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Scientific Reports Jun 2024Chimeric antigen receptor T-cell (CAR-T) therapies are a paradigm-shifting therapeutic in patients with hematological malignancies. However, some concerns remain that...
Chimeric antigen receptor T-cell (CAR-T) therapies are a paradigm-shifting therapeutic in patients with hematological malignancies. However, some concerns remain that they may cause serious cardiovascular adverse events (AEs), for which data are scarce. In this study, gradient boosting machine algorithm-based model was fitted to identify safety signals of serious cardiovascular AEs reported for tisagenlecleucel in the World Health Organization Vigibase up until February 2024. Input dataset, comprised of positive and negative controls of tisagenlecleucel based on its labeling information and literature search, was used to train the model. Then, we implemented the model to calculate the predicted probability of serious cardiovascular AEs defined by preferred terms included in the important medical event list from European Medicine Agency. There were 467 distinct AEs from 3,280 safety cases reports for tisagenlecleucel, of which 363 (77.7%) were classified as positive controls, 66 (14.2%) as negative controls, and 37 (7.9%) as unknown AEs. The prediction model had area under the receiver operating characteristic curve of 0.76 in the test dataset application. Of the unknown AEs, six cardiovascular AEs were predicted as the safety signals: bradycardia (predicted probability 0.99), pleural effusion (0.98), pulseless electrical activity (0.89), cardiotoxicity (0.83), cardio-respiratory arrest (0.69), and acute myocardial infarction (0.58). Our findings underscore vigilant monitoring of acute cardiotoxicities with tisagenlecleucel therapy.
Topics: Humans; Pharmacovigilance; Machine Learning; Female; Male; Middle Aged; Cardiovascular Diseases; Aged; Adult; Immunotherapy, Adoptive; Adolescent; Young Adult; Child; Receptors, Antigen, T-Cell; Hematologic Neoplasms; Child, Preschool
PubMed: 38871843
DOI: 10.1038/s41598-024-64466-x -
Tuberkuloz Ve Toraks Jun 2024Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB...
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB cases present as extrapulmonary TB. The diagnosis of extrapulmonary TB is often overlooked due to its atypical clinical and radiological manifestations. Differentiating TB from neoplastic conditions poses significant challenges. A 33-year-old female patient was admitted to the emergency clinic with shortness of breath, cough, and abdominal pain. Postero-anterior chest X-ray revealed massive pleural effusion leading to mediastinal shift. With a preliminary diagnosis of malignant pleural effusion, a pleural catheter was inserted, and the patient was referred for a positron emission tomography (PET/CT) to assess the primary site and the optimal location for a biopsy. The PET/CT revealed asymmetric soft tissue thickening on the left side of the nasopharynx, and increased fluorodeoxyglucose (FDG) uptake in the left cervical lymph nodes raised suspicion regarding primary nasopharyngeal cancer. Additionally, there was an increased FDG uptake observed in the mass lesion located in the right upper lobe, mediastinal lymph nodes, pleural surfaces in the left hemithorax, perihepatic areas, and peritoneum, indicating diffuse metastatic disease. Tuberculosis diagnosis was confirmed through biopsies demonstrating granulomatous inflammation in the lung and nasopharynx, along with culturing MTB from pleural effusion. Positron emission tomography played a crucial role in identifying sites of TB involvement. Despite its rarity, healthcare professionals should consider nasopharyngeal TB as a potential diagnosis when evaluating nasopharyngeal masses.
Topics: Humans; Female; Adult; Diagnosis, Differential; Positron Emission Tomography Computed Tomography; Tuberculosis; Fluorodeoxyglucose F18; Neoplasm Metastasis
PubMed: 38869209
DOI: 10.5578/tt.202402915 -
Journal of Surgical Case Reports Jun 2024We present a rare case of ocular diffuse large B-cell lymphoma (DLBCL) unveiled through Pars Plana Vitrectomy in a 74-year-old immunocompromised male, highlighting the...
We present a rare case of ocular diffuse large B-cell lymphoma (DLBCL) unveiled through Pars Plana Vitrectomy in a 74-year-old immunocompromised male, highlighting the surgical insight and multidisciplinary management required for similar cases. The patient's progressive vision impairment led to a Pars Plana Vitrectomy, which confirmed DLBCL through cytogenetic analysis. Initial intraocular rituximab treatment showed promise; however, the lymphoma's systemic progression necessitated a shift to more aggressive chemotherapy, underscored by pleural and pericardial effusions and central nervous system involvement. This case emphasizes the critical role of surgical techniques in diagnosing ocular lymphomas and the importance of a multidisciplinary approach in managing the disease's ocular and systemic manifestations. The complexities introduced by the patient's immunosuppression highlight the necessity for individualized treatment strategies. This case calls for further research into ocular lymphomagenesis and exploring therapies with enhanced efficacy and reduced toxicity, and emphasizes the importance of early diagnosis in ocular DLBCL cases.
PubMed: 38863955
DOI: 10.1093/jscr/rjae399 -
Cureus Jun 2024Unilateral exudative pleural effusions have been described as a rare complication of polycystic liver disease. Surgical debridement of the main cyst reduces recurrence...
Unilateral exudative pleural effusions have been described as a rare complication of polycystic liver disease. Surgical debridement of the main cyst reduces recurrence of the pleural effusion. We describe the case of an elderly Asian woman with recurrent large right-sided pleural effusion and also a large hepatic cyst under her right hemidiaphragm. She was deemed a poor surgical candidate and was treated with an indwelling pleural catheter (IPC). She was discharged from Sengkang General Hospital with improvement in symptoms. An 88-year-old Asian woman presented twice to Sengkang General Hospital with recurrent right-sided exudative pleural effusion. She had a past medical history of hypertension, type 2 diabetes, hyperlipidemia, ischemic heart disease (left ventricle ejection fraction 55%), atrial fibrillation, and chronic kidney disease stage 3 (estimated glomerular filtration rate 53). She denied any family history of polycystic kidney or liver disease. Computer tomography of her chest, abdomen, and pelvis revealed a large right pleural effusion and also a large hepatic cyst. A pleural catheter was inserted and the fluid analysis was consistent with an exudative effusion. The pleural fluid was sterile to culture for bacteria and mycobacterium. The cytology was negative for malignant cells. The pleural effusion recurred quickly despite repeated large-volume drainage from the pleural catheter. Our patient was not suitable for surgical debridement of the hepatic cyst and eventually received an IPC and was discharged. With the advent of IPC, there has been increasing interest in using IPC in the management of non-malignant pleural effusions. While surgical debridement of hepatic cysts is the preferred treatment option in recurrent pleural effusion associated with polycystic liver disease, IPCs now provide another viable and minimally invasive option for clinicians and patients.
PubMed: 38859945
DOI: 10.7759/cureus.62058 -
European Review For Medical and... May 2024The aim of the study was to investigate whether sarcopenia had the potential to predict mortality by analyzing epicardial and visceral fat thickness measurements, which...
OBJECTIVE
The aim of the study was to investigate whether sarcopenia had the potential to predict mortality by analyzing epicardial and visceral fat thickness measurements, which are among the radiological findings and scores known to be crucial in determining the prognosis and risk classification of patients diagnosed with acute pulmonary embolism (PE) in the emergency department.
PATIENTS AND METHODS
The study included patients diagnosed with acute PE in the emergency department from January 2019 to December 2022 and involved the retrospective examination of their demographic characteristics, clinical parameters, and radiological data obtained from computed tomography pulmonary angiography (CTPA) [main pulmonary artery (MPA) diameter, pulmonary artery obstruction, right and left ventricular diameters, epicardial and visceral tissue thicknesses, and pectoralis muscle thickness (PMT)]. The primary endpoint was mortality during the hospitalized treatment and follow-up processes, and the secondary endpoint was mortality within 90 days after diagnosis.
RESULTS
Of the 389 patients included in the study, 11.6% had a fatal outcome in the early period following hospitalization for treatment, and 22.6% had a fatal outcome within the 90-day (late) period after diagnosis. In patients with late-period mortality, pleural fluid (30.8%), pericardial fluid (16.7%), and atelectasis (32.6%) were found to be statistically significantly higher. Among the markers obtained from imaging examinations, only PMT - right: 9.4 [interquartile range (IQR): 6.0-14.0]; left: 9.1 (IQR: 5.4-13.8) - was associated with mortality. According to logistic regression analysis, the MPA diameter was associated with early-period mortality, and it was determined that the right ventricular diameter and the right and left PMT values had a predictive effect on late-period mortality.
CONCLUSIONS
To predict mortality, CTPA-based scoring systems that include markers such as PMT, pericardial and pleural fluid, and atelectasis would be more effective; however, large-scale studies are needed to enrich these findings.
Topics: Humans; Pulmonary Embolism; Female; Male; Retrospective Studies; Aged; Middle Aged; Acute Disease; Computed Tomography Angiography; Prognosis
PubMed: 38856139
DOI: 10.26355/eurrev_202405_36300 -
Cureus Jun 2024Disconnected pancreatic duct syndrome (DPDS) is a rare complication of a common disease. Typically, DPDS occurs in acute necrotizing pancreatitis (ANP), chronic...
Disconnected pancreatic duct syndrome (DPDS) is a rare complication of a common disease. Typically, DPDS occurs in acute necrotizing pancreatitis (ANP), chronic pancreatitis, abdominal surgery, or trauma. We present a case of DPDS from acute non-necrotizing pancreatitis (ANNP). A 41-year-old male with a history of alcohol use and prior AP presented with progressive, severe left-sided abdominal pain that was worse with movement. Labs revealed a lipase of 95 U/L (normal range 11-82 U/L). Computed tomography (CT) of the abdomen/pelvis (A/P) with IV contrast demonstrated a large left-sided pleural effusion, non-necrotic pancreatic pseudocysts, and a large subdiaphragmatic fluid collection. Thoracentesis of the pleural effusion revealed an amylase of 601 U/L confirming pancreatic etiology. A subsequent magnetic resonance cholangiopancreatography (MRCP) confirmed complex peripancreatic ascites, rapid subdiaphragmatic fluid accumulation, and a fistula from the pancreatic tail to retroperitoneum concerning for a rapidly dissecting pancreatic pseudocyst. He ultimately underwent endoscopic retrograde cholangiopancreatography (ERCP) with stent placement in the main pancreatic duct. His left-sided abdominal pain rapidly improved, and the patient was discharged. CT A/P one week after discharge showed a reduced size of subdiaphragmatic fluid collection. DPDS is usually seen in patients with a history of ANP. Our case demonstrates that it can also occur in ANNP, which has not previously been described in the literature. Therefore, a high index of clinical suspicion must be maintained for DPDS even in ANNP given its potential for severe complications.
PubMed: 38855497
DOI: 10.7759/cureus.61894 -
Translational Lung Cancer Research May 2024Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without...
BACKGROUND
Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution.
METHODS
We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells and RNA-seq was performed. Epidermal growth factor receptor () antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings.
RESULTS
The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen ()- interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN mesothelial cells and EGFR epithelial cells.
CONCLUSIONS
Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.
PubMed: 38854934
DOI: 10.21037/tlcr-24-118 -
The Pan African Medical Journal 2024
Topics: Humans; Hemothorax; Hemorrhage; Adrenal Gland Diseases; Male; Female
PubMed: 38854866
DOI: 10.11604/pamj.2024.47.130.42845 -
The Pan African Medical Journal 2024
Topics: Humans; Empyema, Tuberculous; Male; Chronic Disease; Adult
PubMed: 38854864
DOI: 10.11604/pamj.2024.47.126.42736 -
Frontiers in Oncology 2024Hepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for...
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery.
METHOD
We retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators.
RESULT
A total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA.
CONCLUSION
The nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.
PubMed: 38854717
DOI: 10.3389/fonc.2024.1395740