Long-term effect of tocilizumab on mortality, readmissions, persistent symptoms and lung function in SARS-CoV-2 patients 1 year after hospital discharge: A matched cohort study.

Background: Tocilizumab is presumed to be an effective and safe treatment for severe SARS-Cov-2, but its usefulness has not been investigated yet for long-term outcomes. This study aimed to evaluate the influence of tocilizumab on mortality in patients with SARS-CoV-2 throughout the year following discharge.

Methods: A retrospective observational analysis was performed on electronic medical records of patients with SARS-CoV2 who were discharged from our hospital after surviving the first wave in March-April 2020.

Poor sleep quality, COPD severity and survival according to CASIS and Pittsburgh questionnaires.

Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated.

Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data.

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD).

Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register.

Higher mortality and intubation rate in COVID-19 patients treated with noninvasive ventilation compared with high-flow oxygen or CPAP.

The effectiveness of noninvasive respiratory support in severe COVID-19 patients is still controversial. We aimed to compare the outcome of patients with COVID-19 pneumonia and hypoxemic respiratory failure treated with high-flow oxygen administered via nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV), initiated outside the intensive care unit (ICU) in 10 university hospitals in Catalonia, Spain. We recruited 367 consecutive patients aged ≥ 18 years who were treated with HFNC (155, 42.

Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients.

Study Objectives: To investigate the association between moderate or severe obstructive sleep apnea treated with home continuous positive airway pressure (CPAP) and severe coronavirus disease 2019 (COVID-19).

Methods: Retrospective study of patients admitted for COVID-19. Patients with obstructive sleep apnea treated with home CPAP were identified and for each of them we selected 5 patients admitted consecutively in the following hours.

Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study.

Study Objectives: In patients treated with noninvasive ventilation, sleep-related breathing changes can modify patient-ventilator interactions, which could reduce its effectiveness. The aim of this prospective observational study was to determine the impact of sleep/wake state on leaks, upper airway obstructive events, and asynchronies in patients treated by long-term noninvasive ventilation.

Methods: Stable patients adapted to noninvasive ventilation were considered for nocturnal polysomnography.

Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis.

Background: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS).

Methods: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD.

Calreticulin is important for the development of renal fibrosis and dysfunction in diabetic nephropathy.

Previously, our lab showed that the endoplasmic reticulum (ER) and calcium regulatory protein, calreticulin (CRT), is important for collagen transcription, secretion, and assembly into the extracellular matrix (ECM) and that ER CRT is critical for TGF-β stimulation of type I collagen transcription through stimulation of ER calcium release and NFAT activation. Diabetes is the leading cause of end stage renal disease. TGF-β is a key factor in the pathogenesis of diabetic nephropathy.

Predictors of respiratory complications in patients with C5-T5 spinal cord injuries.

Study Design: Retrospective chart audit.

Objectives: Describing the respiratory complications and their predictive factors in patients with acute traumatic spinal cord injuries at C5-T5 level during the initial hospitalization.

Setting: Hospital Vall d'Hebron, Barcelona.

Identification of Inhibitors of Thrombospondin 1 Activation of TGF-β.

TGF-β has been a target of interest for the treatment of fibrotic diseases and certain cancers. Approaches to target TGF-β include antagonists of the active ligand or TGF-β receptor kinase activity. These approaches have failed in clinical trials due to a lack of effectiveness and a limited therapeutic window.

Asbestos-related disease in upholsterers.

Before its use was banned in developed countries, asbestos was widely applied in upholstery. However, the risk of asbestos diseases among upholsterers has only rarely been reported. In this case series, we present a first series of 6 workers employed in small workshops who developed several asbestos-related diseases, including pleural plaques, pleural fibrosis, and asbestosis.

Overexpression of a pine Dof transcription factor in hybrid poplars: A comparative study in trees growing under controlled and natural conditions.

In this work, the role of the pine transcriptional regulator Dof 5 in carbon and nitrogen metabolism has been examined in poplar trees. The overexpression of the gene and potential effects on growth and biomass production were compared between trees growing in a growth chamber under controlled conditions and trees growing in a field trial during two growth seasons. Ten-week-old transgenic poplars exhibited higher growth than untransformed controls and exhibited enhanced capacity for inorganic nitrogen uptake in the form of nitrate.

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

Background: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure.

Calreticulin Regulates Neointima Formation and Collagen Deposition following Carotid Artery Ligation.

Background/aims: The endoplasmic reticulum (ER) stress protein, calreticulin (CRT), is required for the production of TGF-β-stimulated extracellular matrix (ECM) by fibroblasts. Since TGF-β regulates vascular fibroproliferative responses and collagen deposition, we investigated the effects of CRT knockdown on vascular smooth-muscle cell (VSMC) fibroproliferative responses and collagen deposition.

Methods: Using a carotid artery ligation model of vascular injury, Cre-recombinase-IRES-GFP plasmid was delivered with microbubbles (MB) to CRT-floxed mice using ultrasound (US) to specifically reduce CRT expression in the carotid artery.

Inhibition of Transforming Growth Factor-β Activation Diminishes Tumor Progression and Osteolytic Bone Disease in Mouse Models of Multiple Myeloma.

Transforming growth factor (TGF)-β supports multiple myeloma progression and associated osteolytic bone disease. Conversion of latent TGF-β to its biologically active form is a major regulatory node controlling its activity. Thrombospondin1 (TSP1) binds and activates TGF-β.

Hyperglycemic arterial disturbed flow niche as an in vitro model of atherosclerosis.

Type 2 diabetes significantly elevates the risk of cardiovascular disease. This can be largely attributed to the adverse effects of hyperglycemic conditions on normal endothelial cell (EC) function. ECs in both large and small vessels are influenced by hyperglycemic conditions, which increase susceptibility to EC dysfunction and atherosclerotic lesion formation.

Ambulatory adaptation to noninvasive ventilation in restrictive pulmonary disease: a randomized trial with cost assessment.

Background: Home mechanical ventilation is usually initiated in hospital. However, cost-effectiveness of inpatient set up has never been compared to outpatient adaptation in a randomized design. A Prospective, multicenter, non-inferiority trial was conducted comparing the effectiveness of adaptation to noninvasive mechanical ventilation (NIMV) performed in the ambulatory or hospital setting in patients with chronic respiratory failure secondary to restrictive thoracic disease, obesity-hypoventilation syndrome or neuromuscular disease.

Calreticulin regulates transforming growth factor-β-stimulated extracellular matrix production.

Endoplasmic reticulum (ER) stress is an emerging factor in fibrotic disease, although precise mechanisms are not clear. Calreticulin (CRT) is an ER chaperone and regulator of Ca(2+) signaling up-regulated by ER stress and in fibrotic tissues. Previously, we showed that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM).

Thrombospondin-1 opens the paracellular pathway in pulmonary microvascular endothelia through EGFR/ErbB2 activation.

Thrombospondin-1 (TSP1) is a multidomain protein that contains epidermal growth factor (EGF)-like repeats that indirectly activate the EGF receptor (EGFR) and selected downstream signaling pathways. In these studies, we show that TSP1 opens the paracellular pathway in human lung microvascular endothelial cells (HMVEC-Ls) in a dose-, time-, and protein tyrosine kinase (PTK)-dependent manner. TSP1 increased tyrosine phosphorylation of proteins enriched to intercellular boundaries including the zonula adherens (ZA) proteins, vascular endothelial-cadherin, γ-catenin, and p120 catenin.

Predictors of mortality in chest wall disease treated with noninvasive home mechanical ventilation.

Rationale: The long-term evolution of patients with chest wall disease and chronic respiratory failure treated with noninvasive home mechanical ventilation (NIHMV) is poorly known.

Objectives: The aim of this prospective observational study was to analyze the variables associated with mortality in a cohort of chest wall disease patients with chronic respiratory failure undergoing long-term follow-up after starting treatment with NIHMV.

Methods: Chest wall disease patients who began NIHMV between 1996 and 2005 were followed up, with death as the primary outcome.

The calreticulin-binding sequence of thrombospondin 1 regulates collagen expression and organization during tissue remodeling.

Amino acids 17-35 of the thrombospondin1 (TSP1) N-terminal domain (NTD) bind cell surface calreticulin to signal focal adhesion disassembly, cell migration, and anoikis resistance in vitro. However, the in vivo relevance of this signaling pathway has not been previously determined. We engineered local in vivo expression of the TSP1 calreticulin-binding sequence to determine the role of TSP1 in tissue remodeling.

Modulation of mammary cancer cell migration by 15-deoxy-delta(12,14)-prostaglandin J(2): implications for anti-metastatic therapy.

Recently, a number of steps in the progression of metastatic disease have been shown to be regulated by redox signalling. Electrophilic lipids affect redox signalling through the post-translational modification of critical cysteine residues in proteins. However, the therapeutic potential as well as the precise mechanisms of action of electrophilic lipids in cancer cells is poorly understood.

Intracellular calreticulin regulates multiple steps in fibrillar collagen expression, trafficking, and processing into the extracellular matrix.

Calreticulin (CRT), a chaperone and Ca(2+) regulator, enhances wound healing, and its expression correlates with fibrosis in animal models, suggesting that CRT regulates production of the extracellular matrix. However, direct regulation of collagen matrix by CRT has not been previously demonstrated. We investigated the role of CRT in the regulation of fibrillar collagen expression, secretion, processing, and deposition in the extracellular matrix by fibroblasts.

Stainless steel ions stimulate increased thrombospondin-1-dependent TGF-beta activation by vascular smooth muscle cells: implications for in-stent restenosis.

Background/aims: Despite advances in stent design, in-stent restenosis (ISR) remains a significant clinical problem. All implant metals exhibit corrosion, which results in release of metal ions. Stainless steel (SS), a metal alloy widely used in stents, releases ions to the vessel wall and induces reactive oxygen species, inflammation and fibroproliferative responses.

Epidermal growth factor-like repeats of thrombospondins activate phospholipase Cgamma and increase epithelial cell migration through indirect epidermal growth factor receptor activation.

Thrombospondin (TSP) 1 is a trimeric multidomain protein that contains motifs that recognize distinct host cell receptors coupled to multiple signaling pathways. Selected TSP1-induced cellular responses are tyrosine kinase-dependent, and TSP1 contains epidermal growth factor (EGF)-like repeats. Specific receptor interactions or functions for the EGF-like repeats have not been identified.