Osteomyelitis of the Jaw: A 10-Year Retrospective Analysis at a Tertiary Health Care Centre in Canada.

BACKGROUND: Osteomyelitis (OM) of the jaw is a rare medical condition. In this review, we provide a descriptive analysis of the experience with this condition at a single tertiary health care centre in Canada over 10 years. MATERIALS AND METHODS: We conducted a retrospective chart review of adult patients aged ≥ 18 years presenting with OM of the jaw at the University of Manitoba Health Sciences Centre between January 2009 and May 2019. We included cases with consistent clinical symptoms and radiographic and/or microbiologic evidence of OM of the jaw. Excluded were cases with a previous history of head and neck cancer, radiation therapy in the head and neck regions and use of anti-resorptive medications. RESULTS: Of the 37 patients who met our criteria, the mean age was 44 years (standard deviation [SD] ± 16 years), 21 (56.8%) were male, 16 (43.2%) were diagnosed with acute OM and 21 (57.8%) with chronic OM. Underlying comorbidities, such as diabetes mellitus and chronic kidney diseases, were reported in 6 (16.2%) and 3 patients (8.1%), respectively. Traumatic injuries to the facial skeleton were the most common predisposing factor (11 patients [29.7%]). The most commonly isolated infective organisms were viridans group streptococci (VGS; 75.8%), followed by Prevotella spp. (45.4%). Results showed a higher level of resistance to penicillin of the isolated organisms in chronic OM compared with acute OM. CONCLUSIONS: This description of acute and chronic forms of OM of the jaw will enable clinicians to better understand OM patient profiles, leading to early diagnosis, improved patient care and better outcomes.

The Contribution of Insomnia and Obstructive Sleep Apnea on the Transition from Acute to Chronic Painful Temporomandibular Disorders and their Persistence: A Prospective 3-Month Cohort Study.

Background: Insomnia, and Excessive Daytime Sleepiness (EDS), a surrogate marker of Obstructive Sleep Apnea (OSA), are common sleep-related conditions among painful temporomandibular disorders (TMD) patients. OSA was found to increase the risk of chronic painful TMD. Aims: This prospective cohort study aims to determine the contribution of insomnia and EDS on acute to chronic painful TMD transition as well as its persistence when chronic pain is defined by: (i) duration (> 3 months), and (ii) dysfunction (Graded Chronic Pain Scale [GCPS II-IV]). Methods: From 456 patients recruited between 2015 to 2021, through four locations in Canada, 378 completed the follow-up. A diagnosis was obtained using the Research Diagnostic Criteria or the Diagnostic Criteria for TMD. Insomnia was assessed with the Insomnia Severity Scale (ISS), and OSA was assessed using the Epworth Sleepiness Scale (ESS) which measures EDS, both at baseline. Patients completed the GCPS form at baseline and 3-month follow-up. Results: Borderline associations were found between EDS and the transition or persistence of chronic painful TMD when chronic pain was defined by pain duration (RR adjusted_duration = 1.11, P = 0.07) and dysfunction (RRadjusted_dysfunction =1.40, P = 0.051). Furthermore, EDS was specifically associated with persistent painful TMD when chronic pain was defined by pain duration (RR = 1.13, 95%CI: 1.00-1.26, P = 0.04). Insomnia was not related to the study outcomes (RRadjusted_duration = 0.94, P = 0.27, RRadjusted_dysfunction =1.00, P = 0.99). Conclusion: Results indicate that EDS contrary to insomnia predicted the persistence of chronic painful TMD at a 3-month follow-up.

Contexte: L'insomnie et la somnolence excessive en journée, un marqueur substitut de l'apnée du sommeil obstructive, sont des affections courantes liées au sommeil chez les patients souffrant de troubles temporo-mandibulaires douloureux. On a découvert que l'apnée obstructive du sommeil augmentait le risque de troubles temporo-mandibulaires douloureux chroniques.Objectifs: Cette étude de cohorte prospective vise à déterminer la contribution de l'insomnie et de la somnolence excessive en journée à la transition des troubles temporo-mandibulaires douloureux aigus à chroniques, ainsi qu'à leur persistance lorsque la douleur chronique est définie par : (i) la durée (> 3 mois), et (ii) la dysfonction (Échelle de douleur chronique graduée [GCPS II-IV]).Méthodes: Sur 456 patients recrutés entre 2015 et 2021 dans quatre endroits au Canada, 378 ont terminé le suivi. Un diagnostic a été établi en utilisant les Critères de diagnostic pour la recherche ou les Critères de diagnostic pour les troubles temporo-mandibulaires douloureux. L'insomnie a été évaluée à l'aide de l'Indice de sévérité de l'insomnie (ISI) et l'apnée obstructive du sommeil a été évaluée à l'aide de l'Échelle de somnolence d'Epworth (ESS), qui mesure la somnolence excessive en journée, tous deux au début de l'étude. Les patients ont rempli le formulaire GCPS au début de l'étude et lors du suivi à trois mois.Résultats: Des associations marginales ont été trouvées entre la somnolence excessive en journée et la transition ou la persistance des troubles temporo-mandibulaires douloureux chroniques lorsque la douleur chronique était définie par la durée de la douleur (RR ajusté pour la durée = 1,11, P = 0,07) et la dysfonction (RR ajusté pour la dysfonction = 1,40, P = 0,051). De plus, la somnolence excessive en journée était spécifiquement associée à la persistance des troubles temporo-mandibulaires douloureux lorsque la douleur chronique était définie par la durée de la douleur (RR = 1,13, IC à 95 % : 1,00-1,26, P = 0,04). L'insomnie n'était pas liée aux résultats de l'étude (RR ajusté pour la durée = 0,94, P = 0,27, RR ajusté pour la dysfonction = 1,00, P = 0,99).Conclusion: Les résultats indiquent que la somnolence excessive en journée, contrairement à l'insomnie, prédisait la persistance des troubles temporo-mandibulaires douloureux chroniques lors du suivi de trois mois.

The contribution of pain and disability on the transition from acute to chronic pain-related TMD: A 3-month prospective cohort study.

Although most cases of pain-related temporomandibular disorders (TMD) are mild and self-limiting, about 10% of TMD patients develop severe disorders associated with chronic pain and disability. It has been suggested that pain intensity contributes to the transition from acute to chronic pain-related TMD. Therefore, the aims of this current prospective cohort study were to assess if pain intensity, pain always being present, pain or stiffness on awakening, jaw activities, and interference, were associated with the transition from acute to chronic pain-related TMD at 3 months of follow-up. One hundred and nine participants, recruited from four clinics in Montreal and Ottawa, received examinations and completed the required instruments at baseline and at the 3rd month of follow-up. In a multivariable analysis including sex, age, characteristic pain index (CPI) (OR = 1.03, 95%CI = 1.01-1.06, P = 0.005), moderate to severe average pain intensity (OR = 3.51, 95%CI = 1.24-9.93, P = 0.02), disability points score (OR = 1.29, 95%CI = 1.06-1.57, P = 0.01), interferences (ORs = 1.30-1.32, P = 0.003-0.005), screening score (OR = 1.37, 95%CI = 1.08-1.76, P = 0.01), and pain always present (OR = 2.55, 95%CI = 1.08-6.00, P = 0.03) assessed at first-visit were related to the transition outcome at the 3rd month of follow-up. Further, we found that if 4 patients with acute pain-related TMD on average were exposed to these risk factors at baseline, 1 would have the transition from acute to chronic pain at 3 months of follow-up. Results indicate that these factors are associated with the transition from acute to chronic pain-related TMD, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with pain-related TMD.

Acute and Chronic Temporomandibular Disorder Pain: A critical review of differentiating factors and predictors of acute to chronic pain transition.

AIMS: The aims of this critical review were to: (i) assess the factors that differentiate acute from chronic temporomandibular disorders (TMD) pain; (ii) assess the risk factors associated with the transition from acute to chronic TMD pain; and (iii) summarize and appraise the studies. METHOD: The databases used were MEDLINE, Embase, and Cochrane Database of Systematic Reviews. Eligible studies included articles comparing acute to chronic TMD pain, and cohort studies assessing the risk factors implicated in the transition from acute to chronic TMD pain. RESULTS: Seven articles were selected: one case-control study, three cross-sectional studies, and three cohort studies. These studies found that psychological factors were more common in chronic than acute TMD pain patients; however, these factors did not increase the transition risk in the multivariable model. Myofascial and baseline pain intensity were associated with the transition from acute to chronic TMD pain at a 6-month follow-up. Due to methodological weaknesses in the available literature, more research is required to establish the risk factors implicated in the transition from acute to chronic TMD pain. CONCLUSION: This review found some evidence that myofascial pain is associated with the transition risk from acute to chronic TMD pain at a 6-month follow-up and that pain intensity at baseline is associated with more intense TMD pain 6 months later. There is insufficient evidence to draw conclusions about the role of demographics and psychological disorders as independent risk factors.

Orofacial pain education in dentistry: A path to improving patient care and reducing the population burden of chronic pain.

Dentists stand in an optimal position to prevent and manage patients suffering from chronic orofacial pain (OFP) disorders, such as temporomandibular disorders, burning mouth syndrome, trigeminal neuralgia, persistent idiopathic dentoalveolar pain, among others. However, there are consistent reports highlighting a lack of knowledge and confidence in diagnosing and treating OFP among dental students, recent graduates, and trained dentists, which leads to misdiagnosis, unnecessary costs, delay in appropriate care and possible harm to patients. Education in OFP is necessary to improve the quality of general dental care and reduce individual and societal burden of chronic pain through prevention and improved quality of life for OFP patients. Our aims are to emphasize the goals of OFP education, to identify barriers for its implementation, and to suggest possible avenues to improve OFP education in general, postgraduate, and continuing dental education levels, including proposed minimum OFP competencies for all dentists. Moreover, patient perspectives are also incorporated, including a testimony from a person with OFP. General dentists, OFP experts, educators, researchers, patients, and policy makers need to combine efforts in order to successfully address the urgent need for quality OFP education.

Greater palatine block for V2 trigeminal neuralgia: Case report.

AIMS: This study describes a novel nerve block directed at the maxillary (V2) division of the fifth cranial nerve as treatment for medication-refractory trigeminal neuralgia (TN). METHODS AND RESULTS: The authors present three cases of TN treated with V2 nerve block using commonly available local anesthetics injected through the greater palatine foramen. Patients' medications were noted before and after the procedure. Following the injection, patients were followed over time and outcome was assessed. Patients experienced rapid and long-lasting pain relief allowing for significant reduction in antineuralgia medications. This was done with the objective of breaking the pain cycle with subsequent discontinuation or reduction of analgesic medications. CONCLUSION: This technique may be an effective treatment for medication-refractory V2 TN. By interrupting the pain cycle, this renders the condition amenable to long-term control using diminished doses of standard antineuralgia pharmaceuticals. The practical implications of the described procedure are that it is simple, safe, and well-tolerated with few or no adverse effects. This novel technique is a diagnostic feature for the dentist to differentiate between sources of facial pain.

Regulation of platelet Rac1 and Cdc42 activation through interaction with calmodulin.

Rac1 and Cdc42 are members of the Rho family of small GTPases and have been shown to induce lamellipodia and filopodia formation, respectively. This leads to changes in cytoskeleton organization and as a consequence affects cell migration. In the present work we demonstrate that endogenous Rac1 and Cdc42 interact with calmodulin (CaM) in a Ca(2+)-dependent fashion. The interaction of Rac1 and Cdc42 with CaM was shown to be direct. This novel interaction was further confirmed in platelets using co-immunoprecipitation studies. Using CaM database analysis and in vitro peptide competition assays we have identified a 14 amino acid region in Rac1 that is essential for CaM binding. The scrambled form of the peptide did not bind CaM demonstrating specificity of the predicted CaM binding region in Rac1. A similar region capable of binding CaM exists in Cdc42. Furthermore, using the optimal activation time-point for each GTPase, the role of CaM in the function of Rac1 and Cdc42 was examined. Results demonstrate that in human platelets, thrombin caused maximal activation of Rac1 and Cdc42 at ~60 s and ~25 s respectively. The potent CaM antagonist W7 abolished thrombin-mediated activation of Rac1. However, addition of W7 resulted in the activation of Cdc42 over basal and W7 did not inhibit thrombin-mediated activation of Cdc42. The less potent CaM inhibitor, W5, did not have any effect on Rac1 and Cdc42 activation. The results demonstrate that in platelets, binding of CaM to Rac1 increases its activation while its binding to Cdc42 reduces the activation of this GTPase. This suggests an important role for CaM in coordinating Rac1 and Cdc42 activation and in the regulation of cytoskeleton remodeling.

Ral-GTPase interacts with the beta1 subunit of Na+/K+-ATPase and is activated upon inhibition of the Na+/K+ pump.

Na+/K+-ATPase functions as both an ion pump and a signal transducer. Cardiac glycosides partially inhibit Na+/K+-ATPase, causing activation of multiple interrelated growth pathways via the Na+/K+-ATPase/c-Src/epidermal growth factor receptor complex. Such pathways include Ras/MEK/ERK and Ral/RalGDS cascades, which can lead to cardiac hypertrophy. In search of novel Ral-GTPase binding proteins, we used RalB as the bait to screen a human testes cDNA expression library using the yeast 2-hybrid system. The results demonstrated that 1 of the RalB interacting clones represented the C-terminal region of the beta1 subunit of Na+/K+-ATPase. Further analysis using the yeast 2-hybrid system and full-length beta1 subunit of Na+/K+-ATPase confirmed the interaction with RalA and RalB. In vitro binding and pull-down assays demonstrated that the beta1 subunit of Na+/K+-ATPase interacts directly with RalA and RalB. Ral-GTP pull-down assays demonstrated that short-term ouabain treatment of A7r5 cells, a rat aorta smooth muscle cell line, caused activation of Ral GTPase. Maximal activation was observed 10 min after ouabain treatment. Ouabain-mediated Ral activation was inhibited upon the stimulation of Na+/K+-ATPase activity by Ang II. We propose that Ral GTPase is involved in the signal transducing function of Na+/K+-ATPase and provides a possible molecular mechanism connecting Ral to cardiac hypertrophy during diseased conditions.

Calmodulin binding to the small GTPase Ral requires isoprenylated Ral.

Ral, a member of the Ras-p21 superfamily of small GTPases, has been shown to require the calcium-signaling protein calmodulin (CaM) for activation. In the present work, we investigated the properties of the Ral-CaM interaction. Using CaM affinity binding assay with lysates from mammalian cells overexpressing various Ral mutants, we found that RalB(V23, DeltaCAAX) lacking the C-terminal isoprenylation region bound significantly less efficiently to CaM. Binding of other mutants containing critical amino acid changes in the nucleotide or substrate binding regions (residues 23, 28, and 49) was not affected. In addition, all mutants bound significantly better in the presence of calcium versus the calcium chelator EGTA. Using in vitro transcription-translation in the presence of geranylgeranyl pyrophosphate, we demonstrate enhanced Ral binding to CaM. Inhibition of isoprenylation in cells in culture with lovastatin resulted in decreased binding of CaM to Ral. The present results show that post-translational isoprenylation of Ral is important in Ral-CaM interaction.