Conditioned Medium of Mesenchymal Stromal Cells Loaded with Paclitaxel Is Effective in Preclinical Models of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is a very aggressive disease even in its early stages and is characterized by a severe prognosis. Neoadjuvant chemotherapy is one of the milestones of treatment, and paclitaxel (PTX) is among the most active drugs used in this setting. However, despite its efficacy, peripheral neuropathy occurs in approximately 20-25% of cases and represents the dose-limiting toxicity of this drug. New deliverable strategies to ameliorate drug delivery and reduce side effects are keenly awaited to improve patients' outcomes. Mesenchymal stromal cells (MSCs) have recently been demonstrated as promising drug delivery vectors for cancer treatment. The aim of the present preclinical study is to explore the possibility of a cell therapy approach based on the use of MSCs loaded with PTX to treat TNBC-affected patients. For this purpose, we in vitro evaluated the viability, migration and colony formation of two TNBC cell lines, namely, MDA-MB-231 and BT549, treated with MSC-PTX conditioned medium (MSC-CM PTX) in comparison with both CM of MSCs not loaded with PTX (CTRL) and free PTX. We observed stronger inhibitory effects on survival, migration and tumorigenicity for MSC-CM PTX than for CTRL and free PTX in TNBC cell lines. Further studies will provide more information about activity and potentially open the possibility of using this new drug delivery vector in the context of a clinical study.

Pros and Cons of CAD/CAM Technology for Infection Prevention in Dental Settings during COVID-19 Outbreak.

The purpose of this commentary is to update the evidence reported in our previous review on the advantages and limitations of computer-aided design/computer-aided manufacturing technology in the promotion of dental business, as well as to guarantee patient and occupational safety. The COVID-19 pandemic led to an unprecedented focus on infection prevention; however, waves of COVID-19 follow one another, asymptomatic cases are nearly impossible to identify by triage in a dental setting, and the effectiveness of long-lasting immune protection through vaccination remains largely unknown. Different national laws and international guidelines (mainly USA-CDC, ECDC) have often brought about dissimilar awareness and operational choices, and in general, there has been very limited attention to this technology. Here, we discuss its advantages and limitations in light of: (a) presence of SARS-CoV-2 in the oral cavity, saliva, and dental biofilm and activation of dormant microbial infections; (b) the prevention of SARS-CoV-2 transmission by aerosol and fomite contamination; (c) the detection of various oral manifestations of COVID-19; (d) specific information for the reprocessing of the scanner tip and the ward from the manufacturers.

Computer-Aided Design and Computer-Aided Manufacturing Versus Conventional Free Fibula Flap Reconstruction in Benign Mandibular Lesions: An Italian Cost Analysis.

PURPOSE: The cost of computer-aided design and computer-aided manufacturing (CAD-CAM) technology has created obstacles for its widespread use despite its several advantages. This study compared the cost of CAD-CAM technology with that of the conventional freehand technique in fibula reshaping for mandibular reconstruction. MATERIALS AND METHODS: A retrospective comparative study was conducted at the Maxillofacial and Dental Unit of the Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico (Milan, Italy). The study compared 15 patients in the CAD-CAM group with 10 patients in the conventional freehand group. Only benign pathologic lesions that required at least 3 fibular segments for reconstruction were included. The consumption of resources was estimated using micro-costing analysis (activity-based costing approach). RESULTS: The CAD-CAM group included 15 patients (7 men and 8 women) with a mean age of 42.2 ± 1.5 years, and the conventional freehand group included 10 patients (4 men and 6 women) with a mean age of 40.8 ± 0.9 years. Although CAD-CAM was a statistically expensive procedure in the perioperative phase (P < .0001), no significant difference was shown in total health care costs between the 2 groups (P = .98). CONCLUSION: CAD-CAM technology had a comparable expense to the conventional freehand technique, specifically for defects requiring at least 3 fibular segments.

The Effect of Orthognathic Surgery on Soft-Tissue Facial Asymmetry: A Longitudinal Three-Dimensional Analysis.

In modern orthognathic surgery, the functional results cannot disregard a good aesthetic outcome. In this study, a stereophotogrammetric longitudinal analysis of the symmetry of facial thirds was performed in 18 patients affected by Class III skeletal malocclusion, with clinical asymmetry, treated with a bimaxillary osteotomy. Their 3-dimensional facial images were acquired in the preoperative phase and 6, 12, and 24 months after surgery, and compared to those obtained in a control group of 23 subjects with Class I skeletal occlusion, without clinical asymmetry and no history of traumas or alterations at the maxillo-facial area. Images of the hemi-faces of the subjects were divided into thirds (upper, middle, lower), mirrored and superimposed to their contralateral ones; soft-tissue facial symmetry was obtained as the root mean square distance between the hemi-faces in the three thirds.In patients, no significant differences in facial symmetry (root mean square distance) were found among the study time points (analysis of variance, P > 0.05); the lower facial third was more asymmetric than the upper one (Tukey honestly significant difference P < 0.05). Patients were significantly more asymmetric than the control subjects (Student t, P < 0.05). In conclusion, patients with Class III malocclusion exhibited a higher level of facial asymmetry than control subjects; their asymmetry did not change significantly in the different phases of the surgical and orthodontic treatment and throughout a 24-month follow-up. In skeletal Class III patients, bimaxillary osteotomy did not modify the level of asymmetry in any facial third.

Donor-Site Morbidity After Osteocutaneous Free Fibula Transfer: Longitudinal Analysis of Gait Performance.

PURPOSE: The purpose was to evaluate donor-site clinical morbidity and changes in kinematic gait parameters after the harvest of a vascularized free fibula flap for facial reconstruction. MATERIALS AND METHODS: We enrolled 14 patients (aged 50 ± 15 years) in a longitudinal study. Every patient underwent a double evaluation in which a presurgical assessment and 6-month postsurgical assessment were performed. Subjective donor-site evaluation was carried out through unstructured clinical questioning about pain, paresthesia, walking ability, and restrictions in activity. Further subjective evaluations were assessed through the Western Ontario and McMaster Universities Osteoarthritis Index and the Point Evaluation System for Lower Extremity Fibulectomy. A clinical evaluation of the donor site assessed muscular deficits, sensibility disturbance, and wound healing. Temporal and spatial kinematic parameters were measured through gait analysis during overground walking at a comfortable speed. RESULTS: Postsurgical clinical examinations detected 1 patient affected by a neurologic disorder and 3 patients with donor-site pain, whereas 10 patients (71%) declared no residual alterations in the operated leg. On average, the Western Ontario and McMaster Universities Osteoarthritis Index score was 367 of 2,400, and the Point Evaluation System for Lower Extremity Fibulectomy score was 19 of 24. Presurgical versus postsurgical gait analysis comparison showed no significant differences in gait parameters except for a 6% reduction in the double-support phase. Stance values were higher for the operated limb in both evaluations (+1.3% before surgery, +1.8% after surgery). No alterations were detected in the range of motion of the lower-limb joints. CONCLUSIONS: Considering the slight modification of the gait pattern, which is not usually perceived by patients, vascularized free fibula flap harvest was generally associated with successful functional and subjective outcomes of the donor site.

Evaluation of the Accuracy of Virtual Planning in Orthognathic Surgery: A Morphometric Study.

BACKGROUND: The purpose of this study was to prospectively test the accuracy of computer-aided orthognathic surgery comparing the virtual surgical planning with the three-dimensional (3D) outcome. METHODS: Patients that underwent computer-assisted orthognathic surgery were retrospectively evaluated. The postoperative results were compared with the surgical plan, superimposing the postoperative computed tomography (CT) scan onto the virtual plan. Surface-based superimpositioning of the postoperative CT scan onto the 3D preoperative plan was carried out to visualize the discrepancy between preoperative virtual plan and postoperative 3D CT result. RESULTS: A total of 17 consecutive patients that underwent two-jaw computer-assisted orthognathic surgery were enrolled in the study.The average linear differences for selected points were <1 mm in 12 patients out of 17. In 5 patients out of 17, the average differences for selected points were <2 mm. CONCLUSIONS: An overall high degree of accuracy between the virtual plan and the postoperative result was found.

Three-Dimensional Stereophotogrammetric Evaluation of the Efficacy of Autologous Fat Grafting in the Treatment of Parry-Romberg Syndrome.

Autologous fat grafting is a surgical procedure used to correct volumetric defects, atrophies, and sclerosis. Three-dimensional (3D) facial photography may enable researchers to quantify the success of surgical procedures through volumetric and surface assessments. Using 3D photography, the authors assessed the results of autologous fat grafting performed in a 15-year-old patient affected by Parry-Romberg syndrome, a rare condition resulting in progressive hemifacial atrophy of skin, subcutaneous tissues and, ultimately, bone. Stereophotogrammetric acquisitions were performed before and 4 months after the surgical intervention. The obtained results were objectively assessed in terms of facial symmetry through calculation of root mean square deviation point-to-point distance between the treated and healthy side, and volume modifications between pre- and postsurgical 3D facial scans. Four months after surgery, 73% of injected adipose tissue was resorbed, whereas facial symmetry increased up to 63%. The proposed method is not invasive and provides quantitative information about the surgical and esthetic outcomes. Clinicians could better plan surgery, and the patients could be more motivated and compliant to the treatment.

Oral Surgery in Patients With Glanzmann Thrombasthenia: A Case Series.

Glanzmann thrombasthenia is a severe defect of platelet function caused by an inherited deficiency or dysfunction of the glycoprotein IIb/IIIa complex, the platelet fibrinogen receptor. Patients with Glanzmann thrombasthenia experience lifelong spontaneous and post-traumatic mucocutaneous bleeding diathesis. Surgery is usually very challenging, requiring close cooperation among surgeons, hematologists, and anesthesiologists. For anatomic reasons, oral surgery is particularly difficult owing to the inherent risk of hemorrhage and the difficulty in achieving local hemostasis. In the present report, we describe 3 successful cases of oral surgery in patients with Glanzmann thrombasthenia and report the surgical and hematologic management of each case.

Pre-augmentation soft tissue expansion: an overview.

OBJECTIVES: The aim of this study was to explore the development of soft tissue expanders, their different types and their potential applications prior to bone augmentation and implant placement. MATERIAL AND METHODS: A review of pertinent literature was performed using PubMed to comprehend the dynamics of soft tissue expanders and determine the current position of their pre-augmentation applications. RESULTS: There is promising, albeit preliminary information regarding the benefits of pre-augmentation soft tissue expansion. Findings cannot be generalised due to relatively small sample size. CONCLUSIONS: Further clinical trials with larger sample sizes and long-term follow-up are needed before soft tissue expanders can be confidently applied in everyday clinical practice.

Resorbable Materials for Reconstruction of the Orbital Floor in Children.

The best treatment of pediatric orbital fractures is debated and different strategies are proposed in the literature. Resorbable materials, due to their features and the specific requirements of the pediatric population, seem a very suitable choice. The authors present their experience by describing 3 cases and explaining their mesh modeling technique. Two fractures were caused by accidental falls, whereas the other resulted from aggression. Clinical and radiological evaluation (computed tomography scanning) was performed before surgery. No complications occurred either immediately after surgery or in the long term (maximum follow-up of 3 y). As there has been little experience of the use of resorbable mesh in maxillofacial pediatric traumatology, the authors describe their technique, which may facilitate the use of this material in orbital fractures.

Stair ascent and descent in assessing donor-site morbidity following osteocutaneous free fibula transfer: a preliminary study.

PURPOSE: The aim of this study was to investigate gait kinematic parameters during stair ascent and descent after fibula free flap removal for facial reconstruction. MATERIALS AND METHODS: Eight patients who underwent facial reconstruction with fibula free flap removal ascended and descended 3 standard steps. Their movements were recorded by a motion analyzer; gait kinematic parameters were obtained and compared with those calculated in 8 control subjects. RESULTS: Stride time, percentage of swing, and support phases did not differ among healthy and operated limbs and control subjects (Kruskal-Wallis, P > .05). No significant differences were found for hip and knee movements, pelvis rotation and tilt, and body center of mass displacements. During stair descent, the patients had significantly larger pelvis inclinations than the control subjects (P < .05). CONCLUSIONS: No functional limitations during stair performance were found. The only significant difference could indicate a minor control of the pelvis and should be used to define specific rehabilitative interventions.

Maxillary sinusitis after sinus lift due to Gemella morbillorum: antibiotic and surgical treatment.

Sinus lift is a predictable procedure for increasing alveolar bone height in the posterosuperior alveolar regions to allow oral prosthetic rehabilitation. Several complications have been documented in the literature and vary from sinus membrane perforation to maxillary rhinosinusitis. The authors present a case of Gemella morbillorum acute sinusitis after sinus lift surgery. The purpose of this report is to describe the surgical and pharmacological management of a patient allergic to penicillin.

Regeneration of Critical-Sized Mandibular Defects Using 3D-Printed Composite Scaffolds: A Quantitative Evaluation of New Bone Formation in In Vivo Studies.

Mandibular tissue engineering aims to develop synthetic substitutes for the regeneration of critical size defects (CSD) caused by a variety of events, including tumor surgery and post-traumatic resections. Currently, the gold standard clinical treatment of mandibular resections (i.e., autologous fibular flap) has many drawbacks, driving research efforts toward scaffold design and fabrication by additive manufacturing (AM) techniques. Once implanted, the scaffold acts as a support for native tissue and facilitates processes that contribute to its regeneration, such as cells infiltration, matrix deposition and angiogenesis. However, to fulfil these functions, scaffolds must provide bioactivity by mimicking natural properties of the mandible in terms of structure, composition and mechanical behavior. This review aims to present the state of the art of scaffolds made with AM techniques that are specifically employed in mandibular tissue engineering applications. Biomaterials chemical composition and scaffold structural properties are deeply discussed, along with strategies to promote osteogenesis (i.e., delivery of biomolecules, incorporation of stem cells, and approaches to induce vascularization in the constructs). Finally, a comparison of in vivo studies is made by taking into consideration the amount of new bone formation (NB), the CSD dimensions, and the animal model.

Mesenchymal stromal cells loaded with Paclitaxel (PacliMES) a potential new therapeutic approach on mesothelioma.

Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone. An in vivo approach to treat in situ mesothelioma xenografts using a minimal amount of 106 mesenchymal stromal cells loaded with Paclitaxel showed the same efficacy of a systemic administration of 10 mg/kg of Paclitaxel. These data strongly support drug delivery system by mesenchymal stromal cells as a useful approach against many solid tumors. We look with interest at the favourable opinion recently expressed by the Italian Drug Agency on the procedure for the preparation of mesenchymal stromal cells loaded with Paclitaxel in large-scale bioreactor systems and their storage until clinical use. This new Advanced Medicinal Therapy Product, already approved for a Phase I clinical trial on mesothelioma patients, could pave the way for mesenchymal stromal cells use as drug delivery system on other solid tumors for adjuvant therapy associated with surgery and radiotherapy.

Micro-fragmented Fat Inhibits the Progression of Human Mesothelioma Xenografts in Mice.

BACKGROUND: Malignant pleural mesothelioma is a pathology with no effective therapy and a poor prognosis. Our previous study demonstrated an in vitro inhibitory effect on mesothelioma cell lines of both the lysate and secretome of adipose tissue-derived Mesenchymal Stromal Cells. The inhibitory activity on tumor growth has been demonstrated also in vivo: five million Mesenchymal Stromal Cells, injected "in situ", produced a significant therapeutic efficacy against MSTO-211H xenograft equivalent to that observed after the systemic administration of paclitaxel. OBJECTIVE: The objective of this study is to evaluate the efficacy of low amount (half a million) Mesenchymal Stromal Cells and micro-fragmented adipose tissues (the biological tissue from which the Mesenchymal Stromal Cells were isolated) on mesothelioma cells growth. METHODS: Tumor cells growth inhibition was evaluated in vitro and in a xenograft model of mesothelioma. RESULTS: The inhibitory effect of micro-fragmented fat from adipose-tissue has been firstly confirmed in vitro on MSTO-211H cell growth. Then the efficacy against the growth of mesothelioma xenografts in mice of both micro-fragmented fat and low amount of Mesenchymal Stromal Cells has been evaluated. Our results confirmed that both Mesenchymal Stromal Cells and micro-fragmented fat, injected "in situ", did not stimulate mesothelioma cell growth. By contrast, micro-fragmented fat produced a significant inhibition of tumor growth and progression, comparable to that observed by the treatment with paclitaxel. Low amount of Mesenchymal Stromal Cells exerted only a little anticancer activity. CONCLUSION: Micro-fragmented fat inhibited mesothelioma cell proliferation in vitro and exerted a significant control of the mesothelioma xenograft growth in vivo.