Search Results (26)

Background: Parapneumonic effusion is a common complication of community-acquired pneumonia and can range from a simple inflammatory transudate to an organized purulent collection, known as empyema. Progression to empyema significantly worsens the prognosis, leading to increased morbidity, longer hospital stays, and a greater need for invasive interventions. Several risk factors for pleural effusion and progression to empyema have been identified, but the absence of standardized criteria underline the need for better risk stratification. We analyzed clinical and laboratory data from a cohort of children hospitalized with pneumonia associated with pleural effusion or empyema, to identify predictive risk factors associated with these complications. Methods: We retrospectively analyzed clinical and laboratory data from patients admitted to our Pediatric Emergency Department with pneumonia complicated by pleural effusion and compared patients with simple effusion to those with empyema. Results: Seventeen children with simple pleural effusion and eighteen with empyema were enrolled. Patients with empyema had higher absolute neutrophil count, higher levels of C-reactive protein, procalcitonin, and ferritin, and lower serum albumin levels. Furthermore, they took a longer time for normalization of inflammatory markers when compared with those with pleural effusion. Invasive interventions, such as pleural drainage, and the need for intensive care were more frequent in the empyema group. Conclusions: Pleural effusion and empyema are two common complications of pediatric community-acquired pneumonia. Children developing pleural empyema have higher inflammatory markers and lower levels of serum albumin compared to patients with simple pleural effusion. Morbidity is significantly worse in children with empyema as they are more prone to require invasive interventions and intensive care. Full article

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE. Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary of current practices. Results: The review highlights different etiologies of NMPE, including organ-specific factors. Imaging, pleural fluid analysis, and clinical correlation remain crucial in diagnosing the etiology of NMPE. Treatment strategies are largely dependent on the underlying condition. Medical management remains the mainstay for many causes. In some cases, interventions, such as thoracentesis, tunneled indwelling pleural catheter, or pleurodesis, are necessary. Conclusions: NMPE is a heterogeneous condition with a wide prevalence and significant implications. They present a diagnostic and management challenge due to patient complexity and evolving therapeutic options. Full article

Background: Bacterial aggregation has been well described to occur in synovial fluid, but it is unknown if bacteria form aggregates in body fluids beyond the synovial fluid. Consequently, this translational study evaluated the ability to form bacterial aggregates in different pleural fluids. Methods: Four of the most common causes of thoracic empyema—Streptococcus mitis, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa—were used here. The different pleural fluids included one transudative and two exudative pleural fluids. Twenty-four-well microwell plates were used to form the aggregates with the aid of an incubating shaker at different dynamic conditions (120 RPM, 30 RPM, and static). The aggregates were then visualized with SEM and evaluated for antibiotic resistance and the ability of tissue plasminogen activator (TPA) to dissolve the aggregates. Statistical comparisons were made between the different groups. Results: Bacterial aggregates formed at high shaking speeds in all pleural fluid types, but no aggregates were seen in TSB. When a low shaking speed (30 RPM) was used, only exudative pleural fluid with a high protein content formed aggregates. No aggregates formed under static conditions. Furthermore, there was a statistical difference in the CFU/mL of bacteria present after antibiotics were administered compared to bacteria with no antibiotics (p < 0.005) and when TPA plus antibiotics were administered compared to antibiotics alone (p < 0.005). Conclusions: This study shows that bacteria can form aggregates in pleural fluid and at dynamic conditions similar to those seen in vivo with thoracic empyema. Importantly, this study provides a pathophysiological underpinning for the reason why antibiotics alone have a limited utility in treating empyema. Full article

In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment. The present study aimed to test the safety of 17-AAG in dogs by evaluating plasma pharmacokinetics, dose-proportionality, and the tolerability of 17-AAG in response to a dose-escalation protocol and multiple administrations at a single dose in healthy dogs. Two protocols were used: Study A: four dogs received variable intravenous (IV) doses (50, 100, 150, 200, or 250 mg/m²) of 17-AAG or a placebo (n = 4/dose level), using a cross-over design with a 7-day “wash-out” period; Study B: nine dogs received three IV doses of 150 mg/m² of 17-AAG administered at 48 h intervals. 17-AAG concentrations were determined by a validated high-performance liquid chromatographic (HPLC) method: linearity (R² = 0.9964), intra-day precision with a coefficient of variation (CV) ≤ 8%, inter-day precision (CV ≤ 20%), and detection and quantification limits of 12.5 and 25 ng/mL, respectively. In Study A, 17-AAG was generally well tolerated. However, increased levels of liver enzymes–alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)–and bloody diarrhea were observed in all four dogs receiving the highest dosage of 250 mg/m². After single doses of 17-AAG (50–250 mg/m²), maximum plasma concentrations (Cmax) ranged between 1405 ± 686 and 9439 ± 991 ng/mL, and the area under the curve (AUC) plotting plasma concentration against time ranged between 1483 ± 694 and 11,902 ± 1962 AUC 0–8 h μg/mL × h, respectively. Cmax and AUC parameters were dose-proportionate between the 50 and 200 mg/m² doses. Regarding Study B, 17-AAG was found to be well tolerated at multiple doses of 150 mg/m². Increased levels of liver enzymes–ALT (28.57 ± 4.29 to 173.33 ± 49.56 U/L), AST (27.85 ± 3.80 to 248.20 ± 85.80 U/L), and GGT (1.60 ± 0.06 to 12.70 ± 0.50 U/L)–and bloody diarrhea were observed in only 3/9 of these dogs. After the administration of multiple doses, Cmax and AUC 0–48 h were 5254 ± 2784 μg/mL and 6850 ± 469 μg/mL × h in plasma and 736 ± 294 μg/mL and 7382 ± 1357 μg/mL × h in tissue transudate, respectively. In conclusion, our results demonstrate the potential of 17-AAG in the treatment of CVL, using a regimen of three doses at 150 mg/m², since it presents the maintenance of high concentrations in subcutaneous interstitial fluid, low toxicity, and reversible hepatotoxicity. Full article

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. Full article

Tongkat ali (Eurycoma longifolia Jack) (ELJ) is a plant in the Simaroubaceae family. Its roots are used in traditional Thai medicine to treat inflammation, pain, and fever; however, the antiulcer abilities of its ethanolic extract have not been studied. This study examined the anti-inflammatory, antinociceptive, antipyretic, and gastroprotective effects of ethanolic ELJ extract in animal models and found that ELJ effectively reduced EPP-induced ear edema in a dose-dependent manner and that a high dose of ELJ inhibited carrageenan-induced hind paw edema formation. In cotton-pellet-induced granuloma formation, a high dose of ELJ suppressed the increases in wet granuloma weight but not dry or transudative weight. In the formalin-induced nociception study, ELJ had a significant dose-dependent inhibitory impact. Additionally, the study found that yeast-induced hyperthermia could be significantly reduced by antipyretic action at the highest dose of ELJ. In all the gastric ulcer models induced by chemical substances or physical activity, ELJ extracts at 150, 300, and 600 mg/kg also effectively prevented gastric ulcer formation. In the pyloric ligation model, however, the effects of ELJ extract on gastric volume, gastric pH, and total acidity were statistically insignificant. These findings support the current widespread use of Eurycoma longifolia Jack in traditional medicine, suggest the plant’s medicinal potential for development of phytomedicines with anti-inflammatory, antinociceptive, and antipyretic properties, and support its use in the treatment of gastric ulcers due to its gastroprotective properties. Full article

The traditional veterinary classification (TVC) of effusions based on cell count and total protein (TP) does not adequately reflect the aetiology. Light’s criteria (LC) (activity of lactate dehydrogenase [LDH] in the effusion [LDHef], effusion/serum LDH ratio [LDHr], effusion/serum TP ratio [TPr]), serum–effusion albumin gradient (ALBg), acute phase proteins (APPs) [serum amyloid A (SAA), α₁-acid glycoprotein (AGP), haptoglobin] might aid classification. The aim was to evaluate the utility of these parameters except LDHr in differentiating exudates from transudates. Sixty-five cats with effusions (33 peritoneal, 31 pleural, 1 pericardial), with 18 transudates and 47 exudates based on aetiological classification (AC), were included. The sensitivity, specificity and accuracy of several parameters to identify exudates (based on AC) was assessed. APPs were compared between exudates and transudates based on AC and TVC, with receiver operating characteristics analysis identifying the best APP to recognise exudates. Simplified LC (LDHef, TPr) had an accuracy of 79% and TVC of 48%. ALBg had the highest sensitivity (98%) and LDHef the highest specificity (83%) in identifying exudates in cats. All APPs but effusion SAA could differentiate exudates from transudates based on AC (effusion AGP had the largest area under the curve 0.79) but not TVC. All parameters were better than TVC in identifying exudates. The conformity of APPs with AC but not TVC favours the use of AC to classify effusions. Full article

Persistent pleural effusions (PPEf) represent a known complication of orthotopic liver transplant (OLT). However, their clinical relevance is not well described. We evaluated the clinical, biochemical, and cellular characteristics of post-OLT PPEf and assessed their relationship with longitudinal outcomes. We performed a retrospective cohort study of OLT recipients between 2006 and 2015. Included patients had post-OLT PPEf, defined by effusion persisting >30 days after OLT and available pleural fluid analysis. PPEf were classified as transudates or exudates (Exud^Light) by Light’s criteria. Exudates were subclassified as those with elevated lactate dehydrogenase (Exud^LDH) or elevated protein (Exud^Prot). Cellular composition was classified as neutrophil- or lymphocyte-predominant. Of 1602 OLT patients, 124 (7.7%) had PPEf, of which 90.2% were Exud^Light. Compared to all OLT recipients, PPEf patients had lower two-year survival (HR 1.63; p = 0.002). Among PPEf patients, one-year mortality was associated with pleural fluid RBC count (p = 0.03). While Exud^Light and Exud^Prot showed no association with outcomes, Exud^LDH were associated with increased ventilator dependence (p = 0.03) and postoperative length of stay (p = 0.03). Neutrophil-predominant effusions were associated with increased postoperative ventilator dependence (p = 0.03), vasopressor dependence (p = 0.02), and surgical pleural intervention (p = 0.02). In summary, post-OLT PPEf were associated with increased mortality. Ninety percent of these effusions were exudates by Light’s criteria. Defining exudates using LDH only and incorporating cellular analysis, including neutrophils and RBCs, was useful in predicting morbidity. Full article

The zoonotic hepatitis E virus genotype 3 (HEV-3) causes most autochthonous human hepatitis E cases in Europe, which are due to the consumption of raw or undercooked food products of animal origin. Pigs and wild boars are considered the main reservoirs of this genotype, while rabbits are the reservoir of a distinct phylogenetic group named HEV-3ra, which is classified within the HEV-3 genotype but in a separate clade. Evidence for the zoonotic potential of HEV-3ra was suggested by its detection in immunocompromised patients in several European countries. HEV-3ra infection was found in farmed and feral rabbit populations worldwide and its circulation was reported in a few European countries, including Italy. Furthermore, Italy is one of the major rabbit meat producers and consumers across Europe, but only a few studies investigated the presence of HEV in this reservoir. The aim of this study was to assess the presence of HEV in 328 Italian hares and 59 farmed rabbits collected in 3 Italian macro-areas (North, North-Central, and South-Central), between 2019 and 2021. For this purpose, liver samples were used to detect HEV RNA using broad-range real-time RT-PCR and nested RT-PCR. Using 28 liver transudates from hares, the ELISA test for anti-HEV IgG detection was also performed. Neither HEV RNA nor anti-HEV antibodies were detected. Further studies will be conducted to assess the HEV presence in Italian lagomorphs to establish the role of this host and the possible risk of transmission for workers with occupational exposure, to pet owners and via food. Full article

Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2/VEGF pathway may confer a potential treatment strategy for TBPE. Full article

Background and Objective: Intravenous therapy is widely used in clinics to deliver medications and fluids to patients, and overuse may cause intravenous-infusion-associated circulatory overload (IACO) and death. However, forensic data on deaths from the overuse of intravenous therapy are limited. We performed a retrospective study to identify whether causes of death in forensic practice were associated with IACO. Methods: A total of 572 medical-related cases with a history of intravenous infusion who suffered from injuries or illnesses and died after treatment in hospitals were recruited from two centers of forensic medicine between 2002 and 2018. Results: The results demonstrated that 6.47% of cases (37/572) were exposed to an infusion overdose that resulted in deaths related to IACO, and 43.24% of cases (16/37) had a net fluid retention ranging from 3.0 L/d to 13.8 L/d. The highest case was administered 1.4 L blood products and 13.6 L fluids within 25 h. We observed significant decreases in red blood cells, hematocrit, hemoglobin, and platelets from the time of “on admission” to “before death”, except for white blood cells. Autopsy findings of 16 cases revealed some organ or tissue pathological alterations related to IACO, including pale-yellow liquid overflow under the abdominal epidermis, much transudate in body cavities, and lung edema with a high tissue density and no obvious slurry deposition in the alveolar lumen. Another 21 cases died after a rapid infusion rate ranging from 111 to 293 drops/min, which resulted from viral myocarditis on autopsy. Conclusions: Our data on excessive or irrational use of intravenous therapy indicate a severe circulatory overload, which may eventually result in lethal outcomes. Therefore, the use of improper intravenous therapy should be reduced to ameliorate adverse health consequences during clinical treatment. Full article

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy. Microscopic analysis and flow cytometry of the patient’s ascitic fluid were consistent with CLL, and he was treated with six cycles of obinutuzumab immunotherapy with the addition of acalabrutinib, resulting in near resolution of malignant ascites. A few cases have reported CLL manifesting as transudative or exudative ascites in elderly patients. A few previous cases have reported the development of ascites between 12 and 21 months after the initial treatment of CLL with chemotherapy. A unique feature of our patient is the presentation with malignant ascites nearly 7 years after the initial CLL treatment with chemotherapy. The intent of this case report is to bring awareness of ascites as a possible initial presenting symptom of CLL in patients with isolated abdominal distention with or without common clinical features of leukemia (i.e., splenomegaly, lymphadenopathy, and B-symptoms) and the therapeutic management thereafter. Malignant ascites may be associated with relapse or the transformation of leukemia; thus, prompt diagnosis and treatment should not be delayed. Full article

Pleural effusions (PEs) are common in clinical practice and can be due to many different underlying diseases such as cancer, congestive heart failure, or pneumonia. An accurate differential diagnostic categorization is essential, as the treatment and prognosis of PEs largely depend on its cause. In this study, we tested the hypothesis that nitrite and nitrate concentrations in PEs are associated with the inflammation and infection conditions. We therefore measured the nitrite and nitrate levels in 143 PE samples using a sensitive liquid chromatography-tandem mass spectrometry method and investigated their diagnostic potential in differentiating PEs. The results showed that nitrite concentrations and nitrite/nitrate ratios were higher in exudates than in transudates (NO₂⁻: 2.12 vs. 1.49 μM; NO₂⁻/NO₃⁻: 23.3 vs. 14.0). Both the nitrite concentrations and the nitrite/nitrate ratios were positively correlated with the three Light’s criteria. Moreover, the receiver operating characteristic curve analysis revealed that the nitrite/nitrate ratio with an area under the curve of 0.71 could be a potential diagnostic biomarker in separating infectious PEs (IPEs) from other types of PEs. Taken together, the nitrite/nitrate ratio not only reflected the statuses of inflammation, but also the nitrate reduction by pathogenic bacteria infection in the pleural cavity. The nitrite/nitrate ratio could be a better biomarker in the differential diagnosis of PEs than the nitrite concentration alone. Full article

Purpose: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. Patients and methods: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital “Fondazione Casa Sollievo della Sofferenza” of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3–8 MHz). For pleural effusions with a depth of 2–3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). Results: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a “safe” quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light’s criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. Conclusions: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures. Full article

Background: There is still no wide agreement regarding the efficacy of the serum levels of C-reactive protein (CRPs), pleural fluid levels of CRP (CRPpf), and their ratio (CRPr) in the discrimination between transudative (Tr) and exudative (Ex) pleural effusions (PEs). Most of the previous studies were conducted on small cohorts, and the role of CRPs in the CRPpf gradient (CRPg) in this discrimination has not been previously reported. The present study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPg, and CRPr in the discrimination between TrPE and ExPE in a relatively large cohort of patients with PE. Methods: The study population included 492 patients with PE, 210 of them with TrPE and 282 with ExPE. The levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: The mean levels of CRPs, CRPpf, CRPg, and CRPr of the TrPEs were 11.3 ± 5.7 mg/L, 4.6 ± 2.8 mg/L, 6.7 ± 3.9 mg/L, and 0.40 ± 0.14, respectively, and for the ExPEs, they were 140.5 ± 112.8 mg/L, 52.8 ± 53.2 mg/L, 87.2 ± 72.4 mg/L, and 0.37 ± 0.15, respectively. The levels of CRPs, CRPpf, and CRPg were significantly higher in the ExPEs than in the TrPEs (p < 0.0001). No significant difference was found between the two groups for the levels of CRPr (p = 0.15). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating TrPE from ExPE was for CRPs, 20.5 mg/L with area under the curve (AUC) = 97% and p < 0.0001; for CRPpf, 9.9 mg/L with AUC = 95% and p < 0.0001; and for CRPg, 13.6 mg/L with AUC = 96% and p < 0.0001. Conclusion: CRPs, CRPpf, and CRPg are strong markers for discrimination between TrPE and ExPE, while CRPr has no role in this discrimination. Full article