Transoral percutaneous radiofrequency ablation with a steerable needle and cementoplasty under CBCT and infrared augmented reality navigation system guidance for the treatment of a C1 solitary plasmacytoma: A case report.

We report a case of a 40-year-old female with a solitary plasmacytoma of the right transverse apophysis of C1 who underwent combined transoral ablation using a curved steerable needle and cementoplasty under CBCT and infra-red augmented reality navigation system. An imaging work-up revealed an osteolytic lesion determining partial collapse of the right lateral mass of C1 and involving the vertebral foramen. After a biopsy, that revealed a solid tissue consistent with plasmacytoma, it was decided to proceed with radiation therapy. Subsequent PET-CT restaging scans showed residual tumors treated with a transoral percutaneous approach, combining ablation and cementoplasty. This report evaluates the benefits of this combined procedure and the transoral approach, focusing on the advantages of steerable devices and navigation systems.

Shifts in immune responses of an invasive alien species: A test of the evolution of increased competitive ability hypothesis using American Eastern gray squirrels in Italy.

Based on the Evolution of Increased Competitive Ability (EICA) hypothesis, a reduced investment in immunity, consequent to parasite loss, could partly explain the success of invasive alien species. We investigated variation in parasite load and immune responses of alien Eastern gray squirrels (Sciurus carolinensis) along the invasion wave of an expanding population. We first verified by fecal analyses that 1) parasite abundance decreased moving from the core towards the invasion front. Next, we used multiple measures of immunity to investigate whether, in response to the lower parasite pressure, individuals at the invasion front 2) dampened their costly inflammatory response, and 3) increased their investment in less expensive acquired immunity. We first explored variation in hematological variables related either to the inflammatory or the acquired response. On a subset of individuals, we carried out ex vivo cell cultures to analyse the basal expression of MHC class II genes and the expression of TNF-α genes in response to an immune challenge. Platelet counts and TNF-α expression suggested higher inflammation in individuals living at the invasion core, whereas parameters associated with an acquired response (lymphocyte counts and MHC II expression by spleen cells), conversely, were higher in squirrels at the front. Overall, our results suggest a shift between different immune strategies along the invasion wave, supporting a reduced investment in costly inflammatory responses and an increased investment in acquired immunity in individuals at the expanding edge of the range, which are subjected to high selective pressures for dispersal and reproduction.

Case of IV Stage Juvenile Nasopharyngeal Angiofibroma Presurgically Treated with a Single ECA Stop-Flow Embolization Technique Using Onyx 18.

Background: Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor that mainly affects young boys. Its intervention may be complex due to its high vascularity, location, and extension. Preoperative embolization is used to prevent intrasurgical and postsurgical bleeding. Two main kinds of embolization are described in literature: intratumoral and transarterial, and numerous embolic materials are used. Case Presentation. We want to present a case of presurgical embolization of a stage IV JNA, performed using a single stop-flow balloon assisted technique with the balloon cuffed exclusively in the external carotid artery and using Onyx 18 as an embolic agent. Conclusions: The embolization with an exclusive external carotid artery single stop-flow technique using Onyx 18 is a safe, effective, and a definitive approach.

3D bioprinted osteosarcoma model for experimental boron neutron capture therapy (BNCT) applications: Preliminary assessment.

Osteosarcoma is the most frequently primary malignant bone tumor characterized by infiltrative growth responsible for relapses and metastases. Treatment options are limited, and a new therapeutic option is required. Boron neutron capture therapy (BNCT) is an experimental alternative radiotherapy able to kill infiltrative tumor cells spearing surrounding healthy tissues. BNCT studies are performed on 2D in vitro models that are not able to reproduce pathological tumor tissue organization or on in vivo animal models that are expensive, time-consuming and must follow the 3R's principles. A 3D in vitro model is a solution to better recapitulate the complexity of solid tumors meanwhile limiting the animal's use. Objective of this study is to optimize the technical assessment for developing a 3D in vitro osteosarcoma model as a platform for BNCT studies: printing protocol, biomaterial selection, cell density, and crosslinking process. The best parameters that allow a fully colonized 3D bioprinted construct by rat osteosarcoma cell line UMR-106 are 6 × 106 cells/ml of hydrogel and 1% CaCl2 as a crosslinking agent. The proposed model could be an alternative or a parallel approach to 2D in vitro culture and in vivo animal models for BNCT experimental study.

Tobacco Seed-Based Oral Vaccination against Verocytotoxic O138 Escherichia coli as Alternative Approach to Antibiotics in Weaned Piglets.

Post-weaning diarrhoea and enterotoxaemia caused by Escherichia coli are serious threats in the pig (Sus scrofa domesticus) livestock industry and are responsible for economic losses related to mortality, morbidity and stunted growth. The aim of this study was to evaluate the effect of an engineered tobacco seeds-based edible vaccine in O138 Escherichia coli-challenged piglets throughout a multidisciplinary approach. Thirty-six weaned piglets were enrolled and randomly divided into two experimental groups, a control (C; n = 18) group and a tobacco edible vaccination group (T, n = 18), for 29 days of trial. At days 0, 1, 2, 5 and 14, piglets of the T group were fed with 10 g of the engineered tobacco seeds line expressing F18 and VT2eB antigens, while the C group received wild-type tobacco seeds. After 20 days, 6 piglets/group were orally challenged with the Escherichia coli O138 strain (creating four subgroups: UC = unchallenged control, CC = challenged control, UT = unchallenged tobacco, CT = challenged tobacco) and fed with a high protein diet for 3 consecutive days. Zootechnical, clinical, microbiological, histological and immunological parameters were assayed and registered during the 9 days of post-challenge follow up. At 29 days post-challenge, the CT group displayed a lower average of the sum of clinical scores compared to the CC group (p < 0.05), while the CC group showed a higher average sum of the faecal score (diarrhoea) (p < 0.05) than the CT group. A decreased number of days of shedding of the pathogenic strain was observed in the CT compared to the CC group (p < 0.05). Specific anti-F18 IgA molecules were significantly higher in the CT group compared to the CC group's faecal samples during the post-challenge period (p < 0.01). In conclusion, edible vaccination with engineered tobacco seeds showed a protective effect on clinical symptoms and diarrhoea incidence during the post-challenge period, characterized by a limited time of pathogenic strain shedding in faeces.

Antioxidant Activity of Different Tissues from Rabbits Fed Dietary Bovine Colostrum Supplementation.

Recent advances in animal nutrition have indicated that bovine colostrum (BC), due to its content of macronutrients, micronutrients and bioactive compounds, is an excellent health supplement. To the best of our knowledge, no studies on the effect of BC on antioxidant status have been performed in rabbits. This study aimed to investigate the effect of two BC concentrations on antioxidant status and gene expression of antioxidant enzymes in some tissues of rabbits. Thirty New Zealand White male rabbits were randomly divided into three experimental diets, containing 0% (CON), 2.5%, and 5% of BC (BC-2.5 and BC-5, respectively). The activity of antioxidant enzymes in plasma (catalase: CAT; glutathione peroxidase: GPx; superoxide dismutase: SOD), and the enzymes' gene expression in the liver and longissimus dorsi muscle, were determined. Results showed no significant differences, neither in plasma nor in tissues. A significant tissue-related effect has been observed regarding the mRNA levels of SOD and GPx, which were higher in the LD (p = 0.022) and liver (p = 0.001), respectively. Further studies, considering modifications of the length and dosage of dietary BC supplementation, are required to update the current state of knowledge in rabbits, as well as to fully understand the potential value of BC for possible application in farming use.

Characterization of a Bioink Combining Extracellular Matrix-like Hydrogel with Osteosarcoma Cells: Preliminary Results.

Three-dimensional (3D) bioprinting allows the production of artificial 3D cellular microenvironments thanks to the controlled spatial deposition of bioinks. Proper bioink characterization is required to achieve the essential characteristics of printability and biocompatibility for 3D bioprinting. In this work, a protocol to standardize the experimental characterization of a new bioink is proposed. A functionalized hydrogel based on gelatin and chitosan was used. The protocol was divided into three steps: pre-printing, 3D bioprinting, and post-printing. For the pre-printing step, the hydrogel formulation and its repeatability were evaluated. For the 3D-bioprinting step, the hydrogel-printability performance was assessed through qualitative and quantitative tests. Finally, for the post-printing step, the hydrogel biocompatibility was investigated using UMR-106 cells. The hydrogel was suitable for printing grids with good resolution from 4 h after the cross-linker addition. To guarantee a constant printing pressure, it was necessary to set the extruder to 37 °C. Furthermore, the hydrogel was shown to be a valid biomaterial for the UMR-106 cells' growth. However, fragmentation of the constructs appeared after 14 days, probably due to the negative osteosarcoma-cell interference. The protocol that we describe here denotes a strong approach to bioink characterization to improve standardization for future biomaterial screening and development.

A "blood theft" after liver transplantation: the role of interventional radiology in the management and treatment of splenic artery steal syndrome.

Splenic artery steal syndrome is a rare complication after liver transplant. It could lead to rapidly evolving major issues such as ischemic cholangiopathy and acute graft failure. Although the pathophysiology is not yet well understood, if diagnosed in time it could be easily managed with interventional radiology treatments. We present a case of a 47-year-old man presented to our institute with radiological findings typical for multifocal hepatocellular carcinoma in a cirrhotic liver. After therapy he underwent transplant. Some days after surgery he developed signs of acute liver failure. Steal syndrome was suspected by laboratory tests and radiology exams. The syndrome was confirmed by angiography and treated. The graft was saved, and the patient is still alive and free of disease. The purpose of this paper is to explain the importance of radiology exams in the diagnosis of splenic steal syndrome, explain its pathogenesis and describe the interventional management of this complication.

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre.

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1-9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.

IL-1R8 Downregulation and Concomitant TLR7 and TLR9 Upregulation Are Related to the Pathogenesis of Canine Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy in humans and dogs. Several studies disclosed some similarities between the two species, including the constitutive activation of the NF-κB pathway as a fundamental underlying pathogenetic mechanism. In humans, the downregulation of IL-1R8 is implicated in DLBCL development, but its role in dogs has not been explored so far. To gain insight into the pathogenesis of this tumor in dogs, we evaluated the mRNA and protein expression of IL-1R8 in 12 control lymph nodes obtained from dogs not bearing tumors and from 50 dogs with DLBCL. Moreover, we analyzed through qRT-PCR the expression of TLR7, TLR9, MYC, and p52 genes that are known to be involved in the IL-1R8 regulatory network. IL-1R8 and p52 were downregulated in DLBCLs compared to control lymph nodes (p < 0.001), while a higher expression of TLR7, TLR9, and MYC was observed in DLBCLs (p < 0.01). Immunohistochemistry confirmed the gene expression results, revealing a significantly lower IL-1R8 staining score in DLBCLs compared to control lymph nodes (p < 0.0001). Taken together, these results suggest that IL-1R8 downregulation may represent one of the mechanisms driving DLBCL pathogenesis in dogs, mainly through the dysregulation of the Toll-like/interleukin receptors signaling cascade and the aberrant activation of the classical NF-κB pathway.

Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease.

Interleukin-1 (IL-1) is a primary cytokine of innate immunity and inflammation. IL-1 belongs to a complex family including ligands with agonist activity, receptor antagonists, and an anti-inflammatory cytokine. The receptors for these ligands, the IL-1 Receptor (IL-1R) family, include signaling receptor complexes, decoy receptors, and negative regulators. Agonists and regulatory molecules co-evolved, suggesting the evolutionary relevance of a tight control of inflammatory responses, which ensures a balance between amplification of innate immunity and uncontrolled inflammation. IL-1 family members interact with innate immunity cells promoting innate immunity, as well as with innate and adaptive lymphoid cells, contributing to their differentiation and functional polarization and plasticity. Here we will review the properties of two key regulatory receptors of the IL-1 system, IL-1R2, the first decoy receptor identified, and IL-1R8, a pleiotropic regulator of different IL-1 family members and co-receptor for IL-37, the anti-inflammatory member of the IL-1 family. Their complex impact in pathology, ranging from infections and inflammatory responses, to cancer and neurologic disorders, as well as clinical implications and potential therapeutic exploitation will be presented.

Long Term Survival Analysis in a Cohort of 125 Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using Small Drug Eluting Beads.

PURPOSE: Different types of drug-eluting beads have been proposed for hepatocellular carcinoma (HCC) treatment, but long-term results are not well known. We report safety, efficacy and long-term overall survival of HCC patients not amenable of curative therapies treated with transcatheter arterial chemoembolization (TACE) using drug-eluting beads sized 70-150 micron. MATERIALS AND METHODS: This single-center retrospective study included 125 patients with Barcelona Clinic Liver Cancer stage A (80), B (45) and compensated cirrhosis. TACE was executed injecting drug-elutings microparticles loaded with 75 mg of Doxorubicine and was repeated in patients with partial response or stable disease after one month. Adverse events, response according to modified Response Evaluation Criteria in Solid Tumors and overall survival were assessed. RESULTS: Chemoembolization with 70-150 micron beads revealed an objective response rate of 88% according to mRECIST criteria and complete response was 60%. After a median follow-up of 53.3 months, overall survival was 36.6 months. Data were censored at the date of liver transplantation in 35 patients. 33 on 125 patients (26,4%) experienced at least one adverse event. We recorded a total of 102 adverse events and 18 were of a high grade (G3-G4). 30 day mortality was 0%. CONCLUSION: Chemoembolization with very small particles (70-150 µm) is an effective and safe treatment in unresectable HCC both as a primary therapy or as bridge to transplantation.

Preliminary Evidence of Endotoxin Tolerance in Dairy Cows during the Transition Period.

The blastogenic response of bovine peripheral blood mononuclear cells (PBMCs) to lipopolysaccharides (LPS) has been investigated for a long time in our laboratories. In particular, a possible correlation between the blastogenic response to LPS and the disease resistance of dairy cows has been suggested in previous studies. Isolated PBMCs from eight cows at three different time points during the transition period (T0 = 15 days before calving; T1 = 7 days post-calving; T2 = 21 days post-calving) were cultured in the presence or absence of LPS, and the blastogenic response was assayed 72 h after in vitro stimulation. Moreover, the gene expression of proinflammatory cytokines and kynurenine pathway molecules was investigated by real-time RT-PCR on both unstimulated and stimulated PBMCs. The cows were retrospectively divided into healthy and diseased, based on the development of peripartum diseases (subclinical ketosis and placenta retention). The comparison between healthy and diseased cows suggested that healthy animals seemed to better control the response to LPS. On the contrary, diseased animals showed a much higher inflammatory response to LPS. Moreover, cows were retrospectively classified as high and low responders based on the in vitro proliferative response of PBMCs to LPS, using the median value as a threshold. Unstimulated PBMCs of low responders showed higher expression of the proinflammatory cytokines Interleukin 1-ß (IL-1ß), Interleukin 6 (IL-6) and Tumor Necrosis Factor-α (TNF-α), compared to high responders. Our preliminary data suggest that, during the peripartum period, high responders seem to be more tolerant to endotoxins and develop a lower inflammatory response to different stressors. Instead, low responders could be more prone to the development of unwanted inflammatory conditions in response to mild/moderate stressors.

Proliferation Pattern of Pediatric Tumor-Derived Mesenchymal Stromal Cells and Role in Cancer Dormancy: A Perspective of Study for Surgical Strategy.

The explanation for cancer recurrence still remains to be fully elucidated. Moreover, tumor dormancy, which is a process whereby cells enter reversible G0 cell cycle arrest, appears to be a critical step in this phenomenon. We evaluated the cell cycle proliferation pattern in pediatric tumor-derived mesenchymal stromal cells (MSCs), in order to provide a better understanding of the complex mechanisms underlying cancer dormancy. Specimens were obtained from 14 pediatric patients diagnosed with solid tumors and submitted to surgery. Morphology, phenotype, differentiation, immunological capacity, and proliferative growth of tumor MSCs were studied. Flow cytometric analysis was performed to evaluate the cell percentage of each cell cycle phase. Healthy donor bone marrow-derived mesenchymal stromal cells (BM-MSCs) were employed as controls. It was noted that the DNA profile of proliferating BM-MSC was different from that of tumor MSCs. All BM-MSCs expressed the typical DNA profile of proliferating cells, while in all tumor MSC samples, ≥70% of the cells were detected in the G0/G1 phase. In particular, seven tumor MSC samples displayed intermediate cell cycle behavior, and the other seven tumor MSC samples exhibited a slow cell cycle. The increased number of tumor MSCs in the G0-G1 phase compared with BM-MSCs supports a role for quiescent MSCs in tumor dormancy regulation. Understanding the mechanisms that promote dormant cell cycle arrest is essential in identifying predictive markers of recurrence and to promote a dedicated surgical planning.

Therapeutic and Prophylactic Use of Oral, Low-Dose IFNs in Species of Veterinary Interest: Back to the Future.

Cytokines are important molecules that orchestrate the immune response. Given their role, cytokines have been explored as drugs in immunotherapy in the fight against different pathological conditions such as bacterial and viral infections, autoimmune diseases, transplantation and cancer. One of the problems related to their administration consists in the definition of the correct dose to avoid severe side effects. In the 70s and 80s different studies demonstrated the efficacy of cytokines in veterinary medicine, but soon the investigations were abandoned in favor of more profitable drugs such as antibiotics. Recently, the World Health Organization has deeply discouraged the use of antibiotics in order to reduce the spread of multi-drug resistant microorganisms. In this respect, the use of cytokines to prevent or ameliorate infectious diseases has been highlighted, and several studies show the potential of their use in therapy and prophylaxis also in the veterinary field. In this review we aim to review the principles of cytokine treatments, mainly IFNs, and to update the experiences encountered in animals.

The first report on coronavirus disease 2019 (COVID-19) vaccine refusal by patients with solid cancer in Italy: Early data from a single-institute survey.

INTRODUCTION: Patients with cancer have an increased risk of complications from coronavirus disease 2019 (COVID-19) infection, including death, and thus, they were considered as high-priority subjects for COVID-19 vaccination. We report on the compliance with the COVID-19 vaccine of patients affected by solid tumours. MATERIALS AND METHODS: Patients with cancer afferent to Medical Oncology 1 Unit of Regina Elena National Cancer Institute in Rome were considered eligible for vaccination if they were receiving systemic immunosuppressive antitumor treatment or received it in the last 6 months or having an uncontrolled advanced disease. The Pfizer BNT162b2 vaccine was proposed to all candidates via phone or during a scheduled visit. The reasons for refusal were collected by administrating a 6-item multiple-choice questionnaire. RESULTS: From 1st March to 20th March 2021, of 914 eligible patients, 102 refused vaccination (11.2%, 95% confidence interval [CI] 9.1-13.2). The most frequent (>10%) reasons reported were concerns about vaccine-related adverse events (48.1%), negative interaction with concomitant antitumor therapy (26.7%), and the fear of allergic reaction (10.7%). The refusal rate (RR) after 15th March (date of AstraZeneca-AZD1222 suspension) was more than doubled compared with the RR observed before (19.7% versus 8.6%, odds ratio [OR] 2.60, 95% CI 1.69-3.99; P < 0.0001). ECOG-PS 2 was associated with higher RR compared with ECOG-PS 0-1 (OR 2.94, 95% CI 1.04-8.34; P = 0.04). No statistically significant differences in RR according to other clinical characteristics were found. CONCLUSIONS: Our experience represents the first worldwide report on the adherence of patients with cancer to COVID-19 vaccination and underlines how regulatory decisions and media news spreading could influence the success of the campaign.

Goji Berries Supplementation in the Diet of Rabbits and Other Livestock Animals: A Mini-Review of the Current Knowledge.

In the last decades, several nutraceutical substances have received great attention for their potential role in the prevention and treatment of different diseases as well as for their beneficial effects in promoting the health of humans and animals. Goji berries (GBs) are the fruit of Lycium barbarum and other species of Lycium, used in traditional Chinese medicine, and they have recently become very popular in the Occidental world because of their properties, such as anti-aging, antioxidant, anticancer, neuroprotective, cytoprotective, antidiabetic, and anti-inflammatory activities. These effects are essentially evaluated in clinical trials in humans; in experimental animal models, such as mice and rats; and in cell lines in in vitro studies. Only recently has scientific research evaluated the effects of GBs diet supplementation in livestock animals, including rabbits. Although studies in the zootechnical field are still limited and the investigation of the GB mechanisms of action is in an early stage, the results are encouraging. This review includes a survey of the experimental trials that evaluated the effects of the GBs supplementation on reproductive and productive performances, immune system, metabolic homeostasis, and meat quality principally in the rabbit with also some references to other livestock animal species. Evidence supports the idea that GB supplementation could be used in rabbit breeding, although future studies should be conducted to establish the optimal dose to be administered and to assess the sustainability of the use of GBs in the diet of the rabbit.

Full-Digital Workflow for Fabricating a Custom-Made Direct Metal Laser Sintering (DMLS) Mandibular Implant: A Case Report.

Direct Laser Metal Sintering (DLMS) is an additive manufacturing (AM) technique that is capable of manufacturing metal parts according to a three-dimensional (3D) design made using computer-assisted-design (CAD) software, thanks to a powerful laser beam that melts selectively micro-powder layers, one on top of the other, until the desired object is generated. With DMLS, it is now possible to fabricate custom-made titanium implants for oral and maxillofacial applications. We present the case of a 67-year-old woman diagnosed with a squamous cell carcinoma of the mandible. The patient underwent subtotal mandibular resection; conventional reconstruction procedures failed to rehabilitate the function of the mandible. A prosthesis replacing the resected mandible was designed and fabricated using a digital workflow. The extensive bone defect was rehabilitated with a prosthesis replacing the mandibular bone and supporting a morse-taper dental prosthesis. The masticatory function was reestablished.

Remodeling of collagen constituting interlobular septa of subcutaneous adipose tissue following microwaves application.

In this study, the application of a recently introduced device based on electromagnetic energy transfer by microwaves for fat reduction, permitted to study specifically the modifications of thick fibrous collagen interlobular septa in the subcutaneous adipose tissue, related to the formation of large clusters of adipocytes. The use of Picrosirius red staining associated with circularly polarized microscopy gave evidence of appreciable modifications of the fibrous connective tissue forming septa. Compact fibrotic bundles of collagen I forming interlobular septa appeared reduced or dissolved, in part substituted by the increase of more diffuse and finely reticular collagen III. Remodeling of fibrous collagen, which formed bridles involved in the appearance at the surface of the skin of dimpling/orange peer pattern typical of cellulite, was observed.