Eradication of Staphylococcus aureus Post-Sternotomy Mediastinitis Following the Implementation of Universal Preoperative Nasal Decontamination With Mupirocin: An Interrupted Time-Series Analysis.

BACKGROUND: Although presurgical nasal decontamination with mupirocin (NDM) has been advocated as a measure for preventing postsurgical mediastinitis (PSM) due to Staphylococcus aureus, this strategy is not universally recommended due to lack of robust supporting evidence. We aimed to evaluate the role of preoperative NDM in the annual incidence of S. aureus PSM at our institution. METHODS: An interrupted time-series analysis, with an autoregressive error model, was applied to our single-center cohort by comparing preintervention (1990-2003) and postintervention (2005-2018) periods. Logistic regression was performed to analyze risk factors for S. aureus PSM. RESULTS: 12 236 sternotomy procedures were analyzed (6370 [52.1%] and 5866 [47.9%] in the pre- and postintervention periods, respectively). The mean annual percentage adherence to NDM estimated over the postintervention period was 90.2%. Only 4 of 127 total cases of S. aureus PSM occurred during the 14-year postintervention period (0.68/1000 sternotomies vs 19.31/1000 in the preintervention period; P < .0001). Interrupted time-series analysis demonstrated a statistically significant annual reduction in S. aureus PSM of -9.85 cases per 1000 sternotomies (-13.17 to -6.5; P < .0001) in 2005, with a decreasing trend maintained over the following 5 years and an estimated relative reduction of 84.8% (95% confidence interval [CI], 89.25-74.09%). Chronic obstructive pulmonary disease was the single independent risk factor for S. aureus PSM (odds ratio, 3.7; 95% CI, 1.72-7.93) and was equally distributed in patients undergoing sternotomy during pre- or postintervention periods. CONCLUSIONS: Our experience suggests the implementation of preoperative NDM significantly reduces the incidence of S. aureus PSM.

[Impact of cardiovascular risk factors in the Extremadura population: HERMEX cohort contributions for a preventive strategy]. / Impacto de los factores de riesgo cardiovascular en la población extremeña: aportación de la cohorte HERMEX para una estrategia preventiva.

OBJECTIVE: To determine the population attributable fraction (PAF) of the major risk factors (RF) for the occurrence of cardiovascular disease in an Extremadura population cohort and therefore recommend priority preventive measures in health. METHODS: Design, Cohort study. LOCATION: Representative population sample of a health area of Extremadura (Spain) PARTICIPANTS: 2833 individuals, from 25 to 79 years old, randomly selected and recruited between 2007 and 2009. Antecedents and clinical parameters were recorded, a follow up until December 31, 2015 were done. MEASUREMENTS: Explanatory variables: Age, sex, obesity, current smoking, arterial hypertension, diabetes mellitus (DM) and hypercholesterolemia. OUTCOME VARIABLE: First event of the combined variable of myocardial infarction, angina pectoris, stroke, peripheral arterial disease and cardiovascular death. Fully adjusted hazard ratios (HR) were calculated by Cox regression. The PAFs were calculated using Levin's formula. RESULTS: 2669 subjects were included, 103 had history of cardiovascular disease and 61 were lost. The follow-up was 6.9 years (IR 6.5-7.5). 134 events were recorded. Incidence rate 7.42/1,000 people-year. Adjusted HR (95% CI) were: hypertension 2.26 (1.40-3.67), hypercholesterolemia 2.23 (1.56-3.18), DM 1.79 (1.24-2.58) and current smoking 1.72 (1.11-2.69). The PAF (95% CI) were: hypertension: 31.1 (12.4-48.8), hypercholesterolemia 27.0% (14.8-40.6), smoking 18.8% (3.3-35.0) and DM 7.9% (2.6-15.2). CONCLUSIONS: Hypertension confers the greatest burden of cardiovascular disease in the population of Extremadura, followed by hypercholesterolemia and smoking. These RF are priority objectives for a population-based preventive strategy.

Active smoking increases microsomal PGE2-synthase-1/PGE-receptor-4 axis in human abdominal aortic aneurysms.

BACKGROUND: The cyclooxygenase- (COX-) 2/microsomal PGE-synthase- (mPGES-) 1/PGE-receptor- (EP-) 4 axis could play a key role in the physiopathology of abdominal aortic aneurysm (AAA) in humans. In this study, we investigated the influence of cardiovascular risk factors on the expression of the PGE2 pathway in human AAA. METHODS: Aortic (n = 89) and plasma (n = 79) samples from patients who underwent AAA repair were collected. Patients were grouped according to risk factors. COX-isoenzymes, mPGES-1, EPs, α-actin, and CD45 and CD68 transcripts levels were quantified by QRT-PCR and plasma PGE2 metabolites by EIA. RESULTS: Current smoking (CS) patients compared to no-CS had significantly higher local levels of mPGES-1 (P = 0.009), EP-4 (P = 0.007), and PGE2 metabolites plasma levels (P = 0.008). In the multiple linear regression analysis, these parameters remained significantly enhanced in CS after adding confounding factors. Results from association studies with cell type markers suggested that the increased mPGES-1/EP-4 levels were mainly associated with microvascular endothelial cells. CONCLUSIONS: This study shows that elements of the PGE2 pathway, which play an important role in AAA development, are increased in CS. These results provide insight into the relevance of tobacco smoking in AAA development and reinforce the potential of mPGES-1 and EP-4 as targets for therapy in AAA patients.

Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm.

We investigated the prostaglandin (PG)E2 pathway in human abdominal aortic aneurysm (AAA) and its relationship with hypervascularization. We analyzed samples from patients undergoing AAA repair in comparison with those from healthy multiorgan donors. Patients were stratified according to maximum aortic diameter: low diameter (LD) (<55 mm), moderate diameter (MD) (55-69.9 mm), and high diameter (HD) (≥70 mm). AAA was characterized by abundant microvessels in the media and adventitia with perivascular infiltration of CD45-positive cells. Like endothelial cell markers, cyclooxygenase (COX)-2 and the microsomal isoform of prostaglandin E synthase (mPGES-1) transcripts were increased in AAA (4.4- and 1.4-fold, respectively). Both enzymes were localized in vascular cells and leukocytes, with maximal expression in the LD group, whereas leukocyte markers display a maximum in the MD group, suggesting that the upregulation of COX-2/mPGES-1 precedes maximal leukocyte infiltration. Plasma and in vitro tissue secreted levels of PGE2 metabolites were higher in AAA than in controls (plasma-controls, 19.9 ± 2.2; plasma-AAA, 38.8 ± 5.5 pg/ml; secretion-normal aorta, 16.5 ± 6.4; secretion-AAA, 72.9 ± 6.4 pg/mg; mean ± SEM). E-prostanoid receptor (EP)-2 and EP-4 were overexpressed in AAA, EP-4 being the only EP substantially expressed and colocalized with mPGES-1 in the microvasculature. Additionally, EP-4 mediated PGE2-induced angiogenesis in vitro. We provide new data concerning mPGES-1 expression in human AAA. Our findings suggest the potential relevance of the COX-2/mPGES-1/EP-4 axis in the AAA-associated hypervascularization.

Outcome of moderate-severe tricuspid regurgitation after pulmonary endarterectomy or balloon pulmonary angioplasty.

INTRODUCTION AND OBJECTIVES: The management of persistent moderate-severe tricuspid regurgitation (TR) in patients with chronic thromboembolic pulmonary hypertension after treatment with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) is not well defined. This study aimed to analyze the progression and predictors of significant persistent postintervention TR and its prognostic impact. METHODS: This single-center observational study included 72 patients undergoing PEA and 20 who completed a BPA program with a previous diagnosis of chronic thromboembolic pulmonary hypertension and moderate-to-severe TR. RESULTS: The postintervention prevalence of moderate-to-severe TR was 29%, with no difference between the PEA- or BPA-treated groups (30.6% vs 25% P=.78). Compared with patients with absent-mild postprocedure TR, those with persistent TR had higher mean pulmonary arterial pressure (40.2±1.9 vs 28.5±1.3mmHg P <.001), pulmonary vascular resistance (472 [347-710] vs 282 [196-408] dyn.s/cm5; P <.001), and right atrial area (23.0 [21-31] vs 16.0 [14.0-20.0] P <.001). The variables independently associated with persistent TR were pulmonary vascular resistance> 400 dyn.s/cm5 and postprocedure right atrial area> 22cm2. No preintervention predictors were identified. The variables associated with increased 3-year mortality were residual TR and mean pulmonary arterial pressure> 30mmHg. CONCLUSIONS: Residual moderate-to-severe TR following PEA-PBA was associated with persistently high afterload and unfavorable postintervention right chamber remodeling. Moderate-to-severe TR and residual pulmonary hypertension were associated with a worse 3-year prognosis.

The Modification of Diet in Renal Disease 4-calculated glomerular filtration rate is a better prognostic factor of cardiovascular events than classical cardiovascular risk factors in patients with peripheral arterial disease.

OBJECTIVE: Risk prediction is important in medical management, especially to optimize patient management before surgical intervention. No quantitative risk scores or predictors are available for patients with peripheral arterial disease (PAD). Surgical risk and prognosis are usually based on anesthetic scores or clinical evaluation. We suggest that renal function is a better predictor of risk than other cardiovascular parameters. This study used the four-variable Modification of Diet in Renal Disease (MDRD-4)-calculated glomerular filtration rate (GFR) to compare classical cardiovascular risk factors with prognosis and cardiovascular events of hospitalized PAD patients. METHODS: The study evaluated 204 patients who were admitted for vascular intervention and diagnosed with grade IIb, III, or IV PAD or with carotid or renal stenosis. Those with carotid or renal stenosis were excluded, leaving 188 patients who were randomized from 2004 to 2005 and monitored until 2010. We performed a life-table analysis with a 6-year follow-up period and one final checkpoint. The following risk factors were evaluated: age, sex, ischemic heart disease, ictus (as a manifestation of cerebrovascular disease related to systemic arterial disease), diabetes, arterial hypertension, dyslipidemia, smoking, chronic obstructive pulmonary disease, type of vascular intervention, and urea and creatinine plasma levels. The GFR was calculated using the MDRD-4 equation. Death, major cardiovascular events, and reintervention for arterial disease were recorded during the follow-up. RESULTS: Patients (73% men) were a mean age of 71.38 ± 11.43 (standard deviation) years. PAD grade IIb was diagnosed in 41 (20%) and grade III-IV in 147 (72%). Forty-two minor amputations (20.6%), 21 major amputations (10.3%), and 102 revascularizations (50%) were performed. A major cardiovascular event occurred in 60 patients (29.4%), and 71 (34.8%) died. Multivariate logistic regression analysis showed that the MDRD-4 GFR, age, and male sex were independent variables related to death and that the MDRD-4 GFR and chronic obstructive pulmonary disease were related to major cardiovascular events. A statistically significant relationship was also found between serum creatinine levels and reintervention rates. CONCLUSIONS: The MDRD-4 GFR was a better predictor of risk of death or infarction than classical cardiovascular risk factors in patients with PAD. This suggests that its routine use in the initial evaluation in patients with PAD is beneficial.

Pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension: the Spanish experience.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) can be cured by pulmonary endarterectomy (PEA). It is considered the best and only curable treatment option for patients with accessible lesions evaluated as optimal candidates. We describe the experience of the two reference centers in Spain, in order to reinforce the need for referring CTEPH patients to a specialized center to be assessed by a Multidisciplinary Expert Team. Methods: We included a population of 338 patients who met the definition for CTEPH and underwent PEA between January 2007 and December 2019. The surgery was indicated in almost 60% of patients assessed. Demographic, anthropometric, hemodynamic and echocardiographic features are listed for PEA patients. Immediate and one-year postoperative outcomes as well as overall mortality were analyzed. Results: Mean age was 53.5±15.0 years, 53.8% were men; a total of 68.5% were in WHO functional class III-IV; and most of them were in a preoperative hemodynamic condition: mean pulmonary arterial pressure (mPAP) was 46.5±13.1 mmHg and mean pulmonary vascular resistance (PVR) was 764.5±392.8 dyn·s·cm-5. PEA surgery was performed with cardiopulmonary bypass (CBP) and circulatory arrest, with very few complications [including neurological, postoperative reperfusion edema, extracorporeal membrane oxygenation (ECMO) implant and cardiac failure] and optimal postoperative results, where exercise capacity increased and mPAP and PVR values decreased significantly. Presence of persistent pulmonary hypertension (PH) at the six-month right heart catheterization was evaluated. A 3.3% perioperative mortality was achieved. Overall, one-, three- and five-year survival rates were analyzed by Kaplan-Meier's method (94.8%, 93.3% and 90.5% respectively), as well as for residual PH patients. Mortality risk factors were assessed. Conclusions: Outstanding PEA results were seen in the immediate, one-year and long-term outcomes. The incidence of complications, including in-hospital mortality and long-term mortality were also below European rates.

Analysis of HLA-ABC locus-specific transcription in normal tissues.

We developed a novel human leukocyte antigen HLA-ABC locus-specific quantitative real-time polymerase chain reaction (PCR) to determine the locus-specific gene expression of HLA-ABC in peripheral blood leukocytes (PBLs, n = 53), colon mucosa (n = 15), and larynx mucosa (n = 15). Laser-assisted tissue microdissection allowed us to study the selected cells without interference from surrounding stroma. We report evidence on the specificity of the technique, describing the HLA-ABC locus-specific gene expression patterns found in the PBLs and two solid tissues studied. PBLs showed a higher gene expression of HLA-B than of HLA-A or HLA-C (p = 4.7 × 10(-10) and p = 1.6 × 10(-6), respectively). In solid tissue, HLA-A and HLA-B gene expressions were similar and HLA-C expression lower. In particular, in larynx mucosa, significant differences were found between HLA-A and HLA-C expressions and between HLA-B and HLA-C expressions (p = 6.5 × 10(-4) and p = 8.1 × 10(-4), respectively). The same differences were observed in colon mucosa, but significance was not reached (p = 0.08 and p = 0.06, respectively). Differences in locus-specific regulation may be related to the control of cytotoxic responses of NK and CD8 positive T cells. Gene expression of HLA-ABC specific locus showed no intra-individual variability, but there was a high inter-individual variability. This may result from differences in the expression of common regulatory factors that control HLA-ABC constitutive expression.

A polymorphism in the interleukin-10 promoter affects the course of disease in patients with clear-cell renal carcinoma.

In the tumor microenvironment, interleukin (IL)-10 production has a pleiotropic ability to positively and negatively influence the function of innate and adaptive immunity against cancer. This study investigated whether IL-10 genetic polymorphisms that influence gene expression levels play a role in the risk and clinical course of clear-cell renal cell carcinoma (RCC). We analyzed the allelic and haplotype frequency formed by alleles at -1082(G/A), -819(C/T), and -592(C/A) of the IL-10 gene in RCC (n = 126) and healthy individuals (n = 176). The frequency of IL-10 polymorphic variants was similar between patients and controls. However, -1082 G/A IL-10 genotype showed a significant association with three prognostic indicators: advanced disease stage (p = 0.002), higher tumor size (p = 0.001), and presence of adenopathy (p = 0.006). Our results can be explained by the contradictory antitumor or pro-tumorigenic relationship between this molecule and cancer. Genotypes associated with high or low levels of IL-10 gene expression (GG or AA-1082 IL-10) were both associated with a more favorable course of the disease. We propose the hypothesis that the -1082 GA medium expression genotype confers a tumor-promoting phenotype, likely resulting from the immunosuppressive effects of anti-tumor Th-1 responses in conjunction with the insufficient inhibition of tumor angiogenesis at this intermediate level of IL-10 expression.

Anticardiolipin antibodies in patients with type 2 diabetes mellitus.

BACKGROUND: There is controversy about an increased prevalence of antiphospholipid antibodies in diabetic patients. The possible implications are little known. METHODS: We prospectively studied all consecutive outpatients with type 2 diabetes mellitus (DM) attended to in an Internal Medicine office. IgM and IgG anticardiolipin antibodies (ACA) were determined by standardized enzyme-linked immunoassay. RESULTS: Fifty-six patients were included. Only one patient (1.8%) had a titer of IgM ACA higher than 15 MPL units and no patient had a titer of IgG ACA higher than 15 GPL units. Six patients (10.7%) had low IgM ACA titers (4-15 MPL units) and 18 patients (32.1%) had low IgG ACA titers (4-15 GPL units). There were no differences in the frequencies of a low IgM or IgG ACA titer or in the means of IgM and IgG ACA titers in patients with complicated and uncomplicated DM, with and without cardiovascular disease, with and without nephropathy, or with and without retinopathy. CONCLUSIONS: Moderate to high ACA titers must be exceptional in patients with type 2 DM. Low ACA titers may occur in patients with type 2 DM. These low titers do not seem to be associated with complicated DM, cardiovascular disease, nephropathy or retinopathy.

Broodmate aggression and life history variation in accipitrid birds of prey.

Aggressive sibling competition for parental food resources is relatively infrequent in animals but highly prevalent and extreme among certain bird families, particularly accipitrid raptors (Accipitriformes). Intense broodmate aggression within this group is associated with a suite of traits including a large adult size, small broods, low provisioning rates, and slow development. In this study, we apply phylogenetic comparative analyses to assess the relative importance of several behavioral, morphological, life history, and ecological variables as predictors of the intensity of broodmate aggression in 65 species of accipitrid raptors. We show that intensity of aggression increases in species with lower parental effort (small clutch size and low provisioning rates), while size effects (adult body mass and length of nestling period) are unimportant. Intense aggression is more closely related to a slow life history pace (high adult survival coupled with a restrained parental effort), rather than a by-product of allometry or food limitation. Consideration of several ecological variables affecting prey abundance and availability reveals that certain lifestyles (e.g., breeding in aseasonal habitats or hunting for more agile prey) may slow a species' life history pace and favor the evolution of intense broodmate aggression.

Evaluation of functional single nucleotide polymorphisms of different genes coding for the immunoregulatory molecules in patients with monoclonal large granular lymphocyte lymphocytosis.

TCR alpha beta+/CD4+ T-large granular lymphocyte (LGL) lymphocytosis is a subgroup of monoclonal T-LGL lymphoproliferative disorders that are different from the CD8+ TCR alpha beta T-LGL. An increasing evidence supports the involvement of a common antigen-driven mechanism in the etiology of TCR alpha beta+/CD4+ T-LGL. In this study, we tested several polymorphic markers associated with chronic viral infections and autoimmune diseases, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), RANTES, IL-1 alpha, FAS, FAS-ligand (FASL), and NKG2D, to investigate the potential association of these immunogenetic factors with the development of T-LGL. Overall, 38 patients with CD4+ T-LGL were analyzed and compared with a group of both CD8+/TCR alpha beta+ T-LGL patients (n = 43) and a group of control subjects (n = 176). Our results did not show any clear association between the different single nucleotide polymorphisms (SNPs) analyzed and the development of CD4+/TCR alpha beta T-LGL. An increase in the frequency of -380 (AA/GA) TNF-alpha genotype associated with a greater production of this cytokine was found among CD8+ T LGL patients in comparison to the CD4+LGL patients and the control group. Our results suggest that the frequency of SNP of the genes coding for the studied immunoregulatory molecules are not associated with the development of CD4+/TCR alpha beta+ T-LGL.

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer.

BACKGROUND: Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. METHODS: A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. RESULTS: Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09-2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09-2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. CONCLUSION: Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.

Adverse outcomes in patients with venous thromboembolic disease from a rural population.

OBJECTIVE: To study the adverse outcomes and its predictors during anticoagulant therapy in patients with venous thromboembolic disease (VTD) from a rural population. METHODS: This is a prospective observational study of 94 consecutive patients. The patients were diagnosed in a first-level hospital from a rural Spanish area using objective methods of VTD. RESULTS: The mean follow-up with anticoagulant therapy was 7.1 months (range: 0-29 months). Eighteen patients (19.1%) had an adverse outcome: 10 (10.6%) during the first month and 8 (8.5%) after the first month. Sixteen patients (17%) died, 6 (6.4%) had a major hemorrhage, and 4 (4.3%) had a thromboembolic recurrence. Comorbidity, cancer, nonidiopathic VTD, and pulmonary thromboembolism were significantly associated with adverse outcomes. CONCLUSIONS: Adverse outcomes during anticoagulant therapy are frequent in patients from a rural population with VTD. These adverse outcomes occur frequently during the first month of treatment and are associated with the patient's prior status and the presence of pulmonary thromboembolism.

Incidence, Risk Factors and Outcomes of Early Acute Kidney Injury After Heart Transplantation: An 18-year Experience.

BACKGROUND: Little is known about the incidence of acute kidney injury (AKI), as defined using the Kidney Disease Improving Global Outcome classification, after heart transplantation (HT). Our objective was to evaluate the impact of AKI in a cohort of HT recipients. (Setting: University Hospital.) METHODS: We studied 310 consecutive HT recipients from 1999 to 2017, with AKI being defined according to the Kidney Disease Improving Global Outcome criteria. Risk factors were analyzed by multivariable analyses, and survival by Kaplan-Meier curves and a risk-adjusted Cox proportional hazards regression model. RESULTS: One hundred twenty-five (40.3%) patients developed AKI, with 73 (23.5%), 18 (5.8%), and 34 (11%) patients having AKI stages 1, 2, and 3, respectively. Cardiac tamponade (odds ratio [OR], 16.82; 95% confidence interval [CI], 1.06-138), acute right ventricular failure (OR, 3.54; 95% CI, 1.82-6.88), and major bleeding (OR, 2.46; 95% CI, 1.18-5.1) were the principal risk factors for AKI. Patients with AKI had a greater hospital mortality (3.8% vs 16%, P < 0.05), especially those requiring renal replacement therapy (46.9% vs 5.4%, P = 0.006). Acute kidney injury requiring renal replacement therapy was independently associated with hospital mortality (OR, 11.03; 95% CI, 4.08-29.8). With a median follow-up after hospital discharge of 6.7 years (interquartile range, 2.4-11.6), overall survival at 1, 5, and 10 years was 95.4%, 85.1%, and 75.4% versus 85.2%, 69.8% and 63.5% among patients without AKI and with AKI stages 2 to 3, respectively (P = 0.08). CONCLUSIONS: The onset of AKI after HT is mainly associated with postoperative complications. Only severe AKI stage predicts worse short-term outcome, with this impact appearing to be lost at long-term follow-up.

Vitamin D and thyrotropin in type 2 diabetic patients.

Vitamin D status and thyroid function may be related. Using our data from two previous studies in type 2 diabetic patients, we found slightly higher serum thyrotropin levels in patients with vitamin D deficiency (at the limit of statistical significance) and no effect of correction of vitamin D deficiency in serum thyrotropin levels.

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension. / Resultados de la tromboendarterectomía pulmonar en la hipertensión pulmonar tromboembólica crónica.

BACKGROUND AND OBJECTIVE: Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. MATERIAL AND METHODS: Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm-5, and group 2, which included the remaining 120 patients. RESULTS: Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). CONCLUSIONS: Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery.

NOR-1/NR4A3 regulates the cellular inhibitor of apoptosis 2 (cIAP2) in vascular cells: role in the survival response to hypoxic stress.

Vascular cell survival is compromised under pathological conditions such as abdominal aortic aneurysm (AAA). We have previously shown that the nuclear receptor NOR-1 is involved in the survival response of vascular cells to hypoxia. Here, we identify the anti-apoptotic protein cIAP2 as a downstream effector of NOR-1. NOR-1 and cIAP2 were up-regulated in human AAA samples, colocalizing in vascular smooth muscle cells (VSMC). While NOR-1 silencing reduced cIAP2 expression in vascular cells, lentiviral over-expression of this receptor increased cIAP2 mRNA and protein levels. The transcriptional regulation of the human cIAP2 promoter was analyzed in cells over-expressing NOR-1 by luciferase reporter assays, electrophoretic mobility shift analysis and chromatin immunoprecipitation, identifying a NGFI-B site (NBRE-358/-351) essential for NOR-1 responsiveness. NOR-1 and cIAP2 were up-regulated by hypoxia and by a hypoxia mimetic showing a similar time-dependent pattern. Deletion and site-directed mutagenesis studies show that NOR-1 mediates the hypoxia-induced cIAP2 expression. While NOR-1 over-expression up-regulated cIAP2 and limited VSMC apoptosis induced by hypoxic stress, cIAP2 silencing partially prevented this NOR-1 pro-survival effect. These results indicate that cIAP2 is a target of NOR-1, and suggest that this anti-apoptotic protein is involved in the survival response to hypoxic stress mediated by NOR-1 in vascular cells.

Metabolic effects of supplementation with vitamin D in type 2 diabetic patients with vitamin D deficiency.

AIM: Epidemiological studies suggest that vitamin D status influences type 2 diabetes mellitus. We investigate the metabolic effects of vitamin D. MATERIAL AND METHODS: We studied consecutive type 2 diabetic patients without insulin therapy with vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) lower than 20ng/ml). They were treated with 16,000IU of calcifediol orally once a week for a minimum of 8 weeks. RESULTS: Twenty eight patients were treated for a mean time of 84.1 days (range 56 to 120 days). All patients achieved serum levels of 25(OH)D higher than 20ng/ml. There was a significant reduction in fasting glucose (145.6±35.5 vs. 131.7±30.4mg/dl, p<0.001). There were small non-significant reductions in HbA1c, fasting insulin and Homeostasis Model Assesment (HOMA)-insulin resistance (IR). There were small non-significant increases in HOMA-insulin sensitivity (S) and HOMA-beta cell function (B) and a small significant increase in Quantitative Insulin Sensitivity Check Index (QUICKI). CONCLUSIONS: Correction of vitamin D deficiency in type 2 diabetic patients decreases fasting glucose. Our results do not rule out improvements in metabolic control, insulin-resistance and function of the beta cell.

Serum-free thyroxine and thyrotropin concentrations in euthyroid patients with decompensated congestive heart failure.

We realized a prospective study of 106 consecutive patients hospitalized in an Internal Medicine Service with decompensated CHF. Between the 95 patients with normal serum-free thyroxine and thyrotropin concentrations, patients older than 70 years had a significant higher serum free thyroxine concentration (13.1+/-2.6 vs. 10.1+/-1.5 pmol/l, p=0.006) and a lower, but not significant, serum thyrotropin concentration (1.3+/-1.2 vs. 1.7+/-1.1 mU/l, p=0.11). No correlation was found between the functional class, the echocardiographic ejection fraction or the in-hospital stay and the serum free thyroxine and thyrotropin concentrations. The sex, the presence of systolic dysfunction, diastolic dysfunction, atrial fibrillation or comorbidity did not determine significant differences in the serum-free thyroxine and thyrotropin concentrations.