Medication-related osteonecrosis of the jaw (MRONJ) systemic review: mevalonate pathway mechanisms explored.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but devastating condition caused by bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, anti-angiogenic medications, and disease-modifying antirheumatic drugs. While the clinical spectrum of MRONJ has a wide range, there is a subgroup of patients that do not improve with antibiotics and conservative surgical debridement resulting in pathologic fractures, draining fistulas, and/or osteomyelitis. For the severely affected individuals, the only cure is surgical resection with micro-vascular free flap reconstruction. The etiology of MRONJ is unknown because of the lack of understanding of the biological underpinnings of the disorder connected to the mechanisms of action of the various medications. This limited knowledge has resulted in the classification of patients by clinical presentation rather than underlying pathology. Therefore, the aim of this article is to present a mechanistic framework of MRONJ through the mevalonate pathway in the context of the medications that are known to induce it and explore potential novel therapeutics.

Dental Trauma and Alveolar Fractures.

A dentoalveolar fracture requires thorough clinical and radiographic examination for an accurate diagnosis to guide appropriate treatment. Dentoalveolar fractures can be classified into the following 4 groups: (1) crown/root fractures, (2) luxation/displacement of teeth, (3) avulsion, and (4) alveolar fractures. Treatment can be divided into nonrigid fixation (splinting with wires and composite) and/or rigid fixation (Erich arch bars, Risdon cable wires) depending on the extent of dentoalveolar fractures. Special considerations must be made for primary teeth and mixed dentition to avoid injuring tooth buds and arising permanent dentition.

Investigation of chemical reactivity of 2-alkoxy-1,4-naphthoquinones and their anticancer activity.

To establish the structure-activity relationship of 5-hydroxy-1,4-naphthoquinones toward anticancer activity, a series of its derivatives were prepared and tested for the activity (IC50 in µM) against three cell lines; colo205 (colon adenocarcinoma), T47D (breast ductal carcinoma) and K562 (chronic myelogenous leukemia). Among them 2 (IC50: 2.3; 2.0; 1.4 µM), 6 (IC50: 1.9; 2.2; 1.3 µM), 9 (IC50: 0.7; 1.7; 0.9 µM) and 10 (IC50:1.7; 1.0; 1.2 µM) showed moderate to excellent activity. Our perception toward the DNA substitution of alkoxy groups at the C2 position of these naphthoquinones for the anticancer activity led us to investigate their reactivity of substitution toward dimethylamine as a nucleophile. The ease of the substitution of alkoxy groups at the C2 position with dimethylamine is strongly accelerated by hydroxyl group at C5 position and is well correlated with the found anticancer activity results.

Identification of novel 2-benzyl-1-indanone analogs as interleukin-5 inhibitors.

A novel series of 2-benzyl-1-indanone analogs were investigated as IL-5 inhibitory activity. Among the synthesized compounds, 7-(cyclohexylmethoxy)-2-(4-hydroxybenzyl)-2,3-dihydro-1H-inden-1-one (7s, 100.0% inhibition at 30 µM, IC50 = 4.0 µM), and 7-(cyclohexylmethoxy)-2-(3-hydroxybenzyl)-2,3-dihydro-1H-inden-1-one (7t, 95.0% inhibition at 30 µM, IC50 = 6.0 µM) showed the best inhibitory activity against IL-5. The 2-benzyl-1-indanone analogs showed moderate to strong IL-5 inhibitory activity. Especially, hydroxyl (HBD/HBA) substituent at position 3 or 4 on phenyl ring B showed potent IL-5 inhibition. Additionally, the bulky hydrophobic cyclohexylmethoxy group at position 7 of the 1-indanone ring is favorable for the inhibitory activity.

Surgery of the head and neck in patient with Kniest dysplasia: Is wound healing an issue?

Kniest dysplasia is a type II collagen disorder that arises from a genetic mutation of the COL2A1 gene that results in short stature, midface anomalies, tracheomalacia, and hearing loss. Disruption of the normal collagen pathway can lead to many changes given its critical role in the body, and can cause complications with respect to wound healing. We present a case in which a patient with Kniest dysplasia successfully underwent multiple procedures in the head and neck region including cochlear implantation, mandibular distraction, palatoplasty, and laryngotracheal reconstruction. All procedures did not have any associated complications with respect to wound healing, indicating that surgery in this population can take place as indicated and surgery should not be contraindicated or delayed.

Does the Age of a Patient Affect the Outcome of Temporomandibular Joint Arthroscopic Surgery?

PURPOSE: Although temporomandibular joint (TMJ) disorders encompass all age groups, it is generally considered to affect young to middle-age adults. The aim of this investigation was to study patients who met the criteria for TMJ arthroscopy and to determine whether there was a difference in outcomes between younger and older patients. MATERIALS AND METHODS: This was a retrospective chart review of patients who underwent TMJ operative arthroscopy. The primary variable studied was patient age. Major outcome variables included changes in subjective pain measured by a visual analog scale (VAS) and changes in maximum interincisal opening (MIO) after arthroscopic surgery. Other variables of interest included the presence of systemic disease, synovitis, and osteoarthritis diagnosed arthroscopically. Data analysis included the Student t test, regression analysis (R Studio, Boston, MA), and χ2 test with a P value less than .05 indicating statistical significance. RESULTS: The study population consisted of 103 patients diagnosed with internal derangement and severe inflammatory or degenerative TMJ disease (Wilkes stages II to V) who underwent operative arthroscopy. Patients were divided into 2 groups based on age (group Y, <40 yr old, n = 51, mean age, 26 yr; group O, >40 yr old, n = 52, mean age, 56 yr). The presence of osteoarthritis diagnosed arthroscopically was significantly greater in group O than in group Y (P < .01). There was significant postoperative improvement in pain (VAS) and MIO in group Y (P < .01) and group O (P < .01). Although the 2 groups showed substantial improvement after arthroscopy, when comparing differences in outcomes between the groups, the absolute postoperative pain level for group O was significantly lower than for group Y (P < .05). Comparison of postoperative MIO did not show a significant difference between group Y and group O (P = .286). CONCLUSIONS: Groups Y and O showed substantial improvement in pain (VAS) and mandibular mobility (MIO) after surgical TMJ arthroscopy. Group O had a higher prevalence of arthroscopically diagnosed osteoarthritis and lower postoperative pain levels compared with group Y. Older patients with advanced TMJ disease responded well to TMJ arthroscopy.

Minimally Invasive Treatment of Temporomandibular Joint Ankylosis and Fibrosis of Temporalis Muscle.

A case of severe mandibular hypomobility due to fibrosis of the left temporalis tendon, combined with ankylosis of the temporomandibular joint, is presented. This case emphasizes the importance of reconstructing the historical timeline to establish a correct diagnosis, ultimately leading to appropriate treatment. The use of minimally invasive surgical techniques and the importance of postoperative rehabilitation are emphasized.

Retinal ganglion cell layer thickness and local visual field sensitivity in glaucoma.

OBJECTIVE: To compare loss in sensitivity measured using standard automated perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured using frequency-domain optical coherence tomography in the macula of patients with glaucoma. METHODS: To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC+IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC+IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea. RESULTS: The RGC+IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman ρ = 0.71-0.74). Agreement was worse (0.53-0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC+IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°. CONCLUSION: In the central 7.2°, local RGC+IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement.

[Effects of breast massage on breast pain, breast-milk sodium, and newborn suckling in early postpartum mothers].

PURPOSE: In this study the effects of breast massage on breast pain, breast-milk sodium, and newborn suckling in early postpartum mothers were investigated. METHODS: The design was a non-synchronized nonequivalent control group pretest-posttest design. Sixty postpartum mothers who were admitted to a postpartum care center and had problems with breastfeeding were recruited. Of these mothers, 44 were assigned to the intervention group and received two 30-minute breast massages within 10 days of postpartum period. The others were assigned control group and received only routine care. Breast pain was measured using a numeric pain scale and number of times newborns suckled was observed throughout breastfeeding. Breast milk was self-collected to evaluate breast-milk sodium. RESULTS: Mean age of postpartum mothers was 30 years old. Compared to the control group, women in the intervention group reported significant decreases in breast pain (p<.001), increases in number of times newborns suckled after the first and second massage (p<.001), and a decrease in breast-milk sodium after the first massage (p=.034). CONCLUSION: Breast massage may have effects on relieving breast pain, decreasing breast-milk sodium, and improving newborn suckling. Breast massage can be used to solve breast problems. Further research is needed to validate our findings.

Reliability of a computer-aided manual procedure for segmenting optical coherence tomography scans.

PURPOSE: To assess the within- and between-operator agreement of a computer-aided manual segmentation procedure for frequency-domain optical coherence tomography scans. METHODS: Four individuals (segmenters) used a computer-aided manual procedure to mark the borders defining the layers analyzed in glaucoma studies. After training, they segmented two sets of scans, an Assessment Set and a Test Set. Each set had scans from 10 patients with glaucoma and 10 healthy controls. Based on an analysis of the Assessment Set, a set of guidelines was written. The Test Set was segmented twice with a ≥1 month separation. Various measures were used to compare test and retest (within-segmenter) variability and between-segmenter variability including concordance correlations between layer borders and the mean across scans (n = 20) of the mean of absolute differences between local border locations of individual scans, MEAN{mean( ΔLBL )}. RESULTS: Within-segmenter reliability was good. The mean concordance correlations values for an individual segmenter and a particular border ranged from 0.999 ± 0.000 to 0.978 ± 0.084. The MEAN{mean( ΔLBL )} values ranged from 1.6 to 4.7 µm depending on border and segmenter. Similarly, between-segmenter agreement was good. The mean concordance correlations values for an individual segmenter and a particular border ranged from 0.999 ± 0.001 to 0.992 ± 0.023. The MEAN{mean( ΔLBL )} values ranged from 1.9 to 4.0 µm depending on border and segmenter. The signed and unsigned average positions were considerably smaller than the MEAN{mean( ΔLBL )} values for both within- and between-segmenter comparisons. Measures of within-segmenter variability were only slightly larger than those of between-segmenter variability. CONCLUSIONS: When human segmenters are trained, the within-and between-segmenter reliability of manual border segmentation is quite good. When expressed as a percentage of retinal layer thickness, the results suggest that manual segmentation provides a reliable measure of the thickness of layers typically measured in studies of glaucoma.

Measurement of local retinal ganglion cell layer thickness in patients with glaucoma using frequency-domain optical coherence tomography.

OBJECTIVE: To explore the feasibility of obtaining a local measurement of the thickness of the retinal ganglion cell layer in patients with glaucoma using frequency-domain optical coherence tomography (fdOCT) and a computer-aided manual segmentation procedure. METHODS: The fdOCT scans were obtained from the horizontal midline for 1 eye of 26 patients with glaucoma and 20 control subjects. The thickness of various layers was measured with a manual segmentation procedure aided by a computer program. The patients were divided into low- and high-sensitivity groups based on their foveal sensitivity on standard automated perimetry. RESULTS: The RGC plus inner plexiform and the retinal nerve fiber layers of the low-sensitivity group were significantly thinner than those of the high-sensitivity group. While these layers were thinner in the patients than the controls, the thicknesses of inner nuclear layer and receptor layer were similar in all 3 groups. Further, the thinning of the retinal ganglion cell plus inner plexiform layer in 1 glaucoma-affected eye showed qualitative correspondence to the loss in 10-2 visual field sensitivity. CONCLUSIONS: Local measures of RGC layer thickness can be obtained from fdOCT scans using a manual segmentation procedure, and these measures show qualitative agreement with visual field sensitivity.