Obtaining patient phenotypes in SARS-CoV-2 pneumonia, and their association with clinical severity and mortality.

BACKGROUND: There exists consistent empirical evidence in the literature pointing out ample heterogeneity in terms of the clinical evolution of patients with COVID-19. The identification of specific phenotypes underlying in the population might contribute towards a better understanding and characterization of the different courses of the disease. The aim of this study was to identify distinct clinical phenotypes among hospitalized patients with SARS-CoV-2 pneumonia using machine learning clustering, and to study their association with subsequent clinical outcomes as severity and mortality. METHODS: Multicentric observational, prospective, longitudinal, cohort study conducted in four hospitals in Spain. We included adult patients admitted for in-hospital stay due to SARS-CoV-2 pneumonia. We collected a broad spectrum of variables to describe exhaustively each case: patient demographics, comorbidities, symptoms, physiological status, baseline examinations (blood analytics, arterial gas test), etc. For the development and internal validation of the clustering/phenotype models, the dataset was split into training and test sets (50% each). We proposed a sequence of machine learning stages: feature scaling, missing data imputation, reduction of data dimensionality via Kernel Principal Component Analysis (KPCA), and clustering with the k-means algorithm. The optimal cluster model parameters -including k, the number of phenotypes- were chosen automatically, by maximizing the average Silhouette score across the training set. RESULTS: We enrolled 1548 patients, each of them characterized by 92 clinical attributes (d=109 features after variable encoding). Our clustering algorithm identified k=3 distinct phenotypes and 18 strongly informative variables: Phenotype A (788 cases [50.9% prevalence] - age ∼ 57, Charlson comorbidity ∼ 1, pneumonia CURB-65 score ∼ 0 to 1, respiratory rate at admission ∼ 18 min-1, FiO2 ∼ 21%, C-reactive protein CRP ∼ 49.5 mg/dL [median within cluster]); phenotype B (620 cases [40.0%] - age ∼ 75, Charlson ∼ 5, CURB-65 ∼ 1 to 2, respiration ∼ 20 min-1, FiO2 ∼ 21%, CRP ∼ 101.5 mg/dL); and phenotype C (140 cases [9.0%] - age ∼ 71, Charlson ∼ 4, CURB-65 ∼ 0 to 2, respiration ∼ 30 min-1, FiO2 ∼ 38%, CRP ∼ 152.3 mg/dL). Hypothesis testing provided solid statistical evidence supporting an interaction between phenotype and each clinical outcome: severity and mortality. By computing their corresponding odds ratios, a clear trend was found for higher frequencies of unfavourable evolution in phenotype C with respect to B, as well as more unfavourable in phenotype B than in A. CONCLUSION: A compound unsupervised clustering technique (including a fully-automated optimization of its internal parameters) revealed the existence of three distinct groups of patients - phenotypes. In turn, these showed strong associations with the clinical severity in the progression of pneumonia, and with mortality.

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

Bacteremic pneumococcal pneumonia: arrhythmogenic disease

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Bacteraemic pneumococcal pneumonia and SARS-CoV-2 pneumonia: differences and similarities.

OBJECTIVE: To analyse differences in clinical presentation and outcome between bacteraemic pneumococcal community-acquired pneumonia (B-PCAP) and sSvere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pneumonia. METHODS: This observational multi-centre study was conducted on patients hospitalized with B-PCAP between 2000 and 2020 and SARS-CoV-2 pneumonia in 2020. Thirty-day survival, predictors of mortality, and intensive care unit (ICU) admission were compared. RESULTS: In total, 663 patients with B-PCAP and 1561 patients with SARS-CoV-2 pneumonia were included in this study. Patients with B-PCAP had more severe disease, a higher ICU admission rate and more complications. Patients with SARS-CoV-2 pneumonia had higher in-hospital mortality (10.8% vs 6.8%; P=0.004). Among patients admitted to the ICU, the need for invasive mechanical ventilation (69.7% vs 36.2%; P<0.001) and mortality were higher in patients with SARS-CoV-2 pneumonia. In patients with B-PCAP, the predictive model found associations between mortality and systemic complications (hyponatraemia, septic shock and neurological complications), lower respiratory reserve and tachypnoea; chest pain and purulent sputum were protective factors in these patients. In patients with SARS-CoV-2 pneumonia, mortality was associated with previous liver and cardiac disease, advanced age, altered mental status, tachypnoea, hypoxaemia, bilateral involvement, pleural effusion, septic shock, neutrophilia and high blood urea nitrogen; in contrast, ≥7 days of symptoms was a protective factor in these patients. In-hospital mortality occurred earlier in patients with B-PCAP. CONCLUSIONS: Although B-PCAP was associated with more severe disease and a higher ICU admission rate, the mortality rate was higher for SARS-CoV-2 pneumonia and deaths occurred later. New prognostic scales and more effective treatments are needed for patients with SARS-CoV-2 pneumonia.

RDW-based clinical score to predict long-term survival in community-acquired pneumonia: a European derivation and validation study.

An excess long-term mortality has been observed in patients who were discharged after a community-acquired pneumonia (CAP), even after adjusting for age and comorbidities. We aimed to derive and validate a clinical score to predict long-term mortality in patients with CAP discharged from a general ward. In this retrospective observational study, we derived a clinical risk score from 315 CAP patients discharged from the Internal Medicine ward of Cuneo Hospital, Italy, in 2015-2016 (derivation cohort), which was validated in a cohort of 276 patients discharged from the pneumology service of the Barakaldo Hospital, Spain, from 2015 to 2017, and from two internal medicine wards at the Turin University and Cuneo Hospital, Italy, in 2017. The main outcome was the 18-month follow-up all-cause death. Cox multivariate analysis was used to identify the predictive variables and develop the clinical risk score in the derivation cohort, which we applied in the validation cohort. In the derivation cohort (median age: 79 years, 54% males, median CURB-65 = 2), 18-month mortality was 32%, and 18% in the validation cohort (median age 76 years, 55% males, median CURB-65 = 2). Cox multivariate analysis identified the red blood cell distribution width (RDW), temperature, altered mental status, and Charlson Comorbidity Index as independent predictors. The derived score showed good discrimination (c-index 0.76, 95% CI 0.70-0.81; and 0.83, 95% CI 0.78-0.87, in the derivation and validation cohort, respectively), and calibration. We derived and validated a simple clinical score including RDW, to predict long-term mortality in patients discharged for CAP from a general ward.

Alteración funcional pulmonar en el seguimiento precoz de pacientes con neumonía por COVID-19 / Pulmonary Function in Early Follow-up of patients with COVID-19 Pneumonia

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Factors Associated with Depression in COPD: A Multicenter Study.

INTRODUCTION: Depression is a prevalent comorbidity in COPD and has an impact on the prognosis of these patients, thereby making it important to study the factors associated with depression in patients with COPD. METHOD: A multicenter, observational and cross-sectional study was conducted to study the factors associated with depression in patients with COPD measured by the hospital anxiety and depression (HAD) questionnaire. We analyzed anthropometric variables and the number of exacerbations in the previous year and calculated the 6-min walking test and the body mass index, airflow obstruction, dyspnea, and exercise (BODE) index. All the patients completed the quality of life EQ-5D and the LCADL physical activity questionnaires. The relationship of these variables with depression was evaluated with two multiple logistic regression models. RESULTS: One hundred fifteen patients were evaluated (93 % male) with a mean age of 66.9 years (SD 8.8) and a mean FEV1 % of 44.4 % (SD 15.7 %). 24.3 % presented symptoms of depression (HAD-D > 8). These latter patients had worse lung function, greater dyspnea, reduced exercise capacity, a higher score in the BODE index, poorer quality of life, reduced physical activity, and more exacerbations. In the first logistic regression model, quality of life and the BODE index were associated with depression (AUC: 0.84; 0.74-0.94). In the second model including the variables in the BODE index, quality of life and dyspnea measured with the MRC scale (AUC: 0.87; 0.79-0.95) were associated with depression. CONCLUSIONS: Nearly one-quarter of the patients with COPD in this study presented clinically significant depression associated with worse quality of life, reduced exercise capacity, greater dyspnea, and a higher score in the BODE index.

Factors associated with high healthcare resource utilisation among COPD patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) places a huge economic burden on healthcare systems, especially patients with frequent exacerbations and co-morbidities. OBJECTIVES: To identify factors associated with high utilisation of healthcare resources in a population of patients with COPD. METHOD: We conducted an observational, cross-sectional, multicentre study with the aim of identifying the factors associated with high resource utilisation among patients with COPD. Sociodemographic and anthropometric characteristics of the study population, as well as data on health-related quality of life, respiratory symptoms, presence of anxiety and depression, physical activity and lung function were collected. We examined the relationship between these variables and high utilisation of healthcare resources, by performing a multivariate analysis based on a logistic regression model. RESULTS: 115 patients (64 were high users of healthcare resources, and 51 control patients) from 13 hospitals were selected. Patients presenting high resource utilisation had worse FEV1, worse basal SpO2, less distance walked in the 6-minute walk test, and increased dyspnoea. They also had a worse BODE index, worse scores in all dimensions of the EURO-QOL 5D and the LCADL scale, and displayed a higher prevalence of depression. Multivariate analysis yielded a statistically significant association between SpO2, LCADL scores, serum fibrinogen values and total leukocyte count, and high healthcare resource utilisation. CONCLUSIONS: COPD patients who incur higher healthcare resource utilisation show reduced physical activity, increased respiratory failure and increased systemic inflammation.

Evaluación diagnóstica y pronóstica del paciente con hipertensión pulmonar / Diagnostic and prognostic evaluation in patients with pulmonary hypertension

La hipertensión pulmonar (HP) es un trastorno hemodinámico que se puede observar en el contexto de una serie de patologías de diferente índole. Se define por la presencia de un valor medio de presión en arteria pulmonar (PAPm) ≥ 25 mmHg. Desde un punto de vista clínico, se clasifica en 5 grupos; de ellos el grupo I o hipertensión arterial pulmonar, aunque infrecuente, merece especial consideración por las implicaciones terapéuticas específicas que conlleva. Sobre la base de una sospecha clínica y/o resultado de un ecocardiograma, el diagnóstico de esta entidad se basa en el seguimiento de un estricto protocolo que debe incluir la realización de un cateterismo cardiaco derecho. La HP es una enfermedad progresiva y grave cuyo pronóstico va a depender fundamentalmente del grado de afectación del ventrículo derecho. Una vez confirmado el diagnóstico, resulta indispensable evaluar la gravedad del cuadro para instaurar el tratamiento más acorde a la situación clínica del paciente. Para ello, utilizaremos diversos parámetros clínicos, biológicos, ecocardiográficos-hemodinámicos y relacionados con la capacidad de esfuerzo (AU)

Pulmonary hypertension (PH) is a hemodynamic disorder that occurs in a series of distinct diseases and is defined by the presence of a mean pulmonary artery pressure of ≥ 25 mm Hg. Clinically, this disorder is classified in five groups. Of these, group I, or pulmonary arterial hypertension (PAH), although infrequent, deserves special attention due to the specific therapeutic implications involved. Based on clinical suspicion and/or the results of echocardiogram, the diagnosis of this entity is established by following a strict protocol that should include right-sided cardiac catheterization. PH is a severe, progressive disease whose prognosis mainly depends on the degree of right ventricular involvement. Once the diagnosis has been confirmed, severity must be evaluated to initiate the most appropriate treatment for the patient’s status. To do this, several clinical, biological, and echocardiographic-hemodynamic parameters and indicators of exercise capacity can be used (AU)

[Diagnostic and prognostic evaluation in patients with pulmonary hypertension]. / Evaluación diagnóstica y pronóstica del paciente con hipertensión pulmonar.

Pulmonary hypertension (PH) is a hemodynamic disorder that occurs in a series of distinct diseases and is defined by the presence of a mean pulmonary artery pressure of ≥ 25 mm Hg. Clinically, this disorder is classified in five groups. Of these, group I, or pulmonary arterial hypertension (PAH), although infrequent, deserves special attention due to the specific therapeutic implications involved. Based on clinical suspicion and/or the results of echocardiogram, the diagnosis of this entity is established by following a strict protocol that should include right-sided cardiac catheterization. PH is a severe, progressive disease whose prognosis mainly depends on the degree of right ventricular involvement. Once the diagnosis has been confirmed, severity must be evaluated to initiate the most appropriate treatment for the patient's status. To do this, several clinical, biological, and echocardiographic-hemodynamic parameters and indicators of exercise capacity can be used.

Tromboembolismo pulmonar / Pulmonary thromboembolism

El tromboembolismo pulmonar es una enfermedad frecuente en los servicios de urgencias. A menudo, representaun problema diagnóstico, por lo que es necesario utilizar estrategias adecuadas. La información clínica,los datos de laboratorio como el D-dímero y las técnicas de imagen, como la angiografía por tomografía computarizada,la ecografía Doppler, la gammagrafía de ventilación-perfusión o la ecocardiografía, ayudan a establecerla probabilidad diagnóstica y la gravedad del paciente. Disponiendo de toda esta información se puedenconstruir escalas de riesgo, como la escala PESI, con elevada sensibilidad para establecer la posibilidad defallecimiento. El tratamiento debe iniciarse rápidamente con heparina, en general de bajo peso molecular. Sila situación es de riesgo alto puede estar indicado el uso de fibrinolíticos, poniendo especial atención en queno exista ninguna contraindicación. En algunos casos, puede ser necesario soporte hemodinámico(AU)

Pulmonary thromboembolism is a frequent disease in emergency departments and often poses a diagnosticchallenge that requires appropriate strategies. Clinical information, laboratory tests such as a D-dimer andimaging techniques such as computed tomography (CT) angiography, ventilation-perfusion scintigraphy orechocardiography help to establish clinical probability and the severity of the disease. With all thisinformation, risk scores can be constructed, such as the Pulmonary Embolism Severity Index (PESI) score,which has high sensitivity in predicting mortality. Treatment should be started immediately with heparin,usually low molecular weight heparin. If the patient is at high risk, thrombolytic therapy is indicated, althoughpossible contraindications should be thoroughly assessed. Supportive treatment may be considered in a fewpatients(AU)

Circulación pulmonar: aportaciones del año 2009 / Pulmonary Circulation: Contributions of the Year 2009

Durante el año 2009 se ha publicado un importante número de estudios en el ámbito de las enfermedadescirculatorias pulmonares que probablemente tengan un impacto clínico notable. El tratamiento anticoagulanteestá en puertas de experimentar un cambio signifi cativo con la llegada de los nuevos fármacos oralescon efecto inhibitorio en el factor X (rivaroxaban, apixaban) o la trombina (dabigatran). Nuevos estudioshan mostrado una efi cacia comparable a enoxaparina en prevención de enfermedad tromboembólica (ET)y, en algunos casos, un riesgo hemorrágico menor. Además, es interesante un estudio sobre la incidencia detromboembolia pulmonar en pacientes con enfermedad pulmonar obstructiva crónica, un aspecto pococonocido. También se revisa un trabajo que demuestra cierta efi cacia de la rosuvastatina en la prevenciónde ET, algo que podría cambiar nuestras pautas de actuación.La hipertensión pulmonar (HP) sigue dando pie a numerosas publicaciones. En un estudio francés se hademostrado el relativamente riesgo bajo de desarrollar HP en pacientes con esclerosis sistémica en un períodode 3 años. Respecto al tratamiento, ambrisentan parece confi rmar su menor riesgo de hepatotoxicidaden comparación con otros antagonistas de la endotelina. Durante 2009 ha aparecido con fuerza en elpanorama de la HP un nuevo inhibidor de la fosfodiesterasa 5, tadalafi lo. Sus resultados son similares aotros fármacos orales con una posología cómoda. El tratamiento quirúrgico de la HP secundaria a tromboemboliacrónica en uno de los hospitales de España se ha presentado con unos resultados que, sobre todoen los últimos años, son perfectamente comparables a otros centros de prestigio.En resumen, 2009 ha seguido aportando importantes noticias en el área de la circulación pulmonar(AU)

A signifi cant number of studies on pulmonary circulation diseases have been published in 2009 that arelikely to have a notable clinical impact. Anticoagulant treatment is on the verge of a signifi cant changewith the arrival of new oral drugs that have an inhibitory effect over factor X (rivaroxaban, apixaban) orthrombin (dabigatran). New studies have shown an effi cacy comparable to enoxaparin in the prevention ofthromboembolic disease and in some cases a lower risk of haemorrhage. Also interesting is a study on theincidence of pulmonary thromboembolism in patients with chronic obstructive pulmonary disease, a littleknown aspect. A study that demonstrates some effi cacy of rosuvastatin in the prevention of thromboembolicdisease, something that could change our current practices.Pulmonary hypertension (PH) continues to produce numerous publications. One French study has shown arelatively low risk of developing PH in patients with systemic sclerosis over a period of 3 years. As regardstreatment, ambrisentan seems to confi rm it lower risk of hepatoxicity compared to other endothelinantagonists. A new phosphodiesterase-5 inhibitor, tadalafi l, has made a strong impact on the PH sceneduring this year. Its results are similar to other oral drugs with a convenient posology. The surgicaltreatment of PH due to chronic thromboembolism in one of the hospitals of our country has been presentwith results that, particularly in the past few years, are perfectly comparable to other centres ofexcellence.To summarise, 2009 has continued to provide important news in the area of pulmonary circulation(AU)

[Pulmonary thromboembolism]. / Tromboembolismo pulmonar.

Pulmonary thromboembolism is a frequent disease in emergency departments and often poses a diagnostic challenge that requires appropriate strategies. Clinical information, laboratory tests such as a D-dimer and imaging techniques such as computed tomography (CT) angiography, ventilation-perfusion scintigraphy or echocardiography help to establish clinical probability and the severity of the disease. With all this information, risk scores can be constructed, such as the Pulmonary Embolism Severity Index (PESI) score, which has high sensitivity in predicting mortality. Treatment should be started immediately with heparin, usually low molecular weight heparin. If the patient is at high risk, thrombolytic therapy is indicated, although possible contraindications should be thoroughly assessed. Supportive treatment may be considered in a few patients.