Natural antibodies targeting LPS in pleural effusions of various etiologies.

Respiratory infection, cancer, and heart failure can cause abnormal accumulation of fluid in the pleural cavity. The immune responses within the cavity are orchestrated by leucocytes that reside in the serosal-associated lymphoid tissue. Natural antibodies (NAbs) are abundant in the serum (S) having a major role in systemic and mucosal immunity; however, their occurrence in pleural fluid (PF) remains an open question. Our aim herein was to detect and measure the levels of NAbs (IgM, IgG, IgA) targeting lipopolysaccharides (LPS) in both the pleural fluid and the serum of 78 patients with pleural effusions (PEs) of various etiologies. The values of anti-LPS NAb activity were extracted through a normalization step regarding the total IgM, IgG, and IgA levels, all determined by in-house ELISA. In addition, the ratios of PF/S values were analyzed further with other critical biochemical parameters from pleural fluids. Anti-LPS NAbs of all Ig classes were detected in most of the samples, while a significant increase of anti-LPS activity was observed in infectious and noninfectious compared with malignant PEs. Multivariate linear regression confirmed a negative correlation of IgM and IgA anti-LPS PF/S ratio with malignancy. Moreover, anti-LPS NAbs PF/S measurements led to increased positive and negative predictive power in ROC curves generated for the discrimination between benign and malignant PEs. Our results highlight the role of anti-LPS NAbs in the pleural cavity and demonstrate the potential translational impact that should be further explored.NEW & NOTEWORTHY Here we describe the detection and quantification of natural antibodies (NAbs) in the human pleural cavity. We show for the first time that IgM, IgG, and IgA anti-LPS natural antibodies are detected and measured in pleural effusions of infectious, noninfectious, and malignant etiologies and provide clinical correlates to demonstrate the translational impact of our findings.

IR808@MnO nano-near infrared fluorescent dye's diagnostic value for malignant pleural effusion.

BACKGROUND: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. RESEARCH QUESTION: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. STUDY DESIGN AND METHODS: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. RESULTS: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 µl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 µl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. INTERPRETATION: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption.

Management of malignant pleural effusion and trapped lung: a survey of respiratory physicians and thoracic surgeons in Australasia.

BACKGROUND: Malignant pleural effusions (MPEs) are common, and a third of them have underlying trapped lung (TL). Management of MPE and TL is suspected to be heterogeneous. Understanding current practices in Australasia is important in guiding policies and future research. AIMS: Electronic survey of Australia-New Zealand respiratory physicians, thoracic surgeons and their respective trainees to determine practice of MPE and TL management. RESULTS: Of the 132 respondents, 56% were respiratory physicians, 23% were surgeons and 20% were trainees. Many respondents defined TL as >25% or any level of incomplete lung expansion; 75% would use large-volume thoracentesis to determine whether TL was present. For patients with TL, indwelling pleural catheters (IPCs) were the preferred treatment irrespective of prognosis. In those without TL, surgical pleurodesis was the most common choice if prognosis was >6 months, whereas IPC was the preferred option if survival was <3 months. Only 5% of respondents considered decortication having a definite role in TL, but 55% would consider it in select cases. Forty-nine per cent of surgeons would not perform decortication when the lung does not fully expand intra-operatively. Perceived advantages of IPCs were minimisation of hospital time, effusion re-intervention and usefulness irrespective of TL status. Perceived disadvantages of IPCs were lack of suitable drainage care, potentially indefinite duration of catheter-in-situ and catheter complications. CONCLUSION: This survey highlights the lack of definition of TL and heterogeneity of MPE management in Australasia, especially for patients with expandable lungs. This survey also identified the main hurdles of IPC use that should be targeted.

Postoperative Trapped Lung After Orthotopic Liver Transplantation is a Predictor of Increased Mortality.

Pleural effusions are a common complication of orthotopic liver transplantation (OLT), and chronic post-OLT pleural effusions have been associated with worse outcomes. Furthermore, "trapped lung" (TL), defined as a restrictive fibrous visceral pleural peel preventing lung re-expansion, may have prognostic significance. We performed a retrospective analysis of adult OLT recipients over a 9-year period at UCLA Medical Center. Post-OLT patients with persistent pleural effusions, defined by the presence of pleural fluid requiring drainage one to 12 months after OLT, were included for analysis. Outcomes for patients with and without TL were compared using univariate and multivariate analysis. Of the 1722 patients who underwent OLT, 117 (7%) patients met our criteria for persistent postoperative pleural effusion, and the incidence of TL was 21.4% (25/117). Compared to patients without TL, those with TL required more surgical pleural procedures (OR 59.8, 95%CI 19.7-181.4, p < 0.001), spent more days in the hospital (IRR 1.56, 95%CI 1.09-2.23, p = 0.015), and had a higher risk of mortality (HR 2.47, 95%CI 1.59-3.82, p < 0.001) following transplant. In sum, we found that post-OLT TL was associated with higher morbidity, mortality, and healthcare utilization. Future prospective investigation is warranted to further clarify the risk factors for developing postoperative pleural effusions and TL.

HΜGB1/sRAGE levels differ significantly between transudates and exudates.

High mobility group box 1(HMGB1) protein operates as an alarmin with multiple roles in immunity and cell homeostasis. It is highly expressed in epithelial barrier sites and acts via the binding to the receptor for advanced glycation end products (RAGE). Production of HMGB1 and soluble RAGE (sRAGE), a decoy receptor for HMGB1, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of HMGB1 and sRAGE in transudative, malignant and parapneumonic pleural effusions (PEs) and to investigate the effect of low and high HMGB1 pleural fluid levels on MeT-5A cell adhesion, migration and spheroid formation, in each group. HMGB1 and sRAGE levels were significantly lower and higher in transudative PEs compared to malignant and parapneumonic PEs, respectively. Patients above 65 years of age had significantly lower HMGB1 and higher sRAGE levels compared to patients below 65 years old. Furthermore, incubation of MeT-5A cells with malignant or parapneumonic PEs bearing low or high levels of HMGB1 yielded significant differential effects on MeT-5A cell adhesion, migration and spheroid formation. In all types of effusions, high HMGB1 levels correlated with more adherence compared to low HMGB1 levels. In transudative and malignant PEs high HMGB1 levels correlated with decreased migration of MeT-5A cells while in parapneumonic ones the effect was the opposite. Only samples from parapneumonic PEs high in HMGB1 achieved uniform spheroid formation. These results reveal a clinical context-dependent effect of the HMGB1/sRAGE axis in PEs.

The Utility of Pleural Fluid Lactate Dehydrogenase to Adenosine Deaminase Ratio in Pleural Tuberculosis.

In high-burden settings, the diagnosis of pleural tuberculosis (TB) is frequently inferred in patients who present with lymphocyte predominant exudative effusions and high adenosine deaminase (ADA) levels. Two recent small retrospective studies suggested that the lactate dehydrogenase (LDH)/ADA ratio is significantly lower in TB than in non-TB pleural effusions and that the LDH/ADA ratio may be useful in differentiating pleural TB from other pleural exudates. We compared the pleural LDH/ADA ratios, ADA levels, and lymphocyte predominance of a prospectively collected cohort of patients with proven pleural TB (n = 160) to those with a definitive alternative diagnosis (n = 68). The mean pleural fluid LDH/ADA ratio was lower in patients with pleural TB than alternative diagnoses (6.2 vs. 34.3, p < 0.001). The area under the receiver operating characteristic curve was 0.92 (p < 0.001) for LDH/ADA ratio and 0.88 (p < 0.001) for an ADA ≥40 U/L alone. A ratio of ≤12.5 had the best overall diagnostic efficiency, while a ratio of ≤10 had a specificity of 90% and a positive predictive value of 95%, with a sensitivity of 78%, making it a clinically useful "rule in" value for pleural TB in high incidence settings. When comparing the LDH/ADA ratio to an ADA level ≥40 U/L in the presence of a lymphocyte predominant effusion, the latter performed better. When lymphocyte values are unavailable, our data suggest that the LDH/ADA ratio is valuable in distinguishing TB effusions from other pleural exudates.

Trastuzumab-emtansine induced pleural and pericardial effusions.

INTRODUCTION: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate which combine trastuzumab (T), a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), and a cytotoxic molecule derived from maytansine (DM1). CASE REPORT: We report the first case of T-DM1-associated pleural and pericardial effusions three weeks after the second course of T-DM1 in a patient with breast cancer. Drug-induced pleural and pericardial effusions was implicated in the absence of other etiologies. The Naranjo Scale indicated a probable drug-induced adverse reaction.Management & outcome: The patient fully recovered after thoracentesis and discontinuation of T-DM1. The patient has reported no side effect after the sixth course of trastuzumab. DISCUSSION: To our knowledge, this is the first case in the literature of bilateral pleural and pericardial effusions in a patient treated with T-DM1. The successful initiation of treatment with trastuzumab following withdrawal of T-DM1 suggests that emtansine played a role in the development of bilateral pleural and pericardial effusions. We hypothesize that the patient's condition was a result of a local inflammatory reaction to emtansine by direct toxicity.

miR-9 Does Not Regulate Lamin A Expression in Metastatic Cells from Lung Adenocarcinoma.

In lung adenocarcinoma, low lamin A expression in pleural metastatic cells has been proposed as a pejorative factor. miR-9 physiologically inhibits the expression of lamin A in neural cells and seems to be a central actor in the carcinogenesis and the metastatic process in lung cancer. Thus, it could be a good candidate to explain the reduction of lamin A expression in lung adenocarcinoma cells. miR-9 expression was analyzed in 16 pleural effusions containing metastatic cells from lung adenocarcinoma and was significantly reduced in patients from the 'Low lamin A expression' group compared to patients from the 'High lamin A expression' group. Then, carcinoma cells selection by fluorescence-activated cell sorting (FACS) was performed according to epithelial membrane antigen (EMA) expression, reflecting lamin A expression. miR-9 was underexpressed in lamin A- carcinoma cells compared to lamin A+ carcinoma cells in patients from the 'Low lamin A expression' group, whereas there was no difference of miR-9 expression between lamin A+ and lamin A- carcinoma cells in patients from the 'High lamin A expression' group. These results suggest that miR-9 does not regulate lamin A expression in metastatic cells from lung adenocarcinoma. On the contrary, miR-9 expression was shown to be reduced in lamin A-negative carcinoma cells.

[Pleural effusion as the first manifestation of pleural isolated myeloid sarcoma: a case report and literature review].

Objective: To analyze the clinic features of isolated myeloid sarcoma (IMS) involving the pleural cavity. Methods: A case of pleural isolated myeloid sarcoma (PIMS) with pleural effusion as the first manifestation was described. The related cases in literatures were reviewed with"myeloid sarcoma"and"pleural effusions"as the keywords to search China HowNet, Wanfang database and PubMed database. Results: A 59-year-old man complained of right chest pain for 2 months and worsening pain with distress and shortness of breath for 2 weeks. The chest CT scan showed pleural effusion on the right side. Flow cytometric analysis of pleural fluid showed that a population of blasts with CD34 expressing was 37.6% of the total nucleated cells. The pleural biopsy through medical thoracoscopy indicated lymphoproliferative lesions by pathological examination. Immunohistochemistry was performed on pleural histological sections and cell blocks of pleural effusions, which showed CD34 and CD117 positive expression. The diagnosis of PIMS was finally made. Two literature papers with 2 complete cases were found and reviewed. The 3 cases were analyzed. There were 2 males and 1 female. The age was 59, 51, 56 years respectively. One case was a patient with 3 weeks of right upper quadrant and epigastric pain, nausea, and weight loss. Cytological examination of the pleural fluid showed numerous poorly differentiated malignant cells. Histology from an open laparotomy in duodenal biopsies, gallbladder, and mesenteric lymph nodes supported the diagnosis of IMS. The other case was a patient with 6 weeks of dyspnea and a large swelling in the upper vestibular region. Thoracentesis showed 82% myeloid blasts in the pleural fluid. A gingival biopsy showed a diffuse infiltration by cells with a blastic appearance and supported IMS. Conclusion: PIMS was a very rare cause of pleural effusions. The cytological and histopathological evidences were useful to diagnose IMS involving the pleural cavity.

Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD-1 receptor.

The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death-1 (PD-1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE-ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD-1 expression on NK/ILC by multiparametric flow-cytometric analysis, while the expression of PD-1 ligand (PD-L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD-1, moreover, both tumor samples and malignant PE-derived tumor cell lines were PD-L1+ suggesting that the interaction between PD-1+ ILC and PD-L1+ tumor cells may hamper antitumor immune responses mediated by NK and ILC.

A 2-year retrospective study on pleural effusions: A cancer centre experience.

BACKGROUND: Cytopathological examination of pleural effusions is a fast and minimally invasive method for verification of the presence of neoplastic cells. We report our 2-year experience using a categorised diagnostic system and reporting risks of malignancy (ROMs) for each defined category. METHODS: Cytological reports of patients between November 2016 and October 2018 were collected, with results primarily classified into a five-tiered classification scheme. Immunohistochemistry markers used in cytology and their results were also recorded. Final agreement to histology and overall test performance was calculated for cases with available concomitant (up to 3 months) pleural biopsies. RESULTS: A total of 519 samples from 385 patients were collected, being 29 (5.6%) classified as non-diagnostic, 291 (56%) as negative, 28 (5.4%) as atypical, 30 (5.8%) as suspicious and 141 (27.2%) as positive. Most requested markers were calretinin, TTF1, Ber-EP4 and Gata-3, being conclusive in 45 (76.3%) cases. Total cyto-histological agreement was achieved in 49 (80.3%) specimens, with an overall sensitivity and specificity of 69.4% and 93.3%, respectively. Positive predictive value was 96.2% and negative predictive value was of 56%. ROM for each diagnostic category was 50% for non-diagnostic, 44% for negative, 50% for atypical, 83.3% for suspicious and 96.2% for positive. CONCLUSIONS: Our 2-year retrospective study has shown a high specificity and positive predictive value for pleural cytology. The use of a five-tiered system has also shown to be highly effective, with a concordantly progressive higher ROM for the assigned diagnostic categories.

OK-432 Treatment of Early Fetal Chylothorax: Pregnancy Outcome and Long-Term Follow-Up of 14 Cases.

BACKGROUND: The treatment options for fetal chylothorax include thoracocentesis, thoracoamniotic shunting, and pleurodesis using OK-432. Knowledge on the long-term outcomes after treatment with OK-432 is limited. OBJECTIVE: The aim of this study was to assess the long-term outcomes of children treated in utero with OK-432. METHODS: We performed follow-up on pregnancies and children treated in utero with OK-432 between 2003 and 2009 at Copenhagen University Hospital Rigshospitalet for pleural effusions at gestational age (GA) 16+0-21+6 weeks. Anamnestic information, physical examination, pulmonary function test, neuropediatric examination, and intelligence testing using the Wechsler Intelligence Scale were used for evaluation. RESULTS: Fourteen cases, all chylothorax, were treated with OK-432. None had preterm premature rupture of membranes (PPROM), and the median GA at delivery was 38+5 (24+4-41+5) weeks. Twelve children were eligible for follow-up. The median age at follow-up was 11.4 (7.8-13.8) years. Pulmonary function was normal in all children and the mean full-scale IQ did not differ from that of normal children. Four children had a diagnosed medical condition, attention deficit disorder, or genetic syndrome. The remaining children had normal follow-up. CONCLUSION: Children treated with OK-432 have comparable survival rates and long-term neurodevelopmental outcomes to those treated with thoracoamniotic shunts. There seems to be a lower risk of procedure-related PPROM.

MicroRNAs - novel biomarkers for malignant pleural effusions.

Lung cancer is one of the most common causes of cancer death. Its poor prognosis can be attributed to the patients' advanced or metastatic presentation at the time of diagnosis. To improve and accelerate the diagnosis, better therapeutic and diagnostic methods are constantly being sought. MicroRNAs (miRNAs) are short nucleotide sequences of single-stranded, non-coding RNA that function as critical post-transcriptional regulators of gene expression. They are identified not only intracellularly, but also in physiological and pathological body fluids. These molecules are responsible for the regulation of approximately 33% of human genes, either regulating the expression of both oncogenes and suppressor genes or acting directly as an oncogene or suppressor gene itself. MiRNAs can contribute to the formation of cancer. The high specificity and sensitivity of miRNAs have been demonstrated with various malignant diseases, and for this reason, they raise particular interest as new and perspective biomarkers of tumours. Our work summarises the available information from recent years regarding the possibility of using miRNAs as biomarkers in the diagnosis of neoplasms. In this review, we focused on malignant pleural effusions with an emphasis on non-small cell lung cancer (NSCLC).

Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.

Thoracic injection of low-dose interleukin-2 as an adjuvant therapy improves the control of the malignant pleural effusions: a systematic review and meta-analysis base on Chinese patients.

BACKGROUND: Interleukin-2 (IL-2) is an important immunotherapy cytokine for various diseases including cancer. Some studies reported the efficacy and safety on cisplatin combined with IL-2 versus cisplatin alone for treating malignant pleural effusion (MPE) through thoracic injection. METHODS: We searched these studies from medical electronic database. A total of 18 studies that met the inclusion criteria were recruited in this meta-analysis. Pooled odds ratios (OR) with 95% confidence intervals (CI) were determined by the fixed effects model of meta-analysis. RESULTS: The objective response rate (ORR) and disease control rate (DCR) of cisplatin plus IL-2 for controlling MPE was significantly higher than that of cisplatin alone (p < 0.001). In addition, compared with cisplatin alone, the presence of IL-2 improved the quality of life (QOL) of patients with MPE (p < 0.001). Although the use of IL-2 seemed to increase the probability of fever in patients (p = 0.001), it did not lead to extra other side effects (AEs) including myelotoxicity, nausea/vomiting and chest pain (p > 0.05). CONCLUSIONS: The low-dose IL-2 improved the ORR, DCR and QOL of patients in the treatment of MPE. Although it may cause fever in patients, it did not increase other AEs.

Intensive Care of Pulmonary Complications Following Liver Transplantation.

Chronic liver disease has been associated with pulmonary dysfunction both before and after liver transplantation. Post-liver transplantation pulmonary complications can affect both morbidity and mortality often necessitating intensive care during the immediate postoperative period. The major pulmonary complications include pneumonia, pleural effusions, pulmonary edema, and atelectasis. Poor clinical outcomes have been known to be associated with age, severity of liver dysfunction, and preexisting lung disease as well as perioperative events related to fluid balance, particularly transfusion and fluid volumes. Delineating each and every one of these pulmonary complications and their associated risk factors becomes paramount in guiding specific therapeutic strategies.

Local Anaesthetic (Medical) Thoracoscopy Services in the UK.

BACKGROUND: Local anaesthetic thoracoscopy (LAT) is an important procedure in the management pathway of patients with pleural effusions, particularly those with suspected malignancy. The last survey evaluating the use and development of LAT services in the UK was conducted over a decade ago. OBJECTIVES: We performed a survey of LAT practices in the UK to explore procedural preferences and variations in practice. METHODS: The online survey was cascaded via regional pleural specialists to sites performing LAT. One response per site was accepted. RESULTS: Thirty-seven responses were received from England, Scotland and Wales. Most centres have regular access to a dedicated list and a designated area to perform LAT. 97% of the centres have at least 2 trained thoracoscopists. Some variation in practice is seen with patient preparation pre-procedure and medication use. Other procedures, such as insertion of indwelling pleural catheters and adhesiolysis, are not uncommon to be undertaken at the time of LAT. CONCLUSIONS: Overall, the results are comparable, excepting some minor variations in patient preparation pre-procedure. We hope that this survey functions as an information resource for centres developing a LAT service or for those considering expansion.

Diagnostic Accuracy of Lateral Decubitus Chest Radiography before Pleural Maneuvers for the Management of Pleurisies in the Era of Chest Ultrasound.

BACKGROUND: Chest ultrasound (CUS) is the gold standard to detect pleural adhesions before pleural maneuvers. However, the CUS technique is not available in all countries where the assessment is only based on clinical examination and chest radiography. OBJECTIVE: To assess the value of lateral decubitus chest radiography (LDCR) to detect pleural adhesions. METHODS: Consecutive patients with pleural effusions undergoing LCDR followed by medical thoracoscopy the day after were identified from an institutional database. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for LDCR were calculated. RESULTS: Eighty-six patients were included in the study. The sensitivity, specificity, PPV, and NPV of LDCR for the presence of adhesions taking into account the shape of the horizontal level were 71.2% (56.7-82.5), 44.1% (27.6-61.9), 66.1% (52.1-77.8), and 50% (31.7-68.3), respectively. The accuracy to predict pleural adhesions for the sign "incomplete horizontal level" was 60.5 (49.3-70.7). The accuracy to predict pleural adhesions in case of irregular aspect of the horizontal level was 53.5 (42.5-64.2). CONCLUSIONS: The accuracy of LDCR for the detection of pleural adhesions is low in patients with pleural effusion and LDCR is not sufficient before pleural maneuvers. This has to be taken into account in countries with a high prevalence of pleural tuberculosis which usually lead to loculated pleural effusions. CUS has to be urgently included in dedicated educational programs in these areas in order to decrease the complications related to unexpected pleural adhesions and achieve better planning for the management of pleural effusions.

Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial.

RATIONALE: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. OBJECTIVES: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. METHODS: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34-83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. CONCLUSIONS: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Lung Ultrasound Findings Detected During Inpatient Echocardiography Are Common and Associated With Short- and Long-term Mortality.

OBJECTIVES: Although pulmonary abnormalities are easily seen with standard echocardiography or pocket-sized ultrasound devices, we sought to observe the prevalence of lung ultrasound apical B-lines and pleural effusions and their associations with inpatient, 1-year, and 5-year mortality when found in hospitalized patients referred for echocardiography. METHODS: We reviewed 486 initial echocardiograms obtained from consecutive inpatients over a 3-month period, in which each examination included 4 supplemental images of the apex and the base of both lungs. Kaplan-Meier survival curves were used to compare mortality rates among patients with versus without lung findings. Cox proportional hazard regression was used to determine the relative contributions of age, sex, effusions, and B-lines to overall mortality. RESULTS: Of the 486 studies, the mean patient age ± SD was 68 ± 17 years; the median age was 70 years (interquartile range, 27 years); and 191 (39%) had abnormal lung findings. The presence versus absence of abnormal lung findings was related to initial-hospital (8.9% versus 2.0%; P = .001), 1-year (33% versus 14%; P < .001), and 5-year (56% versus 31%; P < .001) mortality. Ultrasound apical B-lines and pleural effusions were both independently associated with increased mortality during initial hospitalization (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.7-11.0; and HR, 2.5; 95% CI, 1.1-6.0, respectively). Pleural effusions were also associated with increased 1-year mortality (HR, 2.3; 95% CI, 1.5-3.4). CONCLUSIONS: In hospitalized patients undergoing echocardiography, the simple addition of 4 quick 2-dimensional pulmonary views to the echocardiogram often detects abnormal findings that have important implications for short- and long-term mortality.