Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

SYNTAX Score is associated with worse outcomes after off-pump coronary artery bypass grafting surgery for three-vessel or left main complex coronary disease

ObjectiveThe SYNergy between percutaneous intervention with TAXus drug eluting stents and cardiac surgery (SYNTAX) Score is a tool for risk stratification of patients according to the complexity of coronary lesions developed during the SYNTAX trial. We examined the influence of the SYNTAX Score on the incidence of major adverse cardiac and cerebrovascular events.MethodsAll patients with de novo left main or 3-vessel disease undergoing coronary artery bypass grafting from January 2005 to December 2008 at our institution (Hospital Clínico San Carlos, Madrid, Spain) were retrospectively assessed, and their SYNTAX Score was calculated. The influence of the SYNTAX Score on postprocedural and follow-up mortality and combined major adverse cardiac and cerebrovascular events (including death, myocardial infarction, cerebrovascular accident, and repeat revascularization) was identified by multivariate analysis. Balancing score analysis was performed to eliminate the effect of potential confounders.ResultsA total of 716 patients were enrolled. Mean SYNTAX Score was 34.5 (standard deviation, 6.7; range, 11.5–76). Three groups of patients were identified according to the score terciles: low (≤33), intermediate (33–37), and high (>37). These terciles scores differed greatly from those reported by the SYNTAX trial investigators. The multivariate analysis identified that the SYNTAX Score was associated with follow-up mortality (hazard ratio = 1.046, P = .015) and combined early and follow-up major adverse cardiac and cerebrovascular events (odds ratio = 1.079, P < .001; and hazard ratio = 1.034, P = .026, respectively). Balancing score-adjusted analyses demonstrated that the SYNTAX Score was independently associated with early and late major adverse cardiac and cerebrovascular events (odds ratio = 1.65, P < .001; and hazard ratio = 1.034, P = .027, respectively).ConclusionsSYNTAX Score was remarkably high among patients undergoing surgical off-pump myocardial revascularization at our institution. In this subset of patients, a higher SYNTAX Score was associated with a higher incidence of in-hospital and follow-up major adverse cardiac and cerebrovascular events after coronary artery bypass grafting, but not with early or late mortality

Variations in Chronic Obstructive Pulmonary Disease Outpatient Care in Respiratory Clinics: Results From the 2021 EPOCONSUL Audit

Introduction: The aim of our work has been to describe the results of the clinical audit carried out in 2021 and to compare the results with 2015 EPOCONSUL audit. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021, and January 31, 2022. Results: A total of 45 hospitals participated in the 2021 audit and 4.225 clinical records of patients were evaluated. Clinical phenotype according to the Spanish National Guidelines for COPD care (GesEPOC) was reported in 63.1% of the audited patients, and the COPD type assessment for the Global initiative for chronic Obstructive Lung Disease (GOLD) was present in 38.3%. There was an improved compliance with clinical practice guideline (CPG) recommendations in the 2021 audit with respect to the 2015 audit. There was an increase in the proportion of cases with alfa-1-antitrypsin serum level testing available (audit 1: 18.9%; audit 2: 38.7%, p<0.001) and 6-min walk test carried out (audit 1: 24%; audit 2: 45.2%, p<0.001). However, these significant variations adherence to CPG recommendations were not reached for the clinical evaluation and therapeutic intervention category when adjusting for patient and resource variables. Conclusions: The 2021 EPOCONSUL audit showed increased adherence to recommendations although they seem to be related to the availability of resources for care. These results should be taken into account in order to establish improvements in resources to achieve a better quality of care.Depto. de MedicinaFac. de MedicinaTRUEpu

Detection of Alpha-1 Antitrypsin Levels in Chronic Obstructive Pulmonary Disease in Respiratory Clinics in Spain: Results of the EPOCONSUL 2021 Audit

Background: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021–2022, as well as to compare with a previous audit conducted in 2014–2015. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. Results: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 p p p p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. Conclusions: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit

Objective: The aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022. Results: 4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p300mm3 [OR: 2.16 (1.10-4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15-4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41-2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29-7.41), p<0.011]. Conclusions: Inhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy.Depto. de MedicinaFac. de MedicinaTRUEpu

Variations in Chronic Obstructive Pulmonary Disease Outpatient Care in Respiratory Clinics: Results From the 2021 EPOCONSUL Audit

[Introduction] The aim of our work has been to describe the results of the clinical audit carried out in 2021 and to compare the results with 2015 EPOCONSUL audit.[Methods] EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021, and January 31, 2022.[Results] A total of 45 hospitals participated in the 2021 audit and 4.225 clinical records of patients were evaluated. Clinical phenotype according to the Spanish National Guidelines for COPD care (GesEPOC) was reported in 63.1% of the audited patients, and the COPD type assessment for the Global initiative for chronic Obstructive Lung Disease (GOLD) was present in 38.3%. There was an improved compliance with clinical practice guideline (CPG) recommendations in the 2021 audit with respect to the 2015 audit. There was an increase in the proportion of cases with alfa-1-antitrypsin serum level testing available (audit 1: 18.9%; audit 2: 38.7%, p < 0.001) and 6-min walk test carried out (audit 1: 24%; audit 2: 45.2%, p < 0.001). However, these significant variations adherence to CPG recommendations were not reached for the clinical evaluation and therapeutic intervention category when adjusting for patient and resource variables.[Conclusions] The 2021 EPOCONSUL audit showed increased adherence to recommendations although they seem to be related to the availability of resources for care. These results should be taken into account in order to establish improvements in resources to achieve a better quality of care.This study has been promoted and sponsored by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR).Peer reviewe

Determinants of medical prescriptions for COPD care: an analysis of the EPOCONSUL clinical audit

Purpose: Current COPD management recommendations indicate that pharmacological treatment can be stepped up or down, but there are no recommendations on how to make this adjustment. We aimed to describe pharmacological prescriptions during a routine clinical visit for COPD and study the determinants of changing therapy. Methods: EPOCONSUL is a Spanish nationwide observational cross-sectional clinical audit with prospective case recruitment including 4,508 COPD patients from outpatient respiratory clinics for a period of 12 months (May 2014–May 2015). Prescription patterns were examined in 4,448 cases and changes analyzed in stepwise backward, binomial, multivariate, logistic regression models. Results: Patterns of prescription of inhaled therapy groups were no treatment prescribed, 124 (2.8%) cases; one or two long-acting bronchodilators (LABDs) alone, 1,502 (34.6%) cases; LABD with inhaled corticosteroids (ICSs), 389 (8.6%) cases; and triple therapy cases, 2,428 (53.9%) cases. Incorrect prescriptions of inhaled therapies were observed in 261 (5.9%) cases. After the clinical visit was audited, 3,494 (77.5%) cases did not modify their therapeutic prescription, 307 (6.8%) cases had a step up, 238 (5.3%) cases had a change for a similar scheme, 182 (4.1%) cases had a step down, and 227 (5.1%) cases had other nonspecified change. Stepping-up strategies were associated with clinical presentation (chronic bronchitis, asthma-like symptoms, and exacerbations), a positive bronchodilator test, and specific inhaled medication groups. Stepping down was associated with lung function impairment, ICS containing regimens, and nonexacerbator phenotype. Conclusion: The EPOCONSUL study shows a comprehensive evaluation of pharmacological treatments in COPD care, highlighting strengths and weaknesses, to help us understand how physicians use available drugs.Sociedad Española de Neumología y Cirugía TorácicaDepto. de MedicinaFac. de MedicinaTRUEpu

The Spanish version of the Constant-Murley Shoulder Score: translation, cultural adaptation, and validity

Background: The Constant-Murley Score (CMS) is one of the most employed tools for assessing shoulder function. It was first devised in 1987 for the English population and is now widely used internationally. However, it had yet to be cross-culturally adapted and validated to Spanish, which is the world's second-most native language. Formal adaptation and validation of clinical scores is paramount for them to be used with rigorous scientific methodology. Methods: Following international recommendations for the cross-cultural adaptation of self-report measures, the CMS was first adapted into Spanish in six stages: translation, synthesis, back-translation, a review by expert committee, pretesting, and final appraisal by expert committee. After conducting a pretest with 30 individuals, the Spanish version of the CMS was tested on 104 patients with various shoulder pathologies to assess content, construct, criterion validity, and reliability. Results: No major conflicts were encountered in the process of cross-cultural adaptation, with 96.7% of pretested patients having a full understanding of every item in the test. The validation showed excellent content validity (content validity index = .90), construct validity (strong correlation between items within the same subsection of the test), and criterion validity (CMS - Simple Shoulder Test, Pearson r = .587, P = .01; CMS - American Shoulder and Elbow Surgeons, Pearson r = .690, P = .01). Reliability of the test was also excellent, with high internal consistency (Cronbach's α = .819), interrater reliability (intraclass correlation coefficient = .982), and intrarater reliability (intraclass correlation coefficient = .937), without showing ceiling or floor effects. Conclusion: Spanish version of the CMS has been proved to accurately reproduce the original score and to be easily comprehensible by native Spanish speakers with acceptable intrarater-interrater reliability and construct validity. INTRODUCCIóN: La escala de Constant-Murley (CMS) es una de las más empleadas para evaluar la función del hombro. Se ideó por primera vez para la población inglesa en 1987 y actualmente es ampliamente empleada a nivel internacional. Sin embargo, su validación y adaptación transcultural no se han realizado al español, la segunda lengua nativa más hablada en el mundo. Actualmente no puede resultar admisible el empleo de escalas en las que no tengamos la seguridad de que existe una equivalencia conceptual, cultural y lingüística entre la versión original y la empleada. MATERIAL Y MéTODO: La versión traducida al español de la CMS se realizó siguiendo las recomendaciones internacionales: traducción, síntesis de la traducción, retrotraducción, revisión por comité de expertos, pretest y validación. Tras la realización del pretest en 30 individuos, la versión española de la escala de CMS se probó en 104 pacientes con diferentes patologías de hombro para evaluar las propiedades psicométricas de la escala: contenido, constructo, validez de criterio y fiabilidad. Resultados: No se encontraron problemas importantes durante el proceso de adaptación transultural con un entendimiento completo de todos los ítems del pretest por el 96.7% de los pacientes. La escala adaptada demostró una excelente validez de contenido (índice de validez de contenido = .90), de constructo (fuerte correlación entre ítems de la misma subsección del test), y de criterio (CMS-SST Pearson's r = .587, p = .01; CMS-ASES Pearson's r = .690, p = .01). La Fiabilidad del test resultó excelente, con una elevada consistencia interna (Cronbach's α = .819), fiabilidad interobservador (ICC = .982) e intraobservador (ICC = .937), sin efectos techo y suelo. CONCLUSIóN: La versión Española de la CMS garantiza la equivalencia con respecto al cuestionario original. Los presentes resultados, sugieren que esta versión es válida, fiable y reproducible para la evaluación de la patología de hombro en nuestro entorno.Depto. de CirugíaFac. de MedicinaTRUEpu

Determinants of medical prescriptions for COPD care: an analysis of the EPOCONSUL clinical audit.

Current COPD management recommendations indicate that pharmacological treatment can be stepped up or down, but there are no recommendations on how to make this adjustment. We aimed to describe pharmacological prescriptions during a routine clinical visit for COPD and study the determinants of changing therapy. EPOCONSUL is a Spanish nationwide observational cross-sectional clinical audit with prospective case recruitment including 4,508 COPD patients from outpatient respiratory clinics for a period of 12 months (May 2014-May 2015). Prescription patterns were examined in 4,448 cases and changes analyzed in stepwise backward, binomial, multivariate, logistic regression models. Patterns of prescription of inhaled therapy groups were no treatment prescribed, 124 (2.8%) cases; one or two long-acting bronchodilators (LABDs) alone, 1,502 (34.6%) cases; LABD with inhaled corticosteroids (ICSs), 389 (8.6%) cases; and triple therapy cases, 2,428 (53.9%) cases. Incorrect prescriptions of inhaled therapies were observed in 261 (5.9%) cases. After the clinical visit was audited, 3,494 (77.5%) cases did not modify their therapeutic prescription, 307 (6.8%) cases had a step up, 238 (5.3%) cases had a change for a similar scheme, 182 (4.1%) cases had a step down, and 227 (5.1%) cases had other nonspecified change. Stepping-up strategies were associated with clinical presentation (chronic bronchitis, asthma-like symptoms, and exacerbations), a positive bronchodilator test, and specific inhaled medication groups. Stepping down was associated with lung function impairment, ICS containing regimens, and nonexacerbator phenotype. The EPOCONSUL study shows a comprehensive evaluation of pharmacological treatments in COPD care, highlighting strengths and weaknesses, to help us understand how physicians use available drugs