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The rate of implant removal and the factors influencing its indication in patients with distal radius fracture (DRF) in Japan are unclear.We retrospectively evaluated the incidence rate of implant removal in a large cohort of DRF patients obtained from the Diagnosis Procedure Combination database in Japan between April 2014 and March 2019. Patient- and hospital-related factors possibly affecting removal rate, including age, sex, annual number of open reduction and internal fixation (ORIF) for DRF procedures per hospital, number of hospital beds, advanced or general care hospital, and hospital location were analyzed as well. Hospital location was classified into three types based on population and population density as 1) large city, 2) local city, and 3) sparse area.Implant removal was performed in 3242 (26.3%) of 12,328 DRF patients receiving ORIF. According to multivariate analysis, the significant factors related to a decreased probability of removal were older patients, male, large annual number of ORIF for DRF procedures per hospital, large number of hospital beds, advanced care hospital, and hospital in large city.This study clarified the current implant removal rate and trends following ORIF for DRF in Japan. Both patient- and hospital-related factors significantly impacted the decision for implant removal.

Summary The novel use of blood-based biospecimens from a retrospective cohort of 50 patients with osteosarcoma was recently studied. The potential clinical utility of sorting cell-free DNA by fragment size was defined, with shorter tumor-specific DNA enrichment providing prognostic value and allowing for streamlined molecular profiling of circulating tumor material. See related article by Udomruk et al., p. 2085

We evaluated the tendon length and excursion after extensor tendon grafting following ruptures at the distal radioulnar joint in eight patients. The mean patient age was 70.8 years (range 58 to 84), and the mean follow-up period was 63 months (range 12 to 129). Radiographic markers were placed on ends of the grafted tendon to assess changes in length and passive excursion. The mean length of the grafted tendon and mean passive excursion were 68.2 mm and 4.4 mm immediately after tendon grafting, 76.1 mm and 7.1 mm at 1 year postoperatively, and 76.3 mm and 7.3 mm at final follow-up, respectively. The mean elongation of the grafted tendon was 12% and mean increase of excursion was 2.9 mm. We recommend that tension set during extensor tendon grafting should be with the metacarpophalangeal joint of the affected finger in a slightly extended position as compared with adjacent fingers. Level of evidence IV

We report a dorsal trans-scaphoid perilunate fracture-dislocation associated with dorsal dislocation of the thumb carpometacarpal joint in a 25-year-old man. This is a rare injury and we discuss a possible mechanism for the injury. Level of Evidence: Level V (Therapeutic)

Background: In the conservative management of distal radial fractures (DRFs), the optimal dorsi-volar angulation of the wrist at cast immobilization and proper cast molding to minimize the risk of redisplacement are unclear. This study identified the predictors of fracture redisplacement during cast immobilization for adult DRFs. Methods: We examined for dorsi-volar angulation, gap index, volar tilt (VT), radial inclination (RI), and radial length (RL) in lateral or posteroanterior radiographs of 90 DRFs. We investigated possible predisposition factors for redisplacement including patient age, sex, extra- or intra-articular fracture, metaphyseal comminution, original displacements, dorsi-volar angulation of the wrist at cast immobilization, restoration of the volar cortex at cast immobilization, and gap index of the cast. Results: Neither dorsi-volar angulation nor gap index had significant association with an unacceptable alignment nor decrease of VT, RI, and RL. In multivariate analysis, patient age, original displacement, and intra-articular fracture were the significant predictors of an unacceptable alignment or decrease of VT and RI. Conclusions: Our findings indicate dorsi-volar angulation and cast molding quality have no clinical effect on preventing fracture redisplacement. The predictive factors of the displacement were patient age, original displacement, and intra-articular fracture.

Oncofertility is a developing field of increasing importance, particularly in pediatric oncology, where most patients are likely to survive long-term and have not yet had the opportunity to have children.We performed a quality improvement initiative to increase our rates of fertility preservation counseling and referral through the implementation of a pediatric oncofertility team, and we report outcomes 7 years following implementation of our initiative.We compare our baseline oncofertility survey to 44 post-intervention survey respondents and electronic medical record documentation for 149 patients treated in 2019. Ninety-five percent of post-intervention survey respondents recalled fertility counseling (baseline 70%, p = .004) and 89.3% were appropriately referred for fertility preservation (baseline 50%, p = .017). Counseling was documented in 60.4% of charts; 81% of patients analyzed by chart review were appropriately referred for fertility preservation. Fertility preservation outcomes differed by sex assigned at birth.Creation of an oncofertility team produced improvements in fertility counseling and fertility preservation referral across an extended period of time.

The detection of tumor-specific nucleic acids from blood increasingly is being used as a method of liquid biopsy and minimal residual disease detection. However, achieving high sensitivity and high specificity remains a challenge. Here, we perform a direct comparison of two droplet digital PCR (ddPCR)-based detection methods, circulating plasma tumor RNA and circulating plasma tumor DNA (ptDNA), in blood samples from newly diagnosed Ewing sarcoma patients. First, we developed three specific ddPCR-based assays to detect EWS-FLI1 or EWS-ERG fusion transcripts, which naturally showed superior sensitivity to DNA detection on in vitro control samples. Next, we identified the patient-specific EWS-FLI1 or EWS-ERG breakpoint from five patient tumor samples and designed ddPCR-based, patient-specific ptDNA assays for each patient. These patient-specific assays show that although plasma tumor RNA can be detected in select newly diagnosed patients, positive results are low and statistically unreliable compared with ptDNA assays, which reproducibly detect robust positive results across most patients. Furthermore, the unique disease biology of Ewing sarcoma enabled us to show that most cell-free RNA is not tumor-derived, although cell-free-DNA burden is affected strongly by tumor-derived DNA burden. Here, we conclude that, even with optimized highly sensitive and specific assays, tumor DNA detection is superior to RNA detection in Ewing sarcoma patients.

The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

We report outcomes 7 years following implementation of a pediatric oncofertility team. We compare our baseline oncofertility survey to 44 post-intervention survey respondents and electronic medical record documentation for 149 patients treated in 2019. 95% of post-intervention survey respondents recalled fertility counseling (baseline 70%, p=0.004) and 89.3% were appropriately referred for fertility preservation (baseline 50%, p=0.017). Counseling was documented in 60.4% of charts; 81% of patients were appropriately referred for fertility preservation. Fertility preservation outcomes differed by sex. Creation of an oncofertility team produced sustained improvements in fertility counseling and fertility preservation referral.

Purpose Advanced-stage trapeziometacarpal (TMC) osteoarthritis of the thumb often presents with concomitant hyperextension deformity of the metacarpophalangeal (MCP) joint. Although several studies have reported simultaneous procedures to correct this deformity, the indication for these procedures remains controversial. The purpose of this study was to evaluate changes in the range of motion (ROM) of the thumb MCP joint before and after TMC arthrodesis . Methods We evaluated the functional flexion and extension and functional ROM of the MCP joints during the performance of 10 activities of daily living tasks before and after TMC arthrodesis in 10 thumbs of 9 patients with Eaton stage III TMC osteoarthritis and hyperextension deformity of the MCP joint. Results The mean functional flexion of the MCP joint increased from 26° to 38°, and the mean functional extension of the MCP joint decreased from 16° to 5° of hyperextension. There was no change in the mean total arc of functional ROM of the MCP joint. Conclusions The MCP joint motion shifted from extension to flexion after TMC arthrodesis, and the total arc of functional ROM of the MCP joint was similar before and after arthrodesis. Type of study/level of evidence Therapeutic V

Background: Trigger digit(s) (TD) is one of the most common disorders of the hand in the elderly population. The aim of this study is to determine the prevalence and identify the risk factors for TD in an elderly Japanese population. Methods: We randomly sampled 1,297 subjects between the ages of 50 and 89 years from the population registry of a town in Japan. About 413 subjects agreed to participate in the study, and all were examined for the presence of TD. Subjects were divided into three groups namely history of treatment for TD in the past (PTD), current evidence of TD (CTD) or both (BTD). The prevalence of TD was weighted by age according to the composition of the Japanese population. Age, female gender, obesity, hard manual work, exposure to vibration tools, sports activity, smoking, alcohol, wrist fracture, hypertension, hypothyroidism, diabetes mellitus, rheumatoid arthritis and carpal tunnel syndrome were assessed as risk factors for TD using univariate and multivariate logistic regression analysis. Results: Forty subjects had TD. This included 18, 19 and 3 subjects with PTD, CTD and BTD, respectively. The weighted prevalence of TD was 9.7% (female, 14.3%; male, 4.4%) in the Japanese population aged 50–89 years. Age 70–79 and female gender were identified as risk factors for TD. Conclusions: The random sampling of a Japanese population registry between the ages of 50 and 89 years revealed the prevalence of TD as 9.7% and identified age between 70 and 79 and female gender as risk factors for developing TD. Level of Evidence: Level II (Therapeutic)

A man in his 70s was observed to have GIST recurrence 19 months after surgery. Chemotherapy was initiated with imatinib 400 mg/day orally. The dose was eventually reduced to 100 mg/day to avoid side effects. Tumor reduction was confirmed 3 months after treatment initiation. Currently, 84 months after the onset of GIST, the patient survives with continuous intake of the same dose of oral imatinib. We were able to observe long-term survival in a patient with recurrent GIST after the administration of a small dose of imatinib.

Although the use of aneurysmal common iliac artery (CIA) as the landing zone during endovascular aortic aneurysm repair EVAR remains an essential procedure, this procedure may increase the risk of late complications such as ongoing CIA dilatation and type Ib endoleak (CIA-related complications). We hypothesized that incomplete sealing of the aneurysmal CIA segment during EVAR could increase the incidence of CIA-related complications. In this study, we evaluated the midterm results of EVAR with aneurysmal CIA used as the landing zone and assessed the importance of distal sealing in this procedure.We retrospectively reviewed all cases of endovascular aneurysm repair using CIA as landing zone between 2007 and 2015 that had at least 3 years' follow-up. We defined aneurysmal CIA as maximum diameter ≥18 mm. The main outcome was the incidence of CIA-related complications. We compared midterm results between normal CIA and aneurysmal CIA. Next, we analyzed risk factors for CIA-related complications in aneurysmal CIA.Four complications occurred in normal CIA (mean follow-up, 66.5 ± 22.1 months); 21 occurred in aneurysmal CIA (mean follow-up, 62.2 ± 20.5 months). The 5-year portion of freedom from CIA-related complications was 97.3% in normal CIA and 69.4% in aneurysmal CIA (P 0.001). Multivariable analysis in aneurysmal CIA showed that unsealed CIA segment length was only risk factor for CIA-related complications. Given the receiver operating characteristic curve results, we defined the unsealed CIA segment ≥10 mm as incomplete sealing. The hazard ratio for incomplete sealing associated with CIA-related complications was 3.92 (95% confidence interval 1.62-9.46, P = 0.02).Use of aneurysmal CIA as landing zone increases the risk of CIA-related complications. However, maximum sealing of the aneurysmal CIA segment could prevent these complications.

Lessons from extinction can be used in trials designed to pursue a cure for cancer. When cancer cannot be cured, similar strategies may be unwise, and strategies that leverage the adaptations of cancer to therapy should be considered.

Objective/Background It was hypothesised that a helical stent with expanded polytetrafluoroethylene (ePTFE) grafts could provide a preventive effect for external iliac artery (EIA) limb occlusion following endovascular aortic aneurysm repair (EVAR). Therefore, a post-hoc analysis of a Japanese multicentre database was conducted to assess the impact of the stent graft design on EIA limb occlusion rates. Methods Patients who underwent EVAR with EIA limb deployment between 2008 and 2016 were evaluated. The stent graft limbs were divided into two groups: group A comprised stent graft limbs made of a helical stent with ePTFE grafts (Excluder; n = 255), and group B comprised stent graft limbs made of a Z stent with polyester grafts (Zenith, Flex and Endurant; n = 173). The main outcome was the incidence of limb occlusion and severe limb stenosis (EIA related limb complications). The risk factors for EIA related limb complications were analysed and the midterm results between groups A and B compared. Fine–Gray generalisation of the proportional hazards model was used after propensity score matching to calculate the hazard ratio (HR). Results One complication occurred in group A and 10 complications occurred in group B. The risk factors for EIA related limb complications for the entire group were a stent graft limb size ≤10 mm (HR 5.41; p = .01) and inclusion in group B (HR 14.9; p = .009). After propensity matching, group A (n = 159) was matched with group B (n = 159). The cumulative incidence function of EIA related limb complications at five years was 0.66% in group A and 7.8% in group B (HR 8.67; p = .039). Conclusion Stent graft design can affect limb patency in EIA limb deployment. When EIA limb deployment is necessary for patients with a small EIA, such as Japanese patients, stent graft limbs made of a helical stent with ePTFE should be used to reduce the risk of limb occlusion.

BackgroundThis study compared hand function and the cost effectiveness of treatment between collagenase Clostridium histolyticum (CCH) injection and limited fasciectomy for patients with Dupuytren’s contracture (DC).Materials and MethodsThe CeCORD-J study is a prospective, multicenter, non-randomized controlled, observational study of two parallel groups. Participants were DC patients with multiple affected fingers, including flexion contracture of the proximal interphalangeal (PIP) joint. The primary outcome was the Hand10 score, as a patient-reported outcome measure. We set secondary outcomes of EQ-5D-5L score, degree of extension deficit, and direct cost. Propensity score adjustment was used to balance differences in patient characteristics between groups.ResultsParticipants comprised 52 patients in the Collagenase group and 26 patients in the Surgery group. Hand10 score was significantly better in the Collagenase group at 1 and 2 weeks. EQ-5D-5L score was significantly higher in the Collagenase group at 8 weeks. Mean direct cost was 248,000 yen higher in the Surgery group than in the Collagenase group. Extension deficit angle of the PIP joint was significantly larger in the Collagenase group at 26 weeks.ConclusionsCCH injection provides better short-term hand function and cost effectiveness than surgery.UMIN-CTR (UMIN000029826)

Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT).The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE.This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.

Ewing sarcoma (ES) is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single-cell RNA sequencing (scRNA-seq) to characterize the transcriptional landscape of primary ES tumors, and to identify circulating tumor cells (CTCs) in peripheral blood at the time of diagnosis in order to further understand ES transcriptional heterogeneity and factors that drive metastasis. Methods: Viably frozen primary tumor and peripheral blood samples were obtained from 7 ES patients at the time of diagnosis and prior to the initiation of treatment. Tumors were dissociated into a single cell suspension and sorted for viability using FACS (fluorescence activated cell sorting) whereas peripheral blood samples were subjected to a size-based selection with the CellSieve microfiltration system. ScRNA-seq was performed using the 10xChromium platform and count matrices were generated using 10x Genomics Cell Ranger software. Quality control, integration, and cluster analysis was performed with Seurat. Results: Cluster analysis of integrated, primary tumor samples demonstrated that candidate ES cell clusters express FLI1 and ES marker NKX2-2 and cluster separately from immune cell populations. Additionally, using inferCNV, ES clusters were demonstrated to harbor chromosomal copy number alterations known to be associated with ES and that were previously identified clinically on preliminary pathology reports for each patient; further GSEA analysis showed significant overlap between published ES gene sets and genes upregulated in ES clusters. Further analysis of ES cells demonstrated that cell-cycle phase determined a cluster enriched in pro-proliferation gene signatures, and overall heterogeneity of expression of previously known therapeutic targets. Candidate ES CTCs were identified among the peripheral blood samples among clusters which corresponded with distinct immune cell populations. The candidate ES CTCs expressed NKX2-2 and demonstrated enrichment in oncogenic gene signatures. Conclusion: ScRNA-seq of primary ES tumors is feasible and demonstrates that ES tumor cells are largely homogeneous in nature; and candidate ES CTCs can be identified in peripheral blood at the time of diagnosis in ES patient and warrant further investigation as to their utility as a biomarker of metastatic disease. Citation Format: Sarah K. Nelson-Taylor, Avery Bodlack, Andrew Goodspeed, Amy Treece, Nathan Donaldson, Carrye Cost, Tim Garrington, Brian Greffe, Sandra Luna-Fineman, Jenna Sopfe, Masanori Hayashi. Single cell RNA sequencing of primary Ewing sarcoma tumors and identification of circulating tumor cells in patient-matched peripheral blood samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1681.

Introduction: Metastatic Ewing sarcoma (ES) has a dismal prognosis, and clarifying the molecular and cellular mechanism of metastasis is the most pressing need to improving prognosis. Recently, the heterogenous expression of the driving fusion gene EWS-FLI1, as well as canonical Wnt/β-catenin signaling activity has been increasingly recognized as a potential mediator of metastatic progression. However, targeting the pathway has been difficult due to its complexity and cross-activity, and not much is known of the mechanism of how ES cells maintain Wnt signaling heterogeneity. Cadherin-11 (CDH11) is a member of the cadherin super-family, which modulates calcium ion-dependent cell-cell adhesion and signal transduction, and is highly expressed in ES. CDH11 has been found to regulate the expression level of β-catenin, and play a key role in enhancing the stem cell, migration and invasion in other carcinomas, however the relationship between CDH11 and β-catenin in ES is not clear. Methods: Wnt/β-catenin dependent transcriptional activity of ES cells in vitro and in vivo were assessed by flow cytometry, immune fluorescence, as well as single cell RNA-seq. β-catenin and CDH11 knock-down cell lines were generated, and affected on invasion/migration, and metastatic progression was assessed in vitro and in vivo. Furthermore, the interaction of CDH11 with β-catenin, and the contribution of the protein-protein interaction to the heterogenous activation of Wnt/β-catenin was assessed by immunofluorescence, flowcytometry, Western blot, and co-immunoprecipitation. Results: At baseline, only a small fraction of ES cells have activated Wnt/β-catenin dependent transcriptional activity both in vitro and in vivo, which can respond rapidly with Wnt ligand stimulation. β-catenin knockdown reduced clonogenicity in vitro, and metastatic tumor burden in the orthotopic implantation amputation mouse model of ES. We further identified that most of the tested ES cells had abundant β-catenin bound to CDH11 in the cell membrane, which would rapidly be released through the cytoplasm and into the nucleus within 2 hours of adding exogenous Wnt ligand. CDH11 knockdown reduced β-catenin expression, rapid activation of signaling by Wnt ligands, and metastasis progression. Conclusion: Our data suggests that the cell surface CDH11- β-catenin complex contributes to the heterogenous and dynamic activation of the Wnt/β-catenin pathway in ES that drives ES metastasis. Targeting the CDH11- β-catenin complex can present a novel strategy to interfere with Wnt driven metastasis in ES. Citation Format: Ryota Shirai, Tyler Biebighauser, Sarah Nelson-Taylor, Avery Bodlak, Timothy Porfilio, Deandra Walker, Naoki Oike, Masanori Hayashi. Cadherin-11 contributes to the heterogenous and dynamic Wnt-β-catenin pathway activation in Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 957.

Purpose: To compare the long-term outcomes of the most widely used third-generation stent grafts, the Endurant and Excluder stent grafts, in Japanese patients using a multicenter registry. Materials and Methods: A retrospective analysis of endovascular aneurysm repairs for abdominal aortic and iliac artery aneurysms using either the Endurant or the Excluder stent grafts from January 2012 to July 2019 at 10 Japanese hospitals was performed. Results: A total of 332 and 378 repairs using the Endurant and Excluder stent grafts, respectively, were analyzed. Although the patients’ characteristics were generally similar in the two groups, the Endurant group exhibited significantly shorter (Endurant: 31.5±18.6 mm, Excluder: 37.4±21.0 mm; pConclusions: There were no statistically significant differences between the Endurant and the Excluder stent grafts in terms of intraoperative, perioperative, and late complication rates; however, the anatomical characteristics of the patients were significantly different.

Background The epidemiology of primary elbow osteoarthritis (PEOA) remains unknown. We aimed to evaluate the prevalence and associated factors of PEOA in a cross-sectional resident cohort from a municipal registry of a Japanese town. Methods A total of 415 residents over 50 years of age were randomly sampled from a Japanese town and were adjusted for age and gender. Those with diseases that could potentially cause a secondary osteoarthritis of the elbow were excluded. The remaining 318 subjects (150 males, 168 females) underwent bidirectional radiography of the elbow. Subjects were diagnosed with PEOA if one of their elbows was Kellgren-Lawrence (KL) grade 2 or greater. In addition, motion pain and tenderness at the elbow were examined by orthopedic surgeons. associated factors for the PEOA were statistically analyzed. Results The prevalence of PEOA was 25.2% (male, 27.3%; female, 23.2%), and the prevalence of symptomatic PEOA was 0.9%. The age-stratified prevalence of PEOA was as follows: 50-59, 6.2% (male, 5.0%; female, 7.3%); 60-69, 15.4% (male, 17.5%; female, 13.7%); 70-79, 29.5% (male, 35.3%; female, 25.0%); 80-89, 55.9% (male, 55.6%; female, 56.3%). Age and body mass index (BMI) were revealed as associated factors that increased the prevalence of PEOA with KL grade 2 or greater. The use of vibrating tools was demonstrated as an independent associated factor that increased the prevalence of PEOA with KL grade 4 in addition to the two aforementioned factors. Conclusions The prevalence of PEOA in Japanese subjects was 25.2% for those aged 50-89 with a mean age of 69.2 years, most of which were asymptomatic OA without motion pain or tenderness at the elbow. Age and BMI increased the prevalence of PEOA with KL grade 2 or greater. The prevalence of PEOA increased with age, but the disease was self-accommodated by most people. Level of Evidence Level III; Cross-Sectional Design; Epidemiology Study

Objective: The purpose of this study was to evaluate the effect of atheromatous aorta on thromboembolic complications after endovascular aortic aneurysm repair (EVAR) and to assess the risk factors for these complications. Materials and Methods: This retrospective study included patients who underwent EVAR for an abdominal aortic aneurysm at the Shizuoka Red Cross Hospital from 2007 to 2018. We defined atheromatous aorta as a thoracic shaggy aorta or abdominal aorta with neck thrombus. The main outcome was renal dysfunction and peripheral embolization (thromboembolic complications). We compared the incidence of thromboembolic complications between patients with normal aorta and atheromatous aorta. Moreover, we assessed the risk factors associated with thromboembolic complications in patients with atheromatous aorta. Results: Patients with atheromatous aorta had significantly more thromboembolic complications, such as renal dysfunction (24.5% vs. 3.9%; P

For many pediatric sarcoma patients, multi-modal therapy including chemotherapy, radiation, and surgery is sufficient to cure their disease. However, event-free and overall survival rates for patients with more advanced disease are grim, necessitating the development of novel therapeutic approaches. Within many pediatric sarcomas, the normal immune response, including recognition and destruction of cancer cells, is lost due to the highly immune suppressive tumor microenvironment (TME). In this setting, tumor cells evade immune detection and capitalize on the immune suppressed microenvironment, leading to unchecked proliferation and metastasis. Recent preclinical and clinical approaches are aimed at understanding this immune suppressive microenvironment and employing cancer immunotherapy in an attempt to overcome this, by renewing the ability of the immune system to recognize and destroy cancer cells. While there are several factors that drive the attenuation of immune responses in the sarcoma TME, one of the most remarkable are tumor associated macrophage (TAMs). TAMs suppress immune cytolytic function, promote tumor growth and metastases, and are generally associated with a poor prognosis in most pediatric sarcoma subtypes. In this review, we summarize the mechanisms underlying TAM-facilitated immune evasion and tumorigenesis and discuss the potential therapeutic application of TAM-focused drugs in the treatment of pediatric sarcomas.

BACKGROUND: The combination of gemcitabine and docetaxel is often used to treat patients with recurrent sarcoma. Nab-paclitaxel is a taxane modified to improve drug exposure and increase intratumoral accumulation and, in combination with gemcitabine, is standard therapy for pancreatic cancer. Applying the dosages and schedule used for pancreatic cancer, we performed a phase II trial to assess the response rate of gemcitabine and nab-paclitaxel in patients with relapsed Ewing sarcoma. PROCEDURE: Using a Simon’s two-stage design to identify a response rate of ≥ 35%, patients received nab-paclitaxel 125 mg/m(2) followed by gemcitabine 1000 mg/m(2) i.v. on days 1, 8, and 15 of four-week cycles. Immunohistochemical analysis of archival tissue was performed to identify possible biomarkers of response. RESULTS: Eleven patients from four institutions enrolled, with a median age of 22 years (range, 14–27). Patients were heavily pretreated (median 3 prior regimens, range, 1–7). Thirty-five cycles were administered (median 2, range, 1–8). Accrual was stopped after 11 patients, due to only one confirmed partial response. Two other patients had partial responses after two cycles, but withdrew because of adverse effects or progression before confirmation of continued response. The predominant toxicity was myelosuppression, and four (36%) patients were removed due to hematologic toxicity despite pegfilgrastim and dose reductions. Expression of secreted protein, acidic and rich in cysteine (SPARC) and CAV-1 in archival tumors was not predictive of clinical benefit in this small cohort of patients. CONCLUSIONS: In patients with heavily pretreated Ewing sarcoma, the confirmed response rate of 9% was similar to multi-institutional studies of gemcitabine and docetaxel.

For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single-cell RNA-sequencing (scRNA-seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size-exclusion membranes followed by scRNA-seq of enriched CTCs and carry-over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial-mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD-1/PD-L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA-seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune-evasive competence.

Background Hand osteoarthritis (OA) has a wide spectrum of clinical presentations and physical function is one of the core domains where patients suffer. The Functional Index for Hand Osteoarthritis (FIHOA) is a leading assessment tool for hand OA-related functional impairment. Our objective was to make a Japanese version of FIHOA (J-FIHOA) and validate it among Japanese hand OA patients. Methods Forward and backward translation processes were completed to create a culturally adapted J-FIHOA. A prospective, observational multicenter study was undertaken for the validation process. Seventeen collaborating hospitals recruited Japanese hand OA patients who met the American College of Rheumatology criteria. A medical record review and responses to the following patient-rated questionnaires were collected: J-FIHOA, Hand20, Health Assessment Questionnaire (HAQ), numerical rating scale for pain (NRS pain) and Short Form 36 Health Survey (SF-36). We explored the structure of J-FIHOA using factor analysis. Cronbach’s alpha coefficients and item-total correlations were calculated. Correlations between J-FIHOA and other questionnaires were evaluated for construct validity. Participants in clinically stable conditions repeated J-FIHOA at a one- to two-week interval to assess test-retest reliability. To evaluate responsiveness, symptomatic patients who started new pharmacological treatments had a 1-month follow-up visit and completed the questionnaires twice. Effect size (ES) and standardized response mean (SRM) were calculated with pre- and post-treatment data sets. We assessed responsiveness, comparing ES and SRM of J-FIHOA with other questionnaires (construct approach). Results A total of 210 patients participated. J-FIHOA had unidimensional structure. Cronbach’s alphas (0.914 among females and 0.929 among males) and item-total correlations (range, 0.508 to 0.881) revealed high internal consistency. Hand20, which measures upper extremity disability, was strongly correlated with J-FIHOA (r = 0.82) while the mental and role-social components of SF-36 showed no correlations (r = − 0.24 and − 0.26, respectively). Intraclass correlation coefficient for test-retest reliability was 0.83 and satisfactory. J-FIHOA showed the highest ES and SRM (− 0.68 and − 0.62, respectively) among all questionnaires, except for NRS pain. Conclusions Our results showed J-FIHOA had good measurement properties to assess physical function in Japanese hand OA patients both for ambulatory follow-up in clinical practice, and clinical research and therapeutic trials.

Background: The aim of this study was to identify the risk factors for median nerve dysfunctions after volar locking plate (VLP) fixation for distal radius fracture (DRF).Methods: We prospectively assessed the incidence of median nerve symptoms (MNS) such as numbness, pain, paresthesia, or hypesthesia in the area innervated by the median nerve and evaluated post-operative nerve conduction (NC) in 91 hands of 121 patients after VLP fixation for DRF. Multivariate logistic regression analysis was conducted to identify factors independently associated with MNS and abnormal NC in the injured wrist.Results: There were 18 cases (20%) of MNS on the injured side, 9 hands (10%) of both MNS and abnormal NC, 11 hands (12%) with only abnormal NC, and 9 hands with only MNS. Sensitivity, specificity, and diagnostic accuracy of abnormal NC for diagnosing MNS were 50%, 86%, and 78%, respectively. Four cases did not respond to conservative treatment and received carpal tunnel release concomitantly with plate removal. Logistic regression examination revealed that volar placement of the plate and short stature were significant independent predictors of MNS, while patient age was the sole independent predictor of abnormal NC.Conclusions: Our study demonstrated that plate prominence, short stature, and age were significant independent risk factors for median nerve dysfunctions after VLP fixation for DRF.

Background: Cubital tunnel syndrome (CuTS) is generally treated successfully by surgery and recurrent cases are rare. This study retrospectively investigated the clinical characteristics of recurrent CuTS caused by ganglion.Methods: We evaluated nine patients who were surgically treated for recurrent CuTS caused by ganglion. Age distribution at recurrence ranged from 43 to 79 years. The initial surgery for CuTS had been performed using various methods. The asymptomatic period from initial surgery to recurrence ranged from 22 to 252 months. Clinical, diagnostic imaging, and operative findings during the second surgery were analyzed. All patients were treated by anterior subcutaneous ulnar nerve transposition with ganglion resection and later examined directly within a mean of 71 months after the second surgery.Results: The interval from recurrence to consultation was shorter than two months for eight cases. Chief complaints included numbness with or without pain in the ring and little fingers in all patients and resting pain in the medial elbow in five patients. Elbow osteoarthritis was present in all cases. Although four of 10 ganglia were palpable, ultrasonography and magnetic resonance imaging could identify all ganglia preoperatively. The ulnar nerve typically had become entrapped by the ganglion posteriorly and by fascia, scar tissue, and/or muscle anteriorly. Chief complaints and ulnar nerve function were improved in all patients following revision surgery.Conclusions: The acute onset of numbness with or without intolerable pain in the ring and little fingers after a long-term remission period following initial surgery for CuTS in patients with elbow osteoarthritis appears to be the characteristic clinical profile of recurrent CuTS caused by ganglion. As ganglia are often not palpable, ultrasonography and magnetic resonance imaging are recommended for accurate diagnosis.

Background During the surgery for a distal radius fracture, we encountered a large anomalous muscle lying across the distal radius. The muscle was identified as a flexor carpi radialis brevis muscle (FCRB), based on its location, function, and innervation. This experience led us to clarify its prevalence in living subjects and alert surgeons of its presence. Methods We reviewed wrist MRI scans of 515 hands of 379 patients with carpal tunnel syndrome (CTS). The prevalence of the FCRB was calculated. The cross sectional area (CSA) of the FCRB was compared with that of the hypothenar muscles. Signal intensity and fat infiltration of the FCRB were assessed using semiquantitative methods. The anterior compartment ratio (CSA of the anterior compartment of the forearm was divided by CSA of the forearm. CSA of the FCRB was excluded for measurement) was compared between patients with and without FCRB. Results We found seven hands of six patients (1.6%) with a FCRB. All of these tendons were inserted into the second metacarpal base. CSA of FCRB was smaller than that of the hypothenar muscles. Semiquantitative assessment revealed normal signal intensities of the FCRB compared with those of other muscles. The anterior compartment ratio was smaller in patients with FCRB than without FCRB. None of the FCRB in our series demonstrated any sign of tendinitis on MRI. Furthermore, the postoperative clinical course for those patients was uneventful. Conclusions Prevalence of FCRB in patients with CTS was 1.6%. FCRB should function as a wrist flexor. Its strength varied according to the individuals but was not greater than that of the hypothenar muscles. It is still unclear if the FCRB could cause the development of CTS. However, it was found that the FCRB could be a mass which occupies and narrows the anterior compartment.

Metastatic disease is the most important factor in determining the survival of sarcoma patients. Since sarcoma metastasis is predominantly hematogenous, we hypothesized that detection and quantification of circulating tumor cells (CTCs) could reflect response to therapy and risk of metastatic relapse. We evaluated the presence of CTCs using a novel animal model and in the blood of patients with high grade sarcomas utilizing the CellSieve™ size-based low pressure microfiltration system. Sarcoma CTCs were identified based on antibody staining patterns and nuclear morphology. Additionally, RNA was extracted from the CTCs for molecular analysis including demonstration of an EWS-FLI1 translocation, identification of a previously unrecognized p53 mutation in a patient with Ewing sarcoma, and single cell RNA sequencing of CTC from a child with alveolar rhabdomyosarcoma. In mouse xenograft models, the presence of CTC correlates with disease burden and with clinically silent metastases. In human patients, CTCs were readily detected at diagnosis, decreased with successful treatment, and were detectable in the blood of patients with no radiographic evidence of disease prior to the development of overt metastasis. Although evaluation of CTC is established in the care of patients with carcinomas, this technology has yet to be effectively applied to the evaluation and treatment of sarcoma patients. Our work demonstrates that the CellSieve™ microfiltration system can be used to study the biology of CTC in both mouse models and human sarcoma patients, with the potential for application to the monitoring of disease response and prediction of metastatic relapse.