Search Results (92)

Myxoma virus (MYXV) is a leporipoxvirus that causes lethal disease in Leporids. Hares and rabbits belong to the Leporidae family and are believed to have had a common ancestor 12 million years ago. After seventy years of contact with European hares without causing mortalities or disease manifestation, a recombinant MYXV infected Iberian hares (Lepus granatensis) causing high mortalities. Like all poxviruses, MYXV encodes a wealth of immune modulators required for successful virulence that also mediate host species jumping, for example, into hares. Here, we summarize the data of known MYXV immune modulators, their cellular functions, and their effects on European rabbits. Additionally, we suggest that the critical restrictions MYXV would encounter in colonizing a potentially new host species stem from their interactions with the host’s innate immune environment. Lastly, we synthesize our understanding of some poxvirus genome architectural features that might have facilitated the host species jump of MYXV into hares from rabbits. Full article

Background: Cardiac tumors are rare neoplasms with a wide spectrum of clinical presentations, ranging from asymptomatic cases to fatal outcomes. According to the 2021 thoracic tumor classification of the World Health Organization (WHO), papillary fibroelastoma (PFE) is the most common primary cardiac tumor. This study aimed to aggregate and examine data regarding the prevalence, clinical characteristics, and histological results of cardiac tumors. Methods: This multicenter retrospective study was conducted across seven tertiary care institutions and included 274 patients diagnosed with histopathologically confirmed cardiac tumors between January 2013 and December 2024. Results: This study included 274 patients, with an average age of 52.6 ± 16.6 years. Of the study participants, 120 (43.8%) were male and 154 (56.2%) were female. The most prevalent clinical manifestations were dyspnea (43.7%), thoracic pain (22.5%), and cardiac palpitations (21.1%). Echocardiography was the principal diagnostic method, revealing an average tumor size of 3 cm. The most commonly observed mass was cardiac myxoma (CM) in 192 patients (70.1%). The second most frequently detected mass was PFE (28 cases, 10.2%). The third most common cardiac mass was a metastatic tumor (6.9%). Surgical resection was performed in all patients, with infection being the most prevalent consequence, followed by effusion. Conclusions: Cardiac tumors, albeit uncommon, provide considerable diagnostic and treatment difficulties. Our research is founded on an extensive case series that has been histopathologically validated and sourced from various national tertiary centers. This comprehensive dataset offers epidemiological and clinical insights regarding heart tumors in Turkey. Another key finding of our study is that, even though the 5th edition of the 2021 WHO Classification of Thoracic Tumors lists PFE as the most common primary cardiac tumor, myxoma is actually the most common primary cardiac tumor in our study and in many other studies. This finding demonstrates a significant discrepancy between the current international classification and real-world data and suggests that tumor distribution may be related to regional and demographic differences. Full article

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4⁺ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine. Full article

Background: Protein kinase R (PKR) inhibits general mRNA translation by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2). PKR also modulates NF-κB signaling during viral infections, but comparative studies of PKR-mediated NF-κB responses across mammalian species and their regulation by viral inhibitors remain largely unexplored. This study aimed to characterize the conserved antiviral and inflammatory roles of mammalian PKR orthologs and investigate their modulation by poxviral inhibitors. Methods: Using reporter gene assays and quantitative RT-PCR, we assessed the impact of 17 mammalian PKR orthologs on general translation inhibition, stress-responsive translation, and NF-κB-dependent induction of target genes. Congenic human and rabbit cell lines infected with a myxoma virus strain lacking PKR inhibitors were used to compare the effects of human and rabbit PKR on viral replication and inflammatory responses. Site-directed mutagenesis was employed to determine key residues responsible for differential sensitivity to the viral inhibitor M156. Results: All 17 mammalian PKR orthologs significantly inhibited general translation, strongly activated stress-responsive ATF4 translation, and robustly induced NF-κB target genes. Inhibition of these responses was specifically mediated by poxviral K3 orthologs that effectively suppressed PKR activation. Comparative analyses showed human and rabbit PKRs similarly inhibited virus replication and induced cytokine transcripts. Amino acid swaps between rabbit PKRs reversed their sensitivity to viral inhibitor M156 and NF-κB activation. Conclusions: Our data show that the tested PKR orthologs exhibit conserved dual antiviral and inflammatory regulatory roles, which can be antagonized by poxviral K3 orthologs that exploit eIF2α mimicry to modulate the PKR-NF-κB axis. Full article

Cardiac tumors, though rare, present significant diagnostic and therapeutic challenges due to their heterogeneous nature and anatomical complexity. This narrative review synthesizes current evidence on prevalence, diagnostic modalities, and management strategies for primary and metastatic cardiac tumors. Echocardiography, cardiac MRI, and CT remain cornerstone imaging tools for differentiating tumors from non-neoplastic masses, while advances in PET/CT and tissue characterization techniques refine staging and treatment planning. Surgical resection with clear margins (R0) is critical for resectable tumors, particularly benign myxomas, though malignant tumors like sarcomas require multimodal approaches combining surgery, radiotherapy, and systemic therapies. Emerging strategies such as heart autotransplantation and staged resections offer promise for complex cases, while oligometastatic disease management highlights the role of stereotactic radiotherapy and immunotherapy. Key challenges include standardizing resection margins, optimizing neoadjuvant therapies, and addressing high recurrence rates in malignancies. Future directions emphasize integrating AI-driven imaging analysis, molecular biomarkers, and genomic profiling to personalize therapies, alongside global registries to enhance data on rare tumors. Equitable access to advanced diagnostics and multidisciplinary collaboration are essential to improve outcomes. This review underscores the need for standardized guidelines, technological innovation, and patient-centered research to address gaps in cardiac oncology. Full article

Background: Primary cardiac tumors (PCTs) are rare entities, with only a minority being malignant and capable of distant dissemination. Among the rarest and most challenging metastatic events are brain metastases originating from cardiac tumors. Due to the heart’s direct access to systemic circulation, even benign tumors such as atrial myxomas may cause cerebral embolic phenomena. Understanding the distinct biological behavior, diagnostic pathways, therapeutic strategies, and prognostic implications of these cases remains limited by the scarcity of the available literature. Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, Embase, and other major databases were systematically searched using specific MeSH terms and keywords related to cardiac tumors and brain metastases. After applying strict inclusion and exclusion criteria, nineteen studies were included, comprising sixteen single-patient case reports and three multi-patient series. Extracted data included tumor histology, cardiac and brain imaging findings, neurological presentation, treatment approaches, and patient outcomes. Results: A total of 320 patients were analyzed. Atrial myxomas represented the predominant benign tumors causing embolic cerebral events, while angiosarcomas and other cardiac sarcomas were responsible for true hematogenous brain metastases. Brain involvement was frequently hemorrhagic and manifested with seizures, focal deficits, or signs of intracranial hypertension. Cardiac echocardiography and cardiac magnetic resonance imaging (CMR) were essential for tumor detection, while brain MRI, including SWI and DWI sequences, and CT scanning were critical for cerebral lesion characterization. Treatment strategies varied according to tumor type and included surgery, radiotherapy, and systemic therapies. Malignant cardiac tumors correlated with a poor prognosis, with median survival post-CNS involvement ranging from 12 to 14 months. Conclusions: Brain metastases from PCTs, though rare, represent a distinct and serious clinical phenomenon. Benign tumors like myxomas mainly cause embolic cerebral events, whereas malignant tumors, particularly sarcomas, lead to true metastatic brain lesions. Recognizing this biological distinction is crucial for diagnosis, prognostication, and therapeutic planning. An integrated multidisciplinary approach combining advanced cardiac and neuroimaging techniques is vital for early detection and appropriate management. Despite multimodal treatment, survival remains limited, underscoring the urgent need for novel targeted therapies and improved surveillance strategies. Full article

Background: Primary intracardiac tumors may be diagnosed incidentally, sometimes in the case of complications. Case Report: This case report presents a 64-year-old woman who was admitted to the emergency department with cardiac complications, including heart palpitations and shortness of breath. Initial investigations revealed the presence of ground glass opacity in the left lung and significant mediastinal adenopathy. Transthoracic echocardiography (TTE) indicated severe mitral stenosis caused by a mass attached to the mitral valve, and the transesophageal echocardiography (TEE) confirmed the presence of a tumor, raising concerns about a myxoma with a high risk of embolism. The patient experienced transitory neurological dysfunction, and subsequent imaging uncovered a thrombus occluding the left internal carotid artery. An emergency surgical procedure was performed, including extracorporeal circulation and rapid deep cooling, to facilitate safe mass excision and carotid embolectomy. Histopathological analysis of the extracted tissue revealed undifferentiated pleomorphic sarcoma (FNCLCC Grade 3). Following the surgery, the patient needed extended mechanical ventilation and subsequently underwent a tracheostomy because of her ongoing respiratory support requirements. Conclusions: Despite the complexity of the surgical intervention, the prognosis remained poor due to the aggressive nature of the tumor and neurologic complications. This case underscores the rarity of primary cardiac sarcomas, the challenges in diagnosis, and the need for prompt surgical intervention to mitigate risks associated with embolic events. Full article

Odontogenic myxoma (OM) is a rare, benign intraosseous tumor that arises from the dental follicle, dental papilla, or periodontal ligament. It typically affects the mandible, maxilla, and sinuses, more frequently in women than men. The histopathology of OM is characterized by a myxoid stroma with varying degrees of collagenization and spindle cells. Treatment is surgical, but there are no standardized guidelines. Available options include enucleation and curettage, with conservative approaches offering better aesthetics and functionality but a higher recurrence risk. This case report aims to discuss a rare presentation of OM in the anterior part of the mandible of a 22-year-old female patient with Hashimoto’s thyroiditis and idiopathic thrombocytopenic purpura. The patient presented with painless swelling and tooth mobility in the symphysis region. Radiographic evaluation revealed a unilocular lesion extending from the left second incisor to the right first incisor, with no root resorption. Histopathological analysis confirmed the OM diagnosis. Due to the patient’s young age and the size of the lesion, a conservative treatment approach was chosen, with the potential for future implant-prosthodontics rehabilitation. The case underscores the importance of thorough clinical, radiological, and histopathological assessment to ensure accurate diagnosis and management of OM. Long-term follow-up is essential due to the increased risk of recurrence in younger patients. Full article

Cardiac tumors (CTs), although rare, can be a significant cause of sudden cardiac death (SCD), particularly when not diagnosed early. The tumors most associated with SCD include myxomas, fibromas, rhabdomyomas, and sarcomas, which can cause fatal arrhythmias, blood flow obstruction, or embolization. Myxomas, which often develop in the left atrium, can cause valvular obstruction or cerebral emboli, while malignant tumors, such as sarcomas, can infiltrate the myocardium or conduction system, causing serious arrhythmias. Rhabdomyomas, which are common in children and associated with tuberous sclerosis, can lead to ventricular tachyarrhythmias. Early diagnosis using advanced imaging techniques such as echocardiography and magnetic resonance imaging is crucial for preventing SCD. Timely diagnosis and precise characterization of lesions can help reduce the risk of SCD, thus improving the clinical management of patients, with the aim of supporting personalized treatment and improving life prospects. In this state-of-the-art review, we analyze the association between CTs and SCD, with particular attention to the histological features of benign and malignant neoplasms. Through an updated overview of the pathological aspects, we aim to improve the understanding of these tumors and promote a more effective multidisciplinary diagnostic and therapeutic approach to prevent fatal events. Full article

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC. Full article

Background/Objectives: Odontogenic tumors in pediatric patients are uncommon; among all, the intraosseous occurrence of odontogenic myxoma is very rare, accounting for almost 8.5–11.6% of all odontogenic tumors in children. The radiological appearance is highly variable and is often responsible for the diagnostic delay and treatment. Methods: We report a case of odontogenic myxoma occurring in the posterior mandible of a 12-year-old female, found on a panoramic radiograph performed for the delayed eruption of the second inferior molar, treated by conservative surgery. A comprehensive analysis of the literature was also carried out. Results: The radiological features of the presented case were unique, as the lesion was encompassed within the uncompleted (developing) dental crown still unerupted, as confirmed by the macroscopic appearance. Then, the differential diagnosis included odontogenic fibroma, immature dental pulp or follicle from a developing tooth, and ameloblastic fibrodontoma. The histological examination led to the final diagnosis of odontogenic myxoma. As for the literature analysis, after a PRISMA-based selection of the papers, a total of 23 articles (case reports and case series on odontogenic myxomas in pediatric patients, a total of 33 cases) were finally selected and studied; all the pertinent data are widely discussed within the paper. Conclusions: The current case highlights the importance of the radiological investigation in pediatric patients when a delayed eruption lasts for several months, leading to an early diagnosis necessary to avoid more aggressive surgical therapies and possible recurrence; data from the literature about site of occurrence, sex, age, kind of surgical procedure, and recurrence rate are discussed too. Full article

Background/Objectives: Computer-assisted mandibular reconstruction requires sophisticated technical expertise alongside surgical knowledge. This study aims to establish and validate an efficient collaborative protocol between oral and maxillofacial surgeons and bioengineers for virtual surgical planning in mandibular reconstruction. Methods: We developed a structured protocol with four sequential phases: (1) generation of 3D models from CT data, (2) virtual resection planning, (3) reconstruction design, and (4) surgical guide fabrication. Protocol efficiency was assessed through seven simulation trials measuring planning duration and required revisions. Clinical validation was performed in four mandibular reconstruction cases. Accuracy was evaluated by comparing virtual surgical plans to postoperative outcomes using 3-matic 13.0 software analysis. Results: Protocol implementation showed consistent efficiency across simulations with a mean planning duration of 2.86 working days (SD = 1.35). Only two of seven simulations required design revisions. Clinical application in four cases (three ameloblastomas, one odontogenic myxoma) demonstrated high precision with a mean virtual-to-actual discrepancy of 0.90 mm (SD = 0.34). Successful reconstructions were achieved across varying defect spans (29–53 mm) using both bicortical deep circumflex iliac artery (DCIA) flaps and monocortical iliac block bone grafts. The collaborative workflow resulted in optimized surgical guide design, reduced planning iterations, and improved surgical precision. Conclusions: The established surgeon–bioengineer collaborative protocol enhances the efficiency and accuracy of computer-assisted mandibular reconstruction while making advanced surgical planning techniques more accessible. While initial results are promising, future studies with larger patient cohorts and extended follow-up periods are needed to fully validate the protocol’s long-term benefits and broader applicability. Full article

Background: Cardiac myxomas are benign tumors of the heart. They occur mostly in the left atrium. The preferred treatment is surgical resection, which can be performed via conventional median sternotomy, minimally invasive, or robotic-assisted approaches. This study aimed to evaluate the outcomes, advantages, and limitations of these surgical methods, with a focus on their safety, efficacy, and impact on patient recovery. Methods: This systemic review was conducted according to PRISMA guidelines. The chosen databases were systematically searched using the keywords “cardiac myxoma”, “resection”, “approach”, “minimally invasive”, and “robotic surgery”. The comparison between the surgical strategies was based on thirteen articles, which met the inclusion criteria. Results: Median sternotomy remains the standard technique, providing excellent surgical access but is associated with longer hospital stays, higher blood loss, and increased risk of complications such as stroke. Minimally invasive approaches demonstrated comparable safety with shorter ICU stays, reduced blood loss, and lower postoperative pain but presented challenges, including limited exposure and longer procedure times. Robotic-assisted surgery showed potential as a safe alternative but was limited by high costs and technical demands. However, the data on minimally invasive and robotic methods are limited due to the rarity of cardiac myxomas. Conclusions: The choice of surgical technique should be individualised by considering the tumour size, location, patient condition, and surgeon expertise. Routine postoperative echocardiographic monitoring is essential to detect residual or recurrent tumours. Further studies are needed to validate the long-term efficacy of minimally invasive and robotic approaches. Full article

Even if rarely detected, right atrial (RA) masses represent a diagnostic challenge due to their heterogeneous presentation. Para-physiological RA structures, such as a prominent Eustachian valve, Chiari’s network, and lipomatous atrial hypertrophy, may easily be misinterpreted as pathological RA masses, including thrombi, myxomas, and vegetations. Each pathological mass should always be correlated with adequate clinical, anamnestic, and laboratory data. However, the differential diagnosis between pathological RA masses may be challenging due to common constitutional symptoms, as in the case of vegetations and myxoma, which present with fever and analogous complications such as systemic embolism. The implementation of transthoracic echocardiography (TTE) with pulsed wave (PW) tissue Doppler imaging (TDI) may improve the visualization and differentiation of intracardiac masses through different color coding of the pathological structure compared to surrounding tissue. More remarkably, PW-TDI can provide a detailed assessment of the specific pattern of motion of each intracardiac mass, with important clinical implications. Specifically, a TDI-derived pattern of incoherent motion is typical of right-sided thrombi, myxomas, and vegetations, whereas right-sided pseudomasses are generally associated with a TDI pattern of concordant motion synchronous with the cardiac cycle. An increased TDI-derived mass peak antegrade velocity may represent an innovative marker of the embolic potential of mobile right-sided pathological masses. During the last two decades, only a few authors have used TTE implemented with PW-TDI for the characterization of intra-cardiac masses’ morphology and mobility. Herein, we report two clinical cases of totally different right-sided cardiac masses diagnosed using a multimodality imaging approach, including PW-TDI, followed at our institution. The prevalence and physiopathological characteristics of the most relevant RA masses and pseudomasses encountered in clinical practice are described in the present narrative review. In addition, we will discuss the principal clinical applications of PW-TDI and its potential value in improving the differential diagnosis of pathological and para-physiological right-sided cardiac masses. Full article

Objective: Our aim is to present two cases of infantile sinonasal tract myxoma with orbital involvement and conduct a comprehensive literature review of the topic. We aim to provide a summary of the presentation of infantile sinonasal tract myxomas to effectively aid clinicians in considering this rare entity as a potential diagnosis. Methods: We present a case series and a retrospective review of the published literature in the English language. A search was conducted between 1945 and 2023 on sinonasal myxoma. Cases of infantile (<3 years) sinonasal myxoma in the literature were reported as well as two cases of our own. Data was collected from each of the identified articles on the age of presentation, sex, initial presentation, tumor location, imaging, pathology, and treatment. Results: Forty-eight cases of sinonasal myxoma in children <3 years of age were identified. These cases had a slight male preponderance (F:M, 1:1.39) and an average age of diagnosis of sixteen months. Of the cases included, the majority involved the maxilla and maxillary sinuses (83.3%) and commonly presented with a painless slow-growing mass in the region of the tumor. Characteristic CT findings are homogenous solid masses with heterogeneous contrast enhancement. On MRI, these lesions appear hypointense on T1 with highly variable contrast enhancement and hyperintense on T2. Conclusions: We present two cases of infantile sinonasal myxoma with secondary orbital involvement followed by a major review. Treatment of these cases with surgical excision (confirmed clear margins) provided 0% rates of recurrence in the reported cases. Due to the rarity of these tumors and recent histological reclassification, a comprehensive review of this condition will assist clinicians in their management of it. Full article