Polydimethylsiloxane, was designed to improve the stability of the cell-laden hydrogel, where bubble deprived conditioning media flow laterally to the gel. We report the correct procedure to fill the device with the cell populated gel avoiding the entrapment of gas bubbles, yet maintaining cell viability. Numerical simulations and experiments with fluorescent probes demonstrated the establishment and stability of a concentration gradient across the gel. Finally, chemotaxis experiments of human Mesenchymal Stem Cells under the effects of Bone Morphogenetic Protein-2 gradients were performed in order to demonstrate the efficacy of the system in controlling cell microenvironment. The proposed procedure is sufficiently versatile and simple to be used also for different device geometries or experimental setups.

The nose and sinus manometry: a bio-physical model applied to functional endoscopic sinus surgery.

The effectiveness of sinus ventilation is due to a regular anatomy of inner nose structures such as the maxillary sinus ostium. With the aid of nose and sinus manometric measurements, it is possible to show that better functional results can be achieved using a conservative surgical technique. The present study compared 30 patients subdivided in two groups. Group A underwent conservative endoscopic sinus surgery whereas group B was operated on using non-conservative endoscopic sinus surgery. Thirty days later, both groups underwent a manometric survey of the maxillary sinus ostium by means of the digital manometry system. The pressure values obtained by nasal and sinus manometry in Group A or Group B patients were referred to those obtained in a Standard Group without nasal-sinus pathologies, calculating a percentage index of functional efficacy (maxillary sinus functional efficacy). The average percentage of the maxillary sinus functional efficacy was 98,35 percent for group-A patients, and 49,73 percent for group-B patients. Student t test revealed a statistical difference only between group B patients and standard group patients (p less than 0.4). Patients submitted to a more aggressive endoscopic approach showed inadequate sinus ventilation when compared to the standard reference group.

Myocardial ß(2) -adrenoceptor gene delivery promotes coordinated cardiac adaptive remodelling and angiogenesis in heart failure.

BACKGROUND AND PURPOSE: We investigated whether ß(2) -adrenoceptor overexpression could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodeling of the failing heart. EXPERIMENTAL APPROACH: We explored the angiogenic effects of ß(2) -adrenoceptor overexpression in a rat model of post-myocardial infarction (MI) heart failure (HF). Cardiac adenoviral-mediated ß(2) -adrenoceptor overexpression was obtained via direct intramyocardial injection 4-weeks post-MI. Adenovirus(Ad)-GFP and saline injected rats served as controls. Furthermore, we extended our observation to ß(2) -adrenoceptor -/- mice undergoing MI. KEY RESULTS: Transgenes were robustly expressed in the LV at 2 weeks post-gene therapy, whereas their expression was minimal at 4-weeks post-gene delivery. In HF rats, cardiac ß(2) -adrenoceptor overexpression resulted in enhanced basal and isoprenaline-stimulated cardiac contractility at 2-weeks post-gene delivery. At 4 weeks post-gene transfer, Ad-ß(2) -adrenoceptor HF rats showed improved LV remodeling and cardiac function. Importantly, ß(2) -adrenoceptor overexpression was associated with a markedly increased capillary and arteriolar length density and enhanced in vivo myocardial blood flow and coronary reserve. At the molecular level, cardiac ß(2) -adrenoceptor gene transfer induced the activation of the VEGF/PKB/eNOS pro-angiogenic pathway. In ß(2) -adrenoceptor-/- mice, we found a ~25% reduction in cardiac capillary density compared with ß(2) -adrenoceptor+/+ mice. The lack of ß(2) -adrenoceptors was associated with a higher mortality rate at 30 days and LV dilatation, and a worse global cardiac contractility compared with controls. CONCLUSIONS AND IMPLICATION: ß(2) -Adrenoceptors play an important role in the regulation of the angiogenic response in HF. The activation of VEGF/PKB/eNOS pathway seems to be strongly involved in this mechanism.

Plasma visfatin concentrations after a lifestyle intervention were directly associated with inflammatory markers.

BACKGROUND AND AIMS: The biological activity and regulation of the novel adipokine visfatin are still largely unknown. Our aim was to evaluate if visfatin plasma concentrations may be influenced by a lifestyle intervention. METHODS AND RESULTS: Out of 335 dysmetabolic patients from a population-based cohort, randomized to receive a lifestyle intervention program (intervention group) or family physician usual care (controls), 20 patients per group were randomly selected for plasma visfatin determination. The before-after variation (Delta) in visfatin concentration at 1-year from randomization, and the correlations between (Delta)visfatin and intervention-induced changes in waist circumference, fasting glucose, markers of inflammation, and oxidative stress were evaluated. The intervention group showed a significant improvement in waist circumference, and many metabolic/inflammatory variables, while the controls worsened. Visfatin concentrations slightly decreased in the former and significantly increased in the controls ((Delta)visfatin=-2.4 vs 66.0 ng/ml, p<0.001). In robust regression models, the following variables resulted associated with (Delta)visfatin: (Delta)waist circumference, (Delta)fasting glucose, (Delta)hs-CRP (high-sensitivity C-reactive protein) and (Delta)TNFalpha (tumor necrosis factor-alpha). Significant effects on (Delta)visfatin of (Delta)TNFalpha (beta=16.8; 6.1-25.6; p=0.003) and, modified by group, of (Delta)hs-CRP (beta=29.8; 95% CI 15.4-44.2; p<0.001 and beta=4.2; 2.9-5.5; p<0.001 in the control and intervention group, respectively) were detected. By controlling for (Delta)waist, the effects of (Delta)TNFalpha and of (Delta)hs-CRP on (Delta)visfatin by group did not change, while (Delta)waist was no longer associated. The association between (Delta)visfatin and (Delta)glucose was no longer significant, after adjusting for (Delta)hs-CRP. CONCLUSION: Visfatin values increased with waist circumference and were associated with variations of inflammatory markers, suggesting participation in inflammatory mechanisms.

Associations between serum uric acid and adipokines, markers of inflammation, and endothelial dysfunction.

AIM: Serum uric acid is associated with the metabolic syndrome and its components, while its relationship with cardiovascular disease is controversial. The aim of the study was to evaluate the association between uric acid and adipokines, markers of inflammation, oxidative stress, and endothelial dysfunction, which are all linked to cardiovascular disease. METHODS: The associations between uric acid and adiponectin, resistin, leptin, high-sensitivity-C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-alpha, nitrotyrosine, Total Antioxidant Status (TAS), E-selectin, vascular adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were cross-sectionally evaluated in a randomly collected sample of 100 men from a population-based cohort. RESULTS: Subjects within the highest uric acid quartile showed a worse metabolic pattern and a higher prevalence of the metabolic syndrome [odds ratio (OR)=3.6; 95% confidence interval (CI) 1.6-8.2; p<0.001 for each 50 micromol/l uric acid increment in a logistic regression model after multiple adjustments]. Nitrotyrosine and adiponectin were significantly lower, while TAS, hs-CRP, E-selectin, ICAM-1, and VCAM-1 were higher in the groups with increased uric acid levels. In a multiple regression model, after adjustments for multiple confounders, uric acid levels were inversely associated with nitrotyrosine (p<0.001) and adiponectin (p=0.02), and directly with TAS (p<0.001), and E-selectin (p=0.006). CONCLUSION: Serum uric acid showed opposite relationships, being associated with both beneficial (inverse association with nitrotyrosine, direct association with TAS) and detrimental (inverse association with adiponectin, direct association with E-selectin) markers, thus providing a possible explanation for the previously reported controversial and not linear association between uric acid and cardiovascular disease.

Comparison of two enzyme immunometric assays to measure tumor necrosis factor-alpha in human serum.

BACKGROUND: Tumor necrosis factor-alpha is a 17.5 kDa, 157 amino acid protein that is a potent lymphoid factor, which exerts cytotoxic effects on a wide range of tumor cells and other target cells. TNF-alpha has been suggested to play a pro-inflammatory role by influencing transendothelial migration of monocytes and elicits the expression of proteolytic enzymes by macrophages and smooth muscle cells within the atherosclerotic plaque. METHODS: We compared two methods for the quantitative determination of human tumor necrosis factor-alpha in serum samples. Either kit follows the same assay procedure. Serum samples do not need to be diluted before sampling. Standard is provided lyophilized and serial dilutions after reconstitution generate the standard point curves. The tests are enzyme immunometric assays based on a standard 96-well microtiter plate. The wells are coated with anti-human TNF-alpha antibody. RESULTS: The range of the standard curve is similar in both kits. It spans from 1000 through 15.6 pg/mL. The median TNF-alpha concentration in samples measured by Pierce assay (n=368) was 4.23 pg/mL, (range, 1.34-77.2 pg/mL). A very different median was obtained for the same specimen measured with the Titerzyme EIA (median, 176.96 pg/mL; range, 54.7-283.9 pg/mL; n=364). Substantial significant differences were observed between the two methods. CONCLUSION: Our results show that the two kits are unmatchable for results they can give when TNF-alpha concentrations are measured in serum samples. One reason of this disagreement could be the matrix effect or a cross-reactivity of one of the two methods. This study shows that the determination of human serum TNF-alpha needs to be standardized, especially when a comparison of results is required.

C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia.

OBJECTIVES AND STUDY DESIGN: Increasing evidences support an inflammatory origin for gestational hyperglycemia. This paper aims at investigating, cross-sectionally and prospectively, the relationships between tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) levels in normoglycemic and hyperglycemic pregnancies of women with and without conventional risk factors for gestational diabetes (GDM). RESULTS: Both at simple and multiple correlations TNF-alpha levels are associated to fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) values and gestational hyperglycemia, while high sensitivity CRP (hsCRP) levels to body mass index (BMI). Furthermore, the TNF-alpha levels of the second trimester and their increments in the third trimester are significant predictors of insulin levels measured at 32-36 weeks in the subgroup of hyperglycemic women with < or = 35 yr, BMI <25 kg/m2 and the absence of a first-degree relative with Type 2 diabetes (respectively, beta=1.1; 95%CI 0.66-1.48; p=0.002 and beta=1.0; 95%CI 0.36-1.66; p=0.02), in a multiple regression model, after multiple adjustments. In a second cohort of women at low risk for GDM (<25 yr, BMI <25 kg/m2 and absence of a first-degree relative with Type 2 diabetes), 24-28 weeks TNF-alpha levels are highly associated with corresponding insulin and HOMA values in the same model (respectively, beta=0.27; 95%CI 0.11-0.43; p=0.001 and beta=0.30; 95%CI 0.14-0.46; p<0.001). CONCLUSIONS: The data support the developing hypothesis that low-grade systemic inflammation is associated to GDM, in particular for pregnant women without conventional risk factors for gestational hyperglycemia, whose insulin resistance seems less explainable.

Plasma nitrotyrosine levels, antioxidant vitamins and hyperglycaemia.

AIMS: Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury, in diabetes are limited and discordant; the amount of antioxidants might represent a possible explanation for the discordant results. The aim of this paper is to evaluate the association between plasma NT levels and glucose tolerance status, according to antioxidant vitamin intakes. METHODS: In three hundred men randomly selected from a population-based cohort, NT levels were measured and dietary intake assessed by a food-frequency questionnaire. Results NT values were similar in patients with diabetes (n = 34), impaired fasting glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with lower than recommended daily intakes of antioxidant vitamins C and A, NT levels were significantly higher in the diabetic patients. In a multiple regression model, after adjustments for age, body mass index (BMI) and smoking habits, NT levels were significantly associated with fasting glucose in patients with lower intakes of vitamin C (beta = 11.4; 95% CI 1.3-21.5) and vitamin A (beta = 14.9; 95% CI 3.9-25.9), but not in subjects with lower intake of vitamin E. CONCLUSION: A significant positive correlation between NT levels and fasting glucose is evident only in the presence of a reduced intake of some antioxidant vitamins. These findings might explain, at least in part, the discrepant results of previous studies and, if confirmed by further studies, suggest a simple measure (a balanced diet) to alleviate the increased oxidative stress of diabetes.

Relationships between human serum resistin, inflammatory markers and insulin resistance.

OBJECTIVE: Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)). SUBJECTS: A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values. RESULTS: Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45). CONCLUSIONS: Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.

Does C-reactive protein identify a subclinical metabolic disease in healthy subjects?

BACKGROUND: Highly sensitive C-reactive protein (hs-CRP) levels are significant predictors of subsequent diabetes and metabolic syndrome (MS). Owing the strong correlations between components of the MS and obesity with hs-CRP levels, previous studies about the associations of hs-CRP with insulin resistance might have been confounded by the inclusion of overweight or dysmetabolic subjects. DESIGN: Our aim was to evaluate the associations between hs-CRP levels and fasting insulin and insulin resistance (evaluated by the Homeostasis Model Assessment: HOMA IR) in a subgroup of subjects with normal body mass index (BMI) and without any metabolic abnormalities. Out of a cohort of 1658 middle-aged subjects, representative of the local sanitary districts of the province of Asti (north-western Italy) enrolled for metabolic screening: 241 (14.5%) showed normal BMI, glucose tolerance, blood pressure and waist values and no dyslipidaemia. RESULTS: In this subgroup of subjects, those with hs-CRP levels > or = 3 mg L(-1) showed significantly higher median insulin and HOMA-IR values (respectively: 20.4 vs. 6.0 pmol L(-1), and 0.8 vs. 0.2 microU mL(-1)x mmol L(-1)). In a multiple regression model, insulin and insulin resistance remained significantly and independently related to hs-CRP levels, after adjustments for age, sex, BMI, waist, alcohol consumption, level of physical activity and smoking habits. Very few individuals within lower fasting insulin quartiles showed hs-CRP values > or = 3 mg L(-1) when compared with approximately 60% of those within the highest quartile. CONCLUSIONS: The novel finding is that a state of low-grade systemic inflammation is present in normal BMI subjects who show subclinical insulin resistance but no other metabolic abnormalities.

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) has been associated with the metabolic syndrome. However, it is not clear whether insulin resistance is an independent feature of NAFLD, and it remains to be determined which of the in vivo actions of insulin are impaired in this condition. METHODS: We performed a two-step (1.5 and 6 pmol min(-1) kg(-1)) euglycaemic insulin clamp coupled with tracer infusion ([6,6-2H2]glucose and [2H5]glycerol) and indirect calorimetry in 12 non-obese, normolipidaemic, normotensive, non-diabetic patients with biopsy-proven NAFLD and six control subjects. RESULTS: In NAFLD patients, endogenous glucose production (basal and during the clamp) was normal; however, peripheral glucose disposal was markedly decreased (by 30% and 45% at the low and high insulin doses, respectively, p<0.0001) at higher plasma insulin levels (p=0.05), due to impaired glucose oxidation (p=0.003) and glycogen synthesis (p<0.001). Compared with control subjects, glycerol appearance and lipid oxidation were significantly increased in NAFLD patients in the basal state, and were suppressed by insulin to a lesser extent (p<0.05-0.001). The lag phase of the in vitro copper-catalysed peroxidation of LDL particles was significantly shorter in the patients than in the control subjects (48+/-12 vs 63+/-13 min, p<0.04). Lipid oxidation was significantly related to endogenous glucose production, glucose disposal, the degree of hepatic steatosis, and LDL oxidisability. CONCLUSIONS/INTERPRETATION: Insulin resistance appears to be an intrinsic defect in NAFLD, with the metabolic pattern observed indicating that adipose tissue is an important site.

Renal damage in patients with Type 2 diabetes: a strong predictor of mortality.

AIMS: (i) To compare mortality rates in a cohort of Type 2 diabetic patients with those of the general population; (ii) to assess the prognostic role of pre-existing chronic conditions; (iii) to evaluate the impact of different severity of renal damage on mortality. METHODS: All 3892 patients with Type 2 diabetes attending our Diabetic Clinic during 1995 and alive on 1 January 1996 were identified and followed for 4.5 years. Information on vital status (100% complete) and causes of death (98.5% complete) for 599 deceased subjects was derived from death certificates. RESULTS: In comparison with the general population, standardized mortality ratios (x 100) were: 125 (95% confidence interval 104-148) in patients aged < 75 and 85 (75-95) in patients > or = 75 years. Cardiovascular diseases and diabetes were responsible for most of the excess deaths. In a Cox-proportional hazard model, renal damage was a powerful predictor of death (hazard ratio = 2.39; 95% confidence intervals = 2.00-2.85). The severity of renal damage was associated with increasing hazard ratios for death from all-cause mortality and from specific causes (especially coronary artery disease, other cardiovascular causes and diabetes) after multiple adjustments. Other significant predictors of death were: greater age, glycated haemoglobin, smoking, lower body mass index, pre-existing coronary and peripheral artery disease and known co-morbidity (cirrhosis and cancer). CONCLUSIONS: Renal damage of any severity is significantly associated with subsequent mortality from all causes and from cardiovascular diseases. These associations are not confounded by pre-existing co-morbidity or coronary diseases.

Nose: aesthetics and function. Rhinoplasty and functional problems related to anterior ethmoid.

Aesthetic nasal surgery has progressed in the last years, as concerning both surgical techniques and surgical instruments, which allowed the finding of new and more sophisticated surgical solutions. Clinical practice led to observe sometimes functional surgical failures, due rather than an inaccurate surgical technique, to an incomplete diagnostic approach to the patient. It has been observed that modifying the external conformation of nasal pyramidis inner-nose volumes and spaces will be subsequently reduced, giving as a result a condition which is only aesthetically but not functionally valid. 32 subjects, selected for a rhinoplasty and presenting nasal respiratory obstruction and anterior ethmoid abnormalities, confirmed by nasal endoscopy and nasal CT, were evaluated and subdivided into two groups: the first (A) group underwent only to an aesthetic rhinoplasty, the second group (B) was operated of a rhinoplasty combined with functional endoscopic sinus surgery (FESS) in order to correct the above mentioned anatomical abnormalities. The nasal airflow, and though the nasal cavities patency, was evaluated pre- and post-operatively in the two groups of patients, referring to rhinomanometric conductance values. Patients of group A reported decreased post-operative conductance values, patients of group B reported increased post-operative conductance values, showing though the functional involvement of anterior ethmoid in nasal obstruction and the necessity of correcting its anatomical abnormalities, in order to reach not only a new nasal profile, but also a better respiratory performance.

A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years.

AIMS: To assess if a clinically orientated approach improves screening for latent autoimmune diabetes in adults (LADA) in patients developing diabetes over age 50. METHODS: From a clinic-based cohort of 3327 patients with Type 2 DM diagnosed over age 50 we recruited those with at least one feature suggestive of insulin deficiency: (i) fasting blood glucose > or = 15 mmol/l and/or HbA(1c) > or = 10% in spite of adequate compliance to diet and treatment; (ii) decreasing body weight > or = 10% in the previous 3 months in spite of constant diet; (iii) BMI < 25 mg/kg(2). A control group of 240 patients not presenting any of the previous criteria was randomly selected from the out-patient clinic. RESULTS: We identified 220 (6.6%) patients, of whom 70 were positive for glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA), giving a prevalence of LADA of 31.8% (95% CI 25.7-38.4). In contrast, no patient randomly selected from the remaining cohort had marker positivities. With respect to patients negative for both ICA and GADA, those who were positive had lower C-peptide values (0.53 +/- 0.51 vs. 0.88 +/- 0.42 nmol/l, P < 0.001); the lowest levels were found in patients in whom both antibodies were positive. In linear regression analysis, variables independently associated with fasting C-peptide were GADA (beta = -0.25, P < 0.001), ICA (beta = -0.15, P = 0.04), BMI (beta = 0.03, P < 0.001) and duration of diabetes (beta = -0.02, P < 0.001). CONCLUSION: This study shows that: (i) a clinically orientated approach increases the efficiency of a screening programme for LADA, so that one in three screened patients are classified correctly; (ii) ICA and GADA positivity were negatively associated with residual beta-cell function, independent of BMI and duration of the disease; (iii) positivity for both ICA and GADA identifies patients with the lowest residual beta-cell function.

[Intraperitoneal hemorrhage from rupture of an aneurysm of splenic artery: case report and literature review]. / Emoperitoneo da fissurazione di aneurisma dell'arteria splenica: case report e revisione della letteratura.

Splenic artery aneurysm presented with rupture is an unusual and potentially deadly reason of intraperitoneal hemorrhage. There are a lot of pathogenetic hypothesis; timing according to disease severity and surgical choices aren't definitely codified authors present one patient with hemoperitoneum for ruptured splenic artery aneurysm affected by chronic lymphatic leukaemia too and review international literature; they underline pathogenesis, symptoms, preoperative investigations and therapy. Degeneration of the media, atherosclerotic changes and high blood flow due to pregnancy and portal hypertension could be the main pathogenetic factors. Ultrasonography is the first investigation we have to practice if we suspect hemoperitoneum. We can practice computed tomography and angiography too if cardiovascular condition are good. Rupture showing acute abdominal pain and cardiovascular collapse suggest strongly urgent operation. The choice of operation is determined by location of the aneurysm. When located in the distal third of the splenic artery, the aneurysm is resected with spleen; alternatively, when it is located in prossimal third we can perform conservative operation.