The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)

Efficacy of Antibiotic Prophylaxis Before the Implantation of Pacemakers and Cardioverter-Defibrillators Results of a Large, Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial

Background-Although routinely administered, definitive evidence for the benefits of prophylactic antibiotics before the implantation of permanent pacemakers and implantable cardioverter-defibrillators from a large double-blinded placebo-controlled trial is lacking. The purpose of this study was to determine whether prophylactic antibiotic administration reduces the incidence of infection related to device implantation. Methods and Results-This double blinded study included 1000 consecutive patients who presented for primary device (Pacemaker and implantable cardioverter-defibrillators) implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of I g of cefazolin (group 1) or placebo (group 2) was done immediately before the procedure. Follow-up was performed 10 days, 1, 3, and 6 months after discharge. The primary end point was any evidence of infection at the surgical incision (pulse generator pocket), or systemic infection related to be procedure. The safety committee interrupted the trial after 649 patients were enrolled due to a significant difference in favor of the antibiotic arm (group 1: 2 of 314 infected patients-0.63%; group 11: 11 of 335 to 3.28%; RR=0.19; P=0.016). The following risk factors were positively correlated with infection by univariate analysis: nonuse of preventive antibiotic (P=0.016); implant procedures (versus generator replacement: P=0.02); presence of postoperative hematoma (P=0.03) and procedure duration (P=0.009). Multivariable analysis identified nonuse of antibiotic (P=0.037) and postoperative hematoma (P=0.023) as independent predictors of infection. Conclusions-Anti biotic prophylaxis significantly reduces infectious complications in patients undergoing implantation of pacemakers or cardioverter-defibrillators. (Circ Arrhythmia Electrophysiol. 2009;2:29-34.)

Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT

Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR +) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR + advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane ( n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups ( hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate ( 7.4% v 6.7%; P = .736) and clinical benefit rate ( 32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Immunohistochemistry and polymerase chain reaction on paraffin-embedded material improve the diagnosis of cutaneous leishmaniasis in the Amazon region

Background Recently, there has been an increase in the incidence of cutaneous leishmaniasis (CL), which represents an important health problem. This increase may be related to the epidemiologic expansion of the infective agent and the increase in tourism in tropical areas. The difficulty in clinical diagnosis, mainly in areas in which CL is not the first consideration of local physicians, has intensified efforts to describe diagnostic tests, which should be specific, sensitive, and practical. Amongst the new tests described are those including nucleic acid amplification (polymerase chain reaction, PCR) and immunohistochemistry (IHC). Methods In this study, we evaluated the sensitivity of a PCR based on small subunit (SSU) ribosomal DNA, in comparison with IHC using Leishmania spp. antibodies, in biopsies embedded in paraffin. Result The results indicated a total sensitivity of 96% (90.9% with PCR and 68.8% with IHC), showing the possibility of using paraffin-embedded biopsies to diagnose CL. Conclusion We propose the use of the two tests together as a routine protocol for diagnosis. This would require the provision of local medical services to perform molecular biology techniques and adequate Leishmania antibodies.

Seven-year trend analysis of nosocomial candidemia and antifungal (fluconazole and caspofungin) use in Intensive Care Units at a Brazilian University Hospital

Candidemia is associated with high morbidity and mortality resulting in significant increases in the length of patients` hospitalization and in healthcare costs. Critically ill patients are at particular risk for candidemia because of their debilitated condition and frequent need for invasive procedures. The aim of this study was to characterize the incidence and epidemiology of candidemia over a seven-year period in intensive care units (ICUs) and the use of fluconazole and caspofungin in a large university-affiliated hospital. All cases of candidemia were identified by surveillance, using the Centers for Diseases Control and Prevention criteria. Demographic variables, use of antifungal (fluconazole and caspofungin) and patient outcomes were evaluated. The 2 test for linear trend was employed to evaluate the distribution of Candida spp. and the use of fluconazole and caspofungin by defined daily dose (DDD) per 1,000 patients-days during the study period. One hundred and eight episodes of candidemia were identified. The overall incidence of candidemia (P=0.20) and incidence of non-Candida albicans Candida infections (P=0.32) remained stable over the study period and ranged from 0.3-0.9 episodes per 1,000 catheter-days and 0.39-0.83 episodes per 1,000 patients-days. However, the use of fluconazole and caspofungin increased significantly (P0.001). While there were no reports of the use of fluconazole for prophylaxis in 1999, its use for this purpose increased from 3% in 2000 to 7.0% (P=0.07) in 2006. C. albicans was the most frequent specie isolated and burns and cancer were the most frequent underlying conditions. The overall mortality was 76%. There was no difference between C. albicans and non-C. albicans Candida infections when the crude and 14-day mortality rates were compared. Our data demonstrated that C. albicans is still the most frequent species causing candidemia in our intensive care units. Our rates of candidemia are lower than those reported from the region and similar to American and European hospitals. Although the incidence of blood stream infections (BSI) and candidemia remained stable, the use of fluconazole and caspofungin increased significantly over the years included in this study but had no impact on the incidence of infections caused by non-C. albicans Candida species.

Polymorphisms in Alcohol Metabolizing Genes and the Risk of Head and Neck Cancer in a Brazilian Population

Aims: The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC. Methods: A hospital-based case-control study was conducted in Sao Paulo, Brazil. We here investigated ADH1C Ile(350)Val, ADH1B Arg(48)His, ADH1B Arg(370)Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital. Results: Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg(48)His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21-0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20-0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13-0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg(48)His who consume alcohol > 30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21-16.11). Conclusions: The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is < 30.655 g/L/day.

Potential Effect of Using ABO-Compatible Living-Donor Liver Transplantation

Liver transplantation increased 1.84-fold from 1988 to 2004. However, the number of patients on the waiting list for a liver increased 2.71-fold, from 553 to 1500. We used a mathematical equation to analyze the potential effect of using ABO-compatible living-donor liver transplantation (LDLT) on both our liver transplantation program and the waiting list. We calculated the prevalence distribution of blood groups (O, A, B, and AB) in the population and the probability of having a compatible parent or sibling for LDLT. The incidence of ABO compatibility in the overall population was as follows: A, 0.31; B, 0.133; O, 0.512; and AB, 0.04. The ABO compatibility for parent donors was blood group A, 0.174; B, 0.06; O, 0.152; and AB, 0.03; and for sibling donors was A, 0.121; B, 0.05; O, 0.354; and AB, 0.03. Use of LDLT can reduce the pressure on our liver transplantation waiting list by decreasing its size by at least 16.5% at 20 years after its introduction. Such a program could save an estimated 3600 lives over the same period.

Endomyocardial fibrosis: pathological and molecular findings of surgically resected ventricular endomyocardium

Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown etiology prevalent in tropical regions affecting the inflow tract and apex of one or both ventricles, which show fibrous thickening of the endocardium and adjacent myocardium. Surgical treatment is recommended for patients in functional classes III or IV (New York Heart Association). The gross and histological features of the heart have been comprehensively studied in autopsies, but studies in surgical samples are still lacking. Histological and immunohistochemical features of EMF in surgical samples collected from 32 patients were described and correlated with clinical data. Polymerase chain reaction (PCR) and reverse transcription-PCR, performed on formalin fixed endomyocardial samples, were used retrospectively to detect genomes of certain cardiotropic viruses and Toxoplasma gondii. Ventricular endocardium was thickened by superficial acellular hyaline collagen fibers type I and III, with predominance of the former type. Besides fibrosis, a chronic inflammatory process and an anomalous lymphatic rich vascular pattern were observed in the deep endocardium, connected to the terminal coronary circulation of the myocardium, which might be an important pathological finding concerning EMF pathogenesis. Molecular analysis of the endomyocardium revealed high incidence of cardiotropic infective agents (6/12, 50%); however, their role in the disease pathogenesis is still controversial.

Assessment of flow in perforating arteries during intracranial aneurysm surgery using intraoperative near-infrared indocyanine green videoangiography

OBJECTIVE: Perforating arteries are commonly involved during the surgical dissection and clipping of intracranial aneurysms. Occlusion of perforating arteries is responsible for ischemic infarction and poor outcome. The goal of this study is to describe the usefulness of near-infrared indocyanine green videoangiography (ICGA) for the intraoperative assessment of blood flow in perforating arteries that are visible in the surgical field during clipping of intracranial aneurysms. In addition, we analyzed the incidence of perforating vessels involved during the aneurysm surgery and the incidence of ischemic infarct caused by compromised small arteries. METHODS: Sixty patients with 64 aneurysms were surgically treated and prospectively included in this study. Intraoperative ICGA was performed using a surgical microscope (Carl Zeiss Co., Oberkochen, Germany) with integrated ICGA technology. The presence and involvement of perforating arteries were analyzed in the microsurgical field during surgical dissection and clip application. Assessment of vascular patency after clipping was also investigated. Only those small arteries that were not visible on preoperative digital subtraction angiography were considered for analysis. RESULTS: The ICGA was able to visualize flow in all patients in whom perforating vessels were found in the microscope field. Among 36 patients whose perforating vessels were visible on ICGA, 11 (30%) presented a close relation between the aneurysm and perforating arteries. In one (9%) of these 11 patients, ICGA showed occlusion of a P1 perforating artery after clip application, which led to immediate correction of the clip confirmed by immediate reestablishment of flow visible with ICGA without clinical consequences. Four patients (6.7%) presented with postoperative perforating artery infarct, three of whom had perforating arteries that were not visible or distant from the aneurysm. CONCLUSION: The involvement of perforating arteries during clip application for aneurysm occlusion is a usual finding. Intraoperative ICGA may provide visual information with regard to the patency of these small vessels.

Isolation and Genotyping of Rubella Virus From a Case of Congenital Infection in Brazil

The incidence of CRS and CRI has decreased markedly worldwide with the implementation of efficient vaccination programs. We report a congenital rubella case with fetal death occurred at 29th week of gestation. RV was confirmed in placenta. The results of phylogenetic analysis showed that the RVs/Sao-Paulo01.- BRA/08.CRI belongs to the genotype 2B of RV. J. Med. Virol. 83:2048-2050, 2011. (C) 2011 Wiley-Liss, Inc.

Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and predictors

One hundred forty-two women with polycystic ovary syndrome (PCOS) with an average body mass index (BMI) of 29.1 kg/m(2) and average age of 25.12 years were studied. By BMI, 30.2% were normal, 38.0% were overweight and 31.6% were obese. Thirty-one eumenorrheic women matched for BMI and age, with no evidence of hyperandrogenism, were recruited as controls. The incidence of dyslipidemia in the PCOS group was twice that of the Control group (76.1% versus 32.25%). The most frequent abnormalities were low high-density lipoprotein cholesterol (HDL-C; 57.6%) and high triglyceride (TG) (28.3%). HDL-C was significantly lower in all subgroups of women with PCOS when compared to the subgroups of normal women. No significant differences were seen in the total cholesterol (p = 0.307), low-density lipoprotein cholesterol (LDL-C; p = 0.283) and TGs (p = 0.113) levels among the subgroups. An independent effect on HDL-C was detected for glucose (p = 0.004) and fasting insulin (p = 0.01); on TG for age (p = 0.003) and homeostatic model assessment insulin resistance (p = 0.03) and on total cholesterol and LDL-C for age (p = 0.02 and p = 0.033, respectively). In conclusion, dyslipidemia is common in women with PCOS, mainly due to low HDL-C levels. BMI has a significant impact on this abnormality.

Prematurity prevention: the role of progesterone

Purpose of review This review summarizes the evidence of the effectiveness of progesterone on the rate of preterm birth and evaluates the most recent studies. Recent findings The incidence of preterm delivery is about 7-11% of all pregnant women and preterm birth is one of the most important causes of neonatal morbidity and mortality. Interventions to reduce such complications have been attempted for several years. Most efforts so far have been tertiary interventions, such as treatment with antenatal corticosteroids, tocolytic agents, and antibiotics. Some of these measures have reduced perinatal morbidity and mortality, but the incidence of preterm birth is increasing. Recently, researches have suggested prophylactic progesterone could reduce the preterm birth rate in a select group presenting previous preterm birth and a short cervical length by transvaginal scan at mid-trimester pregnancy. Summary This review intends to define the current indication for administration of progesterone for pregnant women. On the basis of current knowledge, progesterone should be offered to women with a documented history of a previous spontaneous birth at less than 37 weeks and for those found to have a short cervical length of 15 mm or less. Studies are needed to evaluate progesterone efficacy on other risk factors.

Surgical Treatment of Myelomeningocele Carried Out at `Time Zero` Immediately after Birth

Background/Aims: To present a protocol of immediate surgical repair of myelomeningocele (MMC) after birth (`time zero`) and compare this surgical outcome with the surgery performed after the newborn`s admission to the nursery before the operation. Methods: Data from the medical files of 31 patients with MMC that underwent surgery after birth and after admission at the nursery ( group I) were compared with a group of 23 patients with MMC admitted and prospectively followed, who underwent surgery immediately after birth - `at time zero` ( group II). Results: The preoperative rupture of the MMC occurred more frequently in group I (67 vs. 39%, p < 0.05). The need for ventriculoperitoneal shunt was 84% in group I and 65% in group II and 4 of them were performed during the same anesthetic time as the immediate MMC repair, with no statistically significant difference. Group I had a higher incidence of small dehiscences when compared to group II ( 29 vs. 13%, p < 0.05); however, there was no statistically significant difference regarding infections. After 1 year of follow-up, 61% of group I showed neurodevelopmental delay, whereas only 35% of group II showed it. Conclusions: The surgical intervention carried out immediately after the birth showed benefits regarding a lower incidence of preoperative rupture of the MMC, postoperative dehiscences and lower incidence of neurodevelopmental delay 1 year after birth. Copyright (C) 2009 S. Karger AG, Basel

Influence of vitrification on mouse metaphase II oocyte spindle dynamics and chromatin alignment

Objective: To evaluate influences of vitrification and warming of metaphase II (MII) mouse oocytes on survival, spindle dynamics. spindle morphology, and chromatin alignment on metaphase plates. Design: Experimental animal Study. Setting: University animal laboratory. Animal(s): Eight-week-old B6D2F1 mice. Intervention(s): Denuded MII oocytes were used fresh (control), exposed to vitrification/warming solutions (Sol Expos), or vitrified and warmed (Vitr). Main Outcome Measure(s): Oocyte recovery and survival after warming and the influence of solution exposure and cryopreservation on spindle dynamics and chromatin alignment. Result(s): Cryopreservation of two or 10 oocytes per straw resulted in recovery (100% +/- 0% and 95% +/- 4%, respectively; mean SE) and survival (95% 2% and 98% 2%, respectively). Immediately after warming (Vitr), significantly fewer oocytes assessed with immunocytochemistry contained spindles, compared with control and Sol Expos. When oocytes were placed into a 3 degrees 7C environment for 2 hours after exposure or warming, the ability to recognize spindles by immunocytochemistry was not significantly different between groups. Using live-cell time-lapse imaging with LC-Polscope, similar time-dependent spindle formation dynamics were observed. At 2 hours after collection or treatment, spindle morphology and length were not significantly different between the groups, nor was the incidence of aberrant alignment of chromatin on metaphase plates. Conclusion(s): Immediately after warming of vitrified MII oocytes, beta-tubulin is depolymerized and chromatin remains condensed on the metaphase plate. Within a 2-hour period, beta-tubulin repolymerizes, forming morphologically normal metaphase spindles with properly aligned chromatin.

Prenatal diagnosis of posterior mediastinal lymphangioma by two- and three-dimensional ultrasonography

Lymphangioma is a rare benign tumor characterized by proliferating lymph vessels and composed of large cyst spaces with endothelium-lined channels of varying dimensions. The incidence of lymphangioma is approximately one in 6000 pregnancies. Less than 1 % of lymphangiomas are purely mediastinal. The great majority of cases are of cystic lymphangioma, but very rarely there is a mixed lesion consisting of multiple cysts of dilated capillary and lymph vessels. We report a case of posterior mediastinal lymphangioma diagnosed at 28 weeks` gestation, in which three-dimensional ultrasonography was helpful in determining the precise location of the tumor. A Cesarean section was performed at 39 weeks and the tumor was resected on the 5(th) day postdelivery; histological examination revealed a mixed cystic lymphangioma. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.