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Background: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. Methods: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. Results: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. Conclusion: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients. [ABSTRACT FROM AUTHOR]

Preprocedural, real-time, and computer-aided three-dimensional ultrasound has been widely used for neuraxial puncture; however, the optimal guidance is unclear. We examined the comparative efficacy of three ultrasound guidance and anatomical landmarks for neuraxial puncture in adults. We searched for randomised controlled studies comparing the efficacy of ultrasound guidance and anatomical landmarks for neuraxial puncture in adults using electronic databases and unpublished studies. The primary outcomes were first-pass success and patient satisfaction. A random-effects network meta-analysis (NMA) was used. We identified 74 eligible studies (7090 patients). Preprocedural ultrasound and real-time ultrasound-guided neuraxial puncture improved first-pass success compared with anatomical landmarks (risk ratio [RR] 1.6; 95% credible interval [CrI] 1.3–1.9; RR 1.9; 95% CrI 1.3–2.9, respectively, moderate confidence). Computer-aided ultrasound-guided neuraxial puncture also increased first-pass success (RR 1.8; 95% CrI 0.97–3.3, low confidence), although estimates were imprecise. However, real-time ultrasound-guided neuraxial puncture resulted in minimal difference in first-pass success compared with preprocedural ultrasound (RR 1.2; 95% CrI 0.8–1.8, moderate confidence). Preprocedural ultrasound improved patient satisfaction slightly compared with anatomical landmark use (standardised mean differences 0.28; 95% CrI 0.092–0.47, low confidence). This NMA provides evidence supporting ultrasound-guided neuraxial puncture compared with use of anatomical landmarks, including indirect comparisons. Among the three ultrasound guidance methods, preprocedural ultrasound appears to be a better adjunctive option. [ABSTRACT FROM AUTHOR]

This study aimed to longitudinally evaluate speech perception ability and sound-field thresholds with the first, second, or bilateral cochlear implants (CIs) and MAP parameters of second CI in children. Eighteen children who underwent bilateral cochlear implantation at Kyoto University Hospital were included. We evaluated speech perception under quiet and noisy conditions using the first, second, or bilateral CIs, CI-aided sound-field thresholds using the first or second CI, and MAP parameter values (C-levels, T-levels, and dynamic range) of the second CI of more than 5 years after the second implantation. Patients with a second CI after 7 years of age had significantly worse speech perception ability with the second CI even long after the surgery than those with a second CI before 7 years of age. CI-aided sound-field thresholds using the first or second CI were similar, regardless of the second implantation timing. Speech perception in noise with bilateral CIs was enhanced by the addition of a second CI, even after 7 years of age. Patients undergoing second cochlear implantation before 3.5 years of age showed significantly higher C-levels and wider dynamic ranges in the second CI MAP parameters. When the second implantation was performed after 7 years of age, the second CI effects were limited even with long-term use, which is attributed to unstable MAP parameters. The second CI-aided sound-field threshold contributed to the better outcome of bilateral CIs in noise, even if the second implantation was performed at age of ≥7 years. [ABSTRACT FROM AUTHOR]

Background: Although previous studies have reported general inexperience with the Epley manoeuvre (EM) among general physicians, no report has evaluated the effect of EM on benign paroxysmal positional vertigo (BPPV) in primary care by using point estimates or certainty of evidence. We conducted this systematic review and meta-analysis and clarified the efficacy of EM for BPPV, regardless of primary-care and subspecialty settings. Methods: Systematic review and meta-analysis of randomised sham-controlled trials of EM for the treatment of posterior canal BPPV in primary-care and subspecialty settings. A primary-care setting was defined as a practice setting by general practitioners, primary-care doctors, or family doctors. A systematic search was conducted in January 2022 across databases, including Cochrane Central Resister of Controlled Trial, MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. Primary outcomes were the disappearance of subjective symptoms (vertigo), negative findings (Dix–Hallpike test), and all adverse events. We evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results: Twenty-seven randomised controlled trials were identified. In primary-care settings, EM reduced the subjective symptoms [risk ratio (RR), 3.14; 95% confidence interval (CI), 1.96–5.02]; however, there was no applicable article for all adverse events. In the subspeciality setting, EM reduced the subjective symptoms (RR, 2.42; 95% CI, 1.64–3.56), resulting in an increase in negative findings (RR, 1.81; 95% CI, 1.40–2.34). The evidence exhibited uncertainty about the effect of EM on negative findings in primary-care settings and all adverse events in subspecialty settings. Conclusions: Regardless of primary-care and subspecialty settings, EM for BPPV was effective. This study has shown the significance of performing EM for BPPV in primary-care settings. EM for BPPV in a primary-care setting may aid in preventing referrals to higher tertiary care facilities and hospitalisation for follow-up. Trial registration: The study was registered in protocols.io (PROTOCOL INTEGER ID: 51,464) on July 11, 2021. [ABSTRACT FROM AUTHOR]

Purpose: Spinal nerve injections have traditionally been performed under fluoroscopic (FL) and computed tomography (CT) guidance. Recently, ultrasound (US)-guided procedures have provided an alternative guidance approach that does not expose the patient and operator to radiation. The aim of this study was to compare the efficacy and safety of US-guided spinal nerve injections compared with FL- or CT-guided spinal nerve injections. Methods: MEDLINE, Cochrane Library, EMBASE, international clinical trials registry platform (ICTRP) and ClinicalTrials.gov database searches for inclusion until February 2023 were independently performed by two authors using predefined criteria. Randomized controlled trials (RCTs) were included. Primary outcomes were change in pain score (numeric rating scale or visual analogue scale) and major adverse events. Secondary outcomes were procedure time, change in functional disability score and minor adverse events. Meta-analysis was performed using random-effect model. We evaluated the certainty of evidence based on the Grading of Recommendations, Assessment and Development (GRADE) approach. Results: Eight RCTs involving 962 patients were included. There might be little to no difference in the mean score of the pain change between the US-guided methods and the FL- or CT-guided injections (standard mean difference -0.06; 95% confidence interval [CI] −0.26 to 0.15). US guidance probably reduced major adverse events (0.7% [3/433] and 6.5% [28/433], respectively), reduced procedure time (mean difference −4.19 min; 95% CI −5.09 to −3.30), and probably reduced minor adverse events (2.1% [9/433] and 4.2% [18/433], respectively) compared with FL or CT guidance. There was probably little to no difference in the change in functional disability score with either method. Conclusion: US-guided spinal nerve injections remained effective and reduced adverse events compared with conventional FL- or CT-guided spinal nerve injections. Further RCTs are required to verify our results. Study registration: Open Science Forum (Available from: https://osf.io/vt92w/). [ABSTRACT FROM AUTHOR]

Accurate disclosure of financial conflicts of interest (COI) among clinical practice guideline (CPG) developers is critical to ensure the quality of CPGs. However, there is limited evidence on the impact of underreporting COIs on the quality of CPGs. This study aimed to examine the proportion of underreported COI disclosures in the development of Japanese CPGs and to estimate the association between underreported COIs and CPG quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II. Twenty-three Japanese CPGs published in 2019 and their 1114 developers were included in the study. The results show that underreporting of COIs occurred in 52% of the included CPGs and 8% of all CPG developers. Underreporting COI disclosures was negatively associated with low-quality CPG (Odds ratio [OR], 0.57; 95% confidence interval [CI]: 0.11, 3.04). On the other hand, CPGs that had more than 13% of CPG developers with voting rights on recommendation decisions and underreporting of COI disclosures were positively associated with low quality (OR, 1.78; 95% CI: 0.25, 12.45). For individual CPG developers with voting rights for recommendation decisions, the presence of a COI was positively associated with low quality (OR, 1.11; 95% CI: 0.71, 1.75). This study demonstrates that the involvement and underreporting of COIs did not seriously distort the CPG development process. However, the COI-related factors of CPG developers with voting rights for recommendation decisions may be associated with low CPG quality. [ABSTRACT FROM AUTHOR]

Systematic reviews (SRs) with complete reporting or rigorous methods can lead to less biased recommendations and decisions. A comprehensive analysis of the epidemiological and reporting characteristics of SRs in orthopedics is lacking. We evaluated 360 SRs, including 165 and 195 published in orthopedic journals in 2012 and 2022. According to the established reporting guidelines, we examined these SRs for key epidemiological characteristics, including focus areas, type of meta-analysis (MA), and reporting characteristics. Most SRs (71%) were therapy-related, with a significant proportion originating from authors in the USA, UK, and China. Pairwise MA was performed on half of the SRs. The proportion of protocol registrations improved by 2022 but remained low (33%). Despite a formal declaration of adherence to the reporting guidelines (68%), they were often not used and reported enough. Only 10% of the studies used full search strategies, including trial registries. Publication bias assessments, subgroup analyses, and sensitivity analyses were not even planned. The risk of bias assessment improved in 2022; however, the certainty of the evidence remained largely unassessed (8%). The use and reporting of standard methods in orthopedic SRs have remained suboptimal. Thus, authors, peer reviewers, journal editors, and readers should criticize the results more. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective cohort study, predictive factors for graft survival were investigated in 123 patients who underwent reconstructions using a tumor-bearing frozen autograft after bone tumor resection of the extremities. The graft survival rates were 83.2% at 5 years and 70.2% at 10 years. Multivariate analysis using the Cox proportional hazards regression model revealed that BMI of ≥23.6 (HR, 3.4; p = 0.005), tibia (HR, 2.3; p = 0.047), and freezing procedure (HR, 0.3; p = 0.016) were independently associated with graft survival. Based on the results, pedicle or hemicortical freezing techniques are recommended in cases where these techniques can be applied. Tumor-bearing frozen autografts have been widely used for reconstruction of bone defects caused by tumor resection. However, some patients undergo removal of the grafted bone due to surgical site infection, tumor recurrence, or fractures of the grafted bone. In this retrospective cohort study, predictive factors for graft survival were investigated in 123 patients who underwent reconstructions using a tumor-bearing frozen autograft after bone tumor resection of the extremities. To determine the independent predictors of graft survival, the association between various parameters and graft survival was investigated. The graft survival rates were 83.2% at 5 years and 70.2% at 10 years. Among the 123 frozen autografts, 25 (20.3%) were removed because of complications. In univariate analyses, male sex, BMI of ≥23.6, tibia, and chemotherapy were significantly associated with poor graft survival, whereas the pedicle/hemicortical freezing procedure was significantly associated with better graft survival. Multivariate analysis using the Cox proportional hazards regression model revealed that BMI of ≥23.6 (HR, 3.4; p = 0.005), tibia (HR, 2.3; p = 0.047), and freezing procedure (HR, 0.3; p = 0.016) were independently associated with graft survival. Based on the results, pedicle or hemicortical freezing techniques are recommended in cases where these techniques can be applied. [ABSTRACT FROM AUTHOR]

Backgrounds: Immune checkpoint inhibitors (ICIs) can significantly prolong the survival of patients with advanced non‐small‐cell lung cancer (NSCLC); however, few studies on the therapeutic effects of ICIs on bone metastases were performed. Methods: This retrospective study aimed to investigate the therapeutic effects of ICIs and determine predictors of favorable ICI response and prognosis in 55 advanced NSCLC patients with bone metastases who initiated ICI treatment between 2016 and 2019, with a mean follow‐up period of 23.2 months. Patients were classified into responders (complete or partial response) and non‐responders (stable or progressive disease) according to the MD Anderson Cancer Center (MDA) criteria, and the predictors of therapeutic response were identified using multivariate logistic regression analysis. Furthermore, overall survival from the time of ICI administration to the final follow‐up or death was evaluated, and prognostic predictors were identified using Cox proportional hazards regression analysis. Results: ICI response rate was 30.9% (complete in three cases, partial in 14). Median survival time was 9.3 months, with 1‐year and 2‐year survival rates of 40.6% and 19.3%, respectively. Responders survived significantly longer than non‐responders (p = 0.03). Based on the receiver operating characteristic curve, the predictive cutoff value of the pretreatment neutrophil‐to‐lymphocyte ratio (NLR) was 2.1. Multivariate analysis identified female sex (p = 0.03), use of ICIs as first‐line therapy (p < 0.01), and NLR <2.1 (p = 0.03) as significant predictors of therapeutic response, whereas concomitant use of a bone‐modifying agent (p < 0.01), Katagiri score ≤6 points (p < 0.01), and NLR <2.1 (p = 0.02) were identified as significant predictors of good prognosis. Conclusions: This study identified some novel predictors for favorable therapeutic response and prognosis in advanced NSCLC patients with bone metastases undergoing ICI treatment. Pretreatment NLR less than 2.1 can be considered the most important predictor. [ABSTRACT FROM AUTHOR]

Calcium phosphate cement (CPC) is often used to repair bone defects that occur after bone tumor and fracture treatment. To address bone defect cases with a high infection risk, developing CPCs with a longlasting wide-spectrum antibacterial effect is critical. Povidone-iodine has a wide antibacterial spectrum. Though there have been some reports of CPC containing antibiotics, no report of CPC with iodine has been described. In this study, the antibacterial effect and biological reaction of CPC impregnated with iodine was investigated. Iodine release from CPC and bone cement with various iodine contents (2.5, 5, and 20%) was evaluated, and 5 %-iodine CPC retained more iodine than the other CPCs after one week. Antibacterial activity against Staphylococcus aureus and Escherichia coli was also investigated, showing that 5 %-iodine had an antibacterial effect for up to eight weeks. Cytocompatibility was assessed, and 5 %-iodine CPC showed the same amount of fibroblast colony formation as control samples. CPCs with varying iodine contents (0, 5, and 20%) were then inserted into lateral femora of Japanese white rabbits for histological analysis. Osteoconductivity was evaluated using scanning electron microscopy, and hematoxylin-eosin staining. Consecutive bone formation was observed around all CPCs at eight weeks. These results indicate that CPC impregnated with iodine exhibits antimicrobial activity and cytocompatibility, and therefore, it may be effective for bone defect cases with high infection risk. Graphical Abstract [ABSTRACT FROM AUTHOR]

The Surgical Patient Safety System (SURPASS) has been proven to improve patient outcomes. However, few studies have evaluated the details of litigation and its prevention in terms of systemic and diagnostic errors as potentially preventable problems. The present study explored factors associated with accepted claims (surgeon-loss). We retrospectively searched the national Japanese malpractice claims database between 1961 and 2017. Using multivariable logistic regression models, we assessed the association between medical malpractice variables (systemic and diagnostic errors, facility size, time, place, and clinical outcomes) and litigation outcomes (acceptance). We evaluated whether or not the factors associated with litigation could have been prevented with the SURPASS checklist. We identified 339 malpractice claims made against general surgeons. There were 159 (56.3%) accepted claims, and the median compensation paid was 164,381 USD. In multivariable analyses, system (odds ratio, 27.2 95% confidence interval 13.8–53.5) and diagnostic errors (odds ratio 5.3, 95% confidence interval 2.7–10.5) had a significant statistical association with accepted claims. The SURPASS checklist may have prevented 7% and 10% of the accepted claims and systemic errors, respectively. It is unclear what proportion of accepted claims indicated that general surgeon loses should be prevented from performing surgery if the SURPASS checklist were used. In conclusion, systemic and diagnostic errors were associated with accepted claims. Surgical teams should adhere to the SURPASS checklist to enhance patient safety and reduce surgeon risk. [ABSTRACT FROM AUTHOR]

Introduction: The cumulated ambulation score (CAS) has been developed as an index for evaluating mobility in the early postoperative period. This study aimed to estimate the association between CAS and independent ambulation after surgery for proximal femur fractures. Materials and methods: This retrospective cohort study included 223 elderly patients who underwent surgery for proximal femur fractures and had independent ambulation before the injury. Multivariable logistic regression analyses with cognitive impairment, pre-injury Barthel index, and CAS as the test variables were used to predict independent ambulation at 2 weeks (model 1) and 3 months (model 2) postoperatively. We established scoring systems based on the modeling results. Results: The number of patients with independent ambulation at 2 weeks and 3 months postoperatively was 115 and 169, respectively. Univariate analysis showed that the CAS was significantly associated with independent ambulation at 2 weeks and 3 months postoperatively. Multivariable analysis showed that models 1 and 2 had good predictive accuracies, with areas under the receiver-operating characteristic curve of 0.855 and 0.868, respectively. Among the explanatory variables, only the CAS in model 2 was not significantly associated with the postoperative ambulatory ability. Scoring systems for both models 1 and 2 also had good predictive accuracies, with cut-off scores of 3.5 for model 1 and 9.5 for model 2. Conclusions: The CAS predicted independent ambulation at 2 weeks postoperatively; however, this relationship was limited at 3 months postoperatively. Therefore, the CAS may help estimate independent ambulation at discharge from an acute-care hospital. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19). Otologic surgeries with drilling by powered instruments induce significant aerosols, which may induce SARS-CoV-2 transmission to medical staff if SARS-CoV-2 exists in the middle ear and mastoid cavity. During a COVID-19 pandemic, therefore, confirming a negative COVID-19 test prior to otologic surgery is recommended. However, previous coronavirus studies demonstrated that coronavirus was detected in the middle ear in some patients even though the polymerase chain reaction (PCR) test using their nasopharyngeal swab was negative. This study aimed to elucidate the probability of a positive SARS-CoV-2 PCR test in the middle ear or mastoid specimens from otologic surgery patients in whom SARS-CoV-2 was not detected by preoperative PCR test using a nasopharyngeal swab. We conducted a prospective, multicenter clinical study. Between April 2020 and December 2021, during the COVID-19 pandemic, 251 ears of the 228 participants who underwent otologic surgery were included in this study. All participants had no symptoms suggesting COVID-19 or close contact with a confirmed COVID-19 patient two weeks prior to the surgery. They were also negative in the SARS-CoV-2 PCR tests using a nasopharyngeal swab before surgery. We collected mucosa, granulation, bone dust with mucosa or fluid from the middle ear or mastoid for the SARS-CoV-2 PCR tests during each otologic surgery. The median age of the participants at surgery was 31.5 years old. Mastoidectomy using a powered instrument was conducted in 180 of 251 otologic surgeries (71.8%). According to intraoperative findings, active inflammation in the middle ear or mastoid cavities was evident in 20 otologic surgeries (8.0%), while minor inflammation was observed in 77 (30.7%). All SARS-CoV-2 PCR tests of otologic specimens showed a negative result. No patient suffered from COVID-19 within two months after otologic surgery. Furthermore, no hospital-acquired infections associated with otologic surgery occurred in our institutions Our results showed that PCR testing did not detect SARS-CoV-2 in middle ear and mastoid specimens, suggesting that the risk of transmission of SARS-CoV-2 is not high in otologic surgeries even using powered instruments when both clinical and laboratory tests are confirmed to be negative for COVID-19. [ABSTRACT FROM AUTHOR]

Medical litigation resulting from medical errors has a negative impact on health economics for both patients and medical practitioners. In medical litigation involving orthopedic surgeons, we aimed to identify factors contributing to plaintiff victory (orthopedic surgeon loss) through a comprehensive assessment. This retrospective study included 166 litigation claims against orthopedic surgeons using a litigation database in Japan. We evaluated the sex and age of the patient (plaintiff), initial diagnosis, diagnostic error, system error, the time and place of each claim that led to malpractice litigation, the institution's size, and clinical outcomes. The main outcome was the litigation outcome (acceptance or rejection) in the final judgment. Acceptance meant that the orthopedic surgeon lost the malpractice lawsuit. We conducted multivariable logistic regression analyses to examine the association of factors with an accepted claim. The median age of the patients was 42 years, and 65.7% were male. The litigation outcome of 85 (51.2%) claims was acceptance. The adjusted median indemnity paid was $151,818. The multivariable analysis showed that diagnostic error, system error, sequelae, inadequate medical procedure, and follow-up observation were significantly associated with the orthopedic surgeon losing the lawsuit. In particular, claims involving diagnostic errors were more likely to be acceptance claims, in which the orthopedic surgeon lost (adjusted odds ratio 16.7, 95% confidence intervals: 4.7 to 58.0, p < 0.001). All of the claims in which the orthopedic surgeon lost were associated with a diagnostic or system error, with the most common one being system error. System errors and diagnostic errors were significantly associated with acceptance claims (orthopedic surgeon losses). Since these are modifiable factors, it is necessary to take measures not only for individual physicians but also for the overall medical management system to enhance patient safety and reduce the litigation risk of orthopedic surgeons. [ABSTRACT FROM AUTHOR]

Bone sarcoma often occurs in childhood, as well as in adolescents and young adults (AYAs). AYAs differ from pediatric patients in that their bone is skeletally mature and the physis has almost disappeared with the completion of growth. Although AYAs spend less time outside, they often participate in sports activities, as well as driving, working, and raising a family, which are natural activities in daily living. Multidisciplinary approaches involving imaging, multi-agent chemotherapy, surgical procedures, and careful postoperative care has facilitated an increase in limb-sparing surgery for bone sarcoma. In addition, recent advances in imaging modalities and surgical techniques enables joint-preservation surgery, preserving the adjacent epiphysis, for selected patients following the careful assessment of the tumor margins and precise tumor excision. An advantage of this type of surgery is that it retains the native function of the adjacent joint, which differs from joint-prosthesis replacement, and provides excellent limb function. Various reconstruction procedures are available for joint-preserving surgery, including allograft, vascularized fibula graft, distraction osteogenesis, and tumor-devitalized autografts. However, procedure-related complications may occur, including non-union, infection, fracture, and implant failure, and surgeons should fully understand the advantages and disadvantages of these procedures. The longevity of the normal limb function for natural activities and the curative treatment without debilitation from late toxicities should be considered as a treatment goal for AYA patients. This review discusses the concept of joint-preservation surgery, types of reconstruction procedures associated with joint-preservation surgery, and current treatment outcomes. [ABSTRACT FROM AUTHOR]

Anteroposterior (AP) alignment assessment for nondisplaced femoral neck fractures is important for determining the treatment strategy and predicting postoperative outcomes. AP alignment is generally measured using the Garden alignment index (GAI). However, its reliability remains unknown. We compared the reliability of GAI and a new AP alignment measurement (valgus tilt measurement [VTM]) using preoperative AP radiographs of nondisplaced femoral neck fractures. The study was designed as an intra- and inter-rater reliability analysis. The raters were four trauma surgeons who assessed 50 images twice. The main outcome was the intraclass correlation coefficient (ICC). To calculate intra- and inter-rater reliability, we used a mixed-effects model considering rater, patient, and time. The overall ICC (95% CI) of GAI and VTM for intra-rater reliability was 0.92 (0.89–0.94) and 0.86 (0.82–0.89), respectively. The overall ICC of GAI and VTM for inter-rater reliability was 0.92 (0.89–0.95), and 0.85 (0.81–0.88), respectively. The intra- and inter-rater reliability of GAI was higher in patients aged <80 years than in patients aged ≥80 years. Our results showed that GAI is a more reliable measurement method than VTM, although both are reliable. Variations in patient age should be considered in GAI measurements. [ABSTRACT FROM AUTHOR]

Background. We report a retrospective case series analysis of clinical outcomes of patients with soft tissue sarcoma around the elbow. Methods. Twenty-two patients underwent surgical tumor excision between January 1999 and May 2017, with a mean follow-up of 85.2 months. Results. Six tumors were localized in the upper arm, nine in the elbow, and seven in the forearm. Sixteen tumors were deep-seated, and six were superficially located. Fifteen patients underwent wide excision, including one amputation, and 18 achieved (81.8%) negative margins histologically. Two local recurrences and four distant metastases developed. The mean Musculoskeletal Tumor Society score was 92.0% (range, 33.3–100). The 5-year local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate were 90.0%, 77.0%, and 79.7%, respectively. Conclusions. Local control and limb function can have favorable outcomes when the tumor excised has a histologically negative margin without sacrificing the major structure. [ABSTRACT FROM AUTHOR]

Background: Under most circumstances, the resection of soft tissue sarcomas of the extremities can be limb-sparing, function-preserving oncologic resections with adequate margins. However, en bloc resection may require resection of the major peripheral nerves, causing poor function in the extremities. Although liquid nitrogen treatment has been used to sterilize malignant bone tumors, its use in the preparation of nerve grafts has, to our knowledge, not been reported. Hence, this study aimed to investigate the tumor recurrence and function after peripheral nerve reconstruction using liquid nitrogen–treated tumor-bearing nerves in a rat model. Questions/purposes: (1) Do liquid nitrogen–treated frozen autografts have regeneration capabilities? (2) Do liquid nitrogen–treated tumor-bearing nerves cause any local recurrences in vivo in a rat model? Methods: Experiment 1: Twelve-week-old female Wistar rats, each weighing 250 g to 300 g, were used. A 10-mm-long section of the right sciatic nerve was excised; the prepared nerve grafts were bridge-grafted through end-to-end suturing. The rats were grouped as follows: an autograft group, which underwent placement of a resected sciatic nerve after it was sutured in the reverse orientation, and a frozen autograft group, which underwent bridging of the nerve gap using a frozen autograft. The autograft was frozen in liquid nitrogen, thawed at room temperature, and then thawed in distilled water before application. The third group was a resection group in which the nerve gap was not reconstructed. Twenty-four rats were included in each group, and six rats per group were evaluated at 4, 12, 24, and 48 weeks postoperatively. To assess nerve regeneration after reconstruction using the frozen nerve graft in the nontumor rat model, we evaluated the sciatic functional index, tibialis anterior muscle wet weight ratio, electrophysiologic parameters (amplitude and latency), muscle fiber size (determined with Masson trichrome staining), lower limb muscle volume, and immunohistochemical findings (though neurofilament staining and S100 protein produced solely and uniformly by Schwann cells associated with axons). Lower limb muscle volume was calculated via CT before surgery (0 weeks) and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 weeks after surgery. Experiment 2: Ten-week-old female nude rats (F344/NJcl-rnu/rnu rats), each weighing 100 g to 150 g, were injected with HT1080 (human fibrosarcoma) cells near the bilateral sciatic nerves. Two weeks after injection, the tumor grew to a 10-mm-diameter mass involving the sciatic nerves. Subsequently, the tumor was resected with the sciatic nerves, and tumor-bearing sciatic nerves were obtained. After liquid nitrogen treatment, the frozen tumor-bearing nerve graft was trimmed to a 5-mm-long tissue and implanted into another F344/NJcl-rnu/rnu rat, in which a 5-mm-long section of the sciatic nerve was resected to create a nerve gap. Experiment 2 was performed with 12 rats; six rats were evaluated at 24 and 48 weeks postoperatively. To assess nerve regeneration and tumor recurrence after nerve reconstruction using frozen tumor-bearing nerve grafts obtained from the nude rat with human fibrosarcoma involving the sciatic nerve, the sciatic nerve's function and histologic findings were evaluated in the same way as in Experiment 1. Results: Experiment 1: The lower limb muscle volume decreased once at 4 weeks in the autograft and frozen autograft groups and gradually increased thereafter. The tibialis anterior muscle wet weight ratio, sciatic functional index, muscle fiber size, and electrophysiologic evaluation showed higher nerve regeneration potential in the autograft and frozen autograft groups than in the resection group. The median S100-positive areas (interquartile range [IQR]) in the autograft group were larger than those in the frozen autograft group at 12 weeks (0.83 [IQR 0.78 to 0.88] versus 0.57 [IQR 0.53 to 0.61], difference of medians 0.26; p = 0.04) and at 48 weeks (0.86 [IQR 0.83 to 0.99] versus 0.74 [IQR 0.69 to 0.81], difference of median 0.12; p = 0.03). Experiment 2: Lower limb muscle volume decreased at 4 weeks and gradually increased thereafter. The median muscle fiber size increased from 0.89 (IQR 0.75 to 0.90) at 24 weeks to 1.20 (IQR 1.08 to 1.34) at 48 weeks (difference of median 0.31; p< 0.01). The median amplitude increased from 0.60 (IQR 0.56 to 0.67) at 24 weeks to 0.81 (IQR 0.76 to 0.90) at 48 weeks (difference of median 0.21; p < 0.01). Despite tumor involvement and freezing treatment, tumor-bearing frozen grafts demonstrated nerve regeneration activity, with no local recurrence observed at 48 weeks postoperatively in nude rats. Conclusion: Tumor-bearing frozen nerve grafts demonstrated nerve regeneration activity, and there was no tumor recurrence in rats in vivo. Clinical Relevance: A frozen nerve autograft has a similar regenerative potential to that of a nerve autograft. Although the findings in a rat model do not guarantee efficacy in humans, if they are substantiated by large-animal models, clinical trials will be needed to evaluate the efficacy of tumor-bearing frozen nerve grafts in humans. [ABSTRACT FROM AUTHOR]

Background: The supra-acetabulum is a common site for malignant bone tumors, which can be difficult to differentiate from insufficiency fractures. We report a rare case of a stress fracture of the supra-acetabulum that required differentiation from a malignant bone tumor.Case Presentation: A 74-year-old Japanese man presented to the hospital because of right hip joint pain. X-rays showed no obvious abnormalities. Magnetic resonance imaging showed an abnormality in the right supra-acetabulum, and he was referred to our department. A linear, low-signal region and its surrounding equal signal region were observed at the same site in the T1-weighted image, and a linear low-signal region and high signal region were observed in the surrounding area in the T2-weighted image. On the contrast-enhanced magnetic resonance imaging, the lesion was still unclear and the whole area was gradually enhanced. A computed tomography-guided needle biopsy was performed, but no tumor cells were observed, therefore the lesion was presumed to be a fracture healing. The bone density was 66% for the lumbar spine (young adult mean, L2-4), and blood biochemistry showed an increase in alkaline phosphatase and total type I procollagen N-terminal propeptide.Conclusion: This case was diagnosed as an insufficiency fracture of the supra-acetabulum in a male patient with primary osteoporosis by biopsy specimen. Initially, a pathological fracture associated with a malignant lesion was considered. On magnetic resonance imaging, the boundary around the fracture line was unclear and a signal change that was gradually enhanced by gadolinium was observed. This is likely to be bone marrow edema associated with the stress fracture, and we believe this to be a useful finding that may help in differentiating a stress fracture from a pathological fracture secondary to a malignant lesion. [ABSTRACT FROM AUTHOR]

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78–2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary. [ABSTRACT FROM AUTHOR]

Fixation using cephalomedullary nails (CMNs) with additional cement augmentation (CA) was developed as a novel treatment option for the osteosynthesis of osteoporotic trochanteric fractures, though the effectiveness of CA on early postoperative mobility remains uncertain. This multicenter prospective cohort study aimed to estimate the effectiveness of CA on early postoperative mobility in patients with trochanteric fractures. We enrolled patients with femoral trochanteric fractures aged >60 years who were able to walk independently before the injury. The primary outcome was the postoperative 3-day cumulated ambulation score (CAS); the secondary outcome was the visual analog scale (VAS) pain score at rest and during movement on postoperative days 1–3. The outcomes of the patients treated using CMNs with or without CA were compared. Sixty-three eligible patients were categorized into CA (n = 32) and control (n = 31) groups. In univariate analysis, the CA group had significantly higher CAS values, lower VAS scores at rest on day 1 postoperatively, and lower VAS scores during movement on day 3. In multivariable linear regression analyses, the CA group had significantly higher CAS values (beta, 2.1; 95% confidence interval, 0.5 to 3.6; p = 0.01). The CA group had a negative adjusted beta value in their VAS scores during movement. This study indicated that CA was associated with a high CAS value in patients with geriatric trochanteric fractures. However, CA was not associated with pain reduction at rest and during movement during the initial postoperative days. [ABSTRACT FROM AUTHOR]

Failed internal fixations for trochanteric fractures have a strong negative impact owing to increased postoperative mortality and high medical costs. However, evidence on the prognostic value of postoperative radiographic findings for failed internal fixations is limited. We aimed to clarify the association between comprehensive immediate postoperative radiographic findings and failed internal fixation using relative and absolute risk measures. We followed the meta-analysis of observational studies in epidemiology guidelines and the Cochrane handbook. We searched specific databases in November 2021. The outcomes of interest were failed internal fixation and cut-out. We pooled the odds ratios and 95% confidence intervals using a random-effects model and calculated the number needed to harm for each outcome. Thirty-six studies involving 8938 patients were included. The certainty of evidence in the association between postoperative radiographic findings and failed internal fixation or cut-out was mainly low or very low except for the association between intramedullary malreduction on the anteromedial cortex and failed internal fixation. Moderate certainty of evidence supported that intramedullary malreduction on the anteromedial cortex was associated with failed internal fixation. Most postoperative radiographic findings on immediate postoperative radiographs for trochanteric fractures were uncertain as prognostic factors for failed internal fixations. [ABSTRACT FROM AUTHOR]

• We evaluated the synergistic effects and safety of denosumab with ICIs in NSCLC. • Combination therapy with ICIs and denosumab showed favorable therapeutic effects. • Significant improvement observed in RR, OS and PFS in bone metastases. • No correlation between concomitant duration and incidence of irAEs observed. The concomitant use of denosumab and immune checkpoint inhibitor (ICI) treatment may have synergistic effects and enhance antitumor activity; however, this has not been fully evaluated. This study aimed to evaluate the clinical outcomes of non-small cell lung cancer (NSCLC) patients with bone metastases receiving combination therapy and to identify the best combination regimen. Eighty-six NSCLC patients with bone metastases who received ICI treatment were enrolled in this study. The patients were divided into two groups; a denosumab combination group (D + ICI group; n = 47) and a non-combination group (non-D + ICI group; n = 39). The response rate (RR) for bone metastases, disease control rate (DCR), overall survival (OS), real world progression-free survival (rwPFS), and the incidence of immune-related adverse events (irAEs) were evaluated. Additionally, the time when denosumab treatment should commence and concomitant treatment duration were evaluated. The D + ICI group showed significantly better RR (40.4 % vs. 20.5 %, p = 0.01), DCR (67.3 % vs. 38.7 %, p = 0.02), OS (14.2 vs. 8.6 months, p = 0.02), and rwPFS (7.4 vs. 3.6 months, p < 0.01) than the non-D + ICI group; however, incidence of irAEs showed no difference (29.7 % vs. 12.8 %, p = 0.07). Although clinical outcomes did not differ regardless of whether denosumab was initiated before or after ICI treatment, the group that received concomitant denosumab for more than four months had significantly better RR (46.2 % vs. 17.4 %, p = 0.03), OS (20.3 vs. 3.8 months, p < 0.01), and rwPFS (10.9 vs. 2.8 months, p < 0.01) than the group that received concomitant denosumab for less than four months. However, the landmark analysis showed no significant differences in OS (20.4 vs. 12.7 months, p = 0.11) and rwPFS (22.8 vs. 11.2 months, p = 0.21), and the results of denosumab duration were influenced by long-term survivors. Denosumab showed favorable synergistic effects with ICI treatment and may significantly improve the response to bone metastasis and prognosis without increasing the incidence of irAEs. [ABSTRACT FROM AUTHOR]

Although there are limited treatment options for sarcoma patients, recent studies have demonstrated promising therapeutic targets, anticancer agents, and combinations of these treatments. Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours. Chondrosarcoma, the second most common primary bone sarcoma, is characterised by the production of cartilaginous matrix and accounts for approximately 30% of malignant bone tumours. [Extracted from the article]

Introduction: Recent studies on posterior malleolar fractures mainly focus on the reduction quality and fixation of the posterior fragment since it contributes to ankle stability and articular congruency. However, the association of pre-and postoperative factors considering the whole ankle joint in postoperative functional outcomes remains unclear. Therefore, this study aimed to examine the association between pre-and postoperative variables for postoperative functional outcomes in patients with posterior malleolar fragments (classified as Haraguchi type I or II) and considered the association between reduction and fixation for small posterior malleolar fragments of less than 25% of the intra-articular surface.Methods: This multicenter retrospective cohort study included 110 adult patients who underwent internal fixation for ankle fractures with posterior malleolar fragments. The primary outcome was the American Orthopaedic Foot and Ankle Society (AOFAS) score 12-months postoperatively. As pre-and postoperative variables, the preoperative demographic data, radiographic findings, operative method, postoperative radiographic findings, and complications were evaluated. In addition, univariable and multivariable logistic regression analyses were conducted to examine the association between pre-and postoperative variables and AOFAS scores.Results: Twenty-four (21.8%) cases had postoperative complications. Univariate analysis showed that age was significantly according to AOFAS score-stratified groups in patients with Haraguchi type II fractures. Multivariable logistic regression analysis using bootstrapping in the Haraguchi type II group showed that postoperative complications were significantly associated with low AOFAS scores, indicating poor functionality. In both fracture types, postoperative complications had the highest odds ratio among the explanatory variables. In patients with small posterior malleolar fragments, fragment reduction, fixation, and ankle stability were not associated with AOFAS scores.Conclusions: Our results suggest that postoperative complications were associated with AOFAS scores at postoperative 12 months in patients with ankle fractures with posterior malleolar fragments. In patients with small posterior malleolar fragments, reduction and fixation were not associated with AOFAS scores. Therefore, clinical decisions for posterior fragment fixation should be made based on the possible risk of complications related to the surgical procedures in addition to the posterior malleolar fragment size. [ABSTRACT FROM AUTHOR]

Introduction: Proximal peri-implant femoral fractures occur following intramedullary nailing (IMN) fixation for trochanteric, femoral shaft, and distal femoral fractures. However, analyses of secondary hip fractures (SHFs) using large clinical samples are lacking. Therefore, we aimed to report the incidence and clinical outcomes of SHF after nailing fixation (IMN or cephalomedullary nailing [CMN]) for overall femoral fractures. In addition, we focused on IMN for femoral shaft fractures and investigated the risk factors for SHF.Methods: This multicenter, retrospective, cohort study included 2,293 patients aged > 60 years who underwent nailing fixation for femoral fractures. The primary outcome was the incidence of SHF. In the assessment of clinical outcomes, we evaluated reoperation and the regaining of walking ability following SHF management. In addition, we conducted multivariable logistic regression analyses to examine the association between risk factors and SHF.Results: Seventeen (0.7%) patients had SHFs, including 12 femoral neck fractures and 5 trochanteric fractures. Antegrade IMN was the most common type of nailing fixation. Multivariable analysis demonstrated that the absence of femoral head fixation was significantly associated with the incidence of SHF following IMN for femoral shaft fractures (odds ratio, 17.0; 95% confidence interval, 1.9-2265.7; p=0.006). In the assessment of clinical outcomes, there were two reoperations (16.7%) in the secondary femoral neck fracture group. Patients with secondary trochanteric fractures tended to have a lower probability of regaining walking ability than those with secondary femoral neck fractures (20% vs. 50%).Conclusions: In this multicenter study, the incidence of SHF after nail fixation for femoral fractures was 0.7%. The absence of femoral head fixation was significantly associated with SHF, and the clinical outcomes were poor. Therefore, femoral head fixation at the initial IMN fixation for femoral fractures may be a fixation option for surgeons to consider as an SHF prevention measure. [ABSTRACT FROM AUTHOR]

Background: Giant cell tumor of bone (GCTB) is an intermediate tumor commonly arising from the epiphysis of the distal femur and proximal tibia. Standard GCTB treatment is joint-preserving surgery performed using thorough curettage and the filling of the cavity with allo-, auto-, polymethyl methacrylate (PMMA), or synthetic bone graft. Calcium phosphate cement (CPC) is an artificial bone substitute, which has the benefit of being able to adjust defects, consequently inducing immediate mechanical strength, and promoting biological healing. Secondary osteoarthritis may occur following GCTB treatment and may need additional surgery if severe. However, details regarding surgery for secondary osteoarthritis have not been fully elucidated. There are no reports on the use of total knee arthroplasty (TKA) for the treatment of secondary osteoarthritis following CPC packing. The insertion of an alignment rod is a standard procedure in TKA; however, it was difficult to perform in this case due to CPC. Therefore, we used a computed tomography (CT)-free navigation system to assist the distal femur cut. This study presents a knee joint secondary osteoarthritis case following CPC packing for GCTB curettage that was treated with standard TKA.Case Presentation: A 67-year-old Japanese woman, who was previously diagnosed with left distal femur GCTB and was treated by curettage and CPC packing 7 years ago, complained of severe knee pain. Left knee joint plain radiography revealed Kellgren and Lawrence (K-L) grade 4 osteoarthritis without evidence of tumor recurrence. Therefore, she was scheduled for TKA. There are no reports on the cutting of a femoral condyle surface with massive CPC with accurate alignment. Because it is difficult to insert the alignment rod intramedullary and cut the femoral condyle with CPC, we planned CT-free navigation-guided surgery for accurate bone cutting using an oscillating tip saw system to prevent CPC cracks. We performed standard TKA without complications, as planned. Postoperative X-ray showed normal alignment. Knee Society Knee Score (KSKS) and Knee Society Function Score (KSFS) ameliorated from 27 and 29 to 64 and 68, respectively The patient can walk without a cane postoperatively.Conclusion: There was no report about the surface TKA guided by CT-free navigation after primary GCT surgery with CPC. We believe that this case report will help in planning salvage surgery for secondary osteoarthritis after CPC packing. [ABSTRACT FROM AUTHOR]

Introduction: Cephalomedullary nailing (CMN) is the standard treatment for internal fixation of trochanteric fractures. Complications related to CMN include intraoperative fracture (IF), which is difficult to detect using only plain radiographs. However, analyses of IFs using plain radiographs and computed tomography (CT) with a large sample size of clinical cases are lacking. Therefore, this study aimed to report the incidence of IFs diagnosed by CT, the risk factors for IFs, and a comparison of clinical outcomes between patients with and without IFs.Methods: This multicenter retrospective cohort study included 638 patients who underwent CMN fixation for trochanteric fractures. We evaluated IF using pre-and postoperative plain radiographs and CT. The primary outcome was reoperation and the secondary outcome was the proportion of patients who regained independent mobility at 3 months postoperatively. Furthermore, we conducted multivariable logistic regression analyses to examine the association between risk factors and IFs.Results: Seventy-five (11.8%) patients had IFs, including 53 patients with occult IFs (8.3%). The most common location of IF was at the interference with the lag screw entry (45.3%). The nail insertion procedure (17.3%) was the most common reason for IF. In the assessment of clinical outcomes, patients with IFs had no reoperations and independent mobility at postoperative 3 months was lower (69.6% vs. 79.1%). Regarding regaining independent walking in the IF group, IF distal to lag screw entry and obvious IF diagnosed with plain radiographs were poor factors. The multivariable analysis showed that only inadequate reduction on the anteroposterior view based on the plain radiograph was significantly associated with the incidence of IFs (odds ratio 3.91; 95% CI, 1.28-11.94; p = 0.017).Conclusions: This multicenter study indicated that the incidence of IFs detected by CT in CMN treatment for trochanteric fractures was 11.8%. An inadequate reduction in the anteroposterior view based on plain radiographs was the only independent risk factor of IFs. In the assessment of clinical outcomes, patients with IF had no incidences of reoperation. However, patients with IFs tended not to regain independent mobility compared with those without IFs. [ABSTRACT FROM AUTHOR]

Thickness loss due to corrosion wear generally occurs on ship structural members in corrosive environments. For corrosion wear, a probabilistic model can be successfully identified from the thickness measurements data to evaluate and estimate wear conditions. On the other hand, thickness loss due to mechanical wear may occur in some ship structural members in addition to thickness loss due to corrosion wear. In this study, a new probabilistic model for the case where mechanical wear is superimposed to corrosion wear is proposed. The condition observed in the actual structure is a mixture of corrosion wear condition and condition of corrosion wear with mechanical wear. When identifying a probabilistic model based on the plate thickness measurements data, it is impossible to distinguish whether the measurements data represent a corrosion condition due to corrosion wear or corrosion wear with mechanical wear. Therefore, a method is examined to obtain a model that would be the maximum likelihood by classifying the data using latent variables. By classifying the data and identifying both of a probability model of corrosion wear and a probability model of corrosion wear with mechanical wear, respectively, the posterior distribution of the latent variables is updated. These processes are repeated until the likelihood of the mixed probability models is maximized. For verification, a set of corrosion data consisting of mixed wear conditions were simulated and analyzed. It shows that both probability models could be properly identified with the proposed method, and in particular, the amount of diminution corresponding to high cumulative probability could also be properly estimated. Furthermore, this method was applied to thickness measurements data of ship structural members in the lower cargo holds of bulk carriers, where mechanical wear is also a concern, and it was confirmed that there was no difference in the corrosion wear condition of the members in the lower part of cargo holds of bulk carriers, however, significant differences were observed in the degree and extent of mechanical wear, indicating that the influence of mechanical damage is very significant in the wear condition of these members. • A model of thickness diminution when mechanical wear is superimposed on corrosion wear was proposed, and a probability model was constructed to represent the state of diminution of a mechanically damaged member. • A procedure to classify the thickness measurements data representing only thickness diminution into the data due to corrosion wear and data due to corrosion data with mechanical wear was studied. • By applying the proposed model to the thickness measurements data of inner bottom plate, bilge hopper plate and lower stool side plate in the cargo holds of bulk carriers, the degree of mechanical damage and the extent of damaged area of each member was clarified. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm that requires long-term management. Several reports describe disseminated intravascular coagulation (DIC) associated with angiosarcoma, but no association with EHE has been reported. We encountered a patient with DIC complicated by multifocal EHE. The patient was an 83-year-old woman with spinal lesions, small lung nodules, and a soft tissue mass in the right buttock. The tumor was biopsied and diagnosed as EHE. The patient received pain control therapy without antitumor therapy. One month later, DIC developed with tumor progression. DIC subsided with nafamostat mesylate infusion, and oral apixaban was administered. DIC was managed for 5 months until the patient died of brain metastases. This is the first report of a patient with DIC complicated by EHE. It should be noted that progression of EHE can cause DIC. We were able to manage DIC using anticoagulant agents. [ABSTRACT FROM AUTHOR]

Age affects the clinical outcomes of cancer treatment, including those for bone sarcoma. Successful reconstruction using frozen autograft after excision of bone sarcoma has been reported; however, little is known about the clinical outcomes of frozen autograft reconstruction according to age. The purpose was to evaluate the clinical outcomes of the frozen autograft reconstruction focusing on skeletally mature adolescents and young adults (AYAs) that was 15 to 39 years of age. A total of 37 AYA patients with primary bone sarcoma on the appendicular skeleton were enrolled in this study. The mean follow-up period was 89 months. The graft survival (GS), overall survival (OS), recurrence-free survival (RFS), complications and the function were retrospectively evaluated using medical records. The 10-year GS, OS, and RFS rates were 76%, 84%, and 79%, respectively. Bone union was achieved with a rate of 94% within 1 year after surgery, and nonunion (n = 1) and fracture (n = 2) were infrequently observed. Graft removal was performed in 7 cases, and the most common reason for the removal was infection (n = 5). The Musculoskeletal Tumor Society score was excellent in 23 cases of the available 29 cases. Frozen autograft reconstruction for AYAs showed excellent clinical outcomes, although the long-term follow-up is required. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric trochanteric fractures are a major global issue, and their incidence is steadily rising. Bone quality, fracture type, fracture reduction quality, implant selection, and implant placement affect bone-implant stability in osteoporotic fractures. Our aim in this study was to evaluate the association between bone-implant stability factors, including nail construct, and the rate of reoperation in a more extensive case series with comprehensive variables.Methods: This was a retrospective cohort study of 390 patients with trochanteric fractures aged ≥60 years and treated with intramedullary nailing. The primary outcome was the rate of reoperation due to any cause. Univariate and multivariable logistic regression analyses were used to identify factors associated with reoperation.Results: In this study, 15 patients (3.8%) required reoperation. Univariate analysis showed that the following variables were significantly different between patients who required reoperation and those who did not: T-score at the total hip and lumbar spine, cortical thickness index, fracture type, and reduction quality. Multivariable logistic regression analysis showed that the odds ratio (OR) for A3 fracture type was 2.76 (95% confidence interval [CI], 0.77-9.76; p=0.116) and that for inadequate reduction, assessed by computed tomography, was 2.94 (95% CI, 0.89-9.69; p=0.076). These were independent predictors of reoperation. There was only one case (6.7%) of reoperation among patients with a distal femoral fragment fixation ratio (FR) >0.8. Considering the intraoperative decision-making process, the combination of inadequate reduction and an FR ≤0.8 were associated with the highest reoperation at a rate of 9.3% (OR, 3.327; 95% CI, 1.091-10.142; p=0.043).Conclusions: Risk factors on bone-implant stability for reoperation were the reduction quality and fracture type. Regarding the intraoperative decision-making process, the selection of a nail length with an FR >0.8 is a better option when the intramedullary reduction has been maintained intraoperatively. [ABSTRACT FROM AUTHOR]

Introduction: Regaining independent ambulatory ability is one of the primary goals of treatment in patients with trochanteric fractures. This study aimed to develop and evaluate the discriminative accuracy of a clinical prediction model for ambulatory ability outcomes 3 months after surgery for trochanteric fractures.Methods: This retrospective cohort study included 346 patients treated with intramedullary nailing for trochanteric fractures who had independent ambulatory ability before their injury. Multiple regression models with preoperative and postoperative factors were used to predict ambulatory ability outcomes at 3 months. A clinical prediction model (CPM) was created based on a decision tree developed using a chi-square automatic interaction detector technique.Results: Three months after surgery, 263 (76.0%) and 83 (24.0%) patients regained and lost independent ambulatory ability, respectively. Univariate analysis showed that the Barthel index (BI) total score at 2 weeks predicted the ambulatory ability outcome at 3 months with good discriminative accuracy (area under the receiver operating characteristic curve [AUROC]: 0.819; 95% confidence interval [CI]: [0.769, 0.868], cut-off value: 22.5; sensitivity: 69.5%; specificity: 82.3%). Multiple logistic regression analysis showed that preoperative factors (residence before injury, diagnosis of dementia, and serum albumin at admission) and postoperative factors (BI total score at 2 weeks) predicted ambulatory ability outcomes at 3 months (AUROC: 0.710; 95%CI: [0.636, 0.783]; sensitivity: 91.3%; specificity: 41.8%). The CPM with the BI total score at 2 weeks (≤10; 10<, ≤50; >50 points) and dementia status (present; absent) had a moderate discriminative accuracy (AUROC: 0.676; 95%CI: [0.600, 0.752]; sensitivity: 94.7%; specificity: 40.5%).Conclusions: We developed a CPM with moderate accuracy to predict ambulatory ability outcomes in patients 3 months after surgery for trochanteric fractures. Our results demonstrate the importance of the BI score measured soon after surgery and dementia status for the prediction of postoperative ambulation. [ABSTRACT FROM AUTHOR]

Background: Evidence for the association between earthquakes and adverse perinatal outcomes is limited. Objectives: To evaluate the association between earthquakes and perinatal outcomes including preterm birth and low birth weight. Search Strategy: We searched studies using MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov on February 9, 2023. Selection Criteria: We included before‐and‐after studies that evaluated the associations between earthquakes and perinatal outcomes in women living in affected areas. Data Collection and Analysis: Two independent reviewers extracted data. We calculated the pooled odds ratio (OR) with the random‐effects model. We analyzed outcomes in subgroups of Asians and others. We evaluated the certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation system. Main Results: We included 2 607 405 women in 13 studies. Earthquakes may not increase preterm birth (nine studies, 1 761 760 participants: OR 1.10, 95% confidence interval [CI] 0.98–1.24, low certainty of evidence) or low birth weight (seven studies, 1 753 891 participants: OR 1.10, 95% CI 0.94–1.28, low certainty of evidence). Subgroup analyses showed that earthquakes may be associated with an increase of preterm birth among populations in Asia (OR 1.44, 95% CI 1.07–1.95), but this was not evident in others (OR 0.93, 95% CI 0.83–1.05). Conclusions: Perinatal outcomes might not change after earthquakes. Further research on the association between earthquakes and perinatal outcomes, combined with an assessment of the characteristics of the region, is needed. Synopsis: Preterm birth and low birth weight might not change after earthquakes. However, earthquakes may be associated with an increase of preterm birth in Asia. [ABSTRACT FROM AUTHOR]

Recent clinical studies have suggested that inhalation of incense smoke (IS) may result in impaired lung function and asthma. However, there is little experimental evidence to link IS with airway hyperresponsiveness (AHR) and bronchial epithelial barrier function. Using mouse and cell culture models, we evaluated the effects of IS exposure on AHR, expression of multiple epithelial tight junction (TJ)- and adherens junction-associated mRNAs and proteins in the lungs, and the barrier function of bronchial epithelial cells assessed by transepithelial electronic resistance (TEER). Exposure of BALB/c mice to IS increased AHR and inflammatory macrophage recruitment to BALF; reduced claudin-1, -2, -3, -7, -10b, -12, -15, and -18, occludin, zonula occludens-1 [ZO-1], and E-cadherin mRNA expression; and caused discontinuity of claudin-2 and ZO-1 protein immunostaining in lung tissue. IS extract dose-dependently decreased TEER and increased reactive oxygen species production in bronchial epithelial cell cultures. Treatment with N-acetyl-l-cysteine, but not glucocorticosteroids or long-acting β2-agonists, prevented the detrimental effects of IS. IS exposure can be problematic for respiratory health, as evidenced by AHR, increased recruitment of inflammatory macrophages and disruption of TJ proteins in the lung, and damage to epithelial barrier function. However, antioxidants may be useful for the treatment of IS-induced airway dysfunction. [ABSTRACT FROM AUTHOR]

Background: A histological diagnosis obtained from an intraoperative frozen section (FS) during biopsy confirms the adequacy of tumor tissue in the specimen. However, some cases show a discrepancy among the intraoperative FS diagnosis, permanent section (PS) diagnosis of the biopsy specimen, and the final diagnosis of the excised tumor specimen. In this study, we retrospectively investigated the diagnostic accuracy of the FS and PS for different types of bone tumors. Methods: This study included 377 patients with 411 bone tumors who underwent tumor excision after an open biopsy with intraoperative FS diagnosis. FS, PS, and final diagnoses of the patients were classified into benign tumors/tumor-like lesions, intermediate malignancies, and malignant tumors. To assess diagnostic accuracy, the histological grades in FS and PS diagnoses were compared with those in the final diagnoses. Results: The overall diagnostic accuracies of FS and PS were 93% and 97%, respectively. The accuracy of FS and PS for histological grade was 84% and 93% for chondrogenic tumors, 90% and 96% for osteogenic tumors, 97% and 98% for osteoclastic giant cell-rich tumors, 100% and 100% for tumors of undefined neoplastic nature, and 95% and 99% for other bone tumors, respectively. Conclusion: These data suggest that surgical planning based on PS diagnosis is recommended for chondrogenic and osteogenic tumors. [ABSTRACT FROM AUTHOR]

Background: Anterior wall fractures with comminution at the anterior cortex in pertrochanteric fractures are relatively rare. We aimed to investigate the prevalence and clinical findings of anterior wall fractures in this comparative cohort study.Methods: We reviewed 516 consecutive patients who underwent internal fixation. Anterior wall fractures were classified into three types: proximal, distal, and proximal/distal. Outcome measures included demographic data, residual anterior cortex length, fracture reduction, tip-apex distance (TAD), sliding distance, bone union, and revision surgery. We compared radiological outcomes between patients with anterior wall fractures and posterior comminuted fractures without an anterior wall fracture. The groups were matched for age and sex.Results: Anterior wall fractures were noted in 44 patients (8.5%). Residual anterior cortex length was shorter for the proximal/distal type. The distal type was the most common, was the most difficult to achieve an acceptable reduction status for, and was associated with the longest sliding distance. The proportion of unacceptable reduction status was higher for anterior wall fractures. However, there were no statistically significant differences between anterior wall fractures and posterior comminuted fractures without an anterior wall fracture in terms of TAD, sliding distance, bone union, and revision rate.Conclusions: This study suggests that anterior wall fracture is not a significant predictor of over-sliding distance. [ABSTRACT FROM AUTHOR]

Background: Low-grade myofibroblastic sarcoma (LGMS) is described as a distinct atypical myofibroblastic tumor often with fibromatosis-like features and predilection for the head and neck, especially the oral cavity and larynx. LGMS arising in the levator scapulae muscle is extremely rare.Case Presentation: A 69-year-old woman was admitted to our hospital because she noticed a hard mass in her left neck six months prior. Magnetic resonance images (MRI) showed a soft tissue tumor of the left levator scapulae muscle. A core needle biopsy showed cellular fascicles or a storiform growth pattern of spindle-shaped tumor cells with minimally atypia. Immunohistochemistry revealed focally positive for α-smooth muscle actin (α-SMA), negative for S-100, and a low-grade spindle cell sarcoma was suspected. Following a biopsy, the tumor was resected with a wide surgical margin. Immunohistochemical staining was a positive for vimentin and α-SMA and negative for desmin, CD34, nuclear β-catenin, and h-caldesmon. LGMS diagnosis was determined based on the histopathological findings. The patient was alive with no evidence of disease eight years after the surgery.Conclusions: To the best of our knowledge, this is the first case report of LGMS arising in the levator scapulae muscle. In addition to the case report, 48 reports with 103 LGMS cases are reviewed and discussed. In previous reports of LGMS, there were 43 females and 60 males, with a mean age of 43.0 years (range, 2-75). There were 13 (12.6%) patients aged < 18 years, 67 (65.1%) patients aged 18 to 59 years, and 23 (22.3%) patients aged ≥60 years. The average tumor size was 4.4 cm (range: 0.4-22.0). The commonest sites of LGMS was the tongue. Tumor growth patterns were evaluated in 52 cases, and 44 cases (84.6%) showed infiltrative growth patterns. Local recurrence was 26.7%, and distant metastasis was 4.4%. Because of the locally aggressive feature, it is important to diagnose LGMS with biopsy and to excise the tumor with an adequately wide margin. [ABSTRACT FROM AUTHOR]

Background: For excised tumor specimens, histological grades can differ between the biopsy diagnosis and the final diagnosis. Methods: We retrospectively investigated the diagnostic accuracies of histological grades for frozen-section and permanent-section diagnoses from patients with soft-tissue tumors. Frozen-section, permanent-section, and final diagnoses were classified as benign tumors/tumor-like lesions, intermediate malignancies, or malignant tumors. Diagnostic accuracies of the histological grades from the frozen and permanent sections were evaluated by comparing the final diagnoses for the resected specimens. Results: The diagnostic accuracies of the histological grades for the frozen- and permanent-section diagnoses were 95% (387/408 lesions) and 97% (395/408 lesions), respectively. Among the tumor types, the diagnostic accuracies of the histological grades for the frozen-section and permanent-section diagnoses were 84% and 87% for adipocytic tumors, 87% and 91% for fibroblastic/myofibroblastic tumors, 99% and 100% for nerve-sheath tumors, 98% and 98% for fibrohistiocytic tumors, 90% and 98% for tumors of uncertain differentiation, 100% and 100% for vascular tumors, and 97% and 98% for other tumors, respectively. Conclusions: Histological grades from frozen-section diagnoses yielded low diagnostic accuracies in adipocytic and fibroblastic/myofibroblastic tumors. Treatment should be planned based on permanent-section diagnosis and radiological findings for these tumors. [ABSTRACT FROM AUTHOR]

Background: Vacuum phenomenon (VP) in closed pelvic fracture is a rare disorder. This study aimed to examine the prevalence and clinical findings of VP in closed pelvic fracture.Methods: We retrospectively reviewed 197 patients with closed pelvic fracture who presented to our institution from January 2012 to December 2018. Pelvic fractures were diagnosed by plain radiography and computed tomography (CT). First, we investigated the prevalence and clinical findings of VP in pelvic fractures. Second, we compared the clinical findings between pelvic fracture with and without VP. Finally, VP in pelvic fracture was evaluated clinically and radiologically.Results: VP in pelvic fractures was detected by CT in 9 (3.6%) of the 197 patients with pelvic fractures. Patients with VP had a significantly greater proportion of fracture progression than those without VP (42.9% vs. 11.3%, P = 0.02). Patients with VP had a greater proportion of fragility fractures of the pelvis (FFP), and a lesser proportion of bone union than those without VP, although the differences were not significant. In nine pelvic fractures with VP, all sacral fractures were classified as type 1 according to the Denis classification, and all pubic fractures were classified as type 1 according to the Nakatani classification. Two (22.2%) nonunion in nine pelvic fractures with VP occurred at the pubic fracture site alone.Conclusions: Orthopedic clinicians should be aware of the potential of CT for detecting VP in pelvic fractures, especially in the course of FFP progression. [ABSTRACT FROM AUTHOR]

Extraskeletal osteosarcoma is a rare soft tissue sarcoma and typically appears as a solid mass with variable mineralization. A few cases of extraskeletal osteosarcoma have shown extensive hemorrhagic changes or bleeding due to its high-grade malignancy; however, to the best of our knowledge, no previous reports have described the pathological characteristics of tumors with non-hemorrhagic cystic change. The present report discusses three cases involving cystic lesions with a solid area at the periphery that arose in soft tissues. The large cystic spaces contained only yellowish-brown fluid and little or no blood, with no clear pathological necrotic tissue. The solid component comprised a focal area of osteoid production by highly anaplastic sarcomatous cells. All of the cases showed high-grade malignancy histologically, and the average maximum diameter was approximately 175 mm. The tumors were located at the adductor muscles in two cases and at the intermuscular region of the hamstring muscles in one case. All of the patients consulted a doctor after more than half a year had passed since the recognition of swelling or a mass on their affected extremities. Surgical treatment was performed for all patients. One patient had lymph node metastasis, and another had lymphoedema after surgery, but no histological invasion to the lymphatic ducts was observed in the excised specimen. Degenerative changes in the fluid content over a long time-course as a result of tumor bleeding or necrosis, rather than lymphorrhea by lymphatic channel invasion of the tumor, might have contributed to the formation of the cystic lesion. Only 1 patient who underwent chemotherapy remained clinically disease-free over 10 years after surgery. Chemotherapy regimens for osteosarcoma rather than those for soft tissue sarcoma are mostly effective for extraskeletal osteosarcoma, so the diagnosis by a biopsy is essential. It is important to consider extraskeletal osteosarcoma in the differential diagnosis of soft tissue tumor with cystic form and calcification and a long clinical course before consulting a doctor. [ABSTRACT FROM AUTHOR]

Background: Postoperative thrombosis of the external iliac artery (EIA) following open reduction and internal fixation for acetabular fracture is extremely rare.Purpose: To report a patient with EIA thrombosis following open reduction and internal fixation using the modified ilioinguinal approach for acetabular fractures.Study Design: This is a case report of a 69-year-old male with a left acetabular fracture who was treated surgically.Methods: A 69-year-old male presented with left hip pain after a 1.5-m fall. Radiographs revealed left acetabular anterior wall and posterior hemitransverse fractures with dome impaction. Computed tomography (CT) showed atherosclerotic changes in many arteries. Open reduction and internal fixation were performed using the modified ilioinguinal approach. Adhesion around the external iliac vessels was severe, and the external iliac vein (EIV) ruptured during exposure. After EIV repair, anatomical reduction was achieved and the fracture was fixed using a reconstruction plate. Nine hours after surgery, the left lower limb showed acute ischemic symptoms. Contrast-enhanced CT indicated complete occlusion of the left EIA. The patient was immediately taken for a thrombectomy via EIA cut-down using a Fogarty catheter. Postoperatively, he had palpable dorsalis pedis and posterior tibial pulses; however, post-reperfusion compartment syndrome developed. Fasciotomy of the left leg was performed.Results: At the 2-year and 4-month follow-up, he was pain-free in his hip and leg. Although he was walking with a cane, activity was limited due to a mild foot drop.Conclusions: It is very important for surgeons to consider EIA thrombosis as a potential complication following open reduction and internal fixation. In this case, EIA thrombosis could be explained by preoperative atherosclerotic changes and intraoperative vascular handling procedures. Preoperative screening and management, and meticulous surgical procedures are necessary for patients with a high risk of thrombosis. [ABSTRACT FROM AUTHOR]

The pedicle freezing procedure by liquid nitrogen is a method for the reconstruction of tumor-bearing bone after malignant tumor resection. However, the regenerative mechanism of bone after the pedicle freezing procedure is unclear. We investigated the complete process from devitalization to revitalization of bone after the pedicle freezing procedure in 13 rabbits. After osteotomy the 5 mm distal femurs were immersed in liquid nitrogen, and the specimens were divided into frozen area and sub-frozen area. The bilateral femurs were harvested for evaluation of bone regeneration by histological and immunohistochemical examination (VEGF, CD31, BMP-2 and Runx2) from 1 week to 52 weeks. The diameter of operating femurs was compared with contralateral femurs from 6 weeks to 52 weeks. No viable cells could be found from 1 to 8 weeks in the frozen area, and a mean 1.83 cm necrotic range were detected in the sub-frozen area. The periosteal reaction, massive fibrous tissue and immature bone matrix invaded from the normal area to the necrotic area from 12 weeks. Subsequently, the necrotic bone was gradually replaced by newly formed bone by creeping substitution, with endochondral and intramembrane bone formation. The diameter of frozen femurs was significantly larger than the contralateral femur at the same period from 8 weeks to 52 weeks (P < 0.01). All immunohistochemical factors were positively expressed in both areas at different time points. The active osteoblasts and microvessel migrated from marrow cavity and periosteum into dead bone. This study suggested that the frozen bone not only provides a scaffold but also possesses excellent osteoinductive properties. Image 1 [ABSTRACT FROM AUTHOR]

Background: Calcaneal insufficiency fracture (IF) following total knee arthroplasty (TKA) is a rare disorder. This study aimed to examine the prevalence and clinical findings of calcaneal IF following TKA.Methods: We retrospectively reviewed 3,585 consecutive patients undergoing primary TKA between 2012 and 2017 in four hospitals. Calcaneal IF following TKA was diagnosed by plain radiography or magnetic resonance imaging. First, we investigated the prevalence and clinical findings of calcaneal IF following TKA. Second, we classified calcaneal IF into three types based on its location: type 1, fracture by traction force around the Achilles tendon insertion; type 2, compression fracture around the posterior subtalar joint; and type 3, fracture by ground reaction force at the bottom of the calcaneus. Finally, we compared the clinical findings between calcaneal IF with and without TKA.Results: Calcaneal IF following TKA was seen in 17 (0.5%) of the 3,585 patients undergoing primary TKA. All patients were female, with a mean age of 76.5 ± 5.9 years, relatively high body mass index (BMI), and osteoporosis. All fractures achieved bone union with conservative treatment. Type 1 fractures were the most common. Calcaneal IFs following TKA were significantly shorter in height and the patients had higher BMI than those without TKA. The locations of calcaneal IF following TKA varied, while only type 1 calcaneal IFs were seen in cases without TKA. However, there were no significant differences with regard to the bone union period or malunion between the two groups.Conclusions: Calcaneal IF should be suspected in patients presenting with ipsilateral foot pain following TKA, particularly in female patients with a relatively high BMI and osteoporosis. Calcaneal IF can be classified into three types based on the fracture location. These variations in calcaneal IF may be due to differences in conditions and changes in mechanical loading of the lower extremity and bone quality following TKA. [ABSTRACT FROM AUTHOR]

Background: Managing pain during movement after hip fracture surgery is important for achieving earlier hip mobilisation and for preventing postoperative complications. In the present study, we tested the hypothesis that the fascia iliaca compartment block (FICB) would improve postoperative pain on movement compared with intravenous acetaminophen.Methods: In this prospective, randomised, controlled, parallel trial, patients were assigned to either the intravenous acetaminophen or the ultrasound-guided FICB group. Visual analog scale (VAS) pain scores were evaluated at 6, 9, 12, 18, 24 h, 2 days, and 7 days postoperatively. The primary outcome was VAS scores on movement at 24 h after surgery. The secondary outcomes were VAS scores on movement at the other time points, VAS scores at rest, the total number of rescue analgesics required and incidence of delirium during the first 24 h postoperatively, potential drug or block-related complications, and the time to first standing.Results: VAS scores on movement at 24 h after surgery were significantly lower in the FICB group than in the intravenous acetaminophen group [median (the 25th to 75th percentiles), 20 (10-30) vs 40 (30-53); P < 0.01]. The VAS scores on movement at any other time point and the scores at rest at 12 h after surgery were also significantly lower in the FICB group than in the intravenous acetaminophen group. The two groups did not differ in terms of the total number of rescue analgesics required or the incidence of delirium during the first 24 h postoperatively; complications; or the time to first standing.Conclusions: FICB improved postoperative pain on movement compared with intravenous acetaminophen without increasing the complication rate. However, the total number of rescue analgesics required and the time to first standing were not significantly different between the two groups. [ABSTRACT FROM AUTHOR]

Bone defect reconstruction with artificial materials may produce good functional recovery in the short term. Over time, the durability of artificial materials becomes an issue, and therefore, artificial materials cannot be considered a permanent solution to reconstruction. For long-term outcomes, the goal is to regain function, permanence, and form that are as close to normal as possible. Thus, physiological materials are desirable for use in reconstruction. Biological reconstruction involves the use of materials that are modified in vivo following reconstruction of bone defects. The goal is to achieve bone union, bone revival and remodeling, with biointegration of soft tissue and bone. Allograft use has been the mainstay of bone defect reconstruction in most parts of the world, although in some countries like Japan, allogeneic bone is difficult to obtain due to socio-religious concerns. Therefore, we developed new biological reconstruction techniques to overcome this problem. Bone derived from distraction osteogenesis is autologous bone, which must be an ideal reconstruction material for its biological affinity, strength, resilience, and immunity to infection. When applying this method to patients with malignant disease however, it is important to preserve as much of the local soft tissue as possible, and the clinician must be especially careful of infection and callus formation. Liquid nitrogen treatment of tumor-bearing bone produces equal, if not better, bone revitalization compared to other forms of treatment to date. Reconstruction with liquid nitrogen-treated bone involves resecting the diseased bone and returning it to the body following liquid nitrogen treatment (free-freezing method). Another method involves dislocating the joint proximal to the tumor, or cutting the bone while the distal side remains attached to the body and the limb inverted and treated with liquid nitrogen (pedicle freezing method). When both methods are possible, the pedicle freezing method is preferable since it is performed with minimal osteotomy. Our recent research has looked into the possible role of adipose-derived stem cells in promoting bone fusion and revitalization. This method has produced promising results for the future of biological reconstruction. [ABSTRACT FROM AUTHOR]

Abstract Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection. There is currently no effective vaccine or antiviral treatment available against DENV. In previous studies, we showed that Lactococcus lactis strain Plasma (LC-Plasma) could activate plasmacytoid dendritic cells, which play an important role against virus infection. LC-Plasma administration ameliorated symptoms of viral diseases and its effect appeared to be associated with IFN-α induction. However the precise mechanism of LC-Plasma protection remained unclear. In this study, we investigated the effects of LC-Plasma-induced humoral factors on DENV replication using HepG2 cells as an in vitro infection model. When HepG2 cells were preincubated with supernatants of LC-Plasma-stimulated bone marrow-derived dendritic cells, the replication of DENV was significantly inhibited in a dose dependent manner and its activity was evident regardless of the DENV serotype. In addition, the expression of interferon-stimulated genes, including ISG15 , IFITM-1 , MxA , RSAD2 , and RyDEN, was significantly upregulated by humoral factors. We also compared the effects of representative strains of lactic acid bacteria and found that the ability to prevent DENV replication was unique to LC-Plasma. In addition, it was revealed that both anti-DENV replication activity and ISG induction depended on type I IFN rather than type III IFN signaling. Taken together, since LC-Plasma induces, in a more natural form, potent anti-DENV replication activities irrespective of viral serotypes via induction of type I IFN, LC-Plasma could be safely used as a prophylactic anti-DENV option. Highlights • LC-Plasma-induced humoral factors prevented replication of all serotypes of dengue viruses in vitro and induced IFN-stimulated genes. • Preventive effect on dengue virus replication by LC-Plasma was a unique phenotype among various strains of lactic acid bacteria. • Type I IFN signaling was essential for the anti-viral effects of LC-Plasma-induced humoral factors. [ABSTRACT FROM AUTHOR]