Objectives: . Facial nerve monitoring (FNM) can be used to identify the facial nerve, to obtain information regarding its course, and to evaluate its status during parotidectomy. However, there has been disagreement regarding the efficacy of FNM in reducing the incidence of facial nerve palsy during parotid surgery. Therefore, instead of using electromyography (EMG) to identify the location and state of the facial nerve, we applied an intraoperative neuromonitoring (IONM) system using a surface pressure sensor to detect facial muscle twitching. The objective of this study was to investigate the feasibility of using the IONM system with a surface pressure sensor to detect facial muscle twitching during parotidectomy. Methods: . We evaluated the stimulus thresholds for the detection of muscle twitching in the orbicularis oris and orbicularis oculi, as well as the amplitude and latency of EMG and the surface pressure sensor in 13 facial nerves of seven rabbits, using the same stimulus intensity. Results: . The surface pressure sensor detected muscle twitching in the orbicularis oris and orbicularis oculi in response to a stimulation of 0.1 mA in all 13 facial nerves. The stimulus threshold did not differ between the surface pressure sensor and EMG. Conclusion . The application of IONM using a surface pressure sensor during parotidectomy is noninvasive, reliable, and feasible. Therefore, the IONM system with a surface pressure sensor to measure facial muscle twitching may be an alternative to EMG for verifying the status of the facial nerve.

BACKGROUND: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. METHODS: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. RESULTS: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. CONCLUSION We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

Background: Patients with chronic kidney disease (CKD) are at a high risk of stroke-related morbidity, mortality, and bleeding. However, the overall risk/benefit of anticoagulant therapy among patients with CKD remains unclear. Methods: The MEDLINE, EMBASE, and CENTRAL databases were comprehensively searched until July 31, 2020, to investigate the safety and efficacy of apixaban in patients with stage 4 or 5 CKD, as compared with warfarin. The primary outcome was an incidence of major bleeding. Secondary outcomes included composite bleeding (major, clinically relevant, and minor bleeding), venous thromboembolism (VTE), stroke, and death. Results: In total, seven studies consisting of 10,816 patients were included. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding (OR 0.49, 95% CI 0.41-0.58). In terms of composite bleeding, apixaban tended to pose a significantly lower risk than warfarin (OR 0.51, 95% CI 0.37-0.71). There was no difference between apixaban and warfarin with respect to the risk of stroke or death (stroke: OR 1.23, 95% CI 0.49-3.12; death: OR 0.73, 95% CI 0.45-1.18). Conclusion Among patients with stage 4 or 5 CKD, the use of apixaban was associated with a lower risk of bleeding compared to warfarin and was also found to pose no excess risk of thromboembolic events.

Background: Patients with chronic kidney disease (CKD) are at a high risk of stroke-related morbidity, mortality, and bleeding. However, the overall risk/benefit of anticoagulant therapy among patients with CKD remains unclear. Methods: The MEDLINE, EMBASE, and CENTRAL databases were comprehensively searched until July 31, 2020, to investigate the safety and efficacy of apixaban in patients with stage 4 or 5 CKD, as compared with warfarin. The primary outcome was an incidence of major bleeding. Secondary outcomes included composite bleeding (major, clinically relevant, and minor bleeding), venous thromboembolism (VTE), stroke, and death. Results: In total, seven studies consisting of 10,816 patients were included. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding (OR 0.49, 95% CI 0.41-0.58). In terms of composite bleeding, apixaban tended to pose a significantly lower risk than warfarin (OR 0.51, 95% CI 0.37-0.71). There was no difference between apixaban and warfarin with respect to the risk of stroke or death (stroke: OR 1.23, 95% CI 0.49-3.12; death: OR 0.73, 95% CI 0.45-1.18). Conclusion Among patients with stage 4 or 5 CKD, the use of apixaban was associated with a lower risk of bleeding compared to warfarin and was also found to pose no excess risk of thromboembolic events.

BACKGROUND: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. METHODS: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. RESULTS: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. CONCLUSION We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

Background: Micropigmentation is a medical tattooing procedure in which pigments are implanted into the superficial dermis using a manual or electrically driven needle. Objective: We aimed to assess the benefit and risk of micropigmentation in the treatment of acral vitiligo refractory to the conventional treatment. Methods: An open-label study was conducted from December 2018 to March 2019. A total of 12 patients with 20 acral vitiligo lesions were treated with micropigmentation using an electric tattooing machine. The micropigmentation treatment was repeated for a few sessions to achieve optimal pigmentation. Color matching between the lesion and peri-lesional skin was assessed using a 4-point grading scale (poor, fair, good, and excellent). Results: Overall, 85% (17 of 20) showed excellent color matching after a median of 2 (range: 1∼5) treatment sessions. The post-treatment color was darker than the surrounding skin immediately after the procedure, but it gradually faded over time. Pain during the procedure was not mild, but local anesthetic injection was not required. Post-treatment erythema and swelling occurred, but they resolved within a few days. No allergic reaction to the pigment or koebnerization of the vitiligo was noted. Conclusion Micropigmentation could be a promising treatment option for refractory acral vitiligo. A few treatment sessions (i.e., retouch) may be required for desired outcomes. The crucial parts of micropigmentation are pigment selection and implantation depth. It does not require injection of local anesthetics and provides immediate treatment effects after the procedure.

Background: The indication of denosumab for osteoporosis was expanded from second-line to first-line therapy in 2019. The aim of this study was to evaluate the efficacy of denosumab as both first- and second-line therapy in postmenopausal women with osteoporosis and osteopenia with risk factors by using the Fracture Risk Assessment Tool (FRAX). Methods: We conducted a medication use evaluation of denosumab in 98 patients who had been treated three or more times for osteoporosis or osteopenia at Chungnam National University Hospital from July 1st , 2017 to January 31st , 2020. Risk factors were identified using quantitative Ngram analyses of FRAX estimations. Patient information, including menopause status and results of bone mineral density tests (Tscore), was obtained from electronic medical records. Results: Age, body mass index (BMI), prior medication use, and T-score were identified as risk factors and were included as variables in the evaluation of denosumab use. Since no significant differences were detected between groups, denosumab is likely effective regardless of age or BMI. In addition, no significant difference was detected in T-scores following denosumab treatment, between groups who took bisphosphonates and selective estrogen receptor modulators (SERMs) with denosumab as first-line therapy for postmenopausal osteoporosis. Denosumab may, therefore, be effective as second-line therapy. Conclusion Efficacy of denosumab was evaluated in postmenopausal women with osteoporosis.Denosumab may be used as first- and second-line therapy regardless of age, BMI, and prior use of bisphosphonates and SERMs.

Background: The indication of denosumab for osteoporosis was expanded from second-line to first-line therapy in 2019. The aim of this study was to evaluate the efficacy of denosumab as both first- and second-line therapy in postmenopausal women with osteoporosis and osteopenia with risk factors by using the Fracture Risk Assessment Tool (FRAX). Methods: We conducted a medication use evaluation of denosumab in 98 patients who had been treated three or more times for osteoporosis or osteopenia at Chungnam National University Hospital from July 1st , 2017 to January 31st , 2020. Risk factors were identified using quantitative Ngram analyses of FRAX estimations. Patient information, including menopause status and results of bone mineral density tests (Tscore), was obtained from electronic medical records. Results: Age, body mass index (BMI), prior medication use, and T-score were identified as risk factors and were included as variables in the evaluation of denosumab use. Since no significant differences were detected between groups, denosumab is likely effective regardless of age or BMI. In addition, no significant difference was detected in T-scores following denosumab treatment, between groups who took bisphosphonates and selective estrogen receptor modulators (SERMs) with denosumab as first-line therapy for postmenopausal osteoporosis. Denosumab may, therefore, be effective as second-line therapy. Conclusion Efficacy of denosumab was evaluated in postmenopausal women with osteoporosis.Denosumab may be used as first- and second-line therapy regardless of age, BMI, and prior use of bisphosphonates and SERMs.