Collaborative approach to paediatric chronic non-bacterial osteomyelitis of the mandible: Great Ormond Street Hospital case series.

This paper outlines a 10-patient case series of chronic non-bacterial osteomyelitis (CNO) of the mandible at a tertiary paediatric hospital in the UK. Our findings highlight the homogeneous presenting signs and symptoms of an intermittently painful, swollen angle and ramus of the mandible. We present the typical laboratory investigative findings (normal inflammatory markers) and imaging appearances (sclerosis and periosteal oedema). Our paper outlines an investigation protocol, including recommendations for extraoral bone biopsies and systemic magnetic resonance imaging (MRI). We explain the importance of multidisciplinary care, with combined care by rheumatologists and infectious disease specialists. Finally we demonstrate the efficacy of our treatment algorithm for oral non-steroidal anti-inflammatory drugs (NSAIDs), and in those cases refractory to NSAIDS, intravenous pamidronate. This paper provides a useful addition to the literature by informing OMF surgeons of this rare condition and given the clinical equipoise in treatments, it can hopefully guide clinicians in an investigation pathway and management protocol.

Remodelling of mandibular condylar head after fixation of fractures with ultrasound activated resorbable pins: A retrospective case series.

The aim of this study was to assess whether the resorption of poly-lactic acid pins, used for condylar head fracture fixation, adversely affect remodelling of the condylar head. A retrospective review of patients was performed that underwent ORIF of CHF with ultrasound activated resorbable poly-lactic acid pins and had CT/CBCT scans of the condyle at least 18 months after surgery, at which point the fixation material was expected to be resorbed. We reviewed the size, shape and position of the condylar head and compared this to the normal side and compared this to the results of conservative management and ORIF with titanium screws in the literature. Most patients had condylar heads normally positioned and shaped, with minimal bone changes. The position of the condyle in the fossa, its shape and bone changes compare favourably with previous studies on CHF managed conservatively or with titanium screw fixation. There was no radiographic evidence of the pins after 18 months. In conclusion, ultrasound activated resorbable pins can provide suitable fixation for ORIF of condylar head fractures, avoiding the need for screw removal, and there was no evidence that the resorption process adversely affected the remodelling of the condylar head.

Management of the secondary growth defect.

Temporomandibular reconstruction has clear aims including the restoration of mandibular form and function, to decrease patient disability and to prevent disease progression. In addition paediatric patients have growth and re-modelling considerations and the need to minimise any secondary growth defect. The involvement of a multidisciplinary team is deemed essential for both the child and parents. In some patients crisis intervention may be required and early reconstruction might be necessary dependant on the severity of impairment. The aetiology of end stage TMJ disease, unilateral/bilateral disease and the degree of patient compromise will guide timing and choice of treatment. Reducing repeated surgery and facilitating patient compliance may potentiate mandibular growth.

Autogenous Reconstruction of the Temporomandibular Joint.

Reconstruction of the temporomandibular joint can optimize many basic functions (airway obstruction, feeding, speech difficulties) and rectify facial deformity. In children, it can restore potential growth. Reconstruction in adults is now mainly performed with alloplastic techniques but autogenous vascularized grafts are often required in patients with large composite facial defects or postradiation treatment. In children, autogenous grafting remains the primary reconstructive choice despite a high further surgery rate and increasing interest in alloplastic techniques. The costochondral graft remains the most widely used technique due to the potential for growth restoration and low donor site morbidity.

Predictive risk factors for persistent pain following total prosthetic temporomandibular joint replacement.

The aim of this study was to determine the rate of persistent pain following total TMJ replacement and to identify potential predictive risk factors. A retrospective review of case notes treated by a single surgeon in a tertiary unit was performed. For each patient a number of variables were recorded including visual analogue pain scores (0 to 10) and opioid usage pre surgery and at 12 months or last follow up beyond 12 months. Persistent pain scores of 5 to 7 were regarded as moderate and 8 to 10 as severe. The mean pain score at last follow-up was significantly lower than preoperatively (2.1 vs. 6.3, p < 0.001) with a mean follow-up time of 40.1 months (range 12-44). 16.4% of the patients reported moderate to severe pain and 13.7% were still on regular opioids at the last follow-up. Therefore 15 patients (20.5%) suffered from chronic postoperative pain after TMJ replacement surgery. Patients reporting severe preoperative pain scores (p = 0.04), regular opioid use (p = 0.001) or multiple previous open TMJ surgeries (p = 0.03) were more likely to suffer from chronic persistent pain and these should be regarded as predictive risk factors. The identification of these factors allows for better risk stratification of patients, informed consent and the agreement of expected outcomes. Patients with true articular disease and a single failed surgery should be considered for early total TMJ replacement to minimise multifactorial persistent pain.

The ESTMJS (European Society of Temporomandibular Joint Surgeons) Consensus and Evidence-Based Recommendations on Management of Condylar Dislocation.

Although condylar dislocation is not uncommon, terminology, diagnostics, and treatment concepts vary considerably worldwide. This study aims to present a consensus recommendation based on systematically reviewed literature and approved by the European Society of TMJ Surgeons (ESTMJS). Based on the template of the evidence-based German guideline (register # 007-063) the ESTMJS members voted on 30 draft recommendations regarding terminology, diagnostics, and treatment initially via a blinded modified Delphi procedure. After unblinding, a discussion and voting followed, using a structured consensus process in 2019. An independent moderator documented and evaluated voting results and alterations from the original draft. Although the results of the preliminary voting were very heterogenous and differed significantly from the German S3 guideline (p < 0.0005), a strong consensus was achieved in the final voting on terminology, diagnostics, and treatment. In this voting, multiple alterations, including adding and discarding recommendations, led to 24 final recommendations on assessment and management of TMJ dislocation. To our knowledge, the ESTMJS condylar dislocation recommendations are the first both evidence and consensus-based international recommendations in the field of TMJ surgery. We recommend they form the basis for clinical practice guidelines for the management of dislocations of the mandibular condyle.

The design of a randomized, placebo-controlled, dose-ranging trial to investigate the efficacy and safety of the ADAMTS-5 inhibitor S201086/GLPG1972 in knee osteoarthritis.

Objective: This study aims to assess the efficacy of the anticatabolic 'a disintegrin and metalloproteinase with thrombospondin motif-5' (ADAMTS-5) inhibitor, S201086/GLPG1972, in slowing cartilage loss in participants with knee osteoarthritis (OA). Design: ROCCELLA (NCT03595618) is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial. We plan to enrol a total of 852 participants with knee OA across 12 countries. Participants will be randomized 1:1:1:1 to receive 75, 150 or 300 â€‹mg S201086/GLPG1972, or placebo orally, once daily for 52 weeks. Eligible participants will be aged 40-75 years and have predominantly medial knee OA with centrally read Kellgren-Lawrence grade 2 or 3, OARSI atlas medial femorotibial joint space narrowing grade 1 or 2, and consistent moderate to severe baseline pain. The primary endpoint will be the change from baseline to week 52 in magnetic resonance imaging-assessed central medial femorotibial compartment cartilage thickness. Secondary endpoints will include other structural outcomes, and patient-reported outcomes, as well as safety and pharmacokinetic assessments. Study sites will be assessed for eligibility based on factors including imaging quality, and images will be centrally read and quality checked. Conclusions: Using strict inclusion criteria and leading imaging techniques with stringent quality controls, the ROCCELLA trial will evaluate the efficacy of S201086/GLPG1972 in slowing cartilage loss in participants with knee OA. The selected eligibility criteria should enrich for participants with OA who experience sufficient cartilage loss to allow detection of a substantial treatment effect.

Treatment of calcium pyrophosphate deposition in the temporomandibular joint with resection and simultaneous reconstruction using a custom joint prosthesis.

PURPOSE: The authors present a rare case of calcium pyrophosphate deposition disease (CPPD) in the temporomandibular joint (TMJ), successfully treated with complete resection and immediate reconstruction using a custom-made prosthesis. This one-stage approach has prevented the patient from requiring two surgeries and has proven effective in the management of the condition. METHODS: Our patient, a 56-year-old male, presented with left TMJ pain and trismus. Investigations showed a destructive left TMJ mass, confirmed by biopsy to be tophaceous pseudogout. The treatment involved excising all the affected tissues followed by condylectomy, coronoidectomy, and a total TMJ replacement. The patient recovered well from surgery with good mouth opening. RESULTS: CPPD disease is a metabolic arthropathy of poorly understood aetiology. Management options vary from conservative non-surgical to surgical treatment depending on the severity. CONCLUSION: This case demonstrates the feasibility of a one-stage procedure with reconstruction using a custom-made prosthesis and virtual planning.

Treatment of fractures of the mandibular condylar head with ultrasound-activated resorbable pins: early clinical experience.

Controversy continues about the benefits and disadvantages of open reduction and internal fixation of fractures of the condylar head. Once a decision to treat surgically has been made, an appropriate method of fixation must be chosen. Standard titanium fixation has a number of complications, including the risk of protrusion of the screw beyond the condylar head and the possible need for removal later. Resorbable fixation is an alternative, and ultrasound-activated resorbable pins are a new innovation. We have treated a series of 15 patients with 17 fractures of the condylar head, in which the use of ultrasound-activated resorbable fixation has provided adequate strength and stability during early healing. Complications included technical difficulties in achieving complete anatomical reduction as a result of fragmentation of the condylar head, and three facial nerve palsies, two of which recovered within three months. No pins failed, and there was no sign of instability during healing.

Why is hepatocellular carcinoma less attributable to viral hepatitis in Yemen?

The hepatitis B virus (HBV) and the hepatitis C virus (HCV) are still public health problems in Yemen, with older individuals having much higher prevalence than younger generations. However, research on the prevalence of viral hepatitis in association with hepatocellular cancer (HCC) has not yet been undertaken in Yemen. The aim of this study was to determine the prevalence of HBV and HCV infection among HCC patients and to estimate the risk of these infections being associated with the development of HCC. A cross-sectional study was conducted on patients attending oncology outpatient in Sana'a, Yemen, through the period 2008-mid 2010 with confirmed diagnosis of HCC. A total of 88 cases were studied thoroughly with different investigations such as CT-scan, ultrasound, tumour marker, alpha-feto-protein and histopathological biopsy. A structured questionnaire was also applied and physical examination done to assess the general condition of the patients. Statistical package (SPSS version 16) was used for analysis of the data. The mean age of the cases was 61.2 years (± 12.6) with half over 60 years. There were fewer male patients (36%) compared to females and most (97%) only had basic /no formal education. Seventy nine (89%) were diagnosed as HCC cases with histopathological biopsy while the rest were diagnosed by ultrasound, CT scan, tumour marker, and alpha-feto-protein. Around one-third of the subjects were positive for HBsAg and HCV antibodies. Multivariate analysis showed infection with HCV and use of smoking was associated with HCC diagnosis. Although an association was observed between the occurrence of HCC and viral hepatitis (either HBV or HCV) and cigarette smoking, but the rate of viral infection was lower than what has been reported elsewhere.

Involvement of p53 in gemcitabine mediated cytotoxicity and radiosensitivity in breast cancer cell lines.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdCyd) is one of the anti-metabolites drugs that target DNA replication. We evaluated dFdCyd cytotoxicity and its radiosensitizing ability in human breast cancer cell lines, MCF-7 (wild-type p53) and MDA-MB-231 (mutant-type p53) along with normal mammary epithelial cell line (MCF-12) for comparison. Radiosensitivity and cytotoxicity were measured by the clonogenic survival assays. DNA DSBs was studied by Pulse Field Gel Electrophoresis (PFGE) and cell cycle distribution was analyzed by flow cytometry. MDA-MB-231 cells were the most sensitive to the cytotoxicity of dFdCyd (IC(50) 5 nM) then MCF-7 (IC(50) 10nM), whereas MCF-12 cells were the most resistant to the cytotoxicity of dFdCyd (IC(50) 70 nM). MCF-12 and MCF-7 cell lines did not show any radiosensitization to dFdCyd, whereas the MDA-MB-231 cells showed significantly increased radioresistant to dFdCyd at equimolar concentration (p=0.002) and at IC(50) concentration (p<0.001). The DNA double strand breaks (DSBs) repair showed that dFdCyd neither increases DNA DSBs nor decreases the rate of their repair in MCF-12 and MCF-7 cell lines, while the same treatment in MDA-MB-231 cell line led to decrease the rate of DSBs or increase the rate of DNA repair (p=0.034). Therefore, dFdCyd is a cytotoxic agent, especially in the cancer cells irrespective of having wild-type or mutated p53 protein, but it is not effective as radiosensitizer in the cell lines used in this study. dFdCyd combined with radiation reduces the efficacy of chemo-radiotherapy in p53 mutated cells. Therefore, p53-mutated cancer could be a counter-indication for radiation-gemcitabine combined treatment.

Applications of multi-nuclear magnetic resonance spectroscopy at 7T.

AIM: To discuss the advantages of ultra-high field (7T) for (1)H and (13)C magnetic resonance spectroscopy (MRS) studies of metabolism. METHODS: Measurements of brain metabolites were made at both 3 and 7T using (1)H MRS. Measurements of glycogen and lipids in muscle were measured using (13)C and (1)H MRS respectively. RESULTS: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these metabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen ((13)C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) ((1)H) following exercise and re-feeding. Glycogen levels were significantly decreased following exercise (-28% at 50% VO(2) max; -58% at 75% VO(2) max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study. CONCLUSION: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies.

Chronic pain related to first bite syndrome: report of two cases.

First bite syndrome is the classic symptomatology of pain in the parotid region that occurs in response to the first bite of a meal. We report two cases of this syndrome in patients after operations to the parapharyngeal space.

Combined internal and external Le Fort III distraction osteogenesis--the "elusive vector".

This article describes a modified surgical technique using both internal and external distractors for distraction osteogenesis at the Le Fort III level. This technique optimizes vector control, superior to single-device techniques, resulting in excellent control and, ultimately, a functional occlusion.

Acute bilateral tongue necrosis--a case report.

We report the case of an 88-year-old lady who presented with acute necrosis of the whole tongue. Giant cell arteritis was suspected, and early treatment with corticosteroids led to complete resolution and no need for further intervention. We emphasise the importance of early diagnosis of giant cell arteritis and treatment with corticosteroids to stabilise the condition and to avoid serious ocular complications.

Regional grey matter volumetric changes in forensic schizophrenia patients: an MRI study comparing the brain structure of patients who have seriously and violently offended with that of patients who have not.

BACKGROUND: The aim was to carry out the first voxel-based morphometry study of grey matter changes in the whole brain in schizophrenia associated with a history of seriously and violently offending. METHODS: Structural cerebral magnetic resonance imaging scans of 26 patients with schizophrenia were analyzed using voxel-based morphometry: 13 of the patients had seriously and violently offended directly as a result of schizophrenia prior to admission, the offences consisting of homicide, attempted murder or wounding with intent to cause grievous bodily harm; the other 13 patients did not have a history of violence. There was no history of comorbid psychoactive substance misuse disorder in any of the patients. Voxelwise generalized linear modelling was applied to the processed magnetic resonance data using permutation-based non-parametric testing, forming clusters at t > 2.3 and testing clusters for significance at p < 0.05, corrected for multiple comparisons across space. RESULTS: The two groups of patients were matched with respect to age, gender and duration of illness, but the group with a history of serious violence was on average receiving a higher dose of antipsychotic medication than the group without a history of violence. There were local regions of reduced grey matter volume in the schizophrenia patient group with a history of serious and violent offending, compared with the schizophrenia patient group without such a history. Significant voxels (p < 0.05, corrected for multiple comparisons) were noted bilaterally in the cerebellum and in BA 39 and 40. CONCLUSION: These regions are important in verbal working memory. The cerebellum may integrate inputs from ventrolateral prefrontal cortex and parietal regions, providing a corrective signal that refines the process of rehearing the contents of the phonological store. A strong connection has been hypothesized between the supramarginal region corresponding to BA 39/40 and Broca's area, which may correspond largely to the arcuate fasciculus, with the connectional pattern of the language regions of this model fitting the network of parietotemporal-prefrontal connections that participate in working memory. Therefore our results point to the possibility of an abnormality in neural circuits involved in verbal working memory in this group of patients.