Characteristics of women with ischemic sudden cardiac death.

BACKGROUND: Sudden cardiac death (SCD) is a significant mode of death causing 15-20% of all deaths in high-income countries. Coronary artery disease (CAD) is the most common cause of SCD in both sexes, and SCD is often the first manifestation of underlying CAD in women. This case-control study aimed to determine the factors associated with SCD due to CAD in women. METHODS: The study group consisted of women with CAD-related SCD (N = 888) derived from the Fingesture study conducted in Northern Finland from 1998 to 2017. All SCDs underwent medicolegal autopsy. The control group consisted of women with angiographically verified CAD without SCD occurring during the 5-year-follow-up (N = 610). To compare these groups, we used medical records, autopsy findings, echocardiograms, and electrocardiograms (ECGs). RESULTS: Subjects with SCD were older (73.2 ± 11.3 vs. 68.8 ± 8.0, p < 0.001) and were more likely to be smokers or ex-smokers (37.1% vs. 27.6%, p = 0.045) compared to control patients. The proportion of subjects with prior myocardial infarction (MI) was higher in controls (46.9% vs. 41.4% in SCD subjects, p = 0.037), but in contrast, SCD subjects were more likely to have underlying silent MI (25.6% vs. 2.4% in CAD controls, p < 0.001). Left ventricular hypertrophy (LVH) was more common finding in SCD subjects (70.9% vs. 55.1% in controls, p < 0.001). Various electrocardiographic abnormalities were more common in subjects with SCD, including higher heart rate, atrial fibrillation, prolonged QTc interval, wide or fragmented QRS complex and early repolarization. The prevalence of Q waves and T inversions did not differ between the groups. CONCLUSIONS: Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with CAD-related SCD. These results suggest that untreated CAD with concomitant myocardial disease is an important factor in SCD in women.

Underlying LVH and previous MI with myocardial scarring are common and often undiagnosed in women with ischemic SCD.Untreated CAD with concomitant myocardial disease is an important factor in SCD among women.Improvements in the diagnosis and management of ischemic cardiomyopathy are likely to reduce the SCD burden in women.

Determination of consensus k Q values for megavoltage photon beams for the update of IAEA TRS-398.

The IAEA is currently coordinating a multi-year project to update the TRS-398 Code of Practice for the dosimetry of external beam radiotherapy based on standards of absorbed dose to water. One major aspect of the project is the determination of new beam quality correction factors, k Q , for megavoltage photon beams consistent with developments in radiotherapy dosimetry and technology since the publication of TRS-398 in 2000. Specifically, all values must be based on, or consistent with, the key data of ICRU Report 90. Data sets obtained from Monte Carlo (MC) calculations by advanced users and measurements at primary standards laboratories have been compiled for 23 cylindrical ionization chamber types, consisting of 725 MC-calculated and 179 experimental data points. These have been used to derive consensus k Q values as a function of the beam quality index TPR20,10 with a combined standard uncertainty of 0.6%. Mean values of MC-derived chamber-specific [Formula: see text] factors for cylindrical and plane-parallel chamber types in 60Co beams have also been obtained with an estimated uncertainty of 0.4%.

Calculated beam quality correction factors for ionization chambers in MV photon beams.

The beam quality correction factor, [Formula: see text], which corrects for the difference in the ionization chamber response between the reference and clinical beam quality, is an integral part of radiation therapy dosimetry. The uncertainty of [Formula: see text] is one of the most significant sources of uncertainty in the dose determination. To improve the accuracy of available [Formula: see text] data, four partners calculated [Formula: see text] factors for 10 ionization chamber models in linear accelerator beams with accelerator voltages ranging from 6 MV to 25 MV, including flattening-filter-free (FFF) beams. The software used in the calculations were EGSnrc and PENELOPE, and the ICRU report 90 cross section data for water and graphite were included in the simulations. Volume averaging correction factors were calculated to correct for the dose averaging in the chamber cavities. A comparison calculation between partners showed a good agreement, as did comparison with literature. The [Formula: see text] values from TRS-398 were higher than our values for each chamber where data was available. The [Formula: see text] values for the FFF beams did not follow the same [Formula: see text], [Formula: see text] relation as beams with flattening filter (values for 10 MV FFF beams were below fits made to other data on average by 0.3%), although our FFF sources were only for Varian linacs.

Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation.

The development of de novo donor-specific HLA antibodies (dnDSA) after transplantation is associated with graft failure, mortality, and cost. There is no effective therapeutic intervention to prevent dnDSA or ameliorate associated injury. The aims of this study were to identify specific HLA factors associated with dnDSA development and to propose primary prevention strategies that could reduce the incidence of dnDSA without prohibitively limiting access to transplant. The investigation cohort included heart transplant recipients from 2008 to 2015 (n = 265). HLA typing was performed and HLA antibody testing was undertaken before and after transplantation. HLAMatchmaker analysis was performed for persistent dnDSA to identify potentially more immunogenic eplet differences. Validation was performed in recipients of lung transplants from 2008 to 2013 (n = 433). The majority of recipients with dnDSA had antibodies to identical eplet positions on DQ2 and DQ7. A high-risk epitope mismatch (found in DQA1*05 +  DQB1*02/DQB1*03:01(7)) was associated with a 4.2- and 4.9-fold increased risk of dnDSA in heart and lung recipients respectively. HLA electrostatic potential modeling provided a plausible explanation for this observed immunogenicity. A theoretical allocation algorithm avoiding high-risk epitope mismatches was generated and predicted to reduce dnDSA by up to 72% without additional testing, eplet analysis, or cost.

Mechanisms of photoinduced magnetization in Pr0.6Ca0.4MnO3 studied above and below charge-ordering transition temperature.

We report the effect of photonic field on the electronic and magnetic structure of a low bandwidth manganite [Formula: see text] [Formula: see text]MnO3 (PCMO) thin film. In particular, the present study confirmed a mechanism that was recently proposed to explain how optical excitation can bias or directly activate the metamagnetic transition associated with the colossal magnetoresistance (CMR) effect of PCMO. The transition is characterized by a shift in the dynamic equilibrium between ferromagnetic (FM) and antiferromagnetic clusters, explaining how it can be suddenly triggered by a sufficient external magnetic field. The film was always found to support some population of FM-clusters, the proportional size of which could be adjusted by the magnetic field and, especially in the vicinity of a thermomagnetic irreversibility, by optical excitation. The double exchange mechanism couples the magnetic degrees of freedom of manganites to their electronic structure, which is further coupled to the ion lattice via the Jahn-Teller mechanism. In accordance, it was found that producing optical phonons into the lattice could lower the free energy of the FM phase enough to significantly bias the CMR effect.

Dirty limit scattering behind the decreased anisotropy of doped YBa2Cu3O7-δ thin films.

We measured the resistivity of pulsed-laser-deposited BaCeO3 (BCO)-doped YBCO thin films containing spherical BCO particles in fields up to 30 T. The average diameter of the particles depends on the dopant concentration being below 4 nm in all the samples. Raised values of the upper critical field, Bc2, were observed in all the samples. Additionally, the parameter γ, describing the electron mass anisotropy, decreased from 6.2 in the undoped sample to 3.1 in the 8 wt.% BCO-doped sample. These results can be explained by the increased number of defects decreasing the mean free path of electrons and thus lowering the coherence length, which in turn increases Bc2.

The low-temperature magnetostructure and magnetic field response of Pr0.9Ca0.1MnO3: the roles of Pr spins and magnetic phase separation.

With the goal of elucidating the background of photoinduced ferromagnetism phenomena observed in the perovskite structured (Pr,Ca) manganites, the low-temperature magnetostructure of the material Pr0.9Ca0.1MnO3 was revised using cold neutron powder diffraction, SQUID magnetometry and ab initio calculations. Particular emphasis was placed on determining the presence of nanoscale magnetic phase separation. Previously published results of a canted A-AFM average ground state were reproduced to a good precision both experimentally and theoretically, and complemented by investigating the effects of an applied magnetic field of 2.7 T on the magnetostructure. Explicit evidence of nanoscale magnetic clusters in the material was obtained based on high-resolution neutron diffractograms. Along with several supporting arguments, we present this finding as a justification for extending the nanoscale magnetic phase separation model of manganites to the material under discussion despite its very low Ca doping level in the context of the model. In the light of the new data, we also conclude that the low temperature magnetic moment of Pr must be ca. 300% larger than previously thought in this material, close to the high spin value of 2µB per formula unit.

Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion.

The growing demand for suitable lungs for transplantation drives the quest for alternative strategies to expand the donor pool. The aim of this study is to evaluate the outcomes of lung transplantation (LTx) with donation after circulatory determination of death (DCDD) and the impact of selective ex vivo lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%) of them using DCDDs (seven bridged cases). Cases bridged with mechanical ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%) underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological determination of death (DNDD) donors were similar, with 1 and 5-year survivals of 85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23 days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2 vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for transplantation, providing similar results to DNDDs. EVLP seems an important technique in the armamentarium to safely increase lung utilization from DCDDs; however, further studies are necessary to better define the role of EVLP in this context.

Characteristics of "malignant" vs. "benign" electrocardiographic patterns of early repolarization.

The electrocardiographic (ECG) pattern of early repolarization (ER) has historically been regarded as a benign ECG variant, but during the past few years, this concept has been challenged based on multiple reports linking the ER pattern with an increased risk of sudden cardiac death. Although the mechanistic basis of ventricular arrhythmogenesis in patients with ER pattern is still incompletely understood, there is increasing information about the ECG and phenotype characteristics of "malignant" vs. "benign" patterns of ER. This review presents the current evidence of markers of "benign" and a more severe nature of ER.

Vascular endothelial growth factor plays a major role in development of experimental obliterative bronchiolitis.

Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. The exact molecular and cellular mechanisms contributing to obliterative lesion formation are unknown. Pathological characteristics of OB are epithelial damage, peribronchial inflammation, and increasing obliteration of bronchioli. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that exerts proinflammatory effects by increasing endothelial permeability and inducing expression of endothelial adhesion molecules. We investigated the role of VEGF in the development of OB in rat tracheal allografts and the role of VEGF receptors (VEGFR)-1 and -2 in the development of OB in mouse tracheal allografts. In nontreated allografts, with increasing loss of epithelium and airway occlusion, VEGF messenger RNA (mRNA) and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells compared with syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF164 gene led to a decrease in epithelial necrosis but increased luminal occlusion by >50% compared with AdLacZ-treated rat tracheal allografts. When compared with the control immunoglobulin (Ig)G group, simultaneous treatment with antibodies against VEGFR-1 and -2 significantly lowered the degree of luminal occlusion of mouse tracheal allografts.

Prevention of cytomegalovirus infection-enhanced experimental obliterative bronchiolitis by antiviral prophylaxis or immunosuppression in rat tracheal allografts.

In this study, the prevention of rat cytomegalovirus (RCMV) infection-enhanced experimental obliterative bronchiolitis in rat tracheal allografts was investigated. RCMV infection markedly enhanced cell proliferation and histological changes of obliterative bronchiolitis, a form of chronic rejection after lung transplantation. These alterations were linked to increased interleukin (IL)-2 and tumor necrosis factor-alpha (TNF-alpha) immunoreactivity, and reduction of IL-10 expression. In recipient rats with acute RCMV infection, prophylaxis with either ganciclovir (DHPG) or hyperimmune serum (HIS) totally prevented RCMV infection-enhanced tracheal occlusion. DHPG treatment initiated during acute RCMV infection also reduced lesion development but markedly less than DHPG prophylaxis. Treatment of acute RCMV infection with HIS alone or in combination with DHPG had no significant effect on tracheal occlusion. Inhibition of the transcription of cytokines by high doses of cyclosporine A significantly reduced RCMV infection-enhanced tracheal obliteration. In rats with chronic RCMV infection, obliterative alterations were prevented by DHPG prophylaxis initiated at the time of transplantation. Prophylaxis either with DHPG or HIS did not affect the amount of infectious RCMV recovered from host salivary glands, nor were there differences seen in RCMV major immediate early DNA expression in tracheal allografts between different antiviral drug regimens. Immunohistochemical analysis of allografts revealed that inhibition of tracheal occlusion by antiviral prophylaxis was associated with a reduction in the number of ED1(+) macrophages and cells staining for Th1 cytokines and TNF-alpha, while immune modulation by cyclosporine A up-regulated IL-10 production. In conclusion, the results of the present study suggest that the CMV infection-enhanced chronic rejection develops independently of viral load but requires both immune activation and simultaneous CMV gene expression beyond immediate early genes.

Cytological monitoring of peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and cytomegalovirus infection in lung and heart--lung allograft recipients.

STUDY OBJECTIVES: Acute rejection and cytomegalovirus (CMV) infection are important complications after lung and heart--lung transplantation. We sought to investigate whether acute rejection and CMV infection demonstrated as CMV antigenemia had an effect on the cell profiles of peripheral blood (PB), bronchoalveolar lavage fluid (BAL-F), or TBB histology. PATIENTS AND DESIGN: In this prospective study, composition of cells in PB, BAL-F, and TBB samples from 20 lung or heart-lung transplantation patients were analyzed during episodes of acute rejection or CMV antigenemia. Rejection was graded according to the International Society for Heart and Lung Transplantation criteria. As controls, samples with no evidence of rejection or infection were used. To evaluate the effect of time on cellular findings, samples were divided into three groups according to time after transplantation: 1--30, 31--180, and more than 180 d after transplantation. RESULTS: Acute rejection was associated with mild blood basophilia (p<0.05; specificity 94%, sensitivity 42%). In BAL-F during rejection, the number of basophils (p<0.05), eosinophils (p<0.05), and lymphocytes (p<0.05; specificity 77%, sensitivity 64%) was increased compared to controls during the post-operative month 1. Later-occurring rejections were associated with increased amounts of neutrophils in BAL-F (p<0.05; specificity 82%, sensitivity 74%). In TBB histology, acute rejections were associated with perivascular and/or peribronchial infiltration of lymphocytes (p<0.001) and plasma cells (p<0.05) compared to controls. In our patients receiving gancyclovir prophylaxis, CMV antigenemia did not significantly alter the cell profiles in PB and BAL-F nor the inflammatory cell picture in TBB histology. CONCLUSION: TBB histology remains the 'gold standard' for diagnosing rejection in lung and heart-lung transplantation patients, as the inflammatory cell findings in TBB specimens are highly specific for rejection. The cellular changes associated with rejection, mild PB basophilia and increased proportions of lymphocytes in early- and neutrophils in later-occurring rejection, observed in BAL-F cannot be considered specific for rejection, but may warrant clinical suspicion of rejection.