Treatment Of Tumors Research Articles

A deep learning-based system for accurate diagnosis of pelvic bone tumors

Bone image analysis and categorizing bone cancers have both seen advancements thanks to deep learning (DL), more notably convolution neural networks (CNN). This study suggests a brand-new CNN-based methodology for categorizing pelvic bone tumors specifically. This work aims to create a pelvic bone computed tomography (CT) image categorization system based on deep learning. The proposed technique uses a convolutional neural network (CNN) architecture to automatically extract information from the CT images and classify them into distinct categories of tumors. A total of 178 3D CT pictures was discovered and added retroactively. DenseNet created the image-based model with Adam optimizer and cross entropy loss. The suggested system's accuracy is assessed using a variety of performance indicators, including sensitivity, specificity, and F1-score. As demonstrated by the experiment findings, the suggested deep learning based classification system has a high degree of accuracy (94%), making it useful for the diagnosis and treatment of pelvic bone tumors. Our promising results might hasten the use of DL-assisted CT diagnosis for pelvic bone tumors in the future.

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46%, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

Recent Advances in the Development of RET Inhibitors

Background: Rearranged during transfection (RET) is a receptor tyrosine kinase and a bona fide oncogene that drives various cancers. Oncogenic RET induces abnormal activation of RET kinase, causing tumorigenesis. RET can be abnormally activated through RET point mutations and RET fusions. Although RET kinase has been discovered in tumors more than 30 years ago, patients with RET-altered tumors gain limited benefits from multikinase inhibitors (MKIs). In 2020, pralsetinib and selpercatinib were approved by FDA for the treatment of RET-altered tumors. Objective: Recently reported RET inhibitors were reviewed to provide an overview of the development of novel RET inhibitors. Methods: Literatures, patents, and conference proceedings published in the past five years were collected. Only RET inhibitors with novel scaffolds or in vivo efficacy were discussed in this review. The enzymebased and cell-based activities, PK profiles, antitumor activities in vivo, and clinical efficacy of the selected RET inhibitors were described. Results: Great efforts have been spent on the development of RET inhibitors, leading to increased RETtargeted therapies. Due to high potency and specificity, pralsetinib and selpercatinib resulted in a >8- month improvement in overall survival, compared to MKIs. However, solvent-front mutants emerged and contributed to the acquired resistance to pralsetinib and selpercatinib. To overcome solvent front mutants, TPX-0046, TAS0953, and LOX-260 are investigated in early clinical studies. Conclusion: Zeteletinib, SYHA1815, TPX-0046, TAS0953, and LOX-260 are potential therapies for RET-altered cancers. In addition, macrocyclic inhibitors, allosteric inhibitors, and PROTACs are three promising strategies to address the potential drug resistance of RET.

Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy.

Despite little progress in survival rates with regular therapies, which do not provide complete care for curing pediatric brain tumors (PBTs), there is an urgent need for novel strategies to overcome the toxic effects of conventional therapies to treat PBTs. The co-inhibitory immune checkpoint molecules, e.g., CTLA-4, PD-1/PD-L1, etc., and epigenetic alterations in histone variants, e.g., H3K27me3 that help in immune evasion at tumor microenvironment have not gained much attention in PBTs treatment. However, key epigenetic mechanistic alterations, such as acetylation, methylation, phosphorylation, sumoylation, poly (ADP)-ribosylation, and ubiquitination in histone protein, are greatly acknowledged. The crucial checkpoints in pediatric brain tumors are cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PDL1), OX-2 membrane glycoprotein (CD200), and indoleamine 2,3-dioxygenase (IDO). This review covers the state of knowledge on the role of multiple co-inhibitory immunological checkpoint proteins and histone epigenetic alterations in different cancers. We further discuss the processes behind these checkpoints, cell signalling, the current scenario of clinical and preclinical research and potential futuristic opportunities for immunotherapies in the treatment of pediatric brain tumors. Conclusively, this article further discusses the possibilities of these interventions to be used for better therapy options.

Automated classification of brain tumor-based magnetic resonance imaging using deep learning approach

The treatment of brain tumors poses significant challenges and contributes to a significant number of deaths on a global scale. The process of identifying brain tumors in medical practice involves the visual analysis of photographs by healthcare experts, who manually delineate the tumor locations. However, this approach is characterized by its time-consuming nature and susceptibility to errors. In recent years, scholars have put forth automated approaches to early detection of brain tumors. However, these techniques face challenges attributed to their limited precision and significant false-positive rates. There is a need for an effective methodology to identify and classify tumors, which involves extracting reliable features and achieving precise disease classification. This work presents a novel model architecture that is derived from the EfficientNetB3. The suggested framework has been trained and assessed on a dataset consisting of 7,023 magnetic resonance images. The findings of this study indicate that the fused feature vector exhibits superior performance compared to the individual vectors. Furthermore, the technique that was provided showed superior performance compared to the currently available systems and attained a 100% accuracy rate. As a result, it is viable to employ this technique within a clinical environment for the purpose of categorizing brain tumors based on magnetic resonance images scans.

Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an “active” state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the “immunosilent” TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a “reactive oxygen species (ROS) storm”. Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.

Role of TIM-1 in the development and treatment of tumours

T-cell immunoglobulin and mucin structural domain 1 (TIM-1, also known as hepatitis A virus cell receptor 1) is a co-stimulatory molecule that is expressed predominantly on the surface of T cells. TIM-1 promotes the activation and proliferation of T cells, cytokine secretion, and can also be overexpressed in various types of cancer. Upregulation of TIM-1 expression may be associated with the development and progression of cancer. After reviewing the literature, we propose that TIM-1 affects tumour development mainly through two pathways. In the Direct pathway: overexpression in tumours activates tumour-related signaling pathways, mediates the proliferation, apoptosis, invasion and metastasis, and directly affects tumour development directly. In the indirect pathway: In addition to changing the tumour microenvironment and influencing the growth of tumours, TIM-1 binds to ligands to encourage the activation, proliferation, and generation of cytokines by immune cells. This review examines how TIM-1 stimulates the development of tumours in direct and indirect ways, and how TIM-1 is exploited as a target for cancer therapy.

Comparison of the latest cancer statistics, cancer epidemic trends and determinants between China and the United States

Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

Antisense Oligonucleotides for Rapid Translation of Gene Therapy in Glioblastoma

Purpose: The limited efficacy of current treatments for malignant brain tumors necessitates novel therapeutic strategies. This study aimed to assess the potential of antisense oligonucleotides (ASOs) as adjuvant therapy for high-grade gliomas, focusing on their CNS penetration and clinical translation prospects. Methods: A comprehensive review of the existing literature was conducted to evaluate the implications of ASOs in neuro-oncology. Studies that investigated ASO therapy’s efficacy, CNS penetration, and safety profile were analyzed to assess its potential as a therapeutic intervention for high-grade gliomas. Results: ASOs present a promising avenue for enhancing targeted gene therapies in malignant gliomas. Their potent CNS penetration, in vivo durability, and efficient transduction offer advantages over conventional treatments. Preliminary in vivo and in vitro studies suggest ASOs as a viable adjuvant therapy for high-grade gliomas, warranting further exploration in clinical trials. Conclusions: ASOs hold significant promise as adjuvant therapy for high-grade gliomas, offering improved CNS penetration and durability compared with existing treatments. While preliminary studies are encouraging, additional research is needed to establish the safety and efficacy of ASO therapy in clinical settings. Further investigation and clinical trials are warranted to validate ASOs as a transformative approach in neuro-oncology.

GASTRIC GASTROINTESTINAL STROMAL TUMOR WITH SUCCINATE DEHYDROGENASE B DEFICIENCY: CLINICAL CASE

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors found in the gastrointestinal tract, constituting a diverse group of c-Kit positive mesenchymal (stromal or connective tissue) tumors. Their development is primarily associated with mutations in the c-Kit proto-oncogene, leading to structural alterations in the type III transmembrane tyrosine kinase receptor (Kit). This receptor is crucial for regulating mitotic activity and cell differentiation. The activation of the Kit-receptor in tumor cells is identified through the expression of the immunohistochemical marker CD 117 (tyrosine kinase receptor protein), with approximately 80-90% of GISTs testing positive for CD 117. The objective of our study is to improve the diagnosis and treatment of gastrointestinal stromal tumors. The clinical case underscores the challenge of diagnosing gastrointestinal stromal tumors (GISTs) due to the absence of specific and definitive symptoms. In this instance, only radical surgical intervention facilitated an accurate diagnosis. Given the location of the tumor in the pyloric part of the gastric submucosal layer, a reliable biopsy during video esophagogastroduodenoscopy was unfeasible, as the gastric mucosa above the tumor appeared unaffected. Consequently, surgery with complete tumor excision and subsequent pathohistological and immunohistochemical analysis emerged as the primary diagnostic and therapeutic approach. These investigations confirmed the presence of a gastrointestinal stromal tumor of the stomach with succinate dehydrogenase B deficiency. In approximately 80% of GIST cases, succinate dehydrogenase deficiency plays a pivotal role. The absence of succinate dehydrogenase disrupts the Krebs cycle, leading to an accumulation of succinate, an oncometabolite that fuels carcinogenesis. Such tumors exhibit distinctive clinical characteristics, prognostic outcomes, and responsiveness to targeted therapies. Succinate dehydrogenase deficiency can arise from mutations or epigenomic alterations affecting gene expression. Notably, mutations or epigenomic disruptions in any succinate dehydrogenase subunit inevitably result in the loss of subunit B expression.

PrCRS: a prediction model of severe CRS in CAR-T therapy based on transfer learning

BackgroundCAR-T cell therapy represents a novel approach for the treatment of hematologic malignancies and solid tumors. However, its implementation is accompanied by the emergence of potentially life-threatening adverse events known as cytokine release syndrome (CRS). Given the escalating number of patients undergoing CAR-T therapy, there is an urgent need to develop predictive models for severe CRS occurrence to prevent it in advance. Currently, all existing models are based on decision trees whose accuracy is far from meeting our expectations, and there is a lack of deep learning models to predict the occurrence of severe CRS more accurately.ResultsWe propose PrCRS, a deep learning prediction model based on U-net and Transformer. Given the limited data available for CAR-T patients, we employ transfer learning using data from COVID-19 patients. The comprehensive evaluation demonstrates the superiority of the PrCRS model over other state-of-the-art methods for predicting CRS occurrence. We propose six models to forecast the probability of severe CRS for patients with one, two, and three days in advance. Additionally, we present a strategy to convert the model's output into actual probabilities of severe CRS and provide corresponding predictions.ConclusionsBased on our findings, PrCRS effectively predicts both the likelihood and timing of severe CRS in patients, thereby facilitating expedited and precise patient assessment, thus making a significant contribution to medical research. There is little research on applying deep learning algorithms to predict CRS, and our study fills this gap. This makes our research more novel and significant. Our code is publicly available at https://github.com/wzy38828201/PrCRS. The website of our prediction platform is: http://prediction.unicar-therapy.com/index-en.html.

Adverse events associated with chimeric antigen receptor T-Cell therapy in ophthalmology: a narrative review

Chimeric antigen receptors are synthetically produced receptors engineered to engage with target cells with high specificity. These cells are created by inserting an artificial T-cell receptor into an immunoglobulin’s antigen-binding region, allowing the cells to combine and target specific antigens. The use of chimeric antigen receptor (CAR) T-cell therapy has been a remarkable achievement in the field of immunotherapy, particularly in the treatment of ophthalmic tumors like retinoblastoma and uveal melanoma. However, there are some documented side effects, such as cytokine release syndrome (CRS) and immunological effector cell-associated neurotoxicity syndrome (ICANS). Additionally, ocular side effects such as blurred vision, vision impairment, and intraocular infections are also concerning and require further evaluation. This review highlights the advances made in chimeric antigen receptor (CAR) immunotherapy, including its structure and manufacture, as well as relevant clinical discoveries and associated adverse effects. By identifying the gaps in current research, this analysis provides insights into potential strategies and solutions for addressing some of the most severe side effects.

Radiologically guided interventional therapies for the treatment of neuroendocrine tumors

The majority of patients with neuroendocrine tumors (NET) develop liver metastases during the course of the disease, significantly impacting prognosis and quality of life. Radiologically guided interventional therapies, such as thermal ablation, transarterial embolization (TAE)/chemoembolization (TACE), and selective internal radiotherapy (TARE), can play acrucial role in the treatment of metastatic NET. Due to the rarity of the disease, the majority of evidence is based on retrospective studies. For thermal ablation, the complete response rates ranging from 31.6to 95.3% depending on the study. No significant differences in outcomes were found between TAE, TACE, and TARE. In several studies, all intra-arterial procedures led to areduction of tumor-related symptoms and achieved disease control. Thermal ablation can be used as acurative therapy in oligometastatic patients with nonresectable liver metastases from NETs. In cases of disseminated liver metastases, intra-arterial therapy using TAE, TACE, or TARE can be employed.

Primary mediastinal seminoma with azoospermia: case report and review of the literature

IntroductionSince the first report, primary mediastinal seminoma has a low incidence in the population, and it mainly affects young and middle-aged men, is clinically rare, and accounts for a very small proportion of mediastinal tumors. In this study, we describe the first case of primary mediastinal seminoma with azoospermia and hypothesize that the coexistence of the two disorders may not be a coincidence.Case reportA 16-year-old man presented with chest tightness and chest pain, a mediastinal mass on chest CT, and abnormal 18F-fluoro-deoxyglucose uptake on a PET-CT scan. By biopsy of the mass, the pathological diagnosis was a primary mediastinal seminoma. Because chemotherapy is included in the treatment of the tumor, the patient underwent sperm freezing before treatment, considering that chemotherapy can affect fertility, but the patient was diagnosed with azoospermia. Finally, the patient underwent tumor resection and postoperative chemotherapy. No tumor recurrence was observed at the current follow-up.ConclusionPrimary mediastinal seminoma is mainly confirmed by histopathological examination, and surgery and chemoradiotherapy are the current treatments. In patients with mediastinal seminoma or azoospermia, doctors should be aware that the two disorders may coexist, especially in men who have fertility requirements or long-term infertility, and that examination of the mediastinum and semen may lead to unexpected findings in the diagnosis and treatment. For mediastinal germ cell tumors, genetic testing is of great value in the treatment of tumors and the prediction of associated diseases. Future studies exploring the potential correlation between mediastinal seminoma and azoospermia will be prospective.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention (EPR) effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, we demonstrate that the adaptive microdrugs (even up to 3.0μm in size) are more efficient than their nanodrugs (less than 200nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibited enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. We believe that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors. This article is protected by copyright. All rights reserved.

Relevant MicroRNAs of MMPs and TIMPs with Certain Gut Microbiota Could Be Involved in the Invasiveness and Metastasis of Malignant Tumors

Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation, invasion, and/or metastasis. In particular, cancer stem cells within these tumors might be responsible for the invasiveness and the property of recurrence of malignancies. It has been reported that matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) could contribute to the development of tumor invasiveness. Remarkably, specific MMPs can drive the malignant phenotype of tumors counting the acquisition of stem cell feature, in which STATs signaling might play an important role. Furthermore, MMPs might be crucial for extra-cellular matrix remodeling in the pathological condition of cancer stem cells. Some immune responses against cancer stem cells in the connection to MMPs and/or TIMPs have been revealed, which might be an important issue in the treatment of aggressive cancers. MicroRNAs (miRNAs) have emerged as favorable biomarkers owing to their important roles in gene regulation and/or stability. Differential expression patterns of specific miRNA may be associated with different types of tumor. In addition, miRNAs can be detected in various body fluids, proposing easily available specimens for diagnostic purposes in tumor microenvironment. Remarkably, it has been shown that miRNA expression might be also related with the gut microbiota composition. Early detection and accurate monitoring of tumors are critical for effective treatment and/or improved patient outcomes. A better understanding of this mechanism of epigenetics could be of use to bring about innovative tactics for the treatment of malignant tumors.

Inducing ferroptosis via nanomaterials: a novel and effective route in cancer therapy

Abstract The use of nanomaterials for cancer ferroptosis presents a promising avenue for research and clinical applications. The unique properties of nanomaterials, such as their small size, large surface area, and ability to be engineered for specific tasks, make them ideal candidates for ferroptosis inducing cancer therapies. Ferroptosis is a new type of cell death mechanism that is distinct from apoptosis and necrosis. It has been shown to be critical in the treatment of various tumors. The ferroptotic mechanism has been mainly linked with the regulation of iron, amino acid, glutathione, and lipid metabolism of cells. The relationship between ferroptosis mechanisms and cancer nanomedicine has attracted considerable interest in recent years. It has been reported that the combination of nanomedicine and ferroptosis can achieve high therapeutic efficacy for the treatment of different cancer types. This review will provide an overview of recent work in ferroptosis-related cancer nanomedicine. First, general information is given about the definition of ferroptosis and its differences from other cell death mechanisms. Later, studies exploring the role of ferroptosis in the cancer nanomedicine field are discussed in detail. Specific focus has been given to the use of combinatorial treatment strategies which combine ferroptosis with chemodynamic therapy, photodynamic therapy, photothermal therapy, immunotherapy and sonodynamic therapy. Considering the fact that ferroptosis inducing nanoparticles have already been introduced into clinical studies, nanoscientists can further accelerate this clinical translation as they tailor the physicochemical characteristics of nanomaterials. This review provides enlightening information for all researchers interested in the molecular characterization and relationship between ferroptosis and cancer-directed nanoparticles.

AUTOIMMUNE MYOCARDITIS IN MELANOMA IMMUNOTHERAPY–COMPLEX CLINICA PRESENTATION AND ADVERSE THERAPEUTIC RESPONSE

Abstract A 68–year–old Caucasian female presented to the ED with cardiac chest pain and dyspnea. The patient had a history of arterial hypertension and was equipped with a biventricular pacemaker due to atrial fibrillation with low ventricular response. She had recently been diagnosed with metastatic melanoma and initiated treatment with nivolumab and ipilimumab two weeks prior. Troponin levels were elevated (700 ng/ml), and no ST–segment elevation was observed on the electrocardiogram (ECG). In suspicion of NSTEMI–ACS, coronary angiography was performed, revealing an intact epicardial coronary circulation without stenotic lesions. The echocardiogram showed borderline left ventricular systolic function (EF 50%), and the right ventricle exhibited initial signs of reduced systolic function (TAPSE, 15 mm; S RV, 9.5 m/s). The following day, there was a deterioration in hemodynamics and respiratory exchange, with evidence of apical and mid–distal interventricular septum hypokinesia of the left ventricle (EF 40%) and dilated right ventricle (BD 4.8 cm; MD 4 cm) with severely reduced systolic function (TAPSE 10 mm, S RV 7 m/s, FAC, 20%), and severe tricuspid regurgitation. Urgent computed tomography pulmonary angiography (CTPA) excluded pulmonary embolism. Additionally, there was a new troponin increase (5000 ng/ml) and elevated hepatic biomarkers. The clinical picture raised suspicion of myocarditis related to immune checkpoint inhibitor therapy. Corticosteroid therapy was initiated with a daily administration of methylprednisolone 1000 mg. Diagnostic confirmation was sought through autoimmune panel and viral marker assessments, which yielded negative results. Endomyocardial biopsy (EMB) revealed CD4 and CD8–positive lymphocytic infiltration and myocardial necrosis. Despite initial clinical improvement, an arrhythmic storm developed. Despite treatment with a defibrillator, intravenous antiarrhythmic therapy (beta–blocker, amiodarone, and lidocaine), and sedation, the patient unfortunately succumbed. Immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of many solid tumors. However, the dysregulation of immune mechanisms can rarely (2%) lead to autoimmune events involving multiple organs. Myocarditis, despite optimal treatment, is characterized by a mortality rate exceeding 50%, representing a significant challenge in the Intensive Care Unit.

Patient classification and attribute assessment based on machine learning techniques in the qualification process for surgical treatment of adrenal tumours

Adrenal gland incidentaloma is frequently identified through computed tomography and poses a common clinical challenge. Only selected cases require surgical intervention. The primary aim of this study was to compare the effectiveness of selected machine learning (ML) techniques in proper qualifying patients for adrenalectomy and to identify the most accurate algorithm, providing a valuable tool for doctors to simplify their therapeutic decisions. The secondary aim was to assess the significance of attributes for classification accuracy. In total, clinical data were collected from 33 patients who underwent adrenalectomy. Histopathological assessments confirmed the proper selection of 21 patients for surgical intervention according to the guidelines, with accuracy reaching 64%. Statistical analysis showed that Supported Vector Machines (linear) were significantly better than the baseline (p < 0.05), with accuracy reaching 91%, and imaging features of the tumour were found to be the most crucial attributes. In summarise, ML methods may be helpful in qualifying patients for adrenalectomy.

Sustained Secretion of CCL21 via an Implantable Cell Reservoir Hydrogel Enhances the Systemic Antitumor Effect of Radiotherapy.

The combination of radiotherapy (RT) and immunotherapy shows promise in improving the clinical treatment of solid tumors; however, it faces challenges of low response rates and systemic toxicity. Herein, an implantable alginate/collagen hydrogel encapsulating C-C motif ligand 21 (CCL21)-expressing dendritic cells (CCL21-DCs@gel) was developed to potentiate the systemic antitumor effects of RT. The hydrogel functioned as a suitable reservoir for in vivo culture and proliferation of CCL21-DCs, thereby enabling sustained CCL21 release. The local CCL21 gradient induced by CCL21-DCs@gel significantly enhanced the efficacy of RT in suppressing primary tumor growth and inhibiting distant metastasis across several mouse models. Furthermore, the combination of RT with CCL21-DCs@gel provided complete prophylactic protection to mice. Mechanistic investigations revealed that CCL21-DCs@gel potentiated RT by promoting tumor lymphangiogenesis and attracting immune cell infiltration into the tumor. Collectively, these results suggest that CCL21-DCs@gel is a promising adjunct to RT for effectively eradicating tumors and preventing tumor recurrence.