Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is complex and multifactorial, as it touches on several cellular and molecular systems. Understanding the molecular background of cardiac hypertrophy is essential in order to protect the myocardium from pathological remodeling, or slow down the destined progression to heart failure. In this review we highlight the most important molecular aspects of cardiac hypertrophic growth in light of the currently available published research data.

Papillary renal cell carcinoma (PRCC) has 2 histologic subtypes. Almost half of the cases fail to meet all morphologic criteria for either type, hence are characterized as PRCC not otherwise specified (NOS). There are yet no markers to resolve the PRCC NOS category. Accurate classification can better guide the management of these patients. In our previous PRCC study we identified markers that can distinguish between the subtypes. A PRCC patient cohort of 108 cases was selected for the current study. A panel of potentially distinguishing markers was chosen from our previous genomic analysis, and assessed by immunohistochemistry. The panel exhibited distinct staining patterns between the 2 classic PRCC subtypes; and successfully reclassified the NOS (45%) cases. Moreover, these immunomarkers revealed a third subtype, PRCC3 (35% of the cohort). Molecular testing using miRNA expression and copy number variation analysis confirmed the presence of 3 distinct molecular signatures corresponding to the 3 subtypes. Disease-free survival was significantly enhanced in PRCC1 versus 2 and 3 (P=0.047) on univariate analysis. The subtypes stratification was also significant on multivariate analysis (P=0.025; hazard ratio, 6; 95% confidence interval, 1.25-32.2). We propose a new classification system of PRCC integrating morphologic, immunophenotypical, and molecular analysis. The newly described PRCC3 has overlapping morphology between PRCC1 and PRCC2, hence would be subtyped as NOS in the current classification. Molecularly PRCC3 has a distinct signature and clinically it behaves similar to PRCC2. The new classification stratifies PRCC patients into clinically relevant subgroups and has significant implications on the management of PRCC.

Right ventricular failure (RVF) is an unfortunate complication that continues to limit outcomes following durable left ventricular assist device (LVAD) implantation. Despite several ‘RVF risk scores’ having been proposed, preoperative prediction of post-LVAD RVF remains a guesstimate at best. Current strategies for institution of temporary RVAD support are invasive, necessitate additional re-thoracotomy, restrict postoperative mobilization, and/or entail prolonged retention of prosthetic material in-situ. The authors propose a novel surgical strategy comprising simultaneous implantation of a permanent LVAD and percutaneous TandemHeart® plus ProtekDuo® to provide temporary RVAD support and preempt RVF in patients with impaired RV function.

Aims The occurrence of hyperbilirubinaemia after heart surgery using cardiopulmonary bypass or post‐operative heart failure is fairly common. We investigated the incidence, predictive value, and post‐operative outcome of hyperbilirubinaemia after cardiac surgery in an effort to identify potential risk factors and significance on clinical outcome. Methods and results Between 2006 and 2016, 1272 (10.1%) out of 12 556 patients developed hyperbilirubinaemia, defined as bilirubin concentration >3 mg/dL, during post‐operative course at our institution. All patients who were operated using cardiopulmonary bypass were included. Hepatic dysfunction was diagnosed preoperatively in 200 patients (15.7%), whereas mean model of end‐stage liver disease score was 11.22 ± 4.99. Early mortality was 17.4% with age [hazard ratio (HR) 1.019, 95% confidence interval (CI) 1.008–1.029; P = 0.001], diabetes (HR 1.115, CI 1.020–1.220; P = 0.017), and emergent procedures (HR 1.315, CI 1.012–1.710) as multivariate predictors. Post‐operative predictors were low‐output syndrome (HR 3.193, 95% CI 2.495–4.086; P < 0.001), blood transfusion (HR 1.0, CI 1.0–1.0; P < 0.001), and time to peak bilirubin (HR 1.1, CI 1.0–1.1; P < 0.001). We found an increased correlation with mortality at 3.5 post‐operative day as well as an optimal cut‐off value for bilirubin of 5.35 mg/dL. A maximum bilirubin of 25.5 mg/dL was associated with 99% mortality. Survival analysis showed significantly decreased survival for patients who developed late, rather than early, hyperbilirubinaemia. Conclusions Post‐operative hyperbilirubinaemia is a prevalent threat after cardiopulmonary bypass, associated with high early mortality. The timing and amount of peak bilirubin concentration are linked to the underlying pathology and are predictors of post‐operative outcome. Patients with late development of steep hyperbilirubinaemia warrant meticulous post‐operative care optimizing cardiac and end organ functions before reaching the point of no return.

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BackgroundA retrospective analysis was conducted of the early and long-term outcomes after surgery for infective endocarditis (IE).Material/MethodsWe included 360 patients with IE operated upon between 1993 and 2012. The primary endpoint was overall cumulative postoperative survival at 30 days. Secondary endpoints were early postoperative outcomes and complication rates. Factors associated with 30-day mortality were analyzed.ResultsMean age was 58.7±14.7 years and 26.9% (n=97) were female. The mean follow-up was 4.41±4.53 years. Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years, and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore, non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048), aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001, p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively). Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95-CI: 1.096–19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008–1.042, p=0.004) as independent predictors of 30-day mortality.ConclusionsSurgical treatment of IE shows satisfactory early, midterm, and long-term results. Multivariate logistic regression analysis revealed cirrhosis and longer CPB time as independent predictors of 30-day mortality.

Background: Modern left ventricular assist devices (LVAD) have evolved to become standard of care in severe heart failure (HF) patients. Right HF (RHF) is a major complication responsible for early mortality. Several techniques for temporary right ventricular assist device (t-RVAD) have been described before, baring relevant disadvantages such as limited mobilization or the need for re-thoracotomy. We describe the results of an alternative technique for t-RVAD using the Tandem Heart™ with ProtekDuo™ cannula. Methods: An institutional retrospective single centre outcome analysis was performed including all permanent LVAD recipients with concomitant groin-free t-RVAD support. Results: Between October 2015 and September 2017, 11 patients (10 male, 90.9%) were included. Preoperative NYHA class was 3.8±0.75 and INTERMACS class 3.5±1.5. Four (36.4%) patients were already on mechanical circulatory support (MCS) at time of implantation with 4 (36.4%) patients already on inotropic support. All LVAD implantations were performed on-pump and 3 cases (27.3%) were redo cases. Mean t-RVAD duration was 16.8±9.5 days. Ten patients (90.9%) could be weaned from temporary RVAD support, 1 patient deceased on support. Mean ICU stay was 23.8±16.5 days, while 30-day survival was 72.7%. Follow-up was complete with 214.7±283 days. Three patients (27.3%) died following multi-organ failure (MOF), 1 patient (9.1%) following intracranial bleed 12 days after t-RVAD explantation. No severe t-RVAD associated complications were observed. Conclusions: Our technique allows for safe groin-free t-RVAD providing all advantages of percutaneous implantation including complete mobilization and bedside explantation without any need for operation.

The GATA3 transcription factor is one of the most frequently mutated genes in breast cancer. Heterozygous mutations, mostly frameshifts, are seen in 15% of estrogen receptor positive breast cancers, the subtype in which these mutations are almost exclusively found. Mouse studies have shown that Gata3 is critical for breast development and that GATA3 gene dosage affects breast tumor progression. Human patient data have shown that high Gata3 expression, a feature of luminal subtype breast cancers, is associated with a better prognosis. Although the frequency of GATA3 mutation suggests an important role in breast cancer development or progression, there is little understanding of how mutations in GATA3 affect its function in luminal breast epithelial cells and what gene expression changes result as a consequence of the mutations. Here, using gene editing, we have created two sets of isogenic human luminal breast cancer cell lines with and without a hotspot truncating GATA3 mutation. GATA3 mutation enhanced tumor growth in vivo but did not affect sensitivity to clinically used hormonal therapies or chemotherapeutic agents. We identified genes with upregulated and downregulated expression in GATA3 mutant cells, a subset of which was concordantly differentially expressed in GATA3 mutant primary luminal breast cancers. Addback of mutant GATA3 recapitulated mutation-specific gene expression changes and enhanced soft agar colony formation, suggesting a gain of function for the mutant protein.