Introduction of a new scoring tool to identify clinically stable heart failure patients.

INTRODUCTION: Heart failure (HF) poses a burden on specialist care, making referral of clinically stable HF patients to primary care a desirable goal. However, a structured approach to guide patient referral is lacking. METHODS: The Maastricht Instability Score-Heart Failure (MIS-HF) questionnaire was developed to objectively stratify the clinical status of HF patients: patients with a low MIS-HF (0-2 points, indicating a stable clinical condition) were considered for treatment in primary care, whereas high scores (> 2 points) indicated the need for specialised care. The MIS-HF was evaluated in 637 consecutive HF patients presenting between 2015 and 2018 at Maastricht University Medical Centre. RESULTS: Of the 637 patients, 329 (52%) had a low score and 205 of these 329 (62%) patients were referred to primary care. The remaining 124 (38%) patients remained in secondary care. Of the 308 (48%) patients with a high score (> 2 points), 265 (86%) remained in secondary care and 41 (14%) were referred to primary care. The primary composite endpoint (mortality, cardiac hospital admissions) occurred more frequently in patients with a high compared to those with a low MIS-HF after 1 year of follow-up (29.2% vs 10.9%; odds ratio (OR) 3.36, 95% confidence interval (CI) 2.20-5.14). No significant difference in the composite endpoint (9.8% vs 12.9%; OR 0.73, 95% CI 0.36-1.47) was found between patients with a low MIS-HF treated in primary versus secondary care. CONCLUSION: The MIS-HF questionnaire may improve referral policies, as it helps to identify HF patients that can safely be referred to primary care.

Telemedicine in heart failure-more than nice to have?

Telemedicine in chronic diseases like heart failure is rapidly evolving and has two important goals: improving and individualising care as well as reducing costs. In this paper, we provide a critical and an updated review of the current evidence by discussing the most important trials, meta-analyses and systematic reviews. So far, evidence for the CardioMEMS device is most convincing. Other trials regarding invasive and non-invasive telemonitoring and telephone support show divergent results, but several meta-analyses and systematic reviews uniformly reported a beneficial effect. Voice-over systems and ECG monitoring had neutral results. Lack of direct comparison between different modalities makes it impossible to determine the most effective method. Dutch studies showed predominantly non-significant results, mainly due to underpowered studies or because of a high standard of usual care. There are no conclusive results on cost-effectiveness of telemedicine because of the above shortcomings. The adherence of elderly patients was good in the trials, being essential for the compliance of telemedicine in the entire heart failure population. In the future perspective, telemedicine should be better standardised and evolve to be more than an addition to standard care to improve care and reduce costs.

Effects of tailored telemonitoring on functional status and health-related quality of life in patients with heart failure.

BACKGROUND: Functional status and health-related quality of life (HRQoL) are important in patients with heart failure (HF). Little is known about the effect of telemonitoring on functional status and HRQoL in that population. METHODS AND RESULTS: A total of 382 patients with HF (New York Heart Association class 2-4) were included in a randomised controlled trial to investigate the effect of tailored telemonitoring on improving HRQoL and functional status in HF patients. Randomisation was computer-generated with stratification per centre. At baseline and after 12 months, patients' functional status was determined by metabolic equivalent scores (METS). HRQoL was measured with the EuroQol five dimensions questionnaire (EQ-5D), visual analogue scale (VAS) and Borg rating of perceived exertion scale (Borg). Additional outcome data included number of HF-related outpatient clinic visits and mortality. Telemonitoring was statistically significantly related to an increase in METS after 1 year (regression coefficient 0.318; p = 0.01). Telemonitoring did not improve Borg, EQ-5D or VAS scores after 1 year. EQ-5D [hazard ratio (HR) 0.20, 95% confidence interval (CI) 0.07-0.54], VAS (HR 0.98, 95% CI 0.96-0.99), Borg (HR 1.21, 95% CI 1.11-1.31) and METS (HR 0.73, 95% CI 0.58-0.93) at baseline were significantly associated with survival after 12 months. CONCLUSIONS: Tailored telemonitoring stabilised the functional status of HF patients but did not improve HRQoL. Therefore, telemonitoring may help to prevent deterioration of exercise capacity in patients with HF. However, because our study is a reanalysis of a randomised controlled trial (RCT), this is considered hypothesis-generating and should be confirmed by adequately powered RCTs.

Impact of airflow limitation in chronic heart failure.

BACKGROUND: Comorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF. METHODS: 205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV1/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated. RESULTS: Almost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different. CONCLUSION: COPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.

The role of CAF derived exosomal microRNAs in the tumour microenvironment of melanoma.

Exosomes play a crucial role in the crosstalk between cancer associated fibroblasts (CAFs) and cancer cells, contributing to carcinogenesis and the tumour microenvironment. Recent studies have revealed that CAFs, normal fibroblasts and cancer cells all secrete exosomes that contain miRNA, establishing a cell-cell communication network within the tumour microenvironment. For example, miRNA dysregulation in melanoma has been shown to promote CAF activation via induction of epithelial-mesenchymal transition (EMT), which in turn alters the secretory phenotype of CAFs in the stroma. This review assesses the roles of melanoma exosomal miRNAs in CAF formation and how CAF exosome-mediated feedback signalling to melanoma lead to tumour progression and metastasis. Moreover, efforts to exploit exosomal miRNA-mediated network communication between tumour cells and their microenvironment, and their potential as prognostic biomarkers or novel therapeutic targets in melanoma will also be considered.

SFPQ promotes an oncogenic transcriptomic state in melanoma.

The multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234, demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ-RNA interactions promoting the expression of numerous oncogenic transcripts.

gamma-2 Herpes virus post-transcriptional gene regulation.

gamma-2 herpes viruses, which include Kaposi's sarcoma-associated herpes virus, are an important subfamily of herpes virus because of their oncogenic potential. Herpes virus saimiri (HVS) is the prototype gamma-2 herpes virus and is a useful model to study the basic mechanisms of lytic replication in this subfamily. Like all herpes viruses, HVS has two distinct life cycles, latent persistence and lytic replication. Analysis of herpes virus genomes has demonstrated that, in contrast to cellular genes, most virus genes that are expressed lytically do not have introns. Herpes viruses replicate in the nucleus of the host cell, and therefore require that the viral intron-lacking mRNAs are exported from the nucleus to allow virus mRNA translation. This review focuses upon the role of HVS ORF 57, a post-transcriptional regulatory protein, which is conserved in all herpes viruses. HVS ORF 57 is a multifunctional protein involved in both trans-activation and trans-repression of target mRNAs. The major role of the ORF 57 protein in mediating viral mRNA export is considered, and the ORF 57-host cell interactions that are required for this function are discussed.

Yeast myosin light chain, Mlc1p, interacts with both IQGAP and class II myosin to effect cytokinesis.

MLC1 (myosin light chain) acts as a dosage suppressor of a temperature sensitive mutation in the gene encoding the S. cerevisiae IQGAP protein. Both proteins localize to the bud neck in mitosis although Mlc1p localisation precedes Iqg1p. Mlc1p is also found at the incipient bud site in G(1) and the growing bud tip during S and G(2) phases of the cell cycle. A dominant negative GST-Mlc1p fusion protein specifically blocks cytokinesis and prevents Iqg1p localisation to the bud neck, as does depletion of Mlc1p. These data support a direct interaction between the two proteins and immunoprecipitation experiments confirm this prediction. Mlc1p is also shown to interact with the class II conventional myosin (Myo1p). All three proteins form a complex, however, the interaction between Mlc1p and Iqg1p can be separated from the Mlc1p/Myo1p interaction. Mlc1p localisation and maintenance at the bud neck is independent of actin, Myo1p and Iqg1p. It is proposed that Mlc1p therefore functions to recruit Iqg1p and in turn actin to the actomyosin ring and that it is also required for Myo1p function during ring contraction.