RESUMO
Calcium phosphate cements, primarily brushite cements, require the addition of setting retarders to ensure adequate processing time and processability. So far, citric acid has been the primary setting retarder used in this context. Due to the poor biocompatibility, it is crucial to explore alternative options for better processing. In recent years, the setting retarder phytic acid (IP6) has been increasingly investigated. This study investigates the biological behaviour of calcium phosphate cements with varying concentrations of IP6, in addition to their physical properties. Therefore cytocompatibility in vitro testing was performed using osteoblastic (MG-63) and osteoclastic (RAW 264.7 differentiated with RANKL) cells. We could demonstrate that the physical properties like the compressive strength of specimens formed with IP6 (brushite_IP6_5 = 11.2 MPa) were improved compared to the reference (brushite = 9.8 MPa). In osteoblast and osteoclast assays, IP6 exhibited significantly better cytocompatibility in terms of cell activity and cell number for brushite cements up to 11 times compared to the brushite reference. In contrast, the calcium-deficient hydroxyapatite (CDHA) cements produced similar results for IP6 (CDHA_IP6_0.25 = 27.0 MPa) when compared to their reference (CDHA = 21.2 MPa). Interestingly, lower doses of IP6 were found to be more effective than higher doses with up to 3 times higher. Additionally, IP6 significantly increased degradation in both passive and active resorption. For these reasons, IP6 is emerging as a strong new competitor to established setting retarders such as citric acid. These cements have potential applications in bone augmentation, the stabilisation of non-load bearing fractures (craniofacial), or the cementation of metal implants.
Assuntos
Cimentos Ósseos , Fosfatos de Cálcio , Teste de Materiais , Osteoblastos , Osteoclastos , Ácido Fítico , Ácido Fítico/química , Animais , Fosfatos de Cálcio/química , Camundongos , Cimentos Ósseos/química , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Células RAW 264.7 , Humanos , Osteoclastos/efeitos dos fármacos , Força Compressiva , Materiais Biocompatíveis/química , Durapatita/químicaRESUMO
OBJECTIVES: Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF is also a suitable bio-carrier for clindamycin (CLI). METHODS: PRF membranes were produced from 36 patients receiving intravenous therapy with CLI (e.g. due to the diagnosis of an osteonecrosis of the jaw or infections). Concentrations of CLI in PRF membranes were measured with liquid chromatography-tandem mass spectrometry, and the antimicrobial effects were investigated in vitro in agar diffusion tests with fresh PRF and PRF stored for 24 h. Storage was performed in an incubator at 36 °C to simulate the in-vivo situation. RESULTS: The mean concentration of CLI in plasma was 1.0 ± 0.3 µg/100 mg plasma; in resulting PRF membranes 0.7 ± 0.4 µg/100 mg PRF. Agar diffusion tests were performed with Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus mitis, Porphyromonas gingivalis, and Fusobacterium nucleatum. Mean inhibition zones, in mm, for fresh PRF were 17.3, 12.2, 18.8, 17.1, 25.8 and 18.1, 12.7, 19.2, 17.3, and 26.3 for stored PRF, respectively. CONCLUSION: The results demonstrate that PRF is a suitable bio-carrier for CLI when administered systemically to patients. The concentration in PRF generated from patients after infusion of 600 mg CLI dose suffices to target clinically relevant bacteria. CLINICAL RELEVANCE: Using PRF as a carrier for local antibiotic application can prevent infections in oral and maxillofacial surgery. Within the study limitations, the findings could expand the scope of PRF application by adding CLI as a new antibiotic to the spectrum of PRF therapy.
Assuntos
Fibrina Rica em Plaquetas , Humanos , Clindamicina/farmacologia , Ágar , Antibacterianos/farmacologia , Staphylococcus aureusRESUMO
Although inhibitors targeting the PD1/PD-L1 immune checkpoint are showing comparably good outcomes, a significant percentage of head and neck squamous cell carcinoma (HNSCC) patients do not respond to treatment. Apart from using different treatment strategies, another possibility would be to target other immune checkpoints operating in these non-responding tumors. To obtain an overview of which checkpoint ligands are expressed on HNSCC tumor cells and if these ligands are affected by HGF/MET signaling, we used mRNA sequencing and antibody-based techniques for identifying checkpoint ligands in six HNSCC tumor cell lines. Furthermore, we compared our results to mRNA sequencing data. From the checkpoint ligands we investigated, VISTA was expressed the highest at the RNA level and was also the most ubiquitously expressed. PD-L2 and B7-H3 were expressed comparably lower and were not present in all cell lines to the same extent. B7-H4, however, was only detectable in the Detroit 562 cell line. Concerning the effect of HGF on the ligand levels, PD-L2 expression was enhanced with HGF stimulation, whereas other checkpoint ligand levels decreased with stimulation. B7-H4 levels in the Detroit 562 cell line drastically decreased with HGF stimulation. This is of interest because both the checkpoint ligand and the growth factor are reported to be connected to epithelial-mesenchymal transition in the literature.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Fator de Crescimento de Hepatócito , Proteínas de Checkpoint Imunológico , Proteínas Proto-Oncogênicas c-met , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/genética , Linhagem Celular Tumoral , Proteínas de Checkpoint Imunológico/metabolismo , Proteínas de Checkpoint Imunológico/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/genética , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Antígenos B7/metabolismo , Antígenos B7/genéticaRESUMO
BACKGROUND: Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC. METHODS: We investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction ("0"), cortical bone erosion ("1"), or medullary bone invasion ("2"). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities. RESULTS: Our results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI. CONCLUSION: Our data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Tomografia Computadorizada de Feixe Cônico , Células Epiteliais , Imageamento por Ressonância Magnética , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Synthetic bone substitutes which can be adapted preoperatively and patient specific may be helpful in various bony defects in the field of oral- and maxillofacial surgery. For this purpose, composite grafts made of self-setting and oil-based calcium phosphate cement (CPC) pastes, which were reinforced with 3D-printed polycaprolactone (PCL) fiber mats were manufactured. MATERIALS AND METHODS: Bone defect models were acquired using patient data from real defect situations of patients from our clinic. Using a mirror imaging technique, templates of the defect situation were fabricated via a commercially available 3D-printing system. The composite grafts were assembled layer by layer, aligned on top of these templates and fitted into the defect situation. Besides, PCL-reinforced CPC samples were evaluated regarding their structural and mechanical properties via X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM), and 3-point-bending testing. RESULTS: The process sequence including data acquisition, template fabrication, and manufacturing of patient specific implants proved to be accurate and uncomplicated. The individual implants consisting mainly of hydroxyapatite and tetracalcium phosphate displayed good processability and a high precision of fit. The mechanical properties of the CPC cements in terms of maximum force and stress load to material fatigue were not negatively affected by the PCL fiber reinforcement, whereas clinical handling properties increased remarkably. CONCLUSION: PCL fiber reinforcement of CPC cements enables the production of very freely modelable three-dimensional implants with adequate chemical and mechanical properties for bone replacement applications. CLINICAL RELEVANCE: The complex bone morphology in the region of the facial skull often poses a great challenge for a sufficient reconstruction of bony defects. A full-fledged bone replacement here often requires the replication of filigree three-dimensional structures partly without support from the surrounding tissue. With regard to this problem, the combination of smooth 3D-printed fiber mats and oil-based CPC pastes represents a promising method for fabricating patient specific degradable implants for the treatment of various craniofacial bone defects.
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Implantes Dentários , Humanos , Teste de Materiais , Crânio/cirurgia , Durapatita , Cimentos Dentários , Cimentos de Ionômeros de Vidro , Fosfatos de Cálcio/química , Cimentos Ósseos/químicaRESUMO
OBJECTIVES: Different platelet-rich fibrin (PRF) protocols exist and are known to differ in resulting mechanical and bioactive properties. Centrifugation parameters may also influence drug release, in particular antibiotics, when using PRF as a bio-carrier. We thus evaluated three common protocols regarding effects on the bio-carrier properties. MATERIALS AND METHODS: In a prospective trial comprising 33 patients, we compared different protocols for PRF as a bio-carrier for ampicillin/sulbactam (SAM). Blood samples were taken shortly after a single dose of ampicillin/sulbactam (2 g/1 g) was administered to patients intravenously. PRF was obtained by centrifugation and three protocols were used: protocol A (1300 rpm, 8 min, RCF-max = 208 g), B (2300 rpm, 12 min, RCF-max = 652 g), and C (1500 rpm, 14 min, RCF-max = 276 g). The antibacterial activity of PRF was investigated against five oral species in vitro, based on agar diffusion methodology. RESULTS: The study demonstrates that a single dose of SAM is sufficient to reach high concentrations in PRF in all protocols (150 µg/ml), which is comparable to the plasma SAM concentration. Antibacterial activity was inferred from the diameter of inhibition zones seen in agar diffusion tests using PRF discs. Protocol B resulted in the largest inhibition zones. One-way ANOVA revealed statistically improved results for protocol B for some bacteria. CONCLUSIONS: The study provides valuable data on PRF antibiotic enrichment, notably SAM. A single dose of SAM is sufficient to reach clinically relevant concentrations in PRF. CLINICAL RELEVANCE: These findings potentially extend the application of PRF, for example in patients with osteonecrosis of the jaw or in oral surgery (e.g., stick bone).
Assuntos
Fibrina Rica em Plaquetas , Humanos , Sulbactam/farmacologia , Ágar , Estudos Prospectivos , Peptídeos e Proteínas de Sinalização Intercelular , Centrifugação/métodos , Antibacterianos/farmacologia , Ampicilina/farmacologiaRESUMO
OBJECTIVES: Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously. MATERIALS AND METHODS: We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. RESULTS: Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. CONCLUSIONS: The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. CLINICAL RELEVANCE: We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.
Assuntos
Fibrina Rica em Plaquetas , Humanos , Sulbactam/farmacologia , Ampicilina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Since Otto Warburg reported in 1924 that cancer cells address their increased energy requirement through a massive intake of glucose, the cellular energy level has offered a therapeutic anticancer strategy. Methionine restriction (MetR) is one of the most effective approaches for inducing low-energy metabolism (LEM) due to the central position in metabolism of this amino acid. However, no simple in vitro system for the rapid analysis of MetR is currently available, and this study establishes the murine cell line L929 as such a model system. L929 cells react rapidly and efficiently to MetR, and the analysis of more than 150 different metabolites belonging to different classes (amino acids, urea and tricarboxylic acid cycle (TCA) cycles, carbohydrates, etc.) by liquid chromatography/mass spectrometry (LC/MS) defines a metabolic fingerprint and enables the identification of specific metabolites representing normal or MetR conditions. The system facilitates the rapid and efficient testing of potential cancer therapeutic metabolic targets. To date, MS studies of MetR have been performed using organisms and yeast, and the current LC/MS analysis of the intra- and extracellular metabolites in the murine cell line L929 over a period of 5 days thus provides new insights into the effects of MetR at the cellular metabolic level.
Assuntos
Fibroblastos/metabolismo , Metionina/metabolismo , Animais , Morte Celular , Linhagem Celular , Proliferação de Células , Ligantes , Metaboloma , Camundongos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Fator de Crescimento de Hepatócito/genética , Recidiva Local de Neoplasia/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/sangue , Estudos de Coortes , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Fator de Crescimento de Hepatócito/sangue , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Ipilimumab/uso terapêutico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/sangue , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/sangue , Proteína Quinase 3 Ativada por Mitógeno/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Nivolumabe/uso terapêutico , Prognóstico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/sangue , Proteínas Proto-Oncogênicas c-met/genética , RNA Interferente Pequeno/sangue , RNA Interferente Pequeno/genética , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss-which is most often caused by thrombosis-can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. CASE PRESENTATION: We present three exemplary male Caucasian patients aged 53-57 years with free flap loss owing to an underlying, hidden thrombophilia. CONCLUSION: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Trombofilia , Trombose , Humanos , Masculino , Anticoagulantes/uso terapêutico , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Trombofilia/complicações , Trombofilia/tratamento farmacológico , Trombose/etiologia , Pessoa de Meia-IdadeRESUMO
The aim of this study was to investigate the jawbone concentration of clindamycin (CLI) in patients with an osteonecrosis of the jaw (ONJ). Patients with medication-related ONJ (MRONJ) and osteoradionecrosis (ORN) with an antibiotic treatment with CLI were included. Plasma, vital and necrotic bone samples were collected. Plasma and jawbone samples were analyzed by liquid chromatography-tandem mass spectrometry. Patients with MRONJ exhibited a mean plasma CLI concentration of 9.6 µg/mL (SD ± 3.6 µg/mL) and mean concentrations of 2.3 µg/g CLI (SD ± 1.4 µg/g) and 2.1 µg/g CLI (SD ± 2.4 µg/g) in vital and necrotic bone samples, without statistical significance (p = 0.79). In patients with ORN, mean concentration in plasma was 12.0 µg/mL (SD ± 2.6 µg/mL), in vital bone 2.1 µg/g (SD ± 1.5 µg/g), and in necrotic bone 1.7 µg/g (SD ± 1.2 µg/g). Vital and necrotic bone concentrations did not differ significantly (p = 0.88). The results demonstrate that CLI concentrations are considerably lower than in plasma, but sufficient for most bacteria present in ONJ. Within the limitations of the study, it seems that CLI is a relevant alternative to other antibiotics in the treatment of ONJ because it reaches adequate concentrations in jawbone.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteonecrose , Osteorradionecrose , Humanos , Clindamicina/uso terapêutico , Estudos Prospectivos , Osteonecrose/induzido quimicamente , Osteorradionecrose/etiologia , Arcada Osseodentária , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , DifosfonatosRESUMO
BACKGROUND: This study investigated whether patient-specific condylar positioning devices (CPDs) are beneficial compared to the conventional manual positioning of the condyles. METHODS: In this prospective, randomized trial, patients undergoing orthognathic surgery with a bilateral sagittal split osteotomy of the mandible were included. The ascending ramus was positioned with computer-aided designed and computer-aided manufactured (CAD/CAM) patient-specific devices in the CPD group and manually in the control group. Postoperatively, cone-beam computed tomography (CBCT) was performed to align the virtually planned position with the postoperative result. RESULTS: Thirty patients were enrolled in the study, with 14 randomized to the CPD group and 16 to the control group. In the CPD group, the ascending ramus differed in the postoperative CBCT scan from the virtually planned position by 0.8 mm in the left/right, 0.8 mm in the front/back, and 1.3 mm in the cranial/caudal direction. The corresponding control-group values were 1.1 mm, 1.3 mm, and 1.6 mm. CPD and controls differed significantly for the left/right movement of the rami (p = 0.04) but not for the other directions or rotations (p > 0.05). CONCLUSIONS: The results demonstrate that both methods are accurate, and postoperative results matched the virtually planned position precisely. It can be assumed that the described CPDs are beneficial when a condylar position different from the preoperative is desired.
RESUMO
Bone defects resulting from trauma, diseases, or surgical procedures pose significant challenges in the field of oral and maxillofacial surgery. The development of effective bone substitute materials that promote bone healing and regeneration is crucial for successful clinical outcomes. Calcium phosphate cements (CPCs) have emerged as promising candidates for bone replacement due to their biocompatibility, bioactivity, and ability to integrate with host tissues. However, there is a continuous demand for further improvements in the mechanical properties, biodegradability, and bioactivity of these materials. Dual setting of cements is one way to improve the performance of CPCs. Therefore, silicate matrices can be incorporated in these cements. Silicate-based materials have shown great potential in various biomedical applications, including tissue engineering and drug delivery systems. In the context of bone regeneration, silicate matrices offer unique advantages such as improved mechanical stability, controlled release of bioactive ions, and enhanced cellular responses. Comprehensive assessments of both the material properties and biological responses of our samples were conducted. Cytocompatibility was assessed through in vitro testing using osteoblastic (MG-63) and osteoclastic (RAW 264.7) cell lines. Cell activity on the surfaces was quantified, and scanning electron microscopy (SEM) was employed to capture images of the RAW cells. In our study, incorporation of tetraethyl orthosilicate (TEOS) in dual-curing cements significantly enhanced physical properties, attributed to increased crosslinking density and reduced pore size. Higher alkoxysilyl group concentration improved biocompatibility by facilitating greater crosslinking. Additionally, our findings suggest citrate's potential as an alternative retarder due to its positive interaction with the silicate matrix, offering insights for future dental material research. This paper aims to provide an overview of the importance of silicate matrices as modifiers for calcium phosphate cements, focusing on their impact on the mechanical properties, setting behaviour, and biocompatibility of the resulting composites.
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OBJECTIVE: Patient-specific osteosynthesis for pseudarthrosis of the acromion. INDICATIONS: Symptomatic pseudarthrosis of the acromion at the level of a meta/mesacromion. CONTRAINDICATIONS: Infection; patient noncompliance regarding postoperative treatment protocol. SURGICAL TECHNIQUE: Preoperatively, a patient-specific three-dimensional model of the scapula is printed. A locking compression plate (LCP) is individually adapted to this model. Via a dorsal surgical approach over the scapular spine, the pseudarthrosis is refreshed and autologous cancellous bone from the iliac crest is embedded in the fracture zone. This is followed by fixed-angle osteosynthesis with the individualized plate. In addition, tension banding with tapes is performed to reduce the tensile and shear forces on the fracture caused by the muscle. POSTOPERATIVE MANAGEMENT: Consistent wearing of a shoulder-arm brace for 6 weeks postoperatively, active-assisted increase in range of motion for an additional 3 weeks, then gradual increase in weight-bearing and initiation of daily activities without additional weights until 12 weeks postoperatively. RESULTS: Treatment with the presented technique resulted in radiographic consolidation of the fracture and significant improvement in range of motion and pain at the 1year follow-up.
Assuntos
Fraturas Ósseas , Pseudoartrose , Humanos , Pseudoartrose/diagnóstico por imagem , Pseudoartrose/cirurgia , Acrômio/diagnóstico por imagem , Acrômio/cirurgia , Resultado do Tratamento , Fraturas Ósseas/cirurgia , Escápula/diagnóstico por imagem , Escápula/cirurgia , Fixação Interna de Fraturas/métodos , Impressão TridimensionalRESUMO
Ampicillin in combination with sulbactam is a widely used drug choice for infection prophylaxis, especially in oral and maxillofacial surgery. Clindamycin serves as an alternative in patients with known allergy to ß-lactam antibiotics. To ensure effective prophylaxis, it is important to achieve sufficiently high concentrations of active antibiotic substances in the tissues affected by the surgery. To this end, a LC-MS/MS method was developed and validated that allows the quantification of ampicillin, sulbactam and clindamycin in jawbone, plasma, and so-called platelet-rich fibrin (PRF). Validation was performed in accordance with the European Medicines Agency guidelines for bioanalytical method validation. For all matrices, sample processing was carried out by protein precipitation with acetonitrile or methanol 80%, containing the isotope labelled internal standards (IS) of the three drugs. Analytes were separated on a pentaflourophenyl column at 20 °C using gradient elution. Furthermore, detection was accomplished by electrospray ionisation in positive-ion mode (ampicillin, clindamycin and corresponding IS) and negative-ion mode (sulbactam and corresponding IS) in combination with multiple reaction monitoring. Depending on the analyte and the matrix under investigation, calibration curves ranged from 0.14 to 59.8 µg/g (jawbone - ampicillin), 2.0-1000 µg/mL (plasma - ampicillin), and 1.0-495 µg/mL (PRF - ampicillin). All analytes fulfilled the requirements of the guideline regarding sensitivity, linearity, selectivity, carryover, within-run and between run accuracy and precision, matrix effect and extraction recovery in all matrices. The method was successfully applied to measure concentrations of ampicillin, sulbactam and clindamycin in real-life samples obtained in routine clinical practice.
Assuntos
Osteonecrose , Fibrina Rica em Plaquetas , Humanos , Cromatografia Líquida/métodos , Clindamicina , Espectrometria de Massas em Tandem/métodos , Sulbactam , Ampicilina , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: The aim of the study was to investigate the impact of different aminopenicillin administration routes on the antimicrobial effects of platelet-rich fibrin (PRF). METHODS: We enrolled patients undergoing treatment with amoxicillin/clavulanic acid (AMC) orally or ampicillin/sulbactam (SAM) intravenously. AMC was applied in a single oral dose (875/125 mg), or in a double oral dose (1750/250 mg), and SAM in a dose of 2000/1000 mg. Blood was obtained one hour after the intake of AMC or 15 min after the infusion of SAM ended. Antimicrobial effects were investigated in agar diffusion tests with fresh PRF, PRF stored for 24, and PRF stored for 48 h. Agar diffusion tests were performed with Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Porphyromonas gingivalis. Inhibition zones (IZs) around a 6 mm PRF disc were measured after 24 h. RESULTS: IZs for fresh PRF and the single oral dose of AMC were 0.0, 4.7, 15.2, 2.3, and 0.9 mm (E. coli, S. aureus, S. pneumoniae, H. influenzae, and P. gingivalis, respectively). For the double oral dose, these values were 0.0, 11.4, 20.0, 8.1, and 7.4 mm. IZs for SAM were 11.9, 18.2, 24.7, 20.3, and 22.1 mm. Differences between parenteral and oral application as well as between different oral doses were significant (p<0.0001, one-way ANOVA). DISCUSSION: The results of our study demonstrate that oral administration is a suitable route to load PRF with these drugs. This could expand the scope of PRF application to prevent infections at the surgical site, especially in an outpatient setting in which drugs are normally applied orally.
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Background: Medical resource management can be improved by assessing the likelihood of prolonged length of stay (LOS) for head and neck cancer surgery patients. The objective of this study was to develop predictive models that could be used to determine whether a patient's LOS after cancer surgery falls within the normal range of the cohort. Methods: We conducted a retrospective analysis of a dataset consisting of 300 consecutive patients who underwent head and neck cancer surgery between 2017 and 2022 at a single university medical center. Prolonged LOS was defined as LOS exceeding the 75th percentile of the cohort. Feature importance analysis was performed to evaluate the most important predictors for prolonged LOS. We then constructed 7 machine learning and deep learning algorithms for the prediction modeling of prolonged LOS. Results: The algorithms reached accuracy values of 75.40 (radial basis function neural network) to 97.92 (Random Trees) for the training set and 64.90 (multilayer perceptron neural network) to 84.14 (Random Trees) for the testing set. The leading parameters predicting prolonged LOS were operation time, ischemia time, the graft used, the ASA score, the intensive care stay, and the pathological stages. The results revealed that patients who had a higher number of harvested lymph nodes (LN) had a lower probability of recurrence but also a greater LOS. However, patients with prolonged LOS were also at greater risk of recurrence, particularly when fewer (LN) were extracted. Further, LOS was more strongly correlated with the overall number of extracted lymph nodes than with the number of positive lymph nodes or the ratio of positive to overall extracted lymph nodes, indicating that particularly unnecessary lymph node extraction might be associated with prolonged LOS. Conclusions: The results emphasize the need for a closer follow-up of patients who experience prolonged LOS. Prospective trials are warranted to validate the present results.
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Objective: This study aims to critically evaluate the effectiveness and accuracy of a time safing and cost-efficient open-source algorithm for in-house planning of mandibular reconstructions using the free osteocutaneous fibula graft. The evaluation focuses on quantifying anatomical accuracy and assessing the impact on ischemia time. Methods: A pilot study was conducted, including patients who underwent in-house planned computer-aided design and manufacturing (CAD/CAM) of free fibula flaps between 2021 and 2023. Out of all patient cases, we included all with postoperative 3D imaging in the study. The study utilized open-source software tools for the planning step, and three-dimensional (3D) printing techniques. The Hausdorff distance and Dice coefficient metrics were used to evaluate the accuracy of the planning procedure. Results: The study assessed eight patients (five males and three females, mean age 61.75 ± 3.69 years) with different diagnoses such as osteoradionecrosis and oral squamous cell carcinoma. The average ischemia time was 68.38 ± 27.95â min. For the evaluation of preoperative planning vs. the postoperative outcome, the mean Hausdorff Distance was 1.22 ± 0.40. The Dice Coefficients yielded a mean of 0.77 ± 0.07, suggesting a satisfactory concordance between the planned and postoperative states. Dice Coefficient and Hausdorff Distance revealed significant correlations with ischemia time (Spearman's rho = -0.810, p = 0.015 and Spearman's rho = 0.762, p = 0.028, respectively). Linear regression models adjusting for disease type further substantiated these findings. Conclusions: The in-house planning algorithm not only achieved high anatomical accuracy, as reflected by the Dice Coefficients and Hausdorff Distance metrics, but this accuracy also exhibited a significant correlation with reduced ischemia time. This underlines the critical role of meticulous planning in surgical outcomes. Additionally, the algorithm's open-source nature renders it cost-efficient, easy to learn, and broadly applicable, offering promising avenues for enhancing both healthcare affordability and accessibility.
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Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44% versus 86.96% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier ("lubrication" layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts.
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Oroantral communication (OAC) is a common complication after tooth extraction of upper molars. Profound preoperative panoramic radiography analysis might potentially help predict OAC following tooth extraction. In this exploratory study, we evaluated n = 300 consecutive cases (100 OAC and 200 controls) and trained five machine learning algorithms (VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50) to predict OAC versus non-OAC (binary classification task) from the input images. Further, four oral and maxillofacial experts evaluated the respective panoramic radiography and determined performance metrics (accuracy, area under the curve (AUC), precision, recall, F1-score, and receiver operating characteristics curve) of all diagnostic approaches. Cohen's kappa was used to evaluate the agreement between expert evaluations. The deep learning algorithms reached high specificity (highest specificity 100% for InceptionV3) but low sensitivity (highest sensitivity 42.86% for MobileNetV2). The AUCs from VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50 were 0.53, 0.60, 0.67, 0.51, and 0.56, respectively. Expert 1-4 reached an AUC of 0.550, 0.629, 0.500, and 0.579, respectively. The specificity of the expert evaluations ranged from 51.74% to 95.02%, whereas sensitivity ranged from 14.14% to 59.60%. Cohen's kappa revealed a poor agreement for the oral and maxillofacial expert evaluations (Cohen's kappa: 0.1285). Overall, present data indicate that OAC cannot be sufficiently predicted from preoperative panoramic radiography. The false-negative rate, i.e., the rate of positive cases (OAC) missed by the deep learning algorithms, ranged from 57.14% to 95.24%. Surgeons should not solely rely on panoramic radiography when evaluating the probability of OAC occurrence. Clinical testing of OAC is warranted after each upper-molar tooth extraction.