Summary Myelodysplastic syndromes (MDS) are clonal haematological disorders characterized by haematopoietic cell dysplasia, peripheral blood cytopenias, and a predisposition for developing acute myeloid leukaemia (AML). Cytogenetics have historically been important in diagnosis and prognosis in MDS, but the growing accessibility of next generation sequencing (NGS) has led to growing research in the roles of molecular genetic variation on clinical decision‐making in these disorders. Multiple genes have been previously studied and found to be associated with specific outcomes or disease types within MDS and knowledge of mutations in these genes provides insight into previously defined MDS subtypes. Knowledge of these mutations also informs development of novel therapies in the treatment of MDS. The precise role of NGS in the diagnosis, prognosis and monitoring of MDS remains unclear but the improvements in NGS technology and accessibility affords clinicians an additional practice tool to provide the best care for patients.

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Carcinoid heart disease (CaHD) is an important complication among patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS). CS patients (25%-65%) eventually develop CaHD; these patients face a significantly increased risk of morbidity and mortality. Guidance papers (eg, clinical practice guidelines, consensus guidelines, and expert statements) have been established by major organizations across the disciplines of cardiology and oncology; however, these recommendations are not routinely implemented. The aim of this article is to encourage the integration of current recommendations from national societies into clinical practice. Early screening upon recognition of CS and prior to the development of CaHD symptoms is paramount, as no existing therapies are approved to reverse the fibrotic damage to the heart once it occurs. Valvular replacement is the only definitive treatment for CaHD once it has developed. When patients are noted to have urinary 5-hydroxyindoleacetic acid (5-HIAA) levels ≥300 µmol/24 h and/or serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels >260 pg/mL, echocardiography is recommended. Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Telotristat is the primary choice for control of diarrhea refractory to SSA. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate.

Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient specific comorbidities have influence on treatment related survival, and are considered in clinical contexts, but have not been routinely incorporated into current prognostic models. We hypothesized that patient specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary MF (sMF) with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995-2016 were identified within Vanderbilt's Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (e.g., DIPSS, DIPSS plus, GPSS, MIPSS 70+) and comorbidities through EHR chart extraction and next generation sequencing (NGS) on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR] 4.3; 95% CI 2.1-8.9; p = 0.0001), intracranial hemorrhage (HR 28.7; 95% CI 7.0-116.8; p=2.83e-06), invasive fungal infection (HR 41.2; 95% CI 7.2-235.2; p=2.90e-05), chronic encephalopathy (HR 15.1; 95% CI 3.8-59.4; p=0.0001). The extended DIPSS model including all four significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (e.g., DIPSS) and other clinical and pathologic factors (e.g., comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.