Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery.

BACKGROUND: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic. METHODS: Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery). RESULTS: Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014). CONCLUSIONS: Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.

A short-term increase in dietary cholesterol and fat intake affects high-density lipoprotein composition in healthy subjects.

BACKGROUND AND AIMS: High-cholesterol and high-fat diets alter biochemical composition and anti-oxidant properties of high-density lipoproteins (HDL) in animals. Whether this occurs in humans is unknown. Therefore, we examined the effect of a short-term elevation in dietary cholesterol and fat intake on HDL composition in healthy subjects. METHODS AND RESULTS: In a randomized, crossover clinical trial, 14 healthy young volunteers followed a 14-day low-cholesterol/low-fat diet (LChF) and a 14-day isocaloric high-cholesterol/high-fat diet (HChF) in a random order. After each diet, we measured HDL concentrations of hydroxyeicosatetraenoic acids (HETE), hydroxyoctadecadienoic acids (HODE), and haptoglobin, as well as serum amyloid A (SAA) and paroxonase-1 activity (PON-1). HDL concentrations of 15-HETE (+254%, p = 0.002), 5-HETE (+116%, p = 0.004), 13-HODE (+102%, p = 0.049), and SAA levels (+75%, p = 0.007) were significantly higher after the HChF than after the LChF. Furthermore, haptoglobin was marginally increased (+32%, p = 0.091) while PON-1 activity was unaffected (-16%, p = 0.366) by the HChF. CONCLUSION: In healthy subjects, a short-term elevation in dietary cholesterol and fat intake increases HDL lipid hydroperoxide content (15-HETE, 5-HETE, 13-HODE) and SAA levels, which are key features of dysfunctional HDL. This is the first study showing that a physiologic manipulation of dietary cholesterol and fat intake affects HDL lipidome and proteome in healthy subjects independently of weight changes. CLINICAL TRIAL REGISTRATION: NCT02549144.

The amino acid response to a mixed meal in patients with type 2 diabetes: effect of sitagliptin treatment.

AIMS: Amino acid (AA) metabolism is altered in type 2 diabetes (T2D), and fasting levels of α-hydroxybutyrate (α-HB), a biomarker for insulin resistance, have been suggested to track AA metabolism. We investigated the changes in AA and α-HB induced by a mixed-meal tolerance test (MTT) and the effects of sitagliptin treatment. METHODS: Forty-seven T2D patients [56 ± 7 years, body mass index (BMI) 29.9 ± 4.2 kg/m(2) ] were randomized to sitagliptin (100 mg/day, 6 weeks) or placebo. Seven age- and BMI-matched non-diabetic subjects served as control (CT). RESULTS: During a 5-h MTT, branched-chain AA (BCAA) peaked earlier in T2D than CT [75(25) vs. 62(3) mmol/l · h over 2 h, median(interquartile range), p = 0.05], and rose higher [5-h increment: 31(23) vs. 19(24) mmol/l · h, p = 0.05]. Fasting α-HB was higher [7.5(2.7) vs. 5.9(1.3) µg/ml, p = 0.04 T2D vs. CT], and its meal-induced increments were larger [24(99) vs. -41(86) µg/ml · h, p = 0.006]. Plasma non-esterified fatty acids (NEFA) declined during MTT, but their increments were greater in patients (53 ± 16 vs. 35 ± 10 mEq/l · h, p = 0.005). Compared to placebo, both BCAA [-6.4(21.1) vs. 0.0(48.0) mmol/l · h, p = 0.01] and α-HB increments [-114(250) vs. 114(428) µg/ml · h, p = 0.002] decreased with sitagliptin, and meal-induced NEFA suppression was improved. Changes in BCAA and α-HB were reciprocally related to changes in insulin sensitivity (ρ = -0.37 and -0.43, p ≤ 0.01). CONCLUSIONS: T2D is associated with a hyperaminoacidaemic response to MTT, which circulating α-HB levels track. Sitagliptin-induced glycaemic improvement was associated with reductions in BCAA and α-HB excursions and better NEFA suppression, in parallel with improved insulin sensitivity, confirming that α-HB is a readout of metabolic overload.

Impact of mild to moderate reductions of glomerular filtration rate on coronary artery disease severity.

BACKGROUND & AIMS: The bases of the link between reduced glomerular filtration rate (GFR) and coronary artery disease (CAD) are complex and to some extent still unclear. We performed this observational, single referral center, cohort study to evaluate whether mild to moderate GFR reduction is associated with more severe CAD and/or with a worse cardiac prognosis independently of proteinuria, diabetes and traditional risk factors. METHODS AND RESULTS: In 1752 consecutive non-diabetic patients without proteinuria or moderate/severe kidney disease undergoing a clinically driven coronary angiography, coronary arteries lesions, myocardial function and hypertrophy and 10-yrs incidence of cardiac events and death were evaluated in relation to classes of estimated GFR defined according the lowest eGFR value (105+, 90+, 75+, 60+, 45+). A reduced eGFR was independently associated with hypertension, myocardial hypertrophy and stress induced ischemia, while the excess coronary lesions and the worse myocardial systolic function were both largely explained by age and cardiovascular risk factors. When compared to subjects 75+, both the risk of cardiac death (1.67[1.10-2.57] and 3.06[1.85-5.10]) and non-fatal myocardial infarction (2.58[1.12-6.49] and 2.73[1.31-6.41]) adjusted for age and comorbidities were higher in eGFR 60+ and 45+ patients. CONCLUSIONS: A mild-moderate reduction of eGFR is closely associated to higher rates of stress-induced ischemia, myocardial hypertrophy and higher risk of fatal and non-fatal cardiac events. The associations of reduced eGFR with coronary atherosclerosis and myocardial systolic dysfunction are both largely explained by age and traditional risk factors.

HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease.

BACKGROUND AND AIMS: We have previously shown that the anti-inflammatory and anti-oxidant functions of HDL are impaired in T2D patients. In this study, we examined whether HDL from T2D patients contains elevated levels of oxidized fatty acids and whether those levels correlate with cardiovascular disease (CVD). METHODS AND RESULTS: HETEs and HODEs on HDL were determined by LC-MS/MS in 40 non-diabetic controls (ND), 40 T2D without CVD (D⁺CVD⁻) and 38 T2D with known history of CVD (D⁺CVD⁺). HDL oxidant index was evaluated by a cell-free assay using dichlorofluorescein. Twenty-six randomly selected subjects from the three groups underwent coronary calcium score evaluation (CAC). Major cardiovascular risk factors were similar among the groups. HETEs and HODEs content were significantly increased in HDL from D⁺CVD⁺ when compared to D⁺CVD⁻ and ND patients. HDL oxidant index was not different among the three groups; however, it was significantly higher in patients with CAC score >100 when compared to patients with CAC score <100. CONCLUSION: Patients with D⁺CVD⁻ and D⁺CVD⁺ are characterized by a severe, graded enrichment of oxidized fatty acids on HDL. In the present study, a loss of HDL function (as estimated by the HDL oxidant index) is observed only in patients with more advanced atherosclerosis.

Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion.

AIMS/HYPOTHESIS: Endogenous NO inhibits insulin release in isolated beta cells and insulin-degrading enzyme activity in hepatocytes, while NO release from endothelial cells has been suggested to enhance insulin action. We assessed the overall effect of systemic inhibition of endogenous NO synthesis on glucose homeostasis in humans. METHODS: Twenty-four non-diabetic volunteers underwent two hyperglycaemic (+7 mmol/l) clamps with either saline or L-NG-nitroarginine methyl ester (L-NAME, at rates of 2.5, 5, 10 and 20 µg min⁻¹ kg⁻¹) infusion. Another five volunteers underwent an OGTT with either saline or L-NAME (20 µg min⁻¹ kg⁻¹) infusion. Blood pressure and heart rate were measured to monitor NO blockade; during the OGTT, endothelial function was assessed by peripheral arterial tonometry and insulin secretion by C-peptide deconvolution and insulin secretion modelling. RESULTS: Compared with saline, L-NAME at the highest dose raised mean blood pressure (+20 ± 2 mmHg), depressed heart rate (-12 ± 2 bpm) and increased insulin clearance (+50%). First-phase insulin secretion was impaired, but insulin sensitivity (M/I index) was unchanged. During the OGTT, L-NAME raised 2 h plasma glucose by 1.8 mmol/l (p < 0.01), doubled insulin clearance and impaired beta cell glucose sensitivity while depressing endothelial function. CONCLUSIONS/INTERPRETATION: In humans, systemic NO blockade titrated to increase blood pressure and induce endothelial dysfunction does not affect insulin action but significantly impairs glucose tolerance by increasing plasma insulin clearance and depressing insulin secretion, namely first-phase and beta cell glucose sensitivity.

Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes.

AIMS/HYPOTHESIS: Bariatric surgery consistently induces remission of type 2 diabetes. We tested whether there are diabetes-specific mechanisms in addition to weight loss. METHODS: We studied 25 morbidly obese patients (BMI 51.7 ± 1.5 kg/m(2) [mean ± SEM]), 13 with non-insulin-treated type 2 diabetes (HbA(1c) 7.1 ± 0.5% [54 ± 5 mmol/mol]), before and at 2 weeks and 1 year after Roux-en-Y gastric bypass (RYGB). Lean (n = 8, BMI 23.0 ± 0.5 kg/m(2)) and obese (n = 14) volunteers who were BMI-matched (36.0 ± 1.2) to RYGB patients at 1 year after surgery served as controls. We measured insulin-stimulated glucose disposal (M) and substrate utilisation (euglycaemic clamp/indirect calorimetry), endogenous glucose production (EGP) by 6,6-[(2)H(2)]glucose, lipolysis (rate of appearance of [(2)H(5)]glycerol) and beta cell function (acute insulin response to i.v. glucose [AIR] as determined by C-peptide deconvolution). RESULTS: At baseline, all obese groups showed typical metabolic abnormalities, with M, glucose oxidation and non-oxidative disposal impaired, and EGP, lipolysis, lipid oxidation and energy expenditure increased. Early after RYGB plasma glucose and insulin levels, and energy expenditure had decreased, while lipid oxidation increased, with M, EGP and AIR unchanged. At 1 year post-RYGB (BMI 34.4 ± 1.1 kg/m(2)), all diabetic patients were off glucose-lowering treatment and mean HbA(1c) was 5.4 ± 0.14% (36 ± 2 mmol/mol) (p = 0.03 vs baseline); AIR also improved significantly. In all RYGB patients, M, substrate oxidation, EGP, energy expenditure and lipolysis improved in proportion to weight loss, and were therefore similar to values in obese controls, but still different from those in lean controls. CONCLUSIONS/INTERPRETATION: In morbidly obese patients, RYGB has metabolic effects on liver, adipose tissue, muscle insulin sensitivity and pattern of substrate utilisation; these effects can be explained by energy intake restriction and weight loss, the former prevailing early after surgery, the latter being dominant in the longer term.

Should treatment of low-level rifampicin mono-resistant tuberculosis be different?

BACKGROUND: Rifampicin resistant tuberculosis (RR-TB) was frequently detected in Suriname after the introduction of Xpert MTB/RIF in 2012. Subsequent phenotypic drug-susceptibility testing (DST) was not conclusive at that moment, while RR-TB patients treated with first-line tuberculostatics had good treatment outcome. In our study, we analysed this interesting observation. METHODS: We collected demographic and clinical characteristics and treatment outcome of TB patients from May 2012-December 2018 and performed a univariate and multivariate analysis to assess possible associations with resistance to rifampicin. Secondly, we conducted whole genome sequencing on all available Mycobacterium tuberculosis isolates that had a rifampicin resistance in the Xpert MTB/RIF test and performed phenotypic DST on selected isolates. FINDINGS: RR-TB was detected in 59 (9.6%) patients confirmed by Xpert. These patients were treated with rifampicin-containing regimens in most (88%) of the cases. In all 32 samples examined, a D435Y mutation in the rpoB gene was identified; only one isolate revealed an additional isoniazid mutation. Phenotypic DST indicated low-level rifampicin resistance. In multivariate analysis, the Creole ethnicity was a factor associated with rifampicin resistance (aOR 3.5; 95%CI 1.9-6.4). The treatment success rate for patients with RR-TB (78.0%) was comparable to the treatment outcome in non-RR-TB patients 77.8%. INTERPRETATION: This study confirms a low-level rifampicin mono-resistance in TB patients of Suriname. These patients could benefit from a first-line regimen with high dose rifampicin (or rifabutin), rather than from the lengthy treatment regimens for rifampicin-resistant and multi-drug resistant TB, a concept of stratified medicine also advocated for the treatment of TB. FUNDING: None.

Salvage of a subacute failure in femoral dialysis loop graft using stent covering the arterial and venous anastomosis.

Endovascular treatment can be considered the first line therapy in the majority of dysfunctioning arteriovenous fistula. However, when early thrombosis of the arteriovenous access occurs, surgical treatment is recommended. In these cases, technical problems are the most frequent cause of the malfunction. We report a case of a subacute thrombosis of an arteriovenous fistula, femoral artery to femoral vein looped ePTFE with venous anastomosis occlusion and subocclusion lesion at the arterial anastomosis. Both anastomoses were treated using self-expandable stents, and no other intervention was necessary until the one-year follow-up for maintain patency.

Mannose is an insulin-regulated metabolite reflecting whole-body insulin sensitivity in man.

Mannose is a glucose-associated serum metabolite mainly released by the liver. Recent studies have shown several unexpected pleiotropic effects of mannose including increased regulatory T cells (Tregs), prevention of auto-immune disease and ability to reduce growth of human cancer cells. We have previously shown in large cohorts that elevated serum mannose levels are associated with future development of type 2 diabetes (T2D) and cardiovascular disease. However, potential direct effects of mannose on insulin sensitivity in vivo or in vitro are unknown. We here show that administration of mannose (0.1 g/kg BW twice daily) for one week in man did not elicit negative effects on meal-modified glucose tolerance, markers of inflammation or insulin levels. Tregs number and insulin signaling in human liver cells were unchanged. These data suggest that mannose is a marker, and not a mediator, of insulin resistance. To verify this, we examined serum mannose levels during long-term euglycemic hyperinsulinemic clamps in non-diabetic and T2D individuals. Mannose was reduced by insulin infusion in proportion to whole-body insulin sensitivity. Thus, mannose is a biomarker of insulin resistance which may be useful for the early identification of diabetic individuals with insulin resistance and increased risk of its complications.

[Endovascular treatment of intracranial venous sinus stenosis in intracranial hypertension: three case reports and a discussion of the literature]. / Tratamiento endovascular de la estenosis de los senos venosos intracraneales en la hipertensión intracraneal: descripción de tres casos y discusión de la bibliografía.

INTRODUCTION: Idiopathic intracranial hypertension is an entity with an incidence of approximately 1.2: 100,000 inhabitants/year. It affects in a greater proportion obese women and women of childbearing age. Headache is the most characteristic symptom, followed by visual disturbances. In recent years, the diagnosis of dural sinus stenosis has increased in cases of intracranial hypertension resistant to conventional treatment. For this reason, the development of endovascular therapy as a therapeutic option in selected patients is booming. CASE REPORTS: We present three cases of intracranial hypertension secondary to dural sinus stenosis, diagnosed and treated in our hospital. Despite the establishment of adequate diuretic treatment and the performance of invasive procedures to bypass the cerebrospinal fluid, they persisted with neurological symptoms and visual deficits. After verifying that they fulfilled the requirements described in the literature, they underwent intracranial stenting, with satisfactory results in all of them, achieving the disappearance of the headache and recovery of visual acuity. CONCLUSION: Stenting of dural sinus stenosis as a cause of intracranial hypertension is an increasingly used technique, which has presented favorable results. Studies are necessary to know its long-term impact.

TITLE: Tratamiento endovascular de la estenosis de los senos venosos intracraneales en la hipertensión intracraneal: descripción de tres casos y discusión de la bibliografía.Introducción. La hipertensión intracraneal idiopática es una entidad con una incidencia anual aproximada de 1,2 por cada 100.000 habitantes. Afecta en mayor proporción a mujeres obesas y en edad fértil. La cefalea es el síntoma más característico, seguido de las alteraciones visuales. En los últimos años, se ha incrementado el diagnóstico de la estenosis de los senos durales en los casos de hipertensión intracraneal resistentes al tratamiento convencional. Por ello, se encuentra en auge el desarrollo de la terapia endovascular como opción terapéutica en pacientes seleccionados. Casos clínicos. Se presentan tres casos de hipertensión intracraneal secundaria a estenosis de los senos durales, diagnosticados y tratados en nuestro hospital. A pesar de la instauración del adecuado tratamiento diurético y de la realización de procedimientos invasivos de derivación del líquido cefalorraquídeo, persistían la clínica neurológica y el déficit visual. Tras comprobar que cumplían los requisitos descritos en la bibliografía, se sometieron a la implantación de stent intracraneal (stenting), con resultado satisfactorio en todos ellos, logrando la desaparición de la cefalea y la recuperación de la agudeza visual. Conclusión. El stenting de la estenosis de los senos durales como causa de hipertensión intracraneal es una técnica cada vez más utilizada que ha presentado resultados favorables. Es necesaria la realización de estudios para conocer su impacto a largo plazo.

Pattern of expression of adiponectin receptors in human liver and its relation to nonalcoholic steatohepatitis.

BACKGROUND: Adiponectin has antisteatosis-anti-inflammatory properties and its circulating levels are reduced in nonalcoholic steatohepatitis (NASH). METHODS: To assess the role of adiponectin in NASH, we measured expression of adiponectin gene (APM1) and receptors (AdipoR1/AdipoR2) in liver and subcutaneous and visceral fat in subjects with biopsy-proven NASH or pure steatosis (PS). In 103 subjects undergoing gastric bypass or elective abdominal surgery (17 with normal liver histology (C), 52 with PS, and 34 with NASH), RNA was extracted from tissue samples, and quantification of APM1, AdipoR1, and AdipoR2 was carried out by real-time polymerase chain reaction. RESULTS: In NASH vs C, circulating adiponectin levels (3.6[2.4] vs 5.3[4.3] microg/ml, median[interquartile range], p < 0.05) and adiponectin concentrations, APM1, AdipoR1, and AdipoR2 expression in visceral fat were all reduced (p < or = 0.03). These differences disappeared when adjusting for obesity. In contrast, liver AdipoR1 (1.40 [0.46] vs 1.00 [0.32] of controls) and AdipoR2 expression (1.20 [0.41] vs 0.78 [0.43]) were increased in NASH, and group differences were statistically significant (p < 0.0001 for AdipoR1 and p = 0.0001 for AdipoR2). Results for PS were generally intermediate between NASH and C. Liver receptor expression was reciprocally related to circulating adiponectin (rho = -0.42, p < 0.003 for AdipoR1 and rho = -0.26, p < 0.009 for AdipoR2). In multivariate models adjusting for sex, age, fasting plasma glucose, and obesity, liver enzymes levels were directly related to both AdipoR1 and AdipoR2 expression in liver. CONCLUSION: In obese patients with NASH, adiponectin receptors are underexpressed in visceral fat-as a likely correlate of obesity-but overexpressed in liver, possibly as a compensatory response to hypoadiponectinemia, and positively associated with liver damage.

Lower respiratory tract viral infections in hospitalized adult patients.

AIM: The epidemiology of lower respiratory tract (LRT) viral infections in adults is probably underestimated and the high frequency of multiple viral infections complicates the evaluation of the possible role of the single viruses. The aim of this study was to investigate the clinical epidemiology and impact of respiratory viral pathogens, in particular of those singularly detected, in bronchoalveolar lavage (BAL) specimens from hospitalized adult patients. METHODS: A panel for the detection of 16 respiratory viruses was used to prospectively evaluate 324 consecutive specimens obtained from 219 patients over a full-year period. RESULTS: Two-hundred-twenty-one specimens (68.2%) were positive for at least one virus, 119/324 (36.7%) to a single viral agent. The most commonly detected viruses were herpesviruses HHV-7 (26.2%), human cytomegalo-virus (HCMV, 22.2%), HHV-6 (19.8%), EBV (12.7%), enteroviruses and rhinoviruses (both 11.7%), parainfluenza viruses (4.9 %), and metapneumovirus (4.0%). Human cytomegalo-virus was significantly more prevalent as single viral pathogen with a viral load >105 copies/ml associated to pneumonia in solid organ transplant recipients. Other viral pathogens might account for some cases of pneumonia or respiratory insufficiency, although multiple infections were common. CONCLUSIONS: The use of a comprehensive diagnostic panel for respiratory viral infections may be useful to clarify the epidemiology and clinical impact of viral pathogens in hospitalized adult patients. The occurrence of multiple infections is a common finding and results should be interpreted taking into account the clinical context as well as viral load and the biological characteristics of each virus.

Pulmonary functionality among workers of a Central Italy waste-to-energy plant: a retrospective study.

BACKGROUND: We are observing a growing trend towards the use of waste incineration in waste-to-energy (WTE) plants in Italy. Various authors started to investigate their potential health effects, but without univocal outcomes. The aim of this study is to assess whether or not main pulmonary function indexes could be decreased in a group of workers employed in a municipal solid WTE plant located in Central Italy, and if there's a correlation between the levels of exposure to airborne pollutants and alterations in the pulmonary apparatus. METHODS: The study was conducted with a retrospective cohort approach. We reviewed data from clinical records of 58 waste-to-energy plant workers undergoing annual health surveillance in the period 2010-2015. We considered the exposure to airborne dust and the main parameters of respiratory function (FVC, FEV1, Tiffeneau Index and FEF 25-75%) at time zero and after a period of 5 years. We divided our study population into two groups: low (< 1 mg/m3) and high (> 1 mg/m3) exposure. We estimated odds ratios (OR) with 95% confidence interval (95% CI) adjusted for potential confounders. RESULTS: We observed a decrease in lung function parameters both in high and in low exposure group after a five-years exposure period. FEV1, FEV1/VC ratio and FEF 25-75% were worst in more exposed group, even if this difference resulted not significant at Wilcoxon test. CONCLUSIONS: Active employee in WTE plants is associated to a non-significant worsening in the main parameters of lung function after 5 years exposure. Clinical significant of these variations need to be assessed.

Single versus double lung transplantation in pulmonary fibrosis: a debated topic.

Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.

Combined cytomegalovirus prophylaxis in lung transplantation: effects on acute rejection, lymphocytic bronchitis/bronchiolitis, and herpesvirus infections.

Lung transplantation recipients are at high risk for herpesvirus infections. We evaluated the effect of combined cytomegalovirus (CMV) prophylaxis on CMV pneumonia, acute rejection episodes (ARE), lymphocytic bronchitis/bronchiolitis (LB), and obliterans bronchiolitis (OB) diagnosed in 180 transbronchial biopsies (TBB) of lung transplant recipients. At our center, 25 patients (control group; 1999-2002) received acyclovir for 12 months and 21 recipients (study group; 2003-2007) received combined CMV prophylaxis consisting of CMV-IG (Cytotect Biotest) for 12 months and ganciclovir or valganciclovir from postoperative day 21 for 3 weeks. Among the study group (since 2005), CMV shell vial viral culture and Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and HHV-7 DNA were determined on BAL specimens. In the study group, the number of LB was significantly lower than in the control group (2% vs 11%; P= .04). Similar results were obtained for ARE (6% vs 17%; P= .04). No difference was observed in OB (5% vs 5%; P= .53, NS). A reduction trend was found in CMV pneumonia (2% vs 7%; P= .23, NS). Logistic regression analysis showed a relationship between prophylaxis and a reduced prevalence of ARE (odds ratio [OR] 3.25, confidence interval [CI] 1.12-9.40; P= .03). Finally, in the study group, BAL EBV-DNA positivity and EBV-CMV coinfections were low (6% and 0%, respectively) compared with other herpesviruses and with the literature. Our data suggested the efficacy of combined CMV prophylaxis to prevent ARE and LB, 2 risk factors for chronic rejection, and a possible role to reduce the trend toward CMV pneumonia and EBV infections.

Effect of pioglitazone on the metabolic and hormonal response to a mixed meal in type II diabetes.

We explored the mechanisms by which a 4-month, placebo-controlled pioglitazone treatment (45 mg/day) improves glycemic control in type II diabetic patients (T2D, n=27) using physiological testing (6-h mixed meal) and a triple tracer technique ([6,6-(2)H(2)]glucose infusion, (2)H(2)O and [6-(3)H]glucose ingestion) to measure endogenous glucose production (EGP), gluconeogenesis (GNG), insulin-mediated glucose clearance and beta-cell glucose sensitivity (by c-peptide modeling). Compared to sex/age/weight-matched non-diabetic controls, T2D patients showed inappropriately (for prevailing insulinemia) raised glucose production (1.05[0.53] vs 0.71[0.36]mmol min(-1) kg(ffm)(-1) pM, P=0.03) because of enhanced GNG (73.1+/-2.4 vs 59.5+/-3.6%, P<0.01) persisting throughout the meal, reduced insulin-mediated glucose clearance (6[5] vs 12[13]ml min(-1) kg(ffm)(-1) nM(-1), P<0.005), and impaired beta-cell glucose-sensitivity (27[38] vs 71[37]pmol min(-1) m(-2) mM(-1), P=0.002). Compared to placebo, pioglitazone improved glucose overproduction (P=0.0001), GNG and glucose underutilization (P=0.05) despite lower insulinemia. GNG improvement was quantitatively related to raised adiponectin. beta-cell glucose sensitivity was unchanged. In mild-to-moderate T2D, pioglitazone monotherapy decreased fasting and post-prandial glycemia, principally via inhibition of gluconeogenesis, improved hepatic and peripheral insulin resistance.

Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.

Insulin-mediated vasodilation has been proposed as a determinant of in vivo insulin sensitivity. We tested whether sustained vasodilation with adenosine could overcome the muscle insulin resistance present in mildly overweight patients with essential hypertension. Using the forearm technique, we measured the response to a 40-min local intraarterial infusion of adenosine given under fasting conditions (n = 6) or superimposed on a euglycemic insulin clamp (n = 8). In the fasting state, adenosine-induced vasodilation (forearm blood flow from 2.6 +/- 0.6 to 6.0 +/- 1.2 ml min-1dl-1, P < 0.001) was associated with a 45% rise in muscle oxygen consumption (5.9 +/- 1.0 vs 8.6 +/- 1.7 mumol min-1dl-1, P < 0.05), and a doubling of forearm glucose uptake (0.47 +/- 0.15 to 1.01 +/- 0.28 mumol min-1dl-1, P < 0.05). The latter effect remained significant also when expressed as a ratio to concomitant oxygen balance (0.08 +/- 0.03 vs 0.13 +/- 0.04 mumol mumol-1, P < 0.05), whereas for all other metabolites (lactate, pyruvate, FFA, glycerol, citrate, and beta-hydroxybutyrate) this ratio remained unchanged. During euglycemic hyperinsulinemia, whole-body glucose disposal was stimulated (to 19 +/- 3 mumol min-1kg-1), but forearm blood flow did not increase significantly above baseline (2.9 +/- 0.2 vs 3.1 +/- 0.2 ml min-1dl-1, P = NS). Forearm oxygen balance increased (by 30%, P < 0.05) and forearm glucose uptake rose fourfold (from 0.5 to 2.3 mumol min-1dl-1, P < 0.05). Superimposing an adenosine infusion into one forearm resulted in a 100% increase in blood flow (from 2.9 +/- 0.2 to 6.1 +/- 0.9 ml min-1dl-1, P < 0.001); there was, however, no further stimulation of oxygen or glucose uptake compared with the control forearm. During the clamp, the ratio of glucose to oxygen uptake was similar in the control and in the infused forearms (0.27 +/- 0.11 and 0.23 +/- 0.09, respectively), and was not altered by adenosine (0.31 +/- 0.9 and 0.29 +/- 0.10). We conclude that in insulin-re15-76sistant patients with hypertension, adenosine-induced vasodilation recruits oxidative muscle tissues and exerts a modest, direct metabolic effect to promote muscle glucose uptake in the fasting state. Despite these effects, however, adenosine does not overcome muscle insulin resistance.

Carotid stenting without use of balloon angioplasty and distal protection devices: preliminary experience in 100 cases.

BACKGROUND AND PURPOSE: A major concern during carotid artery stent placement is the potential for cerebral embolism. Diminishing the number of device manipulations across the lesion might reduce procedural stroke risk. For this purpose, we report our initial experience with carotid stent placement without the use of either balloon angioplasty or distal protection devices. MATERIALS AND METHODS: Eighty-seven consecutive patients with 100 carotid stenoses compose this series. Ninety four of the 100 hundred stented carotid arteries were either symptomatic (58 [58%]) or had a greater than 70% stenosis (36 [36%]). Six percent of them were asymptomatic and had stenosis between 50% and 70%. Patients underwent neurologic evaluation before the procedure and during follow-up at 1, 3, 6, and 12 months and annually thereafter. Carotid sonography and plain films of the neck were performed immediately after the procedure and then at the same time intervals. RESULTS: Primary stent placement was successful in 98 of 100 case subjects. In 2 case subjects, predilation was necessary before stent deployment. Neurologic periprocedural complications included 1 nondisabling and 1 disabling stroke and 5 transient ischemic attacks. The mean duration of follow-up was 23 months (range: 10-36 months). During the follow-up period, there were 5 deaths, all unrelated to the carotid disease, and no major stroke. The degree of stenosis decreased from a mean of 78.85% before the procedure to a mean of 21.23% immediately after. CONCLUSIONS: In this series, carotid stent placement without the use of either balloon angioplasty or distal protection devices was safe and effective with a low incidence of periprocedural complications.

Rapid shell vial culture for the detection of respiratory viruses from bronchoalveolar lavage in immunocompromised patients.

AIM: Viral lower respiratory tract infections (LRTI) are an important cause of morbidity in immunocompromised patients. The aim of this study was to evaluate the clinical impact of rapid shell vial cultures from bronchoalveolar lavage (BAL). METHODS: Sixty-seven BAL samples from 46 patients have been retrospectively examined: 51 from 31 transplant recipients and 16 from 15 immunocompromised patients. BAL were inoculated on human embryonic lung fibroblasts and VERO cells to isolate the following viruses: cytomegalovirus (CMV), herpesviruses, varicella-zoster virus, respiratory syncytial virus, adenovirus, Influenza viruses A and B and Parainfluenza viruses. Clinical, microbiological, laboratory, and radiological data were collected. RESULTS: A LRTI was present in 56.7% of cases: viral 40.3%, bacterial and/or fungal 23.9%, and mixed 7.5%. CMV accounted for 92.6% of viral LRTI. The prevalence of viral infections did not differ between symptomatic and asymptomatic patients; only bacterial and/or fungal infections were significantly more prevalent in symptomatic patients. No clinical, radiological or laboratory feature was significantly associated with the presence of a viral LRTI. In lung transplant recipients the rate of CMV infection was 50%. The result of BAL suggested commencement of antiviral chemotherapy in 25/67 episodes. CONCLUSION: Rapid shell vial culture and immunofluorescence techniques from BAL could play an important role in the clinical management of immunocompromised subjects.