Sex-difference of multifactorial intervention on cardiovascular and mortality risk in DKD: post-hoc analysis of a randomised clinical trial.

OBJECTIVE: Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men. RESEARCH DESIGN AND METHODS: Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure < 130/80 mmHg, HbA1c < 7%, LDL < 100 mg/dL, and total cholesterol < 175 mg/dL) on cardiovascular and mortality risk in patients with type 2 diabetes. In this post-hoc analysis, we stratified patients by sex to compare the occurrence of MACEs (primary endpoint) and all-cause death (secondary endpoint) between women (104 MT and 105 UC) and men (103 MT and 83 UC). RESULTS: Achievement of therapeutic goals was similar by sex, with 44% and 47% of women and men in MT achieving at least 3 targets vs. 16% and 20% of women and men in UC. During a median follow-up of 13.0 years, we recorded 262 MACE (48.5% in women) and 189 deaths (53.6% in women). Compared to the UC group, the risk of MACE in the MT group was reduced by 52% in women and by 44% in men (P = 0.11). Conversely, the reduction in mortality risk by MT was greater in women (44% versus 12%, P = 0.019). CONCLUSIONS: MT similarly reduces the risk of MACEs in either sex. This therapeutic approach is associated with a survival advantage in women as compared with men and it may represent an important rationale to motivate physicians in overcoming their therapeutic inertia often encountered in female patients as well as to encourage patients of both sexes at improving their adherence to multidrug therapy.

Dynamic optical coherence tomography evaluation in locally advanced basal cell carcinoma during sonidegib treatment.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs. OBJECTIVE: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques. METHODS: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions. RESULTS: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology. CONCLUSION: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy.

Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study.

BACKGROUND AND AIMS: Recently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR-DKD in T2DM. METHODS AND RESULTS: A total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (CKD) (p = 0.009), above all in those with CKD and AER ≥0.03 g/24 h (p = 0.005). Multivariate analysis confirmed that eGFR (O.R. 0.976; 95% C.I.: 0.960-1.028; p < 0.001) and AER (O.R. 1.249; 95% C.I. 1.001-1.619; p = 0.004) were independently associated with DR and HDL-cholesterol (O.R.: 1.042; 95% C.I.: 1.011-1.120; p = 0.014). Additionally, among patients with eGFR <60 mL/min/1.73 m2 and albuminuria, both eGFR and AER significantly varied between those with/without DR (p = 0.012 and p = 0.005, respectively), and this finding was observed among only albuminuric patients. Analogous results were obtained considering DR classification. AER was significantly higher among subjects with either proliferative DR (PDR) or severe nonproliferative DR (NPDR), with regard to mild NPDR (0.498 and 0.938 g/die vs. 0.101 g/die; p < 0.001, respectively). Similar results were obtained in the specular subgroups. CONCLUSION: In T2DM with DKD, the AER seems to be related to the presence of DR. This association is confirmed above all in those with more severe DR.

Application and internal validation of lung ultrasound score in COVID-19 setting: The ECOVITA observational study.

BACKGROUND: The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support. METHODS: In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area. RESULTS: One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity). CONCLUSIONS: The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.

Multiparametric correlation of laboratory biomarkers to multiorgan failure outcome in hospitalized COVID-19 patients: a retrospective observational study.

OBJECTIVE: COVID-19 is an extremely contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that will keep broadly circulating and evolving. Collected evidence revealed the clinical profile of COVID-19 patients as a potential predictor of their outcome. The aim of this study was to investigate the causal relationship between poor outcomes and laboratory parameters in hospitalized COVID-19 patients, in this sense observing how SARS-CoV-2 infection affects other organs. PATIENTS AND METHODS: We retrospectively evaluated a cohort of 133 patients, positive for SARS-CoV-2, aged between 30 to 94 years, between January 12th and April 25th, 2021. Discharge from the hospital, transferral to the ordinary ward or nursing home, intensive care unit (ICU) admission, and in-hospital mortality were recorded, along with demographic, laboratory and clinical parameters. The whole sample was summarized by median (interquartile range) for quantitative data, and absolute and relative percentage frequencies for qualitative variables. Univariable logistic regression models were performed to assess the association between all the parameters of interest and COVID-19 adverse outcomes, single (in-hospital mortality) and composite (in-hospital mortality and ICU admission). Hence, a multivariable model was fitted to identify potential independent predictors of the composite outcome. The accuracy of the model was assessed through appropriate fitting indices, such as the C-statistic and Hosmer-Lemeshow test. Moreover, to detect multicollinearity, the variance inflation factor (VIF) was used. RESULTS: Our study sample had a median age of 72 years old (59.0-83.0). The most common comorbidities were hypertension (63.7%), cardiovascular disease (41.9%), diabetes (33.6%), and cerebrovascular disease (21.5%); while as the most common symptoms, we observed dry cough (32.5%), dyspnoea (50.8%), and fatigue (29.8%). Totally, 18 patients died during hospitalization (13.5%), 10 required ICU admission (7.5%), 78 (58.6%) were discharged from the hospital, and 27 (20.3%) were transferred to either ordinary wards or nursing homes. We disclosed an association of older age with both composite [OR 1.06, 95% CI 1.02-1.09; p=0.003] and single outcome [OR 1.10, 95% CI 1.04-1.16; p=0.001]. A higher oxygen saturation (SpO2) was associated with a better outcome [OR 0.75, 95% CI 0.60-0.93; p=0.009 and OR 0.76, 95% CI 0.61-0.95, p=0.009]. Among laboratory parameters, higher levels of neutrophils increased the risk of a poor outcome [OR 1.05, 95% CI 1.00-1.10; p=0.043]; while higher levels of lymphocytes seem associated with a better outcome [OR 0.94, 95% CI 0.88-0.99; p=0.043]. Higher levels of creatinine were associated with a higher risk of both adverse outcomes [OR 6.20, 95% CI 2.16-17.81; p<0.001 and OR 19.90, 95% CI 5.07-78.06; p<0.001, respectively]. Higher levels of sodium (Na) were associated with a higher risk of adverse events [OR 1.15, 95% CI 1.03-1.28; p=0.014 and OR 1.14, 95% CI 1.01-1.27]. Similar findings were also observed for C-reactive protein (CRP) levels [OR 1.01, 95% CI 1.00-1.02; p=0.010 and OR 1.01, 95% CI 1.00-1.02; p=0.024]. Conversely, being positive to IgM and IgG decreases the risk of adverse outcomes [IgM: OR 0.33, 95% CI 0.14-0.77; p=0.011 and OR 0.23, 95% CI 0.08-0.66; p=0.006. IgG: OR 0.30 95% CI 0.13-0.72; p=0.007 and OR 0.22 95% CI 0.07-0.66; p=0.007]. Hence, a multivariable model was fitted to identify potential independent laboratory predictors of the composite outcome, with laboratory parameters that showed an association with composite outcome. The model can be considered accurate according to LH-Test and C-statistic [p>0.83, C-stat=0.90]. CONCLUSIONS: Our findings confirm that COVID-19 is a multiorgan disease. In fact, the analysis of laboratory parameters has revealed a strong relationship between poorer outcomes and multiple organ dysfunction, particularly established by higher levels of neutrophils, creatinine, sodium, and CRP. Alongside, cerebrovascular diseases, chronic kidney disease and older age supported this finding. Of note, higher levels of SpO2, and lymphocytes, as well as positivity to IgM and IgG were associated with a lower risk of a poor outcome.

Clinical application of lung ultrasound score on COVID-19 setting: a regional experience in Southern Italy.

OBJECTIVE: We aimed to assess the correlation between LUS Soldati proposed score and clinical presentation, course of disease and the possible need of ventilation support/intensive care. PATIENTS AND METHODS: All consecutive patients with laboratory confirmed SARS-CoV-2 infection and hospitalized in two COVID Centers were enrolled. All patients performed blood gas analysis and lung ultrasound (LUS) at admission. The LUS acquisition was based on standard sequence of 14 peculiar anatomic landmarks with a score between 0-3 based on impairment of LUS picture. Total score was computed with their sum with a total score ranging 0 to 42, according to Soldati LUS score. We evaluated the course of hospitalization until either discharge or death, the ventilatory support and the transition in intensive care if needed. RESULTS: One hundred and fifty-six patients were included in the final analysis. Most of patients presented moderate-to-severe respiratory failure (FiO2 <20%, PaO2 <60 mmHg) and consequent recommendation to invasive mechanic ventilation (CPAP/NIV/OTI). The median ultrasound thoracic score was 28 (IQR 18-36) and most of patients could be ascertained either in a score 2 (40%) or score 3 pictures (24.4%). The bivariate correlation analysis displayed statistically significant and high positive correlations between the LUS score and the following parameters: ventilation (rho=0.481, p<0.001), lactates (rho=0.464, p<0.001), dyspnea (rho=0.398, p=0.001) mortality (rho=0.410, p=0.001). Conversely, P/F (rho= -0.663, p<0.001), pH (rho = -0.363, p=0.003) and pO2 (rho = -0.400 p=0.001) displayed significant negative correlations. CONCLUSIONS: LUS score improve the workflow and provide an optimal management both in early diagnosis and prognosis of COVID-19 related lung pathology.

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy.

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance. Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function. In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents. A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.

Methicillin-resistant Staphylococcus aureus: epidemiology and antimicrobial susceptibility experiences from the University Hospital 'Luigi Vanvitelli' of Naples.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the important pathogens worldwide showing resistance to several widely used antibiotics. This has made the treatment of MRSA infections harder, especially due to their prevalence in the hospital setting. We evaluated the antibiotic susceptibility patterns of healthcare-associated MRSA infections with a focus on Vancomycin Intermediate S. Aureus (VISA) and macrolide-licosamide-streptogramin B (MLSB) phenotypes. A total of 417 Staphylococcus aureus (S. aureus) cases were isolated between January 2017 and December 2018, through several clinical specimens collected from the University Hospital 'Luigi Vanvitelli' of Naples. We identified bacterial strains using Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) and antimicrobial susceptibility using Phoenix BD (Becton Dickinson, NJ, USA). Out of the total 417 S. aureus cases, 140 were MRSA (33.6%) and of these, 50% were soft tissue infections. All MRSA and Methicillin sensible S.aureus MSSA isolates were susceptible to linezolid and daptomycin. Two MRSA cases exhibited intermediate resistance to vancomycin and were of constitutive MLSB phenotype. Among the MRSA strains, 11.4% were constitutive and 43.6% were inducible MLSB phenotypes and 8.6% were macrolide-streptogramin B phenotype. This study characterized the epidemiological status, antibiotic resistance patterns, and current prevalent phenotypes of healthcare-associated MRSA. This knowledge can aid clinicians in improving the antimicrobial stewardship program by adapting appropriate guidelines for the proper use of MRSA antibacterial agents.

Effects of insulin-glucose infusion on left ventricular function at rest and during dynamic exercise in healthy subjects and noninsulin dependent diabetic patients: a radionuclide ventriculographic study.

OBJECTIVES: The aim of this study was to evaluate: 1) the effects of insulin administration on left ventricular ejection fraction (LVEF) during exercise, and 2) the eventual impairment of the cardiovascular response to insulin in noninsulin dependent diabetes mellitus. BACKGROUND: Insulin influences the cardiovascular system, but its effect on left ventricular function has yet to be established. METHODS: The effects of normal saline (test A) and insulin-glucose (insulin = 1.7 mU x kg(-1) x min(-1); glucose = 6 mg x kg(-1)min(-1)) (test B) infusions on systolic and diastolic functions at rest and during dynamic exercise were examined by radionuclide ventriculography. Twenty-two noninsulin-dependent diabetic patients and 22 gender, age and body mass index matched healthy subjects were investigated. RESULTS: Both groups had normal scintigraphic parameters at rest and during dynamic exercise. Rest- and stress-LVEF as well as rest- and stress-peak filling rate were significantly (p < 0.001) lower in diabetic than in healthy subjects, both in test A and B. Rest-LVEF was significantly higher during test B than it was in test A only in diabetic subjects (p < 0.01). Stress-LVEF was significantly higher (p < 0.05) during test B than it was in test A, in both groups. Insulin-glucose infusion did not modify rest- and stress-peak filling rate in either group. No difference in left ventricular end diastolic volume and in mean blood pressure was found between test A and B at rest and during exercise in either group. A significant linear correlation between LVEF and the index of insulin sensitivity was found in diabetic patients. CONCLUSIONS: In both normal and diabetic humans, insulin induces a very important rise in LVEF after submaximal work. However, the rise is significantly lower in diabetic than in nondiabetic subjects. The increase in exercise-LVEF on insulin is likely due to an enhancement of ventricular contractility. Insulin resistance could justify the lower angioscintigraphic indexes in diabetic subjects.

The involvement of the opioid system in human obesity: a study in normal weight relatives of obese people.

The involvement of the opioid system in human obesity has been demonstrated, but whether the abnormalities in the endorphinergic system play a primary role in overfeeding and weight gain or represent a simple biochemical feature is still unclear. The objectives of this study were to investigate the effects of both physiological and pharmacological plasma beta-endorphin levels on some metabolic and hormonal parameters in a normal weight, but prone to obesity, young population consisting of first degree relatives of obese subjects and in body mass index-, sex, and age- matched control subjects without a family history of obesity. Each subject underwent a 1-h infusion of synthetic human beta-endorphin at a constant rate of 4.5 ng/kg.min (low rate), then after a 1-week interval, at a rate of 500 micrograms/h (high rate). Under basal conditions, there was no significant difference in plasma glucose and pancreatic hormones (insulin, C peptide, and glucagon) between the two groups, except for plasma beta-endorphin levels, which were significantly (P < 0.01) higher in relatives of obese individuals. The low rate of beta-endorphin infusion induced physiological elevations of plasma opioid levels in both groups; no significant change in plasma glucose and pancreatic products in control subjects; and a significant (at least P < 0.05) rise in plasma insulin, C peptide, and glucagon concentrations in relatives of the obese. The high rate of beta-endorphin infusion produced pharmacological elevations of opioid plasma levels in both groups; significant (at least P < 0.05) increments in plasma glucose and glucagon levels and no appreciable modification of plasma insulin and C peptide levels in the control group; and a significant (at least P < 0.05) positive response of plasma glucose, insulin, C peptide, and glucagon levels in relatives of obese subjects. These findings suggest that 1) opioid peptides at least in part play a primary, rather than secondary, role in some metabolic events of obesity; and 2) both physiological and pharmacological plasma levels of beta-endorphin are able to provoke marked islet hormone release in the early phase of human obesity.

A case-control study on risk factors for Peyronie's disease.

The aim of this study was to investigate the relationship between history of selected diseases, genital traumas, and Peyronie's disease. A hospital-based case-control study was conducted at the Andrologic and Surgical Outpatient Units of the Policlinico Gemelli, Rome, where 134 men with Peyronie's disease and 134 male controls were interviewed. The association between Peyronie's disease and selected characteristics was estimated by means of odds ratios (OR) and 95% confidence intervals (CI). Patients who underwent invasive procedures on the penis (i.e., urethral catheterization, cystoscopy, and transurethral prostatectomy) had a 16-fold increased risk for Peyronie's disease (OR = 16.1, 95% CI: 1.8-142), while a nearly three-fold increase was observed among patients who had genital and/or perineal traumatisms (95% CI: 1.0-7.1). A history of urethritis, uricacidemia, and lipoma was also significantly associated with an increased risk for Peyronie's disease. Twenty-one percent of the cases and none of the controls were affected by Dupuytren's contracture, and 4% of cases and none of the controls reported familial history for Peyronie's disease. The frequency of inflammatory or fibromatous lesions of the genital tract of the partner was significantly higher in men with Peyronie's disease than among controls. These results were consistent when performing a stratified analysis according to the type of controls (i.e., controls affected by urologic or by digestive conditions) to rule out the potential effect of recall bias. The findings of the study lend support to clinical reports stressing the importance of genital traumatisms and genetic conditions in the development of Peyronie's disease.

The lectin-binding sites for peanut agglutinin in invasive breast ductal carcinomas and their role as a prognostic factor.

The present study was designed to analyze the expression of lectin-binding sites for peanut agglutinin (PNA) in paraffin sections of primary invasive ductal carcinoma not otherwise specified and to consider PNA lectin histochemistry as a further aid in the prognostic evaluation of breast cancer. The expression of lectin-binding sites was studied using the avidin-biotin complex/ immunoperoxidase technique, and analyzed in relation to the different clinical, pathological, and biological parameters of the primary disease, i.e. the presence or absence of nodal metastases, pre- or post-menopausal age, size of the tumor, mitotic activity index, morphometric prognostic index, DNA content, S-phase fraction, and steroid receptor status. The results show significant differences in PNA binding patterns among malignant epithelial breast cells. There was no expression of PNA-binding sites in 14 out of 157 tumors, while 64 showed mostly apical (membrane) staining and 124 non-apical (membrane and/or cytoplasmic) staining. Apical staining was mostly observed in patients without lymph node metastasis, with positive steroid receptor status, and those who were postmenopausal diagnosis; non-apical staining was mostly observed in lymph-node-positive premenopausal patients negative for steroid receptors and with aneuploid tumor cells. Our results indicate that, in malignant breast cells, there is an alteration of cell-surface glycoconjugates, shown by heterogeneity within a histopathologically defined group, which is related to different properties of tumor cells. The apical PNA binding pattern indicates a better differentiation of tumor cells while non-apical PNA binding suggests a higher metastatic potential. Specific PNA lectin binding patterns should be considered as a further reliable prognostic factor in breast cancer.

Hyperinsulinemia in offspring of non-insulin-dependent diabetes mellitus patients: the role played by abnormal clearance of insulin.

Insulin resistance and hyperinsulinemia are often found in first-degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients, and are currently considered a familial trait of this population at increased risk for diabetes. This study was undertaken to determine the role played by the metabolic clearance rate (MCR) of insulin (MCR-I) in the hyperinsulinism of these subjects. The proband population, consisting of 48 subjects aged 29.2 +/- 4.4 (mean +/- SD) years (18 men and 30 women; body mass index, 24.6 +/- 0.8 kg/m2; fasting plasma glucose, 4.54 +/- 0.37 mmol/L), was assigned in random order to four groups (I, II, III, and IV), each receiving a double insulin/glucose infusion (I, 0.025/2.0; II, 0.050/3.5; III, 0.100/6.0; and IV, 0.200/8.0 U/kg.h and mg/kg.min, respectively) to calculate MCR-I and MCR of glucose (MCR-G). Forty (14 men and 26 women) age- and body mass index-matched healthy individuals served as controls. All subjects had a normal response to an oral glucose tolerance test (75 g) according to World Health Organization criteria. Basal plasma insulin and C-peptide levels in probands were significantly (P < .05) higher than in controls in each study group; similarly, MCR-I was significantly (at least P < .05) lower in probands than in controls in all groups. MCR-G was significantly (at least P < .05) decreased in probands as compared with controls of groups III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased vascular endothelial growth factor mRNA expression in the heart of streptozotocin-induced diabetic rats.

The aim of the present study was to evaluate vascular endothelial growth factor (VEGF), fms-like tyrosine kinase 1 (flt-1), and fetal liver kinase (flk-1) expression in the heart of experimental diabetic rats. Ten young adult male Wistar rats (5 streptozotocin [STZ]-induced diabetic rats, without insulin treatment, and 5 controls) were studied. Ninety days after the induction of diabetes, semiquantitative reverse transcription (RT)-polymerase chain reaction (PCR) coamplification of VEGF/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcription was performed. RT-PCR was also performed for VEGF receptors flk-1 and flt-1. VEGF mRNA expression, at 234 bp, was detectable in the heart of the rats and was significantly higher in those with diabetes. Densitometric analysis of PCR products showed that VEGF mRNA levels were meanly 4.8-fold higher in STZ-induced diabetic rats than controls (VEGF/GAPDH densitometric ratio, 3.46 +/- 0.20 v 0.74 +/- 0.10, P <.001). No significant difference was found in flt-1 and flk-1 amplification products between STZ-induced diabetic rats and controls (flt-1/GAPDH densitometric ratio, 0.58 +/- 0.01 v 0.64 +/- 0.05, P>.1; flk-1/GAPDH densitometric ratio, 0.66 +/- 0.10 v 0.7 +/- 0.06, P >.2). The increase in VEGF mRNA expression observed in this experimental diabetic model is in contrast with the typical impairment in collateral vessels of diabetic hearts. This apparent discrepancy might be explained by a resistance of cardiac tissue to VEGF. The lack of mRNA flt-1 and flk-1 overexpression in diabetic hearts could be one of the mechanisms for this resistance.

Cochlear dysfunction in type 2 diabetes: a complication independent of neuropathy and acute hyperglycemia.

The effects of type 2 diabetes on evoked otoacoustic emissions (e-OAEs) elicited by clicks in subjects with normal hearing and the involvement of the central (CNS) and peripheral nervous system and acute hyperglycemia were investigated. In study 1, 110 type 2 diabetic patients and 106 control subjects matched for age and gender were investigated by e-OAEs. Central and peripheral neuropathy were evaluated respectively by auditory brainstem responses (ABRs) and according to San Antonio Consensus Conference criteria. In study 2, 10 healthy and 10 type 2 diabetic men matched for age, all with normal e-OAEs, underwent a 5-hour hyperglycemic clamp study. e-OAE tests were performed before and during the hyperglycemic clamp. In study 1, e-OAEs were impaired in 51.8% (57 of 110) of the diabetic subjects, in comparison to 4.7% (five of 106) of the control group (P < .0001). Diabetics with impaired e-OAEs (e-OAEs-), in comparison to those with normal e-OAEs (e-OAEs+), were older (51.0+/-5.8 v 45.1+/-6.0 years, P < .001), had diabetes longer (11.5+/-4.4 v 7.0+/-3.9 years, P < .001), achieved poorer metabolic control as judged by hemoglobin A1c ([HbA1c] 6.9%+/-0.4% v 6.5%+/-0.3%, P < .001), and had more peripheral neuropathy (46% v 23%, P < .02). No difference was observed between e-OAEs- and e-OAEs+ subjects for retinopathy or nephropathy. Nevertheless, when the duration of diabetes was corrected by multiple regression analysis, the correlation between sensorineural damage and peripheral neuropathy lost significance (P = .12). Diabetic groups (e-OAEs+ and e-OAEs-) showed greater latency in waves I, III, and V and greater interwave latency for waves I to V than the control group, but there was no significant difference in ABRs between e-OAEs+ and e-OAEs- subjects. In study 2, there were no significant changes in e-OAE intensities compared with basal values during the entire hyperglycemic clamp in either type 2 diabetic or control subjects. No difference was observed between the two groups at each time of the clamp. Thus, type 2 diabetic subjects show a higher rate of compromised e-OAEs than healthy individuals. The e-OAE dysfunction does not associate with either an injury to the auditory nervous pathway or diabetic microvasculopathy. The apparent interference of peripheral neuropathy in e-OAEs loses significance when corrected for the duration of diabetes.

Bladder reconstruction after cystectomy: use of ileocecal segment and three-loop ileal reservoir.

We report on 11 patients who in 1980-1982 had bladder reconstruction, after cystectomy for bladder cancer, utilizing the ileocecal valve as an antireflux mechanism and a direct urethrocecal anastomosis. They received preoperative irradiation (2,000 rad) and had some early complications such as pelvic abscesses and temporary urinary fistulas. We have since omitted preoperative radiation on cases performed in 1984-1987 and they did not have these complications.

Refluxes in orthotopic neobladders: can the ileocecal sphincter be considered an adequate antireflux mechanism?

OBJECTIVES: To evaluate the usefulness of the ileocecal sphincter in preventing ureteral refluxes in ileocecal orthotopic neobladder, thus avoiding the use of antireflux technique for ureteroileal anastomosis. METHODS: From 1980 to 1992, 95 patients underwent orthotopic bladder substitution. In 30 our detubularized ileal reservoir was used and in 65 first only an integral ileocecal segment was used and subsequently multiple transverse teniamyotomies on the cecal portion to increase the capacity and reduce the pressure. The upper urinary tract was indirectly protected in the ileal reservoir technique by leaving an integral 8 to 10 cm long afferent segment folded behind the reservoir and in the ileocecal technique by the ileocecal sphincter, thus keeping the anastomosis between ureters and ileum simple and direct. RESULTS: The mean follow-up of the 65 patients with ileocecourethrostomy is 37 +/- 33 months (range, 2 to 141 months); in 13.8% of the patients (9/65) monolateral refluxes appeared, but without any evident clinical consequences. The appearance of monolateral stenosis on the ureterointestinal anastomosis requiring treatment occurred in 4 patients (6%): 3 underwent an endoscopic treatment and 1 a surgical one. Modifications of renal function with respect to the preoperative status were not verified in any of the patients. CONCLUSIONS: The ileocecal sphincter is an effective antireflux mechanism for an orthotopic neobladder in which multiple transverse teniamyotomies (5 to 7) increase the capacity of the neobladder itself, reduce its internal pressure, and confer a nearly spherical configuration. Moreover, a correct anastomosis between the cecum and membranous urethra decisively reduces the resistance to emptying of the neobladder, thus avoiding too strong pressures against the ileocecal sphincter. The integrity of the circular muscular layer maintains a healthy tonic wall: this fact, combined with the low peripheral resistances, ensures good emptying and a stable capacity. The procedure is easy to perform and not time-consuming; these considerations lead us to consider the ileocecal unit an excellent structure for bladder substitution.