Influence of Genetic Polymorphisms on the Response to Tramadol, Ibuprofen, and the Combination in Patients With Moderate to Severe Pain After Dental Surgery.

PURPOSE: We aimed to elucidate the influence on analgesic effect of genetic polymorphisms in enzymes responsible for biotransformation of tramadol and ibuprofen or other possible genes involved in their mechanism of action. METHODS: The study population comprised 118 patients from a multicenter, randomized, double-blind, placebo-controlled, Phase III clinical trial that assessed the analgesic efficacy and tolerability of a single dose of ibuprofen (arginine)/tramadol 400/37.5 mg compared with ibuprofen arginine 400 mg alone, tramadol 50 mg alone, and placebo in patients with moderate to severe pain after dental surgery. We analyzed 32 polymorphisms in the cytochrome P450 (CYP) enzymes COMT, ABCB1, SLC22A1, OPRM1, and SLC22A1. FINDINGS: We did not find any statistically significant difference among CYP2C9 phenotypes related to ibuprofen response, although CYP2C9 poor metabolizers had a longer effect (higher pain relief at 6 hours). Likewise, we did not find any statistically significant difference among PTGS2 genotypes, contradicting previously publications. IMPLICATIONS: There was not a clear effect of CYP2D6 phenotype on tramadol response, although CYP2D6 poor metabolizers had a slower analgesic effect. Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels. Finally, we found a statistically significant better response in patients carrying the OPRM1 A118G G allele, which contradicts the previous reports. Measuring the active metabolite O-desmethyl-tramadol formation would be of great importance to better evaluate this association because O-desmethyl-tramadol has a higher µ-opioid receptor affinity compared with the parent drug. EudraCT.ema.europa.eu identifier: 2013-004637-33.

Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model

Background: Bisphosphonate-related osteonecrosis of the jaw is a pathological condition without effective established treatment and preventive strategies. The aim of this study was to analyse the effect of adipose-derived stem cells (ASC) in an experimental murine model of osteonecrosis. Material and Methods: 38 Wistar rats were injected intraperitoneally with zoledronic acid. After treatment, upper jaw molars were extracted. The animals were randomly assigned to one of two groups. In the control group, saline solution was applied over the alveolar sockets after the tooth extractions. In the treatment group, ASCs were applied instead of saline solution. The control and treatment groups were subdivided based on the time of euthanasia. A clinical and histological analysis was performed. Results: The presence of osteonecrosis in alveolar bone was observed in a similar distribution in both groups. In the ASC-treated group, new bone formation was greater than in controls. Conclusions: In this study, application of ASCs showed greater new bone formation in an osteonecrosis-like murine model. Previous inhibited post-extraction bone remodelling could be reactivated, and these findings appeared to be secondary to implantation of ASCs

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Derivación de pacientes con síndrome de disfunción temporomandibular desde Atención Primaria / Referral of patients with temporomandibular joint dysfunction from Primary Care

Introducción: El síndrome de disfunción temporomandibular (SDTM) engloba un amplio abanico de síntomas que van desde molestias a la palpación de la musculatura masticadora hasta episodios de imposibilidad para la apertura o el cierre oral e incluso degeneración articular irreversible. El manejo de los pacientes con sintomatología propia de esta enfermedad es controvertido; generalmente los episodios inflamatorios agudos son susceptibles de tratamiento conservador y no precisan, en principio, valoración por un especialista. Como centro de referencia de la Comunidad de Madrid nuestra impresión es que la derivación de esta dolencia desde Atención Primaria es masiva y poco orientada, lo que, de ser cierto, ocasionaría un aumento de los costes sanitarios directos e indirectos, así como una saturación de las consultas de especialidad. Material y métodos: En este trabajo realizamos un análisis prospectivo de la derivación de los pacientes con SDTM desde Atención Primaria al Hospital Universitario La Paz en un período de 6 meses mediante un sistema de cuestionarios anónimos cumplimentados por el especialista y el paciente. Resultados: La muestra del estudio la constituyen 101 pacientes. El 35,6% de los pacientes derivados presentan una evolución crónica (mayor de 6 meses) de la enfermedad, con una sintomatología leve y en el 65,3% de los casos no se había instaurado ningún tipo de tratamiento por un médico/dentista antes de acudir a nuestra consulta. El gasto extra total anual provocado por la incorrecta derivación desde Atención Primaria asciende a 54.309,024 euros anuales. Conclusiones: Por su elevada prevalencia, el SDTM constituye un foco interesante de acción a la hora de optimizar los tratamientos y minimizar el gasto dentro de las entidades maxilofaciales. Este trabajo pone de manifiesto la situación actual y alerta sobre la necesidad de elaborar protocolos de derivación en consenso con Atención Primaria

Introduction: Temporomandibular joint syndrome (TMJS) includes a wide range of signs and symptoms that vary from mild pain in masticatory muscles to inability to open and close the mouth, and even irreversible joint derangement. Management is controversial, with the more acute inflammatory episodes being good candidates for conservative treatment. These patients do not need, at least initially, to be evaluated by a maxillofacial surgeon. As a maxillofacial referral centre in the Madrid area, it seems that patients affected by this syndrome are referred to our centre from Primary Care on a large scale, and are completely uninformed about their disorder. If this is the case, unnecessary direct and indirect health care costs would be increased, as well as contribute to medical consultation overload. Material and methods: A prospective analysis was performed on TMJS patient referral from Primary care to the Hospital Universitario La Paz during a 6 months period. A self-report anonymous questionnaire was also completed by the professional and the patient in order to collect data. Results: Of the101 patients evaluated, 35.6% had chronic onset (more than 6 months) and with mild symptoms. Almost two-thirds (65.3%) of patients had not received any kind of treatment before coming to the centre. Annual additional costs due to incorrect patient referral were 54,309.024 euros. Conclusions: Due to its high prevalence, TMJS is an interesting focus for action when it comes to controlling extra costs and medical consultation overload. This report shows the present situation, and stressed the need for a consensus referral protocol in Primary Care

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

BACKGROUND: Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. METHODS: A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. RESULTS: Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. CONCLUSION: Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. FUNDING: Laboratorios del Dr. Esteve, S.A.U.

Beckwith-Wiedemann Syndrome: Open bite evolution after tongue reduction

Background: Macroglossia causes functional deficits such as airway obstruction, drooling, phonation difficulties, and leads to protrusion of dentoalveolar structures resulting in an anterior open bite and a prognathic mandibular appearance. Macroglossia is present in the majority of patients with Beckwith-Wiedemann syndrome (BWS) and surgical treatment may be indicated. Material and Methods: A retrospective review was conducted including BWS patients who underwent surgical tongue reduction between 2000 and 2015 at the Hospital Universitario La Paz, Madrid. Results: Out of 16 patients with BWS, surgery was performed in 11 cases. Tongue protrusion with open bite was the main indication for surgical treatment. Reduction glossectomy was performed using the keyhole technique. We analysed the relationship between age at surgery and evolution of open bite. Complications were minimal and satisfactory outcomes were observed with a decrease in anterior open bite. Conclusions: In this study we have observed that surgical treatment in patients with BWS and open bite accompanied by macroglossia seems to provide positive results with a satisfactory outcome in dentoskeletal alterations (AU)

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Complicaciones en reconstrucción craneal con prótesis de polieteretercetona / Complications in cranial reconstruction using PEEK prosthesis

Introducción. Los defectos craneales tienen una repercusión importante en el paciente desde un punto de vista estético, psicológico y funcional. Actualmente no existe acuerdo sobre el material ideal para la reconstrucción de estos defectos. Material y métodos. Realizamos un estudio retrospectivo incluyendo a los pacientes con reconstrucción craneal con prótesis de polieteretercetona (PEEK) a medida entre los años 2008 y 2014 en el Servicio de Cirugía Oral y Maxilofacial del Hospital Universitario La Paz, Madrid. Las prótesis son diseñadas de manera específica para cada paciente con el sistema CAD-CAM. Resultados. Se reconstruyó a un total de 7 pacientes con defectos craneales con prótesis de PEEK. Solo en un caso, la resección y reconstrucción fueron realizadas en el mismo acto quirúrgico. En el resto de los casos se realizó una reconstrucción diferida. Las complicaciones que se presentaron fueron: un seroma y una fístula de LCR, que se resolvieron con tratamiento conservador; y una dehiscencia de la herida y un caso con episodios de infecciones repetidas, cuyo defecto estaba próximo al seno frontal, que terminaron con la retirada definitiva de la prótesis. Conclusión. El material ideal para la reconstrucción de defectos craneales no existe. Las prótesis de PEEK están obteniendo buenos resultados estética y funcionalmente. Cuando el hueso autógeno no esté disponible o en determinados casos con defectos grandes, las prótesis de PEEK pueden ser una buena opción. Sin embargo, si el defecto está en comunicación directa con los senos paranasales, debemos valorar bien la indicación (AU)

Introduction. Cranial defects tend to carry functional and aesthetic consequences for the patient. The most suitable material to be used remains controversial. Methods. We report a retrospective review of patients whose cranial defects were reconstructed using a computer designed polyetheretherketone (PEEK)-patient specific implant) between 2008 and 2014 at the Oral and Maxillofacial Surgery Department, in Hospital Universitario La Paz, Madrid. Implants are designed individually to each patient with CAD-CAM system. Results. Seven patients underwent cranial reconstruction using a PEEK-patient specific implant. One case involved a one-step primary reconstruction and the rest of cases underwent a delayed reconstruction. Complications were: one seroma and one CSF leak, resolved with conservative treatment, and a wound dehiscence and an infection case whose defect was near the frontal sinus, resolved with removal of the implant. Conclusion. The ideal material for reconstructing cranial defects does not exist, but PEEK has demonstrated good outcomes. When autologous bone is not available or in selected cases with large defects, PEEK is a good option to reconstruct these defects. However, if the defect is related with paranasal sinuses, indication must be evaluated (AU)

Incidence of and Factors Associated with Sinus Membrane Perforation During Maxillary Sinus Augmentation Using the Reamer Drilling Approach: A Double-Center Case Series.

Maxillary sinus membrane perforation has been reported as the most common intraoperative complication during sinus augmentation, potentially leading to postoperative infection and consequent loss of graft or even implant failure. Numerous anatomical factors have been demonstrated to affect membrane tearing. However, careful use of proper instrumentation, such as a reamer, seems to play an important role in minimizing the incidence of these complications. Hence, the aim of the present study was to (1) investigate the reliability of reamer drilling for lateral window preparation; (2) examine the incidence of membrane perforation; and (3) study the factors that might influence membrane perforation. Results from this study showed the safety and effectiveness of using a reamer to perform lateral window approach sinus augmentation. The sinus membrane perforation rate was found to be 12.5%. A slightly higher perforation rate was noted in thinner maxillary lateral walls (< 1.25 mm). The authors concluded that reamer drilling is a safe and effective alternate technique for opening the lateral window wall when the lateral wall thickness is ≥ 1.25mm.

Orthodontically guided bone transport in the treatment of alveolar cleft: A case report.

INTRODUCTION: Conventional treatments are sometimes not possible in certain alveolar cleft cases due to the severity of the gap which separates the fragments. Various management strategies have been proposed, including sequential surgical interventions or delaying treatment until adulthood to then carry out maxillary osteotomies. A further alternative approach has also been proposed, involving the application of bone transport techniques to mobilise the osseous fragments and thereby reduce the gap between lateral fragments and the premaxilla. CASE REPORT: We introduce the case of a 10-year-old patient who presented with a bilateral alveolar cleft and a severe gap. Stable occlusion between the premaxilla and the mandible was achieved following orthodontic treatment, making it inadvisable to perform a retrusive osteotomy of the premaxilla in order to close the alveolar clefts. Faced with this situation, it was decided we would employ a bone transport technique under orthodontic guidance using a dental splint. This would enable an osseous disc to be displaced towards the medial area and reduce the interfragmentary distance. During a second surgical intervention, closure of the soft tissues was performed and the gap was filled in using autogenous bone. CONCLUSIONS: The use of bone transport techniques in selected cases allows closure of the osseous defect, whilst also preserving soft tissues and reducing the amount of bone autograft required. In our case, we were able to respect the position of the premaxilla and, at the same time, generate new tissues at both an alveolar bone and soft tissue level with results which have remained stable over the course of time. KEY WORDS: Alveolar cleft, bone transport, graft.

Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model.

OBJECTIVES: The main challenge in treating bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the absence of an effective established treatment. We aimed to compare different potentially preventive treatments for BRONJ after dental extractions in zoledronic acid (ZA)-treated animals. We studied the local application of different combinations of adipose-derived stem cells (ASCs) with or without previous stimulation with bone morphogenetic protein 2 (BMP-2) and platelet-rich plasma (PRP) in rats. MATERIAL AND METHODS: Fifty-six male Wistar rats were treated with ZA for 9 weeks. Dental extractions were performed in the eighth week, and the animals were divided into 4 groups. In group 1 (n = 14), alveolar coverage with mucoperiosteal flap was performed. In group 2 (n = 14), PRP was applied over the sockets and covered with the flap. In group 3 (n = 15), allogeneic ASCs with PRP were applied and covered with the flap. In group 4 (n = 13), animals were treated with ASCs cultured with BMP-2, PRP, and flap coverage. Histologic, fluorescence, and radiologic studies of the maxillae were performed. RESULTS: ASC-treated animals showed lower frequency of osteonecrosis (14% vs 50%, p = 0.007) and greater bone turnover (p = 0.024) and osteoclast count (p = 0.045) than those not receiving the ASC treatment. CONCLUSIONS: In this high-risk model, ASC-based treatments seem to prevent BRONJ more effectively than mucosal flap with or without PRP. The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results.

¿Cuál es su diagnóstico? / What would your diagnosis be?

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¿Cuál es su diagnóstico? / What would your diagnosis be

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Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior.

INTRODUCTION: Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. CASE REPORT: A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandibulectomy with an alveolar inferior nerve lateralization was performed. CONCLUSIONS: Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous tumor, parotid mass, parotid gland, salivary gland, rare tumors.

Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats.

INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a pathologic condition of increasing frequency, with a poorly understood pathophysiology and which can be difficult to manage. The aim of this study was to find a reproducible experimental model that directly relates chronic bisphosphonate administration with the development of osteonecrosis with or without tooth extraction, with no other drug involved. MATERIAL AND METHODS: Twenty male Wistar rats were divided into 4 groups (n = 5/group). Animals were injected over 9 weeks with zoledronic acid (0.1 mg/kg). In groups 1 and 2 three times a week intraperitoneally, and in group 3 once a week intravenously. A control group (group 4) received intraperitoneal injections of saline solution three times a week. After 8 weeks of treatment, 3 right upper jaw molars were extracted in groups 1, 3 and 4 and all rats were sacrificed 1 week later. The maxillae were histologically analyzed for presence of osteonecrosis foci, number of osteoclasts, vascularity, bone resorption status and presence of abscess. Radiographic examination was performed with a plain radiograph of each hemi-head. RESULTS: We found that group 1 (dental extractions and highest cumulative dose of zoledronic acid) had the highest incidence of osteonecrosis (80%), absence of bone resorption (100%) and lowest number of osteoclasts (mean 7.9/field at 40×). Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study. CONCLUSIONS: We offer a new animal model of BRONJ after zoledronic acid administration and dental extractions, achieving bone changes similar or superior to previous studies, highlighting the dental extraction as an important trigger factor.

Osteotomía distal mandibular y fractura en tallo verde / No disponible

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The deep inferior epigastric artery perforator (DIEAP) flap for total glossectomy reconstruction.

PURPOSE: Total or subtotal glossectomy following the resection of intraoral tumors causes significant morbidity. However, which reconstructive technique is the most successful remains controversial. PATIENTS AND METHODS: After approval by the Ethics Committee, charts were reviewed retrospectively for patients treated at the Oral and Maxillofacial Surgery Department, University Hospital La Paz (Madrid, Spain), during a 3-year period (2005-2008). All were reconstructed with a deep inferior epigastric artery perforator (DIEAP) flap after total glossectomy. Data collected included affiliation data, extent of extirpation, type of reconstruction, and surgical outcome, including donor-site morbidity, complications, and functional results. RESULTS: Seven patients (5 men, 71.4%; 2 women, 28.6%) with primary squamous cell carcinoma of the tongue underwent total glossectomy and simultaneous microsurgical reconstruction with a DIEAP flap. In all cases, the flap was harvested with a fusiform shape oriented craniocaudally and limited to zone 1. The average size of the flap was 16.7 × 7.2 cm. Functional outcome related to swallowing was poor; 57.1% of the patients required a permanent gastrostomy. Speech was considered intelligible in 85.7% of cases by 2 independent observers. The surgical outcome was uneventful in most of the cases, with only 1 case of local dehiscence at the mouth floor. None of the cases developed abdominal wall dehiscence or an abdominal hernia at mid- or long-term follow-up. CONCLUSIONS: The DIEAP flap is a reliable alternative for tongue reconstruction. It provides a large volume of soft tissue for transfer and is predictable and stable over time with low donor-site morbidity.