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Chung-Yao Chen,1,2 Wen-Chun Tseng,1 Yao-Hung Yang,1 Chia-Ling Chen,3,4 Lain-Li Lin,5 Fang-Ping Chen,2,6,7 Alice MK Wong2,3,8 1Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung 204, Taiwan; 2Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou 333, Taiwan; 4Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; 5Department of Tourism Leisure and Health, Ching Kuo Institute of Management and Health, Keelung 204, Taiwan; 6Keelung Osteoporosis Prevention and Treatment Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan; 7Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Keelung 204, Taiwan; 8Healthy Aging Research Center, Chang Gung University, Taoyuan 333, TaiwanCorrespondence: Chung-Yao ChenDepartment of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, No. 200, Ln. 208, Jijin 1st Road, Anle District, Keelung City 204, TaiwanTel +886-2-2432-9292 #2725Email jongyau2002@gmail.comIntroduction: Sarcopenia is highly prevalent among residents of assisted-living facilities. However, the optimal screening tools are not clear. Therefore, we compared the performance of four recommended screening tools for predicting sarcopenia.Methods: The study recruited 177 people over 65 years of age in assisted-living facilities. Appendicular muscle mass index was measured using bioelectrical impedance analysis. Calf circumference (CC), handgrip, six-meters walking speed, and screening questionnaires including SARC-CalF, SARC-F and 5-item Mini Sarcopenia Risk Assessment (MSRA-5) were evaluated. The diagnosis criteria for sarcopenia were based on the Asian Working Group for Sarcopenia 2019 consensus. The area under the receiver operating characteristic curves (AUC) was used to contrast the diagnostic accuracy of screening tools.Results: The prevalence of sarcopenia was 52.7% among men and 51.2% among women. After adjusting for age, sex, body mass index and SARC-CalF score, CC remained significantly associated with sarcopenia in logistic regression analysis. The prediction model for sarcopenia based on CC alone had the highest accuracy compared to SARC-CalF, MSRA-5 and SARC-F (AUC, 0.819 vs 0.734 vs 0.600 vs 0.576; sensitivity/specificity, 80.4%/71.8% vs 38.0%/80.0% vs 60.7%/54.2% vs 10.9%/91.8%). Differences in AUCs between the prediction models were statistically significant (CC vs. SARC-CalF, P = 0.0181; SARC-CalF vs. MSRA-5, P = 0.0042). Optimal cutoff values for predicting sarcopenia were CC < 34 cm in men and < 33 cm in women.Conclusion: To predict sarcopenia based on low CC alone is accurate, easy and inexpensive for use in assisted-living facility settings. Further validation studies in different populations are suggested.Keywords: sarcopenia, calf circumference, SARC-F, SARC-CalF, MSRA, assisted-living

Ching-Hsiung Liu,1,2 Yen-Ying Kung,2–4 Chun-Liang Lin,1 Jen-Lin Yang,2–4 Ta-Peng Wu,3 Hong-Chun Lin,3 Yang-Kai Chang,3 Ching-Mao Chang,2–4 Fang-Pey Chen2,3 1Department of Neurology, Lotung Poh-Ai Hospital, Ilan, Taiwan, Republic of China; 2Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 4Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of ChinaCorrespondence: Fang-Pey ChenInstitute of Traditional Medicine, School of Medicine, National Yang-Ming University, and Director, Center for Traditional Medicine, Taipei Veterans General Hospital, Number 155, Section 2, Linong Street, Taipei 112, Taiwan, Republic of ChinaTel +8862-2875-7454Fax +8862-2875-7452Email fpchen@vghtpe.gov.twPurpose: To investigate the required sample size for and feasibility of a full-scale randomized controlled trial examining the impact of the “dose” effect of acupuncture in treating sciatica.Patients and methods: Fifty-seven patients with sciatica, aged 35–70 years, were recruited and screened. Thirty-one participants were randomly assigned to receive “low-dose” manual acupuncture (MAL) (n= 15) or “high-dose” manual acupuncture (MAH) (n=16). The acupuncture treatment was administered twice weekly for 4 weeks. The primary outcome was the visual analog scale (VAS) score at baseline and after 4 weeks of acupuncture treatment. Secondary outcomes included the Roland Disability Questionnaire for Sciatica (RDQS), the Sciatica Bothersomeness Index (SBI), and the World Health Organization Quality of Life in the Brief Edition (WHOQOL-BREF) scores at baseline and after 4 weeks of acupuncture treatment.Results: Thirty patients completed the study. For all patients, acupuncture achieved significant improvement in the VAS (5.48±2.0, p

Rationale: Previously, we demonstrated that intranasal infection of BALB/c mice with respiratory syncytial virus (RSV) resulted in an early 40% reduction in alveolar fluid clearance (AFC), an effect mediated via P2Y purinergic receptors.Objectives: To confirm that RSV-induced inhibition of AFC is mediated by uridine triphosphate (UTP), and to demonstrate that inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV.Methods: BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice by instillation of 5% bovine serum albumin into the dependent lung. Some mice were pretreated with leflunomide or 6-mercaptopurine.Measurements and Main Results: RSV-mediated inhibition of AFC is associated temporally with a 20-nM increase in UTP and ATP content of bronchoalveolar lavage fluid, hypoxemia, and altered nasal potential difference. RSV-mediated nucleotide release, AFC inhibition, and physiologic sequelae thereof can be prevented by pretreatment of mice with the de novo pyrimidine synthesis inhibitor leflunomide, which is not toxic to the mice, and which does not affect RSV replication in the lungs. In contrast, pretreatment of mice with 6-mercaptopurine, an inhibitor of de novo purine synthesis, has no beneficial effect on AFC or other indicators of disease progression. Finally, RSV-mediated inhibition of AFC is prevented by volume-regulated anion channel inhibitors.Conclusion: Pyrimidine synthesis or release pathways may provide novel therapeutic targets to counter the pathophysiologic sequelae of impaired AFC in RSV disease. [ABSTRACT FROM AUTHOR]

Chylous ascites is an extremely rare complication of laparoscopic presacral neurectomy (LPSN), and treatment is still controversial. Four patients undergoing LPSN for dysmenorrhoea or chronic pelvic pain were complicated with chylous ascites. Two were successfully treated with bipolar cauterization and one, after the failure of initial treatment by bipolar cauterization, was then effectively managed by compression with Gelform and closure of the peritoneum of the presacral area by suture through laparoscopy. The fourth patient had persistent chyle leakage from the drainage tube after electrocauterization and was finally cured by conservative management including removal of the drainage tube and a low-fat diet for 3 weeks. Chylous ascites has not been reported in laparoscopic presacral neurectomy. Management that is quick, effect and subjects the patients to the least amount of suffering is still unresolved. Repeated laparoscopy can be considered to identify the possibility of injury to lymphatic vessels, to relieve abdominal distention due to chyle accumulation, and to apply electrocauterization or compression with Gelform and closure of the peritoneum. Conservative treatment with a low-fat diet may need a longer time. The use of a drainage tube may provide negative pressure allowing a continuous leakage of chyle. However, more controlled study is required to identify the most proper and effective management. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism., Methods: This multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD., Results: A total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D ≧20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD., Conclusion: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach., Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches., Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment., Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management., Competing Interests: The authors disclosed the following conflicts of interest.1.Ta-Wei Tai received honoraria for lectures, meetings, and/or travel from Amgen and Alvogen/Lotus.2.Swan Sim Yeap has received honoraria for lectures from Amgen.3.Natthinee Charatcharoenwitthaya received honoraria for lectures, meetings, and/or travel from Amgen, Alvogen, and Zuellig Pharma.4.Akira Taguchi has received lecture fees from Asahi Kasei Pharma Corp., Daiichi Sankyo Co. Ltd, Chugai Pharmaceutical Co. Ltd, and Teijin Pharma Ltd.5.Peter R Ebeling has received research funding from Amgen, Alexion and Sanofi, and honoraria from Amgen, Alexion and Kyowa Kirin.6.Fernando Marin has received honoraria for lectures from DKSH and Zuellig Pharma. He is a former employee of Eli Lilly and Company.7.Yoon-Sok Chung has received research funding from Samsung Bioepis and honoraria from Amgen, Alvogen, Celltrion, Daewoong, Hanlim, and Yuyu.8.Ian R Reid has received speaking fees from Amgen and Medison Pharma.9.Manju Chandran has received honoraria and travel sponsorships from Amgen, DKSH, and Kyowa Kirin.10.E. Michael Lewiecki - Amgen: investigator, consultant, speaker; Radius: investigator, consultant; Kyowa Kirin: consultant, speaker; Ultragenyx: investigator; Angitia: consultant; Ascendis: consultant.11.Fen Lee Hew has received honoraria from Amgen and DKSH.12.Tuan Van Nguyen has received a global competitive grant from Amgen and honoraria from Amgen, DKSH, and Bridge Health Care, for giving lectures and travelling to meetings.13.Chung-Hwan Chen received honoraria for lectures, attending meetings, and/or travel from Amgen, and Alvogen/Lotus.14.Chih-Hsing Wu received honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier laboratories, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus.15.The other authors reported that they have nothing to declare for potential conflicts of interest., (© 2024 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.)

Objective: The data on the association between phthalates and breast cancer risk remains inconsistent. This study aimed to explore the possible mechanism of low-dose exposures of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP), on breast tumorigenesis., Methods and Methods: MCF-10A normal breast cells were treated with phthalates (10 and 100 nM) and 17β-estradiol (E 2 , 10 nM), which were co-cultured with fibroblasts from normal mammary tissue. Cell viability, cycle, and apoptosis were detected by MTT assay, flow cytometry, and TUNEL assay respectively. The expression levels of related proteins were determined by Western blot., Results: Like E 2 , both 10 nM and 100 nM phthalates exerted significantly higher cell viability, lower apoptosis, and increased cell numbers in the S and G2/M phases with up-regulation of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1, compared with the control group. Significant increase in PDK1, P13K, p-AKT, p-mTOR, and BCL-2 expression and a decrease in Bax protein, cytochrome C, caspase 8, and caspase 3 levels were noted in cells treated with 10 nM and 100 nM phthalates and E2, compared with the control group and MCF-10A cells co-cultured with fibroblasts. The effects of the three phthalates were noted to be dose-dependent., Conclusions: The results indicate that phthalates at a level below its no-observed-adverse-effect concentration, as defined by the current standards, still induce cell cycle progression and proliferation as well as inhibit apoptosis of normal breast cells. Thus, the possibility of breast tumorigenesis through chronic phthalate exposure should be considered., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background and Purpose: The safety of interventions for critically ill patients is a crucial issue. In recent years, several studies have treated critically ill patients with acupuncture. However, the safety of acupuncture in this setting remains to be systematically measured., Methods: In May 2022, the electronic databases of PubMed and the Cochrane Library were searched for studies comparing acupuncture interventions to control interventions in critically ill patients. Study outcomes examined the incidence of severe adverse events (AEs), minor AEs, adverse reactions, ICU stays, and 28-day mortality., Results: A total of 31 articles were analyzed, and no serious AEs related to acupuncture treatment were identified. No significant differences were found between the groups in the meta-analysis of minor AEs (risk ratio [RR] 5.69 [0.34, 96.60], P = 0.23, I 2 = 76%). A reduced risk in the incidence of adverse reactions following acupuncture intervention was evidenced (RR 0.33 [0.22, 0.50], P = 0.00001, I 2 = 44%). The patients in the acupuncture arm spent significantly less time in the intensive care unit (ICU) (Mean difference -1.45 [-11.94, -10.97], P = 0.00001, I 2 = 56%) and also exhibited lower 28-day mortality rates (odds ratio 0.61 [0.48, 0.78], P = 0.0001, I 2 = 0%)., Conclusion: There is no evidence to indicate a higher risk of severe or minor AEs in patients who receive acupuncture. Acupuncture demonstrated favorable results in both ICU stay and 28-day mortality measurements, in addition to presenting with fewer adverse reactions compared to routine ICU care. However, the low certainty of the evidence resulting from a high risk of bias in the included studies merits substantial consideration, and further research is still warranted., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=142131, identifier: CRD42020142131., 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 © 2023 Ben-Arie, Lottering, Chen, Ho, Lee, Inprasit and Kao.)

Objectives: In this study we aimed to evaluate the nocebo response rate in patients with functional dyspepsia (FD) and to explore its influencing factors., Methods: A literature search of the EMBASE, PubMed, and Cochrane Library databases was conducted for all articles published up to March 2021. Randomized, parallel-designed, placebo-controlled trials on pharmacological interventions for patients with FD were included. A meta-analysis that utilized random effects to analyze the incidence of adverse events (AEs) among participants who were given placebo was conducted, and the correlation between trial characteristics and the magnitude of the nocebo response rate was analyzed., Results: Altogether, 27 studies including 1866 paitents were deemed eligible and included in the analysis. The total nocebo response rate was 26% (95% confidence interval [CI] 18%-33%). The most frequently reported AEs included nasopharyngitis (9%), constipation (6%), headache (5%), and diarrhea (3%). There were significant differences in nocebo response rates among studies conducted in different country or region, treatment duration, types of medication, sponsorship and different versions of the Rome criteria used for FD diagnosis. While number of centers engaged in the study, types of FD diagnosis and dosing frequency were not significantly associated with the nocebo response rate., Conclusions: Patients with FD exhibit notable nocebo response strength in clinical trials. The researchers should adopt a more careful approach when analyzing the relationships between AEs and interventions in such trials., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Traditional Chinese medicine (TCM) is widely used by ethnic Chinese communities. TCM is covered by Taiwan's National Health Insurance (NHI) program. We evaluated the efficacy and outcomes of complementary Chinese herbal medicine (CHM) therapy in patients with cancer., Methods: This population-based cohort study was conducted using the data of patients who received a cancer diagnosis between 2005 and 2015 in Taiwan. Eligible patients were divided into standard and complementary CHM therapy groups. The complementary CHM therapy group was further divided into low cumulative dosage (LCD), medium cumulative dosage (MCD), and high cumulative dosage (HCD) subgroups. Overall survival (OS), mortality risk, cancer recurrence, and metastasis were analyzed for all cancers and five major cancers (lung, liver, breast, colorectal, and oral cancers)., Results: We included 5707 patients with cancer (standard therapy, 4797 [84.1%]; complementary CHM therapy, 910 [15.9%]; LCD, 449 [7.9%]; MCD, 374 [6.6%], and HCD, 87 [1.5%]). For the LCD, MCD, and HCD subgroups, the mortality risk was 0.83, 0.64, and 0.45, and the 11-year OS, 5-year cumulative cancer recurrence, and 5-year cumulative cancer metastasis rates were 6.1 ± 0.2, 6.9 ± 0.2, and 8.2 ± 0.4 years; 39.2%, 31.5%, and 18.8%; and 39.5%, 32.8%, and 16.6%, respectively. The cumulative cancer recurrence and metastasis rates of the standard therapy group were 40.9% and 32.8%, respectively. The cumulative recurrence and metastasis rates of all cancers, lung cancer, and liver cancer and all cancers, colorectal cancer, and breast cancer, respectively, were significantly lower in the HCD subgroup than in the other subgroups and standard therapy group ( p < 0.05)., Conclusion: Patients receiving complementary CHM therapy may have prolonged OS and reduced risks of mortality, recurrence, and metastasis. A dose-response relationship was noted between CHM therapy and mortality risk: increased dosage was associated with improved OS and reduced mortality risk., Competing Interests: Conflicts of interest: Dr, Shinn-Jang Hwang, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: To investigate the prognostic value of corpus uterine invasion (CUI) in cervical cancer (CC), and determine the necessity to incorporate it for staging., Methods: A total of 809 cases of biopsy-proven, non-metastatic CC were identified from an academic cancer center. Recursive partitioning analysis (RPA) method was used to develop the refined staging systems with respect to overall survival (OS). Internal validation was performed by using calibration curve with 1000 bootstrap resampling. Performances of the RPA-refined stages were compared against the conventional FIGO 2018 and 9th edition TNM-stage classifications by the receiver operating characteristic curve (ROC) and decision curve analysis (DCA)., Results: We identified that CUI was independently prognostic for death and relapse in our cohort. RPA modeling using a two-tiered stratification by CUI (positive and negative) and FIGO/T-categories divided CC into three risk groupings (FIGO I'-III'/T1'-3'), with 5-year OS of 90.8%, 82.1%, and 68.5% for proposed FIGO stage I'-III', respectively (p ≤ 0.003 for all pairwise comparisons), and 89.7%, 78.8%, and 68.0% for proposed T1'-3', respectively (p < 0.001 for all pairwise comparisons). The RPA-refined staging systems were well validated with RPA-predicted OS rates showed optimal agreement with actual observed survivals. Additionally, the RPA-refined stages outperformed the conventional FIGO/TNM-stage with significantly higher accuracy of survival prediction (AUC: RPA-FIGO vs. FIGO, 0.663 [95% CI 0.629-0.695] vs. 0.638 [0.604-0.671], p = 0.047; RPA-T vs. T, 0.661 [0.627-0.694] vs. 0.627 [0.592-0.660], p = 0.036)., Conclusion: CUI affects the survival outcomes in patients with CC. Disease extended to corpus uterine should be classified as stage III/T3., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To investigate the impact of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), in breast carcinogenesis., Materials and Methods: MCF-10A normal breast cells were treated with phthalates (100 nM) and 17β-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue adjacent to estrogen receptor positive primary breast cancers. Cell viability was determined using a 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell cycles were analyzed using flow cytometry. The proteins involving cell cycles and P13K/AKT/mTOR signaling pathway were then evaluated by Western blot analysis., Results: MCF-10A co-cultured cells treated with E2, BBP, DBP, and DEHP exhibited a significant increase in cell viability using MTT assay. The expressions of P13K, p-AKT, and p-mTOR, as well as PDK1 expression, were significantly higher in MCF-10A cells treated with E2 and phthalates. E2, BBP, DBP, and DEHP significantly increased cell percentages in the S and G2/M phases. The significantly higher expression of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1 in MCF-10A co-cultured cells were induced by E2 and these three phthalates., Conclusion: These results provide consistent data regarding the potential role of phthalates exposure in the stimulating proliferation of normal breast cells, enhancing cell viability, and driving P13K/AKT/mTOR signaling pathway and cell cycle progression. These findings strongly support the hypothesis that phthalates may play a crucial role in breast tumorigenesis., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Background: To investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC)., Methods: We enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes. Recursive partitioning analysis (RPA) was used to construct a risk stratification model for overall survival (OS). The performance of the RPA-based model was assessed using a receiver operating characteristic (ROC) curve., Results: RCS analysis revealed an association between SCCA and OS and disease-free survival (DFS); SCCA ⩾2.5 ng/mL was robust for risk discrimination in our cohort. SCCA had an interaction effect with FIGO classification: Patients with FIGO I and SCCA ⩾2.5 ng/mL overlapped with those with FIGO II and SCCA < 2.5 ng/mL for OS [hazard ratio, 1.04 (95% confidence interval (CI): 0.49-2.24), p  = 0.903] and DFS [1.05 (0.56-1.98), p  = 0.876]. RPA modeling incorporating SCCA (<2.5 ng/mL and ⩾2.5 ng/mL) and FIGO classification divided CC into three prognostic groups: RPA I, FIGO stage I, and SCCA < 2.5 ng/mL; RPA II, FIGO stage I, and SCCA ⩾ 2.5 ng/mL, or FIGO stage II and SCCA < 2.5 ng/mL; and RPA III, FIGO stage II, and SCCA ⩾ 2.5 ng/mL; with 5-year OS of 94.0%, 85.1%, and 73.5%, respectively ( p  < 0.001). ROC analysis confirmed that the RPA model outperformed the FIGO 2018 stage with significantly improved accuracy for survival prediction [area under the curve: RPA versus FIGO, 0.663 (95% CI: 0.619-0.705] versus 0.621 (0.576-0.664), p  = 0.045]. Importantly, the RPA groupings were associated with the efficacy of treatment regimens. Surgery followed by adjuvant treatment had a higher OS ( p  < 0.01) and DFS ( p  = 0.024) than other treatments for RPA III, whereas outcomes were comparable among treatment regimens for RPA I-II., Conclusion: Herein, the role of SCCA for prognostication was confirmed, and a robust clinicomolecular risk stratification system that outperforms conventional FIGO classification in early-stage squamous and adenosquamous CC was presented. The model correlated with the efficacy of different treatment regimes., Competing Interests: The authors declare no conflict of interest. The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval RDD number as RDDA2023310575., (© The Author(s), 2023.)

Background: Terminally ill patients often experience exacerbations of diseases that render mainstream medicine ineffective in relieving symptoms, prompting attempts at complementary and alternative medicine (CAM). This study collected data from terminally ill patients and their relatives to determine differences between CAM use, behavioral patterns, and perceptions of health information about CAM., Methods: A cross-sectional design using a self-administered questionnaire was adopted. Eight medical institutions in Taiwan with inpatient hospice palliative care units were chosen. Ninety-two terminally ill patients and 267 relatives met the inclusion criteria. The questions concerned the experience of CAM use, the kinds of products/services CAM provided, the purpose of CAM use, the source of CAM information, and the perceptions and attitudes toward CAM., Results: Both terminally ill patients and their relatives have a high proportion of lifetime and one-year prevalence of CAM use (88.0% vs. 88.4%; p = 0.929). CAM use for musculoskeletal and neurological discomfort is higher among terminally ill patients than among their relatives. Relatives/friends are the most frequent sources of information on CAM (53.3% vs. 62.2%; p = 0.133). The percentage of terminally ill patients who discontinued mainstream medical treatment because of CAM use was higher than that of their relatives (18.5% vs. 9.3%; p = 0.026). More than half the terminally ill patients and their relatives had never been asked about CAM by medical staff (64.1% vs. 66.7%), nor had they informed medical professionals about the use of CAM products and services (63% vs. 66.9%). Random inquiries by medical professionals may be associated with increased disclosure of CAM use (terminally ill patients: odds ratio, 9.75; 95% confidence interval, 1.97-48.35 vs. relatives: odds ratio, 5.61; 95% confidence interval, 2.66-11.83)., Conclusions: The high prevalence and concealment of CAM use in terminally ill patients should be considered. Medical professionals should establish a friendly and barrier-free communication model, encourage patients to share CAM experiences, and provide evidence-based information on the use of CAM products and services, to reduce the potential damage caused by harmful use., (© 2023. The Author(s).)

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan., Competing Interests: Declaration of competing interest The authors declared that there was no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics., Competing Interests: Declaration of competing interest Chih-Hsing Wu received honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier laboratories, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. E Michael Lewiecki is an investigator, consultant, and speaker for Amgen, and an investigator for Radius., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population., Methods: This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history., Results: DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis., Conclusions: The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD., Competing Interests: Conflicts of interest None., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Objective: This study investigated the mediating roles of self-esteem and self-efficacy on the relationship between family social networks and personal recovery among Chinese people with mental illness in Hong Kong., Methods: One hundred and twenty-five Chinese adults with mental illness from community mental health centers in Hong Kong were recruited for this study. Data were collected using a structured questionnaire., Results: Study results indicated that a large family network size was indirectly related to high levels of personal recovery through high self-efficacy. High perceived family support was directly related to high levels of personal recovery. In addition, high family criticalness was related to low levels of personal recovery directly and indirectly through low self-esteem., Conclusions and Implications for Practice: These findings suggest that using a family approach to enhance individuals' self-esteem and self-efficacy might promote personal recovery among people with mental illness in the Chinese context. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals., Objective: To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA., Design, Setting, Participants and Intervention: A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output., Main Outcome Measures: The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA., Results: Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05)., Conclusion: Low-level LA gradually reduced older patients' postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care., Trial Registration: ClinicalTrials.gov registration number NCT03995446., (Copyright © 2022. Published by Elsevier B.V.)

Fresh mulberry leaf vegetable is nutritive and becoming popular. However, available preservation technologies are deficient. In present work, the effects of two kinds of modified atmosphere packaging on postharvest quality of fresh mulberry leaf vegetable stored at 4 °C were evaluated. The respiration rate of samples in the modified polyethylene packages (MP20) was 12.88-22.65% lower than that in normal polyethylene packaging (CK). The content of total soluble solids, soluble protein, and total polyphenol in MP20 was less changed than that in CK, and the vitamin C retention was higher as well. Moreover, the lignin content in MP20 was lower than that in CK during storage (19.79% vs 13.38% at day 8), and that was significantly positively related to the polyphenol oxidase and peroxidase activities inhibition. Taken together, a packaging with moderate gas permeability (MP20) is suitable for nutrition maintenance and lignification inhibition of fresh mulberry leaf vegetable during cold storage., (© 2022. The Author(s).)

Objectives: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design., Methods: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups., Results: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05)., Conclusions: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed., Clinical Trial Registration: clinicaltirl.gov: NCT04318496., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: The symptoms of coronavirus disease 2019 (COVID-19) such as hyposmia, rhinorrhea, nasal obstruction, and cough are similar to those of chronic allergic rhinitis (AR). Such symptoms can easily lead AR patients to unnecessary anxiety, misdiagnosis, and invasive diagnostic tests in the COVID-19 pandemic. Interleukin-6 (IL-6) is an important mediator for chronic AR and plays a crucial role in the inflammation of COVID-19. Houttuynia cordata (HC) has been shown to reduce nasal congestion and swelling by suppressing the activation of IL-6 and is used to fight COVID-19. A novel HC-based Chinese herbal formula, Zheng-Yi-Fang (ZYF), was developed to test effects on nasal symptoms of patients with AR in the COVID-19 pandemic., Methods: Participants aged between 20 and 60 years with at least a 2-year history of moderate to severe perennial AR were enrolled. Eligible participants were randomly allocated to either the intervention group (taking ZYF) or the control group (using regular western medicine) for 4 weeks. The Chinese version of the Rhinosinusitis Outcome Measures was used to evaluate impacts on quality of life and nasal symptoms of participants with AR. In addition, the effect of ZYF on lipopolysaccharide (LPS)-induced IL-6 was investigated., Results: Participants with AR taking ZYF improved their symptoms of nasal obstruction, nasal secretion, hyposmia, and postnasal drip in comparison with those of the control group. Meanwhile, ZYF exhibited inhibition of IL-6 secretion in the LPS-induced inflammatory model., Conclusion: ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Background: Benign prostatic hyperplasia (BPH) can affect quality of life and cause various complications. Previous studies have suggested that Chinese herbal medicine can alleviate symptoms in patients with BPH. This study aimed to investigate whether the Chinese herbal medicine prescription VGH-BPH1 can alleviate BPH symptoms when used as an add-on treatment., Methods: In this crossover, randomized, double-blind, placebo-controlled trial, patients with BPH were randomly segregated into two groups: group A received VGH-BPH1, and group B received a placebo for 8 weeks. Subsequently, after a 2-week wash-out period, the two groups were switched to the opposite treatment for another 8 weeks. The International Prostate Symptoms Score and Aging Male Symptoms Score were adopted as the primary outcomes to assess improvement in BPH and patient quality of life. The secondary outcomes were the International Index of Erectile Function, Constitution Chinese Medicine Questionnaire, uroflowmetry results, and postvoid residual urine volume., Results: VGH-BPH1 treatment significantly decreased the International Prostate Symptoms Score total score (p = 0.027); however, no significant difference was observed between the treatment and placebo groups. The Aging Male Symptoms Score "joint pain and muscular ache" score in the VGH-BPH1 group was significantly lower than that of the placebo group (p = 0.022). The "physical exhaustion" score also exhibited a decreasing trend when both groups were compared (p = 0.057)., Conclusion: Although VGH-BPH1 treatment did not outperform the placebo in terms of improving BPH symptoms, it resulted in improvement in several quality of life indicators when relative to the placebo. Future research using a larger sample size with appropriate amendments to the protocol should be conducted to further investigate the effects of VGH-BPH1., Competing Interests: Conflicts of interest: Dr. William J. Huang and Dr. Shin-Jang Hwang, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Background: Sarcopenia and osteoporosis are important health issues faced by older people. These are often associated with each other and share common risk factors and pathologic mechanisms. In the recently revised consensus of the European Working Group on Sarcopenia in Older People, low muscle strength has been defined as the first characteristic of sarcopenia rather than a loss in muscle mass, and walking speed has been stated as an indicator of the severity of sarcopenia. It is believed that these markers of muscle function can be potentially reversed via exercise-based interventions. The purpose of this study was to evaluate the effects of kickboxing exercise training on the parameters of sarcopenia and osteoporosis in community-dwelling adults., Methods: In total, one hundred eligible subjects were randomized into an intervention group ( n = 50) with 76% women and control group ( n = 50) with 86% women. Both the intervention and control groups were provided with classroom lectures and personal consultations pertaining to sarcopenia and osteoporosis, whereas a 12-week kickboxing exercise training was arranged only for the intervention group. All anthropometric, physical performance, body composition, and bone mineral density measurements along with participant completed questionnaires were conducted before and after the training period., Results: After 12 weeks, 41 participants in the intervention group and 34 participants in the control group completed the final assessments. There was no difference between the intervention and control groups in terms of basic demographic data. The BMI (+1.14%) of the control group increased significantly during the study period. The waist circumference (-6.54%), waist-to-height ratio (-6.57%), waist-to-hip ratio (-4.36%), total body fat (-1.09%), and visceral fat area (-4.6%) decreased significantly in the intervention group. Handgrip strength (+5.46%) and gait speed (+5.71%) improved significantly in the intervention group. The lean body mass increased by 0.35% in the intervention group and by 0.9% in the control group. The femoral neck bone mineral density (-1.45%) and T score (-3.72%) of the control group decreased significantly. The intervention group had more improvement in the status of sarcopenia (OR 1.91) and osteoporosis over the control group. Finally, the intervention group had less deterioration in the status of sarcopenia (OR 0.2) and osteoporosis (OR 0.86) compared with the control group., Conclusion: Our study demonstrated that a 12-week kickboxing exercise training program is effective for improving sarcopenic parameters of muscle strength and function, but not muscle mass in adults, aged 50-85 years. Furthermore, markers of osteoporosis also showed improvement. These findings suggest that a 12-week kickboxing program is effective for muscle and bone health among community-dwelling older individuals., 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 Lin, Chen, Chen, Wong, Hsu and Chen.)

Purpose: To quantify the long-term evaluation of optic chiasma (OC) and/or optic nerve(s) (ONs) and to develop predictive models for radiation-induced optic neuropathy (RION) in nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT)., Methods and Materials: A total of 3,662 patients' OC/ONs with full visual acuity and dosimetry data between 2010 and 2015 were identified. Critical dosimetry predictors of RION were chosen by machine learning and penalized regression for survival. A nomogram containing dosimetry and clinical variables was generated for predicting RION-free survival., Results: The median follow-up was 71.79 (2.63-120.9) months. Sixty-six eyes in 51 patients (1.39%) developed RION. Two patients were visual field deficient, and 49 patients had visual acuity of less than 0.1 (20/200). The median latency time was 36 (3-90) months. The 3-, 5-, and 8-year cumulative incidence of RION was 0.78%, 1.19%, and 1.97%, respectively. Dmax was the most critical dosimetry variable for RION (AUC: 0.9434, the optimal cutoff: 64.48 Gy). Patients with a Dmax ≥64.48 Gy had a significantly higher risk of RION (HR = 102.25; 95%CI, 24.86-420.59; P < 0.001). Age (>44 years) (HR = 2.234, 95% CI = 1.233-4.051, p  = 0.008), advanced T stage (T3 vs. T1-2: HR = 7.516, 95% CI = 1.725-32.767, p =0.007; T4 vs. T1-2: HR = 37.189, 95% CI = 8.796-157.266, P < 0.001), and tumor infiltration/compression of the OC/ONs (HR = 4.572, 95% CI = 1.316-15.874, p =0.017) were significant clinical risk factors of RION. A nomogram comprising age, T stage, tumor infiltration/compression of the OC/ON, and Dmax significantly outperformed the model, with only Dmax predicting RION (C-index: 0.916 vs. 0.880, P < 0.001 in the training set; 0.899 vs. 0.874, P =0.038 in the test set). The nomogram-defined high-risk group had a worse 8-year RION-free survival., Conclusions: In the IMRT era, D max <60 Gy is safe and represents an acceptable dose constraint for most NPC patients receiving IMRT. A reasonable trade-off for selected patients with unsatisfactory tumor coverage due to proximity to the optic apparatus would be Dmax <65 Gy. Caution should be exercised when treating elderly and advanced T -stage patients or those with tumor infiltration/compression of the OC/ON. Our nomogram shows strong efficacy in predicting RION., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Yan-Ling Wu et al.)

Only few prospective cohort trials have evaluated the risk factors for the 2-year mortality rate between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC): oral cavity cancer with adjuvant concurrent chemoradiotherapy (CCRT) (OCC) and non-oral cavity cancer with primary CCRT (NOCC), under the recommended calorie intake and investigated the interplay among calorie supply, nutrition-inflammation biomarkers (NIBs), and total body composition change (TBC), as assessed using dual-energy X-ray absorptiometry (DXA). Patients with LAHNSCC who consumed at least 25 kcal/kg/day during CCRT were prospectively recruited. Clinicopathological variables, blood NIBs, CCRT-related factors, and TBC data before and after treatment were collected. Factor analysis was performed to reduce the number of anthropometric and DXA-derived measurements. Cox proportional hazards models were used for analysis. We enrolled 123 patients with LAHNSCC (69 with OCC and 54 with NOCC). The mean daily calorie intake correlated with the treatment interval changes in total body muscle and fat. Patients consuming ≥30 kcal/kg/day had lower pretreatment levels but exhibited fewer treatment interval changes in anthropometric and DXA measurements than patients consuming <30 kcal/kg/day. In the multivariate analysis of the 2-year mortality rate, the prognostic influence of the recommended calorie intake could not be confirmed, but different risk factors (performance status, pretreatment platelet-to-lymphocyte ratio, and treatment interval body muscle changes in patients with OCC; age, pretreatment neutrophil-to-lymphocyte ratio, and body fat storage in patients with NOCC) showed independent effects. Therefore, the inflammation status and body composition, but not the recommended calorie supply, contribute to the 2-year mortality rate for patients with LAHNSCC receiving CCRT.

The aim of this study is to investigate the impact of bisphosphonate treatment on the prognosis of patients with initial hip fracture. Patients aged fifty years and older with initial hip fracture were identified from the Taiwan National Health Insurance Research Database between 2002 and 2011. A multi-state model was established to evaluate the transition between "first to second hip fracture", "first hip fracture to death", and "second hip fracture to death". Transition probability and cumulative hazards were used to compare the prognosis of initial hip fracture in a bisphosphonate treated cohort versus non-treated cohort. In addition, Deyo-Charlson comorbidities, both vertebral and non-vertebral fractures, and cataracts were also included for analysis. After 10-year follow-up, there is decreased cumulative transition probability for both second hip fracture and mortality after both first and second hip fracture in the bisphosphonate treated cohort. Multivariable, transition-specific time-dependent Cox model revealed that bisphosphonate treatment significantly reduced risk for second hip fracture in the first 5 years of the treatment (HR 0.88; 95% CI 0.79-0.99; P: 0.034), first hip fracture mortality (HR 0.88; 95% CI 0.83-0.93; P < 0.001), and second hip fracture mortality in the first 2 years of the treatment (HR 0.78; 95% CI 0.65-0.95; P = 0.011). Female sex, both vertebral and non-vertebral fractures, cataracts, dementia in the first 2 years, and DM with complication were all significantly associated with risk of a second hip fracture. Cerebrovascular disease and hemiplegia comorbidities had less risk of a second hip fracture. The risk of mortality after both first and second hip fracture was significantly associated with congestive heart failure, renal disease, myocardial infarction, and moderate to severe liver disease. Our study demonstrated that bisphosphonate treatment and strict management of comorbidities after the initial hip fracture significantly decrease the risk for a second hip fracture and mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide., Materials and Methods: This prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months., Results: With teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months., Conclusion: P1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Na + -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682&#95;683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC)., Methods: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training ( N  = 9,259) and two validation cohorts ( N  = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts., Results: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival ( p  < 0.001 for all): AHR1, T1N0; AHR2A, T1N1/T2-3N0 cfEBV DNA  < 2,000 (EBV low ); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBV high ) and T1-2N2/T2-3N1 EBV low ; AHR3, T1-2N2/T2-3N1 EBV high and T3N2/T4N0 EBV low ; AHR4, T3N2/T4 N0-1 EBV high and T1-3N3/T4N1-3 EBV low ; AHR5, T1-3N3/T4 N2-3 EBV high . Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98-12.67), hazard discrimination (5.29 versus 6.69-13.35), explained variation (0.248 versus 0.164-0.225), balance (0.385 versus 0.438-0.749) and C-index (0.707 versus 0.662-0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts ( p  < 0.001 for both)., Conclusion: Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval number as RDDA2020001517., (© The Author(s), 2021.)

Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = -0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis., (© 2021. The Author(s).)

Background: Depressive disorders (DD) affect not only mood and behavior but also various physical functions. Traditional Chinese medicine (TCM) has been shown to have some benefits in treating DD. However, one formula or one single herb might be not show high efficacy when used to treat depression. Thus, this study aimed to examine the core prescription pattern of Chinese herbal medicine (CHM) among patients with DD in Taiwan as a reference for related research and clinical applications., Methods: All patients, who had been diagnosed with major depressive disorder or minor depression or dysthymia without any other baseline diseases and had at least one CHM outpatient clinical visit from 2002 to 2011, were extracted from three randomly sampled cohorts, namely the 2000, 2005 and 2010 cohorts of the National Health Insurance Research Database (NHIRD) of Taiwan. The collected data was analyzed to explore the patterns of herbal products., Results: There were 197,146 patients with a diagnosis of DD and of these 1806 subjects had only a diagnosis of DD and utilized CHM. The most common formula was Gan-Mai-Da-Zao-Tang (12.19%), while Suan-Zao-Ren (3.99%) was the most commonly prescribed single herb. The core pattern of prescriptions consisted of a combination of Gan-Mai-Da-Zao-Tang, Jia-Wei-Xiao-Yao-San, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang, He-Huan-Pi, Yuan-Zhi and Shi-Chang-Pu ., Conclusions: This study describes the CHM core prescription pattern used to treat patients in Taiwan with DD and it is a potential candidate for study in future pharmacological or clinical trials targeting DD., (© 2021 Published by Elsevier B.V. on behalf of Korea Institute of Oriental Medicine.)

Background: The optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective., Methods: For each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed., Results: For all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk., Conclusions: The cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients., (© 2021. The Author(s).)

Few prospective cohort trials have evaluated the difference in treatment-interval total body composition (TBC) changes assessed by dual-energy X-ray absorptiometry (DXA) between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC) receiving concurrent chemoradiotherapy (CCRT): oral cavity cancer with adjuvant CCRT (OCC) and non-oral cavity with primary CCRT (NOCC). This study prospectively recruited patients with LAHNSCC. Clinicopathological variables, blood nutritional/inflammatory markers, CCRT-related factors, and TBC data assessed by DXA before and after treatment were collected. Multivariate linear regression analysis identified the factors associated with treatment-interval changes in body composition parameters, including lean body mass (LBM), total fat mass (TFM), and bone mineral content (BMC). A total of 127 patients (OCC ( n = 69) and NOCC ( n = 58)) were eligible. Body composition parameters were progressively lost during CCRT in both subgroups. Extremities lost more muscle mass than the trunk for LBM, whereas the trunk lost more fat mass than the extremities for TFM. BMC loss preferentially occurred in the trunk region. Different factors were independently correlated with the interval changes of each body composition parameter for both OCC and NOCC subgroups, particularly mean daily calorie intake for LBM and TFM loss, and total lymphocyte count for BMC loss. In conclusion, treatment-interval TBC changes and related contributing factors differ between the OCC and NOCC subgroups.

Few prospective cohort trials have evaluated the potential risk factors of early treatment failure of locally advanced oral cavity squamous cell carcinoma (LAOCSCC) patients following the completion of postoperative adjuvant concurrent chemoradiotherapy (CCRT). We collected clinicopathological variables, nutrition-inflammatory markers and total body composition data assessed by dual-energy X-ray absorptiometry (DXA) before and after CCRT. A factor analysis was used to reduce the number of DXA-derived parameters. Cox proportional hazard models were applied to determine the risk factors associated with early treatment failure defined as tumor progression or death within 180 days of CCRT completion. A total of 69 patients were eligible for analysis. After CCRT, the body weight, body mass index, nutritional markers, and muscle mass decreased, whereas C-reactive protein level increased. Five factors reflecting different body composition statuses were identified. A total of 21 patients (30.4%) developed early treatment failure. Comorbidities (hazard ratio ((HR)), 2.699; 95% confidence interval ((CI)), 1.005-7.913; p = 0.044), radiation duration (HR, 1.092; 95% CI, 1.015-1.174; p = 0.018) and the pretreatment body muscle mass (HR, 0.578; 95% CI, 0.345-0.957; p = 0.037) independently contributed to early treatment failure. Comorbidities, longer radiation duration, and lower pretreatment body muscle mass are predictive factors for early treatment failure in LAOCSCC patients following postoperative adjuvant CCRT completion.

Background: To investigate the value of post-induction chemotherapy (IC) cell-free Epstein-Barr virus DNA (cfEBV DNA postIC ) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC)., Methods: A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNA preIC ) and at IC completion. CfEBV DNA postIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNA postIC and critical risk factors., Results: We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNA postIC undetectable and detectable respectively. CfEBV DNA postIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNA postIC negative (P < 0.001 for all). Additionally, cfEBV DNA postIC was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40-2.59), DMFS (1.99, 1.45-2.71) and DFS (2.38, 1.86-3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNA postIC or N2-3 and pre-treatment cfEBV DNA [cfEBV DNA preIC ] <7000), median-risk (N0-1 and detectable cfEBV DNA postIC or N2-3 and cfEBV DNA preIC ≥7000 with undetectable cfEBV DNA postIC ) and high-risk (N2-3 and cfEBV DNA preIC ≥7000 with detectable cfEBV DNA postIC ), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004)., Conclusions: CfEBV DNA postIC represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNA postIC , cfEBV DNA preIC and N-stage classification in LA-NPC., Competing Interests: Conflict of interest statement The authors declare no conflict of interest. The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval number as RDDA2021001944., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Medical staff may have difficulties in using conventional medicine to manage symptoms among terminally ill patients, including adverse effects of the treatment. Traditional Chinese medicine (TCM) is regarded as a complementary or alternative medicine, and has been increasingly used in the field of palliative medicine in recent years. This study aimed to investigate the experiences of and attitudes toward using TCM among palliative care professionals, and to provide preliminary information about its use in palliative care., Methods: This was a cross-sectional survey study conducted in eight inpatient hospice wards in Taiwan between December 2014 and February 2016. The questionnaire was self-administered, and was analyzed with descriptive statistics including Pearson's Chi-square test and Fisher's exact test., Results: A total of 251 palliative care professionals responded to the questionnaire, of whom 89.7% and 88.9% believed that the use of TCM could improve the physical symptoms and quality of life in terminally ill patients, respectively. Overall, 59.8%, of respondents suggested that TCM had rare side effects, and 58.2% were worried that TCM could affect the liver and kidney function of patients. In total, 89.7% and 88.0% of professionals agreed there were no suitable clinical practice guidelines and educational programs, respectively, for TCM use in palliative care., Conclusions: Most of the respondents agreed there was insufficient knowledge, skills-training, and continuing education on the use of TCM in terminally ill patients in Taiwan. These results show that to address patient safety considerations, guidelines about use of TCM in palliative care should be established., (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

Background: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China., Methods: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG&#95;012247.2 (NM&#95;014251.3): c.852&#95;855del, c.1638&#95;1660dup, c.615+5G>A, and c.1751-5&#95;1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests., Results: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ 2 =8.570, P=0.003) in general, with higher c.852&#95;855del (54/6,818 vs. 13/5,492, χ 2 =17.328, P=0.000) but lower c.1751-5&#95;1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638&#95;1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly., Conclusions: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-21-58). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Introduction: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients., Methods: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months., Expected Outcome: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture., Other Information: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022., Protocol Registration: (CMUH109-REC1-002), (NCT04318496)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Total knee replacement is the most effective intervention for late-stage osteoarthritis; however, a major concern is postoperative recovery of physical function. This randomised controlled trial evaluated the effects of acupuncture with low-level laser therapy (ALLLT) on early outcomes of physical function after total knee replacement., Materials and Methods: Eighty-two osteoarthritis patients were recruited and randomly assigned to the experimental group receiving ALLLT or the control group receiving sham ALLLT without laser beam output. Physical function was evaluated by assessing knee joint flexion and stiffness on days 1, 2, and 3 after total knee replacement., Results: Generalised estimating equations revealed a significant difference between the two groups in joint flexion. The experimental group displayed better joint flexion and less stiffness on days 2 and 3 than did the control group., Conclusion: ALLLT can facilitate the recovery of physical function, as evidenced by knee joint flexion and stiffness, in patients receiving total knee replacement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is the most common adverse reaction to initial zoledronic acid infusion. Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR., Introduction: Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is due to immunomodulatory actions and is the most common adverse reaction to zoledronic acid (ZOL). The aims of our study were to compare the differences between acetaminophen and dexamethasone plus acetaminophen on the incidence and severity of APRs and to clarify the clinical factors related to APR with initial ZOL infusion., Methods: Patients with osteoporosis receiving their first ZOL infusion (N = 96) were assigned into two groups and given either acetaminophen (58 patients, control group) or acetaminophen plus dexamethasone (38 patients, study group). APRs were assessed through telephone interviews 2 weeks later post-infusion. Clinical, demographic, and serologic data were recorded., Results: There was a significant increase in the incidence and severity of any APR in the control group than the study group (67% vs. 34%, p = 0.003; 0.69 ± 0.50 vs. 0.34 ± 0.48, p = 0.001). Among the APRs, only myalgia incidence and score were significantly higher in the control group than in the study group. Multivariate analysis demonstrated that previous use of osteoporosis medication and participation in the study group was negatively related to the occurrence of any APR or myalgia. Advanced age was shown to significantly increase myalgia. Study group participants had significantly reduced severity of myalgia. The adherence for redosing ZOL was significantly higher in the study group., Conclusion: Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR, especially myalgia, and increasing adherence following initial ZOL infusion.

Purpose: To develop predictive models with dosimetric and clinical variables for temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT)., Materials and Methods: Data of 8194 NPC patients who received IMRT-based treatment were retrospectively reviewed. TLI was diagnosed by magnetic resonance imaging. Dosimetric factors were selected by penalized regression and machine learning, with area under the receiver operating curve (AUC) calculated. Cox proportional hazards models containing the most predictive dosimetric factor with/without clinical variables were performed. A nomogram was generated as a visualization of Cox regression for predicting TLI-free survival., Results: During median follow-up of 66.8 months (interquartile range [IQR] 54.2-82.2 months), 12.1% of patients (989/8194) developed TLI. Median latency from IMRT to TLI was 36 months (IQR 28-47 months). D 0.5cc (dose delivered to 0.5-cm 3 temporal-lobe volume) was the most predictive dosimetric factor (AUC: 0.799). Tolerance dose for 5% and 50% probabilities to develop TLI in 5 years were 65.06 Gy (95% confidence interval [CI]: 64.19-65.92) and 89.75 Gy (95% CI: 87.39-92.11), respectively. A nomogram comprising age, T stage, and D 0.5cc significantly outperformed the model with only D 0.5cc in predicting TLI (C-index: 0.78 vs. 0.737 in train set; 0.775 vs. 0.73 in test set; both P < 0.001). The nomogram-defined high-risk group had worse 5-year TLI-free survival., Conclusions: D 0.5cc of 65.06 Gy was the tolerance dose of the temporal lobe. Reducing D 0.5cc decreased risk of TLI, especially in older patients with advanced T stage. The nomogram could predict TLI precisely and allow individualized follow-up management., (Copyright © 2021 Elsevier B.V. All rights reserved.)