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Clinical Immunology (Orlando, Fla.) Jun 2024Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We...
Integrated multi-omics analysis and machine learning developed diagnostic markers and prognostic model based on Efferocytosis-associated signatures for septic cardiomyopathy.
Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We used integrated multi-omics analysis to explore the clinical and genetic roles of efferocytosis in SCM. We identified six module genes (ATP11C, CD36, CEBPB, MAPK3, MAPKAPK2, PECAM1) strongly associated with SCM, leading to an accurate predictive model. Subgroups defined by EFFscore exhibited distinct clinical features and immune infiltration levels. Survival analysis showed that the C1 subtype with a lower EFFscore had better survival outcomes. scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from sepsis patients identified four genes (CEBPB, CD36, PECAM1, MAPKAPK2) associated with high EFFscores, highlighting their role in SCM. Molecular docking confirmed interactions between diagnostic genes and tamibarotene. Experimental validation supported our computational results. In conclusion, our study identifies a novel efferocytosis-related SCM subtype and diagnostic biomarkers, offering new insights for clinical diagnosis and therapy.
PubMed: 38944364
DOI: 10.1016/j.clim.2024.110301 -
Journal of Vascular and Interventional... Jun 2024To Describe 6-Month safety, efficacy and multimodal imageability after imageable glass Yttrium-90 radioembolization for unresectable Hepatocellular Carcinoma (HCC) in a...
PURPOSE
To Describe 6-Month safety, efficacy and multimodal imageability after imageable glass Yttrium-90 radioembolization for unresectable Hepatocellular Carcinoma (HCC) in a First-in Human Trial METHODS: Eye90 microspheres® (Eye90), an FDA Breakthrough Designated Device, are glass radiopaque Y-90 microspheres visible on CT and SPECT/CT. Six subjects with unresectable HCC underwent selective (≤ 2 segments) Eye90 treatment in a prospective open-label pilot trial. Key inclusion criteria included liver only HCC, ECOG ≤ 1, total lesion length ≤ 9 cm and Child-Pugh A. Prospective partition dosimetry was utilized. Safety, biochemistry, toxicity, adverse events (AE), multimodal imageability on CT and SPECT/CT and 3 and 6-month MRI local modified RECIST (mRECIST) response was evaluated.
RESULTS
6 subjects with HCC (7 lesions) were treated with Eye90 and followed to 180 days. Administration success was 100%. Eye90 CT radiopacity distribution correlated with SPECT/CT. Target lesion complete response was observed in 3 of 6 subjects (50%) and partial response in 2 (33.3%). Two subjects could not be assessed at 180 days. At 180 days, target lesion complete response was maintained in 3 subjects (50%) and partial response in 1 (16.7%). All subjects reported AEs, and 5 reported AEs related to treatment. There were no treatment related serious AEs.
CONCLUSIONS
Eye90 was safe and effective in six subjects with unresectable HCC up to 6 months. Eye90 was imageable via CT and SPECT/CT with correlation between CT radiopacity and SPECT/CT radioactivity distribution. Eye90 provided previously unavailable CT based tumor targeting information.
PubMed: 38944236
DOI: 10.1016/j.jvir.2024.06.023 -
Oral Oncology Jun 2024Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published...
OBJECTIVES
Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up).
MATERIALS AND METHODS
Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported.
RESULTS
The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy.
CONCLUSION
Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted.
TRIAL REGISTRATION
Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.
PubMed: 38943870
DOI: 10.1016/j.oraloncology.2024.106918 -
Clinical Imaging Jun 2024Clinical trials play a pivotal role in assessing the safety and efficacy of medical therapies. Addressing sex distribution among enrollees in clinical trials of...
PURPOSE
Clinical trials play a pivotal role in assessing the safety and efficacy of medical therapies. Addressing sex distribution among enrollees in clinical trials of radiologic contrast agents is essential for ensuring the generalizability of trial outcomes. Previous research has highlighted the influence of demographic factors, particularly sex, on treatment responses, emphasizing the need for equitable representation in clinical trials. Our study aim was to determine the sex distribution of enrollees in clinical trials of radiologic contrast agents.
METHODS
Our retrospective study included a total of 65 clinical trials conducted between 1990 and 2017 identified on clinicaltrials.gov after a comprehensive review including searching individually for all FDA approved contrast agents. Data collected included the year of FDA approval, the number of participants, sex distribution, trial location, trial phase, and study type. Inter-rater validation ensured data accuracy.
RESULTS
Our analysis revealed fluctuations in sex distribution of trial enrollees. Enrollment of males exceeded females in most years, with a shift towards a more equitable representation in recent trials. Trials conducted in the United States had a higher rate of enrollment by females. Phase I trials had the most balanced representation, whereas Phase IV trials had the highest sex disparity.
CONCLUSION
Across all trials, females made up 47.3 % of enrollees [3316 out of 7016 total enrollees]. Enrollment of males exceeded females in 44 of the 65 trials studied, females outnumbered males in 19 trials, and enrollment was equal between the sexes in 2 trials. While the sex distribution observed across all trials represents an equitable representation of enrollees, the wide variance of sex distribution at the level of individual trials has the potential to limit the generalizability of results.
PubMed: 38943784
DOI: 10.1016/j.clinimag.2024.110194 -
ESMO Open Jun 2024The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone...
Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer.
BACKGROUND
The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT.
METHODS
We retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples.
RESULTS
The HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS.
CONCLUSIONS
HER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.
PubMed: 38943737
DOI: 10.1016/j.esmoop.2024.103619 -
Cardiovascular and Interventional... Jun 2024Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.
PURPOSE
Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.
MATERIALS AND METHODS
An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS).
RESULTS
Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively.
CONCLUSION
IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.
PubMed: 38943032
DOI: 10.1007/s00270-024-03795-w -
Rheumatic Diseases Clinics of North... Aug 2024Imaging methods capable of detecting inflammation, such as MR imaging and ultrasound, are of paramount importance in rheumatic disease management, not only for... (Review)
Review
Imaging methods capable of detecting inflammation, such as MR imaging and ultrasound, are of paramount importance in rheumatic disease management, not only for diagnostic purposes but also for monitoring disease activity and treatment response. However, more advanced stages of arthritis, characterized by findings of cumulative structural damage, have traditionally been accomplished by radiographs and computed tomography. The purpose of this review is to provide an overview of imaging of some of the most prevalent inflammatory rheumatic diseases affecting the lower limb (osteoarthritis, rheumatoid arthritis, and gout) and up-to-date recommendations regarding imaging diagnostic workup.
Topics: Humans; Magnetic Resonance Imaging; Lower Extremity; Gout; Arthritis, Rheumatoid; Rheumatic Diseases; Tomography, X-Ray Computed; Ultrasonography; Osteoarthritis
PubMed: 38942580
DOI: 10.1016/j.rdc.2024.03.010 -
Korean Journal of Radiology Jul 2024To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma.
OBJECTIVE
To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma.
MATERIALS AND METHODS
Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation.
RESULTS
Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, = 0.373 [ = 0.030], AT without emph, = -0.351 [ = 0.042]), FEV1/FVC (normal, = 0.390 [ = 0.022], AT without emph, = -0.370 [ = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 ( = 0.349 [ = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters ( > 0.05).
CONCLUSION
Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma.
Topics: Humans; Male; Female; Asthma; Middle Aged; Tomography, X-Ray Computed; Prospective Studies; Severity of Illness Index; Adult; Treatment Outcome; Respiratory Function Tests; Aged
PubMed: 38942461
DOI: 10.3348/kjr.2024.0110 -
Korean Journal of Radiology Jul 2024In Korea, radiology has been positioned towards the early adoption of artificial intelligence-based software as medical devices (AI-SaMDs); however, little is known...
OBJECTIVE
In Korea, radiology has been positioned towards the early adoption of artificial intelligence-based software as medical devices (AI-SaMDs); however, little is known about the current usage, implementation, and future needs of AI-SaMDs. We surveyed the current trends and expectations for AI-SaMDs among members of the Korean Society of Radiology (KSR).
MATERIALS AND METHODS
An anonymous and voluntary online survey was open to all KSR members between April 17 and May 15, 2023. The survey was focused on the experiences of using AI-SaMDs, patterns of usage, levels of satisfaction, and expectations regarding the use of AI-SaMDs, including the roles of the industry, government, and KSR regarding the clinical use of AI-SaMDs.
RESULTS
Among the 370 respondents (response rate: 7.7% [370/4792]; 340 board-certified radiologists; 210 from academic institutions), 60.3% (223/370) had experience using AI-SaMDs. The two most common use-case of AI-SaMDs among the respondents were lesion detection (82.1%, 183/223), lesion diagnosis/classification (55.2%, 123/223), with the target imaging modalities being plain radiography (62.3%, 139/223), CT (42.6%, 95/223), mammography (29.1%, 65/223), and MRI (28.7%, 64/223). Most users were satisfied with AI-SaMDs (67.6% [115/170, for improvement of patient management] to 85.1% [189/222, for performance]). Regarding the expansion of clinical applications, most respondents expressed a preference for AI-SaMDs to assist in detection/diagnosis (77.0%, 285/370) and to perform automated measurement/quantification (63.5%, 235/370). Most respondents indicated that future development of AI-SaMDs should focus on improving practice efficiency (81.9%, 303/370) and quality (71.4%, 264/370). Overall, 91.9% of the respondents (340/370) agreed that there is a need for education or guidelines driven by the KSR regarding the use of AI-SaMDs.
CONCLUSION
The penetration rate of AI-SaMDs in clinical practice and the corresponding satisfaction levels were high among members of the KSR. Most AI-SaMDs have been used for lesion detection, diagnosis, and classification. Most respondents requested KSR-driven education or guidelines on the use of AI-SaMDs.
Topics: Humans; Republic of Korea; Artificial Intelligence; Surveys and Questionnaires; Societies, Medical; Radiology; Software
PubMed: 38942455
DOI: 10.3348/kjr.2023.1246 -
Journal of Controlled Release :... Jun 2024Tumor-associated macrophages (TAMs) constitute 50-80% of stromal cells in most solid tumors with high mortality and poor prognosis. Tumor-infiltrating dendritic cells...
Tumor-associated macrophages (TAMs) constitute 50-80% of stromal cells in most solid tumors with high mortality and poor prognosis. Tumor-infiltrating dendritic cells (TIDCs) and TAMs are key components mediating immune responses within the tumor microenvironment (TME). Considering their refractory properties, simultaneous remodeling of TAMs and TIDCs is a potential strategy of boosting tumor immunity and restoring immunosurveillance. In this study, mannose-decorated poly(lactic-co-glycolic acid) nanoparticles loading with R848 (Man-pD-PLGA-NP@R848) were prepared to dually target TAMs and TIDCs for efficient tumor immunotherapy. The three-dimensional (3D) cell culture model can simulate tumor growth as influenced by the TME and its 3D structural arrangement. Consequently, cancer spheroids enriched with tumor-associated macrophages (TAMs) were fabricated to assess the therapeutic effectiveness of Man-pD-PLGA-NP@R848. In the TME, Man-pD-PLGA-NP@R848 targeted both TAMs and TIDCs in a mannose receptor-mediated manner. Subsequently, Man-pD-PLGA-NP@R848 released R848 to activate Toll-like receptors 7 and 8, following dual-reprograming of TIDCs and TAMs. Man-pD-PLGA-NP@R848 could uniquely reprogram TAMs into antitumoral phenotypes, decrease angiogenesis, reprogram the immunosuppressive TME from "cold tumor" into "hot tumor", with high CD4+ and CD8+ T cell infiltration, and consequently hinder tumor development in B16F10 tumor-bearing mice. Therefore, dual-reprograming of TIDCs and TAMs with the Man-pD-PLGA-NP@R848 is a promising cancer immunotherapy strategy.
PubMed: 38942083
DOI: 10.1016/j.jconrel.2024.06.062