Publications

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.

JTD Keywords: Acute respiratory failure, Artificial ventilation, Asthmatic-children, Breathing muscle, Clinical monitoring, Clinical practice, Clinical research, Consensus development, Data interpretation, Disease exacerbation, Drive, Electrode positioning, Electrode removal, Electromyography, Force, Home care, Human, Human diaphragm, Humans, Information processing, Inspiratory muscle training, Inspiratory muscles, Intensive care unit, Knowledge gap, Long term care, Mechanical ventilation, Medical procedures, Muscle contraction, Muscle fatigue, Muscle function, Muscle training, Muscle, skeletal, Muscle-activity, Noninvasive ventilation, Patient monitoring, Patient-ventilator asynchrony, Physiology, Prognosis, Quality of life, Reporting and data system, Respiratory failure, Respiratory muscles, Review, Severe exacerbations, Signal processing, Skeletal muscle, Standardization, Surface electromyography, Time factor

Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue's fluidity and stiffness. In vivo, state-of-the-art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta-analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

JTD Keywords: brain, cancer, cells, collective migration, elastic energy, elastography, in vivo magnetic resonance elastography, invasion, medical imaging, solid stress, tissue fluidity, tumor mechanics, viscoelastic properties, Cancer, Collagen, Extracellular-matrix, Humans, In vivo magnetic resonance elastography, Medical imaging, Neoplasms, Prognosis, Tissue fluidity, Tumor mechanics, Tumor microenvironment

Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients.

JTD Keywords: brugada syndrome, depolarization disorders, ensemble classifier, heart-rate recovery, Acute myocardial-ischemia, Autonomics, Brugada syndrome, Brugadum syndrome, Cardiac death, Depolarization, Depolarization disorder, Depolarization disorders, Dynamic ecg, Electrocardiography, Electrophysiology, Ensemble classifier, Ensemble-classifier, Events, Exercise, Forecasting, Heart, Heart-rate, Heart-rate recovery, Prognosis, Qrs, Quantification, Recovery, Repolarization, Sudden cardiac death

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.Copyright © 2021. Published by Elsevier B.V.

JTD Keywords: alcohol associated liver disease, alcohol-associated liver disease, cirrhosis, failure, frailty, impact, list, mass, model, mortality, prognosis, prognostic value, sarcopenia, severe muscle depletion, skeletal muscle index, Alcohol-associated liver disease, Cirrhosis, Liver-transplant candidates, Prognosis, Sarcopenia, Skeletal muscle index

Background & Aims: Prognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites. Methods: A dual-centre observational study of patients with cirrhosis and ascites recruited consecutively in relation to a paracentesis was carried out. Patients were followed up for 1 year, until death or liver transplantation (LTx). Ascites MFAP4 was tested with the model for end-stage liver disease (MELD-Na), CLIF Consortium Acute Decompensation (CLIF-C AD), and Child-Pugh score in Cox regression models. Results: Ninety-three patients requiring paracentesis were included. Median ascites MFAP4 was 29.7 U/L [22.3–41.3], and MELD-Na was 19 [16–23]. A low MELD-Na score (<20) was observed in 49 patients (53%). During follow-up, 20 patients died (22%), and 6 received LTx (6%). High ascites MFAP4 (>29.7 U/L) was associated with 1-year transplant-free survival (p = 0.002). In Cox regression, ascites MFAP4 and MELD-Na independently predicted 1-year transplant-free survival (hazard ratio [HR] = 0.97, p = 0.03, and HR = 1.08, p = 0.01, respectively). Ascites MFAP4 and CLIF-C AD also predicted survival independently (HR = 0.96, p = 0.02, and HR = 1.05, p = 0.03, respectively), whereas only ascites MFAP4 did, controlling for the Child-Pugh score (HR = 0.97, p = 0.03, and HR = 1.18, p = 0.16, respectively). For patients with MELD-Na <20, ascites MFAP4 but not ascites protein predicted 1-year transplant-free survival (HR 0.91, p = 0.02, and HR = 0.94, p = 0.17, respectively). Conclusions: Ascites MFAP4 predicts 1-year transplant-free survival in patients with cirrhosis and ascites. In patients with low MELD-Na scores, ascites MFAP4, but not total ascites protein, significantly predicted 1-year transplant-free survival. Lay summary: Patients with cirrhosis who have fluid in the abdomen, ascites, are at an increased risk of death and in need for liver transplantation. Our study identified patients with ascites and a poor prognosis by measuring microfibrillar associated protein 4 (MFAP4), a protein present in the abdominal fluid. Patients with low levels of the MFAP4 protein are at particularly increased risk of death or liver transplantation, suggesting that clinical care should be intensified in this group of patients. © 2021 The Authors

JTD Keywords: biomarker, clif-c ad, clif consortium acute decompensation, cps, child-pugh score, crp, c-reactive protein, ct, computed tomography, decompensated, ecm, extracellular matrix, fibrosis, fluid protein, gfr, glomerular filtration rate, hr, hazard ratio, inr, internationalised normal ratio, liver disease, liver-cirrhosis, ltx, liver transplantation, markers, meld-na, model for end-stage liver disease, mfap4, microfibrillar associated protein 4, mortality, nash, non-alcoholic steatohepatitis, natural-history, prognosis, risk-factors, sbp, spontaneous bacterial peritonitis, scores, stage, Biomarker, Decompensated, Egfr, estimated gfr, Fibrosis, Liver disease, Mortality, Prognosis, Spontaneous bacterial peritonitis

The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10 % (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher's test). Patients whose tumors expressed FOXA2 had increased relapses (59 vs. 79 %, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95 % = 1.45-7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like tumors, and is associated with increase relapses.

JTD Keywords: Breast carcinoma, Cancer stem cells, FOXA2, Prognosis