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Tsung-You Tsai,1,&ast; Huang-Kai Kao,2,3,&ast; Yenlin Huang,4 Ya-Ting Chang,5 Chi-Kuang Young,1 Shao-Yu Hung,3 Yu-Sun Chang,5 Jau-Song Yu,1,5,6 Kai-Ping Chang1,2,5 1Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan; 5Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan; 6Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan&ast;These authors contributed equally to this workCorrespondence: Kai-Ping Chang, Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, No. 5, Fu-Hsing St, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext.3967, Fax +886-3-3979361, Email dr.kpchang@gmail.comPurpose: Plasma matrix metalloproteinase-1 (MMP-1) is a collagenase encoded by the MMP-1 gene. However, the prognostic value of plasma MMP-1 levels in oral cavity squamous cell carcinoma (OSCC) has yet to be elucidated. The study is the first to use a cohort of OSCC patients to assess the association of plasma MMP-1 levels with clinicopathological factors/survival outcomes in OSCC patients.Patients and Methods: A total of 677 patients were retrospectively enrolled, including 276 oral potentially malignant disease (OPMD) and 401 OSCC patients from 2013 to 2021. Pretreatment plasma MMP-1 levels were measured with an enzyme-linked immunosorbent assay, and the values were compared between OPMD and OSCC patients. Furthermore, the association of plasma MMP-1 levels and clinicopathological characteristics/survival outcomes in OSCC patients was investigated.Results: Plasma MMP-1 levels were significantly higher in OSCC patients than in OPMD patients (p = 0.04). In the OSCC group, plasma MMP-1 levels were significantly higher in females, tumor depth ≥ 10 mm, advanced pT classification and advanced overall stage (p = 0.04, < 0.001, < 0.001, 0.002, respectively). Higher plasma MMP-1 levels were significantly associated with poorer overall, disease-specific, disease-free, locoregional recurrence-free and distant metastasis-free survival (p = 0.003, 0.02, 0.005, 0.01, 0.001, respectively). Multivariate analysis revealed that plasma MMP-1 levels were a significant predictor for overall, disease-free, and distant metastasis-free survival (p = 0.03, 0.02, and 0.010, respectively).Conclusion: Plasma MMP-1 levels are associated with more severe clinicopathological manifestations and can also be regarded as a significant prognostic factor for OSCC posttreatment outcomes.Keywords: oral cancer, MMP, squamous cell carcinoma, ELISA, OSCC

Yenlin Huang,1,2 Chieh Lin,3 Huang-Kai Kao,2,4 Shao-Yu Hung,4 Hung-Ju Ko,2 Yu-Chen Huang,5 Yu-Liang Chang,5 Kai-Ping Chang2,6 1Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Department of Oral & Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Kai-Ping ChangDepartment of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, No. 5, Fu-Hsing Street, Kwei-Shan, Taoyuan 333005, TaiwanTel +886-3-3281200 ext 3972Fax +886-3-3979361Email dr.kpchang@gmail.comPurpose: The presence of CD8+ tumor-infiltrating lymphocytes (TILs) has been reported to be associated with treatment outcomes in many types of solid tumors. However, the results vary due to the various methods of visual estimation and subjective interpretation. The current study is the first to use digital image analyses to evaluate the density of CD8+/CD3+ TILs in tongue squamous cell carcinoma (TSCC).Patients and Methods: From 2005 to 2015, a cohort of 258 TSCC patients were consecutively enrolled in this study. After immunohistochemistry on representative sections, the density of CD8+/CD3+ TILs at tumor invasive margins was evaluated by digital image analysis. The subjects were stratified by the median values of CD3+ cell density, CD8+ cell density, CD8/CD3, and scores (0, 1, and 2) to demonstrate the association with various clinicopathological manifestations.Results: Low CD8+ TIL counts were associated with advanced tumor stages (p=0.034), and low CD8/CD3 ratios were associated with perineural invasion (p=0.043). Both parameters were also associated with increased tumor depths (p=0.034 and 0.004, respectively). Univariate analyses revealed that advanced tumor stages, perineural invasion, extranodal extension, tumor depth, lower CD8 counts, and lower scores (score 0 vs 2) were associated with poorer overall survival, and multivariate analysis further indicated that extranodal extension and low scores (score 0 vs 2) were both independent factors for overall survival (p < 0.0001 and p = 0.0369, respectively).Conclusion: The use of digital image analysis to assess CD8+ TILs at the invasive margins provides an objective indicator of prognoses including overall survival.Keywords: oral cavity, squamous cell carcinoma, oral cancer, SCC, tumor-infiltrating lymphocyte, TIL

George Kuo,1 Wei-Chiao Sun,1 Yueh-An Lu,1 Chao-Yu Chen,1 Huang-Kai Kao,2 YuJr Lin,3 Yung-Chang Chen,4 Cheng-Chieh Hung,1 Ya-Chung Tian,1 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 2Department of Plastic and Reconstructive Surgery, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 3Center for Big Data Analytics and Statistics, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 4Department of Internal Medicine, Division of Nephrology, College of Medicine, Keelung Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan Purpose: Infectious spondylodiscitis is a serious disease that can lead to permanent neurological deficit. Because there were only a few case reports or series featuring infectious spondylodiscitis in chronic dialysis patients, we investigated the epidemiology and outcome in the chronic dialysis patients versus general population.Materials and methods: We retrospectively identified chronic dialysis patients admitted for infectious spondylodiscitis between January 2002 and December 2015. A total of 105 chronic dialysis patients were included, and we performed a 1:2 case–control match on propensity score in non-dialysis patients with infectious spondylodiscitis. The demographic features, clinical manifestation, infection focus, and disease outcome were recorded.Results: A total of 302 patients entered the final analysis. Chronic dialysis patients less frequently had fever (34.3%), and in the majority, bacterial entry was through dialysis vascular access (30.5%). Methicillin-resistant Staphylococcus aureus (MRSA) comprised the majority of causative pathogen. The chronic dialysis group had longer hospital stay, higher in-hospital mortality, and higher 1-year mortality. The odds ratio of in-hospital mortality was 2.20 compared with the non-dialysis group.Conclusions: The study highlighted poorer outcome and high frequency of resistant Staphylococcus of infectious spondylodiscitis in chronic dialysis patients. Therefore, high vigilance, prompt recognition, and empiric coverage of MRSA will be important in the management of infectious spondylodiscitis in chronic dialysis patients. Keywords: end stage renal disease, pyogenic spondylodiscitis, infectious spondylodiscitis, methicillin-resistant Staphylococcus aureus, mortality

Background:  Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence of new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients., Methods:  We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into the following: (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome., Results:  In total, 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%; p  = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF ( p  < 0.001) compared to those without AF or new-onset AF., Conclusion:  Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Pediatric supracondylar humeral fractures present considerable surgical challenges due to the difficulty of achieving proper fracture alignment and stable fixation while avoiding injury to the ulnar nerve. This study assesses the biomechanical performance of a novel Kirschner wire (K-wire) fixation device (KFD), designed to enhance stability and reduce complications linked to traditional K-wire configurations., Methods: Using finite element analysis (FEA), we evaluated four fixation strategies for treatment of pediatric supracondylar humeral simple transverse fractures: crossed pin fixation, crossed pin fixation with KFD, two lateral pin fixation, and two lateral pin fixation with KFD, under various mechanical loads. The analysis focused on the stress and strain experienced by the K-wires at the fracture site during torsional and bending forces., Results: FEA revealed that the KFD significantly reduced the stress and strain on the K-wires in all configurations. In both crossed pin and two lateral pin fixation methods, the addition of the KFD showed lower stress and strain levels compared to setups without the KFD., Conclusion: This study demonstrates the potential of the KFD to enhance fracture stability and reduce mechanical stress at the fracture site, suggesting a promising improvement in the treatment of pediatric supracondylar humeral fractures. This innovation may contribute to safer and more reliable outcomes in pediatric orthopedic surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Tai, Lee, Wang, Mao, Yang, Chang and Kao.)

After a fracture, patients have reduced willingness to bend and extend their elbow joint due to pain, resulting in muscle atrophy, contracture, and stiffness around the elbow. Moreover, this may lead to progressive atrophy of the muscles around the elbow, resulting in permanent functional loss. Currently, a goniometer is used to measure the range of motion, ROM, to evaluate the recovery of the affected limb. However, the measurement process can cause measurement errors ranging from 4 to 5 degrees due to unskilled operation or inaccurate placement, leading to inaccurate judgments of the recovery of the affected limb. In addition, the current measurement methods do not include an assessment of muscle endurance. In this paper, the proposed device combines image recognition and a myoelectric signal sensor to measure the joint movement angle and muscle endurance. The movement angle of the elbow joint is measured using image recognition. Muscle endurance is measured using the myoelectric signal sensor. The measured data are transmitted to a cloud database via an app we have proposed to help medical staff track a patient's recovery status. The average error value of static image recognition and verification is up to 0.84 degrees. The average error value of dynamic image recognition and verification is less than 1%. The average error of total harmonic distortion (THD) verified by the myoelectric signal sensor is less than ±3%. It was proven that our system could be applied to measuring elbow joint range of motion. Since this is pilot research, most of the measurement subjects are healthy people without dysfunction in arm movement, and it is difficult to observe differences in the measurement results. In the future, experiments will be conducted on patients with elbow fractures through the IRB. This is expected to achieve the effect of encouraging patients to be actively rehabilitated at home through their measurement data and images of their actions being displayed in real time using our cheap and compact device and app.

Background: The primary objective of this study was to ascertain the risk factors associated with hardware complications following segmental mandibular reconstruction in head and neck cancer patients. Additionally, we sought to develop a nomogram model that enables accurate risk prediction., Methods: Patients who underwent segmental mandibulectomy with immediate free or local regional tissue transfer between January 2016 and December 2020 were reviewed. Hardware complications were defined. Patient demographics and perioperative parameters were analyzed., Results: A total of 510 patients were analyzed. Postoperative radiation therapy (OR = 2.296, 95% CI = 1.339-3.938, p = 0.003), postoperative wound infection (OR = 2.367, 95% CI = 1.472-3.806, p < 0.001), and debridement for flap-related complications (OR = 5.484, 95% CI = 3.269-9.199, p < 0.001) were identified as independent risk factors. The nomogram model demonstrated good discriminatory ability., Conclusion: This comprehensive analysis identified three independent risk factors, and the nomogram provides a valuable tool for predicting the risks. Further research is needed to validate these findings and explore preventive strategies., (© 2024 Wiley Periodicals LLC.)

Background: Babies born in winter have greater incidence of developmental dysplasia of the hip (DDH) and related surgeries. How weather conditions impact hip development and how screening program reacts weather issue remain unknown. This study tests a hypothesis that winter born babies have more newborn acetabular dysplasia and laxity that is responsible of later DDH., Methods: Retrospective data from newborns who had hip ultrasonography in the first 3 days of life were analyzed. The Graf type IIc, III, IV (shallow acetabulum) and type D (laxity) were classified as abnormal. The association and risks of an abnormal hip were analyzed with gender, gestational age, fetal presentation, parity and external temperature of birth month and the last 3 months before birth using the Pearson chi-square test and logistic regression., Results: A total of 10962 newborns participated in hip ultrasound exams voluntarily in nurseries from 2016 to 2022. Distribution of babies with Graf type I, IIa, IIc, D, III/IV hips were 88.8%, 10%, 0.5%, 0.6%, and 0.1%, respectively. Female was the most significant factor for congenital shallow acetabulum (3.8x) and hip laxity (4x) compared to male (p < 0.001). Preterm babies had a borderline lower risk of abnormal hips (0.4x, p = 0.05). Winter season is not associated with newborn abnormal hips (p = 0.36, statistical power = 80%), but a positive correlation was noted between external temperature and incidence of abnormal hips (r = 0.62, p = 0.03). Cold weather does not have a direct internal effect in acetabular dysplasia or hip laxity at birth., Conclusions: Babies who were born in winter were not associated with acetabular dysplasia and hip laxity at birth but had greater risks of late-diagnosed DDH and surgeries. The postnatal effects from weather should be addressed by a public awareness campaign, and hip screening may not be limited on the neonatal stage., Level of Evidence: level III, diagnostic., Competing Interests: Declaration of competing interest The authors declare that they have no potential conflicts of interest for this study., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this meta-analysis is to evaluate the potential benefits of postoperative radiotherapy (PORT) in patients with pN1 oral cavity squamous cell carcinoma., Methods: A literature search through major databases was conducted until January 2023. The adjusted hazard ratio (aHR) or risk ratio (RR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled., Results: Ten studies published between 2005 and 2022, with a pooled patient population of 2888, were included in this meta-analysis. Due to differences in study design and reported outcomes, the studies were categorized into distinct groups. In pN1 patients without extranodal extension (ENE), PORT was associated with a significant improvement in overall survival (OS) (aHR 0.76, 95% CI: 0.61-0.94). In pN1 patients without ENE and positive margins, PORT improved OS (aHR 0.71, 95% CI: 0.56-0.89) and was associated with a lower regional recurrence rate (RR 0.35, 95% CI: 0.15-0.83). However, in pN1 patients without ENE, positive margins, perineural invasion, and lymphovascular invasion, there were no significant differences observed between the PORT and observation groups in either 5-year OS (RR 0.48, 95% CI: 0.07-3.41) or 5-year disease-free survival (RR 0.37, 95% CI: 0.07-2.06)., Conclusions: The current study demonstrated that PORT has the potential to improve OS in pN1 disease. However, the decision of whether to administer PORT still hinges on diverse clinical scenarios, and additional research is necessary to furnish a more conclusive resolution., Level of Evidence: 2., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Developmental dysplasia of the hip (DDH) is a common congenital disorder that may lead to hip dislocation and requires surgical intervention if left untreated. Ultrasonography is the preferred method for DDH screening; however, the lack of experienced operators impedes its application in universal neonatal screening., Methods: We developed a deep neural network tool to automatically register the five keypoints that mark important anatomical structures of the hip and provide a reference for measuring alpha and beta angles following Graf's guidelines, which is an ultrasound classification system for DDH in infants. Two-dimensional (2D) ultrasonography images were obtained from 986 neonates aged 0-6 months. A total of 2406 images from 921 patients were labeled with ground truth keypoints by senior orthopedists., Results: Our model demonstrated precise keypoint localization. The mean absolute error was approximately 1 mm, and the derived alpha angle measurement had a correlation coefficient of R = 0.89 between the model and ground truth. The model achieved an area under the receiver operating characteristic curve of 0.937 and 0.974 for classifying alpha <60° (abnormal hip) and <50° (dysplastic hip), respectively. On average, the experts agreed with 96% of the inferenced images, and the model could generalize its prediction on newly collected images with a correlation coefficient higher than 0.85., Conclusions: Precise localization and highly correlated performance metrics suggest that the model can be an efficient tool for assisting DDH diagnosis in clinical settings., Competing Interests: Conflicts of interest No Conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: To identify risk factors associated with adverse airway events (AAEs) in primary oral cancer patients undergoing tumor ablation followed by free tissue transfer without prophylactic tracheostomy., Methods: We retrospectively collected primary oral cancer patients who underwent tumor ablation surgery following free-tissue transfer without prophylactic tracheostomy during February 2017 to June 2019 in Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan. 379 patients were included. Data were analysed from 2020 to 2021. Demographics, comorbidities, intraoperative variables and postoperative respiration profile were obtained from the medical record. Main outcome was postoperative AAEs, including requirement of endotracheal intubation after extubation and tracheostomy after prolonged intubation., Results: Of the 379 patients, postoperative AAEs happened in 29 patients (7.6 %). In reintubation group, patients were older with more diabetes mellitus, hypertension and cerebrovascular disease. These patients had lower preoperative hemoglobin, creatinine, and albumin level with more intraoperative blood transfusion. In postoperative respiration profile, rapid shallow breathing index (RSBI) and PaO2/FiO2 (PF) ratio were poorer. On multivariate analysis, patient's age, tumor location, and cross-midline segmental mandibulectomy and a lower PF ratio were independent risk factors for postoperative AAEs., Conclusions: In head and neck cancer patients that underwent tumor ablation followed by free tissue transfer without prophylactic tracheostomy, patient's age, tumor location, cross-midline segmental mandibulectomy and P/F ratio are associated with postoperative AAEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Previous classifications in polydactyly of the thumb were by the level of duplication on radiography. This study aimed to develop a practical algorithm based on physical characteristics for treatment guidelines., Methods: The polydactylies were stratified using four physical characteristics: floating, symmetry, dominant side, and joint angulation/nail size. The algorithm identified the hypoplastic type and then stratified the polydactylies as symmetric and asymmetric. The asymmetric type was divided into ulnar dominant and radial dominant. The symmetric type was divided into adequate type and inadequate type. The prediction of treatments was studied retrospectively by the distribution of surgical procedures in 500 patients with 545 affected thumbs, by the new classification and the Wassel-Flatt classification., Results: Of the 545 polydactylies, 78 (14.5%) were categorized as the hypoplastic type, 369 (67.5%) as the ulnar-dominant type, 8 (1.5%) as the radial-dominant type, 70 (12.8%) as the symmetric adequate nail type, and 20 (3.7%) as the symmetric inadequate type. Treatments were excision and reconstruction in 403 polydactylies (73.9%), simple excision in 135 polydactylies (24.8%), and the Bilhaut-Cloquet procedure, ray amputation, and on-top plasty procedures were only performed in 7 polydactylies (1.3%). The distribution of surgical procedures was distinct among the new classification types and was similar among the Wassel-Flatt types., Conclusions: The new classification stratified polydactylies by physical findings in a stepwise manner. Though surgical technical details are not included, this simple classification is useful for paediatricians and parents to understand how a surgical decision is made., Level of Evidence: Diagnostic Level IV., Competing Interests: Conflict of interest The authors declare that they have no potential conflicts of interest for this study., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation-based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory., Hypothesis: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions., Study Design: Controlled laboratory study., Methods: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively., Results: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation ( P = .015) and migration ( P = .001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 ( P = .005) and interleukin-1α ( P = .042) by M1 macrophages via the COX-2/PGE 2 /EP 4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions ( P = .003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength ( P = .019) and fiber alignment ( P < .001) of the repaired tendons., Conclusion: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration., Clinical Relevance: The present study lays a foundation for future clinical applications of stem cell spheroid-based therapy for the management of tendon injuries., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by the National Science and Technology Council in Taiwan (NSTC 111-2628-B-007-004, NSTC 111-2314-B-007-006, and NSTC 111-2314-B-182-064 [NMRPD1M1231]), the National Health Research Institutes in Taiwan (NHRI-EX112-11131EI), National Tsing Hua University (110Q2509E1, 111F7MDWE1, 112F7MCPE1, 112F7MDCE1, 112Q2714E1, and 112QI015E1), and Chang Gung Memorial Hospital (CORPG3M0061, CORPG3N0111, and CORPG3N0112). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Importance: The management of hypopharyngeal squamous cell carcinoma (HPSCC) continues to be one of the most formidable challenges in the realm of head and neck oncology., Objectives: The aim of this meta-analysis was to evaluate the disparity in survival outcomes between upfront surgery and upfront concurrent chemoradiotherapy as the primary treatment modality in patients with HPSCC., Design: Systemic review with meta-analysis., Setting: The meta-analysis was conducted in strict accordance with the PRISMA guideline. A literature search through PubMed, EMBASE, and the Cochrane Library were conducted until January 2023. The adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled., Participants: Studies that incorporated HPSCC patients without receiving induction chemotherapy., Interventions: Upfront surgery versus upfront concurrent chemoradiotherapy., Main Outcome Measures: Overall survival (OS) and disease-free survival (DFS)., Results: Eight studies published between 2015 and 2023, with a pooled patient population of 1619, were included in this meta-analysis. The outcomes reveal that upfront surgery was notably linked with improved OS (aHR 0.66, 95% CI 0.57-0.78) and DFS (aHR 0.75, 95% CI 0.63-0.90). Subgroup analyses were conducted to investigate the impact of the overall stage of the tumor and the extent of surgery on OS. In patients with advanced HPSCC (stages III and IV), upfront surgery remained associated with better OS (aHR 0.65, 95% CI 0.56-0.77). Concerning the extent of surgery, both subgroups exhibited a superior OS outcome associated with upfront surgery (exclusive total laryngopharyngectomy group: aHR 0.54, 95% CI 0.39-0.75; total/partial laryngopharyngectomy group: aHR 0.71, 95% CI 0.59-0.84)., Conclusions and Relevance: The results demonstrated that upfront surgery showed better OS and DFS than concurrent chemoradiation and remind the clinicians of the potential reduction in survival outcomes when choosing concurrent chemoradiotherapy as primary treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration., Competing Interests: The authors declare no conflict of interests., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Our image recognition system employs a deep learning model to differentiate between the left and right upper limbs in images, allowing doctors to determine the correct surgical position. From the experimental results, it was found that the precision rate and the recall rate of the intelligent image recognition system for preventing wrong-site upper limb surgery proposed in this paper could reach 98% and 93%, respectively. The results proved that our Artificial Intelligence Image Recognition System (AIIRS) could indeed assist orthopedic surgeons in preventing the occurrence of wrong-site left and right upper limb surgery. At the same time, in future, we will apply for an IRB based on our prototype experimental results and we will conduct the second phase of human trials. The results of this research paper are of great benefit and research value to upper limb orthopedic surgery.

Background: Established associated factors for DDH include female sex, breech presentation, family history, congenital malformations, oligohydramnios, and maternal hyperthyroidism. However, evidence for environmental factors that may contribute to DDH is limited and inconsistent., Methods: A systematic review of medical literature was conducted to collect data on environmental factors, including latitude, longitude, average yearly precipitation, average yearly temperature, minimum monthly temperature, and maximum monthly temperature, from all institutions that published articles on DDH. Univariate linear regression analysis was used to examine the correlation between environmental factors and DDH incidence, while multiple regression analysis was conducted to identify significant associated factors for DDH incidence., Results: Data from a total of 93 unique manuscripts were analyzed, revealing a significant negative correlation between DDH incidence and temperature, including average yearly temperature (r = -0.27, p = 0.008), minimum monthly temperature (r = -0.28, p = 0.006), and maximum monthly temperature (r = -0.23, p = 0.029). Additionally, there was a significant positive correlation between DDH incidence and latitude (r = 0.27, p = 0.009), and a significant negative correlation between DDH incidence and average yearly precipitation (r = -0.29, p = 0.004). In the final multiple regression analysis, temperature, including average yearly temperature, minimum monthly temperature, and maximum monthly temperature, were identified as significant associated factors for DDH incidence., Conclusion: The findings of this study suggest an association between cold weather and DDH incidence. Further research should explore the link between cold weather and DDH incidence, offering insights into potential interventions for cold climates., (© 2023. The Author(s).)

Background: Postoperative free flap monitoring is a critical part of reconstructive microsurgery. Postoperative clinical assessments rely heavily on specialty-trained staff. Therefore, in regions with limited specialist availability, the feasibility of performing microsurgery is restricted. This study aimed to apply artificial intelligence in postoperative free flap monitoring and validate the ability of machine learning in predicting and differentiating types of postoperative free flap circulation., Methods: Postoperative data from 176 patients who received free flap surgery were prospectively collected, including free flap photographs and clinical evaluation measures. Flap circulation outcome variables included normal, arterial insufficiency, and venous insufficiency. The Synthetic Minority Oversampling Technique plus Tomek Links (SMOTE-Tomek) was applied for data balance. Data were divided into 80%:20% for model training and validation. Shapley Additive Explanations were used for prediction interpretations of the model., Results: Of 805 total included flaps, 555 (69%) were normal, 97 (12%) had arterial insufficiency, and 153 (19%) had venous insufficiency. The most effective prediction model was developed based on random forest, with an accuracy of 98.4%. Temperature and color differences between the flap and the surrounding skin were the most significant contributing factors to predict a vascular compromised flap., Conclusions: This study demonstrated the reliability of a machine-learning model in differentiating various types of postoperative flap circulation. This novel technique may reduce the burden of free flap monitoring and encourage the broader use of reconstructive microsurgery in regions with a limited number of staff specialists., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Objectives: This study aimed to investigate the association between salivary matrix metalloproteinase-1 (MMP-1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP-1 and other established circulating markers for OSCC., Methods: Saliva specimens from 479 OSCC subjects were examined using an enzyme-linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP-1 and other markers were calculated, and survival analyses were conducted using Kaplan-Meier and multivariate regression methods., Results: Salivary MMP-1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p  = .021) and Charlson comorbidity index (0.568, p  = .048) and comparable with neutrophil-to-lymphocyte ratio (0.620, p  = .987), platelet-to-lymphocyte ratio (0.575, p  = .125), and squamous cell carcinoma antigen (0.609, p  = .605). Elevated levels of salivary MMP-1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth ( p all <.05). Multivariate analyses indicated that a higher level of salivary MMP-1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 [95% confidential interval: 1.014-1.989], p  = .041)., Conclusion: The study found that the salivary MMP-1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post-treatment outcome., Level of Evidence: 3., Competing Interests: None declared., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Traditionally, radial forearm free flaps are utilized for nasal lining reconstruction when local flaps cannot provide adequate coverage. However, according to our clinical observation, the skin of the forearm flap is relatively thin and prone to collapse. We present a series of nasal reconstructions using free flaps harvested from the lower extremities to determine if the thick flap could provide more support and decrease the tendency of airway collapse., Methods: From March 2011 to July 2021, we identified 15 patients who underwent total or subtotal nasal reconstruction with free flap from the lower extremities (10 anterolateral thigh flap, 4 medial sural artery perforator flap, and 1 profunda artery perforator flap). We included 15 patients who underwent free forearm flap reconstruction as controls. The Nasal Obstruction Symptoms Evaluation (NOSE) score was utilized to subjectively evaluate the degree of nasal obstruction symptoms., Results: The lower extremity group had a lower NOSE score than the forearm group (25.4 vs. 40). It took more time (6.5 vs. 4.2 months) and more surgeries (4.6 vs. 2.6) from the first free flap reconstruction till forehead flap reconstruction in the lower extremity group than in the forearm group, although the total number of surgeries was comparable between the 2 groups (7.2 vs. 8.1)., Conclusions: Utilizing free flaps from the lower extremities in total or subtotal reconstruction of the nasal lining may decrease the tendency of flap collapse and alleviate airway obstruction symptoms and may also allow reconstruction of surrounding defects simultaneously compared with using forearm flaps., Competing Interests: Conflict of Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Soft tissue release (STR) is an established treatment for spastic hip displacement, but recurrence of hip displacement is not uncommon. This study aims to (1) evaluate the recurrence of hip displacement after STR, (2) define associated factors of recurrence, and (3) elucidate the effects of guided growth on hip displacement recurrence., Methods: The study subjects included 66 individuals with spastic cerebral palsy treated by STR with or without guided growth for hip displacement. The treatment goal was the maintenance of migration percentage (MP) to <40%. Recurrence was defined by a rebound of the MP by 5% or more after the first postoperative year. Children with recurrence were compared with those without recurrence using the Mann-Whitney U test and the χ 2 test. The risk factors for recurrence were evaluated using multiple logistic regression analysis., Results: Nineteen individuals (29%) had a recurrence of hip displacement after the first postoperative year. They sustained a 2-fold increase in the rate of treatment failure ( P < 0.001) and reoperation ( P = 0.04). Age, sex, motor function, and preoperative radiographic parameters were comparable between individuals with and without recurrence. The use of guided growth was associated with less risk of recurrence than without (5% and 39%, respectively, odds ratio = 0.01 to 0.45, respectively) despite the similar risk of failure (35% and 48%, respectively, odds ratio = 0.15 to 4.82)., Conclusions: Recurrence of the MP >5% after the first postoperative year is an important early indicator for failure to control MP to <40% and reoperation. Guided growth not only decreases coxa valga but also reduces the risk of recurrent hip displacement after STR., Level of Evidence: Level III; case-control study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Peripheral nerve injuries are commonly encountered in extremity traumas. Their motor and sensory recovery following microsurgical repair is limited by slow regeneration speed (<1 mm/d) and subsequent muscle atrophy, which are consequently correlated with the activity of local Schwann cells and efficacy of axon outgrowth. To promote post-surgical nerve regeneration, we synthesized a nerve wrap consisting of an aligned polycaprolactone (PCL) fiber shell with a Bletilla striata polysaccharide (BSP) core (APB). Cell experiments demonstrated that the APB nerve wrap markedly promoted neurite outgrowth and Schwann cell migration and proliferation. Animal experiments applying a rat sciatic nerve repair model indicated that the APB nerve wrap restored conduction efficacy of the repaired nerve and the compound action potential as well as contraction force of the related leg muscles. Histology of the downstream nerves disclosed significantly higher fascicle diameter and myelin thickness with the APB nerve wrap compared to those without BSP. Thus, the BSP-loaded nerve wrap is potentially beneficial for the functional recovery after peripheral nerve repair and offers sustained targeted release of a natural polysaccharide with good bioactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Free flap monitoring is essential for postmicrosurgical management and outcomes but traditionally relies on human observers; the process is subjective and qualitative and imposes a heavy burden on staffing. To scientifically monitor and quantify the condition of free flaps in a clinical scenario, we developed and validated a successful clinical transitional deep learning (DL) model integrated application., Material and Methods: Patients from a single microsurgical intensive care unit between 1 April 2021 and 31 March 2022, were retrospectively analyzed for DL model development, validation, clinical transition, and quantification of free flap monitoring. An iOS application that predicted the probability of flap congestion based on computer vision was developed. The application calculated probability distribution that indicates the flap congestion risks. Accuracy, discrimination, and calibration tests were assessed for model performance evaluations., Results: From a total of 1761 photographs of 642 patients, 122 patients were included during the clinical application period. Development (photographs =328), external validation (photographs =512), and clinical application (photographs =921) cohorts were assigned to corresponding time periods. The performance measurements of the DL model indicate a 92.2% training and a 92.3% validation accuracy. The discrimination (area under the receiver operating characteristic curve) was 0.99 (95% CI: 0.98-1.0) during internal validation and 0.98 (95% CI: 0.97-0.99) under external validation. Among clinical application periods, the application demonstrates 95.3% accuracy, 95.2% sensitivity, and 95.3% specificity. The probabilities of flap congestion were significantly higher in the congested group than in the normal group (78.3 (17.1)% versus 13.2 (18.1)%; 0.8%; 95% CI, P <0.001)., Conclusion: The DL integrated smartphone application can accurately reflect and quantify flap condition; it is a convenient, accurate, and economical device that can improve patient safety and management and assist in monitoring flap physiology., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

As the essential amino acids, branched-chain amino acid (BCAA) from diets is indispensable for health. BCAA supplementation is often recommended for patients with consumptive diseases or healthy people who exercise regularly. Latest studies and ours reported that elevated BCAA level was positively correlated with metabolic syndrome, diabetes, thrombosis and heart failure. However, the adverse effect of BCAA in atherosclerosis (AS) and its underlying mechanism remain unknown. Here, we found elevated plasma BCAA level was an independent risk factor for CHD patients by a human cohort study. By employing the HCD-fed ApoE -/- mice of AS model, ingestion of BCAA significantly increased plaque volume, instability and inflammation in AS. Elevated BCAA due to high dietary BCAA intake or BCAA catabolic defects promoted AS progression. Furthermore, BCAA catabolic defects were found in the monocytes of patients with CHD and abdominal macrophages in AS mice. Improvement of BCAA catabolism in macrophages alleviated AS burden in mice. The protein screening assay revealed HMGB1 as a potential molecular target of BCAA in activating proinflammatory macrophages. Excessive BCAA induced the formation and secretion of disulfide HMGB1 as well as subsequent inflammatory cascade of macrophages in a mitochondrial-nuclear H 2 O 2 dependent manner. Scavenging nuclear H 2 O 2 by overexpression of nucleus-targeting catalase (nCAT) effectively inhibited BCAA-induced inflammation in macrophages. All of the results above illustrate that elevated BCAA promotes AS progression by inducing redox-regulated HMGB1 translocation and further proinflammatory macrophage activation. Our findings provide novel insights into the role of animo acids as the daily dietary nutrients in AS development, and also suggest that restricting excessive dietary BCAA consuming and promoting BCAA catabolism may serve as promising strategies to alleviate and prevent AS and its subsequent CHD., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Wassel classification is commonly used for cases of radial polydactyly but has not been used to predict surgical outcomes. This study aimed to investigate the predictive factors of surgical outcomes using the Wassel type and symmetry of duplication., Methods: Forty-five patients with 47 radial polydactylies were reviewed using the Japanese Society for Surgery of the Hand (JSSH) scores 4.6 years after minor thumb excision and reconstructive surgery. The symmetry index was defined as the metaphyseal width ratio of the minor thumb to the dominant thumb. The relationships between the JSSH scores and operation age, sex, side, follow-up duration, Wassel type, symmetric index, divergent angle, and joint angulation were analyzed by linear regression., Results: The mean JSSH score of the 47 thumbs was 18.3 points (range, 15-20). Five thumbs had fair or poor outcomes (scores <17), all of which were Wassel type IV. The hypoplastic type had a better JSSH score (19.4) than other Wassel types. The symmetric index had a negative relationship with JSSH scores, especially for Wassel type IV (r=-0.68, P =0.001). Linear regression revealed that the symmetric index was the only independent factor significantly associated with JSSH scores among Wassel type IV polydactylies ( P <0.05). The receiver operating characteristic curve suggested a symmetric index <0.74 could predict good or excellent outcomes., Conclusion: The symmetry of the 2 duplicated thumbs is an important factor for surgical outcomes. The Wassel type IV polydactylies with a symmetric index >0.74 are at greater risk of fair or poor outcomes after excision and reconstruction, and further studies are warranted to confirm whether the Bilhaut-Cloquet procedure is a good choice., Level of Evidence: Level IV-Case-control study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A newly introduced pan-immune-inflammation value (PIV) was not evaluated for its role in oral cavity squamous cell carcinoma (OSCC). In this study, the PIV was calculated with the following equation (neutrophil count × platelet count × monocyte count)/lymphocyte count from the results of the automated hematology analyzers in 853 OSCC patients from 2005 to 2017. The optimal cutoff for the preoperative PIV was 268, as determined by a receiver operating characteristic curve. Significant differences were observed for alcohol consumption, smoking, pT status, pN status, overall pathological status, extranodal extension, cell differentiation, depth of invasion, and perineural invasion between higher and lower PIV patients (all p values < 0.05). Kaplan-Meier and univariate regression analyses indicated that higher PIV was associated with worse overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival (all p values < 0.001). Multivariate analyses adjusted by various factors further demonstrated that PIV was an independent prognostic factor for overall and distant metastasis-free survival (p = 0.027, HR: 1.281 and p = 0.031, HR: 1.274, respectively). In conclusion, a higher PIV level was associated with poor clinicopathological factors in OSCC patients and could be used to predict poor posttreatment outcomes, especially for overall and distant metastasis-free survival.

Slow blood flow or no reflow following percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) typically leads to an adverse prognosis. However, it is controversial whether to use prourokinase (Pro-UK) during PCI in patients with acute STEMI. The present meta-analysis compared the efficacy and safety of intracoronary Pro-UK administration in patients with acute STEMI. Published randomized controlled trials (RCTs) were analyzed to compare Pro-UK with non-Pro-UK treatment in patients with acute STEMI. PubMed, Cochrane Library and China National Knowledge Infrastructure were searched and meta-analysis was performed using Review Manager 5.3 software. A total of 13 RCTs were selected and 1,797 patients were considered in the meta-analysis, including 897 patients who received Pro-UK intervention and 900 patients who were in the control group. No significant heterogeneity was identified across these selected studies. Pro-UK therapy significantly decreased the incidence of major adverse cardiac events [risk ratio (RR), 0.68; 95% CI, 0.56-0.82, P<0.0001], left ventricular end-diastolic diameter [standardized mean difference (SMD), -0.26; 95% CI, -0.40 - -0.12; P=0.0003], corrected thrombolysis in myocardial infarction (TIMI) frame count [SMD, -0.45; 95% CI, -0.62 - -0.28; P<0.00001] and cardiac troponin I [SMD, -0.31; 95% CI, -0.46 - -0.17; P<0.0001]. In addition, Pro-UK administration increased TIMI grade 3 flow (RR, 1.16; 95% CI, 1.07-1.25; P=0.0003), TIMI myocardial perfusion grade 3 (RR: 1.39, 95% CI: 1.12-1.74, P=0.004), ST-segment resolution (RR, 1.23; 95% CI, 1.10-1.36; P=0.0002) and left ventricular ejection fraction (SMD, 0.38; 95% CI, 0.27-0.49; P<0.00001). No significant difference was identified in bleeding (RR, 1.12; 95% CI, 0.85-1.47; P=0.41). The present meta-analysis determined that intracoronary Pro-UK administration is efficacious and safe to decrease slow blood flow or no reflow phenomena following PCI and improve the prognosis of patients with acute STEMI., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Fan et al.)

Peripheral nerve injuries are commonly occurring traumas of the extremities; functional recovery is hindered by slow nerve regeneration (<1 mm/day) following microsurgical repair and subsequent muscle atrophy. Functional recovery after peripheral nerve repair is highly dependent on local Schwann cell activity and axon regeneration speed. Herein, to promote nerve regeneration, paracrine signals of adipose-derived stem cells were applied in the form of extracellular vesicles (EVs) loaded in a thermosensitive hydrogel (PALDE) that could solidify rapidly and sustain high EV concentration around a repaired nerve during surgery. Cell experiments revealed that PALDE hydrogel markedly promotes Schwann-cell migration and proliferation and axon outgrowth. In a rat sciatic nerve repair model, the PALDE hydrogel increased repaired-nerve conduction efficacy; contraction force of leg muscles innervated by the repaired nerve also recovered. Electromicroscopic examination of downstream nerves indicated that fascicle diameter and myeline thickness in the PALDE group (1.91 ± 0.61 and 1.06 ± 0.40  μ m, respectively) were significantly higher than those in PALD and control groups. Thus, this EV-loaded thermosensitive hydrogel is a potential cell-free therapeutic modality to improve peripheral-nerve regeneration, offering sustained and focused EV release around the nerve-injury site to overcome rapid clearance and maintain EV bioactivity in vivo ., (© 2022 Author(s).)

Background: Orthopaedic wound complications are often associated with extensive surgeries and patient medical conditions. However, we noticed wound complications in minor growth modification surgeries in children, including guided growth and epiphysiodesis. Herein, we report the complication rate and risk factors associated with pediatric growth modification surgeries., Methods: This retrospective study reviewed surgical wound complications in 622 pediatric orthopaedic patients who underwent growth modification surgeries (418 children) or osteotomies (204 children) in the lower extremities in a single center between 2007 and 2019. The grades II and III complications assessed using the modified Clavien-Dindo-Sink complication classification system were compared between growth modification and osteotomy. Risk factors for complications, including the type of surgery, age, body mass index, neuromuscular disease, operation time, surgical sites per patient, surgical location, and implant types, were analyzed using the logistic regression., Results: The complication rate was 6.9% per patient and 3.6% per surgical site (29 sites in 29 patients comprising 21 grade II and 8 grade III) in the growth modification group, which was >1.0% per patient and 0.6% per site in the osteotomy group (2 sites in 2 patients comprising 2 grade III infections; P =0.001). Among 418 patients with 797 surgical sites in the growth modification group, wound complications were associated with surgical location (5.2% at distal femur vs. 1.0% at proximal tibia, P =0.002) and implant type (0.5% using transphyseal screw vs. 4.3-10.5% using plates or staples, P =0.011)., Conclusion: Surgical wound complication was associated with growth modification surgeries using plates or staples at the distal femur. Our results alert orthopaedic surgeons to this minor but unneglectable problem. Transphyseal screws may be the implant of choice for guided growth and epiphysiodesis at the distal femur in older children, considering the lower risks of wound complication., Level of Evidence: Level III, retrospective comparative study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Guided growth at the proximal femur using one transphyseal screw corrects coxa valga and improves hip displacement in cerebral palsy. This study aimed to validate the effects of adding guided growth (GG) to soft tissue release (STR), in terms of decreasing the migration percentage (MP), compared to those with soft tissue alone., Methods: This retrospective study comprised patients with cerebral palsy who underwent soft tissue release alone (Group STR) or soft tissue release plus guided growth (Group GG) for hip displacement (mean age, 8.1 years; mean follow-up, 4.9 years). Difference in the MP and rate of controlling MP <40% at 2 years postoperatively and rate of revision surgeries at 5 years postoperatively were compared between the groups., Results: The two groups were comparable in age, side, and gross motor function level, but Group GG (n = 24) had more severe hip displacement preoperatively than did Group STR (n = 64). Group GG had a significantly greater 2-year decrease in the MP (-14.8% vs. -11.8%, p < 0.05) than did Group STR. Among patients with a pre-operative MP >50%, the rate of MP <40% was greater in Group GG (73%) than in Group STR (41%). Revision surgeries, mainly repeated guided growth and soft tissue release, were comparable between the groups., Conclusions: This is the first comparative study to support adding guided growth to soft tissue release, as it results in greater improvements in hip displacement than that with soft tissue release alone. Non-ambulatory patients or severe hip displacement with MP 50%-70% could benefit from this less aggressive surgery by controlling the MP under 40% without femoral osteotomy., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Depression is common among patients with head and neck cancer, thereby affecting their survival rate. However, whether close monitoring of depression affects the survival outcomes of these patients is unknown. Therefore, this study aimed to determine whether depression treatment continuity after the diagnosis of cancer affects the survival of these patients., Methods: A total of 55,069 patients diagnosed with head and neck cancer in the Cancer Registration System database in Taiwan were enrolled. This cohort was followed from January 1, 2007 to December 31, 2017. Furthermore, the patients were divided into four groups, namely, "no depression," "pre-cancer only," "post-cancer only," and "both before and after cancer," on the basis of the diagnosis of depression and the duration of the follow-up period in the psychiatric clinic. Further, the Cox proportional hazard model was applied to estimate the hazard of death for the four groups., Results: A total of 6,345 (11.52%) patients were diagnosed with depression in this cohort. The "pre-cancer only" group had a lower overall survival (HR = 1.18; 95% CI = 1.11-1.25) compared with the "no depression" group. Moreover, the "post-cancer only" group had better overall survival (HR = 0.88; 95% CI = 0.83-0.94) compared with the "no depression" group, especially in advanced-stage patients. Patients who were diagnosed with depression before cancer and had continuous depression treatments after the cancer diagnosis had better overall survival (HR = 0.78; 95% CI = 0.71-0.86) compared with patients who had treatment interruptions., Conclusion: Patients with pre-cancer depression had poorer survival outcomes, especially those who did not receive psychiatric clinic visits after their cancer diagnosis. Nonetheless, in patients with advanced-stage cancer, depression treatment may improve overall survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Chang, Marchi, Loh, Lin, Chang and Kao.)

In this study, we developed a range of motion sensing system (ROMSS) to simulate the function of the elbow joint, with errors less than 0.76 degrees and 0.87 degrees in static and dynamic verification by the swinging and angle recognition modules, respectively. In the simulation process, the ɣ correlation coefficient of the Pearson difference between the ROMSS and the universal goniometer was 0.90, the standard deviations of the general goniometer measurements were between ±2 degrees and ±2.6 degrees, and the standard deviations between the ROMSS measurements were between ±0.5 degrees and ±1.6 degrees. With the ROMSS, a cloud database was also established; the data measured by the sensor could be uploaded to the cloud database in real-time to provide timely patient information for healthcare professionals. We also developed a mobile app for smartphones to enable patients and healthcare providers to easily trace the data in real-time. Historical data sets with joint activity angles could be retrieved to observe the progress or effectiveness of disease recovery so the quality of care could be properly assessed and maintained.

(1) Background: Diabetes impairs angiogenesis and wound healing. Paracrine secretion from adipose stem cells (ASCs) contains membrane-bound nano-vesicles called exosomes (ASC-Exo) but the functional role and therapeutic potential of diabetic ASC-Exo in wound healing are unknown. This study aims to investigate the in vivo mechanistic basis by which diabetic ASC-Exo enhance cutaneous wound healing in a diabetic mouse model. (2) Methods: Topically applied exosomes could efficiently target and preferentially accumulate in wound tissue, and the cellular origin, ASC or dermal fibroblast (DFb), has no influence on the biodistribution pattern of exosomes. In vivo, full-thickness wounds in diabetic mice were treated either with ASC-Exo, DFb-Exo, or phosphate-buffered saline (PBS) topically. ASC-Exo stimulated wound healing by dermal cell proliferation, keratinocyte proliferation, and angiogenesis compared with DFb-Exo and PBS-treated wounds. (3) Results: Diabetic ASC-Exo stimulated resident monocytes/macrophages to secrete more TGF-β1 and activate the TGF-β/Smad3 signaling pathway. Fibroblasts activated by TGF-β1containing exosomes from ASCs initiate the production of TGF-β1 protein in an autocrine fashion, which leads to more proliferation and activation of fibroblasts. TGF-β1 is centrally involved in diabetic ASC-Exo mediated cellular crosstalk as an important early response to initiating wound regeneration. (4) Conclusions: The application of diabetic ASC-Exo informs the potential utility of a cell-free therapy in diabetic wound healing.

Background: Distal femur extension osteotomy (DFEO) is a common treatment for knee flexion contracture and crouch gait in patients with cerebral palsy (CP), but skeletally immature patients tend to develop genu valgum deformities after DFEO. This study aimed to report the tendency of valgus changes after DFEO and determine the risk factors for subsequent surgery for excessive genu valgum., Methods: This retrospective case-control study included 25 children with CP who underwent DFEO in 44 limbs for knee flexion contractures ≥15 degrees at a mean age of 11.0 years. Radiologic measurements included the anatomic lateral distal femoral angle (aLDFA), anatomic tibiofemoral angle (aTFA), medial proximal tibia angle, and plate-condyle angle, postoperatively and at the latest follow-up. Age, sex, preoperative knee flexion contracture angle, Gross Motor Function Classification System level, and radiographic measurements were compared between children with and without subsequent guided growth for genu valgum., Results: A significant valgus change was observed at the distal femur in the first postoperative year (aLDFA from 83.6 to 80.1 degrees, P<0.001; aTFA from 176.1 to 172.5 degrees, P<0.01; plate-condylar angle from 5.3 to 9.5 degrees, P<0.001). Valgus changes occurred in 36 of the 44 limbs (82%) by an average of -4.6 degrees in the aLDFA, and subsequent guided growth was performed in 5 patients (20%). Guided growth for genu valgum was associated with a greater postoperative valgus angle (aLDFA: 78.0 vs. 84.9 degrees, P<0.01) but not with age, Gross Motor Function Classification System level, or preoperative flexion contracture., Conclusions: Distal metaphyseal osteotomies and distally placed angled plates near the physis are associated with valgus changes following growth. We recommend making a slight varus alignment during DFEO to compensate for subsequent valgus changes., Level of Evidence: Level III-therapeutic, retrospective comparative study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Double diapering may help to maintain a baby's hips in flexion and abduction posture, but the efficacy in facilitating hip maturation has never been verified. We investigated whether double diapering results in greater improvement of the alpha angle in newborn babies., Methods: This prospective study enrolled newborns with Graf type IIa immature hips and assigned them to the double-diaper or single-diaper group by the day of birth in a week. Parents were instructed on proper hip positioning, except for diapering. Change in the alpha angle from newborn to 1 month after birth, rate of improvement to bilateral Graf type I hips in 1 month, and number of ultrasound examinations and orthopaedic clinic visits in the first year were compared between the two groups., Results: Seventy newborns with 102 type IIa hips were included from January to December 2017. They were allocated to the double-diaper group (n = 33) and single-diaper group (n = 37). With a comparable sex ratio, gestational age, and newborn alpha angle, the double-diaper group had a greater increase of alpha angles in 1 month than the single-diaper group (+7.9° vs. +5.2°, t-test, p = 0.011). Twenty-eight babies in the double-diaper group (84.8%) and 20 babies in the single-diaper group (54.1%) improved to having bilateral Graf type I hips (chi-square test, p = 0.006). Under the same clinical management pathway, subsequent clinical visits and hip ultrasounds before 1 year were significantly reduced in the double-diaper group., Conclusion: Double diapering enhances hip maturation and reduces clinical costs in newborns with physiological immature hips, but the therapeutic role for hip dysplasia requires further study., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

Mechanically processed stromal vascular fraction (mSVF) is a promising source for regenerative purposes. To study the in vivo fate of the mSVF, we herein used a vascularized tissue engineering chamber that insulates the target mSVF from the surrounding environment. In contrast to previous models, we propose an arteriovenous (AV) shunt between saphenous vessels in rats without a venous graft. Mechanical SVF was processed from the fat pads of male Sprague Dawley rats, mixed with a fibrin hydrogel and implanted into an inguinal tissue engineering chamber. An arteriovenous shunt was established between saphenous artery and vein. On the contralateral side, an mSVF-fibrin hydrogel mix without vascular axis served as a non-vascularized control. After two and six weeks, rats were sacrificed for further analysis. Mechanical SVF showed significant numbers of mesenchymal stromal cells. Vascularized mSVF explants gained weight over time. Perilipin and CD31 expression were significantly higher in the mSVF explants after six weeks while no difference in DAPI positive cells, collagen deposition and FABP4 expression was observed. Morphologically, no differentiated adipocytes but a dense cell-rich tissue with perilipin-positive cells was found after six weeks. The phosphorylation of ERK1/2 was significantly enhanced after six weeks while Akt activation remained unaltered. Finally, mSVF explants stably expressed and released VEGF, bFGF and TGFb. Vascularized mSVF is able to proliferate and express adipocyte-specific markers. The AV shunt model is a valuable refinement of currently existing AV loop models in the rat which contributes to the fundamental 3R principles of animal research.

Background: Newborn hip screening aims to prevent the late diagnosis of and subsequent surgical procedures for developmental dysplasia of the hip (DDH). Weather may affect how parents swaddle their babies in early life, but weather has never been formally regarded as a risk factor in hip screening. This study investigates the association between the incidence of surgically treated DDH and the outdoor temperature., Methods: Surgical procedures for late-diagnosed DDH were investigated in 12 birth-year cohorts (1999 to 2010) using the Taiwan National Health Insurance Research Database. The number of children who underwent a DDH-related surgical procedure between 6 months and 5 years of age per total live births was evaluated as an outcome of hip screening. Trend and regression analyses were used to determine the association between the incidence of surgically treated DDH and birth year, birth month, and the temperature during the birth month and first 3 months of life., Results: The mean incidence of surgically treated DDH was 0.48 per 1,000 live births (1,296 surgically treated patients per 2,712,002 live births). The incidence of surgically treated DDH among babies born in winter months (0.70 per 1,000) was significantly higher than that among babies born in summer months (0.32 per 1,000), and it was significantly correlated with mean temperature in the first 3 months of life (r2 = 0.91; p < 0.0001) and birth month (r2 = 0.68; p < 0.001). Multivariable regression revealed that external temperature in the first 3 months of life was the most significant factor (β = -0.034 [95% confidence interval, -0.042 to -0.022]; p < 0.001) for the incidence of surgically treated DDH (adjusted r2 = 0.485). The trend of seasonal differences remained the same throughout the study years following implementation of the hip-screening policy., Conclusions: As the incidence of surgically treated DDH is the ultimate outcome of newborn hip screening, cold weather should be regarded as a risk factor and should be incorporated into future screening programs. Weather patterns of different geographical areas should be studied to determine if children born in the winter are at an increased risk for requiring a surgical procedure for DDH, and newborn hip-screening programs should be revised accordingly., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G793)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: Lymph node burden has been proposed to estimate the cumulative adverse effect of nodal metastasis. In this study, a meta-analysis was conducted to evaluate the prognostic value of lymph node burden in oral cavity squamous cell carcinoma., Study Designs: Systemic review and meta-analysis., Methods: PubMed, EMBASE and the Cochrane Library as well as manual searches were performed until April 2020. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival were extracted and pooled., Results: Eleven included studies were published between 2009 and 2019. The cumulative number of patients was 20,607 (range 35-14,554). Extranodal extension was adjusted or evaluated in all of the studies. The meta-analysis indicated that a higher lymph node burden was significantly related to worse overall survival (HR 2.62, 95% CI 2.12-3.25), worse disease-specific survival (HR 3.14, 95% CI 1.85-5.33) and worse disease-free survival (HR 2.30, 95% CI 1.62-3.26). The highest hazard ratio was observed when the cutoff value was 3 for overall survival, 3 for disease-specific survival, and 4 for disease-free survival. The hazard ratio showed an upward trend before the cutoff value of 3 but no significant incremental change when the cutoff exceeded 3., Conclusions: In oral squamous cell carcinoma, lymph node burden is an independent prognosticator for survival outcomes. However, more prospective or high-quality studies are required to determine the optimal cutoff., Level of Evidence: NA Laryngoscope, 132:88-95, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics., Methods: A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS., Results: Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50-59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly., Conclusions: Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

Background: The administration of postoperative radiotherapy remains controversial in pN1 oral cavity cancer patients without extranodal extension. The aim is to determine whether postoperative radiotherapy reduces the neck recurrence rate and improves the survival outcomes of pN1 patients., Methods: This study consecutively enrolled 1056 patients with newly diagnosed oral squamous cell carcinoma who underwent tumor wide excision and neck dissection from September 2002 to November 2019. One hundred two pN1 patients without extranodal extension were eligible for analysis. Then, a subgroup analysis of 40 patients was performed after patients with other adverse risk factors (positive margins, close margins, lymphovascular invasion, perineural invasion, tumor depth ≥ 10 mm, and poor histological differentiation) were excluded., Results: Of the 102 eligible pN1 patients, 26 patients received surgery alone, and 76 received postoperative radiotherapy. No significant differences were observed in the neck recurrence rate (7.7% vs. 15.8%, p = 0.30). Similarly, in patients without other adverse risk factors, no significant differences were observed in the neck recurrence rate (5% vs. 20%, p = 0.15) between surgery alone group and postoperative radiotherapy group. Moreover, no significant difference was found in the neck recurrence-free survival rate, overall survival, and disease-specific survival (77.1% vs. 52.5%, p = 0.42, 83.5% vs. 64.5%, p = 0.81, and 88.2% vs. 67.9%, p = 0.34, respectively)., Conclusion: Postoperative radiotherapy did not significantly decrease the probability of neck recurrence and survival outcomes in pN1 patients without extranodal extension. Radical surgery alone may be considered sufficient treatment for pN1 patients without other adverse risk factors., (© 2021. The Author(s).)

In the real condition, the small sensor found it difficult to detect the position of the pressure sore because of casting displacement clinically. The large sensor will detect the incorrect pressure value due to wrinkles without close to arm. Hence, we developed a simulated arm with physiological sensors combined with an APP and a cloud storage system to detect skin pressure in real time when applying a short arm cast or splint. The participants can apply a short arm cast or splint on the simulative arm and the pressure in the cast or splint could be immediately displaced on the mobile application. The difference of pressure values from six pressure detection points of the simulated arm between the intern and the attending physician with 20-year working experience were 22.8%, -7.3%, 25.0%, 8.6%, 38.2%, 49.6%, respectively. It showed that the difference of pressure values in two farthest points, such as radius stab and ulnar styloid, was maximal. The pressures on the skin surface of the short arm cast were within acceptable range. Doctors would obtain reliable reference data and instantly understand the tightness of the swathed cast which would enable them to adjust it at any time to avoid complications.

Purpose: This study aimed to compare the efficacy of decreasing leg-length discrepancy (LLD) and postoperative complications between tension band plates (TBP) and percutaneous transphyseal screws (PETS)., Methods: This retrospective study reviewed LLD patients who underwent temporary epiphysiodesis at the distal femur and/or proximal tibia from 2010 to 2017 (minimum two years follow-up). Efficacy of decreasing LLD was assessed one and two years postoperatively. Complications were classified with the modified Clavien-Dindo-Sink complication classification system. Knee deformities were assessed by percentile and zone of mechanical axis across the tibial plateau., Results: In total, 53 patients (25 boys, 28 girls) underwent temporary epiphysiodesis (mean age, 11.4 years). The efficacy of decreasing LLD at two years between the TBP (n = 38) and PETS (n = 15) groups was comparable. Seven grade III complications were recorded in six TBP patients and in one PETS patient who underwent revision surgeries for knee deformities and physis impingement. Four grade I and two grade II complications occurred in the TBP group. The mechanical axis of the leg shifted laterally in the PETS group and medially in the TBP groups (+7.1 percentile versus -4.2 percentile; p < 0.05). Shifting of the mechanical axis by two zones was noted medially in four TBP patients and laterally in two PETS patients., Conclusion: More implant-related complications and revision surgeries for angular deformities were associated with TBP. A tendency of varus and valgus deformity after epiphysiodesis using TBP and PETS was observed, respectively. Patients and families should be informed of the risks and regular postoperative follow-up is recommended., Level of Evidence: Level III., (Copyright © 2021, The author(s).)

Background: Dexamethasone (Dexa) is frequently administrated to patients receiving head and neck microsurgical reconstruction with nasotracheal intubation postoperatively for airway control. Infection is the greatest concern when prolonging the treatment course. We aimed to find out the relationship between flap infection and the safe dose of Dexa., Materials and Methods: A retrospective review of enrolling total 156 patients underwent microsurgical free flap reconstruction for head and neck cancers with nasotracheal intubation from December 2015 to December 2016 was conducted. Among them, 139 patients had received prolonged Dexa treatment course (>2 days). Safe index was then defined as the total amount of used Dexa (in milligrams) over body weight (in kilograms), body mass index (in kilograms per square meter) and body surface area (BSA, in square meter). Statistics were performed for the cutoff level of the safe index and to find out the independent risk factors., Results: The cutoff level of the safe index was 0.76 for body weight group, 2.28 (10-3 m2) for body mass index group, and 33.84 mg/m2 for BSA group. Safe index for BSA group also outweighed other risk factors in multivariant analysis (odds ratio = 6.242, 95% confidence interval = 2.292-17.002, P = 0.000), which is the only independent risk factors for flap infection in our cohort., Conclusions: Throughout our study, the "safe index" helps clinician easily predict flap infection risk when using Dexa as the medication for airway control after head and neck microsurgical reconstruction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The medial sural artery perforator flap is a versatile option in reconstructive microsurgery. However, most reports of this flap have been limited by sample size. This study reviews the experience of a single large-volume center using the medial sural artery perforator flap and its variants for a variety of reconstructive purposes., Methods: A retrospective review of all patients who received the medial sural artery perforator flap reconstruction between March of 2006 and July of 2014 was performed., Results: Two-hundred medial sural artery perforator flaps were used at three anatomical regions: head and neck (n = 129), upper extremity (n = 47), and lower extremity (n = 24). Flaps were transferred as free (n = 189) and pedicled (n = 11). Overall flap survival was 96 percent. Flap variants used included chimeric flap (n = 11) and dual skin paddle (n = 2). Plantaris tendon and saphenous/sural nerve graft were harvested in conjunction in 20 and seven patients, respectively. In 5 percent of the cases harvested in the conventional manner, a reliable perforator could not be found., Conclusions: The medial sural artery perforator flap is a reliable, alternative workhorse flap for nearly any small- to medium-size defect. It can be harvested as free or pedicled and the option to include multiple tissue components further expands its versatility., Clinical Question/level of Evidence: Therapeutic, IV.