Search

Yudai Fujimoto,1,2 Yoshimi Yuri,2 Miki Fujii,1 Hironari Tamiya1,3 1Department of Rehabilitation, Osaka International Cancer Institute, Osaka, Japan; 2Graduate School of Health Sciences, Morinomiya University of Medical Sciences, Osaka, Japan; 3Department of Orthopaedic Surgery (Musculoskeletal Oncology Service), Osaka International Cancer Institute, Osaka, JapanCorrespondence: Yudai Fujimoto, Department of Rehabilitation, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan, Tel +81-6-6945-1181, Fax +81-6-6945-1900, Email yuudai.fujimoto@oici.jpPurpose: This study aimed to determine the combination of factors associated with continuity of care in outpatients with cancer-related edema six months after the initial visit.Patients and Methods: A total of 101 outpatients were divided into two groups: continuation (n=65) and non-continuation (n=36) groups. Details regarding age, body mass index, sex, affected extremities (upper or lower), site of edema (unilateral or bilateral), International Society of Lymphology (ISL) classification, presence of distant metastasis, and overall score on the lymphedema quality of life questionnaire (LYMQOL) were obtained before initial lymphedema care. In this study, we performed a decision tree analysis using a classification and regression tree (CART) to detect the combination of factors associated with the continuity of edema care for cancer-related edema.Results: Significant differences were observed in the site of edema (unilateral or bilateral) and distant metastasis between the two groups. In the decision tree using CART analysis, the factors selected to influence the possibility of continuation were the side of edema as the first layer, and body mass index of 23.0 and distant metastasis (with/without) as the second layer. Outpatients with unilateral edema and a body mass index higher than 23.0 were most likely to be able to continue care. In contrast, outpatients with bilateral edema and distant metastasis had greater difficulty in continuing care.Conclusion: In this study, factors that were suggested to influence the continuity of cancer-related edema care were the side with edema, body mass index higher than 23.0, and distant metastasis. This information may be helpful for developing care strategies and improving patient adherence.Keywords: cancer-related edema, continuation, decision tree analysis, outpatient, predicted factor

Background: Retroperitoneal dedifferentiated liposarcoma is associated with a high risk of recurrence; however, treatment strategies that are more effective than surgery remain to be established. This study aimed to determine the optimal number of surgeries that would be effective for patients with recurrent disease. Furthermore, the improvement in prognosis was evaluated according to the malignancy level., Methods: The effect of each type of surgery on the prognosis of 118 patients with retroperitoneal dedifferentiated liposarcoma treated at the Osaka International Cancer Institute between 1997 and 2022 was investigated. Among the 118 patients, 103 underwent initial surgery, while 54 and 30 patients underwent second and third surgeries, respectively. The overall and disease-free survival rates of each group were compared using the Kaplan-Meier method, and the log-rank test was used to determine statistical significance in univariate analysis. 18 F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) was used to assess malignancy. Maximum standardized uptake values (SUVmax) of ≥ 4 and < 4 were classified as high and low malignancy, respectively., Results: The first and second surgeries resulted in a significant improvement in the overall survival rate, regardless of the malignancy level (p < 0.001); however, no significant improvement in prognosis was observed after the third surgery (p = 0.077). Low-grade malignancies are associated with a better postoperative prognosis, even in cases of recurrence. In contrast, high-grade malignancies exhibit a reduction in surgical efficacy., Conclusions: This study highlights the importance of considering the tumor malignancy level and the patient's overall condition when deciding whether to perform repeated surgical interventions. Surgical treatment can prolong overall survival, even in patients with recurrence; however, it is advisable to assess malignancy levels when determining the suitability of surgery beyond the second recurrence., (© 2024. The Author(s).)

Background Vascular endothelial dysfunction in type 2 diabetes mellitus (T2DM) patients causes atherosclerosis and microvascular damage. This study investigated the relationship between leg circumference and arterial stiffness in patients with T2DM compared to non-T2DM individuals. Methods Data from two studies were combined to form T2DM (T2DM group) and non-T2DM (N group) cohorts. The variables included age, sex, systolic blood pressure (SBP), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index, height, weight, maximum leg circumference, lower leg circumference ratio, duration of T2DM, Achilles tendon reflex disorder, and the hemoglobin A1c level. Multiple regression analysis was performed with ba-PWV as the dependent variable and the interaction term between leg circumference ratio and T2DM as the independent variable. The control variables included leg circumference ratio, T2DM, SBP, Achilles tendon reflex disorder, age, and sex. IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, NY, USA) was used for the statistical analysis, with the significance level set to p < 0.05. Results The interaction term between the lower leg circumference ratio and T2DM (β = -0.17, 95% CI: -46.11 to -10.92; p < 0.01) was significantly associated with ba-PWV (AdjR² = 0.51, variance inflation factor <4.12). Simple slope analysis indicated that a decreased lower leg circumference ratio was significantly associated with an increased ba-PWV (β = -0.20, p < 0.05) in the T2DM group. No significant relationship was found in the N group (β = -0.03, p = 0.69). Conclusion A significant interaction was found between the lower leg circumference ratio and T2DM presence, indicating an association between ba-PWV and the leg circumference ratio specific to patients with T2DM. This result suggests that the leg circumference ratio can be substituted for the ba-PWV to evaluate arterial stiffness in T2DM., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Research Ethics Review Board of the Tokyo Metropolitan Institute of Gerontology issued approval R24-010. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant number 21K17415 to T.F.). . Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Furuya et al.)

Background: Skin conditions in patients with lymphedema have been identified according to changes in skin mechanical properties. The skin elasticity meter is a non-invasive tool for measuring the mechanical properties of the skin; however, its potential use in patients with lymphedema has received little attention. This review aimed to provide an overview of studies measuring the skin mechanical properties of patients with lymphedema using a skin elasticity meter., Materials and Methods: Search terms and synonyms related to lymphedema and skin mechanical property measurement using a skin elasticity meter were identified, and electronic databases containing articles in English were searched., Results: A total of 621 articles were retrieved, and four articles were analyzed after screening. Despite this research subject receiving increasing attention, no consensus has been reached regarding the best methods., Conclusion: Measurement methods are expected to be standardized in the future to elucidate the skin mechanical properties of patients with lymphedema., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade, aggressive soft tissue sarcoma (STS) with a poor prognosis, and no definitive or effective treatment is currently available for it. Pazopanib, an orally available multiple tyrosine kinase inhibitor, has been approved for the treatment of advanced STS. The present study documents the case of a 51-year-old man with advanced UPS with coamplification of platelet-derived growth factor receptor A ( PDGFRA ), vascular endothelial growth factor receptor 2 ( VEGFR2 ) and stem cell factor receptor ( KIT ) genes. The patient exhibited a marked and sustained response to pazopanib. The patient presented with a retroperitoneal tumour with pancreatic head lymph node metastasis, and bone metastases in the second/fifth thoracic vertebrae and left femur. Based on the histological analysis of the retroperitoneal tumour and femoral mass, the patient was diagnosed with UPS. Palliative radiation therapy was administered to the left femur and second/fifth thoracic vertebrae to prevent fractures. After radiation therapy, the patient achieved a partial response after eight courses of doxorubicin. A comprehensive genomic profiling analysis (FoundationOne ® CDx) revealed coamplification of PDGFRA , VEGFR2 and KIT genes. Hence, pazopanib was initiated as a second-line treatment. Notably, the retroperitoneal tumour shrank, and no new lesions developed for 3 years after the initiation of pazopanib treatment. This response suggests that the coamplification of PDGFRA , VEGFR2 and KIT may predict favourable outcomes in response to pazopanib., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Matsuoka et al.)

Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas composed of myofibroblastic and fibroblastic cells, accompanied by inflammatory cell infiltration. Many IMTs exhibit clonal rearrangement of anaplastic lymphoma kinase (ALK). We herein report a 56-year-old woman with uterine IMT harboring a thrombospondin-1::ALK fusion that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Laboratory data before systemic therapy indicated increased interleukin-6 and severe leukocytosis. The patient was treated with lorlatinib; however, the response duration was approximately two months. Similar case reports need to be compiled and evaluated to elucidate the efficacy of lorlatinib in post-allo-HSCT IMT with ALK rearrangement.

Introduction: Belt electrode-skeletal muscle electrical stimulation (B-SES) is a treatment prescribed for individuals with difficulty performing exercise therapy that improves muscle strength, exercise tolerance, and glucose metabolism. However, the effects of B-SES on the hemodynamics of the central and lower extremity conduit arteries have not been studied. Therefore, this study compared the acute effects of B-SES on the central and lower extremity conduit arteries in healthy young males., Methods: This randomized crossover study included nine healthy young males (mean age: 21.0±1.1 years). Participants were assigned to the following experimental conditions, with a washout period of one week: condition 1 included 20 min of electrical stimulation of the lower extremity at the participant's sensation threshold intensity (Sham, n=9) and condition 2 included 20 min of electrical stimulation of the lower extremity at the maximum intensity the participant can tolerate (B-SES, n=9). The heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and total peripheral vascular resistance (TPR) were measured as central hemodynamics. The hemodynamics of the lower extremity conduit arteries were measured and calculated for the shallow femoral artery (SFA), including vessel diameter, mean blood flow velocity (MBFV), shear rate (SR), and mean blood flow (MBF) rate. These indices were measured before stimulation (Pre), 10 min after the start of stimulation (Stimulating), and immediately after the end of stimulation (Post). These indices were compared using a repeated two-way analysis of variance., Results: In B-SES, HR (Pre: 63.2±8.6; Stimulating: 73.7±6.9; Post: 70.0±4.2 bpm, p<0.01), CO (Pre: 5.1±1.0; Stimulating: 6.5±1.5, p<0.01; Post: 6.3±1.2 L/min, p=0.02), and MAP (Pre: 104.0±11.5; Stimulating: 116.4±10.8, p<0.01; Post: 109.6±9.7 mmHg, p=0.02) increased significantly. In addition, B-SES significantly increased MBFV (Pre: 19.2±4.0; Stimulating: 50.5±14.9; Post: 30.1±4.0 cm/s , p<0.01), SR (Pre: 118.9±28.8; Stimulating: 302.7±91. 2, p<0.01; Post: 182.1±70.1/s, p=0.02), and MBF (Pre: 382.0±61.5; Stimulating: 1009.6±321.4; Post: 626.8±176.6 mL/min, p<0.01). However, there were no significant changes in SV and TPR., Conclusions: The findings of this study indicate that B-SES in healthy young males increases CO without increasing SV or TPR and improves the MBFV and SR in the SFA., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Tamiya et al.)

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway., (© 2024. The Author(s).)

Background: It is known that several complications are caused by local surgery after radiotherapy. Clinical reports that describe the postoperative complications associated with surgery after carbon ion radiotherapy are sparse. This study aimed to elucidate local surgery feasibility after carbon ion radiotherapy specifically for primary bone sarcomas., Methods: The medical, surgical, and irradiation records of patients who had local surgery at the area irradiated with carbon ion beams between 2004 and 2018 were reviewed retrospectively to evaluate the feasibility and indication of local surgery after CIRT., Results: There were eight patients who had 10 local surgeries at the irradiated sites among the 42 carbon ion radiotherapy patients. There were seven males and one female with a median age of 50 years (range 26-73 years). The reasons for surgery were three for skin toxicity and associated infection, five for bone collapse, and associated implant failure, and two for tumor regrowth. All surgical fields included the area of more than 60 Gy (RBE) irradiated dose. All three surgical cases caused by skin toxicity and associated infection had Grade I wound complication after surgery according to the Clavien-Dindo Classification., Conclusion: Local surgery after CIRT appeared feasible in selected patients with primary bone sarcoma, especially for the patients with bone collapse and associated implant failure. However, infection and prescribed irradiation dose at the incision site must be carefully evaluated., Competing Interests: Declaration of conflicting interests The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Trabectedin binds covalently to the DNA minor groove and causes DNA to bend toward the main groove, then trabectedin regulates the transcription of the involved genes in cell proliferation or acts on the mononuclear phagocyte system in tumors, which contributes to its antitumor effects. Several clinical trials confirmed the efficacy of trabectedin for patients with advanced soft tissue sarcoma (STS) although clinically useful biomarkers remained unidentified. This study aimed to identify prognostic factors of trabectedin treatment, especially focusing on the systemic inflammatory, immune response, and nutritional status., Methods: This study included 44 patients with advanced STS treated with trabectedin from January 2018 to August 2022. We evaluated the associations of clinical factors that influence the efficacy of trabectedin treatment with progression-free survival (PFS) and overall survival (OS), focusing on systemic inflammatory, immune response, and nutritional status represented by the absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), prognostic nutrition index (PNI), and C-reactive protein (CRP) using the Kaplan-Meier method and the log-rank test., Results: ALC, LMR, PNI, NLR, PLR, and SIRI demonstrated no association with PFS. Patients with CRP of ≥0.3 had a significantly shorter PFS than those with CRP of <0.3 (median PFS: 863 vs. 105 days, P = 0.045). PNI of ≥44 (median: 757 days vs. 232 days, P = 0.021) and CRP of <0.3 (median: 877 days vs. 297 days, P = 0.043) were significantly good prognostic factors in terms of OS., Conclusions: The study results indicate pretreatment PNI and CRP levels as prognostic factors for trabectedin treatment in advanced STS., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sarculator is a validated nomogram designed to predict overall survival (OS) in extremity soft tissue sarcoma (STS). Inflammation plays a critical role in cancer development and progression. There were no reports which investigated the relationship between Sarculator and inflammation., Methods: A total of 217 patients with extremity STS were included. The Sarculator-predicted 10-year probability of OS (pr-OS) was stratified into two subgroups: lower risk (10-year pr-OS ≥ 60%) and higher risk (10-year pr-OS < 60%). The modified Glasgow prognostic score (mGPS) varied from 0 to 2., Results: Out of the 217 patients, 67 were classified as higher risk, while 150 were lower risk. A total of 181 patients had an mGPS of 0, and 36 had a score of 1 or 2. The 5-year OS was 83.3%. When patients were divided into two groups according to the 10-year pr-OS, those with a higher risk had poorer OS than those with a lower risk. Among the patients with a higher risk, those with an mGPS of 1 or 2 had poorer OS compared to those with a score of 0., Conclusions: The mGPS could potentially play an important role in identifying patients who are at high risk of death and metastasis in the higher-risk group on the Sarculator.

Recent studies have reported that direct antiglobulin test (DAT) results were negative in cases of alectinib-induced hemolytic anemia with abnormal red blood cell (RBC) morphology. We herein report the case of a 72-year-old female patient who was diagnosed with alectinib-induced hemolytic anemia who - in contrast to previous reports - showed a positive DAT result. After discontinuing famotidine and alectinib, the DAT results turned negative; however, when alectinib was resumed, hemolysis recurred. Although alectinib-induced hemolytic anemia has been previously thought to be associated with abnormal morphological changes of the RBCs, we suggest that alectinib-induced anemia may manifest as DAT-positive immune hemolytic anemia because of a complementary effect with other drugs.

Introduction Prolonged sitting-induced blood pooling in the lower legs can increase blood pressure through increased sympathetic nerve activity and peripheral vascular resistance, an aspect that has been understudied as a primary outcome. This study compared the effects of prolonged sitting with those of prolonged supination on blood pressure in healthy young men. Methods This randomized crossover study included 16 healthy young men (mean age: 21.6 ± 0.7 years) who were randomly assigned to a three-hour supine (CON) or three-hour sitting (SIT) condition, followed by a washout period of at least one week. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), low-frequency/high-frequency (LF/HF) ratio derived from heart rate variability, and leg circumference were measured at 60, 120, and 180 minutes from baseline. These indices were compared by two-way (time × conditions) analysis of variance (ANOVA). Results In the SIT condition, DBP, MAP, HR, LF/HF ratio, and leg circumference increased significantly over time (P < 0.05) and were significantly higher than those in the CON condition (P < 0.05). However, SBP showed no significant change over time and between conditions. Conclusions The findings indicate the involvement of sympathetic nerve activity and increased peripheral vascular resistance induced by fluid retention in the lower legs with increased DBP and MAP in healthy young men., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Tamiya et al.)

Background Type 2 diabetes mellitus (T2DM) is associated with changes in skeletal muscle quantity and quality, such as increased ectopic fat. Cardiac rehabilitation (CR) aims to improve the exercise capacity and muscle strength. This study aimed to determine the relationship between qualitative changes in the skeletal muscles and exercise function in patients with and without diabetes mellitus. Methods The study included patients with cardiovascular diseases who entered CR. Of 72 CR patients (68.1±9.0 years) who underwent a cardiopulmonary exercise test and skeletal muscle assessment at discharge, 15 patients with T2DM and 15 without DM were selected using propensity score matching by age and gender. Results No significant differences in the skeletal muscle echo intensity (EI) (T2DM: 58.4, Non-DM: 53.4, p=0.32), skeletal muscle index (T2DM: 7.5 kg/m 2 , Non-DM: 7.2 kg/m 2 , p=0.36), or the weight-bearing index (WBI)(T2DM: 0.44, Non-DM: 0.50, p=0.35) existed between the two groups. The phase angle (PhA) (T2DM: 3.67°, Non-DM: 4.49°, p<0.05) and peak oxygen uptake (T2DM: 12.3 mL/kg/min, Non-DM: 14.8 mL/kg/min, p<0.05) were significantly lower in the T2DM group. PhA values showed a significant correlation with the WBI, a parameter of lower limb muscle strength (r=0.50, p<0.05). Conclusion The coexistence of cardiovascular disease and T2DM resulted in a decrease in the PhA, indicating a qualitative decrease in skeletal muscle mass. The PhA is also associated with lower limb muscle strength., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Takahashi et al.)

Although there are a few case reports of patients with small cell lung cancer developing hypophosphatemia, detailed information on this condition is scarce. A 52-year-old patient with advanced stage small cell lung cancer developed hypophosphatemia (1.1 mg/dL) during chemotherapy. A reduced level of the tubular reabsorption of phosphate concomitant with an inappropriately elevated level of fibroblast growth factor (FGF) 23 (48.4 pg/mL) was noted, leading to the diagnosis of FGF23-related hypophosphatemia. Laboratory data also showed hypercortisolemia with an elevated ACTH level and hyponatremia with an inappropriately unsuppressed level of antidiuretic hormone (ADH). These data suggested the overproduction of FGF23 in addition to ACTH and ADH. Because the octreotide loading test did not present a suppressive effect on ACTH or FGF23 levels, the patient was treated with phosphate supplementation, active vitamin D and metyrapone, which partially improved the serum phosphate and cortisol levels. Even after two subsequent courses of chemotherapy, the small cell lung cancer progressed, and the FGF23 level was further elevated (83.7 pg/mL). Although it is very rare, FGF23-related hypophosphatemia is one of the hormonal disturbances that could be observed in patients with small cell lung cancer. This article reviews similar clinical conditions and revealed that advanced states of malignancy seemed to be associated with the development of renal wasting hypophosphatemia, especially in lung cancer and prostate cancer. Therefore, the parameters related to hypophosphatemia should be monitored in patients with advanced small cell lung cancer to prevent the development of hypophosphatemic osteomalacia.

A growing body of evidence suggests that the effects of poor oral hygiene extend beyond the oral cavity and are associated with a variety of systemic diseases, including asthma. Asthma, which results in symptoms of cough, wheezing, and dyspnoea, and is characterized by airflow limitation with variability and (partial or complete) reversibility, is amongst the most prevalent respiratory diseases with approximately 262 million patients worldwide, and its prevalence and disease burden is on the increase. While asthma can occur at a young age, it can also develop later in life and affects a variety of age groups. Both of these diseases have a chronic course, and various researchers have suggested a link between the two. In this article, we aim to provide a literature review focusing on the association between the two diseases. The results demonstrate that medications (primarily, inhaler medicine), hypoxia induced by asthma, and the breathing behaviour of patients potentially trigger periodontal disease. In contrast, oral periodontopathogenic microorganisms and the inflammatory mediators produced by them may be involved in the onset and/or exacerbation of asthma. Common contributing factors, such as smoking, gastro-oesophageal reflux, and type-2 inflammation, should also be considered when evaluating the relationship between the two diseases.

The prevalence of chronic obstructive pulmonary disease (COPD) is increasing worldwide and is currently the third leading cause of death globally. The long-term inhalation of toxic substances, mainly cigarette smoke, deteriorates pulmonary function over time, resulting in the development of COPD in adulthood. Periodontal disease is an inflammatory condition that affects most adults and is caused by the bacteria within dental plaque. These bacteria dissolve the gums around the teeth and the bone that supports them, ultimately leading to tooth loss. Periodontal disease and COPD share common risk factors, such as aging and smoking. Other similarities include local chronic inflammation and links with the onset and progression of systemic diseases such as ischemic heart disease and diabetes mellitus. Understanding whether interventions for periodontal disease improve the disease trajectory of COPD (and vice versa) is important, given our rapidly aging society. This review focuses on the putative relationship between COPD and periodontal disease while exploring current evidence and future research directions.

Sarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that TFRC, an iron uptake protein, was expressed at higher levels in sarcoma cell lines than in noncancer and carcinoma cell lines. Glutathione peroxidase 4 (GPX4) protects cells against ferroptosis, and its inhibition using RAS-selective lethal 3 (RSL3) had an antitumor effect that was more pronounced in sarcoma cell lines, particularly synovial sarcoma cells, compared to non-sarcoma cells. Because NF-κB can provoke ferroptosis, we examined the role of SHARPIN, an activator of NF-κB, in sarcoma. We found that SHARPIN expression was significantly associated with reduced survival in cohorts of patients with cancer, including sarcoma. In addition, SHARPIN promoted the sensitivity of sarcoma cells to ferroptosis. Further analyses revealed that the PGC1α/NRF2/SLC7A11 axis and BNIP3L/NIX-mediated mitophagy are regulated through NF-κB and PRMT5 downstream of SHARPIN. Our findings suggest that ferroptosis could have a therapeutic effect in sarcoma, particularly in subpopulations with high TFRC and SHARPIN expression.

Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. Owing to their rarity, no further analysis of their molecular pathogenesis exists, and thus, no standard treatment has been established. Recently, organoid culture methods have been highlighted for recapturing the tumor microenvironment, and we have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. At our institute, we treated a patient with malignant giant-cell tumor. The remaining sarcoma specimens after surgical resection were cultured according to the air-liquid interface organoid-culture method. Organoids were xenografted into NOD-scid IL2Rgnull mice. The developed tumors were histologically and genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Organoids from malignant giant-cell tumors could be serially maintained using air-liquid interface organoid-culture methods. The tumors developed in xenografted NOD-scid IL2Rgnull mice. After several repetitions of the process, a patient-derived organoid line from the malignant giant-cell tumor was established. Immunohistochemical analyses and next-generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes histologically and genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

This study aimed to determine the effect of long-term exercise on the risk of developing cardiovascular diseases (CVD) and all-cause mortality in patients with diabetic kidney disease (DKD). A single-center, prospective intervention study using propensity score matching was performed over 24 months. The intervention group ( n = 67) received six months of individual exercise instruction from a physical therapist, who performed aerobic and muscle-strengthening exercises under unsupervised conditions. New events were defined as the composite endpoint of stroke or CVD requiring hospitalization, initiation of hemodialysis or peritoneal dialysis, or all-cause mortality. The cumulative survival rate without new events at 24 months was significantly higher in the intervention group (0.881, p = 0.016) than in the control group ( n = 67, 0.715). Two-way analysis of variance revealed a significant effect of the group factor on high density lipoprotein-cholesterol (HDL-C) which was higher in the intervention group than in the control group ( p = 0.004); eGFRcr showed a significant effect of the time factor, which was lower at 24 months than before intervention ( p = 0.043). No interactions were observed for all items. In conclusion, aerobic exercises combined with upper and lower limb muscle strengthening for six months reduce the risk of developing CVD and all-cause mortality in patients with DKD.

Purpose: The aim of this study is to establish a standardized measurement method and to examine the intra- and inter-reliabilities and absolute reliability of measuring skin mechanical properties using a skin elasticity meter (Cutometer®)., Methods: Ten healthy participated in the study. Skin mechanical properties were measured at four sites: upper arm, lower arm, upper leg and lower leg on both sides in supine position using a non-invasive skin elasticity meter by two trained different raters. The measurements include quantitative indices of the maximal distensibility (R0), elasticity (R2, R5, R7), and viscoelasticity (R6). Intra- and inter- relative reliabilities were determined using the intraclass correlation coefficient (ICC) (1,1) and ICC (2,1) methods, respectively. The absolute reliability was assessed via the Bland-Altman analysis. Moreover, we evaluated the minimal detectable change at a 95% confidence level (MDC95)., Results: At each site, the ICC (1,1) values were >0.90, and the ICC (2,1) values were >0.50. The Bland-Altman analysis did not reveal any fixed errors, and several sites and parameters have proportional errors., Conclusions: In this study, intra- and inter-reliabilities were measured at "excellent" and more than "moderate" levels, respectively. However, because some proportional errors were observed, the limits of reliability agreement should be considered when using the proposed methods. We believe that the results of this study can be applied to clinical research in field of rehabilitation treatment.

Decreased physical activity and activities of daily living (ADL) in patients on hemodialysis (HD) are associated with a poor prognosis. Additionally, comorbid peripheral arterial disease is associated with further deterioration. We conducted a cross-sectional study of ADL difficulty and life-space assessment (LSA) in three groups of patients on hemodialysis according to their ankle-brachial index (ABI) values. The 164 patients were divided into ABI Low (ABI < 0.9), Normal (0.9 ≤ ABI < 1.3), and High (1.3 ≤ ABI) groups, and compared using analysis of covariance with LSA and ADL difficulty adjusted for age. The Kihon checklist (KCL) was used to assess the presence of frailty. The LSA was lower in the Low group than in the High group (F = 3.192, p = 0.044). Similarly, the ADL difficulty was significantly lower in the Low group than in the Normal group (F = 3.659, p = 0.028). In the Low group, the proportion of patients with frailty was 47.1% and KCL physical was significantly lower, indicating that patients on HD with a lower ABI had a higher prevalence of frailty and lower LSA and ADL difficulty. In conclusion, patients on HD with decreased ABI values most likely exhibit decline in physical activity and ADL due to frailty and claudication.

A new method based on the interferometric pseudo-lateral-shearing method is proposed to evaluate the pitch variation of a large-scale planar variable-line-spacing (VLS) grating. In the method, wavefronts of the first-order diffracted beams from a planar VLS grating are measured by a commercial Fizeau form interferometer. By utilizing the differential wavefront of the first-order diffracted beam before and after the small lateral shift of the VLS grating, the pitch variation of the VLS grating can be evaluated. Meanwhile, additional positioning errors of the grating in the lateral shifting process could degrade the measurement accuracy of the pitch variation. To address the issue, the technique referred to as the reference plane technique is also introduced, where the least squares planes in the wavefronts of the first-order diffracted beams are employed to reduce the influences of the additional positioning errors of the VLS grating. The proposed method can also reduce the influence of the out-of-flatness of the reference flat in the Fizeau interferometer by taking the difference between the measured positive and negative diffracted wavefronts; namely, self-calibration can be accomplished. After the theoretical analysis and simulations, experiments are carried out with a large-scale VLS grating to verify the feasibility of the proposed methods. Furthermore, the evaluated VLS parameters are verified by comparing them with the readout signal of an absolute surface encoder employing the evaluated VLS grating as the scale for measurement.

Hemodialysis patients with diabetic kidney disease (DKD) experience blood glucose fluctuations owing to insulin removal. We evaluated the effects of single and long-term application of neuromuscular electrical stimulation (NMES) during hemodialysis on glycemic control. This trial was conducted in two stages: Stage 1, following a crossover design and 4 week washout period, eleven outpatients with DKD either underwent a single bout of NMES for 30 min (NMES period) or rested (control period) after receiving nutritional support during hemodialysis; Stage 2, following a crossover design and 4 week washout period, each participant received the intervention for 12 weeks. NMES was administered for 30 min at the maximum tolerable intensity. The mean subcutaneous glucose concentration and mean amplitude of glycemic excursion (MAGE) were determined by flash glucose monitoring for 24 h. Changes in glycoalbumin and MAGE before and after NMES initiation were evaluated. The mean blood glucose level and MAGE after a single bout of NMES were significantly lower than those after rest. Glycoalbumin levels and echo intensity of the rectus femoris tended to decrease, but not significantly by ANOVA due to a lack in statistical power after the dropout of three patients. NMES in end-stage DKD decreased blood glucose levels during and after hemodialysis.

Background: The high rate of aseptic loosening of cemented stems has led to their frequent use in endoprosthetic reconstruction. However, problems, such as stem breakage and stress shielding at the insertion site, remain. The Japanese Musculoskeletal Oncology Group (JMOG) has developed Kyocera Modular Limb Salvage System (KMLS) cementless stems with a unique tapered press-fit and short fixation design. This study aimed to clarify the short-term postoperative outcomes of this prosthesis and validate the stem design., Methods: One hundred cases of KMLS cementless stems (51 male patients; median age, 49 years; mean follow-up period, 35 months), with a minimum follow-up of 2 years, for the proximal femur (PF), distal femur (DF), and proximal tibia were prospectively registered for use. Prosthesis survival, complication rates, postoperative functional, and radiographical evaluation were analyzed. Complications or failures after insertion of the KMLS endoprostheses were classified into five types and functional results were analyzed according to the MSTS scoring system at postoperative 1 year. The diaphyseal interface and anchorage were graded by the ISOLS system at postoperative 2 years., Results: The overall prosthesis survival rates at 2 and 4 years were 88.2 and 79.6%, respectively. The prosthesis-specific survival rate excluding infection and tumor recurrence was 90.2 and 87.9%, respectively. Younger age (p = 0.045) and primary tumor (p = 0.057) were associated with poor prognosis of prosthesis-specific survival excluding infection and tumor recurrence. Complications were observed in 31 patients, 13 patients underwent revision surgery. The mean MSTS functional score at 1 year postoperatively was 68%. Early implant loosening was significantly more common in the DF (p = 0.006) and PF/DF straight stem (p = 0.038). The ISOLS radiographic evaluation at 2 years after surgery revealed good bone remodeling and anchorage in most cases (bone remodeling: 90% / excellent and good, anchorage: 97% / excellent and good)., Conclusions: Tumor endoprosthesis long-term fixation to the diaphysis of the lower extremity remains challenging. The KMLS cementless stem with a unique tapered press fit design showed good short-term results in maintaining bone stock. To prevent early loosening, a curved stem should be used in PF and DF, but long-term follow-up is necessary., (© 2022. The Author(s).)

Background: Polypharmacy and its adverse drug events are a major healthcare challenge related to falls, hospitalisations and mortality. Comprehensive geriatric assessment (CGA) may contribute to polypharmacy improvement, however, there is no clear evidence so far., Methods: Using a national inpatient database in Japan from April 1, 2014 to March 31, 2018, we investigated the association between CGA and polypharmacy. We identified patients aged ≥65 years admitted for ischaemic stroke who could receive oral medications. Propensity score matching was conducted for patients with and without CGA during hospitalisation. The outcomes were polypharmacy (defined as use of five or more types of oral medications) at discharge, the number of medication types prescribed at discharge, and the difference between the numbers of medication types prescribed on admission and at discharge., Findings: A total of 162,443 patients were analysed, of whom 39,356 (24·2%) received CGA, and propensity score matching identified 39,349 pairs. Compared with non-CGA group, the CGA group had a significantly lower proportion of polypharmacy at discharge (34·3% vs. 32·9%, p  < 0·001) and a smaller number of medication types prescribed at discharge (3·84 vs. 3·76, p  < 0·001)., Interpretation: This study shows the clear evidence that there is a positive relationship between CGA and a reduction in the number of medications in older inpatients with ischaemic stroke., Funding: The Ministry of Health, Labour and Welfare, Japan and the Ministry of Education, Culture, Sports, Science and Technology, Japan., Competing Interests: All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work., (© 2022 The Author(s).)

Background: Although biological resources are essential for basic and preclinical research in the oncological field, those of sarcoma are not sufficient for rapid development of the treatment. So far, some sarcoma cell lines have been established, however, the success rate was low and the established sarcoma types were frequently biased. Therefore, an efficient culture method is needed to determine the various types of sarcomas. Organoid culture is a 3-dimentional culture method that enables the recapitulation of the tumor microenvironment and the success rate reported is higher than the 2-dimentional culture. The purpose of this study was to report our newly established organoids from human epithelioid sarcoma using the air-liquid interface organoid culture method., Methods: We treated 2 patients with epithelioid sarcoma in our institute. The remaining sarcoma specimens after surgical resection were embedded in collagen type 1 gels according to the air-liquid interface organoid culture method. After serial passages, we xenografted the organoids to NOD-scid IL2Rgnull (NSG) mice. Using the developed tumors, we performed histological and genomic analyses to compare the similarities and differences with the original epithelioid sarcoma from the patient., Results: Organoids from the epithelioid sarcoma could be serially cultured and maintained in collagen type 1 gels for more than 3 passages. Developed orthotopic tumor xenografts were detected in the NSG mice. After the process was repeated severally, the patient derived organoid lines from the epithelioid sarcoma were established. The established organoids showed loss of integrase interactor 1 expression with polymerase chain reaction and immunohistochemical analyses. The xenografted organoids of the epithelioid sarcoma had histologically similar phenotypes with the original tumor and genetically resembled it to some degree., Conclusions: The present study demonstrated 2 novel established organoid models of epithelioid sarcoma, and our organoid models could be used to investigate the molecular pathogenesis and develop a novel treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wakamatsu, Ogawa, Yoshida, Matsuoka, Shizuma, Imura, Tamiya, Nakai, Yagi, Nagata, Yui, Sasagawa and Takenaka.)

Background: Few studies have described the characteristics and prognostic factors of patients with metastatic extrauterine leiomyosarcoma (euLMS). Therefore, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of patients with euLMS. Methods: We recruited 61 patients with metastatic euLMS treated from 2006 to 2020 and collected and statistically analyzed information on patient-, tumor-, and treatment-related factors. The median follow-up period was 21.1 months. Results: Sixty-one patients with euLMS and a median age of 59 years were included. Furthermore, their five-year overall survival (OS) rate was 38.3%. Univariate analysis revealed that primary tumor size >10 cm, synchronous metastasis, initial metastatic sites >1, and no metastasectomy with curative intent were significantly associated with poor OS rate. Multivariate analysis identified primary tumor size >10 cm as an independent prognostic factor for poor OS. Among 24 patients who received metastasectomy with curative intent, the interval from the initial diagnosis to development of metastasis ≤6 months was significantly correlated with unfavorable OS. Among 37 patients who did not receive metastasectomy, chemotherapy after metastasis development was significantly related to better OS. Conclusions: Complete metastasectomy should be considered for metastatic euLMS treatment. Moreover, chemotherapy could prolong survival in patients with metastasis who are ineligible for metastasectomy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently show physical dysfunction due to loss of muscle mass. This study aimed to clarify the reliability and validity of ultrasound in evaluating muscle mass and to analyze the patterns of change in muscle mass before and after allo-HSCT. We conducted a prospective observational study using data from 68 patients who had undergone their first allo-HSCT. We evaluated the thickness of the quadriceps, biceps, and suprahyoid muscle. Three individual evaluators underwent this examination for each muscle before transplantation and on days 30, 90, and 180 after allo-HSCT. Inter-rater reliability was calculated using the interclass correlation (ICC), and the level of correlation between muscle mass measured by ultrasound and psoas muscle mass assessed using computed tomography (CT) was assessed using Pearson correlation. ICC values ranged from 0.897 to 0.977 in the measurement. The correlation scores were 0.730, 0.546 and 0.579 between psoas muscle and the biceps, quadriceps, and suprahyoid muscle. The thickness of the biceps and quadriceps muscle were both significantly decreased after allo-HSCT from baseline. These results showed that the ultrasound technique was a reliable tool for evaluating muscle mass and detecting changes in muscle mass following allo-HSCT., (© 2022. The Author(s).)

Inhaler devices play an important role in the management of obstructive lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Some of these patients show suboptimal inhaler techniques; however, time for inhaler instruction by pharmacists is limited in daily clinical practice. Therefore, sufficient education regarding inhaler device handling should be provided within a limited time frame. The current study aimed to investigate the instruction methods provided by community pharmacists and their influence on inhaler device handling techniques in outpatient clinical care settings. We retrospectively collected the data of outpatients with obstructive lung diseases who were referred to our hospital and who underwent inhalation technique assessments conducted by community pharmacists. The prevalence of handling errors, clinical characteristics of patients, and instruction methods were analyzed. In total, 138 patients (170 devices) were included in this study. Approximately 70.0% of patients received verbal explanations combined with leaflets about inhaler instructions. In a device-based analysis, 63 (37.1%) of 170 devices had at least one technical error and 18 (10.6%) of the devices had critical errors. Patients without critical errors received practical demonstration instructions from pharmacists combined with leaflets and verbal explanations more frequently than those with critical errors (22.8 vs. 0%, p < 0.01). This study revealed that patients with obstructive lung diseases commonly present with inhaler device handling errors and critical errors were observed with non-negligible frequency in daily practice in Japan. Combined instruction with leaflet, verbal explanation, and pharmacist demonstration may be effective in improving proper inhaler treatment.

Background: Malnutrition of inpatients is often overlooked and remains a serious concern. However, there are few studies on the relations between infused energy and amino acid intakes and clinical outcomes in older patients on parenteral nutrition., Objectives: We aimed to determine the short-term outcomes of infused energy and amino acid intakes in older patients receiving parenteral nutrition., Methods: We conducted a retrospective observational study using a national inpatient database covering >1000 hospitals in Japan. Participants were those who underwent central venous (CV) port insertion between 2011 and 2016, were aged ≥65 y, and did not have cancer. Based on the types and amounts of products used for enteral feeding and intravenous feeding on postoperative day (POD) 7 after CV port insertion, the infused energy and amino acid intakes were estimated. The primary end point was mortality on POD 90. Multivariable logistic regression was performed to investigate the relations of infused energy and amino acid intakes with mortality on POD 90., Results: A total of 10,153 patients aged ≥65 y who underwent CV port insertion were included. The mortality rates at 90 d after central venous port insertion were 14.9% and 14.0% (risk difference, 0.9%; 95% CI: -0.5%, 2.3%; P = 0.216) with infused energy intakes <20 and ≥20 kcal/kg, respectively, and 15.4% and 13.2% (risk difference, 2.2%; 95% CI: 0.9%, 3.6%; P = 0.001) with infused amino acid intakes <0.8 and ≥0.8 g/kg, respectively. The differences were retained after adjustment for multiple variables including hospital, age, sex, BMI, emergency admission, and 27 major underlying diseases. The OR for the ≥0.8-g/kg group compared with the <0.8-g/kg group was 0.87 (95% CI: 0.77, 0.99; P = 0.028)., Conclusions: A positive relation between infused amino acid intake and mortality was found in older patients receiving parenteral nutrition., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Few studies have described the characteristics and prognostic factors of patients with malignant peripheral nerve sheath tumour (MPNST). In this study, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of these patients. Patients and Methods . We recruited patients with MPNST who were treated at our institutions from 1991 to 2020. We collected and statistically analysed information on patient-, tumour-, and treatment-related factors. The median follow-up period was 61 months (range, 1-335.8 months)., Results: A total of 60 patients (31 males, 29 females) with a median age of 55 years (range, 8-84 years) at initial diagnosis were included. The median tumour size was 7 cm (range, 1.6-30 cm) in the greatest dimension. The 5-year overall survival (OS) rate of all patients was 69.5%. Univariate analysis revealed that large-sized tumour, metastasis at diagnosis, and no surgery of the primary tumour were significantly associated with patients with worse OS. Multivariate analysis identified surgery of the primary tumour as an independent prognostic factor for improved OS. Among patients with localised disease at diagnosis who underwent surgery of the primary tumour at our institutions, the 5-year OS, local recurrence-free survival (LRFS), and metastasis-free survival (MFS) rates were 81.1%, 78.2%, and 70.3%, respectively. Univariate analysis revealed that positive surgical margin was significantly correlated with unfavourable OS and LRFS, and high grade was a poor prognostic indicator for MFS., Conclusion: Complete surgical resection with negative surgical margins is necessary for a successful MPNST treatment. Multidisciplinary management of MPNST with aggressive features is important for optimising patient outcomes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Yoshinori Imura et al.)

Spirometry is a standard method for assessing lung function. However, its use is challenging in some patients, and it has limitations such as risk of infection and inability to assess regional chest wall motion. A three-dimensional motion capture system using the one-pitch phase analysis (MCO) method can facilitate high precision measurement of moving objects in real-time in a non-contacting manner. In this study, the MCO method was applied to examine thoraco-abdominal (TA) wall motion for assessing pulmonary function. We recruited 48 male participants, and all underwent spirometry and chest wall motion measurement with the MCO method. A significant positive correlation was observed between the vital capacity (Spearman's ρ = 0.68, p < 0.0001), forced vital capacity (Spearman's ρ = 0.62, p < 0.0001), and tidal volume (Spearman's ρ = 0.61, p < 0.0001) of spirometry and the counterpart parameters of MCO method. Moreover, the MCO method could detect regional rib cage and abdomen compartment contributions and could assess TA asynchrony, indicating almost complete synchronous movement (phase angle for each compartment: - 5.05° to 3.86°). These findings suggest that this technique could examine chest wall motion, and may be effective in analyzing chest wall volume changes and pulmonary function., (© 2021. The Author(s).)

Background: Retroperitoneal sarcomas are rare neoplasms that occur in the retroperitoneum. Complete surgical resection is the only effective treatment option. The prediction of prognosis by histological diagnosis has not yet been established. The purpose of this study was to identify the usefulness of [18-F] fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging for validating the prognosis of retroperitoneal sarcoma (RPS) established by histological diagnosis. Methods: We retrospectively reviewed 201 patients with RPS treated at the Osaka International Cancer Institute between 2010 and 2021. We extracted the clinical data, including standardized uptake values (SUVs), evaluated with FDG-PET, and statistically analyzed the data. Results: The median age of patients was 64 years (range, 31-85 years). A total of 101 (50.2%) patients were men, and 100 (49.8%) were women. Surgical resection was performed in 155 (77.1%) patients. On histological analysis, 75 (37.3%), 52 (25.9%), and 29 (14.4%) patients were diagnosed with dedifferentiated liposarcoma, well-differentiated liposarcoma, and leiomyosarcoma, respectively. The median survival time for patients with high maximum SUV (SUVmax) (≥4) or low SUVmax (<4) was 275.8 months and 79.5 months, respectively. Furthermore, among the patients with dedifferentiated liposarcoma, the overall survival rate for patients with high SUVmax (≥4) was significantly lower than that of those with low SUVmax (<4). Conclusions: The present study demonstrated that SUVmax calculated with FDG-PET was useful as a prognostic factor in RPS, especially in dedifferentiated liposarcoma and Grade2 RPS. To devise a treatment strategy for RPS, SUVmax during FDG-PET scan may be considered for clinical assessment.

Transfusion-related acute lung injury (TRALI) is a severe condition characterised by noncardiogenic pulmonary oedema that develops within 6 h of blood transfusion. Patient factors and blood products have both been implicated in the development of TRALI; however, the role of pulmonary disease has not been investigated. We aimed to determine whether pulmonary disease is a risk factor for TRALI. We conducted a nested case-control study using data from the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan, between July 2010 and March 2015. Case patients who developed TRALI were 1:4-matched with control patients for sex, age and same hospital for receipt of blood transfusion. We conducted a multivariable conditional logistic regression analysis to evaluate the associations of TRALI with various factors including comorbidities, body mass index (BMI) and plasma-containing blood products. We identified 2 019 501 hospitalised patients who received a blood transfusion. Among these patients, 72 developed TRALI. The 72 case patients had higher proportions of haematological malignancy, trauma and interstitial lung disease (ILD) than the 288 matched control patients. The multivariable conditional logistic regression analysis showed that occurrence of TRALI was associated with ILD (odds ratio, 3.88; 95% confidence interval, 1.11-13.6), BMI ≥25.0 kg·m -2 (2.10; 1.05-4.24) and plasma-containing blood products (1.94; 1.10-3.42), but not with infectious lung disease or obstructive airway disease. In conclusion, ILD was an independent risk factor for the development of TRALI. Physicians should be aware of the increased risk of TRALI in patients with ILD., Competing Interests: Conflict of interest: A. Yokoyama has nothing to disclose. Conflict of interest: Y. Sakamoto has nothing to disclose. Conflict of interest: T. Jo received consigned research funding from Tsumura & Co. and belongs to a laboratory that is a joint programme with Tsumura & Co. Conflict of interest: H. Urushiyama has nothing to disclose. Conflict of interest: H. Tamiya has nothing to disclose. Conflict of interest: G. Tanaka has nothing to disclose. Conflict of interest: H. Matsui has nothing to disclose. Conflict of interest: K. Fushimi has nothing to disclose. Conflict of interest: H. Yasunaga reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study. Conflict of interest: T. Nagase has nothing to disclose., (Copyright ©The authors 2021.)

Background: The incidence and prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) are reportedly increasing in many parts of the world. However, there are few published data on NTM-PD-related death. Using data from a national inpatient database in Japan, we aimed in this study to identify the characteristics of patients with NTM-PD and clinical deterioration and to identify risk factors for in-hospital mortality., Methods: We examined data from the Diagnosis Procedure Combination (DPC) database in Japan from July 2010 to March 2014. We extracted data for HIV-negative NTM-PD patients who required unscheduled hospitalization. We evaluated these patients' characteristics and performed multivariable logistic regression analysis to identify risk factors for all-cause in-hospital mortality., Results: A total of 16,192 patients (median age: 78 years; women: 61.2%) were identified. The median body mass index (BMI) was 17.5 kg/m 2 (IQR 15.4-20.0). All cause In-hospital death occurred in 3166 patients (19.6%). The median BMI of the patients who had died was 16.0 kg/m 2 (IQR 14.2-18.4). Multivariable analysis revealed that increased mortality was associated with male sex, lower BMI, lower activities of daily living scores on the Barthel index, hemoptysis, and comorbidities, including pulmonary infection other than NTM, interstitial lung disease, pneumothorax, and malignant disease., Conclusions: We found associations between being underweight and having several comorbidities and increased in-hospital mortality in patients with NTM-PD. Preventing weight loss and management of comorbidities may have a crucial role in improving this disease's prognosis., (© 2021. The Author(s).)

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma.

Angiosarcoma is a rare sarcoma with a poor prognosis and is prone to disseminated intravascular coagulation (DIC), where DIC often interferes with chemotherapy. Primary angiosarcoma of the breast (PASB) is a type of angiosarcoma that is located in mammary parenchyma and is not associated with radiation exposure. The current study reported a 47-year-old female with DIC associated with PASB. The DIC of the patient relapsed during mono-chemotherapy with paclitaxel (PTX) after first-line anticoagulant therapy using thrombomodulin-α. The second-line danaparoid sodium therapy, followed by self-subcutaneous injection of unfractionated heparin calcium (UFH), resulted in long-term stabilization of DIC. Under this second-line anticoagulant therapy, the patient continued chemotherapy and chemoradiotherapy for >13 months in the outpatient setting without impairment of quality of life. The present case suggested that self-subcutaneous injections of UFH may be a useful therapeutic option for long-term control of DIC associated with PASB. However, further prospective clinical trails are needed to verify the efficacy of self-subcutaneous injection of UFH in similar settings., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yagi et al.)

Malignant gastrointestinal neuroectodermal tumors (GNETs), also called clear-cell sarcoma-like tumors of the gastrointestinal tract, are rare and highly aggressive tumors originating in the gastrointestinal tract. These tumors are generally immunohistochemically positive for S-100 protein (S-100) and SRY-related HMG-box 10 (SOX10), and often contain EWSR1-ATF1 or EWSR1-CREB1. The histological features of GNETs overlap with those of clear-cell sarcoma of the tendons and aponeuroses. However, GNETs immunohistochemically lack melanocyte-specific markers and often demonstrate positivity for CD56, synaptophysin and neuron-specific enolase. The present case reports a woman with a history of desmoplastic malignant melanoma exhibiting a BRAF mutation, which later transformed into a GNET of the small intestine with both a BRAF mutation and two subtypes of EWSR1-ATF1 fusion genes. Tumor cells were revealed to be weakly immunoreactive or negative for S-100 and SOX10, lacked markers of melanocytic differentiation and were focally positive for CD56. Combination therapy with dabrafenib mesylate and trametinib dimethyl sulfoxide proved to be temporarily effective against this tumor. The present case is relatively unique as, to the best of our knowledge, there is no case of GNET with a history of melanoma. Furthermore, there is no report of GNET exhibiting both a BRAF mutation and an EWSR1-ATF1 fusion gene. Further accumulation of similar cases is necessary to elucidate the pathological significance of this GNET having a BRAF mutation., (Copyright: © Yagi et al.)