Antimicrobial efficacy of direct air gas soft jet plasma for the in vitro reduction of oral bacterial biofilms.

The aim of this study was to evaluate the antimicrobial efficacy of an air gas soft jet CAP for its potential use in removing oral biofilms, given that plasma-based technologies have emerged as promising methods in periodontology. Two types of biofilms were developed, one by Streptococcus mutans UA 159 bacterial strain and the other by a complex mixture of saliva microorganisms isolated from a patient with periodontitis. This latter biofilm was characterized via Next Generation Sequencing to determine the main bacterial phyla. The CAP source was applied at a distance of 6 mm for different time points. A statistically significant reduction of both CFU count and XTT was already detected after 60 s of CAP treatment. CLSM analysis supported CAP effectiveness in killing the microorganisms inside the biofilm and in reducing the thickness of the biofilm matrix. Cytotoxicity tests demonstrated the possible use of CAP without important side effects towards human gingival fibroblasts cell line. The current study showed that CAP treatment was able to significantly reduce preformed biofilms developed by both S. mutans and microorganisms isolated by a saliva sample. Further studies should be conducted on biofilms developed by additional saliva donors to support the potential of this innovative strategy to counteract oral pathogens responsible for periodontal diseases.

Malnutrition as a Risk Factor in the Development of Oral Cancer: A Systematic Literature Review and Meta-Analyses.

This systematic review and meta-analyses aimed to assess whether malnutrition may increase the incidence of oral cancer. Following the PRISMA statement, the research was conducted on PubMed, Scopus, and MEDLINE via OVID without any time restrictions. The risk of bias was assessed, and the quality of evidence for each performed meta-analysis was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Sixty-one articles met the inclusion criteria and seven studies underwent quantitative evaluation. For our meta-analysis on hypovitaminosis B, three studies with a total of 90,011 patients were included. An odds ratio of 2.22 was found. Our meta-analysis on the correlation between vitamin C and oral cancer included one study with a total of 866 patients and the derived odds ratio was 1.06. Our meta-analysis on the relationship between vitamin D deficiency and the incidence of oral cancer included three studies with a total of 12,087 patients and the odds ratio was -2.58. The GRADE system showed a moderate strength of evidence due to the presence of studies with a high risk of bias and high indirectness of the data given. The present findings suggest that an inadequate intake of vitamins, particularly vitamin D, poses a risk for the onset of oral cancer.

Anti-LGALS3BP antibody-drug conjugate treatment induces durable and potent antitumor response in a preclinical model of adenoid cystic carcinoma.

OBJECTIVES: Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically arises from glandular tissues, most commonly in the salivary glands. Although relatively rare, it represents a serious clinical issue as the management of the disease is highly complex being the only therapeutic options represented by invasive surgery and/or radiotherapy. In the present study, we have explored the potential of galectin-3 binding protein (LGALS3BP) as a novel target for antibody-drug conjugate (ADC) therapy in ACC. MATERIALS AND METHODS: RNAseq was conducted on a panel of 10 ACC patient-derived xenografts (PDX)s tissues and 6 normal salivary glands to analyze LGALS3BP gene expression. Protein expression was assessed in ACC PDX and primary tumor tissues using immunohistochemistry. Anti-LGALS3BP ADC named 1959-sss/DM4, was tested in high LGALS3BP expressing ACC PDX model ST1502B. RESULTS: RNAseq analysis revealed that LGALS3BP expression was highly expressed in ACC PDX tissues compared to normal salivary gland tissues. As evaluated by immunohistochemical analysis, LGALS3BP protein was found to be heterogeneously expressed in 10 ACC PDX and in tumor tissues derived from a cohort of 37 ACC patients. Further, treatment with 1959-sss/DM4 ADC led to durable tumor growth inhibition (TGI) in 100% of animals without observed toxicity. CONCLUSIONS: Our study provides strong evidence that LGALS3BP is a promising therapeutic target for ACC, warranting further expedited preclinical and clinical investigation.

LGALS3BP is a potential target of antibody-drug conjugates in oral squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody-drug conjugate (ADC) therapy. METHODS: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT-PCR, Western Blot analysis, and ELISA. RESULTS: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer-derived extracellular vesicles. Moreover, LGALS3BP high-expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC-payload DM4, with an IC50 around 0.3 nM. CONCLUSIONS: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC-based therapy.

Overexpression of E-Cadherin Is a Favorable Prognostic Biomarker in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR) = 0.41 95% confidence interval (95% CI) (0.32-0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37-0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19-0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.

Comparison of heat production and bone architecture changes in the implant site preparation with compressive osteotomes, osseodensification technique, piezoelectric devices, and standard drills: an ex vivo study on porcine ribs.

This study aimed at investigating differences in heat generation and bone architecture following four different implant site preparation techniques: compressive osteotomes, conventional drills, osseodensification (OD mode with osseodensification drills), and piezoelectric systems. Porcine rib bones were used as a model for implant surgery. Thermocouples were employed to measure temperature changes, and micro-CT to assess the bone architecture. The primary stability and insertion torque values of the implants placed in the differently prepared sites were assessed. The temperature changes were higher with Piezo. The average primary stability using the ISQ scale was the greatest for drills (76.17 ± 0.90) and the lowest for osteotomes (71.50 ± 11.09). Insertion torque was significantly higher with the osseodensification method (71.67 ± 7.99 Ncm) in comparison to drills, osteotomes, and piezo. Osteotomes showed the highest bone to implant contact percentage (39.83 ± 3.14%) and average trabecular number (2.02 ± 0.21 per mm), while drills exhibited the lowest (30.73 ± 1.65%; 1.37 ± 0.34 per mm). Total implant site bone volume was the highest with osseodensification (37.26 ± 4.13mm3) and the lowest for osteotomes (33.84 ± 3.84mm3). Statistical analysis showed a high primary stability and decrease in temperature during implant site preparation with osseodensification technique. The results support the use of osseodensification technique for implant site preparation.

Open Questions in Cold Atmospheric Plasma Treatment in Head and Neck Cancer: A Systematic Review.

Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients' death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.

Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review.

BACKGROUND: Antibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed the progress in ADC development for the treatment of HNC. METHODS: This review was registered in PROSPERO database. A comprehensive search was conducted following PRISMA guidelines and using PubMed, Scopus and Web of Science database. RESULTS: In total, 19 studies were included. Due to the significant heterogeneity of the outcome measures, meta-analysis was not performed, and data were summarized in tables. HNC results are poorly represented in the cohorts of completed clinical trials; published data are mostly focused on safety evaluation rather than efficacy of ADCs. CONCLUSIONS: Although several novel agents against a wide range of different antigens were investigated, showing promising results at a preclinical level, most of the targets reported in this review are not specific for HNC; hence, the development of ADCs tailored for the HNC phenotype could open up new therapeutic perspectives. Moreover, the results from the present systematic review call attention to how limited is the application of current clinical trials in HNC.

The Emerging Role of Cold Atmospheric Plasma in Implantology: A Review of the Literature.

In recent years, cold atmospheric plasma (CAP) technologies have received increasing attention in the field of biomedical applications. The aim of this article is to review the currently available literature to provide an overview of the scientific principles of CAP application, its features, functions, and its applications in systemic and oral diseases, with a specific focus on its potential in implantology. In this narrative review, PubMed, Medline, and Scopus databases were searched using key words like "cold atmospheric plasma", "argon plasma", "helium plasma", "air plasma", "dental implants", "implantology", "peri-implantitis", "decontamination". In vitro studies demonstrated CAP's potential to enhance surface colonization and osteoblast activity and to accelerate mineralization, as well as to determine a clean surface with cell growth comparable to the sterile control on both titanium and zirconia surfaces. The effect of CAP on biofilm removal was revealed in comparative studies to the currently available decontamination modalities (laser, air abrasion, and chlorhexidine). The combination of mechanical treatments and CAP resulted in synergistic antimicrobial effects and surface improvement, indicating that it may play a central role in surface "rejuvenation" and offer a novel approach for the treatment of peri-implantitis. It is noteworthy that the CAP conditioning of implant surfaces leads to an improvement in osseointegration in in vivo animal studies. To the best of our knowledge, this is the first review of the literature providing a summary of the current state of the art of this emerging field in implantology and it could represent a point of reference for basic researchers and clinicians interested in approaching and testing new technologies.

Split crest technique for implant treatment of agenesis of the upper lateral incisors: results of a randomized pilot histological and clinical study at 24-month follow-up

Abstract Agenesis of lateral incisors, besides the functional issues, represents a great esthetic drawback. The selection of an appropriate treatment is a complex decision, which should consider the stability of the clinical outcomes over time. The aim of the present study was a histological and clinical comparison of two-stage split crest technique (SCT), with bone chips alone or mixed with porcine bone in patients affected by unilateral and bilateral agenesis of the upper lateral incisors. Eleven patients were enrolled, and randomly assigned to receive a treatment with autologous bone chips (group 1) or autologous bone chips mixed 1:1 to porcine-derived xenogenic bone (group 2). After a 2-month healing period, implants were placed and biopsies harvested for histomorphometrical evaluation. Clinical assessment, according to ICOI PISA health scale, and radiographic marginal bone loss evaluation at 12- and 24-month follow-ups were conducted. The histomorphometry showed significantly greater new bone formation (p > 0.0229) in group 2. At 12- and 24-month follow-ups, all the evaluated implants, regardless of the group they were allocated, could be categorized as "success" in the ICOI Pisa Health Scale for Dental Implants, and did not show significant difference in crestal bone loss. To the best of our knowledge, these are the first histological and clinical outcomes indicating that the use of bone chips mixed 1:1 to porcine bone in SCT could be a promising technique for the rehabilitation of patients with agenesis of the upper lateral incisors, although studies with a larger number of patients and implants, and a longer follow up are needed.

Effectiveness of Different Commercial Chlorhexidine-Based Mouthwashes After Periodontal and Implant Surgery: A Systematic Review.

OBJECTIVES: The aim of the present study was to review the effectiveness, side effects, and patient acceptance of different concentrations and formulation of chlorhexidine-based mouthwashes used after periodontal and implant surgery. MATERIALS AND METHODS: The PRISMA guideline was adopted in the search strategy using electronic databases PubMed and MEDLINE to identify randomized and case-control prospective studies on humans written in English language and published up to September 2017. RESULTS: A total of 10 articles were selected for a total of 344 patients. Because of the significant heterogeneity of the outcome measures, meta-analysis was not performed, and the data were summarized in a table. A positive relationship between the use of chlorhexidine and reduction of plaque was found, demonstrating the effectiveness of the substance in terms of antisepsis and decrease of inflammation after periodontal and implant surgery. CONCLUSION: Chlorhexidine is recognized as the primary agent for plaque control and the gold standard in preventing infection, although the presence of largely known side effects would affect patient compliance. Future research should be directed at finding chlorhexidine formulation with negligible adverse effects, without compromising or even increasing its effectiveness as the antiseptics and antiplaque agent.

Influence of the Buccal Bone Crest Width on Peri-Implant Hard and Soft Tissues Dimensions: A Histomorphometric Study in Humans.

OBJECTIVE: To histologically evaluate hard and soft tissues adaptation at screw-shaped devices installed at recipient sites in the distal segments of the alveolar edentulous ridge prepared with a buccal bone width of 1 or 2 mm. MATERIAL AND METHODS: Sixteen volunteers received 2 nonsubmerged titanium implants each; after 3 months, biopsies were obtained and processed for histology. The distances between implant shoulder (IS), top of the bony crest (C), coronal level of osseointegration (B), peri-implant mucosa (PM), and apical extension of the junctional epithelium (aJE) were measured. RESULTS: There were no significant statistically differences between test and control sites regarding IS-C, IS-B, PM-IS, PM-B, PM-aJE, aJE-B measurements. The horizontal bone resorption 1 mm below IS was 0.3 ± 0.3 and 1.0 ± 0.7 mm at the test and control sites, respectively. This difference was statistically significant. CONCLUSIONS: Similar hard and soft tissues dimensions were observed in both groups. However, a higher horizontal bone resorption was seen at the control sites. Nonsubmerged implant installation should be performed when a 1 mm buccal bony crest width is present so as to limit the horizontal bone resorption.

Regenerative properties of collagenated porcine bone grafts in human maxilla: demonstrative study of the kinetics by synchrotron radiation microtomography and light microscopy.

OBJECTIVES: Recently, it has been reported that heterologous biomaterials, where the collagen matrix is preserved, seem to facilitate blood clotting and the subsequent invasion of repairing and regenerative cells. This study aimed at evaluating the healing of human extraction sockets grafted with a collagenated cortico-cancellous porcine bone (mp3®, OsteoBiol®, Tecnoss®, Giaveno, Italy) by synchrotron radiation X-ray microtomography (microCT) and histology in order to have a 3D quantitative characterization over time. MATERIALS AND METHODS: Ridge preservation with porcine bone and collagen membrane was performed on 21 patients using a flapless approach and a secondary soft tissue closure. At the time of implant placement, six bone samples were harvested, two in the 3-month group, two in the 6-month group, one in the 12-month group post-surgery, and one spontaneously healed control, and evaluated by microCT and histology. RESULTS: MicroCT revealed that in the grafted sites there were a greater number of trabeculae, although they appeared thinner than in the control sites; these trabeculae homogenously filled the defects, suggesting an improved strength of the socket. Histology showed that over time, the amount of biomaterial decreased and the newly formed bone increased, while less dense bone with wider marrow spaces was detected in the control sample, supporting synchrotron findings. CONCLUSIONS: The morphometric data converge to indicate the suitability of porcine bone for the preservation of post-extraction sockets. CLINICAL RELEVANCE: The use of mp3 is encouraged to preserve and heal sockets.

The Impact of Residual Subgingival Cement on Biological Complications Around Dental Implants: A Systematic Review.

OBJECTIVES: To perform a systematic review on the impact of residual subgingival cement on peri-implant diseases and crestal bone loss. MATERIAL AND METHODS: MEDLINE, SCOPUS, ISI Web of Knowledge and Cochrane Central Register of Controlled Trials (CENTRAL) databases were used to identify articles published without time limits. RESULTS: A total of 6 articles were selected for a total of 389 patients (687 implants). The studies were heterogeneous and had a moderate-to-high risk of bias, but met the inclusion criteria. Four of 6 studies were published by the same research group and assessed similar populations over time. A positive relationship between residual cement and peri-implant inflammation was observed. Data on peri-implant probing depths and crestal bone loss were reported in 1 study. CONCLUSION: Residual subgingival cement seems to be strongly associated with peri-implant mucositis which is a risk factor for increased probing depths crestal bone loss and peri-implantitis. Zinc oxide eugenol cements should be preferred to resin cements especially in patients with a history of periodontitis.

Molecular, Cellular and Pharmaceutical Aspects of Bone Grafting Materials and Membranes During Maxillary Sinus-lift Procedures. Part 1: A General Overview.

Sinus augmentation procedure has been demonstrated to be a highly predictable treatment in posterior maxilla atrophy. All the surgical interventions in the maxillary region require deep knowledge of anatomy and possible anatomical variations. In this article, pre-operative and post- operative assessments of sinus cavity as well as novel approaches to deepen our knowledge of the behavior of bone substitute materials are described. The awareness of the patient's morphologic conditions enables exact planning of invasive surgery and aids to avoid complications. Pre- operative radiologic evaluation of the region before sinus lift is advisable both for a planning of the sinus augmentation and for selection and alignment of the optimum placement of implants. On the orthopantomography it is possible to measure the vertical dimension of graft, but not the volume and 3D changes. Cone-beam computed tomography (CBCT) has become the "gold standard" to plan a comprehensive implant treatment and to achieve a post-operative assessment. A computer-aided design/computer-aided manufacturing (CAD/CAM) technique is proposed to produce custom-made block grafts for sinus lift procedure, and a customized cutting guide to accurately place the lateral wall and ease membrane elevation. This procedure allows to reduce intervention time, to precisely adapt the scaffold, to reduce risk of complications and to improve operation quality. Recently, a novel approach has been used to deepen our knowledge of the behavior of BSBs: by means of synchrotron micro-tomography (SCT). It is a 3-D analyzing method, suitable to examine the dynamic and spatial arrangement of regenerative phenomena in complex anatomical structures such as bone, where tissues with several morphologies (alveolar process, unmineralized extracellular matrix, regenerated vessels, etc.) compete to achieve the final goal of bone regeneration.

Update of Surgical Techniques for Maxillary Sinus Augmentation: A Systematic Literature Review.

OBJECTIVE: A wide range of surgical techniques are available for maxillary sinus augmentation. This review aimed to determine which techniques have achieved the highest success rates and so offer the greatest predictability. MATERIALS AND METHODS: A systematic literature review was performed using the PubMed, MEDLINE, and Scopus databases, identifying clinical trials that assessed different surgical techniques for maxillary sinus augmentation, and registered the success rates of subsequent implant placement. RESULTS: A total of 40 articles described clinical studies involving different maxillary sinus augmentation procedures with follow-up periods of at least 6 months after dental implant placement. Implant success rates varied between 94% and 100% during the follow-up periods. CONCLUSION: A wide variety of clinical techniques are available for maxillary sinus augmentation; the choice of the technique will depend chiefly on the characteristics of the edentulous site, which will permit or prevent the placement of the implant at the moment of sinus augmentation surgery.

Anatomical Remodeling of Buccal Bone Plate in 35 Premaxillary Post-Extraction Immediately Restored Single TPS Implants: 10-Year Radiographic Investigation.

PURPOSE: The anatomical remodeling technique (ART) was proposed to place postextraction implants with the aid of specific osteotomes. This study is a clinical and radiographic evaluation with 10-year follow-up of anterior postextraction single implants placed with the ART and immediately restored. MATERIALS AND METHODS: Thirty-five patients, with a hopeless tooth in the anterior maxilla, were included in the study and 35 implants were inserted according to the ART. Clinical and radiographic evaluations were performed at baseline (T0), after 6 (T1) and 14 months (T2), 4 years after surgery (T3) and every other year up to the 10-year follow-up (T4, T5, and T6). Implant success, survival, and failure rates were evaluated according to the International Congress of Oral Implantologists Pisa Consensus Conference criteria. RESULTS: Twenty-nine patients and 29 implants were available for the 10-year data analysis. After 10 years, the accumulated mean marginal bone loss was 2.69 ± 0.42 mm. The cumulative survival rate of the implants was 100%. CONCLUSIONS: Immediately loaded postextractive implants, placed according to the ART, have been proved to be a predictable method to rehabilitate single tooth in the anterior maxilla.

Management of a fractured, nonremovable implant: a clinical report with a 12-month follow-up.

Implant failures could be due to biological or mechanical factors, which also include fracture of the fixture. The present report presents a case of a single fractured implant placed in the left mandibular molar region. Since the residual portion of the fixture was perfectly osseointegrated with no signs of peri-implantitis, and in direct contact with the roof of the inferior alveolar nerve canal, it was decided to treat the patient with a short implant positioned on top of the fractured, and not removing the fractured implant. Clinical and radiographical follow-up was performed for 12 months after loading. Periimplant soft tissues healing and implant osseointegration were achieved 6 months after implant placement; at the end of the follow-up a periimplant bone remodeling of 0.3 mm was observed. In conclusion, short implants could be taken into consideration as a treatment option in cases of nonremovable implants and sufficient residual bone height.

Outcomes of topical applications of melatonin in implant dentistry: a systematic review.

BACKGROUND: Due to its antioxidant properties and its ability to detoxify free radicals, melatonin may interfere in the function of osteoclasts and thereby inhibit bone resorption. This inhibition of bone resorption may be enhanced by a reaction of indolamine in osteoclastogenesis and this may contribute to certain benefits in implantology. OBJECTIVE: This systematic literature review on the use of melatonin in implant dentistry aims to provide guidelines for clinicians. MATERIALS AND METHODS: PubMed, Science Direct, ISI Web of Knowledge, and the Cochrane base databases were used to identify articles published between 1999 and 2013 on melatonin use in implant dentistry. Ten articles were selected consisting of 9 animal research studies and 1 review article, involving 60 Beagle dogs, 57 rats, and 30 rabbits and a total of 352 implants. RESULTS: Melatonin, which is released into the saliva, has important implications in the oral cavity. To achieve dental implant stability, osseointegration involves a cascade of protein and cell apposition, vascular invasion, bone formation, and maturation. This process may be accelerated by local delivery of growth-promoting factors, as occurs with the topical application of melatonin over the implant surface. CONCLUSIONS: The experimental evidence suggests that topical applications of melatonin may be useful in oral surgery and implant dentistry, increasing bone-to-implant contact values and new bone formation, and so improving the success and long-term survival of implant treatments.