BACKGROUND:Simultaneous pancreas and kidney (SPK) transplants using steroid-free regimens are a frequently used immunosuppressive strategy in low immunologic risk recipients. The long-term effect on recipient outcomes remains incompletely understood. METHODS:We analyzed post-transplant outcomes in 307 SPK recipients from a single center, comparing early steroid withdrawal (after completion of Thymoglobulin) with maintenance steroids. Steroid withdrawal was primarily utilized in low immunologic risk patients. RESULTS:In total, 170 SPK recipients underwent steroid withdrawal, and 137 received maintenance steroids. The withdrawal group had a lower cPRA and included fewer Black recipients. Biopsy-proven rejection rates (kidney, pancreas, or both) were similar between groups (26% vs. 29%, p = 0.523), with worse kidney/pancreas graft survival among those with rejection. Rejection occurred earliest in recipients rejecting both the kidney and pancreas, followed by those rejecting the kidney alone, and then those rejecting the pancreas. Multivariate analysis showed that kidney and pancreas survival were strongly interdependent. Kidney rejection was the primary predictor of graft survival. The steroid regimen was not independently associated with survival of either organ. Obesity at follow-up was associated with an increased risk of pancreas graft failure. CONCLUSION:In this single-center cohort, steroid withdrawal was safe in appropriately selected SPK recipients, with rejection-not the steroid regimen-driving long-term graft outcomes.

In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody–drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. The ability to target HER2-low expression is expected to have substantial clinical implications, irrespective of gender, including in cases of male breast cancer (MBC). However, an estimate of the prevalence of the HER2-low subtype in MBC is missing. This retrospective, observational, multicenter study was aimed at characterizing the HER2-low subtype in MBC. For the purpose of this study, the three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) was used to reclassify the HER2-negative group into HER-0 or HER2-low subtypes. In the whole series of 144 invasive MBCs, 79 (54.9%) were HER2-0 (IHC scores of 0), 39 (27.1%) HER2-low (IHC scores of 1+/2+ with negative ISH), and 26 (18.0%) HER2-positive (IHC scores of 3+/2+ with positive ISH). Specifically, among hormone receptor-positive (HR+) HER2-negative invasive MBCs, 34.8% were HER2-low and 65.2% HER2-0. Compared with HER2-0, HER2-low subtype was associated with a positive lymph node involvement (p = 0.01). Other pathologic characteristics including histology, staging, and grading did not show notable variations between the two subtypes. The presence of germline BRCA1/2 pathogenic variants (PVs) did not significantly differ between HER2-0 and HER2-low MBCs. However, about 13% of HER2-low MBCs had germline PVs in BRCA1/2 genes, mainly BRCA2, a clinically relevant observation in the context of combined target therapy. Overall, our data, which focused on the largest gender-specific breast cancer series, to our knowledge, confirm that the emerging three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) can also be considered in MBC, to mitigate both the gender gap and the underrepresentation of males in clinical trials.

Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, BC can also occur in men. Additionally, transgender individuals may also experience BC. Genetic risk factors play a relevant role in BC predisposition, with important implications in precision prevention and treatment. The genetic architecture of BC susceptibility is similar in women and men, with high-, moderate-, and low-penetrance risk variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) in BRCA1 and BRCA2 genes are the strongest BC genetic risk factor. BRCA1 and BRCA2 PVs are more commonly associated with increased risk of female and male BC, respectively. Notably, BRCA-associated BCs are characterized by sex-specific pathologic features. Recently, next-generation sequencing technologies have helped to provide more insights on the role of moderate-penetrance BC risk variants, particularly in PALB2, CHEK2, and ATM genes, while international collaborative genome-wide association studies have contributed evidence on common low-penetrance BC risk variants, on their combined effect in polygenic models, and on their role as risk modulators in BRCA1/2 PV carriers. Overall, all these studies suggested that the genetic basis of male BC, although similar, may differ from female BC. Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.

BACKGROUND:Germline pathogenic variants (PVs) in BRCA1/2 genes are associated with breast cancer (BC) risk in both women and men. Multigene panel testing is being increasingly used for BC risk assessment, allowing the identification of PVs in genes other than BRCA1/2. While data on actionable PVs in other cancer susceptibility genes are now available in female BC, reliable data are still lacking in male BC (MBC). This study aimed to provide the patterns, prevalence and risk estimates associated with PVs in non-BRCA1/2 genes for MBC in order to improve BC prevention for male patients.METHODS:We performed a large case-control study in the Italian population, including 767 BRCA1/2-negative MBCs and 1349 male controls, all screened using a custom 50 cancer gene panel.RESULTS:PVs in genes other than BRCA1/2 were significantly more frequent in MBCs compared with controls (4.8% vs 1.8%, respectively) and associated with a threefold increased MBC risk (OR: 3.48, 95% CI: 1.88-6.44; p < 0.0001). PV carriers were more likely to have personal (p = 0.03) and family (p = 0.02) history of cancers, not limited to BC. PALB2 PVs were associated with a sevenfold increased MBC risk (OR: 7.28, 95% CI: 1.17-45.52; p = 0.034), and ATM PVs with a fivefold increased MBC risk (OR: 4.79, 95% CI: 1.12-20.56; p = 0.035).CONCLUSIONS:This study highlights the role of PALB2 and ATM PVs in MBC susceptibility and provides risk estimates at population level. These data may help in the implementation of multigene panel testing in MBC patients and inform gender-specific BC risk management and decision making for patients and their families.

Introduction Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). Methods In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. Results and discussion A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.

Background: Simultaneous pancreas and kidney (SPK) transplant outcomes have steadily improved over the last three decades. The concept of sparing steroids has been adopted by many centers in order to avoid their negative side effects and additional beta cell toxicity. The long-term impact of steroid-free immunosuppressive regimens on graft survival remains unknown. Methods: We studied the post-transplant outcomes of 358 SPK recipients at a single center between 2000 and 2018. We performed an intention to treat analysis with the groups stratified based on the initial documented immunosuppressive plan – either steroid early withdrawal (stopped after thymoglobulin completion) or steroid maintenance. Early withdrawal was used primarily in patients with low immunologic risk. Rejection was determined using kidney or pancreas biopsy. Of note, 6-month protocol kidney biopsy was introduced in 2008. Results: A total of 226 SPK recipients received a steroid-free regimen and 132 received a steroid maintenance regimen. The median follow-up was 5.9 years (range, 0 - 19 years). Steroid maintenance and withdrawal groups had similar baseline characteristics, with the exception of a significantly lower panel-reactive antibody and less African-Americans in the steroid withdrawal group (both p<0.001). Biopsy proven rejection was observed in 23.9% of patients in the withdrawal group and 27.3% in the maintenance group (p=0.477). The maintenance group had fewer acute cellular and more antibody-mediated kidney rejections (Table). Five episodes of rejection were detected among the 54 protocol biopsies over this period. The best kidney and pancreas graft survival was observed in patients in the steroid withdrawal group who had no episodes of rejection, followed by those in the steroid maintenance group with no episodes of rejection (Figure). Patients with any biopsy-proven rejection (regardless of steroid group) had the worst organ survival. A total of 73 patients (32.3%) resumed steroid maintenance after being initially assigned to the withdrawal group, half of whom had biopsy proven rejection and an addition quarter of whom had clinical suspicion of rejection. Conclusion: Steroid withdrawal after SPK transplantation is a valid option in selected patients, is well tolerated, and allows similar outcomes compared to steroid maintenance regimen. The occurrence of rejection diminishes graft survival regardless of initial steroid regimen.

Background. Sarcopenia has been identified as a predictive variable for surgical outcomes. We hypothesized that sarcopenia could be a key measure to identify frail patients and potentially predict poorer outcomes among recipients of simultaneous pancreas and kidney (SPK) transplants. Methods. We estimated sarcopenia by measuring psoas muscle mass index (PMI). PMI was assessed on perioperative computed tomography (CT) scans of SPK recipients. Results. Of the 141 patients identified between 2010 and 2018, 107 had a CT scan available and were included in the study. The median follow-up was 4 years (range, 0.5–9.1 y). Twenty-three patients had a low PMI, and 84 patients had a normal PMI. Patient characteristics were similar between the 2 groups except for body mass index, which was significantly lower in low PMI group (P < 0.001). Patient and kidney graft survival were not statistically different between groups (P = 0.851 and P = 0.357, respectively). A multivariate Cox regression analysis showed that patients with a low PMI were 5 times more likely to lose their pancreas allograft (hazard ratios, 5.4; 95% confidence intervals, 1.4-20.8; P = 0.015). Three out of 6 patients lost their pancreas graft due to rejection in the low PMI group, compared with 1 out of 9 patients in the normal PMI group. Among low PMI patients who had a follow-up CT scan, 62.5% (5/8) of those with a functional pancreas graft either improved or resolved sarcopenia, whereas 75.0% (3/4) of those who lost their pancreas graft continued to lose muscle mass. Conclusion. Sarcopenia could represent one of the predictors of pancreas graft failure and should be evaluated and potentially optimized in SPK recipients.

Drug-eluting stents (DES) compared with bare-metal stents, reduce the rate of repeat revascularization [ [1] Stettler C. Wandel S. Allemann S. et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet. 2007; 370: 937-948 Abstract Full Text Full Text PDF PubMed Scopus (1283) Google Scholar ]. However, first-generation DES are associated with an increased risk of late stent thrombosis [ [2] Finn A.V. Joner M. Nakazawa G. et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. May 8 2007; 115: 2435-2441 Crossref PubMed Scopus (1140) Google Scholar ]. Several studies compared BES with PES and SES [ 3 Stefanini G.G. Kalesan B. Serruys P.W. et al. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet. Dec 3 2011; 378: 1940-1948 Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar , 4 Byrne R.A. Kastrati A. Massberg S. et al. Biodegradable polymer versus permanent polymer drug-eluting stents and everolimus- versus sirolimus-eluting stents in patients with coronary artery disease: 3-year outcomes from a randomized clinical trial. J Am Coll Cardiol. Sep 20 2011; 58: 1325-1331 Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar ] and with EES with different results [ 5 Smits P.C. Hofma S. Togni M. et al. Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a randomised, controlled, non-inferiority trial. Lancet. Feb 23 2013; 381: 651-660 Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar , 6 Christiansen E.H. Jensen L.O. Thayssen P. et al. Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V): a randomised non-inferiority trial. Lancet. Feb 23 2013; 381: 661-669 Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar ]. Our purpose was to compare BES versus EES and ZES in a large real-world registry. RUDI 2 was a retrospective, observational, multicenter registry. Out of all population treated with DES, the study included all patients who implanted BES, EES and R-ZES at 4 high-volume centers between November 2008 and November 2011. From a total of 3505 initially shortlisted patients and excluding 295 subjects receiving a mixture of BES, EES or R-ZES, and 71 patients lost to follow-up, a total of 3139 subjects were included. Patients who received BES were 818 (26.1%), 1433 (45.7%) EES and 888 (28.3%) R-ZES. Baseline, procedural and long-term (>12 months) outcome data were entered into a prospectively maintained database. The primary end-point was the long-term rate of major adverse cardiac events (MACE). Moreover, we evaluated the incidence of bleeding according to TIMI classification. Secondary end-points were the rate of stent thrombosis. Information about short-term outcomes was obtained by records review. Clinical follow-up was achieved by phone call and/or direct visit and there was an independent event committee for event's adjudication. Computations were performed with SPSS 20. Differences between continuous variables were analyzed with ANOVA or Kruskal–Wallis test for non-parametric data. Differences between categorical variables were analyzed with the chi-squared test.

Objectives The aim of this study is to assess the efficacy of the high-dose rosuvastatin preadministration in reducing periprocedural myocardial necrosis and major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing elective percutaneous coronary intervention (PCI). Background Elective PCI may be complicated with an elevation of cardiac biomarkers. Several studies suggested that pretreatment with statins may be associated with a reduction in periprocedural myocardial necrosis. Methods One hundred and sixty patients with stable angina who underwent elective PCI were randomly assigned to receive either a preprocedural loading dose (40 mg) of rosuvastatin group (RG, n = 80) or a standard treatment [control group (CG), n = 80].The primary endpoint was the incidence of periprocedural myocardial necrosis. The secondary endpoint was the assessment of MACCE [cardiac death, all-myocardial infarction (MI), stroke, and target vessel revascularization (TVR)] at a 30-day and 12-month follow-up, as well as the rate of periprocedural rise of Troponin T-serum levels >3x upper limit of normal. Results Twelve and 24-hr post-PCI creatinine kinase MB isoform elevation >3x occurred more frequently in the CG than in the RG (22.7 vs. 7.1; P = 0.034 and 26.4 vs. 8.7; P = 0.003). At the 30-day and 12-month follow-up, the incidence of cumulative MACCE was higher in CG than in the RG (30.0% vs. 8.7%; P = 0.001 and 35.0% vs. 12.5%; P = 0.001).The difference between the groups was mainly due to the periprocedural MI incidence (26.4% vs. 8.7%; P = 0.003).The rate of cardiac death, spontaneous MI, TVR, and stroke were similar in the two groups. Conclusions High loading dose of rosuvastatin within 24 hr before elective PCI seems to decrease the incidence of periprocedural myocardial necrosis during a period of 12-months compared to the standard treatment. (c) 2012 Wiley Periodicals, Inc.

We report a clinical case of a 45-year-old male with a diagnosis of inferior myocardial infarction and previous history of rheumatic fever during his childhood. Coronary angiography demonstrated normal coronary arteries. Transthoracic echocardiogram showed hypokinetic left ventricular inferolateral wall and mitral stenosis; furthermore, speckle tracking analysis revealed reduction of global longitudinal strain involving the inferior wall. A three-dimensional transesophaegeal echocardiography, performed to better characterize the anatomy of the valve and to find possible source of embolic infarct in an enlarged left atrium, showed rheumatic valvular involvement. Cardiac magnetic resonance confirmed the ischemic damage and also provided prognostic information. A multimodality imaging approach should be mandatory in patients with acute myocardial infarction and normal coronary angiography, to define possible sources of embolic infarction and to quantify myocardial damage.

OBJECTIVES:The objective of this study is to compare a reloading dose of Rosuvastatin and Atorvastatin administered within 24 h before coronary angioplasty (PCI) in reducing the rate of periprocedural myonecrosis and major cardiac and cerebrovascular events (MACCE) in patients on chronic statin treatment undergoing elective PCI. BACKGROUND:Elective PCI may be complicated with elevation of cardiac biomarkers. Several studies suggested that pretreatment with statins may be associated with a reduction in periprocedural myocardial necrosis. METHODS:Three hundred and fifty patients with stable angina who underwent elective PCI were randomly assigned to receive a pre-procedural reloading dose of Rosuvastatin (40 mg) (Rosuvastatin Group-RG n=175) or Atorvastatin (80 mg) (Atorvastatin Group-AG n=175) and a control group on chronic statin therapy without reloading (Control-Group-CG). The primary end-point was periprocedural myocardial necrosis and the occurrence of MACCE at 30-day,6-12 month follow-up. Also we evaluate the rise of periprocedural Troponin T serum levels >3× the upper limit of normal. RESULTS:Twelve and 24-hour post-PCI Creatine Kinase Muscle and Brain (CK-MB) elevation >3× occurred more frequently in the CG than in the RG and in the AG (at 24-h: 25.0 vs 7.1; p=0.003 and 25.0 vs 6.1; p=0.001). At 30-day, 6-and 12-month follow-up the incidence of cumulative MACCE was higher in CG than in the RG or AG (at 12-month: 41.0% vs 11.4% vs 12.0%; p=0.001). There was no difference between the RG and AG in terms of myocardial post-procedural necrosis and MACCE occurrence at follow-up. CONCLUSIONS:High-dose statin reloading improves procedural and long term clinical outcomes in stable patients on chronic statin therapy. Both Rosuvastatin and Atorvastatin showed similar beneficial effects on procedural and long-term outcomes.

BACKGROUND:Twelve-month dual antiplatelet therapy (DAT) with aspirin and clopidogrel after drug-eluting stent (DES) implantation is routinely recommended. It is unclear if prolonged (>12-month) DAT is also favorable. We compared the outcome of patients discontinuing DAT 12 months after off-label DES implantation versus those with DAT for >12 months. METHODS:Baseline, treatment, and outcome data of patients undergoing off-label DES implantation and free from events 11.5 months after index procedure were retrospectively retrieved. Those discontinuing DAT between 11.5 and 12.5 months (12-month DAT group) were compared to those discontinuing DAT after 12.5 months (>12-month DAT group). The primary end-point was the long-term (>24-month) rate of major adverse cerebro-cardiovascular events (MACCE). RESULTS:Two hundred seventy-two patients met study inclusion criteria: 133 (48.9%) in the 12-month DAT group and 139 (51.1%) in the >12-month DAT group (who were on DAT for an average of 24 months). After an average of 36 months after DES implantation, 14 patients (5.1%) developed MACCE, with 6 (3.5%) cardiac deaths, 7 (2.2%) myocardial infarctions, no stroke, and 5 (1.8%) repeat revascularizations. The >12-month DAT group had a significantly lower risk of MACCE (1 [0.7%] vs. 13 [9.8%] in the 12-month DAT group, P < 0.001) and myocardial infarction (0 vs. 7 [5.3%], P = 0.006), with such differences confirmed at multivariable propensity-adjusted analyses. No significant differences in terms of minor or major bleedings occurred. CONCLUSIONS:In this retrospective registry, patients with off-label DES implantation receiving prolonged (>12 months) DAT presented with lower rates of MACCE and myocardial infarction.

OBJECTIVES:The aim of our study is to evaluate the safety and efficacy of DES implantation in an unselected, "real world," high-risk population. BACKGROUND:Several clinical trials showed that drug-eluting stents (DESs) implantation is safe and effective in selected population. In spite of these encouraging results, there are some concerns about "real world" utilization of these stents. METHODS:One thousand four hundred and fifty-five off-label patients have been included in our registry. Primary end-points were: long-term clinical incidence of major adverse cardiac and cerebrovascular events (MACCE) and thrombosis (ST). We detected the difference between uniDES vs. multiDES implantation in terms of MACCE, death, nonfatal-MI, the composite of death/nonfatal-MI and target lesion revascularization (TLR) and the difference between DES type in term of MACCE. RESULTS:At 36 months follow-up we found: cardiac death occurred in 20 patients (1.6%); 33 patients (2.6%) had a nonfatal MI and 81 patients (6.3%) had a TLR. We observed one (0.1%) acute, 9 subacute (0.6%), 6 late (0.6%), and 1 (0.5%) very late definite ST. No difference were found in terms of overall MACCE, MI, death and composite of death/nonfatal-MI between uni- and multiDES implantation but multiDES group had a higher incidence of TLR. No difference between DES type in term of MACCE was detected. CONCLUSIONS:DES utilization shows their safety and efficacy in off-label patients with complex clinical and angiographic profile in terms of long-term incidence of MACCE. MultiDES implantation is associated with a higher risk of long-term TLR. No difference between DES type was found.

Objectives The purpose of this study was to evaluate the impact on myocardial perfusion and infarct size as assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM) (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary percutaneous coronary intervention (PPCI) in a subset of patients with anterior ST-segment elevation myocardial infarction (STEMI).Background PPCI may cause thrombus dislodgment, leading to microvascular damage.Methods One hundred seventy-five STEMI patients were randomly assigned to standard percutaneous coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points were the occurrence of myocardial blush grade >= 2 and the rate of 90-min ST-segment resolution > 70%. The CE-MRI substudy was performed in 75 patients with anterior STEMI to assess microvascular obstruction and infarct size.Results Myocardial blush grade >= 2 and ST-segment resolution occurred more frequently in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the acute phase, microvascular obstruction extent was significantly lower in the EM-PCI group and at 3 months, infarct size was significantly reduced only in the EM-PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%, log-rank test p = 0.02) was observed at 9 months.Conclusions Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI. (J Am Coll Cardiol 2009; 53: 309-15) c 2009 by the American College of Cardiology Foundation

OBJECTIVE:To evaluate the long-term outcomes after different modalities of treatment of drug-eluting stent (DES) in-stent restenosis (ISR) in a 'real world' setting. METHODS:Actually, few and conflicting data are available about the management of in-stent restenosis (ISR) after DES implantation. In our 'real world' registry 1082 consecutive patients who received a DES implantation were included. At 9-month angiographic follow-up, 93 patients presented a DES ISR that was treated with 'homo-DES' (HMD) (N = 27), 'hetero-DES' (HTD) (N = 19) and conventional balloon angioplasty (POBA) (N = 47). We evaluated the clinical outcomes in terms of major adverse cardiac event (MACE) (death, myocardial infarction and target vessel revascularization) at 18 months. RESULTS:There was no difference for clinical and angiographic characteristics between the three groups, except for the presence of silent ischaemia as clinical presentation (7.7 HMD vs. 2.2% POBA; P = 0.0001). No late stent thrombosis was found. At 18-month clinical follow-up patients treated with HMD, HTD and POBA presented a rate of MACE of 10.2, 0 and 8.7%, respectively (P = NS). Kaplan-Meier survival probability showed that HTD and POBA treatment tended to have more favourable outcomes at 18 months than the HMD treatment. CONCLUSION:In our registry, POBA seems to be as effective as other DES implantations in cases of DES ISR, especially in cases of focal type (Mehran classification IA, IC), in terms of long-term outcomes.

ISEE-0188 Background and Objective: Exposures to non-essential trace metals, including Hg, Cd, and Pb, are ubiquitous and threaten reproductive health. This study aims to investigate associations between body burdens of these metals and in vitro oocyte fertilization among a cohort of women undergoing a first IVF treatment cycle. Methods: Between 2006 and 2008, 55 women between 28–44 years of age initiating their first IVF treatment cycle were recruited to and finished the study. Urine specimens were analyzed for Cd using inductively-coupled plasma mass spectrometry (ICP-MS) and corrected for creatinine concentrations. Whole blood specimens from 50 participants were analyzed for total Hg, Cd, and Pb using ICP-MS. The successful fertilization of a mature oocyte (MII) was defined as the presence of two pronuclei 16–18 hours following insemination. Participants contributed a median of 8 oocytes (range 2–39). Multiple logistic regression models were used to evaluate associations between successful fertilization and metals, while adjusting for potential confounders selected using directed acyclic graphs. Generalized estimating equations were used to adjust standard errors for clustering of outcomes by subject. Results: Median blood concentrations for total Hg (4.15 μg/L) exceeded that reported by NHANES for the 2001–2002 female U.S. population (0.70 μg/L); however concentrations for the other metals were comparable. Adjusting for age, cigarette smoking, and ethnicity, there were no statistically significant associations between successful fertilization and blood total Hg (β = 0.05 P = 0.557), Cd (β = 0.82 P = 0.134), or Pb (β = −0.31, P = 0.587), or urine Cd (β = 0.52 P = 0.503). A comprehensive model simultaneously including blood Hg, Cd and Pb, as well as potential confounders produced similar results, as did a model considering only urine Cd and potential confounding variables. Conclusion: These results are not supportive of a deleterious effect for body burdens of Hg, Cd, or Pb received from background sources on oocyte fertilization during first IVF cycles.

BACKGROUND:In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) may cause thrombus dislodgment leading to microvascular function impairment, which is a negative independent predictor of myocardial function recovery. Compared with conventional stenting, pretreatment with aspiration thrombectomy during primary PCI significantly improves coronary epicardial flow and myocardial tissue perfusion parameters. We sought to evaluate the angiographic findings of two different manual aspiration thrombectomy devices (Diver-Invatec (DI) and Export-Medtronic (EM)) in STEMI patients undergoing primary angioplasty. METHODS:We randomized 103 STEMI patients referred to our hospital to undergo primary PCI (<12 hr from symptoms onset) to DI (n = 52) and EM (n = 51) devices. The primary angiographic composite end-points were the rates of post-thrombectomy thrombus score (TS) < or =2, TIMI flow grade > or =2, and post-stenting myocardial blush grade (MBG) > or =2 in the two groups. RESULTS:Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. After aspiration thrombectomy, a TS < or = 2 was more frequently present in EM group (92.3 vs. 69.3%, P = 0.0052). Also the rate of post-thrombectomy TIMI > or = 2 (69.3 vs. 92.2%, P = 0.0052) and post-stenting MBG > or =2 (88.2 vs. 69.3%, P = 0.029) were significantly higher in EM group. No significative differences were observed in terms of clinical events at 1 and 12 months. CONCLUSIONS:In this single-center, prospective, randomized study, a EM use before stenting in STEMI patients seems to remove more thrombotic burden compared with DI, providing a greater post-thrombectomy epicardial flow and a better post-stenting microvascular perfusion.

The central autonomic network (CAN) has been described in animal models but has been difficult to elucidate in humans. Potential confounds include physiological noise artifacts affecting brainstem neuroimaging data, and difficulty in deriving non-invasive continuous assessments of autonomic modulation. We have developed and implemented a new method which relates cardiac-gated fMRI timeseries with continuous-time heart rate variability (HRV) to estimate central autonomic processing. As many autonomic structures of interest are in brain regions strongly affected by cardiogenic pulsatility, we chose to cardiac-gate our fMRI acquisition to increase sensitivity. Cardiac-gating introduces T1-variability, which was corrected by transforming fMRI data to a fixed TR using a previously published method [Guimaraes, A.R., Melcher, J.R., et al., 1998. Imaging subcortical auditory activity in humans. Hum. Brain Mapp. 6(1), 33-41]. The electrocardiogram was analyzed with a novel point process adaptive-filter algorithm for computation of the high-frequency (HF) index, reflecting the time-varying dynamics of efferent cardiovagal modulation. Central command of cardiovagal outflow was inferred by using the resample HF timeseries as a regressor to the fMRI data. A grip task was used to perturb the autonomic nervous system. Our combined HRV-fMRI approach demonstrated HF correlation with fMRI activity in the hypothalamus, cerebellum, parabrachial nucleus/locus ceruleus, periaqueductal gray, amygdala, hippocampus, thalamus, and dorsomedial/dorsolateral prefrontal, posterior insular, and middle temporal cortices. While some regions consistent with central cardiovagal control in animal models gave corroborative evidence for our methodology, other mostly higher cortical or limbic-related brain regions may be unique to humans. Our approach should be optimized and applied to study the human brain correlates of autonomic modulation for various stimuli in both physiological and pathological states.