Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. METHODS: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. RESULTS: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64-92.5) vs. 99 (88-105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467-600) vs. 611 (550-650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VCO2 slope 32 (28.1-37.4) vs. 29.4 (26.9-31.4); p = 0.022) and high PETCO2 (34.5 (32-39) vs. 38 (36-40); p = 0.025). INTERPRETATION: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

An increase of microRNA-16-1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR-HPV in liquid cytology samples.

Studies of cervical cancer (CC) have reported that microRNA-16-1 (miR-16-1), which is an oncomiR, is increased in the tissues and cell lines of CC. The aim of the present study was to investigate the association of miRNA-16-1 expression level with squamous cell carcinoma (SCC), the presence of squamous intraepithelial lesions (SIL) and the integration of high-risk human papillomavirus (HR-HPV) DNA. The current study analyzed 80 samples obtained from women by liquid-based cytology, which revealed that 20 were negative for SIL (NSIL) and without HPV, 20 were low-grade SIL (LSIL), 20 were high-grade SIL (HSIL), and 20 were diagnosed as SCC with HR-HPV. The genotyping of the viral DNA was conducted via an INNO-LiPA-HPV array, the expression of miR-16-1 was determined by reverse transcription-quantitative PCR, and the physical state of the HR-HPV was ascertained by in situ hybridization with amplification with tyramide. A total of eight HR-HPV genotypes were distinguished; the most frequent of these being HPV16, followed by multiple infection with HR-HPV (including HPV16). The mixed state of the HR-HPV was observed in 60 and 65% of LSIL and HSIL cases, respectively, while an integrated HR-HPV state was identified in 90% of cases with SCC. The expression level of miR-16-1 increased according to the grade of SIL, and cases with HSIL exhibited a significantly higher miR-16-1 expression level compared with women with NSIL (P<0.001; Table II). It can therefore be determined that the expression of miR-16-1 effects cellular proliferation, due to the viral integration of various HR-HPV genotypes in unique infection or in multiple infection. Thus, the overexpression of miR-16-1 could be monitored in women with LSIL, in order to discard a major lesion.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

Influencia de la estructura de los afectos en la evaluación de la artritis reumatoide mediante la escala visual analógica de dolor, el HAQ y el DAS28 / Influence of the structure of mood in the assessment of rheumatoid arthritis through the visual analog scale for pain, HAQ and DAS28

Objetivo: Analizar el efecto de la estructura del afecto en las siguientes herramientas de evaluación de la artritis reumatoide: escala visual analógica (EVA) de dolor, HAQ y DAS28. Pacientes y métodos: Se estudiaron 86 pacientes con artritis reumatoide de reciente comienzo, de los que el 75,7% eran mujeres, con una mediana de edad al inicio de la enfermedad de 55 años. A todos los pacientes se les aplicó la versión adaptada a población española del cuestionario PANAS que evalúa las componentes de afecto positivo (AP) y negativo (AN). Los pacientes pertenecían al registro de artritis de reciente comienzo de nuestro centro por lo que se disponía de información clínica de los enfermos en 282 visitas. Para determinar el efecto de AP y AN en cada una de nuestras variables dependientes se estimaron 3 modelos de regresión lineal multivariable mediante modelos lineales generalizados usando el comando glm del programa Stata 10.1. Resultados: El promedio de la puntuación de AP y AN en nuestros pacientes fue similar al descrito para la población española sana. Las puntuaciones elevadas en la subescala de AN se asociaron a peores puntuaciones, tanto en la EVA de dolor, como en el HAQ. Por el contrario, puntuaciones elevadas en AP se asociaron con una mejor evolución de la actividad de la enfermedad medida por el DAS28. Conclusión: La estructura del afecto puede influir en las herramientas que utilizamos para la evaluación de los pacientes con artritis reumatoide, por lo que podría ser recomendable incluir la realización del PANAS como parte de dicha evaluación (AU)

Objective: To analyze the effect of the structure of mood over the following assessment tools for rheumatoid arthritis: visual analog scale (VAS) for pain, HAQ and DAS28. Patients and methods: We studied 86 patients with recent onset rheumatoid arthritis, of which 75.7% were female, with a mean age at disease onset of 55 years. All patients were administered the Spanish version of the PANAS questionnaire that evaluates the components of positive (PA) and negative mood (AN). Patients belonged to the registry of new-onset arthritis in our center so clinical information was available for 282 patients visits. To determine the effect of PA and AN on each of the dependent variables we performed three multivariate linear regression models using generalized linear models through the Stata glm command 10.1. Results: The mean score for PA and AN in our patients was similar to that described for the healthy Spanish population. The high scores on the subscale of AN were associated with worse scores in both the VAS for pain and the HAQ. By contrast, high scores on PA were associated with better outcomes of disease activity measured by DAS28. Conclusion: The structure of mood may influence the tools we use for evaluating patients with rheumatoid arthritis, so it might be advisable to include the PANAS questionnaire as part of that assessment (AU)

Influence of the structure of mood in the assessment of rheumatoid arthritis through the visual analog scale for pain, HAQ and DAS28.

OBJECTIVE: To analyze the effect of the structure of mood over the following assessment tools for rheumatoid arthritis: visual analog scale (VAS) for pain, HAQ and DAS28. PATIENTS AND METHODS: We studied 86 patients with recent onset rheumatoid arthritis, of which 75.7% were female, with a mean age at disease onset of 55 years. All patients were administered the Spanish version of the PANAS questionnaire that evaluates the components of positive (PA) and negative mood (AN). Patients belonged to the registry of new-onset arthritis in our center so clinical information was available for 282 patients visits. To determine the effect of PA and AN on each of the dependent variables we performed three multivariate linear regression models using generalized linear models through the Stata glm command 10.1. RESULTS: The mean score for PA and AN in our patients was similar to that described for the healthy Spanish population. The high scores on the subscale of AN were associated with worse scores in both the VAS for pain and the HAQ. By contrast, high scores on PA were associated with better outcomes of disease activity measured by DAS28. CONCLUSION: The structure of mood may influence the tools we use for evaluating patients with rheumatoid arthritis, so it might be advisable to include the PANAS questionnaire as part of that assessment.

Interleukin 15 levels in serum may predict a severe disease course in patients with early arthritis.

BACKGROUND: Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). METHODOLOGY AND RESULTS: Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (ß Coefficient [95% confidence interval]: 0.12 [0.06-0.18]; p<0.001) or ACPA (0.34 [0.01-0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18-2.7; p = 0.007). CONCLUSIONS: Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatment.

Estimated cutoff points for the 28-joint disease activity score based on C-reactive protein in a longitudinal register of early arthritis.

OBJECTIVE: To estimate the cutoff points for the 28-joint Disease Activity Score (DAS28) calculated using C-reactive protein (CRP) measurements from patients with early arthritis. METHODS: We analyzed data from 568 visits of 207 patients enrolled in our prospective longitudinal register of early arthritis. Six rheumatologists evaluated the degree of disease activity at each visit on the basis of the available clinical data, and the final degree of disease activity was established by consensus. DAS28 values were calculated for each visit using CRP or erythrocyte sedimentation rate (ESR). Through a ROC analysis, cutoff points for both indices, as well as for minimal disease activity (MDA), were selected on the basis of the best tradeoff values between sensitivity and specificity. RESULTS: The cutoff values to classify disease activity with the DAS28-CRP were 2.3, 3.8, and 4.9, considering remission at < 2.3, low disease activity 2.3-3.8, moderate disease activity 3.8-4.9, and high disease activity > 4.9. The cutoff value for MDA when calculated with CRP was 2.6. The area under the ROC curves was always greater for DAS28-CRP than for DAS28-ESR, reaching statistical significance for low/moderate activity and for the MDA. CONCLUSION: Our study confirms that the cutoff points for DAS28-CRP are lower than those described for DAS28-ESR, suggesting that DAS28-CRP may be more accurate to assess disease activity in our population.