The incidence of non-malignant pleural effusions far outweighs that of malignant pleural effusions and is estimated to be at least 3-fold higher. These so-called benign effusions do not follow a "benign course" in many cases, with mortality rates matching and sometimes exceeding those of malignant pleural effusions. In addition to the impact on patients, healthcare systems are also significantly affected, with recent US epidemiological data demonstrating that 75% of resource allocation for pleural effusion management is spent on non-malignant pleural effusions (excluding empyema). Despite this significant burden of disease, and by existing at the junction of multiple medical specialties, reflecting a heterogenous constellation of medical conditions, non-malignant pleural effusions are rarely the focus of research or the subject of management guidelines. With this European Respiratory Society Task Force, we assembled a multispecialty collaborative across 11 countries and three continents to provide a statement based on systematic searches of the medical literature to highlight evidence in the management of the following clinical areas: a diagnostic approach to transudative effusions, heart failure, hepatic hydrothorax, end-stage renal failure, benign asbestos-related pleural effusion, post-surgical effusion and nonspecific pleuritis.

High endothelial venules (HEVs) are vessels specialized in the extravasation of lymphocytes from the blood to the tissue implicated in the immune microenvironment of several tumors. Their presence has been never studied in the pleural tissue.

We retrospectively studied 149 surgical pleural biopsies by immunohistochemistry for MECA-79 expression, a marker specifically recognizing HEVs. The tissues included 44 (44 %) inflammatory and 105 (56 %) neoplastic diseases. The latter corresponded to 34 (22.8 %) mesotheliomas and 71 (47.7 %) metastases from lung (n=50) or breast (n=21) primaries.

HEVs were present in 102 (68 %) of all pleural specimens with a mean number of foci containing HEVs of 13.33 (±20.64). Neoplastic pleural pathologies harbored HEVs in 73.3 % of the cases compared to the non-neoplastic pathologies which harbored HEVs in 56.8 % of the cases (p=0.048). Their presence did not differ between pulmonary or mammary metastasis (p=0.7).

We show for the first time that HEVs are present in the pleural cavity probably participating in the immune microenvironment of inflammatory and neoplastic pleural disease.

Infective pleural effusions are mainly represented by parapneumonic effusions and empyema. These conditions are a spectrum of pleural diseases that are commonly encountered and carry significant mortality and morbidity rates reaching upwards of 50%. The causative etiology is usually an underlying bacterial pneumonia with the subsequent seeding of the infectious culprit and inflammatory agents to the pleural space leading to an inflammatory response and fibrin deposition. Radiographical evaluation through a CT scan or ultrasound yields high specificity and sensitivity, with features such as septations or pleural thickening indicating worse outcomes. Although microbiological yields from pleural studies are around 56% only, fluid analysis assists in both diagnosis and prognosis by evaluating pH, glucose, and other biomarkers such as lactate dehydrogenase. Management centers around antibiotic therapy for 2-6 weeks and the drainage of the infected pleural space when the effusion is complicated through tube thoracostomies or surgical intervention. Intrapleural enzymatic therapy, used to increase drainage, significantly decreases treatment failure rates, length of hospital stay, and surgical referrals but carries a risk of pleural hemorrhage. This comprehensive review article aims to define and delineate the progression of parapneumonic effusions and empyema as well as discuss pathophysiology, diagnostic, and treatment modalities with aims of broadening the generalist's understanding of such complex disease by reviewing the most recent and relevant high-quality evidence.

Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.

Disorders in the inflammatory process underlie the pathogenesis of numerous diseases. The utilization of natural products as anti-inflammatory agents is a well-established approach in both traditional medicine and scientific research, with studies consistently demonstrating their efficacy in managing inflammatory conditions. Pequi oil, derived from Caryocar brasiliense, is a rich source of bioactive compounds including fatty acids and carotenoids, which exhibit immunomodulatory potential. This systematic review aims to comprehensively summarize the scientific evidence regarding the anti-inflammatory activity of pequi oil. Extensive literature searches were conducted across prominent databases (Scopus, BVS, CINAHL, Cochrane, LILACS, Embase, MEDLINE, ProQuest, PubMed, FSTA, ScienceDirect, and Web of Science). Studies evaluating the immunomodulatory activity of crude pequi oil using in vitro, in vivo models, or clinical trials were included. Out of the 438 articles identified, 10 met the stringent inclusion criteria. These studies collectively elucidate the potential of pequi oil to modulate gene expression, regulate circulating levels of pro- and anti-inflammatory mediators, and mitigate oxidative stress, immune cell migration, and cardinal signs of inflammation. Moreover, negligible to no toxicity of pequi oil was observed across the diverse evaluated models. Notably, variations in the chemical profile of the oil were noted, depending on the extraction methodology and geographical origin. This systematic review strongly supports the utility of pequi oil in controlling the inflammatory process. However, further comparative studies involving oils obtained via different methods and sourced from various regions are warranted to reinforce our understanding of its effectiveness and safety.

The main target is evacuation; however, with evidence about the value of intrapleural instillation of different fibrinolytic agents still under evaluation, our aim was comparing the effectiveness and safety of intrapleural instillation of sodium bicarbonate (NaHCO₃) in comparison with urokinase in patients with infected pleural effusion.

Our prospective cohort study included 40 patients with complicated empyema; the diagnosis was based on analysis of aspirated fluid in association with radiological and bacteriological culture. The patients were subjected to instillation of two different fibrinolytic agents; the first one was NaHCO₃, the second was urokinase.

The commonest underlying chest infection that was visualized by CT was pneumonia 70%. Nearly half of cases had community-acquired infection (45%), and more than half of them (55%) had anaerobic infection, and only five cases had TB pleural effusion based on ADA-positive, tuberculin skin test in addition to Abram's needles closed biopsy. The rate of repeated therapeutic thoracentesis success in each group was 85%; 80% in NaHCO₃ group, and 90% in urokinase group, both of them was significantly equal, P=0.37. Moreover, the frequency of complications in all patients was less than 13%, hence hemothorax and iatrogenic pneumothorax was 12.5%, and only 10% of cases were admitted in ICU after the maneuver, with insignificant difference in between the groups. However, looking at the smaller rate of RTT failure of NaHCO₃ or urokinase, the logistic regression model showed that RTT-NaHCO₃ was insignificantly related to failure in both unadjusted and adjusted models, P=0.37 and 0.32, respectively, and only smoking habits increase the likelihood of failure 9-fold (OR=8.9, P=0.04) with respect to age, sex, and treatment methods.

The efficacy of repeated therapeutic thoracentesis (RTT) with intrapleural instillation of NaHCO₃ was effective and safe, the same as urokinase, with consideration that NaHCO₃ was much more available and affordable than urokinase.

Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.

Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of the efferent sympathetic and parasympathetic innervation in carcinogenesis has been extensively investigated, the role of the afferent sensory neurons and the neuropeptides in tumor development, growth, and progression is recently appreciated. Similarly, current findings point to the significant role of Schwann cells as part of neuro-immune interactions. Hence, in this review, we mainly focus on local and systemic effects of sensory nerve activity as well as Schwann cells in carcinogenesis and metastasis. Specific denervation of vagal sensory nerve fibers, or vagotomy, in animal models, has been reported to markedly increase lung metastases of breast carcinoma as well as pancreatic and gastric tumor growth, with the formation of liver metastases demonstrating the protective role of vagal sensory fibers against cancer. Clinical studies have revealed that patients with gastric ulcers who have undergone a vagotomy have a greater risk of stomach, colorectal, biliary tract, and lung cancers. Protective effects of vagal activity have also been documented by epidemiological studies demonstrating that high vagal activity predicts longer survival rates in patients with colon, non-small cell lung, prostate, and breast cancers. However, several studies have reported that inhibition of sensory neuronal activity reduces the development of solid tumors, including prostate, gastric, pancreatic, head and neck, cervical, ovarian, and skin cancers. These contradictory findings are likely to be due to the post-nerve injury-induced activation of systemic sensory fibers, the level of aggressiveness of the tumor model used, and the local heterogeneity of sensory fibers. As the aggressiveness of the tumor model and the level of the inflammatory response increase, the protective role of sensory nerve fibers is apparent and might be mostly due to systemic alterations in the neuro-immune response. Hence, more insights into inductive and permissive mechanisms, such as systemic, cellular neuro-immunological mechanisms of carcinogenesis and metastasis formation, are needed to understand the role of sensory neurons in tumor growth and spread.