An 88-Year-Old Woman With Pneumothorax and Black Pleural Effusion.

CASE PRESENTATION: An 88-year-old woman was admitted to our hospital with the sudden onset of dyspnea after eating. The patient had undergone nephrectomy for a left renal tumor 24 years previously. The patient had been prescribed ferrous citrate for iron-deficiency anemia. She complained of appetite loss a few days before admission but had no abdominal pain. CT scan showed no abnormalities in the lungs but a mass in the liver.

Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Flow Cytometry Analysis in Breast Implant-Associated Anaplastic Large Cell Lymphoma: Three Case Reports.

Breast Implant-Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare T-cell non-Hodgkin lymphoma associated with breast prosthetic implants and represents a diagnostic challenge. The National Comprehensive Cancer Network (NCCN) guidelines, updated in 2024, recommend for diagnosis an integrated work-up that should include cell morphology, CD30 immunohistochemistry (IHC), and flow cytometry (FCM). CD30 IHC, although the test of choice for BIA-ALCL diagnosis, is not pathognomonic, and this supports the recommendation to apply a multidisciplinary approach. A close collaboration between pathologists and laboratory professionals allowed the diagnosis of three BIA-ALCLs, presented as case reports, within a series of 35 patients subjected to periprosthetic effusions aspiration from 2018 to 2023. In one case, rare neoplastic cells were identified by FCM, and this result was essential in leading the anatomopathological picture as indicative of this neoplasm. In fact, the distinction between a lymphomatous infiltrate from reactive cells may be very complex in the cytopathology and IHC setting when neoplastic cells are rare. On the other hand, one limitation of FCM analysis is the need for fresh samples. In this study, we provide evidence that a dedicated fixative allows the maintenance of an unaltered CD30 expression on the cell surface for up to 72 h.

Detection of the Effects of Root Exudates (Diffusates) on Nematode Hatching and Attraction.

Plant-parasitic nematodes have enormous economic and social impacts. The majority of plant-parasitic nematodes are soil dwelling and feed on plant roots. Exudates from actively growing roots initiate hatch of some nematode species, thus ensuring infective juveniles emerge in close proximity to host plant roots. Several gradients of volatile and non-volatile compounds are established around plant roots, at least some of which are used by nematodes to orientate toward the roots. Plant-parasitic nematodes are microscopic in size (less than 1 mm in length and between 15 and 20 µm in diameter), so investigations into behavior are challenging. Various in vitro techniques have been used to evaluate the effects of root exudates. The techniques can also be used to evaluate the comparative attractiveness of different plants or cultivars of the same plant species. This chapter describes some examples of different types of basic in vitro assays.

Recurrent leishmaniasis infection isolated in the pleural fluid.

We present a rare case of recurrent leishmaniasis infection in a female in her 80s who re-presented with a pleural effusion. The patient was initially investigated as an outpatient for cytopenia and underwent a bone marrow biopsy which subsequently diagnosed visceral leishmaniasis. Following full treatment, and apparent recovery, she re-presented with pleural effusion, hypoalbuminaemia and cytopenia. Leishmania was eventually isolated in a pleural fluid sample obtained on therapeutic drainage, and she was treated for a recurrence at a tertiary infectious disease unit. This interesting and challenging case demonstrates the importance of suspecting leishmaniasis recurrence in previously treated cases and the diagnostic benefit of pleural fluid analysis in the context of suspected leishmaniasis.

Liquid chromatography-tandem mass spectrometry methods for quantification of total and free antibiotic concentrations in serum and exudate from patients with post-sternotomy deep sternal wound infection receiving negative pressure wound therapy.

BACKGROUND: Systemically administered antibiotics are thought to penetrate the wounds more effectively during negative pressure wound therapy (NPWT).To test this hypothesis total and free antibiotic concentrations were quantified in serum and wound exudate. METHODS: UHPLC-MS/MS methods were developed and validated for the determination of ceftazidime, cefepime, cefotaxime, cefuroxime, cefazolin, meropenem, oxacillin, piperacillin with tazobactam, clindamycin, ciprofloxacin, sulfamethoxazole/trimethoprim (cotrimoxazole), gentamicin, vancomycin, and linezolid. The unbound antibiotic fraction was obtained by ultrafiltration using a Millipore Microcon-30kda Centrifugal Filter Unit. Analysis was performed on a 1.7-µm Acquity UPLC BEH C18 2.1 × 100-mm column with a gradient elution. RESULTS: The validation was performed for serum, exudates and free fractions. For all matrices, requirements were met regarding linearity, precision, accuracy, limit of quantitation, and matrix effect. The coefficient of variation was in the range of 1.2-13.6%.and the recovery 87.6-115.6%, respectively. Among the 29 applications of antibiotics thus far, including vancomycin, clindamycin, ciprofloxacin, oxacillin, cefepime, cefotaxime, cotrimoxazole, and gentamicin, total and free antibiotic concentrations in serum and exudate were correlated. CONCLUSION: This method can accurately quantify the total and free concentrations of 16 antibiotics. Comparison of concentration ratios between serum and exudates allows for monitoring individual antibiotics' penetration capacity in patients receiving NPWT.

Differential Diagnosis of Pleural Effusion Using Machine Learning.

Rationale: Differential diagnosis of pleural effusion is challenging in clinical practice. Objectives: We aimed to develop a machine learning model to classify the five common causes of pleural effusions. Methods: This retrospective study collected 49 features from clinical information, blood, and pleural fluid of adult patients who underwent diagnostic thoracentesis between October 2013 and December 2018. Pleural effusions were classified into the following five categories: transudative, malignant, parapneumonic, tuberculous, and other. The performance of five different classifiers, including multinomial logistic regression, support vector machine, random forest, extreme gradient boosting, and light gradient boosting machine (LGB), was evaluated in terms of accuracy and area under the receiver operating characteristic curve through fivefold cross-validation. Hybrid feature selection was applied to determine the most relevant features for classifying pleural effusion. Results: We analyzed 2,253 patients (training set, n = 1,459; validation set, n = 365; extra-validation set, n = 429) and found that the LGB model achieved the best performance in both validation and extra-validation sets. After feature selection, the accuracy of the LGB model with the selected 18 features was equivalent to that with all 49 features (mean ± standard deviation): 0.818 ± 0.012 and 0.777 ± 0.007 in the validation and extra-validation sets, respectively. The model's mean area under the receiver operating characteristic curve was as high as 0.930 ± 0.042 and 0.916 ± 0.044 in the validation and extra-validation sets, respectively. In our model, pleural lactate dehydrogenase, protein, and adenosine deaminase levels were the most important factors for classifying pleural effusions. Conclusions: Our LGB model showed satisfactory performance for differential diagnosis of the common causes of pleural effusions. This model could provide clinicians with valuable information regarding the major differential diagnoses of pleural diseases.

Myelomatous pleural effusion developing after autologous stem cell transplantation in a patient with multiple myeloma: A rare case.

Myelomatous pleural effusion (MPE) is a very rare condition with a poor prognosis. In our case of multiple myeloma (MM) with early recurrence presenting with a MPE, management of the treatment is discussed together with the case presentation. A 35 year old female patient with a diagnosis of lambda light chain MM presented with complaints of dyspnea and pain in the left shoulder 2 months after autologous transplantation. On physical examination, respiratory sounds were decreased in the lower lobe of the left lung and there was dullness. Pleural effusion and plasmacytoma, more prominent on the left, were detected on chest X ray and thorax computed tomography (CT). The pleural fluid collected during therapeutic thoracentesis was examined by flow cytometry, cytology, and peripheral smear examination and as a result, the patient was considered to have early recurrence after autologous transplantation, DRd chemotherapy was immediately started, and clinical and radiological improvement was observed. Pleural effusion developing in patients with MM should be evaluated in terms of MPE. In the presence of MPE, the duration of response to treatment is short, thus effective and dynamic treatment methods for bridging should be used before referral of the patients to clinical trials and hematopoietic stem cell transplantation.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.

BACKGROUND: Lung cancer is the most common cause of malignant pleural effusion (MPE). Serum human epididymis secretory protein 4 (HE4) is a useful diagnostic marker for lung cancer. OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of pleural fluid HE4 for MPE. DESIGN: A prospective, double-blind diagnostic test accuracy study. METHODS: Patients with undiagnosed pleural effusion were enrolled in two cohorts (Hohhot and Changshu). Electrochemiluminescence immunoassay was used to detect pleural fluid HE4. The diagnostic accuracy of HE4 was evaluated by a receiver operating characteristic (ROC) curve, and the net benefit of HE4 was assessed by a decision curve analysis (DCA). RESULTS: A total of 66 MPEs and 86 benign pleural effusions (BPEs) were enrolled in the Hohhot cohort. In the Changshu cohort, 26 MPEs and 32 BPEs were enrolled. In both cohorts, MPEs had significantly higher pleural fluid HE4 than BPEs. The area under the ROC curve (AUC) of HE4 was 0.73 (95% CI: 0.64-0.81) in the Hohhot cohort and 0.79 (95% CI: 0.67-0.91) in the Changshu cohort. At a threshold of 1300 pmol/L, HE4 had sensitivities of 0.44 (95% CI: 0.33-0.56) in the Hohhot cohort and 0.54 (95% CI: 0.35-0.73) in the Changshu cohort. The corresponding specificities were 0.90 (95% CI: 0.83-0.95) in the Hohhot cohort and 0.94 (95% CI: 0.84-1.00) in the Changshu cohort. In subgroup analyses, HE4 had an AUC (95% CI) of 0.78 (0.71-0.85) in exudates and an AUC of 0.69 (0.57-0.81) in patients with negative effusion cytology. The DCA revealed that HE4 determination had a net benefit in both cohorts. CONCLUSION: Pleural fluid HE4 has moderate diagnostic accuracy for MPE and has net benefit in pleural effusion patients with unknown etiology.

A patient with widespread skin lesions presenting with massive pleural effusion.

Mycosis fungoides is the most commonly seen type of cutaneous T-cell lymphoproliferative disease. While mycosis fungoides is linked to an increased risk of developing secondary malignancies, the occurrence of B-cell-originated disease in association with it is exceedingly rare. A 66-year-old male with persistent papillomatous skin eruption was admitted due to dyspnea. Chest X-ray, positron emission tomography, and chest computed tomography revealed axillary and mediastinal lymph node enlargement and right lower pulmonary lobe infiltration along with right-sided massive pleural effusion. Histological and immunohistochemical findings of pleural biopsy and axillary lymph nodes suggested a diagnosis of pulmonary extranodal marginal zone lymphoma. Skin biopsies from the abdomen, chest, and legs revealed CD4/CD8 double-positive patch stage of mycosis fungoides. After completing six cycles of chemotherapy, complete remission of lymphoma was achieved, with the skin eruptions remaining unchanged. Herein, the authors present a unique case of concomitant diagnoses of mycosis fungoides and marginal zone B-cell lymphoma of the respiratory system to emphasize the importance of careful evaluation of each finding.

Pleural Effusion: Diagnostic Approach in Adults.

Pleural effusion affects 1.5 million patients in the United States each year. New effusions require expedited investigation because treatments range from common medical therapies to invasive surgical procedures. The leading causes of pleural effusion in adults are heart failure, infection, malignancy, and pulmonary embolism. The patient's history and physical examination should guide evaluation. Small bilateral effusions in patients with decompensated heart failure, cirrhosis, or kidney failure are likely transudative and do not require diagnostic thoracentesis. In contrast, pleural effusion in the setting of pneumonia (parapneumonic effusion) may require additional testing. Multiple guidelines recommend early use of point-of-care ultrasound in addition to chest radiography to evaluate the pleural space. Chest radiography is helpful in determining laterality and detecting moderate to large pleural effusions, whereas ultrasonography can detect small effusions and features that could indicate complicated effusion (i.e., infection of the pleural space) and malignancy. Point-of-care ultrasound should also guide thoracentesis because it reduces complications. Computed tomography of the chest can exclude other causes of dyspnea and suggest complicated parapneumonic or malignant effusion. When diagnostic thoracentesis is indicated, Light's criteria can help differentiate exudates from transudates. Pleural aspirate should routinely be evaluated using Gram stain, cell count with differential, culture, cytology, protein, l-lactate dehydrogenase, and pH levels. Additional assessments should be individualized, such as tuberculosis testing in high-prevalence regions. Parapneumonic effusions are the most common cause of exudates. A pH level less than 7.2 is indicative of complicated parapneumonic effusion and warrants prompt consultation for catheter or chest tube drainage, possible tissue plasminogen activator/deoxyribonuclease therapy, or thoracoscopy. Malignant effusions are another common cause of exudative effusions, with recurrent effusions having a poor prognosis.

Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

Local anesthetic thoracoscopy (LAT) is a minimally invasive diagnostic procedure gaining recognition among chest physicians for managing undiagnosed pleural effusions. This single-port procedure is conducted with the patient under mild sedation and involves a contralateral decubitus position. It is performed in a sterile setting, typically a bronchoscopy suite or surgical theater, by a single operator with support from a procedure-focused nurse and a patient-focused nurse. The procedure begins with a thoracic ultrasound to determine the optimal entry point, usually in the IV-V intercostal space along the midaxillary line. Lidocaine/mepivacaine, with or without adrenaline, is used to anesthetize the skin, thoracic wall layers, and parietal pleura. A designated trocar and cannula are inserted through a 10 mm incision, reaching the pleural cavity with gentle rotation. The thoracoscope is introduced through the cannula for systematic inspection of the pleural cavity from the apex to the diaphragm. Biopsies (typically six to ten) of suspicious parietal pleura lesions are obtained for histopathological evaluation and, when necessary, microbiological analysis. Biopsies of the visceral pleura are generally avoided due to the risk of bleeding or air leaks. Talc poudrage may be performed before inserting a chest tube or indwelling pleural catheter through the cannula. The skin incision is sutured, and intrapleural air is removed using a three-compartment or digital chest drainage system. The chest tube is removed once there is no airflow, and the lung has satisfactorily re-expanded. Patients are usually discharged after 2-4 h of observation and followed up on an outpatient basis. Successful LAT relies on careful patient selection, preparation, and management, as well as operator education, to ensure safety and a high diagnostic yield.

Supplementation with Ashitaba (Angelica keiskei) Yellow Stem Exudate Prevents Aging-Induced Thrombotic Tendencies and Systemic Inflammation Without Affecting Body Weight Gain in Mice.

Angelica keiskei Koidzumi (Ashitaba) is a traditional folk medicine and health supplement in Japan. Ashitaba yellow stem exudate (AYE) contains abundant chalcones and thus has the potential to treat and prevent many pathological states such as cancer, inflammation, obesity, diabetics, thrombosis, and hypertension. Levels of plasminogen activator inhibitor 1 (PAI-1), a key regulator of the fibrinolytic system, increase with age in mouse plasma. Therefore, we aimed to determine the effects of AYE on plasma thrombotic parameters in aging mice. Long-term (52 weeks) AYE supplementation significantly decreased age-induced increases of PAI-1 in mouse plasma. Supplementation with AYE decreased levels of the acute-phase and fibrinolytic protein plasma plasminogen, and significantly decreased those of tumor necrosis factor α. These results suggested that continuous intake of AYE throughout life decreases age-induced systemic inflammation and prevents thrombotic tendencies without affecting body weight gain in aged mice. Our findings showed that supplementing diets with AYE might help to prevent thrombotic diseases in elderly individuals.

Simulated phytoremediation by root exudates of Sudan grass of soil organochlorine pesticides: impact on the rhizosphere microbial community.

The present work aims to study the efficiency of root exudates of Sudan grass on the degradation of organochlorine pesticides (OCPs) and the consequent impact on the microbial and ecological characteristics of the soil, including population composition, quantity dynamics, and community structure. Pot experiments were carried out to study the effect of root exudates on the degradation of OCPs at initial concentrations ranging from 66.67 to 343.61 mg/kg. In addition, the influence of root exudates on the rhizosphere microbial growth and their community structure was studied by monitoring the microbial biomass carbon, microbial biomass nitrogen, and phospholipid fatty acids (PLFAs) in the soils. In the range of OCP content (66.67 ~ 343.61 mg/kg), the soil-microbial system mediated by root exudates significantly promoted the removal of OCP pollutants. The removal rate of OCPs in the rhizosphere soil (TR2) was as high as 79.32%, 36.86% higher than that in the OCP-contaminated group (TR1) and 60.63% higher than that in the sterilized treatment group (CK). Under the same treatment conditions (pollution level and additive dose), the enhanced removal rate of HCHs, toxaphene, HCB, aldrin, and γ-chlordane by root exudates was much higher than the total amount of OCPs, while the extent of enhanced dissipation of DDTs, mirex, endosulfanI, dieldrin, and heptachlor epoxide was always lower than that in the corresponding soils. During the experiment, the phospholipid fatty acid content of bacteria was dominant, followed by that of fungi, and their variation trend was consistent with the degradation characteristics of OCPs in soil. Root exudates of Sudan grass might change the rhizosphere bacterial and fungal community structure during the process of phytoremediation, leading to enhanced OCP degradation.

Application of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in reporting serous effusion: A retrospective study.

In order to develop uniform diagnostic standards and reporting terminology, the International Academy of Cytology and the American Society of Cytopathology have recommended the establishment of the International System for Reporting Serous Fluid Cytopathology (ISRSFC). ISRSFC has 5 diagnostic categories: non-diagnostic (ND), negative for malignancy (NFM), atypia of unknown significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). So far, very few studies have evaluated the risk of malignancy (ROM) and performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) of different categories. The purpose of this study was to reclassify serous effusions based on the ISRSFC and to assess their ROM and performance characteristics. All serous effusions from January 2017 to December 2022 were categorized according to the ISRSFC. Using histopathological diagnosis as the gold standard, the ROM and performance characteristics were calculated for each group. Finally, a total of 2103 serous effusion specimens were analyzed. After reclassification, 9 (0.4%) cases were classified as ND, 547 (26%) as NFM, 94 (4.5%) as AUS, 386 (18.4%) as SFM, and 1067 (50.7%) as MAL. The ROMs for ND, NFM, AUS, SFM and MAL were calculated to be 50%, 24.9%, 36.8%, 89.0%, and 100%, respectively. As an easy-to-grasp reporting system, ISRSFC provides a consistent standard for better communication between physicians and pathologists.

Conditional diagnostic accuracy according to inflammation status and age for diagnosing tuberculous effusion.

BACKGROUND: Tuberculous effusion varies from lymphocyte-dominant to neutrophilic effusion according to inflammation status. The criteria of adenosine deaminase (ADA) and lymphocyte/neutrophil (L/N) ratio have yet not been evaluated across different disease conditions. METHODS: Patients who conducted pleural fluid analysis from 2009 to 2019 at Asan Medical Center were included. Criteria (ADA of 50 and L/N ratio of 0.75) were evaluated by quantile subgroups according to age, C-reactive protein (CRP), white blood cell (WBC), and lactate dehydrogenase (LD) by the Monte Carlo simulation method to diagnose tuberculosis. The model for the ADA and L/N ratio was evaluated by AUROC. RESULTS: Among the 2,918 reviewed cases, 2034 were included with 229 (11.26%) tuberculosis cases. The mean baseline ADA AUROC was 0.88 across all patients. Increased CRP and WBC showed high proportions of neutrophilic tuberculous effusion, with low sensitivity of approximately 45% and 33% in the fifth WBC and CRP groups, respectively. The AUROC of the models decreased with the increase in WBC and CRP groups (ADA model: 0.69 [the top quantile WBC group], 0.74 [the top quantile CRP group]). The AUROC of the models did not show a trend according to the increase in LD and age. CONCLUSION: Inflammatory status affects the diagnostic metrics for tuberculous effusion due to the progression of tuberculous effusion. Clinicians should consider the low accuracy of tuberculous effusion criteria in high-inflammatory conditions when diagnosing tuberculosis.

Diagnostic accuracy of flow cytometry in detecting malignant epithelial cells in serous effusions.

INTRODUCTION: This study aims to evaluate diagnostic accuracy of flow cytometry (FCM) in detecting malignant epithelial cells in serous effusions. MATERIALS AND METHODS: Flow cytometric assessment of 96 serous fluids (86 ascitic, 10 pleural) was performed by using epithelial cell adhesion molecule (EpCAM) (in all 96 fluids) and MUC-1 (in a subgroup of 40 fluids) as epithelial markers and CD45 and CD14 as leucocyte markers. The percentage of EpCAM positivity and MUC-1 positivity was calculated in the CD14 and CD45 dual negative population by selective gating. The findings were then correlated with the defined gold standard criteria. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for EpCAM was found to be 92.06%, 96.96%, 98.31%, 86.48%, and 93.75%, respectively, while that for MUC-1 was 79.16%, 93.75%, 95%, 71.4%, and 85%, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy for dual positivity for EpCAM and MUC-1 was found to be 83.3%, 100%, 100%, 80%, and 90% respectively. On combining FCM with cytomorphology the sensitivity, specificity, PPV, NPV, and diagnostic accuracy all increased greatly to 95.3%, 100%, 100%, 91.4%, and 96.8%, respectively. CONCLUSIONS: This study highlights the importance of multicolored flow cytometric analysis in detecting epithelial malignancies in effusions specially in cases belonging to the atypia of undetermined significance and suspicious for malignancy categories and in cases with strong clinical suspicion of malignancy with negative fluid cytology. We recommend the combined use of FCM and cytology for this specific subgroup of patients in routine clinical practice for fast and accurate reporting.