Pleural Effusion Research Articles

Correlation of DNA load, genotyping, and clinical phenotype of Mycoplasma pneumoniae infection in children.

This study aimed to investigate the correlation between Mycoplasma pneumoniae (MP)-DNA load in the bronchoalveolar lavage fluid (BALF) of children with MP pneumonia (MPP) and its subtypes, relevant laboratory data, imaging, extrapulmonary complications in infected children, and its clinical significance in evaluating the disease. Children hospitalized with MPP at Tianjin Children's Hospital between December 2017 and December 2020 were selected for the study, excluding those with mixed viral, bacterial, and fungal infections. Children were divided into low- and high-load groups according to the MP DNA load in BALF using real-time quantitative fluorescence polymerase chain reaction (PCR). After a successful MP culture, positive specimens were subjected to PCR-Restriction fragment length polymorphism and Multiple-locus variable number tandem repeat analysis typing. Basic data, clinical information, laboratory data, and radiological results were collected from all children included in the study. The PI-I type dominated the different load groups. Children in the low-load group had more wheezing and shortness of breath; however, children in the high-load group had a higher length of hospitalization, maximum fever temperature, higher chills/chilliness, incidence of abdominal pain, and higher C-reactive protein (CRP), procalcitonin (PCT) and aspartate aminotransferase (AST) levels. Children in the high-load group were more likely to have imaging changes such as pleural effusion, and the incidence of respiratory infections and extrapulmonary complications was higher than that of those in the low-load group. We applied Spearman's correlation analysis to clarify the relationship between MP DNA load and the clinical severity of MPP. We found that MP DNA load was positively correlated with length of hospitalization, maximum fever temperature, CRP, PCT, Interleukin-6 (IL-6), and AST levels, and negatively correlated with fever and cough durations, white blood cell count (WBC), and proportion of monocytes (MONO). The degree of correlation was as follows: length of hospitalization > IL-6 > cough duration > AST > fever duration > PCT > WBC > proportion of MONO > maximum fever temperature > CRP levels. MP DNA load was not correlated with MP typing but was significantly correlated with the children's clinical phenotype. Therefore, the MP DNA load helps in the early diagnosis of infection and can better predict disease regression.

Chest ultrasound to detect postoperative pulmonary complications after thoracic surgery: a comparative study

BackgroundPatients who underwent thoracic surgery procedures were usually subjected to daily chest X-rays until discharge, exposing patients to ionizing radiation and requiring patient movement with chest drains, difficult positioning, and time-consuming. Unlike chest ultrasound, which is a good alternative because it is bedside and accurate in the detection of pulmonary complications. We hypothesize that a thoracic surgery resident with a short training program in chest ultrasound can achieve comparable results to a chest X-ray. Our study aims to analyze the agreement between the two techniques.ResultsThis is an observational prospective study. Eighty-six adult patients who underwent thoracic surgery were included. Every patient had a chest X-ray and chest ultrasound follow-up on day 0, day 3, and day 5 post-operative. Chest ultrasound examinations were performed by the same resident, and the results were revised by an expert sonographer for the detection of pneumothorax, pleural effusion, pulmonary consolidation, and interstitial pattern. Both diagnostic procedures showed substantial agreement for pneumothorax (K = 0.661). For pleural effusion, they showed moderate agreement (K = 0.448, P < 0.001), and no cases developed an interstitial pattern. Overall, both diagnostic procedures showed perfect agreement (K = 0.838, P < 0.001). The time lag to perform a chest ultrasound was statistically lower than that to perform. chest X-ray, with a median of 7 min versus 80 min, respectively.ConclusionsPerforming chest ultrasound by a thoracic surgery resident is a less time-consuming and easy bedside diagnostic tool. Compared chest ultrasound to the postoperative X-ray showed a perfect diagnostic agreement for pulmonary consolidation and moderate agreement for pleural effusion and pneumothorax.Trial registrationNCT04118621

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 having a major role in systemic and mucosal immunity, however their occurrence in pleural fluid remains an open question. Our aim herein was to detect and measure the levels of NAbs targeting LPS of M, G, and A class 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 and in addition the ratio of PF/S values were analyzed further with other critical biochemical parameters from biopsies. 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 non-infectious compared to 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 a potential role of anti-LPS NAbs in the pleural cavity that should be further explored.

The 2023 Dengue Outbreak in Bangladesh: Exploring the Epidemiology in Hospitalized Patients.

For the past two decades, Bangladesh has faced recurrent dengue outbreaks, with the most recent occurring in 2023. We investigated the socioeconomic, clinical, and laboratory aspects of patients diagnosed with dengue during this outbreak. This observational study was conducted from July to September 2023 at Dhaka Medical College Hospital and Chittagong Medical College Hospital, and included 450 confirmed cases of dengue. Sociodemographic information was collected via face-to-face interviews, clinical examinations, and laboratory testing, which was done within 24 hours of admission. Dengue severity was classified according to the 2009 WHO dengue guidelines. Notably, 17% of patients experienced severe dengue, and 89% of those with nonsevere cases exhibited at least one warning sign. Most patients were young adults (mean age, 33 years), with a nearly equal male-to-female ratio. Common clinical presentations included fever (95%), myalgia (62%), and headache (58%), whereas warning signs such as vomiting (54%) and abdominal pain (39%) were prevalent. Plasma leakage indicators, including ascites, pleural effusion, and edema, were found predominantly in severe cases. Laboratory findings revealed leukopenia, thrombocytopenia, and elevated hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in nearly half the patients. An elevated hematocrit level was associated with severe dengue. We report that a substantial number of patients developed severe dengue during the epidemic in 2023, and provide detailed clinical-epidemiological profiles of the patients, offering valuable insight into management of dengue cases.

A Descriptive Study of the Demographic and Clinicopathological Characteristics of Individuals With Gallstone-Induced Pancreatitis in a Tertiary-Level Hospital in Ranchi, Jharkhand.

Gallstones are a major cause of acute pancreatitis, which is associated with high recurrence, morbidity, and mortality. Careful consideration of demographic and clinicopathological features is required to understand the association between the cause and severity of pancreatitis in various populations, and such crucial information is lacking for Jharkhand's population. Here, we sought to describe the demographic and clinicopathological features of gallstone-induced acute pancreatitis at a tertiary hospital in Ranchi. This hospital-based descriptive study was conducted at Rajendra Institute of Medical Sciences in Ranchi. The hospital records of patients admitted to the surgical unit with acute gallstone-induced pancreatitis from January 2023 to December 2023 were analyzed. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Of the 72 patients admitted with acute gallstone-induced pancreatitis (mean age: 42.5 years), 46 (64%) were males and 26 (36%) were females. All 72 patients had abdominal pain and 44 (61%) were vomiting. The severe vs. non-severe pancreatitis groups differed significantly in age (≥40) and male gender (p = 0.013 and 0.031, respectively). A total of 45 (62.5%) patients had severe gallstone-induced pancreatitis, and the most common complication was acute kidney injury, followed by pleural effusion (18 (25%) and 13 (18.1%) cases, respectively). Our study revealed that gallstone-induced pancreatitis was more common in males and that age and gender were significantly associated with severity. However, late presentation to the hospital may have influenced our study, resulting in more severe cases being reported, with the most common complication being acute kidney injury. To our knowledge, this is the first study to describe the demographic, clinicopathological, and outcome data of acute gallstone-induced pancreatitis in Ranchi. These results can guide hospital policy development to improve patient outcomes.

Real-time localization for port-implanted catheter tip by echocardiographic guidance

The clinical data of 23 patients undergoing real-time echocardiography-guided infusion port implantation in the Breast Center of Tsinghua Changgung Hospital in Beijing from January to July 2021 were analyzed. The length of catheter insertion L1 was initially estimated using surface measurement method in all patients. Intraoperatively, transthoracic echocardiography was applied using the parasternal four-chamber view to visualize the catheter image within the right atrium, and the length of catheter insertion L2 was recorded under the guidance of echocardiography. Postoperatively, chest radiographs were taken in the upright position to observe the position of the catheter tip. According to chest CT scans, the ideal length (L) for catheter tip placement was calculated when it was located at the junction of superior vena cava and right atrium. Bland-Altman scatter plot analysis and linear regression fitting test were used on L1 and L2 respectively with L to evaluate the consistency. A total of 23 patients were included in this study, among which one case of left breast cancer patient undergoing breast-conserving surgery had difficulty in identifying the catheter tip position due to residual pleural effusion obscuring the imaging of the cardiac apex four-chamber view. In 22 patients, the results of intraoperative ultrasound imaging were good, including 1 case of catheter ectopic to azygos vein, and 21 cases of right atrial catheter could be detected by ultrasound. Statistical analysis showed that there was a good consistency between L1 and L, L2 and L, and the difference between them was d=0.28 cm (95%CI:-1.76-2.31 cm) and d=0.20 cm(95%CI:-0.84-1.23 cm), respectively, with no statistical significance (P>0.05). In the linear regression model, L2 and L had a higher fit than L1, and the difference was statistically significant (R²=0.954, P<0.001). This study found that real-time echocardiographic localization technique can be applied in adult port surgery to replace X-ray-guided real-time catheter tip detection and adjustment to the optimal position.

Splenic abscess presenting as pneumonia with pleural effusion initially: A rare case in a 2-year-old girl: A case report

Rationale: Splenic abscess is rarely discovered during the toddler period. Although most of the cases are typically marked by fever, abdominal pain, and vomiting, some of them may suffer life-threatening situations. This study aimed to explore how early detection can prevent serious disease complications. Patient concerns: A 2-year-old child with persisted fever and shortness of breathing was admitted. Physical examination was decreasing breathing sound on the left side. We gave empirical antibiotics use with chest tube drainage for 2 days in vain. No fever dropping and persistent left upper abdominal pain were noted. A huge mass was found on left spleen incidentally during abdominal ultrasound screen. Diagnosis: Huge splenic abscess. Intervention: High-resolution ultrasound and abdominal computer tomogram were conducted to confirm the diagnosis. Percutaneous drainage under computer tomography-guided with antibiotic use was smoothly. No obvious adverse effects were noted during the treatment course. Rapid clinical improvement with decreasing size was observed by ultrasound 10 days after the treatment and fever subsided. Outcomes: A period of 3-month follow-up revealed no evidence of recurrence of abscess. Lessons: Early diagnosis and intervention are mandatory for splenic abscess to prevent possible ominous consequences. The case study has shown that computer tomography-guided percutaneous drainage, along with appropriate antibiotic therapy, can significantly impact solitary unilocular splenic abscesses, even if they are large. This approach demonstrates the potential to effectively manage splenic abscesses and avoid the need for more invasive procedures such as splenectomy.

SMARCA4-Deficient Poorly Differentiated Adenocarcinoma of the Gallbladder.

A 64-year-old woman presented with chest pain while eating and was referred to our hospital. Physical examination revealed abdominal distension, tenderness, and lower-extremity edema. Imaging revealed a large gallbladder tumor infiltrating the liver, with ascites and pleural effusion. A biopsy confirmed a poorly differentiated adenocarcinoma with SMARCA4 deficiency (cT3N2M1, cStage IV). Chemotherapy was ineffective and led to tumor progression. The patient died 9 months later. Recently, attention has been paid to SMARCA4 deficiency, which is a genetic mutation found in tumors. Here, we report on poorly differentiated adenocarcinomas of the gallbladder based on imaging findings, including FDG PET.

Clinical manifestations and seasonal occurrence of patients with dengue hospitalized at Dhaka city of Bangladesh in 2021

For the past few years, the intensity of dengue in Bangladesh has been rising. The current study was done among 533 dengue patients hospitalized in 2021 in Dhaka to observe the different aspects of clinical manifestations and seasonal occurrence of dengue. Due to COVID-19 restriction, hospital entry and face-to-face interview of the patients was not possible. Hence, contact numbers of the hospitalized dengue patients were collected from Directorate General of Health Services (DGHS) and patients were interviewed over the phone. Out of 533 patients, majority were from Dhaka south city corporation (DSCC) (53.7%), had a monthly household income of 30001≥ BDT (67.4%), and lived in small sized families (76.9%). High fever (p=0.013), headache (p&lt;0.001), body pain (p&lt;0.001), vomiting/nausea (p=0.0085), skin rash (p=0.033), eye lesion/red eyes (p=0.0011), pleural effusion (p=0.0404), weakness (p=0.017) and gum bleeding (p=0.014)- were significantly associated with age groups whereas vomiting/nausea (p=0.048), skin rash (p=0.002) and eye lesion/red eyes (p=0.032) were significantly associated with gender. 86.7% suffered from thrombocytopenia (&lt;150000 per microliter blood), while 27% were in serious condition with lowest platelet count ≤ 20000 per microliter blood. 3.6% patients were admitted to ICU and 1.7% died of dengue. Death due to dengue was significantly associated with age groups (p &lt;0.05) and majority among them were children (≤ 10 years). Family members of 44.6% patients were also affected with dengue and majority of the patients belonged to small sized families. Dengue occurrence had significant association with season where majority of the patients were from monsoon season (65.29%) followed by post-monsoon (33.21%) season. Dengue manifests a wide spectrum of symptoms as shown by the study, so now it is necessary to identify the changes in pattern of the clinical manifestations, and effective disease management to lessen the severity of the outbreak. Dhaka Univ. J. Biol. Sci. 33(1): 33-46, 2024 (January)

A case of cholesterol crystals detected in 37-year pleural effusion.

A case of cholesterol crystals detected in 37-year pleural effusion.

Hemophagocytic lymphohistiocytosis and myopericarditis induced by campylobacter: a case report

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a severe disorder characterized by excessive activation of the immune system, leading to hypercytokinemia and damage to multiple organs. We report a rare case of HLH with myopericarditis caused by Campylobacter infection.Case presentationA 28-year-old male patient with a history of hypertension without medicine control presented at the hospital after a four-day fever, decreasing urine amount, rashes on his trunk and limbs, and other symptoms. He was admitted with a provisional diagnosis of atypical infection and allergic skin rash related to diclofenac. However, his condition deteriorated, and he developed shock, tachycardia, chest distress, and bilateral pleural effusion after admission. Further investigations revealed cardiogenic shock related to myopericarditis, and he was transferred to the ICU. In addition, a stool PCR panel subsequently revealed a positive result for Campylobacter. On day 6, he was diagnosed with HLH. Under Clarithromycin and dexamethasone infusion, leukocytosis, anemia and thrombocytopenia with cardiogenic shock status improved. Then, he was later discharged in stable condition.ConclusionsHLH and myopericarditis caused by Campylobacter are very rare. Early detection of Campylobacter-induced HLH and multiple organ failure, as well as prompt use of antibiotics and immunosuppressants, can be helpful for prognosis.

Induction of therapeutic immunity and cancer eradication through biofunctionalized liposome-like nanovesicles derived from irradiated-cancer cells.

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Respiratory emergencies in adult horses

SummaryAlthough respiratory distress is encountered infrequently in equine practice, it can be serious and potentially fatal, requiring immediate and decisive intervention. History and physical examination can often give sufficient clues to identify the cause of respiratory distress and initiate emergency treatment. Ultrasonography can also be invaluable when assessing distress caused by lower respiratory tract issues. Upper respiratory tract obstruction, tension pneumothorax and occasionally pulmonary oedema can be rapidly fatal and require immediate intervention by emergency tracheotomy, thoracocentesis and evacuation of pleural air or administration of furosemide and oxygen, if available. Acute severe asthma and substantial pleural effusion are often not an immediate threat to life but nonetheless require fast intervention including administration of bronchodilators and corticosteroids or pleurocentesis, respectively.

Intra-pleural and intra-peritoneal tocilizumab therapy for managing malignant pleural effusions and ascites: The Regional Immuno-Oncology Trial (RIOT)−2 study protocol

BackgroundMalignant pleural effusions (MPE) and malignant ascites (MA) are serious complications of advanced cancer, marked by debilitating symptoms and limited treatment options. Based on a wealth of previous literature implicating the cytokine IL-6 as a central mediator in the pathogenesis of MPE and MA, the Regional Immuno-Oncology Trial 2 (RIOT-2) clinical protocol was developed to explore intra-cavitary delivery of tocilizumab, an IL-6 receptor antagonist, as treatment for these conditions. MethodsThis phase I clinical trial (NCT 06016179) is being conducted to assess the safety and pharmacokinetics of intra-cavitary tocilizumab administration to patients with MPE and MA. Eligible patients are those with pleural effusion or peritoneal ascites due to metastatic cancer who are scheduled to undergo standard-of-care catheter placement for pleural or peritoneal drainage. Following catheter placement, patients will receive a starting dose of tocilizumab 0.5 µg/mL via intra-pleural or intra-peritoneal implantable catheters. Weekly escalating doses of tocilizumab will be given over four weeks. Primary endpoints are frequency and type of adverse events, while secondary endpoints include pharmacokinetic and immunological parameters. This single-center study will proceed until 12 patients have been treated. DiscussionInhibition of the IL-6 signaling pathway with tocilizumab is hypothesized to be a rational mitigating treatment strategy for the maladaptive intra-cavitary immune environment in patients with MPE and MA. The RIOT-2 study aims to assess the safety of intra-cavitary tocilizumab therapy, administered via indwelling catheters. Pharmacologic and translational immunologic findings generated by this study could pave the way for future research into clinical applications of intra-cavitary immunotherapy. Trial registrationThe trial is registered at ClinicalTrials.gov; NCT06016179 (registered on August 29th, 2023).

Association of Cytological and Biochemical Oarameters with Pleural Effusion in Patients attending a Tertiary Care Hospital of Western U.P.

Background: Pleural effusion is the pathological accumulation of fluid in the pleural space. This study was done to assess the association of cytological, biochemical, radiological and microbiological parameters in the evaluation of pleural effusion.Materials and Methods: Present study was done in Saraswathi Institute of Medical Sciences- OPD/IPD ofRespiratory Medicine department. As per the inclusion /exclusion criteria the study included 70 participants.Ethical clearance was taken before the commencement of study. Data was analyzed using SPSS software version 26.Majority of participants in present study were males. Majority belongs to age group 19-29 years with mean age was found to be 34.93 ± 12.99 years. Majority of patients had exudative type of pleural effusion. Lymphocyteswas found to be higher as compare to neutrophils and other cells in Tubercular cases than Non-TB cases. Similar findings were found in other studies too.Conclusion: The present study suggest that a high fluid ADA is a vital diagnostic tool and suggest its usage as a quick diagnostic method to diagnose Tuberculous Pleural Effusion

Early Enteral Nutrition and Clinical Outcomes in COPD Patients Requiring Mechanical Ventilation

Early commencement of enteral nutrition (EEN) in critically ill patients requiring mechanical ventilation may improve outcomes. But there is a lack of enough data regarding EEN effects on COPD exacerbation patients’ outcomes. This retrospective study involved 129 COPD exacerbation patients who received invasive mechanical ventilation in ICU. The clinical outcomes were compared based on the timing of enteral nutrition (&lt;48h vs &gt;48h) during 60 days of ICU stay. We surveyed and analyzed mortality, pleural effusion, ventilator-associated pneumonia, weaning failure, cardiac arrhythmias, GI bleeding, electrolyte imbalances, renal dysfunction and length of ICU stay. All analyses were performed using SPSS software version 22.0. 129 COPD-exacerbated patients (EEN group n=66; DEN group n=63) who met the inclusion criteria were enrolled in the study. EEN group had a lower death rate (39% vs 44.4%) than the DEN group, but no significant difference was found in the overall mortality during the 60-day follow-up (P 0.561). The EEN group also had lower ICU stay and pleural effusion rate than the DEN group (P:0.006 and 0.020 respectively). No significant differences were found in other outcomes. Early enteral nutrition might be associated with shorter ICU stay and lower odd ratio of acquisition of pleural effusion in COPD patients requiring invasive mechanical ventilation. EEN could not decrease mortality rate compared with DEN in the current study.

Abstract CT214: Paricalcitol addition to chemotherapy in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PINBALL)

Abstract Background Vitamin D agonism has been shown in preclinical studies to decrease the production of collagen, decrease myeloid derived suppressor cells, and decrease regulatory T cells in pancreatic ductal adenocarcinoma (PDAC). Paricalcitol is a vitamin D analog used for vitamin D replacement for those with secondary hyperparathyroidism. Two individuals with PDAC who had been developed resistance gemcitabine based combination therapy had shown clinical benefit with the addition of paricalcitol. This clinical study was done to study the effect of adding paricalcitol to individuals with metastatic PDAC receiving gemcitabine based combination therapy (NCT04054362, NCT03415854) . Methods Adults with a histologically- or cytologically-confirmed diagnosis of metastatic PDAC and who were previously untreated were eligible. Individuals received gemcitabine based combination- either gemcitabine plus nab-paclitaxel or gemcitabine plus nab-paclitaxel and cisplatin and had to either demonstrate progressive or stable disease. Paricalcitol was given at a fixed dose of 25 mcg IV three days a week. The combination continued until either disease progression or poor tolerance. The primary objective was to determine the clinical benefit of adding paricalcitol to gemcitabine based combination therapy for metastatic PDAC. Secondary objectives included assessing safety and pharmacodynamic through patient biopsies. Results A total of 34 patients were enrolled across two sites. 16 patients received paricalcitol. The overall response rate was 0% ( CR, PR). Disease control rate at 9 weeks was 21.4% (CR+PR+ SD). PFS upon addition of paricalcitol was 1.6 months. OS upon addition of paricalcitol was 4.8 months. Grade 3/4 AE's attributed to paricalcitol include 13% thrombocytopenia; 19% anemia; 6% transaminitis; 6% pleural effusion; 6% ascites- all grade 3. Conclusions The addition of paricalcitol demonstrated evidence of limited clinical benefit in individuals with metastatic PDAC receiving front-line gemcitabine based therapy. Paricalcitol was generally well tolerated. Tumor analysis is ongoing. Addition studies utilizing prospective treatment of paricalcitol for front line treatment of mPDAC are ongoing (NCT03520790). Trial funding provided by SU2C, CRUK, Lustgarten Foundation, and AACR. Citation Format: David Propper, Gayle Jameson, Denise Roe, Betsy Wertheim, Dan Von Hoff, Erkut H. Borazanci. Paricalcitol addition to chemotherapy in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PINBALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT214.

Abstract CT209: Camrelizumab plus chemotherapy as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): A single-center, randomized, phase II trial

Abstract Background:Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery poses the standard treatment for resectable LA-ESCC. However, post-surgery recurrence remains a concern. The phase III ESCORT-1st trial demonstrated improved survival outcomes on the addition of camrelizumab to first-line chemotherapy over chemotherapy alone. This study aims to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by surgery in resectable LA-ESCC. Methods:In this single-center, open-label, randomized, two-arm, phase II trial, patients with resectable thoracic LA-ESCC (T3-4a or TxN+M0, except T4b) were 1:1 randomized to two groups for 3 cycles of neoadjuvant therapy, each lasting 3 weeks. Group A was treated with a combination of camrelizumab (200 mg, day 1), paclitaxel (80 mg/m², days 1 and 8), and cisplatin (75 mg/m², day 1). Group B received the same dose of camrelizumab and cisplatin, with albumin-bound paclitaxel (130 mg/m², days 1 and 8) instead. Surgery was scheduled within 3-10 weeks after the completion of neoadjuvant therapy. Adjuvant treatment was determined by the investigators, based on postoperative pathological findings. For biomarker analysis, blood and tissue samples were collected at baseline, after 2 cycles of neoadjuvant therapy, and postoperatively. The primary endpoint was the correlation between biomarkers and pathologic complete response (pCR, defined as ypT0N0). The second endpoints included event-free survival, overall survival, and safety. Clinical trial information: NCT04937673 Results:From June 2021 to April 2023, a total of 40 patients were enrolled: 20 patients in each group. By data cutoff on July 31st 2023, 19 patients in group A had completed 3 cycles of neoadjuvant therapy; 17 underwent surgery, with 2 refusals and 1 COVID-19-related delay. In group B, 17 patients completed neoadjuvant therapy, and surgery was performed on 14 patients with 5 refusals and 1 exclusion by investigators. R0 resection was achieved in 16 (94.1%) patients from group A and 14 (100.0%) from group B. In intention-to-treatment (ITT) analysis set, the pCR rate was numerically higher in groups A (30.0% [95%CI: 11.9- 54.3%]) compared to group B (10.0% [95%CI: 1.2-31.7%]). Similarly, a major pathologic response (tumor residual ≤10%) was observed in 50.0% (95% CI: 27.2-72.8%) of group A and 35.0% (95% CI: 15.4-59.2%) of group B patients. Postoperative complications were reported in 5 (29.4%) and 4 (28.6%) patients in groups A and B, respectively. Notably, 1 patient from group A developed grade ≥3 acute renal failure and 1 from group B experienced grade ≥3 pleural effusion requiring drainage. Grade ≥3 TEAEs occurred in 25.0% patients from group A and 40.0% from group B. Conclusions:In resectable LA-ESCC patients, neoadjuvant camrelizumab and cisplatin combined with paclitaxel or albumin-bound paclitaxel was well tolerated and showed promising anti-tumor activity. Citation Format: Zhihao Lu, Yanshuo Cao, Liang Dai, Fengxiao Dong, Lin Shen. Camrelizumab plus chemotherapy as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): A single-center, randomized, phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT209.

Abstract CT040: First-in-human dose-expansion study of NBF-006, a novel investigational siRNA targeting GSTP, in patients with KRAS-mutated non-small cell lung cancer

Abstract Background Glutathione S-transferase Pi (GSTP) has a role in detoxification and anti-oxidative damage response. Additionally, GSTP has a chaperone function which regulates key oncogenic pathways such as the KRAS and JNK. Since redundant pathways could compensate for the inhibition of a single kinase, targeting multiple pathways may lead to more effective therapy. NBF-006 is a novel drug product comprised of GSTP siRNA encapsulated within a proprietary lipid nanoparticle. It is designed to deliver siRNA to localized and metastatic lung tumors. As GSTP downregulation leads to inhibition of KRAS signaling through modulation of both MAPK and PI3K pathways, NBF-006 is being developed to treat KRAS mutant tumors. NBF-006-001 is a first-in-human dose escalation and expansion study evaluating safety, tolerability, PK, and preliminary efficacy of NBF-006 administered intravenously. The dose escalation phase enrolled 21 patients with advanced non-small cell lung cancer (NSCLC), pancreatic, or colorectal cancer. No DLTs or treatment-related SAEs were observed. NSCLC disease control rate of 55% (6/11) was observed in heavily pre-treated patient population, warranting further investigations. Final results from the dose escalation and expansion of NBF-006-001 are reported here. Results Thirty-eight NSCLC patients, with or without KRAS mutation, received treatment at 0.3 mg/kg [n=1], 0.6 mg/kg [n=12], 1.2 mg/kg [n=14], or 1.6 mg/kg [n=11]. NBF-006 was well tolerated with no treatment-related grade 4-5 AEs, SAEs, or DLTs. Two grade 3 events were assessed as possibly related to study treatment, anemia and bilateral pleural effusions (both at 0.6 mg/kg). The most common NBF-006-related AEs were Grade 1 or 2 infusion related reactions (IRRs) (18 %) and nausea (11 %). IRRs (n=8 in seven patients), occurred in the first cycle and were well-managed. One patient discontinued due to recurring IRR. Cytokine elevation was only noted in this patient. No clinically meaningful complement activation nor ADA response has been observed. Linear PK (t1/2 ~41 hrs) was observed with dose proportional increases up to 1.6 mg/kg without exposure accumulation or reduction after repeat doses. GSTP mRNA knock-down in PBMCs was statistically significant at 1.2 and 1.6 mg/kg dose levels. Patients had received 1-7 prior lines of therapy (1 line [n=10], 2 lines [n=10], and ≥ 3 lines [n=16] respectively). Two patients (1.2 and 1.6 mg/kg) experienced a durable PR, 17 patients experienced SD. The disease control rate is 19/38 (59%). Patient enrichment strategies were evaluated with interesting trends observed. Conclusion NBF-006 is well tolerated up to 1.6 mg/kg dose level for over a year with early signs of efficacy in heavily pre-treated pan-KRAS mutant NSCLC patients. The results suggest that further clinical development of NBF-006, alone or in combination with standard therapy, is warranted. Citation Format: Lyudmila Bazhenova, Hirva Mamdani, Alberto Chiappori, Alexander Spira, Wade Iams, Anthony Tolcher, Minal Barve, Afshin Gabayan, Andrae Vandross, Cima Cina, Yael Cohen-Arazi, Zachary Albaugh, Annie Huynh, Joachim Gullbo, Sonya Zabludoff. First-in-human dose-expansion study of NBF-006, a novel investigational siRNA targeting GSTP, in patients with KRAS-mutated non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT040.

The Impact Profile and Adenosine Deaminase of Age and Female Sex on Its Level in Patients with Pleural Effusion Syndrome

Background: Pleural fluid analysis and closed pleural biopsy are integral parts in the investigative work up of an exudative pleural effusion. For diagnosis of tuberculous pleural effusion (TPE), the yield of pleural fluid culture for mycobacteria is low at about 36%. Objective: To evaluate the levels of adenosine deaminase (ADA) in the pleural fluids (P-ADA) of untreated and non-surgically manipulated female and male adult patients with several confirmed causes of PES. Methods: This was an observational study conducted at dept. of Internal Medicine, 250 Bedded Mohammad Ali Hospital, Bogura, Bangladesh from January to June 2023. 100 pleural fluid samples from 100 patients with proven causes of PES. The sample size was appropriate according to the study design. Written consent was obtained from all patients. It was precise enough to calculate descriptive and inferential statistics on type I and II errors, effect size, standard deviation, and was not influenced by administrative issues and costs. Results: 100 patients summarize the prevalence of the causes of PES and the demographic characteristics. TB was the most prevalent cause of PES (28/100, 28%). Most prevalent male sex was in the lymphoma group (4/0, 100%). None of the five patients with lymphoma were female. When the frequencies were compared for males and females, only adenocarcinoma and lymphoma were significant (chi- square tests, p=0.0021 and p=0.0003, respectively). The causes, prevalence, and median P-ADA (n/%/U/L) were tuberculosis (28/28.0/42.0), adenocarcinoma (24/24.0/9.75), transudate (21/21.0/6.85), simple parapneumonic pleural effusions (PPE; 10/10.0/9.38), complicated PPE/empyema (5/5.0/32.9), lymphoma (4/4.0/401.2), squamous cell carcinoma (4/4.0/13.11), and others (4/4/15.2). For P-ADA, Dunn's post hoc test revealed significance for tuberculosis vs. transudates, vs. simple PPE, and vs. adenocarcinoma (all P&lt;0.05), and not significant for CPPE/empyema, lymphoma, SCC, and others (all P&gt;0.05). For age, Dunn’s post hoc test revealed significance for tuberculosis vs. transudates, vs. simple PPE, and vs. adenocarcinomas (all P&lt;0.05). Sex was not significant in the overall PES group (Chi=0.062, P=0.8028). Kendall's correlation of the relationship between P-ADA and age for pleural tuberculosis (n=26) was significant after 1000 iterations with bootstrap for 95% CI (Tau=-0.213, 95% CI - 0.449-0.0833, P=0.0490). A negative LOESS regression was evident between P-ADA and age &gt;40 years. Conclusions: Evaluation of pleural ADA levels is useful for diagnosing pleural tuberculosis, while sex is not. A negative and significant relationship between P- ADA level and age &gt;40 years was evident.