BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

We report a patient who in the course of 3 years developed 3 distinct episodes of an acute demyelinating neuropathy, each fulfilling the criteria set up by an ad hoc committee of the National Institute of Neurological and Communicative Disorders and Stroke for acute Guillain-Barre syndrome. Each episode was associated with strong serological evidence for lupus erythematosus. The episodes were separated by 1–2 years and each was followed by near complete clinical recovery. The only systemic feature was a pleural effusion during the last 2 episodes.

We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFRC329R receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation. Clonal analysis shows that the dominant JAK2V617F-positive clone in this PV patient harbors EGFRC329R, thus this mutation may contribute to clonal expansion. Somatic mutations affecting other ERBB and related receptor tyrosine kinases are observed in myeloproliferative neoplasms (MPN), and we show elevated EGFR levels in MPN samples, consistent with previous reports. Thus activation of this group of receptors, via multiple mechanisms, may contribute to clonal growth and survival of the JAK2V617F disease clone in MPN.

Background: The management of older patients with Myelodysplastic syndrome (MDS) and Acute Myeloid Leukaemia (AML) is currently based on disease biology and performance status despite the heterogeneity of ageing and the increasingly complex care needs of frail and multi-morbid patients. Performance status scores fail to capture deficits across all the domains of ageing therefore patients that are pre-frail or vulnerable fail to be identified early in their journey. Geriatric assessments have been firmly established in the management of oncological patients but not as yet in haematological malignancies. Aims and Methods: This prospective interventional study was conducted at the Royal Adelaide Hospital. The aim was to determine if deficits in ageing were associated with therapy completion rates and survival. After the treatment decision had been made by the haematologists, consented patients had nurse-led geriatric assessments followed by Geriatrician review in participants with abnormal assessments subjective concerns with interventions implemented. Results: A total of 108 patients were enrolled into the study over a 4 year period. Although only 29 (27%) patients had an Eastern Cooperative Oncology Group score ≥2, 86 (79%) patients had deficits in at least one domain of ageing. Deficits were spread across all domains, including dependence for instrumental activity of daily living (iADL) (n=32, 29%). Patients who were iADL-dependent (3.2±5 vs. 10.8±15; p=0.004), were cognitively impaired (2.8±4 vs. 9.9±15; p=0.010) or had impaired mobility measured by the timed-up and got test (3.3±5 vs. 11.±15; p=0.002), completed significantly less cycles of azacitidine therapy than patients without deficits in these domains (Fig 1A-C). The patients who ceased therapy prematurely (less than 6 cycles) also had significantly poorer overall survival (OS) of patients compared to patients completing at least six cycles of azacitidine. (Fig 1D). Other domains predictive of poorer survival were iADL dependence (HR 4.91; p=0.003) and increased comorbidities (HR 4.41; p=0.004) independent of age and disease factors (n=108) (Fig 2A). Additionally iADL dependence was associated with shortened survival regardless of therapy choice reflecting the frailty of this group of patients - azacitidine (6 vs. 19 months, p=0.002) and supportive care cohorts (28 months vs. not reached, p=0.04; Fig 2B-C). Seventy patients were reviewed by the Geriatrician which led to the identification of a significant degree of multimorbidity (87%) and polypharmacy (73%), which have been shown to negatively impact on morbidity. Interventions and recommendations included changes in medications (57%), investigations for further evaluation of non-oncologic conditions (61%), social support referral including Aged Care Assessment (34%), nutritional support by counselling or referral to dietician (37%), formal cognitive evaluation and management (60%), physical therapy program referral or counselling (39%), referral or shared care with other specialists besides haematology and the primary care provider (26%), and psychologist referral (16%). Conclusion: This study demonstrates that geriatric assessment is feasible and instrumental in identifying geriatric related health issues in a significant proportion of patients compared to the use of performance scores. Deficits associated with ageing are associated with premature cessation of therapy and poorer survival. Geriatric assessments should form part of the assessment of older persons with the aim of reducing adverse outcomes and maintaining quality of life. Disclosures Ross: Celgene: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria. Hiwase:Novartis: Research Funding; Celgene: Research Funding.