Luis Jara-Palomares

Hallazgos en el lavado broncoalveolar de pacientes con enfermedad pulmonar intersticial difusa. Estudio de una cohorte prospectiva de 562 pacientes

OBJECTIVE Study of the bronchoalveolar lavage (BAL) fluid in some interstitial lung diseases can reveal patterns typical to each disease and that can support the diagnosis. The objective of this study was to perform a descriptive analysis of the cytologic study and of the lymphocyte subpopulations in BAL fluid from patients with interstitial lung disease. MATERIAL AND METHODS In this prospective, observational study of 562 patients between January 1991 and January 2005, BAL fluid was analyzed to determine the distribution of cell populations and of lymphocyte subsets: CD3, CD4, CD8, CD3(+)CD4(-)CD8(-), and CD56. RESULTS The mean age was 53.4 years and 53.3% of the patients were women. The following diseases were studied: idiopathic pulmonary fibrosis (n=132), sarcoidosis (n=123), connective tissue diseases (n=133), cryptogenic organizing pneumonia (n=89), and extrinsic allergic alveolitis (n=85). Isolated lymphocytic alveolitis was common in sarcoidosis and extrinsic allergic alveolitis. Mixed alveolitis was the most common pattern in the other interstitial lung diseases. The CD4:CD8 ratio was the most useful parameter. It was high in sarcoidosis (median, 2.3); the ratio was low or inverted in the other interstitial lung diseases, with median values of 1.76 in idiopathic pulmonary fibrosis, 0.45 in extrinsic allergic alveolitis, 0.35 in cryptogenic organizing pneumonia, and 0.33 in the connective tissue diseases. CONCLUSIONS BAL parameters, in association with clinical and radiologic data, help to discriminate between interstitial lung diseases. BAL should therefore be considered a very useful tool in clinical management, particularly when pulmonary biopsy is not conclusive or is not possible.

Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate

Background Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. Methods This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. Results Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56–5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20–2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%) had plasma lactate ≥2 mmol/L. Fourteen (10.4%) of them had PE-related complications versus 6 of 361 patients with low lactate (negative predictive value 98.3%; p<0.001). Patients with elevated plasma lactate had an increased rate of PE-related complications (adjusted OR 5.3; 95% CI 1.9 to 14.4; p=0.001) compared with those with low lactate. The combination of elevated plasma lactate with markers of right ventricular dysfunction (by echocardiogram) and myocardial injury (by cardiac troponin) was a particularly useful prognostic indicator (positive predictive value 17.9%; 95% CI 6.1% to 36.9%). Conclusions Plasma lactate represents a powerful predictor of short-term PE-related complications and may provide guidance for decision-making in PE care.

Testing for occult cancer in patients with pulmonary embolism: Results from a screening program and a two-year follow-up survey

INTRODUCTION An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population. MATERIALS AND METHODS A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression. RESULTS The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index >/=1 (odds ratio: 5.467; p=0.007) and idiopathic PE (odds ratio: 12.82; p=0.03) were independent risk factors for occult cancer in our PE patients. CONCLUSIONS A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms.

Utility of high-resolution computed tomography and BAL in cryptogenic organizing pneumonia.

BACKGROUND Cryptogenic organizing pneumonia (COP) is a rare disease, and its diagnosis requires histological confirmation. The objective of our study was to describe the findings of the thoracic high-resolution computed tomography (HR-CT) and bronchoalveolar lavage (BAL) in patients with confirmed COP and evaluate the complementary diagnostic use of BAL and thoracic HR-CT. METHODS Patients recorded in the registry of interstitial pulmonary diseases between 1991 and 2008 were located and the COP patients selected. RESULTS We identified 21 patients with histological confirmation of COP. The median age was 58.0 ± 15.9 years, and 61.9% of patients were female. The most frequent thoracic HR-CT profile was patchy infiltrate (71.4%), followed by parenchymatous consolidation (42.9%). The most frequent BAL profile was mixed alveolitis (62%) with lymphocyte predominance, a CD4/CD8 index of 0.4 and foamy macrophages. The effectiveness of transbronchial biopsy was 66.6%. The diagnostic utility of Polettis BAL criteria gives us a specificity of 88.8%, although the sensitivity obtained was low. The specificity of certain HR-CT profiles is 99%. In addition, we observed a complementary use of the HR-CT and the BAL. CONCLUSIONS The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed.

Bronchoalveolar Lavage Findings in Patients With Diffuse Interstitial Lung Disease: Prospective Study of a Cohort of 562 Patients

Abstract Objective Study of the bronchoalveolar lavage (BAL) fluid in some interstitial lung diseases can reveal patterns typical to each disease and that can support the diagnosis. The objective of this study was to perform a descriptive analysis of the cytologic study and of the lymphocyte subpopulations in BAL fluid from patients with interstitial lung disease. Material and methods In this prospective, observational study of 562 patients between January 1991 and January 2005, BAL fluid was analyzed to determine the distribution of cell populations and of lymphocyte subsets: CD3, CD4, CD8, CD3+CD4−CD8−, and CD56. Results The mean age was 53.4 years and 53.3% of the patients were women. The following diseases were studied: idiopathic pulmonary fibrosis (n=132), sarcoidosis (n=123), connective tissue diseases (n=133), cryptogenic organizing pneumonia (n=89), and extrinsic allergic alveolitis (n=85). Isolated lymphocytic alveolitis was common in sarcoidosis and extrinsic allergic alveolitis. Mixed alveolitis was the most common pattern in the other interstitial lung diseases. The CD4:CD8 ratio was the most useful parameter. It was high in sarcoidosis (median, 2.3); the ratio was low or inverted in the other interstitial lung diseases, with median values of 1.76 in idiopathic pulmonary fibrosis, 0.45 in extrinsic allergic alveolitis, 0.35 in cryptogenic organizing pneumonia, and 0.33 in the connective tissue diseases. Conclusions BAL parameters, in association with clinical and radiologic data, help to discriminate between interstitial lung diseases. BAL should therefore be considered a very useful tool in clinical management, particularly when pulmonary biopsy is not conclusive or is not possible.

Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis of Individual Patient Data

Unprovoked venous thromboembolism (VTE) may be the first sign of occult cancer. Screening often is considered in these patients, with the aim of detecting underlying cancer at an early, curable stage and reducing cancer-related morbidity and mortality. The extent to which patients with unprovoked VTE should be screened for occult cancer is controversial. Although an early study suggested that an extensive screening strategy may detect more cancer than a more limited one (1), recent studies evaluating extensive screening strategies using computed tomography (CT) of the abdomen (24) or whole-body positron emission tomography (PET) (5) could not confirm this finding. Extensive screening tests may yield false-positive findings, requiring additional, sometimes invasive testing, which increases health care costs, exposes patients to potential procedure-related complications, and may lead to patient anxiety. Given the lack of a clear benefit and the potential harms of extensive screening, a more limited occult cancer screening strategy comprising medical history taking, physical examination, basic blood work, chest radiography, and age- and sex-specific testing currently is suggested for patients with unprovoked VTE (6). To guide decisions regarding occult cancer screening and to counsel patients, clinicians need precise estimates of the period prevalence of occult cancer at the time of VTE diagnosis and during follow-up. Clinicians also must be informed about the types and stages of cancer that may potentially be detected by screening and about the tests that are useful for detecting occult cancer. To help clinicians tailor screening decisions, we performed a systematic review and a meta-analysis of individual patient data, combining patient-level data from 10 recently published, prospective studies of occult cancer screening in patients with unprovoked VTE. Methods Methods were prespecified in a previously published protocol (7). The guidance of the PRISMA-IPD (Preferred Reporting Items for Systematic reviews and Meta-Analyses of Individual Participant Data) Statement was followed (Supplement Appendix 1) (8). The systematic review was registered with the International Prospective Registry of Systematic Reviews (PROSPERO: CRD42016033371). Supplement. Supplementary Material Data Sources and Searches Our previously published systematic review (9) was updated by searching the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from 1 November 2007 to 19 January 2016, combining terms for VTE, cancer, and screening (Supplement Table 1). No language restrictions were applied. In addition, conference proceedings of the International Society on Thrombosis and Haemostasis and the American Society of Hematology were searched from 2007 to 2015. Reference lists of eligible articles were hand-searched. Two authors (N.v.E. and M.C.) independently screened the titles and abstracts of articles and assessed the full texts for eligibility. Any differences of opinion regarding study eligibility were resolved by discussion. Study Selection To be eligible, studies must have prospectively included consecutive adult patients with unprovoked, objectively confirmed deep venous thrombosis or pulmonary embolism and followed them for a minimum of 12 months for potential cancer. We accepted the individual study definitions of unprovoked VTE. Studies were required to follow a defined strategy for occult cancer screening, including, at minimum, medical history taking, physical examination, basic blood tests, and chest radiography. Studies that started enrolling patients before 1 January 2000 were excluded, because cancer screening practices (such as age- and sex-specific testing) and diagnostic testing procedures changed substantially since then; therefore, more recent studies were considered more relevant and informative. All studies that enrolled patients before any screening procedures were included in the primary analyses. Studies enrolling patients only after negative results on initial screening were used for additional analyses. Data Extraction and Quality Assessment Corresponding authors of eligible studies were invited to participate in this collaborative project. All contacted authors agreed and provided individual patient data. Study-level information was sought regarding each studys aims, definition of unprovoked VTE, screening strategy, follow-up duration, and assessment of outcomes. Patient-level data about baseline characteristics; risk factors; index VTE; cancer screening tests; and outcomes, including cancer, recurrent VTE, death, and loss to follow-up, were obtained. Patients who enrolled more than 90 days after their VTE diagnosis, as well as those in whom the index VTE was not objectively confirmed, were excluded from the data set. To ensure data consistency, baseline tables and primary analyses reported in the original articles were reconstructed. Discrepancies with the published tables were resolved by contacting the principal investigators. All studies had been approved by the institutional review boards of participating centers. Two reviewers (N.v.E. and Dr. Nomie Kraaijpoel [Academic Medical Center, Amsterdam, the Netherlands]) independently assessed the potential risks of bias for each study by using the NewcastleOttawa Scale (10) and the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies, revised) tool, which was adapted to the present research question (Supplement Appendix 2) (11). Disagreements were resolved by consensus. Data Synthesis and Analysis The primary outcome measure was the point prevalence of previously undiagnosed cancer at 12 months in patients with unprovoked VTE, defined as the proportion of patients in whom solid or hematologic cancer (excluding nonmelanoma skin cancer) was objectively confirmed by histology or cytology or unequivocally diagnosed by imaging or tumor markers. Cancer detection refers to detection by screening tests that subsequently was confirmed by additional testing. Cancer diagnosis is all cases confirmed either at screening or during follow-up. The period prevalence of cancer also was analyzed at different time points, including at initial screening, between screening and 12 months, and between 12 and 24 months of follow-up. Subgroup analyses assessed the effects of screening type (limited vs. extensive) and patient age (by cohorts of 10 years) on the probability of cancer diagnosis. Finally, the probability of a cancer diagnosis was estimated in men, women, current or former smokers, women receiving estrogen-containing oral contraceptive or hormone replacement therapy, patients presenting with pulmonary embolism, and those with previous VTE. Secondary outcomes were early-stage solid cancer (stage 0, I, or II according to the American Joint Committee on Cancer staging system), stage III and IV solid cancer, and hematologic cancer. The proportion of positive findings at limited screening that required additional testing and the proportion of patients who subsequently received a cancer diagnosis were evaluated. Limited screening was defined as the combination of medical history taking; physical examination; basic blood tests (complete blood count and creatinine and liver function tests); chest radiography; and age- and sex-specific tests, such as mammography or prostate-specific antigen testing. Results of limited screening were considered positive if they led to additional investigations for possible cancer detection. Extensive screening strategies were heterogeneous across the studies but often included imaging with CT and ultrasonography of the abdomen or whole-body PET-CT (Supplement Table 2). Patient-level information was obtained from source documentation for each cancer case diagnosed at initial screening. Using detailed narratives based on source documents, 3 authors (N.v.E., G.L.G., and M.C.) independently adjudicated which of the screening tests initially had raised the suspicion of cancer and eventually led to cancer detection. Summary probability estimates were obtained through 1-stage meta-analysis using a generalized linear mixed-effects model, in which a study-specific random effect was included to account for the clustering of observations within studies. Subgroup differences were analyzed with an indicator variable as a fixed effect. When analyzing the effect of screening type, we added a random effect because of the differences in extensive screening strategies across studies and adjusted the analysis for age, sex, smoking, and index VTE because 1 of the comparative studies was nonrandomized. Marginal probability estimates were calculated by integrating the inverse logit of the fixed effect of the intercept over the random-effects distribution by using GaussHermite quadrature approximation, with 10 quadrature points, to arrive at the final point estimates and 95% CIs. The time to cancer detection during a maximum of 2 years of follow-up was estimated separately for each study with KaplanMeier curves, censoring the time to detection in case of death, loss to follow-up, or end of follow-up. To illustrate heterogeneity across the studies, 95% prediction intervals were calculated around the point estimates on the basis of the SE of the fixed effect and the variance of the random effect. Forest plots also were generated to visualize potential heterogeneity. In addition, we performed a predefined sensitivity analysis restricted to patients enrolled within 30 days after the index VTE. All analyses were undertaken on an intention-to-screen basis and performed in R, version 3.3.2 (R Foundation for Statistical Computing), by using the lme4 package, version 1.1-12, for the mixed-effects models. Role of the Funding Source This study received no funding. Results Included Studies A total of 1216 articles were identified, from which 23 full texts were assessed for eligibility (Figure 1). Ten prospective studies met the inclusion criteria, and in

Tinzaparin in cancer associated thrombosis beyond 6 months: TiCAT study

INTRODUCTION The safety and efficacy of low-molecular-weight heparin (LMWH) treatment in patients with cancer-associated thrombosis (CAT) beyond 6months are unknown. Our aim was to determine the safety of long-term tinzaparin use in patients with CAT. METHODS We performed a prospective, open, single arm, multicentre study in patients with CAT receiving treatment with tinzaparin. We evaluated the rate of clinically relevant bleeding events (major and non-major clinically relevant bleeding) and venous thromboembolism (VTE) recurrence. RESULTS A total of 247 patients were recruited, with a crude incidence of major bleeding of 4.9% (12/247). The rate of clinically relevant bleeding during months 1-6 and 7-12, was 0.9% [95% confidence interval (95% CI) 0.5 to 1.6%] and 0.6% (95% CI 0.2 to 1.4%) (p=0.5) per patient and month, respectively. Male gender showed greater risk for clinically relevant bleeding with a hazard ratio (HR) of 2.97 (95% CI 1.01 to 8.1; p=0.02). The incidence of VTE recurrence at months 1-6 and 7-12 was 4.5% (95% CI 2.2 to 7.8%) and 1.1% (95% CI 0.1 to 3.9%), respectively. One patient died due to VTE recurrence and two because of severe bleeding. CONCLUSIONS Treatment with tinzaparin beyond 6months is safe in patients with CAT.

Rivaroxaban for the treatment of venous thromboembolism. A "real-life" perspective in 103 patients.

INTRODUCTION Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE. MATERIAL AND METHODS Open follow-up study of a cohort of patients aged 18 and over diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) treated with rivaroxaban from December 2011 to January 2014. RESULTS The total number of patients treated with rivaroxaban was 103. The mean age was 58+/-17 years. The most frequent co-morbidities were: hypertension (30.0%), dyslipidemia (23.3%) and respiratory disease (25.2%). The type of thromboembolic event treated was: DVT (64.1%), PE (18.4%), DVT+PE (17.5%). Of the rivaroxaban-treated patients, 30% did so from the initial anticoagulant therapy and the other 70% in long-term or extended anticoagulant therapy. The median time of treatment with rivaroxaban was 6 months [corrected]. There was one recurrence and no deaths occurred. Six patients had bleeding, one of which was severe. CONCLUSIONS Rivaroxaban provides a therapeutic alternative in a group of patients with VTE with advantages over VKAs, because of the convenience in dosing, lack of requirements for periodic monitoring and limited interaction with other drugs.

Lung cancer mortality in Spain: estimating the future burden to the year 2028.

OBJECTIVE To use lung cancer mortality rates from 1979 to 2008 in Andalusia, southern Spain (population >8,000,000), to provide an estimate of the future number of deaths for the period 2009-2028. DESIGN The numbers of lung cancer deaths from 1979 to 2008 were obtained from the Andalusian Institute for Statistics (AIS). Data were arranged in 5-year age groups using an age-period-cohort model. Age-standardised rates (ASR) per 100, 000 were calculated for males and females. Population projections for Andalusia 2009-2028 were downloaded from the AIS database. RESULTS In males, the ASR varied from 46.1 in 2004-2008 to 34.6 in 2024-2028, with a projected 33% decrease. In females, the ASR varied from 4.9 in 2004-2008 to 8.9 per 100,000 in 2024-2028, with a projected 45% increase. This reflects an annual change of -1.3% for males and of +2.7% for females for the period 2009-2028. The sex ratio is projected to drop from a male:female ratio of 11 (1979-1983) to 3.8 (2024-2028). CONCLUSIONS Our projections emphasise the significance of a continuously increasing trend in female lung cancer mortality, with a drop in the projected sex ratio.

Predicting the risk of cancer after unprovoked venous thromboembolism: external validation of the RIETE score

Essentials Patients at high‐risk of occult cancer may benefit from extensive screening. We validated the RIETE cancer score in the MVTEP study. One in three patients were classified as high‐risk, 10% of whom had cancer diagnosed. The RIETE score identifies a subgroup at high risk for cancer.