Background:Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection still under study. The objectives of this study were to identify persistent pulmonary lesions 1 year after coronavirus disease 2019 (COVID-19) hospitalization and assess whether it is possible to estimate the probability that a patient develops these complications in the future. Methods:A prospective study of ≥18 years old patients hospitalized for SARS-COV-2 infection who develop persistent respiratory symptoms, lung function abnormalities or have radiological findings 6-8 weeks after hospital discharge. Logistic regression models were used to identify prognostic factors associated with a higher risk of developing respiratory problems. Models performance was assessed in terms of calibration and discrimination. Results:A total of 233 patients [median age 66 years [interquartile range (IQR): 56, 74]; 138 (59.2%) male] were categorized into two groups based on whether they stayed in the critical care unit (79 cases) or not (154). At the end of follow-up, 179 patients (76.8%) developed persistent respiratory symptoms, and 22 patients (9.4%) showed radiological fibrotic lesions with pulmonary function abnormalities (post-COVID-19 fibrotic pulmonary lesions). Our prognostic models created to predict persistent respiratory symptoms [post-COVID-19 functional status at initial visit (the higher the score, the higher the risk), and history of bronchial asthma] and post-COVID-19 fibrotic pulmonary lesions [female; FVC% (the higher the FVC%, the lower the probability); and critical care unit stay] one year after infection showed good (AUC 0.857; 95% CI: 0.799-0.915) and excellent performance (AUC 0.901; 95% CI: 0.837-0.964), respectively. Conclusions:Constructed models show good performance in identifying patients at risk of developing lung injury one year after COVID-19-related hospitalization.

The prognosis of a patient with COVID-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with COVID-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, laboratory, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1152 patients presented with SARS-CoV-2 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 h of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤ 5%, 6–25%, and > 25% exhibited disease progression, respectively. A risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis.

Therapeutic drug monitoring (TDM) of immunosuppressants (IMS) is crucial to prevent rejection or toxicity after solid organ transplantation. Microsampling techniques (sampling <50 μL of blood) can be a good alternative to conventional venous sampling for TDM, due to their numerous advantages, including its easy and low-invasive sampling, enabling self-collection, and cost-saving shipment and storage. Furthermore, volumetric absorptive microsampling (VAMS) enables the collection of precise and accurate blood volumes, overcoming the hematocrit (Hct) effect related to dried blood spots, while offering the same benefits. In this work, an LC–MS/MS method for the determination of the 5 most common IMS (mycophenolic acid -MPA-, tacrolimus -TAC-, sirolimus -SIR-, everolimus -EVE- and cyclosporin A -CsA-) in venous blood collected with Mitra™ VAMS devices was developed and validated, employing a novel LC–MS/MS interface, Unispray™. The method was fully validated including linearity, limits of detection (LOD) and quantification (LLOQ), accuracy, precision, selectivity, carry-over, matrix effect, recovery, impact of Hct on recovery and autosampler and short-/long-term stability, satisfying acceptance criteria in all cases. LLOQs were 0.5 ng/mL for TAC, SIR and EVE, 20 ng/mL for CsA and 75 ng/mL for MPA. No impact of the Hct (range: 0.2 to 0.62 L/L) on recovery was found for any analyte. All compounds were stable in VAMS for at least 8 months at −20 °C. In addition, as part of the VAMS analytical method validation, we performed for the first time a broad statistical study to compare liquid venous blood concentrations from patients under TAC (n = 53) and MPA (n = 20) treatment to those observed when the same specimens were absorbed into VAMS. Our results showed that venous blood VAMS concentrations were correlated to those found in the original liquid venous blood, proving that the VAMS material itself will not bias blood drug concentrations. Therefore, the present method could be applied to evaluate possible correlations between venous blood and capillary blood collected with VAMS.

BACKGROUND:Patients with lung cancer usually present with symptoms at the time of diagnosis, but it is common that neither the doctor nor the patient initially associate them with the possibility of a malignant tumour.OBJECTIVES:The aim of our study is to analyse the symptoms of patients with lung cancer and the relationship with the personal characteristics or the oncological disease.MATERIAL AND METHODS:A retrospective study was conducted on all patients diagnosed with lung cancer in the Pontevedra Health Area over a period of three years. The symptoms presented by the patient, the reason for the consultation and the agreement between both or any factors associated with either of the two are analysed.RESULTS:A total of 358 patients, with a mean age of 68.7 years, and of whom 87% males, were included in the study. The most common initial symptoms were, constitutional in 30.4% of the cases, cough in 20.9% of cases, and in third place was chest pain, which was referred to by 12% of the patients. The most frequent reason for the consultation was dyspnea in 22.1% of patients, an incidental finding in 15.4%, and haemoptysis in 12.8%. There was a moderate association (correlation coefficient = 0.495) between the initial symptoms and the consulting symptom.CONCLUSIONS:A high percentage of patients with lung cancer had symptoms associated with the tumour at the time of diagnosis, even in early stage disease.

Objective: Elderly hypertensive subjects require combined treatment for an adequate control of hypertension. Nocturnal drug administration produces a significant increase in the diurnal/nocturnal ratio of systolic blood pressure (SBP). The objective was to assess the effects of the combination telmisartan (TEL) and amlodipine (AML) administered at different times of the day on ambulatory BP in elderly hypertensive subjects. Methods: We studied 51 untreated elderly hypertensive patients, 76.1 ± 7.3 years-old, assigned to two groups of treatment according time of administration of a combination of TEL 160 mg/AML 5 mg a day, on awakening or at bedtime, for three months. Clinical and biological assessment and ABPM were performed before and after therapeutic intervention, to assess changes at both moments. Results: Significant decrease of 24h-BP and diurnal BP regarding baseline values (p > 0.001) was observed, similar in both groups, (24 h-SBP/DBP/PP: -19.2/6.1/13.6 mmHg on awakening, -19.3/5.3/14.0 mmHg at bedtime; diurnal SBP/DBP/PP: -19.4/5.6/13.8 mmHg on awakening, -18.5/5,0/13,5 mmHg at bedtime). Subjects receiving TEL/AML at bedtime had a higher reduction of nocturnal BP (nocturnal SBP/DBP/PP: -18,7 /5,8/12,9 mmHg on awakening, -22,4/6,1/16,4 at bedtime, p < 0.001 for SBP and PP). Diurnal/nocturnal ratio of BP was only modified with bedtime administration (Ratio SBP/DBP: +3,82, p < 0,001). Conclusions: Combination of TEL/AML is efficient and reduces BP throughout 24 hours in elderly hypertensive subjects, regardless of administration time. In these subjects, who have a loss in diurnal/nocturnal ratio of BP with the subsequent alteration of the circadian pattern, bedtime TEL/AML administration may improve the antihypertensive efficacy.

Background: Body weight (BW) reduction in obese patients favors blood pressure (BP) controls. Evidences have been accumulated mostly in western countries. In Japan, it is far less to see patients as obese as ones studied in those evidences. Distribution of BMI of Japanese is different from those in other countries. Relationship between BP & BW in Japan is to be elucidated. Study aim: This study aimed to clarify the relationship between BW and BP changes in normotensive Japanese women in 5 years. Methods: We retrospectively examined the data obtained in the annual health checks by Fukuoka Foundation of Sound Health, Fukuoka, Japan. A total of 10184 women (mean age: 45.0+-12.2) without anti-hypertensive medications and took health checks both in 2006 and 2011 were studied. We divided the subjects according to the changes of Body Mass Index (BMI) into 3 subgroups: Reduced (&Dgr;BMI=<-1.1), Stayed (-1.1<&Dgr;BMI<1.1) and Gained (1.1=<&Dgr;BMI). We examined the changes of BPs between 2006 and 2011. Results: The average of overall BMI was 21.1+-3.1. Subgroups contained subjects as follows: Reduced-BMI(n:1483), Stayed-BMI(n:6604), Gained-BMI(n:2097). Changes of BPs are: Reduced-BMI(119.1/72.1+-16.3/10.5 to 113.8/68.6+-16.6/10.9), Stayed-BMI(114.9/70.1+-11.3/9.5 to 112.7/68.1+-15.4/10.9), Gained-BMI(113.6/69.6+-14.4/9.6 to 114.3/69.6+-14.8/11.2) mmHg. All changes except for diastolic BP of Gained-BMI were significant at p=<0.005. Only the average systolic BP of Gained-BMI group rose significantly in 5 years. Conclusions: Gain of BMI significantly raised systolic BP in normotensive Japanese women in long term. A BW gain, even tough it stays within the normal range, should be dealt with caution.

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Objectives: AVOID study showed that addition of aliskiren to ARB in diabetic subjects with nephropathy decreases the development of renal damage but has no influence on blood pressure. However, cronotherapeutic effects of the combination were not assessed. The objective is to study the evolution of diabetic nephropathy if aliskiren is added to valsartan at different times. Methods: 71 hypertensive diabetic subjects with proteinuria (albumin/creatinine ratio > 250 mg/g in men and >350 mg/g in women), preserved renal function (eGFR>60 ml/min), previously treated with valsartan 320 mg/day for 12 weeks and with controlled BP were randomised. Aliskiren 300 mg/day was added in three combinations for 24 weeks: valsartan + aliskiren in the morning; valsartan morning + aliskiren at night; valsartan + aliskiren at night. Results: Valsartan + aliskiren in the morning do not increase the antihypertensive efficacy of valsartan alone but have and additional effect of 21% (p < 0.0001) in proteinuria reduction. Valsartan in the morning + aliskiren at night offer more protection against proteinuria (29.5%) than valsartan alone, without significant changes in ambulatory BP. Valsartan + aliskiren at night decreases nocturnal ambulatory BP (p < 0.001), increases diurnal/nocturnal ratio of BP (p < 0.001) and have the highest additional effect (35.1%) in proteinuria reduction. Conclusions: Aliskiren added to valsartan means an additional and significant decrease in protein urinary excretion, higher when the combination is administered at night. This decrease seems independent from control of BP in morning administration and may have to be with an increase in diurnal/nocturnal ratio of BP and with a higher reduction of BP at rest, when the combination is administered at night.

Objectives: Ambulatory monitoring of blood pressure (ABPM) is the best method to define the cardiovascular risk in hypertensive subjects. The objective is to analyse its prognostic value in a cohort of hypertensive subjects after a 12-year follow-up period. Methods: Cohort study in a non-selected sample of 432 hypertensive subjects without previous cardiovascular disease. Clinical-biological assessment and 24h-ABPM were performed. Follow-up implied going through the clinical charts, registering date and kind of event (peripheral artery disease –PAD-, coronary cardiopathy –CC-, heart failure –HF- or cerebrovascular accident –CVA-). Results: Follow-up of 405 subjects (218 women, average age 55.5 years) provided an information of 3721.7 patients/year. During the 12.5-year follow-up period, 174 events were reported, with an incidence rate (IR) of 4.68 events/100 subjects-year. 21 cases of PAD (IR: 0.56/100 subjects-year), 59 of CC (IR: 1.59/100 subjects-year), 56 of HF (IR: 1.50/100 subjects-year) and 38 of CVA (IR: 1.02/100 subjects-year) were observed. Diabetes (incidence rate ratio (IRR): 2.35 [1.74-3.18]), worsening renal function (IRR: 2.49 [1.85-3.37]) and microalbuminuria (IRR: 2.66 [1.96-30.37]) have influence on CV prognosis and increase the incidence of events. From ABPM data, both nocturnal BP (IRR: 2.32 [1.53-3.52]) and non-dipper (IRR: 3.56 [2.39-5.27]) and riser (IRR: 7.09 [4.64-10.86]) patterns had higher prognostic correlation. Conclusions: Nocturnal BP and decrease or loss of diurnal/nocturnal ratio of BP are related with a worse CV prognosis in hypertensive subjects, regardless of target organ subclinical damages, which confirms the importance of prognostic value of ABPM in diagnosis and treatment of hypertension.

Objectives: Left ventricular hypertrophy (LVH) is the earliest sign of cardiac impact in the hypertensive subject and a risk factor for cardiovascular complications. The objective is to know the cardiovascular prognosis of hypertensive subjects with LVH, regarding the variability of blood pressure. Methods: Cohort study in a non-selected sample of 432 hypertensive subjects (218 women, aged 55.5 years) without previous cardiovascular disease. Clinical-biological assessment, 24h-ABPM and echocardiography study (calculating left ventricular mass index -LVMI-) performed. Follow-up implied going through the clinical charts, registering date and kind of event (peripheral artery disease –PAD-, coronary cardiopathy –CC-, heart failure –HF- or cerebrovascular accident –CVA-). Results: Follow-up of 405 subjects (218 women, average age 55.5 years) provided an information of 3721.7 patients/year. Subjects with LVH had more events, IR of 5.99 vs 3.06 without LVH (incidence rate ratio (IRR): 1.96 [1.42–2.72]). Concentric LVH has a worse prognosis: IRR: 3.99: 2.69-5.91. LVH with dipper pattern increases the occurrence of events (IRR: 7.19 [3.29-15.74]) and non dipper and riser patterns, with LVH (12.18 [5.77-25.72]) and 20.98 [9.81-44.91]) and without LVH (9.16 [4.15-20.24]) and 25.41 [9.31-72.75]) increase the risk. Only nocturnal decrease of BP (odds ratio (OD): 0.97 [0.95-0.98], p = 0.0007) along with LVMI (OD: 1.02 [1.01-1.03]), p < 0.0001) had influence on prognosis. Conclusions: Loss in diurnal/nocturnal ratio of BP is related with a worse CV prognosis in hypertensive subjects. Presence of LVH determines higher incidence of CV events. Although eccentric LVH is more frequent, concentric LVH is associated with higher CV risk.

Introduction: The diagnosis of cardiogenic pleural effusion (PE) is often difficult to make. The objective of our study was to evaluate the diagnostic usefulness of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in PE patients with heart failure, in pleural fluid (PF) and blood (B), and to compare the cholesterol in pleural fluid (CHOL PF) and in serum (CHOL S) with the Light criteria.Patients and methods: All the biomarkers were evaluated in 398 PF (26.9% transudates). The area under the curve (AUC) quantified the overall diagnostic precision. The diagnostic precision of the different parameters was also assessed using the ROC curves.Results: The AUC of the ROC for pleural fluid NT-proBNP was 0.894, with no significant differences with CHOL LP (0.914) or with the Light criteria (0.896). The sensitivity, specificity, the positive probability ratio (PPR) and negative probability ratio (NPR) were 85.1% (94.1% for CHOL LP), 79.9% (90.2% for the Light criteria), 4.24 (7.27 for the Light criteria) and 0.19 (0.07 for CHOL LP), respectively. The combination of NT-proBNP in PF >= 276 pg/ml and CHOL LP <= 57 mg/dL managed to classify the highest number PE correctly (sensitivity 97.8%, specificity 85.4%).Conclusions. The diagnostic yield of NT-proBNP in cardiogenic PE is not superior to the CHOL LP or the Light criteria, although it could be diagnostic in transudates of another origin. (C) 2011 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

The determination of pleural fluid triglycerides (PF-TRIG) is useful in the diagnosis of chylothorax, but its diagnostic value for other causes of pleural effusions is unknown. The aim of this study was to evaluate the usefulness of PF-TRIG in the diagnosis of other pleural effusions and investigate the origin of their increase in these fluids. We studied 390 pleural effusions (75 tuberculous, 107 neoplastic, 39 parapneumonic, 30 miscellaneous, 42 idiopathic, and 97 transudates). The correlation was analyzed with the PF-TRIG values as the dependent variable and serum triglycerides (S-TRIG) and the pleural fluid/serum protein ratio (PF/S PROT ratio) as independent variables. The PF-TRIG was significantly higher in exudates. The sensitivity of PF-TRIG for identifying exudates was 84.3%, specificity 61.9%. The correlation between PF-TRIG and S-TRIG was significant in the exudates and in the total pleural effusions. There was a significant correlation between PF-TRIG and S-TRIG and capillary permeability, which worsened when looking at the transudates and exudates separately. No correlations were found between the PF-TRIG and the number of red cells and white cells in any of the groups. Except for diagnosing a chylothorax, the determination of triglycerides in pleural fluid does not appear to be justified. The cause of the increase in PF-TRIG in exudates could not be established because the correlations obtained were insufficient to be able to predict PF-TRIG values from their serum values and the measurement of capillary permeability.

Background: Tuberculous pleural effusions (TPE) are common. The diagnosis is often problematic. As the determination of ADA is often unavailable in some countries, the aim of this study was to evaluate the diagnostic usefulness of other data from pleural fluid analysis, in young patients from populations with high prevalence of tuberculosis (TB).Methods: We analysed 218 patients with pleural effusion (165 tuberculous, 21 infectious, 11 neoplastic, 16 miscellaneous, 3 idiopathic). We performed two regression models; one included pleural fluid ADA values (model 1), and the other without ADA (model 2).Results: Model 1 selected two variables (ADA >35 U/L) and lymphocytes (>31.5%) and correctly classified 216/218 effusions (1 false negative, 1 false positive). Model 2 (without ADA) selected three variables: lymphocytes (>31.5%), fever and cough, and correctly classified 207/218 effusions (8 false negatives, 3 false positives). The sensitivity of models 1 and 2 was 99.4% and 95.2%, specificity 98.1% and 94.3% and accuracy 99% and 95%.Conclusions: In geographic areas with high prevalence of TB and a low prevalence of HIV, in young patients (<= 40 years), it is possible to confidently diagnose TPE with either of the two regression tree models, with the utility of ADA providing superior sensitivity, specificity, and accuracy. (C) 2010 Elsevier Ltd. All rights reserved.

BACKGROUND AND OBJECTIVE:Pleural effusion is relatively common in pneumonia. Because traditional methods for its diagnosis are not always effective, there is a need for new biomarkers to make its differential diagnosis easier.METHODS:A total of 233 patients with pleural effusion were admitted to our hospital between 2005 and 2008. Total and differential leukocyte counts, along with blood and pleural fluid procalcitonin and C-reactive protein (CRP) were performed on all of them. The patients were classified into 5 groups depending on the cause of their effusion: (1) parapneumonic, n = 28; (2) tuberculous, n = 49; (3) neoplastic, n = 57; (4) miscellaneous, n = 46; and (5) transudates, n = 53.RESULTS:Procalcitonin levels were higher in the pleural fluid of the parapneumonic group (PAR, 0.15 ng/mL) compared with those of the rest of the groups, but statistically significant differences were only observed with the miscellaneous and tuberculous groups (P < 0.001). Levels of CRP were also higher in the PAR (0.67 mg/L) compared with those of the rest of the groups, with statistically significant differences observed (P < 0.001-0.004) in all of them. The parameter with the largest area under the receiver operator characteristics curve was the product of the total neutrophil count and the CRP in the pleural fluid, in which an area of 0.836 had a sensitivity of 64.3% and a specificity of 93.4%.CONCLUSIONS:Determination of procalcitonin and CRP, in the pleural fluid and blood, does not seem to provide great value to the diagnosis of PAR. However, calculating the product of the total neutrophil count and the CRP may be useful in the diagnosis of these effusions because increased values have a high specificity and predictive values.

Pleural effusion appears in approximately 40% of patients with pneumonia. Given that microbiology results are often negative, its diagnosis is frequently based on clinical criteria. Our study consisted of 266 patients, divided into infectious (n = 34), tuberculous (n = 54), paraneoplastic (n = 63), miscellaneous exudates (n = 53), and transudates (n = 62). Interleukin (IL)-6, IL-8, and IL-1beta were measured in the pleural fluid and serum of all patients, as well as the different cell populations in the pleural fluid. Analysis of the receiver operating characteristic curves of the different ILs in pleural fluid for the diagnosis of parapneumonic/empyematous effusion showed IL-6 with a sensitivity of 38.2% and specificity of 97.4%, IL-8 with a sensitivity of 73.5% and specificity of 65.1%, IL-1beta with a sensitivity of 55.6% and specificity of 91.3%, and total neutrophil count in pleural fluid (PNEU) with a sensitivity of 62.9% and specificity of 91.1%. The combination of IL-1beta and PNEU improved the yield, with a sensitivity of 75.7% and a specificity of 83.1%.

Pleural fluid (PF) cholesterol is a useful parameter to differentiate between pleural transudates and exudates, although the pathophysiologic mechanisms for its increase in exudates are not fully understood. We aim to elucidate the cause of this increase by analyzing the levels of cholesterol-high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), apolipoprotein A (ApoA), and apolipoprotein B (ApoB)-in PF and blood as well as the number of leucocytes and red cells in the PF. We studied 259 patients with pleural effusion (57 transudates and 202 exudates). The correlations of the pleural and serum (S) levels of these parameters were analyzed, with the pleural cholesterol fractions as the dependent variables and their levels in blood and the pleural/serum protein ratio (P/S prot ratio) as the independent variables. The pleural fluid cholesterol levels (PFCHOL) correlated with their blood levels and the capillary permeability (r=0.885). No significant differences were found between the percentage of LDL, with regard to total cholesterol in the serum [SCHOL], and the same percentage in the exudates, between the PF/S LDL ratio (0.46) and the PF/S CHOL ratio (0.48), or between the PF/S ApoB ratio and the PF/S LDL ratio. The percentage of PF cholesterol bound to HDL and LDL was significantly higher (91.9%) than in the blood (90%). No significant correlations were found between any of the lipids studied and the number of erythrocytes and leucocytes. In conclusion, the PFCHOL may be predicted from the SCHOL, and the capillary permeability may be reflected by the PF/S prot ratio.