Publications by authors named "Xavier Corbella"

97 Publications

Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial.

Front Med (Lausanne) 2021 14;8:691712. Epub 2021 Jun 14.

Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.

Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19. Identifier [NCT04341038/EudraCT: 2020-001445-39].
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http://dx.doi.org/10.3389/fmed.2021.691712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236585PMC
June 2021

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus.

J Clin Med 2021 May 20;10(10). Epub 2021 May 20.

Cardiovascular Risk Unit-Internal Medicine Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.

SLE is associated with increased cardiovascular risk. The objective of this study was to determine the prevalence of asymptomatic carotid atherosclerosis to analyze its relationship with dyslipidemia and related genetic factors in a population of patients with SLE. Seventy-one SLE female patients were recruited. Carotid ultrasound, laboratory profiles, and genetic analysis of the , and genes were performed. SLE patients were divided into two groups according to the presence or absence of carotid plaques. Patients with carotid plaque had higher plasma TG (1.5 vs. 0.9 mmol/L, = 0.001), Non-HDL-C (3.5 vs. 3.1 mmol/L, = 0.025), and apoB concentrations (1.0 vs. 0.9 g/L, = 0.010) and a higher prevalence of hypertension (80 vs. 37.5%, = 0.003) than patients without carotid plaque. The C-allele was present in 83.3% and 16.7% ( = 0.047) of patients with and without carotid plaque, respectively. The CC genotype (OR = 0.026; 95% CI: 0.001 to 0.473, = 0.014), an increase of 1 mmol/L in TG concentrations ( = 12.550; 95% CI: 1.703 to 92.475, = 0.013) and to be hypertensive ( = 9.691; 95% CI: 1.703 to 84.874, = 0.040) were independently associated with carotid atherosclerosis. In summary, plasma TG concentrations, CC homozygosity, and hypertension are independent predictors of carotid atherosclerosis in women with SLE.
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http://dx.doi.org/10.3390/jcm10102218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160900PMC
May 2021

Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry.

J Clin Med 2021 May 20;10(10). Epub 2021 May 20.

Department of Internal Medicine, Infanta Cristina University Hospital, 28981 Parla, Spain.

(1) Background: The inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. (2) Methods: Retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. (3) Results: A total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. (4) Conclusion: The present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters.
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http://dx.doi.org/10.3390/jcm10102214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161115PMC
May 2021

Neuraminidase inhibitors and single dose baloxavir are effective and safe in uncomplicated influenza: a meta-analysis of randomized controlled trials.

Expert Rev Clin Pharmacol 2021 Apr 26:1-18. Epub 2021 Apr 26.

CIBER De Enfermedades Respiratorias (CIBERES), Instituto Salud Carlos III, Madrid, Spain.

: Scarce evidence verifying the clinical impact of baloxavir on influenza complications is found.: PubMed, Cochrane Library, and Web of Science databases were searched through December 2020. Randomized-controlled trials (RCT) that enrolled patients with laboratory-confirmed influenza receiving neuraminidase inhibitors (NAI) or baloxavir comparing to placebo were assessed. PROSPERO Registration-number: CRD42021226854.: Twenty-one RCTs (11,697 patients) were included. Antiviral administration significantly reduced time to clinical resolution (mean difference: -21.3 hours) and total influenza-related complications (OR:0.55, 95%CI: 0.42-0.73). Specifically, antivirals significantly decreased bronchitis (OR:0.54, 95%CI: 0.38-0.75), sinusitis (OR:0.51, 95%CI: 0.33-0.78), acute otitis media (OR:0.48, 95%CI: 0.30-0.77), and antibiotic prescription (OR:0.62; 95%CI: 0.48-0.80). A positive trend favored antivirals administration to reduce pneumonia (OR:0.47, 95%CI: 0.16-1.33), or hospitalization rates (OR:0.65; 95%CI: 0.34-1.24) compared to placebo, but did not reach statistical significance. Adverse events (AE) were reported in 11%, 8.9%, and 5.1% of NAIs, placebo and baloxavir recipients, respectively. Compared with NAIs, administration of baloxavir showed non-significantly reduced AEs (OR:0.74, 95%CI: 0.53-1.04).: Single-dose baloxavir and NAIs were superior to placebo to reduce complications in uncomplicated influenza, with 40% significant reduction in antibiotic prescription. Safety and efficacy of single-dose baloxavir were non-inferior to NAIs.
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http://dx.doi.org/10.1080/17512433.2021.1917378DOI Listing
April 2021

Physicochemical Properties of Lipoproteins Assessed by Nuclear Magnetic Resonance as a Predictor of Premature Cardiovascular Disease. PRESARV-SEA Study.

J Clin Med 2021 Mar 29;10(7). Epub 2021 Mar 29.

Unidad de Lípidos y Riesgo Vascular, Servicio de Medicina Interna, Hospital Universitario de Bellvitge-IDIBELL, 08907 Barcelona, Spain.

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event ( = 125) and a group of control subjects ( = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.
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http://dx.doi.org/10.3390/jcm10071379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037702PMC
March 2021

Clinical Significance of Indeterminate QuantiFERON-TB Gold Plus Assay Results in Hospitalized COVID-19 Patients with Severe Hyperinflammatory Syndrome.

J Clin Med 2021 Feb 26;10(5). Epub 2021 Feb 26.

Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet de Llobregat, Barcelona, Spain.

Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related to an indeterminate QFT-Plus test in COVID-19 hospitalized patients, and to analyze its relationship with in-hospital mortality. A retrospective analysis of all hospitalized COVID-19 patients on whom a QTF-Plus assay was performed in a tertiary care public hospital during the first epidemic wave in Spain (March-April 2020). Out of a total of 96 patients included, 34 (35.4%) had an indeterminate result, in all cases due to a lack of response in the mitogen control. Factors related to COVID-19 severity, such as higher lactate dehydrogenase (LDH) (odds ratio [OR] 1.005 [95% confidence interval [CI] 1.002-1.008]) and previous administration of corticosteroids (OR 4.477 [95% CI 1.397-14.345]), were independent predictors for indeterminate QFT-Plus assay. Furthermore, indeterminate results were more frequent among COVID-19 patients who died during hospitalization (29.1% vs. 64.7%; = 0.005). We conclude that QFT-Plus assay yielded an unexpected, high prevalence of indeterminate results in severe COVID-19 patients. Factors related to worse COVID-19 outcome, such as LDH, as well as corticosteroid use before the QFT-Plus assay, seem to be predictors for an indeterminate result. The role of an indeterminate QFT-Plus result in predicting COVID-19 severity and mortality should be evaluated.
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http://dx.doi.org/10.3390/jcm10050918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956705PMC
February 2021

Implication between Genetic Variants from APOA5 and ZPR1 and NAFLD Severity in Patients with Hypertriglyceridemia.

Nutrients 2021 Feb 8;13(2). Epub 2021 Feb 8.

Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain.

Background: Lipid metabolism disorders, especially hypertriglyceridemia (HTG), are risk factors for non-alcoholic fatty liver disease (NAFLD). However, the association between genetic factors related to HTG and the risk of NAFLD has been scarcely studied.

Methods: A total of 185 subjects with moderate HTG were prospectively included. We investigated the association between genetic factors' (five allelic variants with polygenic hypertriglyceridemia) clinical and biochemical biomarkers with NAFLD severity. The five allelic variants' related clinical and biochemical data of HTG were studied in all the subjects. NAFLD was assessed by abdominal ultrasound and patients were divided into two groups, one with no or mild NAFLD and another with moderate/severe NAFLD.

Results: Patients with moderate/severe NAFLD had higher weight and waist values and a higher prevalence of insulin resistance than patients with no or mild NAFLD. Moderate/severe NAFLD was independently associated with rs3134406 and rs964184 variants, and also showed a significant inverse relationship with lipoprotein(a) [Lp(a)] concentrations.

Conclusions: rs3135506 and rs964184 variants and lipoprotein(a) are associated with moderate/severe NAFLD. This association was independent of body weight, insulin resistance, and other factors related to NAFLD.
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http://dx.doi.org/10.3390/nu13020552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914661PMC
February 2021

Relapsing Haemothorax as an Unusual Presentation of Primary Angiosarcoma of the Spleen.

Eur J Case Rep Intern Med 2020 29;7(12):001944. Epub 2020 Oct 29.

Department of Internal Medicine, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Spain.

Spontaneous haemothorax (SH) is a rare subcategory of haemothorax that involves the accumulation of blood within the pleural space in the absence of trauma. SH especially occurs in middle-aged or elderly patients, but data are usually limited to case reports and case series. Coagulopathy, aneurysm or aortic dissection, Rendu-Osler-Weber syndrome and malignancy have to be considered among the causes of SH.

Aim: We describe a case of primary angiosarcoma of the spleen presenting as relapsing haemothorax.

Results: An 81-year-old woman was referred to our hospital because of a 2-month history of relapsing haemothorax after the performance of urgent splenectomy due to active bleeding from large spleen cysts. No evidence of neoplasm was seen after pathological examination of the spleen. On admission, left haemothorax and 2 new cystic masses in the thoracic wall were documented, both in close relation to the scars of previous surgery and chest tubes. After excision of 1 mass, histological examination revealed angiosarcoma, and a final diagnosis of primary angiosarcoma of the spleen with postsurgical metastatic dissemination to the thorax and pleura was made.

Conclusion: Primary angiosarcoma should be included in the differential diagnosis of haemorrhagic spleen cysts. Clinical diagnosis and management usually requires splenectomy, but it should be carefully planned in order to avoid local metastatic dissemination or haematogenous spread of the tumour.

Learning Points: The differential diagnosis of spleen cysts must include malignant conditions.Despite its absolute rarity, angiosarcoma is considered the most common primary non-haematolymphoid splenic malignancy and has a poor prognosis.Splenectomy is usually required for a prompt diagnosis of primary angiosarcoma of the spleen, but it needs to be performed with extreme caution to avoid metastatic dissemination.
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http://dx.doi.org/10.12890/2020_001944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806299PMC
October 2020

Non-retrieved inferior vena cava filters: causes and long-term follow-up.

Eur J Intern Med 2021 04 7;86:73-78. Epub 2021 Jan 7.

Internal Medicine, Hospital Universitari de Bellvitge - Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.

Background: Temporary inferior vena cava (IVC) filters are not always retrieved. Information about long-term outcomes of patients with indwelling filters is scarce. Aims of our study were to assess reasons that preclude retrieval of temporary IVC filters and long-term outcomes and causes of death in patients with indwelling filters.

Materials And Methods: Retrospective observational study including all consecutive patients undergoing IVC filter insertion from January 2009 through December 2018. Patients with permanent filters and those with temporary filters not retrieved were followed from insertion until June 2020.

Results: We included 271 patients with a mean age of 63.8 years. The main indication for filter insertion was acute venous thromboembolism and contraindication for anticoagulation (83%). The filter was deemed as permanent in 24.4% of patients and temporary in 75.6%. Sixty six percent of temporary filters were retrieved; the main cause of non-retrieval was lack of planning / follow-up (57.9%). One hundred twelve patients (41.3%) remained with indwelling filters. After follow-up, 54.5% were alive and 45.5% had died, with a median survival time of 6.19 (95% CI, 2.63-9.75) years. The most frequent cause of death during follow-up was cancer (49%). The frequency of anticoagulant therapy was similar in both groups (57.4%% versus 54.9%).

Conclusions: The main preventable cause of non-retrieval of temporary IVC filters was lack of planning / follow-up. Structured follow-up programs should be implemented to increase retrieval rates. In patients with indwelling filters, the main cause of death was cancer and extended anticoagulation was not associated with survival.
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http://dx.doi.org/10.1016/j.ejim.2020.12.026DOI Listing
April 2021

The internist and hospital ambulatory medicine.

Authors:
Xavier Corbella

Med Clin (Barc) 2021 03 27;156(6):281-283. Epub 2020 Dec 27.

Servicio de Medicina Interna, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, España; Facultad de Medicina, Universitat Internacional de Catalunya, Barcelona, España; European Federation of Internal Medicine, Bruselas, Bélgica. Electronic address:

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http://dx.doi.org/10.1016/j.medcli.2020.11.023DOI Listing
March 2021

Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis.

PLoS One 2020 28;15(12):e0243533. Epub 2020 Dec 28.

Departments of Internal Medicine, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

Background: A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.

Methods: This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients.

Results: Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.

Conclusions: Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243533PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769556PMC
January 2021

The prevalence and incidence rate of pulmonary arterial hypertension in systemic sclerosis: Systematic review and meta-analysis.

Autoimmun Rev 2021 Jan 13;20(1):102713. Epub 2020 Nov 13.

Autoimmune Diseases Unit, Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain; Group of Evaluation of Health Determinants and Health Policies, Hestia Chair in Integrated Health and Social Care, Barcelona, Spain.

The present study aimed to assess the prevalence and incidence rate of pulmonary arterial hypertension (PAH) in Systemic Sclerosis (SSc). The review was undertaken using MEDLINE and SCOPUS from June 1962 to May 2019 and the terms: ("Scleroderma, Systemic"[MesH]) AND "Hypertension, Pulmonary"[MesH]. The Newcastle-Ottawa Scale (NOS) was used for the qualifying assessment. The inverse variance-weighted method was performed. Twenty-four studies were included in the global PAH prevalence study. They comprised data from 9804 SSc patients. The overall PAH prevalence found was 6.4% (95%CI 5%-8.3%). Fourteen studies were included in the PAH prevalence study for lcSSc. They comprised data from 4987 lcSSc patients. The PAH prevalence found in lcSSc was 7.7% (95%CI 5.3%-11.1%). Twelve studies were included in the PAH prevalence study for dcSSc. They comprised data from 1790 dcSSc patients. The PAH prevalence found in dcSSc was 6.3% (95%CI 4.5%-8.9%). Fifteen studies showed PAH incidence of an entire SSc cohort. They comprised data from 5926 SSc patients. The overall PAH incidence found was 18.2 cases per 1000 person-years (95%CI 12-27.4). Eight studies showed PAH incidence for lcSSc. They comprised data from 2721 patients. The overall PAH incidence found in lcSSc was 20.4 cases per 1000 person-years (95%CI 10.1-41.1). Seven studies showed PAH incidence for dcSSc. They comprised data from 942 dcSSc patients. The overall PAH incidence found in dcSSc was 16.6 cases per 1000 person-years (95%CI 8.5-32.1). CONCLUSION: The overall PAH prevalence found was 6.4% (95%CI 5%-8.3%) and the overall PAH incidence 18.2 cases per 1000 person-years (95%CI 12-27.4).
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http://dx.doi.org/10.1016/j.autrev.2020.102713DOI Listing
January 2021

Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19.

J Clin Med 2020 Oct 29;9(11). Epub 2020 Oct 29.

Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain.

(1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; < 0.001). The multivariate study identified age, gender (male), body mass index (BMI), arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic cardiopathy, chronic heart failure, chronic hepatopathy, Charlson's index, heart rate and respiratory rate upon admission >20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes.
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http://dx.doi.org/10.3390/jcm9113488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693215PMC
October 2020

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

Eur J Nutr 2021 Aug 30;60(5):2381-2396. Epub 2020 Oct 30.

Joan XXIII University Hospital, Tarragona, Spain.

Purpose: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS).

Methods: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment.

Results: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A).

Conclusions: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS.

Trial Registration: ISRCTN89898870. Registration date: July 24, 2014.
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http://dx.doi.org/10.1007/s00394-020-02415-wDOI Listing
August 2021

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

Int J Infect Dis 2020 Dec 6;101:290-297. Epub 2020 Oct 6.

Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.

Objectives: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS).

Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality.

Results: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up.

Conclusions: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.
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http://dx.doi.org/10.1016/j.ijid.2020.09.1486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537652PMC
December 2020

Prevalence of sarcopenia in community-dwelling older adults using the updated EWGSOP2 definition according to kidney function and albuminuria : The Screening for CKD among Older People across Europe (SCOPE) study.

BMC Geriatr 2020 10 2;20(Suppl 1):327. Epub 2020 Oct 2.

Geriatric Unit, Internal Medicine Department, Hospital Universitari de Bellvitge, Systemic Diseases and Ageing Group, Cardiovascular, Respiratory and Systemic Diseases and Cellular Aging Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

Background: Loss of muscle mass and function may be more pronounced in older adults with chronic kidney disease (CKD) and with albuminuria. Thus, we investigated the prevalence of sarcopenia among community-dwelling older adults according to kidney function and grade of albuminuria. We also explored differences in the prevalence of sarcopenia according to three different equations for the estimation of glomerular filtration rate (eGFR).

Methods: A cross-sectional analysis of 1420 community-dwelling older adults (≥75 years old) included in the SCOPE study, a multicenter prospective cohort study, was conducted. Comprehensive geriatric assessment including short physical performance battery (SPPB), handgrip strength test and bioelectrical impedance analysis (BIA) was performed. Sarcopenia was defined using the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). eGFR was calculated using Berlin Initiative Study (BIS), Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and Full Age Spectrum (FAS) equations, and urinary albumin-to-creatinine ratio (ACR) was collected to categorize CKD according to Kidney Disease Improving Global Outcomes guidelines.

Results: Median age was 79.5 years (77.0-83.0), 804 (56.6%) were women. Using EWGSOP2 definition, 150 (10.6%) participants met diagnostic criteria for sarcopenia. Moreover, 85 (6%) participants had severe sarcopenia. Sarcopenia was more prevalent in participants with more advanced stages of CKD according to BIS eq. (9.6% in stages 1 and 2 and 13.9% in stages 3a, 3b and 4, p = 0.042), and also according to CKD-EPI (9.8% vs. 14.2%, p = 0.042) and FAS although not reaching statistical signification (9.8% vs. 12.7%, p = 0.119). Thus, differences in prevalence are observed among CKD categories as estimated by different equations. Prevalence of sarcopenia was also higher with increasing albuminuria categories: 9.3% in normoalbuminuric, 13.2% in microalbuminuric and 16.8% in macroalbuminuric participants, (p = 0.019).

Conclusions: Sarcopenia is common among community-dwelling older adults, especially among those with more advanced CKD categories, with prevalence estimates differing slightly depending on the equation used for the estimation of eGFR; as well as among those with higher albuminuria categories.
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http://dx.doi.org/10.1186/s12877-020-01700-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531109PMC
October 2020

Real-World Epidemiology of Potassium Derangements Among Chronic Cardiovascular, Metabolic and Renal Conditions: A Population-Based Analysis.

Clin Epidemiol 2020 11;12:941-952. Epub 2020 Sep 11.

Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.

Background: The aims of the present analysis are to estimate the prevalence of five key chronic cardiovascular, metabolic and renal conditions at the population level, the prevalence of renin-angiotensin-aldosterone system inhibitor (RAASI) medication use and the magnitude of potassium (K) derangements among RAASI users.

Methods And Results: We used data from more than 375,000 individuals, 55 years of age or older, included in the population-based healthcare database of the Catalan Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus, ischemic heart disease and hypertension. RAASI medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs) and renin inhibitors. Hyperkalemia was defined as K levels >5.0 mEq/L and hypokalemia as K <3.5 mEq/L. The prevalence of chronic cardiovascular, metabolic and renal conditions was high, and particularly that of hypertension (prevalence ranging from 48.2% to 48.9%). The use of at least one RAASI medication was almost ubiquitous in these patients (75.2-77.3%). Among RAASI users, the frequency of K derangements, mainly of hyperkalemia, was very noticeable (12% overall), particularly in patients with CKD or CHF, elderly individuals and users of MRAs. Hypokalemia was less frequent (1%).

Conclusion: The high prevalence of K derangements, and particularly hyperkalemia, among RAASI users highlights the real-world relevance of K derangements, and the importance of close monitoring and management of K levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk.
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http://dx.doi.org/10.2147/CLEP.S253745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494006PMC
September 2020

Study design of Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS).

ESC Heart Fail 2020 Sep 17. Epub 2020 Sep 17.

Community Heart Failure Program, Departments of Cardiology and Internal Medicine, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.

Aims: The role of non-invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) ('vulnerable phase' HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse-based follow-up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strategy based on face-to-face on-site visits at the vulnerable post-discharge phase.

Methods And Results: We designed a 24 week nationwide, multicentre, randomized, controlled, open-label, blinded endpoint adjudication trial to assess the effect on cardiovascular (CV) mortality and non-fatal HF events of a TM-based comprehensive management programme, based on mHealth, for patients with chronic HF. Approximately 508 patients with a recent hospital admission due to HF decompensation will be randomized (1:1) to either structured follow-up based on face-to-face appointments (UC group) or the delivery of health care using TM. The primary outcome will be a composite of death from CV causes or non-fatal HF events (first and recurrent) at the end of a 6 month follow-up period. Key secondary endpoints will include components of the primary event analysis, recurrent event analysis, and patient-reported outcomes.

Conclusions: The HERMeS trial will assess the efficacy of a TM-based follow-up strategy for real-world 'vulnerable phase' HF patients combining telemonitoring and teleintervention.
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http://dx.doi.org/10.1002/ehf2.12962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754948PMC
September 2020

Gender Differences in Health-Related Quality of Life in Patients with Systolic Heart Failure: Results of the VIDA Multicenter Study.

J Clin Med 2020 Aug 31;9(9). Epub 2020 Aug 31.

Unidad de Insuficiencia Cardiaca Comunitaria (UMICO), Servicio de Cardiología, Hospital Universitario de Bellvitge, L' Hospitalet de Llobregat, 08907 Barcelona, Spain.

Previous studies have shown that heart failure is associated with worse health-related quality of life (HRQoL). The existence of differences according to gender remains controversial. We studied 1028 consecutive outpatients with heart failure and reduced ejection fraction (HFrEF) from a multicentre cross-sectional descriptive study across Spain that assessed HRQoL using two questionnaires (KCCQ, Kansas City Cardiomyopathy Questionnaire; and EQ-5D, EuroQoL 5 dimensions). The primary objective of the study was to describe differences in HRQoL between men and women in global scores and domains of health status of patients and explore gender differences and its interactions with heart failure related factors. In adjusted analysis women had lower scores in KCCQ overall summary scores when compared to men denoting worse HRQoL (54.7 ± 1.3 vs. 62.7 ± 0.8, < 0.0001), and specifically got lower score in domains of symptom frequency, symptoms burden, physical limitation, quality of life and social limitation. No differences were found in domains of symptom stability and self-efficacy. Women also had lower scores on all items of EQ-5D (EQ-5D index 0.58 ± 0.01 vs. 0.67 ± 0.01, < 0.0001). Finally, we analyzed interaction between gender and different clinical determinants regarding the presence of limitations in the 5Q-5D and overall summary score of KCCQ. Interestingly, there was no statistical significance for interaction for any variable. In conclusion, women with HFrEF have worse HRQoL compared to men. These differences do not appear to be mediated by clinical or biological factors classically associated with HRQoL nor with heart failure severity.
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http://dx.doi.org/10.3390/jcm9092825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563299PMC
August 2020

Impact on clinical outcomes and health costs of deranged potassium levels in patients with chronic cardiovascular, metabolic, and renal conditions.

Rev Esp Cardiol (Engl Ed) 2021 Apr 19;74(4):312-320. Epub 2020 Jul 19.

Unidad Multidisciplinar de Insuficiencia Cardiaca Comunitaria (UMICO), Servicio de Cardiología, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Departamento de Ciencias Clínicas, Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain. Electronic address:

Introduction And Objectives: Potassium derangements are frequent among patients with chronic cardiovascular conditions. Studies on the associations between potassium derangements and clinical outcomes have yielded mixed findings, and the implications for health care expenditure are unknown. We assessed the population-based associations between hyperkalemia, hypokalemia and clinical outcomes and health care costs, in patients with chronic heart failure, chronic kidney disease, diabetes mellitus, hypertension, and ischemic heart disease.

Methods: Population-based, longitudinal study including up to 36 269 patients from a health care area with at least one of the above-mentioned conditions. We used administrative, hospital and primary care databases. Participants were followed up between 2015 and 2017, were aged ≥ 55 years and had at least 1 potassium measurement. Four analytic designs were used to evaluate prevalent and incident cases and the use of renin-angiotensin-aldosterone system inhibitors.

Results: Hyperkalemia was twice as frequent as hypokalemia. On multivariable-adjusted analyses, hyperkalemia was robustly and significantly associated with an increased risk of all-cause death (HR from Cox regression models ranging from 1.31-1.68) and with an increased odds of a yearly health care expenditure >85th percentile (OR, 1.21-1.29). Associations were even stronger in hypokalemic patients (HR for all-cause death, 1.92-2.60; OR for health care expenditure> percentile 85th, 1.81-1.85).

Conclusions: Experimental studies are needed to confirm whether the prevention of potassium derangements reduces mortality and health care expenditure in these chronic conditions. Until then, our findings provide observational evidence on the potential importance of maintaining normal potassium levels.
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http://dx.doi.org/10.1016/j.rec.2020.06.013DOI Listing
April 2021

No clear beneficial effects of beta-blockers for heart failure with preserved ejection fraction to improve prognostic outcomes in elderly patients with sinus rhythm.

Intern Emerg Med 2020 10 11;15(7):1351-1352. Epub 2020 Jun 11.

Geriatric Unit, Internal Medicine Department, Hospital Universitari de Bellvitge-IDIBELL, L´Hospitalet de Llobregat, 08907, Barcelona, Spain.

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http://dx.doi.org/10.1007/s11739-020-02398-wDOI Listing
October 2020

Comment to: Cluster analysis for clinical sarcoidosis' phenotyping.

Eur J Intern Med 2020 08 29;78:142. Epub 2020 May 29.

Autoimmune Diseases Unit, Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, Barcelona, Spain; School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain; Group of Evaluation of Health Determinants and Health Policies, Hestia Chair in Integrated Health and Social Care, Barcelona, Spain.

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http://dx.doi.org/10.1016/j.ejim.2020.05.024DOI Listing
August 2020

Direct oral anticoagulants versus vitamin K antagonists in antiphospholipid syndrome: A meta-analysis.

Eur J Intern Med 2020 09 29;79:43-50. Epub 2020 May 29.

Internal Medicine Department, Hospital Universitari Bellvitge - IDIBELL, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. Electronic address:

Background: Anticoagulant treatment is recommended in patients with thrombosis and antiphospholipid syndrome (APS). Conflicting results have been reported on the role of direct oral anticoagulants (DOACs) in these patients. We performed a meta-analysis of randomized controlled trials (RCTs) focused on this issue.

Methods: We searched MEDLINE and EMBASE for RCTs comparing DOACs and vitamin K antagonists (VKAs) for secondary thromboprophylaxis in patients with thrombotic APS. The primary objective was to assess the efficacy of DOACs compared to VKAs to prevent recurrence of thromboembolic events. Risk difference (RD) was reported as weighted RD according to Mantel-Haenszel random-effect method.

Results: Three RCTs (426 patients) were included, all comparing rivaroxaban with VKAs. The proportion of recurrences (either arterial or venous) was higher among rivaroxaban patients when compared with those receiving VKAs (9.5% vs 2.8%; RD 6%, 95% CI, -0.05 - 0.18, p=0.29), although non-statistically significant. In patients with an arterial index event, thromboembolic recurrences were more frequent in those treated with rivaroxaban compared to those treated with VKAs (25% vs 6.2%; RD 19%, 95% CI, 0.04 - 0.33; p =0.01; I 49%). In triple aPL positive patients, rivaroxaban showed higher rates of thromboembolic recurrences compared with VKAs (12% vs 3%; RD 9%, 95% CI, 0.02 - 0.15; p= 0.01; I 13%). Non-statistically significant differences were observed in major bleeding events or mortality.

Conclusions: The use of rivaroxaban in APS patients is associated with an increased rate of thromboembolic recurrences compared to VKAs, at least in those with arterial index event or triple aPL positivity.
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http://dx.doi.org/10.1016/j.ejim.2020.05.012DOI Listing
September 2020

Clinical features and outcomes of asymptomatic pulmonary sarcoidosis. A comparative cohort study.

Respir Med 2020 08 15;169:105998. Epub 2020 May 15.

Autoimmune Diseases Unit, Department of Internal Medicine, Bellvitge University Hospital-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain.

Objective: To evaluate the clinical characteristics and outcomes of patients with asymptomatic pulmonary sarcoidosis (APS) detected incidentally and compare them with symptomatic non-Löfgren sarcoidosis (SnLS) patients.

Methods: Patients diagnosed as having APS at a University hospital in Barcelona, Spain, followed prospectively from 1976 to 2018. APS was defined as the presence of bilateral hilar lymphadenopathy (BHL) with or without lung parenchymal involvement discovered incidentally on chest radiograph or CT scan. APS was compared with SnLS.

Results: APS was diagnosed in 50 (13.6%) and SnLS in 317 (86.4%) patients. At diagnosis, stage I chest radiograph was significantly more frequent in APS than in SnLS (p < 0.001) and there were no asymptomatic patients with stages III and IV. SnLS showed more severe impairment in FVC (p = 0.009) and forced expiratory volume in 1st second (FEV1) (p = 0.003) than APS, while DLco was similar in both groups. Extrathoracic involvement at diagnosis and during the follow up was less frequent in APS than in SnLS patients (p < 0.005). Endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS) was the most used diagnostic tool. Treatment was more frequently required in the SnLS than in APS (p < 0.001). At five years, APS patients showed less presence of active disease than SnLS (p = 0.054).

Conclusions: APS showed earlier radiological stages, lesser impairment in lung function, extrapulmonary organ involvement and need for treatment than SnLS. EBUS was the most useful diagnostic tool. In spite of its benign presentation, around one third of patients evolved to persistent disease but usually with mild clinical and functional impairment.
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http://dx.doi.org/10.1016/j.rmed.2020.105998DOI Listing
August 2020

Clinical phenotypes and prediction of chronicity in sarcoidosis using cluster analysis in a prospective cohort of 694 patients.

Eur J Intern Med 2020 07 21;77:59-65. Epub 2020 Apr 21.

Autoimmune Diseases Unit, Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain; Evaluation of Health Determinants and Health Policies Group, Hestia Chair in Integrated Health and Social Care, Barcelona, Spain.

Background: Sarcoidosis is a heterogeneous disease with high variability in natural history and clinical spectrum. The study aimed to reveal different clinical phenotypes of patients with similar characteristics and prognosis.

Methods: Cluster analysis including 26 phenotypic variables was performed in a large cohort of 694 sarcoidosis patients, collected and followed-up from 1976 to 2018 at Bellvitge University Hospital, Barcelona, Spain.

Results: Six homogeneous groups were identified after cluster analysis: C1 (n=47; 6.8%), C2 (n=85; 12.2%), C3 (n=153; 22%), C4 (n=29; 4.2%), C5 (n=168; 24.2%), and C6 (n=212; 30.5%). Presence of bilateral hilar lymphadenopathy (BHL) ranged from 65.5% (C4) to 97.9% (C1). Patients with Löfgren syndrome (LS) were distributed across 3 phenotypes (C1, C2, and C3). In contrast, phenotypes with pulmonary (PS) and/or extrapulmonary sarcoidosis (EPS) were represented by groups C4 (PS 100% with no EPS), C5 (PS 88.7% plus EPS), and C6 (EPS). EPS was concentrated in groups C5 (skin lesions, peripheral and abdominal lymph nodes, and hepatosplenic involvement) and C6 (skin lesions, peripheral lymph nodes, and neurological and ocular involvement). Unlike patients from LS groups, most patients with PS and/or EPS were treated with immunosuppressive therapy, and evolved to chronicity in higher proportion. Finally, the cluster model worked moderately well as a predictive model of chronicity (AUC=0.705).

Conclusion: Cluster analysis identified 6 different clinical patterns with similar phenotypic variables and predicted chronicity in our large cohort of patients with sarcoidosis. Classification of sarcoidosis into phenotypes with prognostic value may help physicians to improve the efficacy of clinical decisions.
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http://dx.doi.org/10.1016/j.ejim.2020.04.024DOI Listing
July 2020

Spanish scleroderma risk score (RESCLESCORE) to predict 15-year all-cause mortality in scleroderma patients at the time of diagnosis based on the RESCLE cohort: Derivation and internal validation.

Autoimmun Rev 2020 May 17;19(5):102507. Epub 2020 Mar 17.

Unit of Autoimmune Diseases, Department of Internal Medicine, Hospital Universitario Vall d'Hebron, Barcelona, Spain.

A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in derivation (DC) and validation cohort (VC). A multivariate analysis to detect variables related to all-cause mortality within the first 15 years from SSc diagnosis was performed, assigning points to the rounded beta values to create the score (RESCLESCORE). 1935 SSc patients were included. The variables in the final model were as follows: age at diagnosis (+2 points > 65 years-old), male gender (+1 point), lcSSc subset (-1 point), mode of onset other than Raynaud's (+1 point), cancer (+1 point) and visceral involvement, such as ILD (+1 point), PAH (+1 point), heart (+1 point) and renal involvement (+2 points). Autoantibodies did not achieve statistical significance in the multivariate analysis. The 3 categories of risk to predict 15-year all-cause mortality at the time of diagnosis were as follows: low risk (5% vs. 7%, p = .189), intermediate risk (26.5% vs. 25.5%, p = .911) and high risk (47.8% vs. 59%, p = .316). The AUC was 0.799 (DC) vs. 0.778 (VC) (p = .530). In conclusion, the RESCLESCORE demonstrated an excellent ability to categorize SSc patients at the time of diagnosis in separate 15-year all-cause mortality risk strata at the time of diagnosis.
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http://dx.doi.org/10.1016/j.autrev.2020.102507DOI Listing
May 2020

Sarcoidosis presenting with and without Löfgren's syndrome: Clinical, radiological and behavioral differences observed in a group of 691patients.

Joint Bone Spine 2020 Mar 11;87(2):141-147. Epub 2019 Oct 11.

Autoimmune Diseases Unit, Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain; Group of Evaluation of Health Determinants and Health Policies, Hestia Chair in Integrated Health and Social Care, Barcelona, Spain.

Objectives: Just a few series of Löfgren's syndrome have been reported. Our aim was to describe the epidemiology and clinical profile of sarcoidosis patients presenting with Löfgren's syndrome vs. non-Löfgren's syndrome.

Methods: Retrospective cohort study of 691consecutive patients with sarcoidosis diagnosed at the Bellvitge University Hospital in Barcelona, Spain, between 1976 and 2018.

Results: Three hundred and nine patients (44.7%) were diagnosed with Löfgren's syndrome and 382with non-Löfgren's syndrome (55.3%). The mean age at diagnosis was 39.8years-old (SD 11.7) vs. 46.6 (SD 14.5) (P<0.001). 249 patients (80.6%) vs. 218 (57.1%) were female (P<0.001), and mostly Caucasians (304, 98.4% vs. 351, 91.9%, P=0.002). Out of the total 309, Löfgren's syndrome patients developed more frequently fever and articular involvement, and 45 (14.6%) presented with isolated periarticular ankle inflammation. When compared, radiological stages at diagnosis were more advanced in non-Löfgren's syndrome patients: stage 0 (2.9% vs. 14.7%), stage I (82.5% vs. 41.4%), stage II (14.6% vs. 29.3%), and stage III/IV (0 vs. 14.7%) (P<0.001). Chronic trend>2years was more prevalent in non-Löfgren's syndrome (66, 22.6% vs. 233, 67.4%; P<0.001), as well as the proportion of patients in whom treatment was needed (58, 18.8% vs. 224, 58.6%; P<0.001). Risk factors related to chronic trend>2 years were older age, stage II at diagnosis and the need of treatment.

Conclusions: Löfgren's syndrome is a well-differentiated form of sarcoidosis with persuasive different epidemiological, clinical, radiological and prognostic features.
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http://dx.doi.org/10.1016/j.jbspin.2019.10.001DOI Listing
March 2020

Survival benefit of multidisciplinary care in amyotrophic lateral sclerosis in Spain: association with noninvasive mechanical ventilation.

J Multidiscip Healthc 2019 19;12:465-470. Epub 2019 Jun 19.

Internal Medicine Department, IDIBELL-Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.

Purpose: Multidisciplinary care has become the preferred model of care for patients with amyotrophic lateral sclerosis (ALS). It is assumed that the sum of interventions associated with this approach has a positive effect on survival. The objective of the study was to evaluate the impact of a multidisciplinary care approach on the survival of patients with ALS.

Patients And Methods: We performed a retrospective review of prospectively collected data in a tertiary referral center in Spain. Participants were patients with definite or probable ALS managed in a multidisciplinary care program. We compared demographic and survival data of patients with definite or probable ALS treated in a referral center without and with implementation of a multidisciplinary care program. We performed time-dependent multivariate survival analysis of the use of noninvasive mechanical ventilation (NIMV) and gastrostomy.

Results: We evaluated 398 consecutive patients, of whom 54 were treated by a general neurologist and 344 were treated in the multidisciplinary care clinic. Patients receiving multidisciplinary care were older (62 vs 58 years), tended to have bulbar onset disease (30% vs 17.7%), and were more likely to receive riluzole (88.7% vs 29.6%, <0.01), NIMV (48.8% vs 29.6%, >0.001), and nutrition via gastrostomy (32.3% vs 3.7%, <0.01). Kaplan-Meier analysis showed a 6-month increase in survival (log-rank, 16.03, <0.001). Application of the Andersen-Gill model showed that the variables associated with reduced mortality were reduced time to NIMV and gastrostomy and the duration of both, thus reflecting compliance.

Conclusions: Multidisciplinary care increased the survival of ALS patients in our study population. Timely use of respiratory support and gastrostomy are fundamental aspects of this benefit.
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http://dx.doi.org/10.2147/JMDH.S205313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590410PMC
June 2019

A Mediterranean Diet Rich in Extra-Virgin Olive Oil Is Associated with a Reduced Prevalence of Nonalcoholic Fatty Liver Disease in Older Individuals at High Cardiovascular Risk.

J Nutr 2019 11;149(11):1920-1929

Ciber Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

Background: Adherence to a Mediterranean diet (MedDiet) is thought to reduce liver steatosis.

Objectives: To explore the associations with liver steatosis of 3 different diets: a MedDiet + extra-virgin olive oil (EVOO), MedDiet + nuts, or a control diet.

Methods: This was a subgroup analysis nested within a multicenter, randomized, parallel-group clinical trial, PREvención con DIeta MEDiterránea (PREDIMED trial: ISRCTN35739639), aimed at assessing the effect of a MedDiet on the primary prevention of cardiovascular disease. One hundred men and women (mean age: 64 ± 6 y), at high cardiovascular risk (62% with type 2 diabetes) from the Bellvitge-PREDIMED center were randomly assigned to a MedDiet supplemented with EVOO, a MedDiet supplemented with mixed nuts, or a control diet (advice to reduce all dietary fat). No recommendations to lose weight or increase physical activity were given. Main measurements were the percentage of liver fat and the diagnosis of steatosis, which were determined by NMR imaging. The association of diet with liver fat content was analyzed by bivariate analysis after a median follow-up of 3 y.

Results: Baseline adiposity and cardiometabolic risk factors were similar among the 3 treatment arms. At 3 y after the intervention hepatic steatosis was present in 3 (8.8%), 12 (33.3%), and 10 (33.3%) of the participants in the MedDiet + EVOO, MedDiet + nuts, and control diet groups, respectively (P = 0.027). Respective mean values of liver fat content were 1.2%, 2.7%, and 4.1% (P = 0.07). A tendency toward significance was observed for the MedDiet + EVOO group compared with the control group. Median values of urinary 12(S)-hydroxyeicosatetraenoic acid/creatinine concentrations were significantly (P = 0.001) lower in the MedDiet + EVOO (2.3 ng/mg) than in the MedDiet + nuts (5.0 ng/mg) and control (3.9 ng/mg) groups. No differences in adiposity or glycemic control changes were seen between groups.

Conclusions: An energy-unrestricted MedDiet supplemented with EVOO, a food with potent antioxidant and anti-inflammatory properties, is associated with a reduced prevalence of hepatic steatosis in older individuals at high cardiovascular risk.
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http://dx.doi.org/10.1093/jn/nxz147DOI Listing
November 2019
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