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Frontiers in Immunology 2024This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize...
BACKGROUND
This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize the assessment of immunotherapy response.
METHODS
A training set comprising 305 HCC cases was obtained from The Cancer Genome Atlas (TCGA) database. Initially, a screening process was undertaken to identify prognostically significant immune-related genes (IRGs), followed by the application of logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods for gene modeling. Subsequently, the final model was constructed using support vector machines-recursive feature elimination (SVM-RFE). Following model evaluation, quantitative polymerase chain reaction (qPCR) was employed to examine the gene expression profiles in tissue samples obtained from our cohort of 54 patients with HCC and an independent cohort of 231 patients, and the prognostic relevance of the model was substantiated. Thereafter, the association of the model with the immune responses was examined, and its predictive value regarding the efficacy of immunotherapy was corroborated through studies involving three cohorts undergoing immunotherapy. Finally, the study uncovered the potential mechanism by which the model contributed to prognosticating HCC outcomes and assessing immunotherapy effectiveness.
RESULTS
SVM-RFE modeling was applied to develop an OS prognostic model based on six IRGs (CMTM7, HDAC1, HRAS, PSMD1, RAET1E, and TXLNA). The performance of the model was assessed by AUC values on the ROC curves, resulting in values of 0.83, 0.73, and 0.75 for the predictions at 1, 3, and 5 years, respectively. A marked difference in OS outcomes was noted when comparing the high-risk group (HRG) with the low-risk group (LRG), as demonstrated in both the initial training set (0.0001) and the subsequent validation cohort (0.0001). Additionally, the SVMRS in the HRG demonstrated a notable positive correlation with key immune checkpoint genes (CTLA-4, PD-1, and PD-L1). The results obtained from the examination of three cohorts undergoing immunotherapy affirmed the potential capability of this model in predicting immunotherapy effectiveness.
CONCLUSIONS
The HCC predictive model developed in this study, comprising six genes, demonstrates a robust capability to predict the OS of patients with HCC and immunotherapy effectiveness in tumor management.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Immunotherapy; Prognosis; Biomarkers, Tumor; Male; Female; Transcriptome; Middle Aged; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Support Vector Machine; Treatment Outcome
PubMed: 38933262
DOI: 10.3389/fimmu.2024.1371829 -
Frontiers in Immunology 2024Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches...
OBJECTIVE
Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches are mostly clinical trials and have reached various conclusions. Our objective is to investigate the efficacy of PD-1 inhibitor-based treatment as first-line therapy for MGC, utilizing real-world data from China, and further analyze predictive biomarkers for efficacy.
METHODS
This retrospective study comprised 105 patients diagnosed with MGC who underwent various PD-1 inhibitor-based treatments as first-line therapy at West China Hospital of Sichuan University from January 2018 to December 2022. Patient characteristics, treatment regimens, and tumor responses were extracted. We also conducted univariate and multivariate analyses to assess the relationship between clinical features and treatment outcomes. Additionally, we evaluated the predictive efficacy of several commonly used biomarkers for PD-1 inhibitor treatments.
RESULTS
Overall, after 28.0 months of follow-up among the 105 patients included in our study, the objective response rate (ORR) was 30.5%, and the disease control rate (DCR) was 89.5% post-treatment, with two individuals (1.9%) achieving complete response (CR). The median progression-free survival (mPFS) was 9.0 months, and the median overall survival (mOS) was 22.0 months. According to both univariate and multivariate analyses, favorable OS was associated with patients having Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. Additionally, normal baseline levels of carcinoembryonic antigen (CEA), as well as the combination of PD-1 inhibitors with chemotherapy and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive MGC, independently predicted longer PFS and OS. However, microsatellite instability/mismatch repair (MSI/MMR) status and Epstein-Barr virus (EBV) infection status were not significantly correlated with PFS or OS extension.
CONCLUSION
As the first-line treatment, PD-1 inhibitors, either as monotherapy or in combination therapy, are promising to prolong survival for patients with metastatic gastric cancer. Additionally, baseline level of CEA is a potential predictive biomarker for identifying patients mostly responsive to PD-1 inhibitors.
Topics: Humans; Stomach Neoplasms; Male; Female; Retrospective Studies; Middle Aged; Aged; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Adult; China; Biomarkers, Tumor; Treatment Outcome; Neoplasm Metastasis; Antineoplastic Combined Chemotherapy Protocols; East Asian People
PubMed: 38933261
DOI: 10.3389/fimmu.2024.1370860 -
Journal of Hepatocellular Carcinoma 2024The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before...
OBJECTIVE
The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before surgery in individuals diagnosed with nodular hepatocellular carcinoma (HCC).
METHODS
A total of 198 patients were included in the study and were randomly stratified into two groups: a training group consisting of 139 patients and a test group comprising 59 patients. The tumor lesion was manually segmented on the largest cross-sectional slice using ITK SNAP, with agreement reached between two radiologists. The selection of radiomics features was carried out using the LASSO (Least Absolute Shrinkage and Selection Operator) algorithm. Radiomics models were then developed through maximum correlation, minimum redundancy, and logistic regression analyses. The performance of the models in predicting MVI grade was assessed using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix.
RESULTS
There were no notable statistical differences in sex, age, BMI (body mass index), tumor size, and location between the training and test groups. The AP and PP radiomic model constructed for predicting MVI grade demonstrated an AUC of 0.83 (0.75-0.88) and 0.73 (0.64-0.80) in the training group and an AUC of 0.74 (0.61-0.85) and 0.62 (0.48-0.74) in test group, respectively. The combined model consists of imaging data and clinical data (age and AFP), achieved an AUC of 0.85 (0.78-0.91) and 0.77 (0.64-0.87) in the training and test groups, respectively.
CONCLUSION
A radiomics model utilizing-contrast-enhanced MRI demonstrates strong predictive capability for differentiating MVI grades in individuals with nodular HCC. This model could potentially function as a dependable and resilient tool to support hepatologists and radiologists in their preoperative decision-making processes.
PubMed: 38933179
DOI: 10.2147/JHC.S461420 -
Frontiers in Medicine 2024Quantitative computed tomography (CT) analysis is an important method for diagnosis and severity evaluation of lung diseases. However, the association between CT-derived...
PURPOSE
Quantitative computed tomography (CT) analysis is an important method for diagnosis and severity evaluation of lung diseases. However, the association between CT-derived biomarkers and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. We aimed to investigate its potential in predicting COPD exacerbations.
METHODS
Patients with COPD were consecutively enrolled, and their data were analyzed in this retrospective study. Body composition and thoracic abnormalities were analyzed from chest CT scans. Logistic regression analysis was performed to identify independent risk factors of exacerbation. Based on 2-year follow-up data, the deep learning system (DLS) was developed to predict future exacerbations. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance. Finally, the survival analysis was performed to further evaluate the potential of the DLS in risk stratification.
RESULTS
A total of 1,150 eligible patients were included and followed up for 2 years. Multivariate analysis revealed that CT-derived high affected lung volume/total lung capacity (ALV/TLC) ratio, high visceral adipose tissue area (VAT), and low pectoralis muscle cross-sectional area (CSA) were independent risk factors causing COPD exacerbations. The DLS outperformed exacerbation history and the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, with an area under the ROC (AUC) value of 0.88 (95%CI, 0.82-0.92) in the internal cohort and 0.86 (95%CI, 0.81-0.89) in the external cohort. The DeLong test revealed significance between this system and conventional scores in the test cohorts ( < 0.05). In the survival analysis, patients with higher risk were susceptible to exacerbation events.
CONCLUSION
The DLS could allow accurate prediction of COPD exacerbations. The newly identified CT biomarkers (ALV/TLC ratio, VAT, and pectoralis muscle CSA) could potentially enable investigation into underlying mechanisms responsible for exacerbations.
PubMed: 38933101
DOI: 10.3389/fmed.2024.1370917 -
World Journal of Nuclear Medicine Jun 2024Our objective was to investigate the basic information of the personnel and facilities of nuclear medicine in Beijing. This survey was performed by the Beijing...
Our objective was to investigate the basic information of the personnel and facilities of nuclear medicine in Beijing. This survey was performed by the Beijing Quality Control Center in 2018. The investigation included personnel, equipment, and clinical applications, and data were then compared with previous surveys. The paper questionnaires were used for the survey, which required information about the personnel, devices, and clinical applications. About 38 nuclear medicine departments in Beijing were involved in the survey. The number of nuclear medicine staff was 531 in 2018, showing an increase of 58.7% over the past decade. Positron emission tomography/computed tomography (PET/CT), single-photon emission computed tomography (SPECT), and single-photon emission computed tomography/computed tomography (SPECT/CT) represented the main nuclear medicine facilities, and the total number of surveyed departments was 18, 24, and 34, respectively. The quality control results showed significant improvement from the 2005 levels. The total number of scintigraphy procedures was estimated at 199,607 (153,185 SPECT and 46,422 PET/CT). The estimated annual number of scintigraphy images was 8.9 per 1,000 population for SPECT and 2.7 per 1,000 population for PET/CT during 2018. The most frequent radioiodine-targeted therapy was I-targeted therapy for hyperthyroidism in 2018. Nuclear medicine has experienced rapid growth in the past 10 years in Beijing, either in personnel, equipment, and scintigraphy. Future efforts will focus on the use of new isotopes in the diagnosis, implementing quality strategy, and enhancing training.
PubMed: 38933075
DOI: 10.1055/s-0044-1778712 -
World Journal of Nuclear Medicine Jun 2024Gallium-68 prostate-specific membrane antigen ( Ga-PSMA) imaging is valuable for staging because an accurate diagnosis, metastatic or nonmetastatic for prostate...
Gallium-68 prostate-specific membrane antigen ( Ga-PSMA) imaging is valuable for staging because an accurate diagnosis, metastatic or nonmetastatic for prostate cancer patients, is required for deciding to treatment approaches and prognostic assessment. The aim of this study was primarily to distinguish between benign and metastatic adrenal gland lesions detected during Ga-PSMA positron emission tomography (PET)/CT imaging, to evaluate the presence of factors predicting its development, and then to determine the life expectancy of patients with metastatic adrenal lesions. We performed a database search for PET/CT records generated from June 2016 to February 2021 for "adrenal gland" in report for patients who underwent Ga-PSMA examination with prostate cancer patients. Twenty-three patients (10 benign and 13 metastatic) were included in this study. The total prostate-specific antigen, adrenal gland size, adrenal gland density, and maximum standardized uptake (SUVmax) values are significantly different between groups ( < 0.05). On receiver operating characteristic curve analysis, the SUVmax cutoff value > 6.8 provided both sensitivity and specificity of 100%. However, with 29 mm as the adrenal gland size cutoff and 21.2 as Hounsfield unit, the sensitivity and specificity were 56.2 and 92.3%, and 93.8 and 92.3%, respectively. The survival of the benign and metastatic groups was compared and a statistically significant difference was found ( = 0.006). The presence of pelvic lymph nodes was statistically negatively affected the surveillance between the groups. The presence of atypical metastases such as adrenal gland is not insignificant in prostate cancer patients. Because of this degree of impact on patient management, accurate staging by imaging with Ga-PSMA should be an integral part of prostate cancer management.
PubMed: 38933065
DOI: 10.1055/s-0044-1786012 -
World Journal of Nuclear Medicine Jun 2024Multiparametric magnetic resonance imaging (mpMRI) is widely used for the evaluation of prostate cancer and is known to have better accuracy. Gallium-68...
Multiparametric magnetic resonance imaging (mpMRI) is widely used for the evaluation of prostate cancer and is known to have better accuracy. Gallium-68 prostate-specific membrane antigen (Ga-68 PSMA) is a radiotracer that shows high localization in prostate cancer cells. The purpose of this study was to assess the sensitivity and utility of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in comparison with mpMRI as a noninvasive imaging technique for the initial diagnosis and locoregional staging of prostate cancer using transrectal ultrasound (TRUS)-guided biopsy as gold standard. This prospective observational study conducted from August 2017 to April 2020 evaluated 60 men ( = 60) with biopsy-proven prostate carcinoma. They underwent mpMRI and Ga-68 PSMA PET/CT scans within 14 days with TRUS biopsy being gold standard. T staging of disease, N staging of lymph nodes within the pelvis, and M staging of lesions in pelvic bones (within the imaging field of mpMRI) were compared using PSPP version 1.0.1 statistical software. All 60 men with a mean age of 69.9 ± 9.35 years showed Ga-68 PSMA avid disease, whereas 55 were detected by mpMRI. The sensitivity in detection of prostate lesions (with 95% confidence interval) was 99.08% for Ga-68 PSMA PET/CT and 84.40% for mpMRI. Ga-68 PSMA PET/CT detected greater number of patients with regional lymph nodal involvement (19/60) as compared with mpMRI (12/60). Ga-68 PSMA PET/CT showed PSMA avid pelvic skeletal lesions in nine patients, whereas mpMRI detected pelvic lesions in six patients. In addition, four other patients showed extrapelvic skeletal lesions on Ga-68 PSMA PET/CT. Ga-68 PSMA PET/CT has superior sensitivity in detection of primary prostate tumor, as compared with mpMRI. Both modalities correlate well in detection of seminal vesicle involvement. Ga-68 PSMA PET/CT outperformed mpMRI in detection of lymph nodal and skeletal metastases. Hence, Ga-68 PSMA PET/CT should be considered as first-line diagnostic modality for carcinoma prostate. : Ga-68 PSMA PET/CT shows superior diagnostic performance than mpMRI in the evaluation of prostate cancer.
PubMed: 38933063
DOI: 10.1055/s-0044-1779749 -
Acta Dermato-venereologica Jun 2024To examine the prevalence of comorbidities in Chinese urticaria patients and assess medication use patterns across different ages (6-11 years, 12-17 years, above 18...
To examine the prevalence of comorbidities in Chinese urticaria patients and assess medication use patterns across different ages (6-11 years, 12-17 years, above 18 years), a retrospective cohort study was performed in 192,647 urticaria patients within the Health Database. After 1:1 propensity score matching, 166,921 people were divided into the urticaria group and the control group, and the follow-up data were collected within 2 years. During the 12-month and 24-month follow-up period, significant comorbidities identified included allergic rhinitis and asthma, with distinct patterns observed across age groups. Chronic urticaria patients often have complications, such as allergic rhinitis, upper respiratory infection, oropharyngeal infection, and dental caries. The study underscores the need for age-specific treatment strategies in urticaria management.
Topics: Humans; Retrospective Studies; Child; Male; Adolescent; Female; China; Comorbidity; Prevalence; Age Factors; Young Adult; Chronic Urticaria; Adult; Rhinitis, Allergic; Time Factors; Urticaria; Risk Factors; Propensity Score; Middle Aged; Databases, Factual; Asthma; East Asian People
PubMed: 38932592
DOI: 10.2340/actadv.v104.24050 -
Viruses Jun 2024Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in...
Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in Victoria, Australia, who inject drugs or are living with hepatitis C, to identify missed opportunities for hepatitis C care. Adult hospital inpatients and emergency department (ED) attendees from 2018 to 2021 with indications for intravenous drug use (IDU) or hepatitis C on their discharge or ED summary were included. Data sources: hospital admissions, pathology, hospital pharmacy, and outpatients. We assessed progression through the testing cascade and performed logistic regression analysis for predictors of hepatitis C care, including testing and treatment. Of 79,923 adults admitted, 1345 (1.7%) had IDU-coded separations and 628 (0.8%) had hepatitis C-coded separations (N = 1892). Hepatitis C virus (HCV) status at the end of the study was unknown for 1569 (82.9%). ED admissions were associated with increased odds of not providing hepatitis C care (odds ratio 3.29, 95% confidence interval 2.42-4.48). More than 2% of inpatients at our hospital have an indication for testing, however, most are not being tested despite their hospital contact. As we work toward HCV elimination in our region, we need to incorporate testing and linkage strategies within hospital departments with a higher prevalence of people at risk of infection.
Topics: Humans; Retrospective Studies; Male; Hepatitis C; Female; Middle Aged; Adult; Inpatients; Hepacivirus; Substance Abuse, Intravenous; Hospitalization; Victoria; Aged; Emergency Service, Hospital; Mass Screening; Young Adult
PubMed: 38932269
DOI: 10.3390/v16060979 -
Viruses Jun 2024The COVID-19 pandemic, caused by SARS-CoV-2, has posed significant health challenges worldwide. While children generally experience less severe illness compared to...
The COVID-19 pandemic, caused by SARS-CoV-2, has posed significant health challenges worldwide. While children generally experience less severe illness compared to adults, pneumonia remains a substantial risk, particularly for those under five years old. This study examines the clinical characteristics and treatment outcomes of pediatric COVID-19 pneumonia patients treated with favipiravir in Thailand, aiming to identify associated factors for pneumonia. A retrospective review was performed on pediatric patients aged 1 month to 18 years hospitalized with COVID-19 at Srinagarind Hospital, Khon Kaen University, from 13 January 2020 to 15 November 2021. Data on demographics, clinical symptoms, treatment, and outcomes were collected, and logistic regression analysis was used to identify factors associated with pneumonia. Among 349 hospitalized children, the median age was 8 years, with 51.9% being male. Symptoms included a fever (100%), a cough (74.2%), and a rash (24.9%). COVID-19 pneumonia was diagnosed in 54.7% of the children. Favipiravir was administered as the standard treatment, showing mild adverse effects, including a rash (4.3%) and nausea (2.8%). Monocytosis was significantly associated with COVID-19 pneumonia (aOR 30.85, 95% CI: 9.03-105.41, < 0.001), with an ROC curve area of 0.77 (95% CI: 0.71-0.83). Pediatric COVID-19 patients typically exhibit mild-to-moderate symptoms, with pneumonia being common in the early pandemic phase. Monocytosis is a significant factor associated with COVID-19 pneumonia. Favipiravir demonstrated mild adverse effects. Further studies are needed to validate these findings across different settings and phases of the pandemic.
Topics: Humans; Amides; Female; Male; Pyrazines; Child; Child, Preschool; Retrospective Studies; COVID-19 Drug Treatment; Antiviral Agents; Adolescent; COVID-19; SARS-CoV-2; Infant; Thailand; Tertiary Care Centers; Treatment Outcome; Hospitalization
PubMed: 38932238
DOI: 10.3390/v16060946