Identification and quantification of prosthetic mitral regurgitation by flow convergence method using transthoracic approach

The present case report illustrates the clinical applicability of the proximal isovelocity surface area (PISA) method in identifying, locating and assessing paravalvular prosthetic mitral regurgitation by transthoracic echocardiography

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes.

In this study we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI [n=1404; 59%], (ii) colonization only [n=353; 15%], (iii) occasional UTI with 1-2 episodes [n=456; 19%], and (iv) recurrent UTI with ≥3 episodes [n=155; 7%]. One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10ml/min lower eGFR at one year (44ml/min vs 54, 53 and 51ml/min; p<0.001). UTI phenotypes had no impact on long-term patient survival (p=0.33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p<0.001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p<0.001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed

Controls on Microbial and Oolitic Carbonate Sedimentation and Stratigraphic Cyclicity Within a Mixed Carbonate-Siliciclastic System: Upper Cambrian Wilberns Formation, Llano Uplift, Mason County, Texas, USA

The upper Cambrian Wilberns Formation in central Texas records deposition on a low-gradient shelf within a mixed carbonate–siliciclastic tidal-flat system that changes offshore to subtidal shelf and open-marine oolitic skeletal shoals with large microbial mounds. Siliciclastic sediment is interpreted to have been delivered to the tidal flat by aeolian processes because of the narrow range in grain size and paucity of clay. Tidal influence is dominant as evidenced by reversing currents and desiccation on the tidal flat, and megaripples with reversing current indicators in offshore shoals. Intraclastic conglomerates were deposited in broad channels on the tidal flats during storm surges. Microbialite deposition is interpreted to be controlled by accommodation favouring amalgamated thin biostromes developed in the tidal flat vs. larger mounds with greater synoptic relief in the offshore, and current energy resulting in preferential elongation of offshore mounds in a NE–SW orientation. Intertidal mounds and biostromes grew in the presence of significant siliciclastic flux and trapped it within their structure, whereas offshore large buildups incorporated little siliciclastic component. Oolite and skeletal grainstone formed in tide agitated shoals associated with large subtidal microbial mounds. Storms extensively recycled and redistributed skeletal and oolitic sands from the offshore shoals across the shelf as thin sand sheets. Spatial mixing of siliciclastic and carbonate sediment occurred across the tidal flat and shelf. Low-frequency and intermediate-frequency stratigraphic cycles were driven by shifts in the shoreline and changes in rate of siliciclastic flux in response to relative sea-level fluctuation. Random facies stacking and the lack of metre-scale cyclicity are interpreted to reflect stratigraphic incompleteness and an episodic signal introduced by storms

Staphylococcus aureus ST398, New York City and Dominican Republic

Closely related Staphylococcus aureus strains of ST398, an animal-associated strain, were identified in samples collected from humans in northern Manhattan, New York, NY, USA, and in the Dominican Republic. A large population in northern Manhattan has close ties to the Dominican Republic, suggesting international transmission

Mitochondria as Target for Tumor Management of Hemangioendothelioma

Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including weak X-ray therapy (XRT, 0.5 Gy) and a standardized natural berry extract (NBE) was tested. This NBE is known to be effective in managing experimental HE and has been awarded with the Food and Drug Administration Investigational New Drug (FDA-IND) number 140318 for clinical studies on infantile hemangioma. Results: NBE treatment alone selectively attenuated basal oxygen consumption rate of EOMA cells. NBE specifically sensitized EOMA, but not murine aortic endothelial cells to XRT-dependent attenuation of mitochondrial respiration and adenosine triphosphate (ATP) production. Combination treatment, selectively and potently, influenced mitochondrial dynamics in EOMA cells such that fission was augmented. This was achieved by lowering of mitochondrial sirtuin 3 (SIRT3) causing increased phosphorylation of AMP-activated protein kinase (AMPK). A key role of SIRT3 in loss of EOMA cell viability caused by the combination therapy was evident when pyrroloquinoline quinone, an inducer of SIRT3, pretreatment rescued these cells. Innovation and Conclusion: Mitochondria-targeting NBE significantly extended survival of HE-affected mice. The beneficial effect of NBE in combination with weak X-ray therapy was, however, far more potent with threefold increase in murine survival. The observation that safe natural products may target tumor cell mitochondria and sharply lower radiation dosage required for tumor management warrants clinical testing

Baseline Chest Computed Tomography as Standard of Care in High-Risk Hematology Patients

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69; 49%), hematology (n = 68; 48%), and others (n = 41; 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome

Herpes-Virus Infection in Patients with Langerhans Cell Histiocytosis: A Case-Controlled Sero-Epidemiological Study, and In Situ Analysis

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that affects mainly young children, and which features granulomas containing Langerhans-type dendritic cells. The role of several human herpesviruses (HHV) in the pathogenesis of LCH was suggested by numerous reports but remains debated. Epstein-barr virus (EBV, HHV-4), & Cytomegalovirus (CMV, HHV-5) can infect Langerhans cells, and EBV, CMV and HHV-6 have been proposed to be associated with LCH based on the detection of these viruses in clinical samples. METHODOLOGY: We have investigated the prevalence of EBV, CMV and HHV-6 infection, the characters of antibody response and the plasma viral load in a cohort of 83 patients and 236 age-matched controls, and the presence and cellular localization of the viruses in LCH tissue samples from 19 patients. PRINCIPAL FINDINGS: The results show that prevalence, serological titers, and viral load for EBV, CMV and HHV-6 did not differ between patients and controls. EBV was found by PCR in tumoral sample from 3/19 patients, however, EBV small RNAs EBERs -when positive-, were detected by in situ double staining in bystander B CD20+ CD79a+ lymphocytes and not in CD1a+ LC. HHV-6 genome was detected in the biopsies of 5/19 patients with low copy number and viral Ag could not be detected in biopsies. CMV was not detected by PCR in this series. CONCLUSIONS/SIGNIFICANCE: Therefore, our findings do not support the hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans cell histiocytosis is accounted for by the infection of bystander B lymphocytes in LCH granuloma. The latter observation can be attributed to the immunosuppressive micro environment found in LCH granuloma