Lateral Distance From the Osteotomy Hinge Point to the Tibial Cortex Is Associated With Lateral Hinge Fracture Type and Fracture Occurrence Time After Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To verify whether the distance from the hinge point to the tibial cortex affects the occurrence time and characteristics of the lateral hinge fracture (LHF) in medial open-wedge high tibial osteotomy. METHODS: We retrospectively reviewed 171 knees in 171 patients (121 women, 50 men; mean age, 53.9 years; range, 36-67 years) who had undergone medial open-wedge high tibial osteotomy with locking plate fixation between January 2011 and December 2020. Osteotomy hinge point and LHFs were identified on intraoperative fluoroscopy and immediate postoperative radiographs. LHF type was classified as suggested by Takeuchi et al. Acute fracture was defined as a fracture that occurred during surgery, and delayed fracture was defined as a fracture observed after 1 month postoperatively. The nearest distances from osteotomy hinge point to lateral, distal, and proximal cortex were measured on postoperative radiographs. We compared the distance between the different types and between acute and delayed LHFs. RESULTS: There were 55 LHFs (32%) (type I, 40 knees; type II, 14 knees; type III, 1 knee) that occurred acutely in 41 knees and were found as delayed fractures in 14 knees. The patient demographics were not significantly different between non-LHFs and each type of LHFs. Proximal and distal distances were not statistically different among fracture types and between occurrence times. However, lateral distances were significantly shorter in type I LHFs (6.2 ± 1.8 mm) and longer in type II LHFs (9.3 ± 2.3 mm) than in non-LHFs (7.1 ± 2.7 mm) (P = .020 and .004, respectively). The lateral cortical distances were also different between acute LHFs (6.4 ± 1.9 mm) and delayed LHF (9.0 ± 2.7 mm) (P < .001). In the case of fracture type, the frequency of type I decreases with increase in the lateral distance, whereas that of type II increases with increase in the lateral cortical distance. In acute fracture, type I was dominant (85.4%), whereas in delayed fracture, type II was dominant (57.2%). CONCLUSIONS: The lateral cortical distance from the hinge point was significantly associated with LHF occurrence. Shorter distance increased the risk for acute type I LHF, whereas longer distance increased the risk for delayed type II LHFs. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Lateral Meniscal Allograft Transplantation Shows a Long-Term Chondroprotective Effect on Quantitative MRI T2 Mapping at 7 Years' Minimum Follow-Up.

PURPOSE: The purpose of this study was to assess the long-term chondroprotective effect of lateral meniscal allograft transplantation (MAT) using quantitative magnetic resonance imaging (MRI) T2 mapping. METHODS: In patients who underwent isolated lateral MAT, quantitative MRI T2 mapping was conducted preoperatively and postoperatively with at minimum follow-up of 7 years to assess the articular cartilage status. On the sagittal section image bisecting the lateral femoral condyle, the weight-bearing portions of the femoral and tibial articular cartilage were divided into 3 segments each-6 segments in total-based on the meniscal coverage area. The regions of interest analysis were performed on the 6 segments to measure the mean T2 value. Then, the whole layer was divided into deep and superficial layers for further zonal analysis. The longitudinal change in T2 values was statistically analyzed using paired t-tests. Clinical outcome was evaluated using the Lysholm score. RESULTS: A total of 31 patients were included in the study, with the MRI follow-up period of a minimum follow-up of 7 years (mean: 8.9 ± 1.3 years; range: 7.0-11.2 years). The mean T2 value of the whole layer showed significant improvement in all segments of the femoral cartilage and the posterior segment of tibial cartilage. In the zonal analysis, the mean T2 value of the tibial cartilage showed significant improvement in the superficial layer of the mid to posterior portion, while the deep layer remained stable. In contrast, the mean T2 value of the femoral cartilage showed significant improvement in the superficial and deep layers in all segments. The mean Lysholm score significantly improved from 62.6 ± 12.8 to 90.9 ± 10.5 (P < .001). CONCLUSION: This study suggests that MAT appears to have a long-term chondroprotective effect on the articular cartilage as judged by quantitative T2 mapping. LEVEL OF EVIDENCE: Level Ⅳ, case series.

Tear patterns and locations are different between lateral and medial compartments in patients with early anatomical failure after meniscal allograft transplantation.

PURPOSE: To investigate the characteristics of anatomically failed grafts within 1 year after meniscal allograft transplantation (MAT) and compare the differences between lateral and medial MATs. METHODS: The records of consecutive patients with anatomically failed grafts within 1 year after primary MAT between 2005 and 2018 were reviewed. Anatomical failure was defined as a tear covering > 50% of the allograft or an unstable peripheral rim. The pattern and location of the graft tears were analyzed using magnetic resonance imaging or arthroscopy. RESULTS: A total of 21 patients were included. All 21 patients had anatomical failure with tears involving > 50% of the allograft, whereas 15 had an unstable peripheral rim of the allograft. The mean failure time was 6.6 ± 3.6 months in all patients (lateral MAT, n = 15; medial MAT, n = 6). In the lateral MAT group, meniscocapsular separation was the most common pattern (n = 10, 66.7%), followed by complex (n = 3, 20.0%), radial (n = 1, 6.7%), and longitudinal (n = 1, 6.7%) tear. In the medial MAT group, a root tear was the most common pattern (n = 5, 83.3%), followed by a complex tear (n = 1, 16.7%). Meanwhile, in the lateral MAT, the midbody was the most frequently affected location (n = 9, 60.0%), followed by the posterior (n = 5, 33.3%) and anterior (n = 1, 6.7%) areas; in the medial MAT group, the posterior (n = 5, 83.3%) was the most frequently affected location, followed by the anterior area (n = 1, 16.7%). Significant differences in the pattern (P = 0.002) and location (P = 0.043) of the graft tears were found between lateral and medial MATs. CONCLUSION: In patients with early failure after MAT, meniscocapsular separation in the midbody of the lateral compartment and root tears in the posterior area of the medial compartment were the most common. Thus, surgeons are encouraged to pay extra attention to these vulnerable areas during the early period after MAT. LEVEL OF EVIDENCE: IV.

1,2-Diphenyl-o-carborane and Its Chromium Derivatives: Synthesis, Characterization, X-ray Structural Studies, and Biological Evaluations.

The objective of this study is to design and synthesize substituted η6-chromium(0) tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-diphenyl-o-carborane (1) units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1 substituted with chromium(0) tricarbonyl affect the biological properties, and 1-(Phenyl-η6-chromium(0) tricarbonyl)-2-phenyl-o-carborane (2) and 1,2-bis(phenyl-η6-chromium(0) tricarbonyl)-o-carborane (3) species were produced in moderate yields. The molecular structures of compounds 1-3 were identified and established by infrared (IR); 1H, 11B, and 13C nuclear magnetic resonance (NMR) and X-ray crystallography analyses. Crystal structures of 1,2-diphenyl-o-carborane and the corresponding chromium complexes 1, 2, and 3 were obtained. In an in vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium(0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we reported previously, compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

Lateral Meniscal Allograft Transplantation Provides a Chondroprotective Effect on Articular Cartilage: Quantitative 3-T Magnetic Resonance Imaging T2 Mapping.

PURPOSE: This study aimed to assess the cartilage status in patients who underwent isolated lateral meniscus allograft transplantation (MAT) using preoperative and postoperative quantitative 3-T magnetic resonance imaging T2 mapping at midterm follow-up period. METHODS: Patients who underwent lateral MAT without cartilage treatment procedures between 2010 and 2019 were assessed by quantitative magnetic resonance imaging preoperatively and postoperatively. On the sagittal section image following the center of the lateral femoral condyle, the weight-bearing area of the articular cartilage was divided into 6 segments based on the meniscal coverage area from anterior to posterior direction. The mean T2 values of each of the 6 segments were measured for 3 regions of interest: overall, deep, and superficial layers. The change in T2 values was statistically analyzed by paired t-tests. The Lysholm score was used to evaluate clinical function. RESULTS: A total of 105 patients were included in the study. The mean follow-up period was 3.2 years (range 2.0-5.4 years). Among the 6 segments, the mean T2 value showed significant improvement in the overall layer of F2 (the middle weight-bearing area of femoral condyle) and TP3 (the posterior weight-bearing area of tibia condyle) segments (P = .013 and .021, respectively) and the superficial layer of the F3 (the posterior weight-bearing area of femoral condyle) segments (P = .028). The mean T2 value of all the other segments did not show a statistically significant change. The mean Lysholm score significantly improved from 66.5 ± 15.8 to 89.3 ± 10.0 (P < .001). Overall, 73.3% and 96.2% of the patients met the minimal clinically important difference and patient acceptable symptomatic state, respectively. CONCLUSIONS: The mean T2 value of the articular cartilage of the weight-bearing area was either maintained or showed statistically significant improvement depending on the location following isolated lateral MAT. Thus, the transplanted meniscus seems to have a chondroprotective effect on the weight-bearing cartilage. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Effect of ICRS Lesion Grade on Graft Survival After Medial Meniscal Allograft Transplantation: MRI-Based Objective Evaluation.

BACKGROUND: Data are lacking regarding the survival rate after medial meniscal allograft transplantation (MAT) alone. Furthermore, little information is available about prognostic factors for graft survival that affect the outcomes of medial MAT. PURPOSE: To investigate the prognostic factors and survival rate of allograft after medial MAT. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The records of 78 consecutive patients who underwent primary medial MAT between 1996 and 2018 were reviewed. Kaplan-Meier survival analysis was performed to analyze the anatomic and clinical survival rates. Anatomic failure was defined as a tear covering >50% of the allograft or unstable peripheral rim. Clinical failure was considered Lysholm score <65 or need for additional surgery such as meniscal repair, revision MAT, realignment osteotomy, and meniscectomy for >50% of the allograft. Patient factors affecting anatomic and clinical failure were analyzed. RESULTS: The mean follow-up period was 6.9 ± 5.3 years (range, 2-21 years). Anatomic failure was noted in 19 patients (24.4%), and none of these patients had a persistent poor Lysholm score of <65; of these, 2 patients who underwent meniscal repair also had clinical failure. Clinical failure was noted in 7 patients (9.0%); 4 patients had Lysholm score <65, 2 patients underwent meniscal repair, and 1 patient underwent realignment osteotomy. The estimated 10-year anatomic and clinical survival rates were 73.89% and 87.90%, respectively. Anatomic survival was significantly associated with only high-grade International Cartilage Regeneration & Joint Preservation (ICRS) lesion (ICRS grade 3 or 4) (hazard ratio, 3.171; 95% CI, 1.124-8.944; P = .029). However, the clinical survival rate was not significantly associated with any factors. Patients with low-grade ICRS lesion (ICRS grade 0, 1, or 2) showed a higher estimated 10-year anatomic survival rate compared with patients with high-grade ICRS lesions (87.6% vs 63.3%, respectively; P = .022). CONCLUSION: Low-grade ICRS lesion was associated with higher anatomic survival rate after medial MAT. In patients with high-grade ICRS lesions, the clinical outcome might be good; however, the status of an allograft might be poor. The surgeon should be aware of this and explain to the patient that close observation is necessary.

Dutomycin Induces Autophagy and Apoptosis by Targeting the Serine Protease Inhibitor SERPINB6.

Autophagy plays an important role in maintaining tumor cell progression and survival in response to metabolic stress. Thus, the regulation of autophagy can be used as a strategy for anticancer therapy. Here, we report dutomycin (DTM) as a novel autophagy enhancer that eventually induces apoptosis due to excessive autophagy. Also, human serine protease inhibitor B6 (SERPINB6) was identified as a target protein of DTM, and its novel function which is involved in autophagy was studied for the first time. We show that DTM directly binds SERPINB6 and then activates intracellular serine proteases, resulting in autophagy induction. Inhibitory effects of DTM on the function of SERPINB6 were confirmed through enzyme- and cell-based approaches, and SERPINB6 was validated as a target protein using siRNA-mediated knockdown and an overexpression test. In a zebrafish xenograft model, DTM showed a significant decrease in tumor area. Furthermore, the present findings will be expected to contribute to the expansion of novel basic knowledge about the correlation of cancer and autophagy by promoting active further research on SERPINB6, which was not previously considered the subject of cancer biology.

Triggered Electrooculography for Identification of Oculomotor and Abducens Nerves during Skull Base Surgery.

OBJECTIVE: Electrooculography (EOG) records eyeball movements as changes in the potential difference between the negatively charged retina and the positively charged cornea. We aimed to investigate whether reliable EOG waveforms can be evoked by electrical stimulation of the oculomotor and abducens nerves during skull base surgery. METHODS: We retrospectively reviewed the records of 18 patients who had undergone a skull base tumor surgery using EOG (11 craniotomies and seven endonasal endoscopic surgeries). Stimulation was performed at 5 Hz with a stimulus duration of 200 µs and an intensity of 0.1-5 mA using a concentric bipolar probe. Recording electrodes were placed on the upper (active) and lower (reference) eyelids, and on the outer corners of both eyes; the active electrode was placed on the contralateral side. RESULTS: Reproducibly triggered EOG waveforms were observed in all cases. Electrical stimulation of cranial nerves (CNs) III and VI elicited positive waveforms and negative waveforms, respectively, in the horizontal recording. The median latencies were 3.1 and 0.5 ms for craniotomies and endonasal endoscopic surgeries, respectively (p=0.007). Additionally, the median amplitudes were 33.7 and 46.4 µV for craniotomies and endonasal endoscopic surgeries, respectively (p=0.40). CONCLUSION: This study showed reliably triggered EOG waveforms with stimulation of CNs III and VI during skull base surgery. The latency was different according to the point of stimulation and thus predictable. As EOG is noninvasive and relatively easy to perform, it can be used to identify the ocular motor nerves during surgeries as an alternative of electromyography.

FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3ß-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.

Discordance of Epidermal Growth Factor Receptor Mutation between Brain Metastasis and Primary Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to compare epidermal growth factor receptor (EGFR) mutations between non-small cell lung cancer (NSCLC) and corresponding brain metastases (BMs) in Korea society. METHODS: From 2011 to 2016, a total of 74 patients underwent surgical resection of a metastatic brain tumor from NSCLC. Among them, we performed retrospective analysis for 46 patients who underwent EGFR sequencing of primary NSCLC tissues. RESULTS: Among these 46 cases, 18 (39.1%) cases showed EGFR mutation in primary lung cancer. Detected mutation sites were exon 19 (8 cases), exon 21 (6 cases), exon 18 (1 cases), and multiple mutations (3 cases). In 18 cases of BM, EGFR mutation studies were done. Among them, 8 (25.6%) cases showed mutation on exon 19 (5 cases) or exon 21 (3 cases). To compare EGFR mutation status between primary lung cancer and BM, 18 paired tissues from both NSCLC and matched BM were collected. Four (22.5%) patients were discordant for the status of EGFR between primary and metastatic sites. CONCLUSION: EGFR mutations were significantly discordant between primary tumors and corresponding metastases in a significant portion of NSCLC. In treatment of BM of EGFR mutant metastatic NSCLC, due to possibility of discordance, pathologic confirming through brain biopsy is recommended.

Does arthroscopic preemptive extensive rotator interval release reduce postoperative stiffness after arthroscopic rotator cuff repair?: a prospective randomized clinical trial.

BACKGROUND: To investigate whether preemptive extensive rotator interval (RI) release during arthroscopic rotator cuff repair (ARCR) would reduce postoperative stiffness. METHODS: From July 2015 to September 2016, a total of 80 patients who were scheduled for ARCR were enrolled and randomly allocated into 2 groups: the preemptive extensive RI release group (group 1, n=40) and the RI nonrelease group (group 2, n=40). The American Shoulder and Elbow Surgeons scale, Constant score, Korean Shoulder Scale (KSS), visual analog scale (VAS) pain score, and range of motion (ROM) were evaluated before surgery; 3, 6, and 12 months after surgery; and at last follow-up. Magnetic resonance imaging was performed at postoperative 12 months. RESULTS: The mean follow-up period was 26.5 months. The functional and pain scores in both groups were significantly improved at the last follow-up (P < .05). Group 1 showed a significantly higher sum of ROM with a difference of 27° and 1.6 vertebral level of internal rotation compared to group 2 at postoperative 3 months (P < .05). Constant score and KSS were significantly higher in group 1 than in group 2 at this time point (P < .05). Functional scores and ROM were not significantly different between 2 groups at postoperative 6 or 12 months or at the last follow-up (P > .05). The retear rate and pathologic change of the long head of the biceps tendon during follow-up were not significantly different between the 2 groups (P > .05). CONCLUSION: Arthroscopic preemptive extensive RI release can reduce early postoperative shoulder stiffness after ARCR but does not significantly change the overall clinical outcome after surgery.

Myxoma arising from the parotid gland.

Myxomas can be divided into two groups: those derived from the facial skeleton, and those derived from external skeletal soft tissue. Soft tissue myxomas of the head and neck are uncommon, with fewer than 50 cases reported. In any form and location, myxoma of parotid gland is rare. We report a case of myxoma arising from the left superficial lobe of the parotid gland with good longterm follow-up after superficial parotidectomy with tumor excision. A 49-year-old man was referred to our department of plastic and reconstructive surgery with a painless palpable mass that had persisted in the left mandible angle region for 2 years. Excision of the facial mass and superficial parotidectomy with facial nerve preservation were performed. The biopsy result was myxoma. Long-term follow-up for 22 months showed favorable results without evidence of recurrence but with temporary facial nerve weakness right after the surgery. Myxoma should be considered as a differential diagnosis when benign tumor of the parotid gland is being considered.

Long-Term Safety and Efficacy of Tacrolimus in Myasthenia Gravis.

PURPOSE: Myasthenia gravis (MG) is a lifelong autoimmune disorder that affects neuromuscular transmission. The long-term treatment plan should include immunotherapy. We investigated the long-term safety and efficacy of tacrolimus for the treatment of MG in real-world clinical practice. MATERIALS AND METHODS: We retrospectively reviewed 160 MG patients treated with tacrolimus from 2005 to 2015. Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA post-intervention status, myasthenic functional score, and dose of oral prednisolone were investigated. RESULTS: Adverse events occurred in 68 patients (42.5%), most of which were minor and well-managed. Clinical severity scales improved after administration of tacrolimus, compared to the baseline. Compared to 6 months before administration of tacrolimus, prednisolone dose significantly decreased at 12 months after treatment (2.85±0.92 mg/day, p=0.002), 18 months after treatment (3.36±0.99 mg/day, p=0.001), and 24 months after treatment (3.71±0.93 mg/day, p<0.001). CONCLUSION: Tacrolimus may be effective in reducing the severity of MG and may permit a reduction in the steroid dose prescribed to the patients. Adverse events due to tacrolimus treatment were not serious.

Risk of osteoporosis in patients with chronic inflammatory neuropathy- a population-based cohort study.

The risk of osteoporosis in patients with chronic inflammatory neuropathy (CIN) has not been evaluated in detail. We conducted a population-based case-control study nested in a retrospective cohort to analyze osteoporosis risk among patients with CIN using a nationwide database. Patients with CIN based on the Korean Classification of Disease diagnostic code were included and were matched to controls. A Cox proportional hazards regression model was used to evaluate the effect of CIN on osteoporosis. After propensity score matching, 585 CIN patients and 585 controls were selected. Patients with CIN had an increased osteoporosis risk (hazard ratio [HR] = 2.293, 95% confidence interval [CI] 1.460-3.601) compared with controls. The osteoporosis risk was higher among male patients with CIN than among male controls (HR = 5.404, 95% CI 2.252-12.969), while there were no significant differences among women. Among the CIN patients, the average daily dose of corticosteroids was higher in those who developed osteoporosis (19.6 mg [10.8-49.3]) than those who did not (16.2 mg [7.2-29.1], p = 0.001). The osteoporosis risk among CIN patients is higher than among controls. High risk of osteoporosis in male patients may indicate that osteoporosis in CIN patients results from the disease itself or related treatments.

A useful additional medial subbrow approach for the treatment of medial orbital wall fracture with subciliary technique.

BACKGROUND: To date, a variety of surgical approaches have been used to reconstruct the medial orbital wall fracture. Still however, there is still a controversy as to their applicability because of postoperative scars, injury of anatomical structures and limited visual fields. The purpose of this study was to introduce a useful additional medial subbrow approach for better reduction and securement more accurate implant pocket of medial orbital wall fracture with the subciliary technique. METHODS: We had performed our technique for a total of 14 patients with medial orbital wall fracture at our medical institution between January 2016 and July 2017. All fractures were operated through subciliary technique combined with the additional medial subbrow approach. They underwent subciliary approach accompanied by medial wall dissection using a Louisville elevator through the slit incision of the medial subbrow procedure. This facilitated visualization of the medial wall fracture site and helped to ensure a more accurate pocket for implant insertion. RESULTS: Postoperative outcomes showed sufficient coverage without displacement. Twelve cases of preoperative diplopia improved to two cases of postoperative diplopia. More than 2 mm enophthalmos was 14 cases preoperatively, improving to 0 case postoperatively. Without damage such as major vessels or extraocular muscles, enophthalmos was corrected and there was no restriction of eyeball motion. CONCLUSION: Our ancillary procedure was useful in dissecting the medial wall, and it was a safe method as to cause no significant complications in our clinical series. Also, there is an only nonvisible postoperative scar. Therefore, it is a recommendable surgical modality for medial orbital wall fracture.

RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity.

Ribosomal S6 kinase 2 (RSK2), regulated by Ras/Raf/MEKs/ERKs, transmits upstream activation signals to downstream substrates including kinases and transcription and epigenetic factors. We observed that ELK members, including ELK1, 3, and 4, highly interacted with RSK2. We further observed that the RSK2-ELK3 interaction was mediated by N-terminal kinase and linker domains of RSK2, and the D and C domains of ELK3, resulting in the phosphorylation of ELK3. Importantly, RSK2-mediated ELK3 enhanced c-fos promoter activity. Notably, chemical inhibition of RSK2 signaling using kaempferol (a RSK2 inhibitor) or U0126 (a selective MEK inhibitor) suppressed EGF-induced c-fos promoter activity. Moreover, functional deletion of RSK2 by knockdown or knockout showed that RSK2 deficiency suppressed EGF-induced c-fos promoter activity, resulting in inhibition of AP-1 transactivation activity and Ras-mediated foci formation in NIH3T3 cells. Immunocytofluorescence assay demonstrated that RSK2 deficiency reduced ELK3 localization in the nucleus. In MDA-MB-231 breast cancer cells, knockdown of RSK2 or ELK3 suppressed cell proliferation with accumulation at the G1 cell cycle phase, resulting in inhibition of foci formation and anchorage-independent cancer colony growth in soft agar. Taken together, these results indicate that a novel RSK2/ELK3 signaling axis, by enhancing c-Fos-mediated AP-1 transactivation activity, has an essential role in cancer cell proliferation and colony growth.

CNT bundle-based thin intracochlear electrode array.

OBJECTIVE: It is known that the insertion of the intracochlear electrode is critical procedure because the damage around cochlear structures can deteriorate hearing restoration. To reduce the trauma during the electrode insertion surgery, we developed a thin and flexible intracochlear electrode array constructed with carbon nanotube (CNT) bundles. METHODS: Each CNT bundle was used for an individual electrode channel after coated with parylene C for insulation. By encapsulating eight CNT bundles with silicone elastomer, an 8-channel intracochlear electrode array was fabricated. The mechanical and electrochemical characteristics were assessed to evaluate the flexibility and feasibility of the electrode as a stimulation electrode. The functionality of the electrode was confirmed by electrically evoked auditory brainstem responses (eABR) recorded from a rat. RESULTS: The proposed electrode has a thickness of 135 µm at the apex and 395 µm at the base. It was demonstrated that the CNT bundle-based electrodes require 6-fold the lower insertion force than metal wire-based electrodes. The electrode impedance and the cathodic charge storage capacitance (CSCc) were 2.70 kΩ âˆ -20.4° at 1 kHz and - 708 mC/cm2, respectively. The eABR waves III and V were observed when stimulation current is greater than 50 µA. CONCLUSION: A thin and flexible CNT bundle-based intracochlear electrode array was successfully developed. The feasibility of the proposed electrode was shown in terms of mechanical and electrochemical characteristics. A proposed CNT bundle-based intracochlear electrode may reduce the risk of trauma during electrode insertion surgery.

Can Preoperative 3D Printing Change Surgeon's Operative Plan for Distal Tibia Fracture?

This study aimed to determine if 3D printing can affect surgeon's selection of plate for distal tibia fracture surgery and to find out whether orthopedic surgeons consider this technology necessary and would use it in their practice. A total of 102 orthopedic surgeons were asked to choose anatomically contoured locking plates among 5 most commonly used types for one simple and one complex distal tibia fracture based on X-ray and CT images. Next, they were provided real-size 3D printed models of the same fractures, allowed to apply each of the 5 plates to these models, and asked if they would change their choice of plate. A 10-point numeric rating scale was provided to measure the extent of the help that 3D printing provided on preoperative planning. Finally, we asked the surgeons if they would use 3D printing in their practice. Seventy-four percent of inexperienced surgeons changed their selection of plate after using 3D printed models for the complex fracture. In contrast, only 9% of experienced surgeons changed their selection of plate for the simple fracture. Surgeons rated the extent of usefulness of the 3D models in preoperative planning as a mean of 4.84 ± 2.54 points for the simple fracture and 6.63 ± 2.54 points for the complex fracture. The difference was significant (p < 0.001). Eighty-six percent of inexperienced surgeons wanted to use 3D models for complex fractures. However, only 18% of experienced surgeons wanted to use 3D printed models for simple fractures. The use of a real-size 3D-printed model often changed surgeon's preoperative selection of locking plates, especially when inexperienced surgeons evaluated a complex fracture. However, experienced surgeons did not find 3D models very useful when assessing simple fractures. Future applications of 3D models should focus on training beginners in fracture surgery, especially when complex fractures are concerned.

Effect of thymectomy in elderly patients with non-thymomatous generalized myasthenia gravis.

Whether thymectomy is beneficial in elderly patients with myasthenia gravis (MG) is unclear. Thus, we assessed whether conducting thymectomy in MG patients aged ≥ 50 years is beneficial. This retrospective cohort study included patients with MG between 1990 and 2018. Thymectomy and control cohorts were selected from among the population of MG patients with an age at onset of ≥ 45 years and elevated concentrations of acetylcholine-receptor antibodies. Patients with evidence of thymic malignancy were excluded. Of these patients, those who underwent thymectomy at the age of ≥ 50 years were designated as the thymectomy group and those who received only medical treatment were designated as the medical treatment group. We compared the Myasthenia Gravis Foundation of America post-intervention status between the thymectomy and medical treatment groups. Landmark analysis was conducted with the landmark set at 24 months. A total of 34 and 105 patients were classified into the thymectomy and medical treatment groups, respectively. Before landmark analysis, the thymectomy group had a higher cumulative incidence of pharmacologic remission (p = 0.009) and complete stable remission (p = 0.022) than the medical treatment group. After landmark analysis, the thymectomy group had a 2.22-fold (95% confidence interval 1.01-4.80) increased chance of achieving pharmacologic remission compared to the medical treatment group after adjustment for age, sex, and disease severity. No significant difference was observed in the rate of relapse after pharmacological remission between the thymectomy (16.7%) and medical treatment groups (21.4%). In conclusion, thymectomy may have a beneficial effect in elderly patients with non-thymomatous generalized MG.

Simple in Vivo Gene Editing via Direct Self-Assembly of Cas9 Ribonucleoprotein Complexes for Cancer Treatment.

Cas9 ribonucleoprotein (RNP)-mediated delivery has emerged as an ideal approach for in vivo applications. However, the delivery of Cas9 RNPs requires electroporation or lipid- or cationic-reagent-mediated transfection. Here, we developed a carrier-free Cas9 RNP delivery system for robust gene editing in vivo. For simultaneous delivery of Cas9 and a guide RNA into target cells without the aid of any transfection reagents, we established a multifunctional Cas9 fusion protein (Cas9-LMWP) that forms a ternary complex with synthetic crRNA:tracrRNA hybrids in a simple procedure. Cas9-LMWP carrying both a nuclear localization sequence and a low-molecular-weight protamine (LMWP) enables the direct self-assembly of a Cas9:crRNA:tracrRNA ternary complex (a ternary Cas9 RNP) and allows for the delivery of the ternary Cas9 RNPs into the recipient cells, owing to its intrinsic cellular and nuclear translocation ability with low immunogenicity. To demonstrate the potential of this system, we showed extensive synergistic anti-KRAS therapy (CI value: 0.34) via in vitro and in vivo editing of the KRAS gene by the direct delivery of multifunctional Cas9 RNPs in lung cancer. Thus, our carrier-free Cas9 RNP delivery system could be an innovative platform that might serve as an alternative to conventional transfection reagents for simple gene editing and high-throughput genetic screening.