Differential Photosensitivity of Fibroblasts Obtained from Normal Skin and Hypertrophic Scar Tissues.

It is unclear whether normal human skin tissue or abnormal scarring are photoreceptive. Therefore, this study investigated photosensitivity in normal skin tissue and hypertrophic scars. The expression of opsins, which are photoreceptor proteins, in normal dermal fibroblasts (NDFs) and hypertrophic scar fibroblasts (HSFs) was examined. After exposure to blue light (BL), changes in the expression levels of αSMA and clock-related genes, specifically PER2 and BMAL1, were examined in both fibroblast types. Opsins were expressed in both fibroblast types, with OPN3 exhibiting the highest expression levels. After peripheral circadian rhythm disruption, BL induced rhythm formation in NDFs. In contrast, although HSFs showed changes in clock-related gene expression levels, no distinct rhythm formation was observed. The expression level of αSMA was significantly higher in HSFs and decreased to the same level as that in NDFs upon BL exposure. When OPN3 knocked-down HSFs were exposed to BL, the reduction in αSMA expression was inhibited. This study showed that BL exposure directly triggers peripheral circadian synchronization in NDFs but not in HSFs. OPN3-mediated BL exposure inhibited HSFs. Although the current results did not elucidate the relationship between peripheral circadian rhythms and hypertrophic scars, they show that BL can be applied for the prevention and treatment of hypertrophic scars and keloids.

Risk factors associated with prognosis of patients with medication-related osteonecrosis of the jaw.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive and/or antiangiogenic agents. As the treatment application for MRONJ is controversial, we aimed to identify the risk factors for poor prognosis and to help determine appropriate management. METHODS: This study included 119 patients. Relevant clinical data were obtained for all the patients. In computed tomography images, osteosclerosis, osteolysis, cortical perforation (buccal or lingual), periosteal reaction, and sequestration were evaluated. RESULTS: Multivariate analyses showed statistically significant associations between poor prognosis in patients with MRONJ and conservative treatment alone (hazard ratio [HR] 1.89), osteolysis (HR 4.67), and the absence of sequestration (HR 5.33). CONCLUSIONS: Conservative treatment alone without clear objectives needs to be avoided, and osteolytic change could be the criteria for surgical intervention. As the boundary between the lesion and vital bone is indistinct, we recommend extensive surgery in cases with unpredictable sequestration.

Is the LRINEC score useful for predicting necrotizing fasciitis as a complication of MRONJ?

INTRODUCTION: Necrotizing fasciitis as a complication of medication-related osteonecrosis of the jaw (MRONJ), which we named "ONJ-NF", has been sometimes reported. This study aimed to investigate the usefulness of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score for predicting ONJ-NF. MATERIALS AND METHODS: We included patients with acute MRONJ who required hospitalization at a single institution from April 2013 to June 2022. They were divided into two groups: patients with ONJ-NF and those with severe cellulitis as a complication of MRONJ, which we named "ONJ-SC." LRINEC scores were compared between the groups and the cut-off value of the score was set by creating a receiver operating characteristic curve. RESULTS: Eight patients with ONJ-NF and 22 patients with ONJ-SC were included. The LRINEC score was significantly higher in patients with ONJ-NF (median: 8.0 points, range 6-10 points) than in those with ONJ-SC (median: 2.5 points, range 0-6 points). A LRINEC score of ≥ 6 points had a sensitivity of 100.0%, a specificity of 77.3%, and an area under the curve of 0.97. Among 6 parameters of LRINEC score, only C-reactive protein (CRP) and white blood cell count (WBC) had significant differences between two groups. Most of the patients with ONJ-NF were rescued by antibiotic therapy and surgical drainage including debridement of necrotic tissues, but unfortunately, one patient did not survive. CONCLUSION: Our results suggested that the LRINEC score may be a useful diagnostic tool to predict ONJ-NF but valuating only CRP and WBC may be sufficient particularly in patients with osteoporosis.

Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice.

Introduction: Occlusal disharmony induced by deteriorating oral health conditions, such as tooth loss and decreased masticatory muscle due to sarcopenia, is one of the causes of cognitive impairment. Chewing is an essential oral function for maintaining cognitive function not only in the elderly but also in young people. Malocclusion is an occlusal disharmony that commonly occurs in children. The connection between a decline in cognitive function and malocclusion in children has been shown with chronic mouth breathing, obstructive sleep apnea syndrome, and thumb/digit sucking habits. However, the mechanism of malocclusion-induced cognitive decline is not fully understood. We recently reported an association between feeding-related neuropeptides and cognitive decline in adolescent mice with activity-based anorexia. The aim of the present study was to assess the effects of malocclusion on cognitive behavior and clarify the connection between cognitive decline and hypothalamic feeding-related neuropeptides in adolescent mice with malocclusion. Methods: Four-week-old mice were randomly assigned to the sham-operated solid diet-fed (Sham/solid), sham-operated powder diet-fed (Sham/powder), or malocclusion-operated powder diet-fed (Malocclusion/powder) group. We applied composite resin to the mandibular anterior teeth to simulate malocclusion. We evaluated cognitive behavior using a novel object recognition (NOR) test, measured hypothalamic feeding-related neuropeptide mRNA expression levels, and enumerated c-Fos-positive cells in the hypothalamus 1 month after surgery. We also evaluated the effects of central antibody administration on cognitive behavior impairment in the NOR test. Results: The NOR indices were lower and the agouti-related peptide (AgRP) mRNA levels and number of c-Fos-positive cells were higher in the malocclusion/powder group than in the other groups. The c-Fos-positive cells were also AgRP-positive. We observed that the central administration of anti-AgRP antibody significantly increased the NOR indices. Discussion: The present study suggests that elevated cerebral AgRP signaling contributes to malocclusion-induced cognitive decline in adolescents, and the suppression of AgRP signaling can be a new therapeutic target against cognitive decline in occlusal disharmony.

Risk factors for pathological fracture in patients with mandibular osteoradionecrosis.

Osteoradionecrosis (ORN) often results in pathological fractures through progression. We aimed to identify the risk factors for pathological fracture in patients with mandibular ORN. Seventy-four patients with mandibular ORN were included in this retrospective study. We investigated various risk factors for pathological fracture in patients with mandibular ORN, including number of mandibular teeth with a poor prognosis each at initial evaluation before radiation therapy (RT) and when fracture occurred, and the proportion of antibiotic administration period in a follow-up duration after RT. The rate of occurrence of pathological fractures in patients with mandibular ORN was 25.7%. The median of duration between RT completion and fracture occurrence was 74.0 months. We found that pathological fracture was significantly associated with a larger number of mandibular teeth with a poor prognosis at initial evaluation before RT (P = 0.024) and when fracture occurred (P = 0.009). Especially, a larger number of mandibular teeth with P4 periodontitis, in other words severe periodontal status, was related to pathological fracture in both timings. The proportion of antibiotic administration period in a follow-up duration was also significant risk factor (P = 0.002). Multivariate analyses showed statistically significant associations between pathological fracture and a larger number of mandibular teeth with a poor prognosis when fracture occurred (hazard ratio 3.669). The patient with a larger number of mandibular teeth with P4 periodontitis may have a risk of not only occurrence of ORN but resulting in pathological fracture by accumulation of infection. Surgeons should consider extraction of those teeth regardless of before/after RT if necessary for infection control.

Relationship between oral health and prognosis in patients with empyema: Single center retrospective study with propensity score matching analysis.

BACKGROUND: Empyema is a life-threatening infection often caused by oral microbiota. To the best of our knowledge, no reports have investigated the association between the objective assessment of oral health and prognosis in patients with empyema. MATERIALS AND METHODS: A total of 63 patients with empyema who required hospitalization at a single institution were included in this retrospective study. We compared non-survivors and survivors to assess risk factors for death at three months, including the Renal, age, pus, infection, diet (RAPID) score, and Oral Health Assessment Tool (OHAT) score. Furthermore, to minimize the background bias of the OHAT high-score and low-score groups determined based on the cut-off value, we also analyzed the association between the OHAT score and death at 3 months using the propensity score matching method. RESULTS: The 3-month mortality rate was 20.6% (13 patients). Multivariate analysis showed that a RAPID score ≥5 points (odds ratio (OR) 8.74) and an OHAT score ≥7 points (OR 13.91) were significantly associated with death at 3 months. In the propensity score analysis, a significant association was found between a high OHAT score (≥7 points) and death at 3 months (P = 0.019). CONCLUSION: Our results indicated that oral health assessed using the OHAT score may be a potential independent prognostic factor in patients with empyema. Similar to the RAPID score, the OHAT score may become an important indicator for the treatment of empyema.

Hematologic and inflammatory parameters for determining severity of odontogenic infections at admission: a retrospective study.

BACKGROUND: Severe odontogenic infections in the head and neck region, especially necrotizing soft tissue infection (NSTI) and deep neck abscess, are potentially fatal due to their delayed diagnosis and treatment. Clinically, it is often difficult to distinguish NSTI and deep neck abscess in its early stage from cellulitis, and the decision to perform contrast-enhanced computed tomography imaging for detection is often a challenge. This retrospective case-control study aimed to examine the utility of routine blood tests as an adjunctive diagnostic tool for NSTI in the head and neck region and deep neck abscesses. METHODS: Patients with severe odontogenic infections in the head and neck region that required hospitalization were classified into four groups. At admission, hematologic and inflammatory parameters were calculated according to the blood test results. In addition, a decision tree analysis was performed to detect NSTI and deep neck abscesses. RESULTS: There were 271 patients, 45.4% in Group I (cellulitis), 22.5% in Group II (cellulitis with shallow abscess formation), 27.3% in Group III (deep neck abscess), and 4.8% in Group IV (NSTI). All hematologic and inflammatory parameters were higher in Groups III and IV. The Laboratory Risk Indicator for Necrotizing Fasciitis score, with a cut-off value of 6 and C-reactive protein (CRP) + the neutrophil-to-lymphocyte ratio (NLR), with a cut-off of 27, were remarkably useful for the exclusion diagnosis for Group IV. The decision tree analysis showed that the systemic immune-inflammation index (SII) of ≥ 282 or < 282 but with a CRP + NLR of ≥ 25 suggests Group III + IV and the classification accuracy was 89.3%. CONCLUSIONS: Hematologic and inflammatory parameters calculated using routine blood tests can be helpful as an adjunctive diagnostic tool in the early diagnosis of potentially fatal odontogenic infections. An SII of ≥ 282 or < 282 but with a CRP + NLR of ≥ 25 can be useful in the decision-making for performing contrast-enhanced computed tomography imaging.

Referral to Pain Specialists for Treatment of Intractable Mandibular Pain Caused by Osteonecrosis of the Jaw: A Case Series Report.

Pain is a problematic symptom in patients with osteonecrosis of the jaws (ONJ). Effective pain management in patients with advanced ONJ still remains an unresolved issue. This case series report presents three patients who were referred to the pain clinic for treatment of intractable pain caused by ONJ. Two patients received mandibular nerve blocks and achieved pain relief. After referral to the pain clinic, these two patients underwent segmental mandibulectomy for ONJ. In the third patient, the effect of pain control was limited. Appropriate cooperation between the oral and maxillofacial surgeon and the pain specialist is essential for pain management in patients with advanced ONJ who experience intense pain.

Factors Associated with Treatment Outcomes and Pathological Features in Patients with Osteoradionecrosis: A Retrospective Study.

A standard treatment for osteoradionecrosis (ORN) has not yet been established because of the diversity. Therefore, identifying the risk factors for a poor prognosis is essential. This study retrospectively investigated the factors associated with the prognosis of ORN in 68 patients. Relevant clinical data of all patients were obtained. Of the patients, 16 who underwent extensive surgery underwent histopathological analysis. The necrotic changes of the anterior and posterior margins in the cortical and cancellous bones were investigated. Multivariate analyses showed statistically significant associations between poor prognosis in patients with ORN and high radiation dose (hazard ratio [HR] 1.15), orocutaneous fistula (HR 2.93), and absence of sequestration (HR 2.49). Histopathological analysis showed a viable anterior margin of the middle portion of the cortical bone for all recovered cases; in contrast, most cases (75%) with a poor prognosis showed necrotic changes. The anterior margin of the cancellous bone was viable and resilient to high irradiation, regardless of the prognosis. These results suggest that patients with orocutaneous fistula should receive early surgical intervention, even if the affected area is limited or asymptomatic. In extensive surgery, a sufficient safety margin of necrotic bone, particularly in the anterior region, is required to improve the prognosis.

Strategy for preventing skin paddle necrosis in mandibular reconstruction with free fibula osteocutaneous flap.

BACKGROUND: Non-thrombotic skin paddle necrosis occasionally occurs during mandibular reconstructions with free fibula osteocutaneous flaps. The number of perforators, size of the skin paddle, and ischemia time of the flap are considered as causes of skin paddle necrosis. The importance of donor side selection has also been highlighted. This study aimed to investigate the leading cause of skin paddle necrosis and the optimal reconstructive procedure. METHODS: A total of 66 patients who underwent mandibular reconstruction using a free fibula osteocutaneous flap were retrospectively analyzed. Skin paddle necrosis, number of cutaneous perforators, size of the skin paddle, and ischemia time of the flap were investigated. An incorrect "laterality" was defined as a skin paddle (septum) covering the reconstruction plate. Donor-site morbidity was recorded. RESULTS: Skin paddle necrosis occurred in 15.2% of patients. An incorrect laterality was associated with a higher incidence of skin paddle necrosis (odds ratio, 22.0; 95% confidence interval, 2.5-195; p = .005). Donor-site morbidity was noted in 18.8% of the patients, without any significant difference in terms of the donor side with and without skin graft (p = .592). The postoperative activities of daily living were not affected. CONCLUSIONS: To prevent skin paddle necrosis, donor side selection is an important safety strategy during mandibular reconstruction with free fibula osteocutaneous flap. The postoperative activities of daily living were found to be little affected by differences in the donor side.

Risk factors associated with post-extraction bleeding in patients on warfarin or direct-acting oral anticoagulants: a retrospective cohort study.

PURPOSE: The purpose of this study was to investigate the risk factors associated with post-extraction persistent bleeding in patients on warfarin or direct-acting oral anticoagulants (DOACs) and the ability of risk scores to predict post-extraction bleeding. METHODS: Three hundred ninety-one patients taking warfarin or DOACs underwent tooth extractions. Various risk factors for post-extraction bleeding, including number of tooth extraction, with antiplatelet therapy, and risk scores, were investigated by univariate and multivariate analyses. A post-extraction bleeding was classified into grades 1-3. RESULTS: The incidence of post-extraction bleeding was 26.8% (77 out of 287 patients; grade 1: 63, grade 2:14) in patients taking warfarin, and 26.0% (27 out of 104 patients; grade 1: 20, grade 2:7) in patients taking warfarin DOACs. Multivariate analyses showed that multiple teeth extractions and HAS-BLED scores (above 3 points) in patients taking warfarin, and only multiple teeth extractions in patients taking DOAC, were significantly associated with post-extraction bleeding, respectively. CONCLUSION: Most of the post-extraction bleedings were grade 1, which can be stopped by eligibly pressing gauze by surgeons. If patients taking anticoagulants are scheduled to undergo multiple teeth extractions or their HAS-BLED score are above 3 points (if warfarin), we recommend informing patients risk of post-extraction bleeding before operation, taking carefully hemostasis, and instructing patients to bite down accurately on the gauze for longer than usual.

The characteristics of oro-cervical necrotizing fasciitis-Comparison with severe cellulitis of oro-cervical region and necrotizing fasciitis of other body regions.

BACKGROUND: Necrotizing fasciitis (NF) is an acute and life-threatening soft-tissue infection however rarely seen in oro-cervical region. Therefore, the details of oro-cervical NF (OCNF) are not well known. The purpose of this study was to investigate the characteristics of OCNF by comparing it with severe cellulitis of oro-cervical region (OCSC) or NF of other body regions (e.g., limb, perineum, and trunk) (BNF), respectively. MATERIALS AND METHODS: At first, various risk factors for OCNF in oro-cervical severe infection (OCSI; composed of OCNF and OCSC), including neutrophil-to-lymphocyte ratio (NLR) and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, were investigated by univariate and multivariate analyses. Next, the differences between OCNF and BNF, including inflammatory markers and mortality, were investigated. RESULTS: In the present study, 14 out of 231 OCSI patients had OCNF. Multivariate analyses of OCSI patients showed that NLR ≥15.3 and LRINEC score ≥6 points were significantly related to OCNF. During the same period, 17 patients had BNF. The OCNF group had significantly higher inflammatory markers than the BNF group when diagnosis, but significantly lower clinical stages at the time and mortality as outcomes. CONCLUSION: We found that compared to BNF, OCNF can be detected at lower clinical stage by using indexes, such as NLR and LRINEC score, besides clinical findings, which may help contributing to patient's relief.

Bacterial Colonization of the Condyle in Patients with Advanced Mandibular Osteoradionecrosis: Analysis of Hemimandibulectomy Specimens.

Advanced mandibular osteoradionecrosis (ORN) sometimes requires extended resection (e.g., hemimandibulectomy). Bacterial infection contributes to ORN pathogenesis. To control infection and determine the extent of debridement required, an understanding of bacterial spread within sites of mandibular ORN is important. The current study used a histopathological approach to assess bacterial colonization in the mandibular condyle and elucidate possible paths of bacterial spread towards the mandibular condyle. Four hemimandibulectomy specimens were selected. Areas of bone destruction were macroscopically assessed and confirmed using hematoxylin and eosin staining. Bacterial presence within mandibular condyle was confirmed with Gram staining. Bone exposure was observed in the molar area in all specimens. Macroscopic bone destruction was apparent especially near the medial side of the cortical wall. Gram staining revealed bacterial colonization of the mandibular condyle in three of the four specimens. In conclusion, bacteria tended to spread posteriorly and through the medial side of the mandibular cortical wall. In patients with advanced ORN, the potential for bacterial colonization of the mandibular condyle should be considered during treatment.

Peripheral facial nerve schwannoma at the inferior mandibular margin: a case report.

Schwannomas commonly occur in the head and neck region as acoustic neuromas. Facial nerve schwannomas are rare and usually occur in the temporal region. A 57-year-old woman presented with a mass at the right mandibular margin. Magnetic resonance imaging revealed a schwannoma located immediately caudal to the mental foramen. We were initially uncertain whether it arose from the trigeminal nerve or the facial nerve. Excision was performed under general anesthesia. The mass was encapsulated and easily detached from the surrounding tissue. The nerve of origin was identified proximal to the tumor. A facial nerve origin was confirmed as the muscles supplied by the marginal mandibular branch of the facial nerve moved on nerve stimulation. Nerve fibers were not found distal to the tumor, possibly because they had been cut during excision. We believe that this is the first report of a schwannoma arising from the peripheral facial nerve.

Occurrence and Treatment Outcome of Late Complications After Free Fibula Flap Reconstruction for Mandibular Osteoradionecrosis.

PURPOSE: This study aimed to evaluate the occurrence and treatment outcome of late complications after free fibula osteocutaneous flap reconstruction for mandibular osteoradionecrosis (ORN). METHODS: We enrolled 15 consecutive patients (14 men, one woman; median age 65 years, range 57-80 years) who underwent free fibula reconstruction for advanced mandibular ORN during 2013-2017 with two or more years of follow-up. Late complications included infection, plate exposure, and recurrence at the resection margin. The effect of perioperative antibiotic administration on late complications was also assessed. RESULTS: Late complications occurred in 33.3% (5/15) of patients, including two infections (local and distant), two plate exposures, and two recurrences (plate exposure and recurrence occurred in one patient). Perioperative antibiotic administration duration did not significantly affect the occurrence of postoperative late complications. All late complications were treated without problems. CONCLUSIONS: Late complications after ORN reconstructive surgery are not uncommon, but can be treated properly.

Wire Myography for Continuous Estimation of the Optimal Concentration of Topical Lidocaine as a Vasodilator in Microsurgery.

BACKGROUND: Intraoperative vasospasm during reconstructive microvascular surgery is often unpredictable and may lead to devastating flap loss. Therefore, various vasodilators are used in reconstructive microsurgery to prevent and relieve vasospasm. Lidocaine is a vasodilator commonly used in microvascular surgery. Although many reports have described its in vitro and in vivo concentration-dependent vasodilatory effects, limited studies have examined the pharmacological effects of lidocaine on blood vessels in terms of persistence and titer. METHODS: In this study, the vasodilatory effect of lidocaine was examined by using the wire myograph system. Abdominal aortas were harvested from female rats, sliced into rings of 1-mm thickness, and mounted in the wire myograph system. Next, 10, 5, 2, and 1% lidocaine solutions were applied to the artery, and the change in vasodilation force, persistence of the force, and time required to reach equilibrium were measured. RESULTS: The vasodilatory effect was confirmed in all groups following lidocaine treatment. Although strong vasodilation was observed in the 10% lidocaine group, it was accompanied by irreversible degeneration of the artery. Vasodilation in the 1% lidocaine group was weaker than that in the other groups 500 seconds after lidocaine addition (p < 0.05). Between the 5 and 2% lidocaine groups, 5% lidocaine showed a stronger vasodilatory effect 400 to 600 seconds after lidocaine addition (p < 0.01); however, there was no significant difference in these groups after 700 seconds. Additionally, there was no difference in the time required for the relaxation force to reach equilibrium among the 5, 2, and 1% lidocaine groups. CONCLUSION: Although our study confirmed the dose-dependent vasodilatory effect of lidocaine, 5% lidocaine showed the best vasodilatory effect and continuity with minimal irreversible changes in the arterial tissue.

Effect of educational intervention on the appropriate use of oral antimicrobials in oral and maxillofacial surgery: a retrospective secondary data analysis.

BACKGROUND: In Japan, oral third-generation cephalosporins with broad-spectrum activity are commonly prescribed in the practices of dentistry and oral surgery. However, there are few reports on the appropriate use of antibiotics in the field of oral surgery. This study aimed to evaluate the appropriateness of antibiotic use before and after an educational intervention in the Department of Oral and Maxillofacial Surgery, Kobe University Hospital. METHODS: The use of oral antibiotics was investigated among inpatients and outpatients before and after an educational intervention conducted by the antimicrobial stewardship team. Additionally, the frequency of surgical site infection after the surgical removal of an impacted third mandibular molar under general anesthesia and the prevalence of adverse effects of the prescribed antibiotics were comparatively evaluated between 2013 and 2018. RESULTS: After the educational intervention, a remarkable reduction was noted in the prescription of oral third-generation cephalosporins, but increased use of penicillins was noted among outpatients. There was reduced use of macrolides and quinolones in outpatients. Although a similar trend was seen for inpatients, the use of quinolones increased in this population. Despite the change in the pattern of antibiotic prescription, inpatients who underwent mandibular third molar extraction between 2013 and 2018 did not show a significant increase in the prevalence of surgical site infections (6.2% vs. 1.8%, p = .336) and adverse effects of drugs (2.1% vs. 0%, p = .466). CONCLUSIONS: This study suggests that the judicious use of oral antibiotics is possible through conscious and habitual practice of appropriate antibiotic use. However, further investigation is required to develop measures for appropriate use of oral antibiotics.

Does prophylactic antibiotic administration for tooth extraction affect PT-INR in patients taking warfarin?

BACKGROUND: Various antibiotics and analgesics have been reported to interact with warfarin. Reports that investigate the effects of medication taken for just a few days during tooth extraction on the prothrombin time-international normalized ratio are rare. METHODS: A total of 110 patients receiving long-term stable warfarin therapy underwent tooth extraction without interruption of warfarin treatment. INR values were measured 1 month before the tooth extraction, the day of the extraction, and 1 week after the extraction. We investigated the changes in INR values between the day of extraction and 1 week after extraction, as well as the various risk factors for increases in INR values. RESULTS: Before and after tooth extraction, the number of patients taking cefcapene pivoxil, amoxicillin, and azithromycin was 57, 36, and 8, respectively. Nine patients were administered ampicillin before tooth extraction and received amoxicillin after their tooth extraction. One week after tooth extraction, the INR values increased beyond the therapeutic range in 3 out of 110 patients (2.7%). The INR values before tooth extraction in these three patients were close to 3.0. The INR value increased by more than twice as much in 1 out of 110 patients (0.9%). CONCLUSION: Our results suggest that prophylactic antibiotic administration has little effect on INR values when patients on stable warfarin therapy undergo tooth extraction. Surgeons have to take attention if the patients whose INR values are close to 3.0 before their extraction.