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Aim: In oncology, thermal therapy is the application of external heat to fight cancer cells. The goal of whole-body thermal treatment (WBTT) is to raise the patient’s core temperature to 39–42°C, and represents the only thermal treatment modality that can act on both the primary tumor and distant metastases. However, WBTT carries potential risks for toxicity when applied without accurate thermometry and monitoring. Methods: ElmediX has developed a medical device, HyperTherm, to deliver long-term controlled and accurate WBTT (41.5°C, up to 8 h). The safety of the device and thermal treatment protocol was initially evaluated in minipigs, and we present the confirmation of tolerability of WBTT in dogs with advanced cancer, in combination with a reduced dose of radiotherapy or chemotherapy. Results: Thermometry in liver, rectum, and tumor confirmed a homogeneous heating of these body parts. Monitoring of clinical parameters showed acceptable and reversible changes in liver, cardiac, muscle and coagulation parameters, as was expected. Combination of WBTT with both radiotherapy and chemotherapy only caused some low-grade adverse events. Conclusion: We conclude that our findings support the safe use of HyperTherm-mediated WBTT for canine patients with advanced malignancies. They also tend to support a genuine therapeutic potential for long-term WBTT which needs to be confirmed on a larger dog patient population. Combined with previously reported safety results in minipigs, these contribute to support the ongoing clinical evaluation of WBTT in advanced human cancer patients. [ABSTRACT FROM AUTHOR]

Study Objective: To describe the clinical, immunologic, and immunogenetic features of a diffuse infiltrative lymphocytic disorder resembling Sjögren syndrome in persons infected with human immunodeficiency virus (HIV).Design: Clinical case study.Setting: University-affiliated hospitals and outpatient clinics.Patients: Consecutive sample of 17 patients.Measurements and Main Results: All of the 17 patients had bilateral parotid gland enlargement; 14 had xerostomia and 6 had xerophthalmia. Of the 17 patients, 14 had generalized lymphadenopathy, 10 had histologically proved lymphocytic interstitial pneumonitis, 4 had neurologic involvement, and 3 had lymphocytic infiltration of the gastrointestinal tract. Gallium scanning in all of 11 tested patients showed abnormal salivary gland uptake. Minor salivary gland biopsies showed more than 2 lymphocytic foci per 4 mm2 tissue in all of 11 tested patients, the infiltrate consisting predominantly of CD8 cells. Fifteen patients had circulating CD8 lymphocytosis; the principal phenotype of these cells was CD8+ CD29+. Rheumatoid factor and antinuclear antibodies were infrequent, and none of the patients had anti-Ro/SS-A or anti-La/SS-B antibodies. HLA-DR5 was significantly more frequent in the black patients (10 of 12) compared with controls (13 of 45). Only one patient developed an opportunistic infection during 544 patient-months of study, and none has died of AIDS.Conclusions: A distinct syndrome primarily characterized by parotid gland enlargement, sicca symptoms, and pulmonary involvement occurs in HIV infection. This disorder is associated with CD8 lymphocytosis and the presence of HLA-DR5, and appears to be a genetically determined host immune response to HIV. [ABSTRACT FROM AUTHOR]

A sicca syndrome with parotid enlargement, pulmonary insufficiency, and lymphadenopathy was seen in 12 patients infected with human immunodeficiency virus (HIV), only 1 of whom has had an opportunistic infection during 304 patient months of study. There was a striking increase in numbers of circulating CD8 lymphocytes and the prevalence of HLA-DR5 was greatly increased. In patients with this diffuse infiltrative lymphocytosis syndrome (DILS) the CD8 lymphocytosis, which probably depends on histocompatibility antigen status, may influence disease progression in HIV infection. [ABSTRACT FROM AUTHOR]

An abstract of the paper "Bone Regeneration in Odontostomatology," by P. Tonelli et al. is presented.

An abstract of the paper "Maxillary Osteoporosis and Genetic Predisposition," by E. Biondi et al. is presented.

Head and neck squamous cell carcinomas are characterized by a high incidence of recurrence, especially in patients with locally advanced disease. Standard treatment strategies can be associated with severe side effects to healthy tissues that can negatively impact the patient's quality of life. Hyperthermia (HT) is a noninvasive treatment modality that has improved the effectiveness of chemotherapy (CT) and/or radiotherapy (RT) for the management of some solid neoplasms. In this context, the association of this approach with rationally designed nanomaterials may further enhance the treatment outcome. In this study, we demonstrate the enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures enclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments and their combinations have been fully evaluated by employing standardized chorioallantoic membrane tumor models of HPV-negative head and neck carcinoma. An improved tumor-shrinking effect was observed by the administration of the trimodal treatment (HT/NAs-CisPt/RT), which also highlighted a significant increase in apoptosis. Our findings demonstrate that the combination of HT with nanotechnology-based CT and RT in a certain order enhances the in vivo treatment outcome. On a broader basis, this study paves the way for the next exploration of noninvasive treatment approaches for the clinical management of oral cancer based on innovative strategies.

Objectives: This study aims to design and fabricate a modular phantom for hyperthermia applications, addressing interpatient variability in thermal regulation mechanisms like sweating rate, metabolic heat production, and blood redistribution., Materials & Methods: The phantom can be constructed in various weights and dimensions by connecting identical units. Each unit consists of an agar-based block, an ethyl cellulose-based top layer, a heat source, deep and superficial water circulation, and a sweating mechanism. Agar and ethyl cellulose gels mimic the thermal properties of human tissues and fat respectively. The blocks are wrapped in PVC foil to prevent water evaporation. A heating wire, coiled around an embedded aluminum tubing simulates metabolic heat production. A superficial water circulation mimics skin capillaries. A water pump ensures a steady flow rate throughout the tubing system. Sweat production is simulated using a water pump and perforated tubing. A programmed controller maintains core temperature in a normal operating mode and simulates an anesthetized patient in anesthesia mode., Results: Temperature uniformity and regulation were assessed under varying environmental conditions. The phantom effectively regulated its core temperature at 37.0 °C +/- 0.7 °C with an ambient temperature ranging between 21 °C and 30 °C. Activating the water circulation reduced the maximum temperature gradient within the phantom from 4.70 °C to 1.92 °C., Conclusion: The versatile phantom successfully models heat exchange processes. Its thermal properties, dimensions, and heat exchange rates can be tuned to mimic different patient models. These are promising results as an effective tool for hyperthermia device validation and verification, representing human physiological responses.

Pancreatic cancer has a poor prognosis due to its aggressive nature and ability to metastasize at an early stage. Currently, its management is still a challenge because this neoplasm is resistant to conventional treatment approaches, among which is chemo-radiotherapy (CRT), due to the abundant stromal compartment involved in the mechanism of hypoxia. Hyperthermia, among other effects, counteracts hypoxia by promoting blood perfusion and thereby can enhance the therapeutic effect of radiotherapy (RT). Therefore, the establishment of integrated treatments would be a promising strategy for the management of pancreatic carcinoma. Here, the effects of joint radiotherapy/hyperthermia (RT/HT) on optimized chick embryo chorioallantoic membrane (CAM) pancreatic tumor models are investigated. This model enables a thorough assessment of the tumor-arresting effect of the combined approach as well as the quantitative evaluation of hypoxia and cell cycle-associated mechanisms by both gene expression analysis and histology. The analysis of the lower CAM allows to investigate the variation of the metastatic behaviors of the cancer cells associated with the treatments. Overall, this study provides a potentially effective combined strategy for the non-invasive management of pancreatic carcinoma., (© 2023 The Authors. Advanced Biology published by Wiley-VCH GmbH.)

Acute kidney injury (AKI) is an abrupt decrease in kidney function widespread in intensive care. Many AKI prediction models have been proposed, but only few exploit clinical notes and medical terminologies. Previously, we developed and internally validated a model to predict AKI using clinical notes enriched with single-word concepts from medical knowledge graphs. However, an analysis of the impact of using multi-word concepts is lacking. In this study, we compare the use of only the clinical notes as input to prediction to the use of clinical notes retrofitted with both single-word and multi-word concepts. Our results show that 1) retrofitting single-word concepts improved word representations and improved the performance of the prediction model; 2) retrofitting multi-word concepts further improves both results, albeit slightly. Although the improvement with multi-word concepts was small, due to the small number of multi-word concepts that could be annotated, multi-word concepts have proven to be beneficial.

Chemotherapy (CT) is the standard care for advanced pancreatic ductal adenocarcinoma (PDAC); however, with limited efficacy. Hyperthermia (HT) treatment has been suggested as a sensitizer to improve outcomes. However, the direct effect of the HT and CT combination is not fully understood. Therefore, we aim to assess the direct cytotoxic effect of HT in PDAC cells as monotherapy or in combination with chemotherapeutics. Different temperatures (37-, 40.5-, 41-, and 41.5 °C) and durations (6-, 12-, and 24 h) were tested in PDAC cell lines (BxPC-3, Capan-1, Capan-2, PANC-1, and MIA-PaCa-2). Different concentrations of gemcitabine, 5-fluorouracil, and cisplatin were also tested in these conditions. The impact on cell metabolic activity was determined by an MTS assay. Enhancement of chemosensitivity was assessed by a reduction in half-maximal inhibitory concentration (IC50). HT and chemotherapeutics interactions were classified as antagonistic, additive, or synergistic using the combination index. HT inhibited cell proliferation in a cell type, temperature, and duration-dependent manner. The induction of apoptosis was seen after 6 h of HT treatment, eventually followed by secondary necrosis. The HT and CT combination led to an IC50 reduction of the tested CT. At 12 h of HT, this effect was between 25 to 90% and reached a 95% reduction at 24 h. The additive or synergistic effect was demonstrated in all cell lines and chemotherapeutics, although, again, this depended on cell type, duration, and temperature. HT is cytotoxic and enhances the therapeutic effectiveness of gemcitabine, 5-fluorouracil, and cisplatin on PDAC cells. This result was further confirmed by the decrease in the expression of RRM2 , TS , and ERCC1 in BxPC-3 and Capan-2 cells. These observations warrant further study in specific subsets of PDAC patients to improve their clinical outcomes.

Objective: Thermal treatment (TT), defined as treatment using supra-physiological body temperatures (39-45 C), somewhat resembles fever in terms of temperature range, one of the first natural barriers for the body to fight exposure to external pathogens. Methods: Whole-body thermal treatment (WBTT) consists of heating up the complete body to a temperature range of 39 to 45 C. Despite the recognized therapeutic potential of hyperthermia, the broad clinical use of WBTT has been limited by safety issues related to medical devices and procedures used to achieve WBTT, in particular adequate control of the body temperature. To circumvent this, a sophisticated medical device was developed, allowing long-term temperature controlled WBTT (41.5 C for up to 8 h). Technical feasibility and tolerability of the WBTT procedure (including complete anesthesia) were tested using female Aachen minipig. Optical fiber temperature sensors inserted in multiple organs were used and demonstrated consistent monitoring and control of different organs temperature over an extended period of time. Results: Clinical evaluation of the animals before, during and after treatment revealed minor clinical parameter changes, but all of them were clinically acceptable. These changes were limited and reversible, and the animals remained healthy throughout the whole procedure and follow-up. In addition, histopathological analysis of selected key organs showed no thermal treatment-related changes. Conclusion: It was concluded that WBTT (41.5 C for up to 8 h) was well tolerated and safe in female Aachen minipigs. Altogether, data supports the safe clinical use of the WBTT medical device and protocol, enabling its implementation into human patients suffering from life-threatening diseases.

Objectives: To test the hypothesis that an implantable sensing system containing accelerometers can detect small-scale autonomous movements, also termed micromotions, which might be relevant to bladder physiology., Methods: We developed a 6-mm submucosal implant containing a pressure sensor (MS5637) and a triaxial accelerometer (BMA280). Sensor prototypes were tested by implantation in the bladders of Gottingen minipigs. Repeated awake voiding cystometry was carried out with air-charged catheters in a standard urodynamic set-up as comparators. We identified four phases of voiding similar to cystometry in other animal models based on submucosal pressure. Acceleration signals were separated by frequency characteristics to isolate linear acceleration from the baseline acceleration. The total linear acceleration was calculated by the root mean square of the three measurement axes. Acceleration activity during voiding was investigated to adjacent 1-s windows and was compared with the registered pressure., Results: We observed a total of 19 consecutive voids in five measurement sessions. A good correlation (r > 0.75) was observed between submucosal and catheter pressure in 14 of 19 premicturition traces. The peak-to-peak interval between maximum total linear acceleration was correlated with the interval between submucosal voiding pressure peaks (r = 0.760, P < 0.001). The total linear acceleration was higher during voiding compared with pre- and postmicturition periods (start of voiding/phase 1)., Conclusions: To the best of our knowledge, this is the first report of bladder wall acceleration, a novel metric that reflects bladder wall movement. Submucosal sensors containing accelerometers can measure bladder pressure and acceleration., (© 2020 The Japanese Urological Association.)

This paper presents a novel fabrication process that allows integration of polydimethylsiloxane (PDMS)-based microfluidic channels and metal electrodes on a wafer with a micrometer-range alignment accuracy. This high level of alignment accuracy enables integration of microwave and microfluidic technologies, and furthermore accurate microwave dielectric characterization of biological liquids and chemical compounds on a nanoliter scale. The microfluidic interface between the pump feed lines and the fluidic channels was obtained using magnets fluidic connection. The tube-channel interference and the fluidic channel-wafer adhesion was evaluated, and up to a pressure of 700 mBar no leakage was observed. The developed manufacturing process was tested on a design of a microwave-microfluidic capacitive sensor. An interdigital capacitor (IDC) and a microfluidic channel were manufactured with an alignment accuracy of 2.5 μm. The manufactured IDC sensor was used to demonstrate microwave dielectric sensing on deionized water and saline solutions with concentrations of 0.1, 0.5, 1, and 2.5 M.

Introduction: The increasing popularity of inertial sensors in clinical practice is not supported by precise information on their reliability or guidelines for their use in rehabilitation. The authors investigated the state of the literature concerning the use of inertial sensors for gait analysis in both healthy and pathological adults comparing traditional systems. Furthermore, trying to define directions for clinicians., Evidence Acquisition: In accordance with the PRISMA statement, authors searched in PubMed, Web of Science and Scopus all paper published from January 1st, 2005 until December 31st, 2017. They included both healthy and pathological adults' subjects as population, wearable or inertial sensors used for gait analysis and compared with classical gait analysis performed in a Motion Lab as intervention and comparison, gait parameters as outcomes. Considering the methodological quality, authors focused on: sample; description of the study; type of gait analysis used for comparison; type of sensor; sensor placement on the body; gait task requested., Evidence Synthesis: From a total of 888 articles, 16 manuscripts were selected and 7 of them were considered for meta-analysis for different gait parameters. Demographic data, tested devices, reference systems, test procedures and outcomes were analyzed., Conclusions: Our results show a good agreement between inertial sensors and classical gait analysis for some gait parameters, supporting their use as a solution for capturing kinematic information over an extended space and time and even outside a laboratory in real-life conditions. Authors can support the use of portable inertial sensors for a practical gait analysis in clinical setting with good reliability. It will then be the experience of the clinician to direct the decision-making process.

In the quest for chronically reliable and bio-tolerable brain interfaces there has been a steady evolution towards the use of highly flexible, polymer-based electrode arrays. The reduced mechanical mismatch between implant and brain tissue has shown to reduce the evoked immune response, which in turn has a positive effect on signal stability and noise. Unfortunately, the low stiffness of the implants also has practical repercussions, making surgical insertion extremely difficult. In this work we explore the use of dextran as a coating material that temporarily stiffens the implant, preventing buckling during insertion. The mechanical properties of dextran coated neural probes are characterized, as well as the different parameters which influence the dissolution rate. Tuning parameters, such as coating thickness and molecular weight of the used dextran, allows customization of the stiffness and dissolution time to precisely match the user's needs. Finally, the immunological response to the coated electrodes was analyzed by performing a histological examination after four months of in vivo testing. The results indicated that a very limited amount of glial scar tissue was formed. Neurons have also infiltrated the area that was initially occupied by the dissolving dextran coating. There was no noticeable drop in neuron density around the site of implantation, confirming the suitability of the coating as a temporary aid during implantation of highly flexible polymer-based neural probes.

This paper investigates the effects on the blood compatibility of surface nanostructuring of Parylene-C coating. The proposed technique, based on the consecutive use of O₂ and SF₆ plasma, alters the surface roughness and enhances the intrinsic hydrophobicity of Parylene-C. The degree of hydrophobicity of the prepared surface can be precisely controlled by opportunely adjusting the plasma exposure times. Static contact angle measurements, performed on treated Parylene-C, showed a maximum contact angle of 158&deg;. The nanostructured Parylene-C retained its hydrophobicity up to 45 days, when stored in a dry environment. Storing the samples in a body-mimicking solution caused the contact angle to progressively decrease. However, at the end of the measurement, the plasma treated surfaces still exhibited a higher hydrophobicity than the untreated counterparts. The proposed treatment improved the performance of the polymer as a water diffusion barrier in a body simulating environment. Modifying the nanotopography of the polymer influences the adsorption of different blood plasma proteins. The adsorption of albumin&mdash;a platelet adhesion inhibitor&mdash;and of fibrinogen&mdash;a platelet adhesion promoter&mdash;was studied by fluorescence microscopy. The adsorption capacity increased monotonically with increasing hydrophobicity for both studied proteins. The effect on albumin adsorption was considerably higher than on fibrinogen. Study of the proteins simultaneous adsorption showed that the albumin to fibrinogen adsorbed ratio increases with substrate hydrophobicity, suggesting lower thrombogenicity of the nanostructured surfaces. Animal experiments proved that the treated surfaces did not trigger any blood clot or thrombus formation when directly exposed to the arterial blood flow. The findings above, together with the exceptional mechanical and insulation properties of Parylene-C, support its use for packaging implants chronically exposed to the blood flow.

Acceleration signals, collected from the inner and the outer heart wall, offer a mean of assessing cardiac function during surgery. Accelerometric measurements can also provide detailed insights into myocardial motion during exploratory investigations. Two different implantable accelerometers to respectively record endocardial and epicardial vibrations, have been developed by packaging a commercially available capacitive transducer. The same coating materials have been deposited on the two devices to ensure biocompatibility of the implants: Parylene-C, medical epoxy and Polydimethylsiloxane (PDMS). The different position-specific requirements resulted in two very dissimilar sensor assemblies. The endocardial accelerometer, that measures accelerations from the inner surface of the heart during acute animal tests, is a 2 mm-radius hemisphere fixed on a polymethyl methacrylate (PMMA) rod to be inserted through the heart wall. The epicardial accelerometer, that monitors the motion of the outer surface of the heart, is a three-legged structure with a stretchable polytetrafluoroethylene (PTFE) reinforcement. This device can follow the continuous motion of the myocardium (the muscular tissue of the heart) during the cardiac cycle, without hindering its natural movement. Leakage currents lower than 1 μA have been measured during two weeks of continuous operation in saline. Both transducers have been used, during animal tests, to simultaneously record and compare acceleration signals from corresponding locations on the inner and the outer heart wall of a female sheep.

Bead-based microwell array technology is growing as an ultrasensitive analysis tool as exemplified by the successful commercial applications from Illumina and Quanterix for nucleic acid analysis and ultrasensitive protein measurements, respectively. High-efficiency seeding of magnetic beads is key for these applications and is enhanced by hydrophilic-in-hydrophobic microwell arrays, which are unfortunately often expensive or labor-intensive to manufacture. Here, we demonstrate a new single-step manufacturing approach for imprinting cheap and disposable hydrophilic-in-hydrophobic microwell arrays suitable for digital bioassays. Imprinting of arrays with hydrophilic-in-hydrophobic microwells is made possible using an innovative surface energy replication approach by means of a hydrophobic thiol-ene polymer formulation. In this polymer, hydrophobic-moiety-containing monomers self-assemble at the hydrophobic surface of the imprinting stamp, which results in a hydrophobic replica surface after polymerization. After removing the stamp, microwells with hydrophobic walls and a hydrophilic bottom are obtained. We demonstrate that the hydrophilic-in-hydrophobic imprinted microwell arrays enable successful and efficient self-assembly of individual water droplets and seeding of magnetic beads with loading efficiencies up to 96%. We also demonstrate the suitability of the microwell arrays for the isolation and digital counting of single molecules achieving a limit of detection of 17.4 aM when performing a streptavidin-biotin binding assay as model system. Since this approach is up-scalable through reaction injection molding, we expect it will contribute substantially to the translation of ultrasensitive digital microwell array technology toward diagnostic applications.

The aim of this study is to investigate the intravascular application of a micro-electro-mechanical system (MEMS) pressure sensor to directly measure the hemodynamic characteristics of a ventricular assist device (VAD). A bio- and hemo-compatible packaging strategy is implemented, based on a ceramic thick film process. A commercial sub-millimeter piezoresistive sensor is attached to an alumina substrate, and a double coating of polydimethylsiloxane (PDMS) and parylene-C is applied. The final size of the packaged device is 2.6 mm by 3.6 mm by 1.8 mm. A prototype electronic circuit for conditioning and read-out of the pressure signal is developed, satisfying the VAD-specific requirements of low power consumption (less than 14.5 mW in continuous mode) and small form factor. The packaged sensor has been submitted to extensive in vitro tests. The device displayed a temperature-independent sensitivity (12 μ V/V/mmHg) and good in vitro stability when exposed to the continuous flow of saline solution (less than 0.05 mmHg/day drift after 50 h). During in vivo validation, the transducer has been successfully used to record the arterial pressure waveform of a female sheep. A small, intravascular sensor to continuously register the blood pressure at the inflow and the outflow of a VAD is developed and successfully validated in vivo.

Background: The chemical, physical, and morphologic characteristics of the implant surface play a fundamental role during the osteointegration process. Implant design is of paramount importance in determining implant primary stability and implant ability to sustain loading during and after osteointegration. LASER treatment of the surface allows defining the precise parameters of roughness to obtain a regular and repeatable surface in total absence of contamination., Purpose: The aim of this study was to analyze the behavior of implant stability of LASER-treated surface implants by repeated resonance frequency analysis (RFA) measurements during 2 years in patients with complete upper maxilla edentulism subject to an immediate-loading protocol., Methods: Ten patients were included, and each treated with the insertion of 6 or 8 LASER surface implants according to the individual surgical-prosthetic planning. During the bone drilling and implant insertion, torque values were monitored with a specific handpiece and software. All implants were loaded within 24 hours from the insertion with the application of a temporary full-arch prosthesis. Subsequent follow-up has been done at 24 months from the loading with radiographic controls (OPT) and RFA measurement on all implants at time of implant insertion and at 1, 3, 6, 12, and 24 months from loading., Results: Resonance frequency analyses at 3 and 6 months from the implant loading have shown a rapid increment of implant stability quotient (ISQ) values in the first phases of bone remodeling, subsequent to the peri-implant bone remodeling. The paired comparisons between mean ISQ values by patient showed a statistically significant decrease in primary stability from baseline up to 1 month (P = 0.0039). Subsequent measurements revealed a statistically significant increase in implant stability from 1 up to 3 months (P = 0.0156), from 3 up to 6 months (P = 0.0020), from 6 up to 12 months (P = 0.020), and 12 up to 24 months (P = 0.0391)., Conclusions: Resonance frequency analysis of the LASER-treated surface implants showed good ISQ values at all time point measurements. These results are consistent with data from literature on the analysis of RFA in protocols of immediate loading at the upper maxilla.

Osteoporosis is a systemic disease in which the skeletal condition is characterized by a decreased mass of normally mineralized bone, due to an augmentation of bone resorption processes. Bone biomarkers serum are used for the diagnosis. On the other hand the main cause of the resorption in the bone jaws are periodontitis, inflammatory cysts, developmental cysts, odontogenic neoplasms. Periodontal diseases can be localized to a single site of the jaws or can affect all the teeth, with a massive bone resorption. The cysts are classified in developmental and inflammatory. They caused a local bone resorption in the jaws. Keratocystic odontogenic tumor produces a large bone resorption for its local aggressive nature. Their diagnosis is clinical and radiological.The aim of our review is to find a correlation between bone biomarkers serum and periodontitis, inflammatory cists, developmental cysts, odontogenetic neoplasms.The RANK/RANKL/OPG system is the most studied not only in osteoporosis but also in the periodontitis, inflammatory cysts, developmental cysts, odontogenic neoplasms. In the last years osteoimmunology was used to study the periodontal disease progression, because the immunity cells start the bone resorption processes.A lot of studies analyze the biomarkers present in the biofluids, as saliva and gingival crevicular fluid, but not the correlation with serum biomarkers.Future studies must be organized to deepen the correlation between bone biomarkers and bone jaws resorption and to allow diagnosis and prognosis of periodontitis, inflammatory cysts, developmental cysts, odontogenic neoplasms.

The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological principles of osteogenesis, osteoinduction and osteoconduction. Several techniques combine these principles with different results, due to the condition of the bone base on which we operate changes, the surgical technique that we use, and finally for the bone metabolic conditions of the patient who can be in a state of systemic osteopenia or osteoporosis; these can also affect the result of jaw bone reconstruction.

Since osteonecrosis of the jaw was related to biphosphonate administration by Marx, studies showing clinical symptoms, drug and surgical therapies overwhelmed the literature. Furthermore, the literature demonstrated the correlation between chronic biphosphonate adsumption and osteonecrosis of the jaw onset. Nitrogen-containing biphosphonates are widely used for the management of metastatic cancer, for prevention and treatment of osteoporosis, for the treatment of Paget's disease, and for the management of acute hypercalcemia. According to our experience, the treatment of BRON-J's lesions is difficult and prolonged. For this reason, in order to avoid these complications it is mandatory to perform a risk staging in patients who must undergo biphosphonate administration. When pharmacologic treatments with antibiotics and local antiseptics are not able to control the development of BRON-J's complications, the clinicians should perform radical surgical treatments such as the resection of the bone involved.

Aims. Bisphosphonates (BPs) are important therapeutic drugs in multiple myeloma and cancers with bone metastases. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) has been described as a potential side effect of the last generation BPs. The Authors evaluated clinical features, preventing measures and treatment strategies.Patients and methods. The Authors retrospectively analyzed 19 patients affected by malignant cancer in endovenous treatment with BPs. Fourteen patients were treated with zoledronate, 1 with pamidronate and 4 with both drugs for breast cancer (9 patients), multiple myeloma (6 patients), prostatic cancer (3 patients) and colon cancer (1 patient).Results. The lenght of therapy was 5-36 months before osteonecrosis was observed; in 15 patients BRONJ involved the mandible, in 2 the maxilla and in 2 both jaws. The trigger factors were tooth extractions, inadequate removable total denture, basic and advanced surgery, root canal treatment. Ten patients received non-surgical treatment, 7 patients minor surgical procedures and 2 patients a partial maxillectomy. Healing was achieved in all maxillary localization, and in one mandibular localization with partial maxillectomy.Conclusions. Prevention is the best important phase in the management of this pathology. Risk factors are the type of bisphosphonate and the length of exposure, while dental surgical procedures are trigger factors. Conservative treatment seems to be the best way to control BRONJ, but bone resection and soft tissue closure have to be performed when the lesion is refractory to conservative approach.

Aim: Growth factors (GFs) as platelet derived growth factor (PDGF) and transforming growth factor (TGF-beta), found in platelet beta-granules also present in platelet-rich-plasma (PRP), accelerate bone revascularization and regeneration and for this reason they have been employed successfully in dental and maxillofacial surgery. Platelet concentrate is commonly used for this purpose as long as platelet release reaction and the consequent GFs loss are avoided. To reduce this phenomenon we set up an easy and fast procedure for preparing a satisfying clotted PRP by adding CaCl2 only (no exogenous thrombin)., Methods: ELISA essay has been used to measure PDGF and TGF-beta in plasma, platelets and serum and platelet GMP-140, with the cytofluorometric technique in order to quantify the degranulation entity., Results: In the 13 examined patients receiving clotted PRP to enhance bone regeneration in post-extractive alveolar sockets, PRP showed no sign of platelet activation (degranulation) and short recalcification times (8-12 min). The autologous clotted PRPs specimen have been evaluated in laboratory in terms of GFs percent: 76% of initial GFs content could be recovered in clotted PRP. This result confirms the absence of platelet degranulation in our procedure., Conclusions: Significant clinical results in alveolar bone regeneration are reached only with a high percentage of GFs inserted in bone matrix, avoiding early platelet degranulation.