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Abstract Background Glucocorticoids are crucial components of the treatment of leukemia and lymphoma. High doses can lead to suppression of the hypothalamic–pituitary–adrenal (HPA) axis and be causative for an impaired stress response during infection. This study aims to evaluate the cortisol response in pediatric oncologic patients during febrile episodes. Methods Totally, 75 children and adolescents (5 months—18 years) with fever during chemotherapy were consecutively enrolled in this study. In total, 47 patients received glucocorticoids as part of their treatment. Random serum cortisol and adrenocorticotropic hormone (ACTH) were analyzed in every patient. A low cortisol response (LCR) was defined as a cortisol level

Abstract Background Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. Results After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. Conclusions The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.

Background: Infective endocarditis (IE) following mitral valve edge-to-edge repair is a rare complication with high mortality.Case summary: A 91-year-old male patient was admitted to intensive care unit with sepsis due to urinary tract infection after insertion of a urinary catheter by the outpatient urologist. Two weeks ago, the patient was discharged from hospital after successful transcatheter edge-to-edge mitral valve repair (TEER) using a PASCAL Ace device. The initially withdrawn blood revealed repeatedly Proteus mirabilis bacteremia as causal for the sepsis due to urinary tract infection. An antibiotic regime with Ampicillin/Sulbactam was initiated and discontinued after 7 days. During the clinical course the patient again developed fever and blood cultures again revealed P. mirabilis. In transesophageal echocardiography (TOE), IE of the PASCAL Ace device was confirmed by a vegetation accompanied by a mild to moderate mitral regurgitation. While the patient was stable at this time and deemed not suitable for cardiac surgery, the endocarditis team made a decision toward a prolonged 6-week antibiotic regime with an antibiotic combination of Ampicillin 2 g qds and Ciprofloxacin 750 mg td. Due to posterior leaflet perforation severe mitral regurgitation developed while PASCAL Ace vegetations were significantly reduced by the antibiotic therapy. Therefore, the patient underwent successful endoscopic mitral valve replacement. Another 4 weeks of antibiotic treatment with Ampicillin 2 g qds followed before the patient was discharged.Discussion:P. mirabilis is able to form biofilms, resulting in a high risk for endocarditis following transcatheter mitral valve repair especially when device endothelization is incomplete. Endoscopic mitral valve replacement could serve as a bailout strategy in refractory Clip-endocarditis.

Abstract Background This paper summarizes the contributions from the Genome-wide Association Study group (GWAS group) of the GAW20. The GWAS group contributions focused on topics such as association tests, phenotype imputation, and application of empirical kinships. The goals of the GWAS group contributions were varied. A real or a simulated data set based on the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study was employed by different methods. Different outcomes and covariates were considered, and quality control procedures varied throughout the contributions. Results The consideration of heritability and family structure played a major role in some contributions. The inclusion of family information and adaptive weights based on data were found to improve power in genome-wide association studies. It was proven that gene-level approaches are more powerful than single-marker analysis. Other contributions focused on the comparison between pedigree-based kinship and empirical kinship matrices, and investigated similar results in heritability estimation, association mapping, and genomic prediction. A new approach for linkage mapping of triglyceride levels was able to identify a novel linkage signal. Conclusions This summary paper reports on promising statistical approaches and findings of the members of the GWAS group applied on real and simulated data which encompass the current topics of epigenetic and pharmacogenomics.

Background This study analyzed the effects on long‐term outcome of residual mitral regurgitation (MR) and mean mitral valve pressure gradient (MVPG) after percutaneous edge‐to‐edge mitral valve repair using the MitraClip system. Methods and Results Two hundred fifty‐five patients who underwent percutaneous edge‐to‐edge mitral valve repair were analyzed. Kaplan–Meier and Cox regression analyses were performed to evaluate the impact of residual MR and MVPG on clinical outcome. A combined clinical end point (all‐cause mortality, MV surgery, redo procedure, implantation of a left ventricular assist device) was used. After percutaneous edge‐to‐edge mitral valve repair, mean MVPG increased from 1.6±1.0 to 3.1±1.5 mm Hg (P4.4 mm Hg was not according to Kaplan–Meier and Cox regression analyses. We then analyzed the cohort with degenerative and that with functional MR separately to account for these different entities. In the cohort with degenerative MR, elevated MVPG was associated with increased occurrence of the primary end point, whereas this was not observed in the cohort with functional MR. Conclusions MVPG >4.4 mm Hg after MitraClip implantation was predictive of clinical outcome in the patient cohort with degenerative MR. In the patient cohort with functional MR, MVPG >4.4 mm Hg was not associated with increased clinical events.

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

Residual mitral regurgitation (MR) is thought to be an important predictor of long-term survival following transcatheter edge-to-edge repair (TEER). Intraprocedural MR assessment using transesophageal echocardiography could be limited by image quality, hemodynamics, and patient sedation. The MitraScore is a validated multimodal approach for intraprocedural MR assessment during TEER. This study aimed to assess the impact of residual MR using the MitraScore on 1-year mortality. Patients undergoing mitral TEER were eligible for inclusion in the prospective, multicenter MITRA-PRO registry (A Prospective Registry Study on 1-Year Mortality and the Prognostic Significance of MitraScore After MitraClip Implantation in Patients With Mitral Regurgitation). Patients with a MitraScore ≤3 were defined as patients with mild residual MR after mitral TEER, whereas a MitraScore ≥4 was considered as relevant residual MR. Mortality, rehospitalization, and major adverse events were assessed 1 year after TEER. A MitraScore ≤3 was found in 1,059 patients (71.0%), whereas 432 patients revealed a MitraScore ≥4 (29.0%). One-year mortality was significantly lower in patients with nonrelevant residual MR (MitraScore ≤3 14.6% vs MitraScore≥4 22.1%). An almost linear relationship between intraprocedural MitraScore after TEER and mortality was observed. The combined clinical endpoint of mortality and rehospitalization within the 1-year follow-up was also significantly lower in the MitraScore ≤3 group (31.5%) than in the MitraScore ≥4 group (40.8%). A subgroup analysis confirmed the predictive value of the MitraScore in patients with primary, secondary, or mixed MR etiologies. Residual MR assessed by intraprocedural MitraScore after TEER predicts 1-year mortality and rehospitalization. Therefore, the multimodal MitraScore improves MR assessment during mitral TEER and might improve patient survival.(A Prospective Registry Study on 1-Year Mortality and the Prognostic Significance of MitraScore After MitraClip Implantation in Patients With Mitral Regurgitation [MITRA-PRO]; DRKS00012288) [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES:To evaluate the predictive value of CT-derived measurements of the aortic annulus for prosthesis sizing in transcatheter aortic valve implantation (TAVI) and to calculate optimal cutoff values for the selection of various prosthesis sizes. METHODS:The local IRB waived approval for this single-center retrospective analysis. Of 441 consecutive TAVI-patients, 90 were excluded (death within 30 days: 13; more than mild aortic regurgitation: 10; other reasons: 67). In the remaining 351 patients, the CoreValve (Medtronic) and the Edwards Sapien XT valve (Edwards Lifesciences) were implanted in 235 and 116 patients. Optimal prosthesis size was determined during TAVI by inflation of a balloon catheter at the aortic annulus. All patients had undergone CT-angiography of the heart or body trunk prior to TAVI. Using these datasets, the diameter of the long and short axis as well as the circumference and the area of the aortic annulus were measured. Multi-Class Receiver-Operator-Curve analyses were used to determine the predictive value of all variables and to define optimal cutoff-values. RESULTS:Differences between patients who underwent implantation of the small, medium or large prosthesis were significant for all except the large vs. medium CoreValve (all p's

Transcatheter treatment techniques for tricuspid regurgitation (TR) have evolved in recent years, with leaflet repair being the most commonly used, but thus far evidence on the PASCAL and PASCAL Ace system is based mainly on compassionate use data. This is the first report on commercial use in a multicenter study with a large patient cohort investigating the safety and efficacy of the PASCAL and PASCAL Ace system in the treatment of TR. In a retrospective, multicenter, observational setting, data from all consecutive patients undergoing leaflet repair for TR at 8 centers was collected, including a centralized analysis of echocardiographic data. A total of 235 high-risk patients (mean age 78 ± 8 years, 49% women, mean Society of Thoracic Surgeons Predicted Risk of Mortality score 8.6% ± 6.8%) were included. TR was functional in 87% of patients and graded severe or higher in 91%. TR was successfully reduced to moderate or less in 78% of patients (P < 0.001). Procedural success was 78% (n = 153). At the latest available follow-up (median 173 days), TR reduction was sustained (78% with TR moderate or less; P < 0.001), and echocardiography showed indications of right ventricular remodeling (mean right ventricular end-diastolic diameter 56 ± 9 mm vs 53 ± 9 mm; P < 0.001). Patients' symptoms diminished significantly (63% were in New York Heart Association functional class I or II at follow-up; P < 0.001). In a device-specific analysis, the PASCAL and PASCAL Ace showed no difference in TR reduction (postprocedural TR moderate or less in 77% vs 78%; P = 0.82). In early clinical experience, the PASCAL (Ace) leaflet repair system has high technical and procedural success rates with efficient TR reduction and significant clinical and echocardiographic improvement at follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]