Extracorporeal membrane oxygenation support in carinal resection for recurrent chondrosarcoma after previous distal tracheal resection

Carinal re-resection for tumour recurrence is rarely performed due to increased difficulty in airway reconstruction. We reported a successful case of carinal resection and reconstruction for recurrent chondrosarcoma after previous distal tracheal resection. Due to the technical complexity of the reconstruction and the poor respiratory reserve of the patient, the veno-venous extracorporeal membrane oxygenation support was used.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination with IT.     

Radiographic Analysis of Graft Dimensional Changes in Transcrestal Maxillary Sinus Augmentation: A Retrospective Study

Background. The maxillary sinus lift is a popular and predictable technique associated with implant-supported rehabilitation of the severely atrophic maxilla. The aim of the present retrospective study was to investigate the effectiveness of transcrestal maxillary sinus augmentation and the graft resorption pattern using different heterologous bone substitutes. Methods. A total of 75 sinus-grafting procedures were performed and 89 implants were placed in 66 patients, 24 males and 42 females, with mean age 67.9 ± 10.64 years (range 43–84 years). Nineteen subjects were smokers. The mean follow-up period was 93.33 ± 54.71 months (range 14–240 months). Clinical and radiographical evaluations were performed. Graft height and width were measured at baseline and at the latest follow-up. Results. Mesiodistal and vertical resorption averaged 9.3 ± 20.7% (standard deviation), and 5.04 ± 9.9% of the postoperative size, respectively, considering the graft as the unit. Linear regression analysis showed that graft resorption in both the vertical and the mesiodistal dimension is independent of the follow-up time. Conversely, there was a trend for greater resorption when increasing the postoperative graft size, in both vertical (p = 0.001) and horizontal (p = 0.007) dimensions. When grouping the dimensional changes by graft particle size (only small (<300 μm) particles, combination of small and medium (>500 μm)/large (>1000 μm) particles, and only medium/large particles), there was a trend for greater resorption associated with smaller particles, but it was not significant; neither in the mesiodistal nor in the vertical dimension (p = 0.17 and p = 0.25, respectively). No implant was lost during the observation period. In conclusion, the transcrestal technique for maxillary sinus augmentation documented a high level of predictability. The low clinical morbidity and the contextual dental implant positioning is clinically useful in relation to a significant reduction of the time required for implant restoration, a consistent decrease of the number of surgical phases, and a cost-effectiveness approach for the rehabilitation. The graft resorption pattern in all cases was compatible with persistent implant protection and support.     

Production of Dense Cu-10Sn Part by Laser Powder Bed Fusion with Low Surface Roughness and High Dimensional Accuracy

Tin-bronze alloys with a tin content of at least 10 wt% have excellent mechanical properties, wear resistance, and corrosion resistance. Among these alloys, Cu-10Sn was investigated in this study for production with the laser powder bed fusion process with a 500W Yb:YAG laser. In particular, a design of experiment (DoE) was developed in order to identify the optimal process parameters to obtain full density, low surface roughness, and high dimensional accuracy. Samples were characterized with Archimedes’ method and optical microscopy to determine their final density. It was shown that the first method is fast but not as reliable as the second one. A first mechanical characterization was performed through microhardness tests. Finally, a set of process parameters was identified to produce fully dense samples with low surface roughness and high accuracy. The results showed that the volumetric energy density could represent an approach that is too simplified, therefore limiting the direct correlation with the physical aspects of the process.