Use of mycophenolate mofetil for the treatment of fibrotic hypersensitivity pneumonitis.

INTRODUCTION: The optimal treatment of fibrosing hypersensitivity pneumonitis (fHP) is not well understood. The aim of the study was to obtain information about the usefulness of mycophenolate mofetil (MMF) in its treatment. MATERIAL AND METHODS: Quasi-experimental analysis of patients diagnosed with fHP and treated with MMF for one year, in a single centre. From the start of treatment, data collection was prospective. RESULTS: 73 were included and 58 completed the study. FVC% and DLCO% decreased until starting MMF (year -1 to year 0). After completion of treatment (year 1), FVC% stabilised (p=0.336) and DLCO% improved significantly (p=0.004) compared to year 0. Dyspnoea, number of patients without corticosteroids and mean corticosteroid dose also improved significantly (p<0.001 in all cases). Being male and having a history of tuberculosis were predictors of poor drug response [AUC = 0.89 (95% CI: 0.80-0.98)]. 45 adverse effects were observed in 34 patients (46.6%). In 4 cases (5.5%), the adverse effect was severe and required discontinuation of treatment. CONCLUSIONS: In patients with fHP, MMF improves lung function and dyspnoea and reduces both the number of patients requiring oral corticosteroids and their mean dose in those who completed 1 year of treatment. The model constructed predicts which patients will respond poorly to treatment, with good discriminative ability and only a small percentage of patients will not tolerate treatment. Further prospective, randomised clinical trials are needed to define the role of this treatment in fHP.

Non-specific pleuritis: long-term follow-up outcomes.

BACKGROUND: The definitive etiology of nonspecific pleuritis (NSP), the influence of the type of pleural biopsy on clinical results and the minimum duration of follow-up is controversial. RESEARCH DESIGN AND METHODS: A retrospective, observational study of patients ≥ 18 years with NSP confirmed by closed pleural biopsy (CPB), local anesthesia pleuroscopy (LAP), or video-assisted thoracic surgery (VATS). RESULTS: A total of 167 patients were included (mean follow-up, 14.4 months), of which 25 (15%) were diagnosed within one month; [15 (60%) malignant]. Of the remaining 142 pleural effusions (PEf), 69 (48.6%) were idiopathic; 49 (34.5%) not-malignant and 24 (16.9%) malignant (4 mesotheliomas and 20 metastasic). The diagnosis of NSP was established by CPB (7; median time to diagnosis, 9.4 months), LAT (5; 15.8 months), and VATS (8; 13.5 months) (p = 0.606). Sixty-eight patients (40.7%) died during follow-up (mean time, 12 months). CONCLUSIONS: In a substantial percentage of patients diagnosed with NSP, a definitive diagnosis will not be obtained, a relevant number of patients will develop a malignant PEf. The diagnostic procedure used for the diagnosis of NSP does not seem to influence delay in the diagnosis of malignant PEf. The data obtained suggest that follow-up should be maintained for at least 24 months.

Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease.

BACKGROUND: The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS: Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS: 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS: The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.

Development of prognostic models to estimate the probability of lung injury one year after COVID-19-related hospitalization-a prospective study.

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.

Characteristics of pleural effusion due to amyloidosis.

The characteristics of patients with pleural amyloidosis (PA) are poorly known. A systematic review was performed of studies reporting clinical findings, pleural fluid (PF) characteristics, and the most effective treatment of PA. Case descriptions and retrospective studies were included. The review included 95 studies with a total sample of 196 patients. The mean age was 63 years, male/female ratio was 1.6:1, and 91.9% of patients were >50 years. The most common symptom was dyspnea (88 patients). PF was generally serious (63%), predominantly lymphocytic, and with the biochemical characteristics of transudates (43.4%) or exudates (42.6%). Pleural effusion was generally bilateral (55%) and <1/3 of the hemithorax (50%), although in 21% pleural effusion (PE) exceeded 2/3. Pleural biopsy was performed in 67 patients (yield: 83.6%; 56/67) and was positive in 54% of exudates and 62.5% of unilateral effusions. Of the 251 treatments prescribed, only 31 were effective (12.4%). The combination of chemotherapy and corticosteroids was effective in 29.6% of cases, whereas talc pleurodesis was effective in 21.4% and indwelling pleural catheter in 75% of patients (only four patients). PA is more frequent in adults from 50 years of age. PF is usually bilateral, serous, and indistinctly a transudate or exudate. A pleural biopsy can aid in diagnosis if effusion is unilateral or an exudate. Treatments are rarely effective and there may be definitive therapeutic options for PE in these patients.

Pleural effusion due to nonmalignant gastrointestinal disease.

Although pleural effusion is a frequent finding in clinical practice, determining its aetiology may be challenging, and up to 20% of cases remain undiagnosed. Pleural effusion may occur secondary to a nonmalignant gastrointestinal disease. A gastrointestinal origin is confirmed based on a review of the medical history of the patient, thorough physical examination and abdominal ultrasonography. In this process, it is crucial to correctly interpret findings on pleural fluid obtained by thoracentesis. In the absence of high clinical suspicion, identifying the aetiology of this type of effusion may be difficult. Clinical symptoms will be determined by the gastrointestinal process causing pleural effusion. In this setting, correct diagnosis relies on the specialist's ability to evaluate pleural fluid appearance, test for the appropriate biochemical parameters and determine whether it is necessary or not to send a specimen for culture. The established diagnosis will determine how pleural effusion is approached. Although this clinical condition is self-limited, many cases will require a multidisciplinary approach because some effusions can only be resolved with specific therapies.

Developing a Compost Quality Index (CQI) Based on the Electrochemical Quantification of Cd (HA) Reactivity.

The present work demonstrates the use of Cd2+ as a reactivity probe of the fulvic acids (FAs), humic acids (HAs) and dissolved organic matter (DOM) compost extracts. Significant differences were observed between the extracts, with the HA extract showing the highest reactivity. Comparing the different composts, the largest reactivity variation was again observed for HA then FA and finally DOM extracts. The Cd2+ binding extent was used to calculate the quality of composts and compared with a reference of uncomposted organic fertiliser (FLW), leading to the definition of an operational scale of compost quality. The parameter equivalent mass of fertiliser (mEF) was used for this scale sorted the seven composts from 0.353 to 1.09 kg FLW, for compost of sewage sludge (CSS) and vermicompost of domestic waste (CVDW), respectively. The significance of this parameter was verified through a correlation analysis between binding extent and the effect of compost application on lettuce crop growth in a field trial. The results demonstrate the potentiality of FA and HA extracts as markers of compost bioactivity and the use of Cd2+ as a reactivity probe.

Sarcoidosis. Disease progression based on radiological and functional course: Predictive factors.

BACKGROUND: Sarcoidosis is a multiorgan granulomatous disease with a variable course. OOBJECTIVES: The purpose of this study is to identify the patients that are more likely to experience disease progression. METHODS: A retrospective study in patients ≥18 years. Pulmonary function and radiological stage (Scadding criteria) were assessed at diagnosis, and at 1, 3 and 5 years. Sarcoidosis progression was established based on deterioration of radiological or pulmonary function (decrease ≥10% of FVC and/or ≥15% of diffusing capacity of the lung (DLCO). RESULTS: The sample included 277 caucasian patients [mean age, 50±13.6; 69.7% between 31-60 years; 56.3% men]. In total, 65% had stage II sarcoidosis, whereas only 8.3% had stage III/IV disease. Mean pulmonary function (FVC, FEV1, FEV1/FVC and DLCO) at diagnosis was 103±21.8, 96±22.2, 76.2±8 and 81.7±21.7, respectively. The percentage of patients with normal FVC and DLCO was 72.2% and 51.8%, respectively. Radiological stage did not change significantly during follow-up (5 years; p=0.080) and only progressed in 13 patients (5.7%). At 3 years, FVC improved, whereas DLCO exacerbated significantly (p<0.001 for the two). Disease progressed in 34.5% of the patients (57/165) whose pulmonary function and radiological stage were available (both baseline and at 3 years). Age was associated with disease progression [OR=1.04 (95%CI=1.01, 1.06)]. Risk increased by 4% for each year older a patient was at diagnosis. CONCLUSIONS: At 3 years, a third of patients experienced sarcoidosis progression. Age was the only factor associated with disease prognosis.

Estimation of phosphate extractability in flooded soils: Effect of solid-solution ratio and bicarbonate concentration.

The Olsen method is widely used to determine bioavailable phosphate (P) in upland soils. It is also used in flooded soils, although different estimates of extractable-P are obtained under anoxic and oxic conditions. In this study, variations in extractable-P in three soils under different redox conditions were evaluated as a function of solid to solution ratio (SSR) (1:5-1:200) and bicarbonate concentration (0.1-1 M). The parameterized CD-MUSIC model was used to describe the data, with optimization of reactive surface area (RSA) and reversibly adsorbed-P (R-PO4). The RSA may vary due to the reductive dissolution of iron minerals and/or the formation of new reactive surfaces upon the establishment of reducing conditions. Changes in SSR and bicarbonate concentration significantly affected extractable-P under both oxic and anoxic conditions; more P was extracted under anoxic than under oxic conditions. The difference was 1.5-2 times greater for the highest SSR considered. In the soil samples with higher organic carbon content, the effect of bicarbonate concentration on extractable-P was remarkable. The large differences in extractable-P under oxic and anoxic conditions were probably due to differences in iron (hydr)oxide content. The CD-MUSIC model successfully predicted the effect of SSR on extractable-P under both conditions. R-PO4 data were fitted for oxic conditions and assumed unchanged for anoxic samples, while RSA data were fitted for both conditions. The RSA values were lower in anoxic than in oxic samples. Overall, our data and model calculations indicate that using wet soil samples obtained in-situ for evaluation of Olsen-P in submerged soils lead to a higher estimation of extractable-P than estimated in oxic soils. If soil testing in the presence of target plants confirms the reliability of in-situ sampling for Olsen-P estimation, the P fertilizer dose applied to submerged soils could be reduced, which is very important from environmental and economic perspectives.

Pulmonary Manifestations of Primary Humoral Deficiencies.

Primary immunodeficiencies are a group of conditions characterized by developmental or functional alterations in the immune system caused by hereditary genetic defects. Primary immunodeficiencies may affect either the innate or the adaptive (humoral and cellular) immune system. Pulmonary complications in primary humoral deficiencies are frequent and varied and are associated with high morbidity and mortality rates. The types of complications include bronchiectasis secondary to recurrent respiratory infections and interstitial pulmonary involvement, which can be associated with autoimmune cytopenias, lymphoproliferation, and a range of immunological manifestations. Early detection is key to timely management. Immunoglobulin replacement therapy reduces the severity of disease, the frequency of exacerbations, and hospital admissions in some primary humoral deficiencies. Therefore, the presence of pulmonary disease with concomitant infectious and/or autoimmune complications should raise suspicion of primary humoral deficiencies and warrants a request for immunoglobulin determination in blood. Once diagnosis is confirmed; early immunoglobulin replacement therapy will improve the course of the disease. Further studies are needed to better understand the pathogenesis of pulmonary disease related to primary humoral deficiencies and favor the development of targeted therapies that improve the prognosis of patients.

Use of combined tools for effectiveness evaluation of tailings rehabilitated with designed Technosol.

Soil and water characteristics and biogeochemical processes can be improved by the application of an integrated technology based on circular economy: designed Technosol. The evaluation of the effectiveness of the superficial application of a designed Technosol, with andic and eutrophic properties, on the rehabilitation of sulfide tailings of a uranium mine (Fé mining area, Spain) was the aim of this study. After 20 months of the Technosol application, the tailing rehabilitation status (Rehabilitated tailing) was compared to a non-rehabilitated tailing (Tailing). To assess the rehabilitation of these systems, several properties were analyzed: chemical characteristics of the materials and their leachates, soil enzymatic activities (dehydrogenase, ß-glucosidase, acid phosphatase and urease), basal respiration and several plant endpoints from direct and indirect bioassays and pot experiment using Lolium perennse L. and Trifolium pratense L.. Potentially toxic concentrations of Co, Mn and Ni were identified in both available fraction and leachates, pointing out the serious environmental risk posed by the tailing. The improvement of overall physicochemical properties in the rehabilitated tailing materials (e.g., decrease of the hazardous element concentrations in leachates and available fraction, and improvement of the fertility and structure) allowed a quick plant cover with pasture species and provided a suitable habitat for active microbial community (evaluated by increasing dehydrogenase activity and basal respiration). This improvement in the rehabilitated tailing contributed to a significant decrease in the ecotoxicological risk and the spread of hazardous elements. The field application of this specific Technosol was a promising and lasting solution for rehabilitation of this type of tailings.

Pleuroparenchymal fibroelastosis: Clinical, radiological and histopathological features.

Pleuroparenchymal fibroelastosis (PPFE) is a rare, generally idiopathic form of interstitial pneumonia with unique clinical, radiological and histopathological features. It is named after the presence of upper lobe pleural and subjacent parenchymal fibrosis, with accompanying elastic fibers. Although it is usually an idiopathic disease, it has been linked to other co-existent diseases. Diagnostic suspicion of PPFE is based on the identification of typical abnormalities on chest CT scan, which are prevailingly located in the upper lobes, adjacent to the apex of the lungs. Diagnosis can be confirmed by histological analysis, although biopsy is not always feasible. The disease is generally progressive, but not uniformly. The course of the disease is frequently slow and involves a progressive loss of upper lobe volume, which results in platythorax, associated with a significant reduction of body mass. PPFE concomitant to other interstitial lung diseases is associated with a poorer prognosis. The disease occasionally progresses rapidly causing irreversible respiratory insufficiency, which leads to death. Currently, there is no effective pharmacological therapy available, and lung transplantation is the best therapeutic option. The purpose of this review is to draw the attention to PPFE, describe its clinical, radiological and histopathological features, analyze its diagnostic criteria, and provide an update on the management of the disease.

Evaluation of the impact of an integrated care pathway for pulmonary embolism: a quasi-experimental pre-post study.

BACKGROUND: An integrated care pathway (ICP) is intended to improve the management of prevalent resource-consuming, life-threatening diseases. The purpose of this study was to determine whether the quality of patient care improved with the establishment of a dedicated unit for pulmonary embolism (PE). METHODS: A quasi-experimental pre-post study (pre: years 2010-2013; post: 2015-2020; year 2014, "washing" period) of PE patients ≥18 years (January 2010-June 2020). The intervention involved the implementation of an ICP for PE. RESULTS: The sample was composed of 1,142 patients (510 pre-intervention and 612 post-intervention) without significant differences between the two populations. In the post-intervention period, significant reductions were observed in the median length of hospital stay (LOS) (8 vs. 6 days); time to start of oral anticoagulation therapy (4.5 vs. 3.5 days; P<0.001); and the percentage of patients with high-risk PE in whom recanalization was not contraindicated (66.7% vs. 96%; P=0.009). In-hospital and 30-day mortality decreased, although not significantly (4.5% vs. 2.8%; P=0.188; 6.1% vs. 5.2%; P=0.531, respectively). Multivariate logistic regression analysis showed that the median LOS intervention decreased significantly according to the service where patients were referred to, and with the use of the simplified PESI. During follow-up, lifelong anticoagulation was prescribed to a higher proportion of patients in the post-intervention period (30.7% vs. 69.3%; P<0.001). CONCLUSIONS: Although an ICP for PE does not reduce mortality significantly, it improves the quality of patient care.

Health Outcomes: Towards the Accreditation of Respiratory Medicine Departments. / Resultados de salud: hacia la acreditación de los servicios de neumología.

National health systems must ensure compliance with conditions such as equity, efficiency, quality, and transparency. Since it is the right of society to know the health outcomes of its healthcare system, our aim was to develop a proposal for the accreditation of respiratory medicine departments in terms of care, teaching, and research, measuring health outcomes using quality of care indicators. The management tools proposed in this article should be implemented to improve outcomes and help us achieve our objectives. Promoting accreditation can serve as a stimulus to improve clinical management and enable professionals to take on greater leadership roles and take action to improve outcomes in patient care.

Health outcomes: Towards the accreditation of respiratory medicine departments.

National health systems must ensure compliance with conditions such as equity, efficiency, quality, and transparency. Since it is the right of society to know the health outcomes of its healthcare system, our aim was to develop a proposal for the accreditation of respiratory medicine departments in terms of care, teaching, and research, measuring health outcomes using quality of care indicators. The management tools proposed in this article should be implemented to improve outcomes and help us achieve our objectives. Promoting accreditation can serve as a stimulus to improve clinical management and enable professionals to take on greater leadership roles and take action to improve outcomes in patient care.

From sinks to sources: The role of Fe oxyhydroxide transformations on phosphorus dynamics in estuarine soils.

The availability of phosphorus (P) in estuarine ecosystems is ultimately controlled by the nature of interactions between dissolved P and the soil components (e.g., soil minerals), especially iron (Fe) oxyhydroxides. P retention on Fe oxyhydroxides and its subsequent availability depends on mineral crystallinity and susceptibility to dissolution. However, in estuarine soils, geochemical conditions (e.g., redox oscillation and high soil organic matter content) may alter the fate of P and decrease the environmental quality of estuarine waters. The large input of Fe-rich tailings into the Rio Doce Estuary in Brazil in 2015 after a rupture of a Fe ore tailings dam (i.e., "Mariana mine disaster") offers a unique framework to evaluate the Fe oxyhydroxides role in P availability in estuarine soils, their potential effects on the cycling of P and eutrophication. We observed a significant correlation between Fe minerals and the P content in the estuary soils, suggesting that P enrichment was promoted by the deposited Fe-rich tailings. Adsorption isotherm curves indicated that mine tailings had a strong affinity for P due to presence of crystalline Fe oxyhydroxides in the tailings. Significant losses of Fe (62%) and P (56%) from the estuarine soil was observed two years after the initial impact and in response to redox conditions oscillations. Additionally, the content of high crystallinity Fe oxyhydroxides decreased significantly, whereas that of low crystallinity Fe oxyhydroxides showed an increase over time. These changes were associated with the dissimilatory Fe reduction, which led an increase in the concentrations of readily available P (2015: 2.30 ± 0.41 mg kg-1; 2017: 3.83 ± 1.82 mg kg-1; p < 0.001) in the studied soils. Moreover, in 2017, the dissolved P content exceeded the recommended environmental safety limits by five times. Our results indicate that Fe oxyhydroxides are a continuous source of dissolved P for the ecosystem, and Fe-rich tailings deposited in the estuarine ecosystem may be linked to a potential eutrophication.

Malignant Pleural Effusion: Diagnosis and Management.

Symptomatic malignant pleural effusion is a common clinical problem. This condition is associated with very high mortality, with life expectancy ranging from 3 to 12 months. Studies are contributing evidence on an increasing number of therapeutic options (therapeutic thoracentesis, thoracoscopic pleurodesis or thoracic drainage, indwelling pleural catheter, surgery, or a combination of these therapies). Despite the availability of therapies, the management of malignant pleural effusion is challenging and is mainly focused on the relief of symptoms. The therapy to be administered needs to be designed on a case-by-case basis considering patient's preferences, life expectancy, tumour type, presence of a trapped lung, resources available, and experience of the treating team. At present, the management of malignant pleural effusion has evolved towards less invasive approaches based on ambulatory care. This approach spares the patient the discomfort caused by more invasive interventions and reduces the economic burden of the disease. A review was performed of the diagnosis and the different approaches to the management of malignant pleural effusion, with special emphasis on their indications, usefulness, cost-effectiveness, and complications. Further research is needed to shed light on the current matters of controversy and help establish a standardized, more effective management of this clinical problem.

Development and validation of a clinical score to estimate progression to severe or critical state in COVID-19 pneumonia hospitalized patients.

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.

Impact of cardiovascular risk factors on the clinical presentation and survival of pulmonary embolism without identifiable risk factor.

BACKGROUND: The nature of pulmonary embolism (PE) without identifiable risk factor (IRF) remains unclear. The objective of this study is to investigate the potential relationship between cardiovascular risk factors (CVRFs) and PE without IRF (unprovoked) and assess their role as markers of disease severity and prognosis. METHODS: A case-control study was performed of patients with PE admitted to our hospital [2010-2019]. Subjects with PE without IRF were included in the cohort of cases, whereas patients with PE with IRF were allocated to the control group. Variables of interest included age, active smoking, obesity, and diagnosis of arterial hypertension, dyslipidemia or diabetes mellitus. RESULTS: A total of 1,166 patients were included in the study, of whom 64.2% had PE without IRF. The risk for PE without IRF increased with age [odds ratio (OR): 2.68; 95% confidence interval (CI): 1.95-3.68], arterial hypertension (OR: 1.63; 95% CI: 1.27-2.07), and dyslipidemia (OR: 1.63; 95% CI: 1.24-2.15). The risk for PE without IRF was higher as the number of CVRF increased, being 3.99 (95% CI: 2.02-7.90) for subjects with ≥3 CVRF. The percentage of high-risk unprovoked PE increased significantly as the number of CVRF rose [0.6% for no CVRF; 23.8% for a CRF, P<0.001 (OR: 9.92; 95% CI: 2.82-34.9); 37.5% for two CRFs, P<0.001 (OR: 14.8; 95% CI: 4.25-51.85); and 38.1% for ≥3, P<0.001 (OR: 14.1; 95% CI: 4.06-49.4)]. No significant differences were observed in 1-month survival between cases and controls, whereas differences in 24-month survival reached significance. CONCLUSIONS: A relationship was observed between CVRF and PE without IRF, as the risk for unprovoked PE increased with the number of CVRF. In addition, the number of CVRF was associated with PE without IRF severity, but not with prognosis.