Notes

Cardiomyocyte-produced miR-339-5p mediates pathology in Duchenne muscular dystrophy cardiomyopathy.
Histological analysis revealed that the cortical regions of gonads from adult Sry (SRY) mice contained few follicles. We successfully replaced genes on the Y chromosome with targeted genome editing using the CRISPR/Cas9 system. Since the Sry (SRY) XY mice did not develop testis, we concluded that human SRY was insufficient to drive testis development in mouse embryos. The difference in response elements and lack of glutamine-rich domains may have invalidated human SRY function in mice. Signal transduction between Sry/SRY expression and Sox9/SOX9 activation is possibly organized in a species-specific manner.
The aim of this study is to provide a thorough, quantified assessment of the substernal space as the site of extravascular implantable cardioverter-defibrillator (ICD) lead placement using computed tomography (CT) scans and summarizing adverse events and defibrillation efficacy across anatomical findings. Subcutaneous ICDs are an alternative to transvenous defibrillators but have limitations related to ICD lead distance from the heart. An alternative extravascular system with substernal lead placement has the potential to provide defibrillation at lower energy and pacing therapies from a single device.

A multi-centre, non-randomized, retrospective analysis of 45 patient CT scans quantitatively and qualitatively assessing bony, cardiac, vascular, and other organ structures from two human clinical studies with substernal lead placement. Univariate logistic regression was used to evaluate 15 anatomical parameters for impact on defibrillation outcome and adjusted for multiple comparisons. Adverse events were
Androstenedione (ASD) levels can aid diagnosis of hyperandrogenism together with other clinical/laboratory findings. We evaluated performance of the new, automated Elecsys® ASD assay vs an ASD isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference measurement procedure and determined reference ranges.

Repeatability/intermediate precision were assessed using 3 control levels and 5 human serum pools (n = 75 each; Clinical and Laboratory Standards Institute EP05-A3). Method comparisons vs commercially available immunoassays [IMMULITE ASD (Siemens) and LIAISON ASD (DiaSorin)] and an ID-LC-MS/MS measurement procedure method were conducted using 421 serum samples; Passing-Bablok regression and Pearson's correlation coefficients were calculated. Reference ranges and distribution of values associated with polycystic ovary syndrome (PCOS) were determined in five clinical cohorts using samples from several sites/vendors.

Repeatability/intermediate precision coefficients of variatind very good agreement with ID-LC-MS/MS. Reference ranges were established to support results interpretation in routine practice.
The aortic arch enlargement in the Norwood procedure is classically carried out using a curved homograft patch on the inner curvature of the neoaortic arch. The study investigates the outcome of a newly used artificial patch from a vascular prosthesis as an alternative to a homograft patch.

Since April 2007, we used curved polytetrafluorethylene (PTFE) patches cut out of a prosthesis as an alternative to homograft patches for the aortic arch reconstruction. The decision for either patch material was made due to anatomic reasons, preferring PTFE patches in larger aortas. In this study, 224 Norwood patients, operated between April 2007 and April 2018, were analysed. A total of 104 patients received a PTFE patch (group PTFE), and 120 patients got a pulmonary homograft patch (group homograft). A single-centre retrospective analysis was carried out concerning postoperative course and long-term follow-up regarding aortic arch interventions and reoperations and comparing the 2 material groups.

There were no material associated operative or postoperative complications. In-hospital mortality was 13% in group PTFE. Six children died late during follow-up (6%). One aortic isthmus dilatation (1%) was carried out 12 months after the Norwood procedure in this group, no arch reoperation was necessary during the complete follow-up.

The curved PTFE patch showed good qualities in operative technical demands and excellent long-term results. In selected cases of hypoplastic left heart syndrome, it can be well used as alternative to the pulmonary homograft.
The curved PTFE patch showed good qualities in operative technical demands and excellent long-term results. In selected cases of hypoplastic left heart syndrome, it can be well used as alternative to the pulmonary homograft.
Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population.

This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazararger in HBR than non-HBR patients.
Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, determine molecular correlates of treatment failure, and develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children's Oncology Group trial AHOD0031 were used for GEP and compared to adult cHL data. Eosinophils, B-cells, and mast cell signatures were enriched in children, while macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs. 90.3%; log-rank P = .0138) independent of interim response, stage, fever and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. TetrazoliumRed ClinicalTrials.gov Identifier NCT00025259.Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals. However, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor immunoglobulin heavy chain (BcR IGH) gene repertoire of 124 CLL patients and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, in 14 CLL patients we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14/16 patients with available samples at diagnosis, the CLL clonotype was already present in the pre-diagnostic samples. Overall, our data indicate that the pre-clinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.
Transcatheter aortic valve replacement (TAVR) represents a valid treatment for patients with aortic valve stenosis and high or intermediate surgical risk. However, biological transcatheter valves can also experience a structural degeneration after years, and a redo-TAVR procedure (TAVR-in-TAVR) can be a valid option. We revised the current available literature for indications, procedural and technical details and outcome on TAVR-in-TAVR procedures for degenerated TAVR valves.

A systematic search was conducted in the public medical database for scientific articles on TAVR-in-TAVR procedures for degenerated transcatheter valves. Data on demographics, indications, first and second transcatheter valve type and size, mortality, complications and follow-up were extracted and analysed.

A total of 13 studies (1 multicentre, 3 case series, 9 case reports) were included in this review, with a total amount of 160 patients treated with TAVR-in-TAVR procedures for transcatheter valve failure. The mean age was 74.8 ±espite these promising results, further studies are required to assess durability and haemodynamic performances of the second TAVR valve.

117, 122, 125.
117, 122, 125.Oesophageal resection is a challenging procedure, and it is more so in patients who have undergone bariatric procedures, especially after laparoscopic sleeve gastrectomy. We present the case of a patient with a history of an laparoscopic sleeve gastrectomy who underwent a hybrid Ivor-Lewis oesophagectomy in which the sleeve was successfully used to reconstruct the upper gastrointestinal tract.
We aimed to study whether pre-eclampsia is associated with childhood asthma, allergic and non-allergic asthma, accounting for family factors and intermediate variables.

The study population comprised 779 711 children born in 2005-2012, identified from Swedish national health registers (n = 14 823/7410 exposed to mild/moderate and severe pre-eclampsia, respectively). We used Cox regression to estimate the associations of mild/moderate and severe pre-eclampsia with incident asthma, before and after age 2 years. Cox regressions were controlled for familial factors using sibling comparisons, then stratified on high and low risk for intermediate variables caesarean section, prematurity and small for gestational age. We used logistic regression for allergic and non-allergic prevalent asthma at 6 years as a measure of more established asthma.

The incidence of asthma in children was 7.7% (n = 60 239). The associations varied from adjusted hazard ratio (adjHR) 1.11, 95% confidence interval (CI) 1.00, 1.24 for mild/moderate pre-eclampsia and asthma at >2 years age, to adjHR 1.
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