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Background: The study investigates the combined efficacy of subacromial hyaluronic acid (HA) injections and extracorporeal shockwave therapy (ESWT) in managing rotator cuff lesions without complete tears., Materials and Methods: Eligible patients were randomized into three groups: three HA injections combined with two sham ESWT (HA), three HA injections combined with one ESWT and one sham ESWT (HA + 1 ESWT), or three HA injections combined with two ESWT (HA + 2 ESWT) with an allocation ratio of 1:1:1. Visual Analogue Scale (VAS), Constant-Murley Score (CMS), range of motion (ROM), and muscle power of shoulder abduction (MP) were assessed preintervention and at 1, 3, 6, and 12 months postinitial HA injection. Shoulder MRI was conducted before and 12 months after the intervention., Results: All pertinent parameters showed no significant between-group differences at baseline but demonstrated significant within-group improvement throughout the study. The HA + 1 ESWT group demonstrated superior improvements in MP ( P =0.011) and CMS ( P =0.018) at 1 month, and in MP ( P =0.014) and CMS ( P =0.005) at 6 months, compared to the HA group. The HA + 2 ESWT group showed greater improvements in FF ( P =0.027), IR ( P =0.019), and SROM ( P =0.025) at 1 month, and in ABD ( P =0.022) at 6 months, compared to the HA group. Notably, the HA + 2 ESWT group exhibited greater improvements in FF ( P =0.013), IR ( P =0.019), and SROM ( P =0.025) at 1 month, and in FF ( P =0.007) at 3 months, than the HA + 1 ESWT group. Moreover, no deterioration in tendinopathy grading or tear status occurred in the HA + 1 ESWT group on MRI scans., Conclusion: ESWT provides additional benefits when combined with HA injections for patients with rotator cuff lesions lacking complete tears., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI., Methods: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S)., Results: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased β-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001)., Conclusions: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice., (© 2024. The Author(s).)

Background: Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear., Methods: Human OA samples were used to assess CCGs expression. Cartilage-specific miR-128a knockout mouse model was established to investigate miR-128a's role in OA pathogenesis. Destabilization of the medial meniscus (DMM) model was employed to simulate OA., Results: Transcription levels of nuclear receptor subfamily 1 group D member 2 (NR1D2) were lower in both human OA samples and wild-type mice undergoing DMM compared to non-OA counterparts. MiR-128a knockout mice showed reduced disturbances in micro-computed tomographic and kinematic parameters following DMM, as well as less severe histologic cartilage loss. Immunohistochemistry staining revealed a lesser decrease in NR1D2-positive chondrocytes after DMM in miR-128a knockout mice than in wild-type mice. NR1D2 agonist rescued the suppressed expression of cartilage anabolic factors and extracellular matrix deposition caused by miR-128a precursor., Conclusions: Cartilage-specific miR-128a knockout mice exhibited reduced severity, less disrupted kinematic parameters, and suppressed NR1D2 expression after DMM. NR1D2 enhanced the expression of cartilage anabolic factors and extracellular matrix deposition. These findings highlight the potential of employing miR-128a and CCG-targeted therapy for knee OA., Competing Interests: Conflicts of interest None., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion ( p = 0.033) and abduction ( p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) ( p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 ( p = 0.042) and S100A9 ( p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.

Chronic pancreatitis (CP) may induce systemic inflammation, potentially increasing cancer susceptibility. However, the link between CP and extra-pancreatic cancer remains underexplored. Employing Taiwanese National Health Insurance Database data from 2000 to 2017, we compared 5394 CP patients with 21,576 non-CP individuals through propensity score matching. CP patients exhibited a significantly higher cancer risk (adjusted hazard ratio (aHR) of 1.32 for females and 1.68 for males) and cumulative incidence ( p < 0.001) compared to non-CP individuals. CP showed notable associations with pancreatic (aHR = 3.51), liver (aHR = 1.62), stomach (aHR = 2.01), and other cancers (aHR = 2.09). In terms of liver cancer, CP was significantly associated with patients without viral hepatitis, regardless of gender (aHR = 2.01 for women; aHR = 1.54 for men). No significant cancer occurrences were observed within the first year following CP diagnosis. Pancreatic or liver cancer developed in approximately half of CP patients within 2-3 years, while gastric cancer in male CP patients predominantly occurred around the fifth year after diagnosis. These findings inform potential cancer-screening plans for CP patients.

This study aimed to evaluate the systemic impact of periodontitis, previously considered a local disease, on cancer occurrence. We enrolled 683,854 participants, comparing cancer incidence among those with and without periodontitis and assessing the impact of periodontal treatment on cancer risk. Regardless of gender, age, Charlson comorbidity index, or the use of non-steroidal anti-inflammatory drugs, periodontitis patients had a lower overall cancer risk than controls. However, men with periodontitis had a higher risk of prostate cancer (adjusted hazard ratio [aHR] = 1.22; 95% confidence interval [CI] = 1.10-1.35), and both men and women had a higher risk of thyroid cancer (women: aHR = 1.20, 95%CI = 1.04-1.38; men: aHR = 1.51, 95% CI = 1.15-1.99). Patients with periodontitis who received treatment showed a reduced cancer risk (aHR = 0.41; 95% CI = 0.38-0.44) compared to untreated patients. Proper treatment for periodontitis may lower an individual's cancer risk more than if they did not have the disease at all, suggesting that periodontitis is a modifiable risk factor for cancer.

Living donor liver transplantation (LDLT) is lifesaving, but can lead to osteoporosis and fractures. In our 3-year study of 25 LDLT recipients, we observed significant reductions in lumbar spine and femoral neck T scores, along with bone resorption marker reductions and liver regeneration marker increases. Serum calcium levels increased, while osteoprotegerin (OPG) decreased and Dickkopf-related protein 1 (DKK-1) increased. Patients who suffered fractures within 3 years of LDLT had higher serum OPG, lower serum nuclear factor kappa B ligand (RANKL), a higher OPG/RANKL ratio and higher serum DKK-1 levels. OPG, RANKL, OPG/RANKL ratio and DKK-1 levels before LDLT predicted hip or spine fractures within three years after LDLT. Further research is necessary to determine the optimal level of osteoclastic activity for preventing fracture onset.

Osteogenesis imperfecta (OI) is not curative nowadays. This study tried to unriddle the therapeutic potential of micro ribonucleic acid-29a (miR-29a) antagonist in treating OI in a mouse animal model (B6C3Fe a/a-Col1a2oim/J). We showed that the expression levels of miR-29a were higher in bone tissues obtained from the OI mice than from wild-type mice demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization assay. We established lentivirus-shuttled vector expressing miR-29a antisense oligonucleotide (miR-29a-AS) and miR-29a precursors (pre-miR-29a), showing that the inferior bony architecture in micro-computed tomography and pertinent morphometric parameters could be rescued by miR-29a-AS and deteriorated by pre-miR-29a. The decreased proliferating cell nuclear antigen (PCNA), increased Dickkopf-1 (DKK1), and decreased β-catenin expression in OI mice could be accentuated by pre-miR-29a and normalized by miR-29a-AS. The decreased osteogenesis and increased osteoclastogenesis in OI mice could also be accentuated by pre-miR-29a and normalized by miR-29a-AS. miR-29a-AS did not seem to possess severe hepatic or renal toxicities.

Understanding how the body plan is established during embryogenesis remains a fundamental biological question. The Wnt/β-catenin signaling pathway plays a crucial and highly conserved role in body plan formation, functioning to polarize the primary anterior-posterior (AP) or head-to-tail body axis in most metazoans. In this chapter, we focus on the roles that the mammalian Wnt/β-catenin pathway plays to prepare the pluripotent epiblast for gastrulation, and to elicit the emergence of multipotent axial progenitors from the caudal epiblast. Interactions between Wnt and retinoic acid (RA), another powerful family of developmental signaling molecules, in axial progenitors will also be discussed. Gastrulation movements and somitogenesis result in the anterior displacement of the RA source (the rostral somites and lateral plate mesoderm (LPM)), from the posterior Wnt source (the primitive streak (PS)), leading to the establishment of antiparallel gradients of RA and Wnt that control the self-renewal and successive differentiation of neck, trunk and tail progenitors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Neuropeptide Y (NPY)-Y1 receptor (Y1R) signaling is known to negatively affect bone anabolism. Our study aimed at investigating the impact of NPY-Y1R signaling in the pathogenesis of glucocorticoid-related osteonecrosis of the femoral head (ONFH). Femoral heads were retrieved from 20 patients with and without ONFH, respectively. The bone marrow stromal cells (BMSCs) from ONFH femoral heads were treated with Y1R agonists and antagonists for subsequent analysis. We showed that the local NPY expression level was lower in ONFH heads. The Y1R agonists and antagonists disturb and facilitate the survival of BMSCs. The transcription of stromal derived factor-1 (SDF-1) was enhanced by Y1R antagonists. Our study showed that the local NPY expression level was lower in ONFH heads. Y1R antagonists facilitate the survival of BMSCs and stimulate the transcription of SDF-1 by BMSCs. These findings shed light on the role of NPY-Y1R signaling in the pathogenesis of ONFH.

Distal femur reaming-free total knee arthroplasty (TKA) was reported to possess lower risk of acute myocardial infarction (AMI) or venous thromboembolism (VTE) than conventional TKA in a retrospective population-based study. We tried to offer prospective biological evidence by comparing the levels of AMI and VTE serum surrogate markers among the patients undertaking navigation and conventional TKAs to support these observations. Thirty-four participants undertaking navigation TKA and 34 patients receiving conventional TKA were recruited between February 2013 and December 2015. Blood samples were drawn from all participants before TKA, and 24 and 72 h after TKA, to assess the concentration of soluble P-selectin, matrix metalloproteinase-9 (MMP-9), C-reactive protein (CRP), and interleukin-8 (IL-8) between the participants undergoing navigation and conventional TKAs. We showed that significantly lower serum levels of soluble P-selectin 24 h after, as well as CRP 24 and 72 h after TKA could be observed in the navigation cohort. The more prominent surge of serum soluble P-selectin and CRP were perceived 24 and 72 h after TKA among the participants undergoing conventional TKA. Based upon our prospective biological evidence, the merits of navigation TKA are strengthened by lower levels of AMI and VTE serum surrogate markers.

Aspirin and clopidogrel are commonly prescribed alone or together among the type 2 diabetes mellitus (T2DM) patients, and both agents could affect bone metabolism. This study aimed at demonstrating the effects of the dosage and the duration of aspirin and/or clopidogrel alone or together on the occurrence of hip fracture among T2DM patients. We chose the patients newly diagnosed with T2DM and divided them into four subgroups which are under aspirin monotherapy (78,522 patients), clopidogrel monotherapy (12,752 patients), dual therapy (7209 patients), and patients not taking antiplatelet drugs (401,686 patients). We found that only higher dosage (>360 cumulative daily defined dose (cDDD)) and longer duration (≥3 years) of antiplatelet agents could be associated with lower fracture risk. Compared with the subjects taking <1-year dual agents, the risk of hip fracture was 0.38-fold for the patients taking ≥3-year dual agents. Lower dosage (28−179 cDDD) and shorter duration (1~2 years) could even be associated with higher fracture risk. Overall, the best regimen to fend off the hip fracture was the use of aspirin and clopidogrel for ≥3 years.

Shoulder stiffness (SS) is a disease that is fibroblastic and inflammatory in nature. Leptin is an adipokine-mediating the fibroblastic and inflammatory processes of various diseases. Our study tried to investigate the role of leptin in SS pathogenesis. Subacromial bursa from stiff and non-stiff shoulders were obtained for reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunoblotting. Subacromial fluid was obtained for enzyme-linked immunosorbent assay. We showed that the expression level of leptin was lower in the subacromial bursae from the stiff shoulders in RT-PCR analysis (p < 0.001) and immunoblotting (p < 0.001). The concentration of leptin was also lower in the subacromial fluid derived from stiff shoulders. The leptin level in the subacromial fluid was positively associated with the constant score, total range of motion, flexion, abduction, and external rotation. The synovial fibroblasts derived from stiff shoulder-retrieved subacromial bursa were treated by 0, 1, and 3 μM leptin. Under RT-qPCR analysis, leptin was shown to dose-dependently decrease the transcription of IL-6, IL-10, and IL-13, but without impact on IL-1β and IL-4 (p < 0.001, p = 0.001, p = 0.001, p = 0.137, and p = 0.883 by ANOVA test, respectively). These results shed light on the role of leptin in orchestrating the disease processes of SS.

Chronic otitis media (COM) has been considered as a localized disease, and its systemic impact is poorly understood. Whether COM-induced inflammation could be associated with systemic bone loss and hip fracture is unknown at present. Our study tried to determine the risk of hip fracture among COM patients. We selected the comparison individuals without the COM coding and paired the controls with COM patients by gender, age, and comorbidities (including osteoporosis) by about a one-to-two ratio. Our study showed that the incidence of hip fracture was 4.48 and 3.92 per 1000 person-years for comparison and COM cohorts respectively. The cumulative incidence of hip fracture is higher in the COM cohort (p < 0.001). After adjustment for gender, age, and comorbidities, the COM patients had a 1.11-fold (aHR = 1.11; 95% CI = 1.05−1.17) risk of hip fracture than the control subjects. Among COM patients, a history of hearing loss is associated with higher (aHR = 1.21; 95% CI = 1.20−1.42) fracture risk. Our study showed that COM patients, especially those with hearing loss, are susceptible to a higher risk for hip fracture.

Background and Objectives: Iron-deficiency anemia (IDA) could predispose the afflicted individuals to various infections and musculoskeletal disorders. This study attempted to investigate the association between IDA and septic arthritis (SA), a musculoskeletal disease. Materials and Methods: We investigated all the eligible subjects in the Taiwanese longitudinal health insurance database (LHID) between 2000 and 2012. Subjects with the diagnosis of IDA (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM): 280) were allocated to the IDA cohort. The control subjects were randomly matched to every subject with IDA coding by age and sex at the 1:4 ratio. All of the recruited subjects were followed since the index date to the onset of SA (ICD-9-CM: 711.0), withdrawal from the insurance (including death), or 31 December 2013. Results: The cumulative incidence of SA was assessed. We showed that the cumulative incidence of SA was higher in the IDA cohort than in the control cohort (p-value < 0.0001). After adjustment of the comorbidities, the IDA patients had a 2.53-fold risk of SA compared to control subjects (aHR = 2.53, 95% CI = 1.89−3.38). Conclusions: IDA was associated with an increased risk of SA.

Background: Conventional total knee arthroplasty (CONV-TKA) inevitably perturbs femoral medullary canal, disturbs medullary micro-architecture and increases blood loss and inflammatory responses. We hypothesized that avoidance of intramedullary violation may lower the incidence of periprosthetic joint infection (PJI). The aim of this study was to verify whether computer-assisted total knee arthroplasty (CAS-TKA) lowers the incidence of PJI as compared with CONV-TKA., Methods: A propensity score matching study of 5342 patients who underwent CAS-TKA (n = 1085) or CONV-TKA (n = 4257) for primary osteoarthritis of the knee from 2007 to 2015 in our institute was performed. Patients who underwent CAS-TKA were matched to those who received CONV-TKA at a 1:2 ratio according to demographics and comorbidities. PJI was defined according to the Musculoskeletal Infection Society diagnostic criteria from the 2013 International Consensus Meeting., Results: After controlling potential risk factors, the use of CAS-TKA resulted in a lower incidence of PJI as compared with CONV-TKA [adjusted hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.18-0.99]. The same trend in PJI reduction was observed with the usage of CAS-TKA under sensitivity testing [HR, 0.33; 95% CI, 0.12-0.95]. The cumulative incidence of PJI was lower in the CAS-TKA group than the CONV-TKA group (log-rank test, p = 0.013)., Conclusion: Avoidance of intramedullary violation during TKA may play a pivotal role in lowering the incidence of PJI. The use of CAS-TKA can reduce the incidence of PJI, with a better survival rate in terms of being free of PJI, as compared with CONV-TKA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

(1) Background: Inexplicable low back and neck pain frequently results from spinal disc degeneration with an imbalanced intervertebral disc (IVD) cell homeostasis. We hypothesize that introducing MSC expressing a sustained cartilage-anabolic factor in the IVD may stimulate the mucoid materials secreted from the IVD cells, promote the MSC's chondrogenesis and maintain the hydration content providing mechanical strength to decelerate the disc degeneration progression; (2) Methods: This study expressed a cartilage-anabolic factor runx1 by a baculoviral vector (BV) transduced MSCs through a Cre/LoxP gene editing and recombination system for sustained recombinant runx1 transcription factor production. The Cre/LoxP BV modified MSCs were encapsulated by hyaluronan hydrogel, due to its' vital composition in ECM of a healthy disc and transplanted to a punctured coccygeal disc in rats through micro-injection, followed by X-ray radiography and histological analysis at the 4- and 12-weeks post-transplantation; (3) Results: Data reveals the Cre/LoxP BV system-mediated long-termed runx1 gene expression, possessing good biosafety characteristics in the in vitro cell transduction and in vivo MSCs transplantation, and maintained superior hydration content in the disc than that of mock transduced MSCs; (4) Conclusions: This proof-of-concept study fulfills the need of implanting therapeutic cells accompanied with microinjection in the disc, such as a discography and paves a road to manufacture composite hyaluronan, such as peptide modified hyaluronan as an MSC carrier for IVD regeneration in the future study.

Aims: The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E 2 -2,3-Q) and 17β-estradiol-3,4-quinone (E 2 -3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts., Settings and Design: Cohort Methods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E 2 -3,4-Q and E 2 -2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment., Statistical Analysis: All data are expressed as mean ± standard deviation of three determinations. We used Student's t -test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0., Results: Result confirmed that logged levels of E 2 -2,3-Q-derived adducts correlated significantly with those of E 2 -3,4-Q-derived adducts (correlation coefficient r =.336-.624). Mean levels of E 2 -2,3-Q-4-S-Alb and E 2 -3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001)., Conclusions: Our findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.

Objective: Endoscopic assisted breast surgery (EABS) or robotic assisted breast surgery (RABS) performed through minimal axillary and/or peri-areolar incisions has become the representative of minimal access breast surgery (MABS). We report the trend and clinical outcome of MABS for treatment of breast cancer., Methods: Information on patients who underwent breast cancer operation by the principal investigator during the period of 2011 to 2020 was collected from a single institute for analysis. The clinical outcome, trend, and cost of MABS were analyzed and compared with conventional breast surgery (CBS)., Results: A total of 824 breast cancer patients operated by a single surgeon were enrolled in this study: 254 received CBS and 570 received MABS, namely, 476 EABS and 94 RABS. From 2011 to 2020, the number of MABS performed annually has shown an increasing trend. Compared with CBS, MABS such as breast conserving surgery and nipple sparing mastectomy (NSM) have effectively reduced wound scar length. Since the sequential uprise from conventional NSM (C-NSM), dual-axillary-areolar-incision two dimensional (2D) endoscopic assisted NSM (E-NSM), single-axillary-incision E-NSM, robotic assisted NSM (R-NSM), and single-port 3D E-NSM, the development of minimal access mastectomies increasingly paralleled with NSM. The operation time of various MABS decreased significantly and showed no statistical difference compared with CBS. R-NSM was associated with highest cost, followed by 3D E-NSM, E-NSM, and C-NSM. The positive surgical margin rate and local recurrence rate of MABS and CBS were not statistically different., Conclusion: MABS showed comparable clinical outcome and preliminary oncologic safety as CBS and has been increasingly performed as the surgical treatment of breast cancer, especially minimal access NSM., 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 © 2021 Lai, Chen, Lin, Lin, Lin, Chen and Kuo.)

Background: Women with unilateral breast cancer are at an increased risk for the development of contralateral breast cancers. We hypothesis that combined breast MRI would detect more contralateral synchronous breast cancer than conventional imaging alone, and resulted in less contralateral metachronous breast cancer during follow-up., Methods: We retrospectively collected two groups of breast cancer patients diagnosed from 2009 to 2013 for evaluating the effectiveness and value of adding pre-operative breast MRI to conventional breast images (mammography and sonography) for detection of contralateral synchronous breast cancer. The new metachronous contralateral breast cancer diagnosed during follow-up was prospectively evaluated and compared., Results: Group A (n = 733) comprised patients who underwent conventional preoperative imaging and group B (n = 735) combined with MRI were enrolled and compared. Seventy (9.5%) of the group B patients were found to have contralateral lesions detected by breast MRI, and 65.7% of these lesions only visible with MRI. The positive predictive value of breast MRI detected contralateral lesions was 48.8%. With the addition of breast MRI to conventional imaging studies, more surgical excisions were performed in contralateral breasts (6% (44/735) versus 1.4% (10/733), P< 0.01), more synchronous contralateral breast cancer detected (2.9% (21/735) versus 1.1% (8/733), P = 0.02), and resulted in numerical less (2.2% (16/714) versus 3% (22/725), p = 0.3) metachronous contralateral breast cancer during a mean follow-up of 102 months., Conclusions: Our study provides useful estimates of the pre-operative breast MRI for the increased detection of contralateral synchronous breast cancer and less subsequent contralateral metachronous breast cancer., Competing Interests: The authors have declared that no competing interests exist.

Background: Endoscopy-assisted breast surgery (EABS) performed through minimal axillary and/or peri-areolar incisions is a possible alternative to conventional breast surgery (CBS) for certain patients with breast cancer. In this study, we report the oncologic safety results of EABS compared with CBS., Methods: Patients underwent EABS for breast cancer during the period June 2010 to March 2020 were collected from the EABS database from single institute, and another cohort of patients, who received CBS, were identified to determine the effectiveness and oncologic safety of EABS. A case-control study was conducted using propensity score matching (PSM) to prevent bias from cases selection., Results: A total of 3426 patients were enrolled in the current study, including 405 patients receiving EABS and 3021 underwent CBS. Before PSM, patients selected for EABS tend to be smaller in tumor size, node negative, early stage, low histologic grade, and HER-2 negative. After PSM, 343 patients underwent EABS were compared with another 343 patients received CBS. The margin involved rate in EABS group is 2.6%, and 5.6% in CBS group (p = 0.054) after PSM. In breast conserving cases, the margin involved rates were 2% in EABS group, and 7.2% in CBS group (p = 0.04). In Kaplan-Meier survival curves analysis, there was no difference in local regional recurrence (p = 0.89), distant metastasis (p = 0.08), and overall survival (p = 0.14)., Conclusion: The preliminary oncologic safety analysis from current study showed EABS is a safe procedure and results in low margin involved rate, and no increase of locoregional recurrence, distant metastasis or mortality compared with CBS., (© 2021. Society of Surgical Oncology.)

Background: The preliminary results of an innovative surgical technique, which incorporated single-port three-dimensional (3D) videoscope and instruments for endoscopic nipple-sparing mastectomy (E-NSM), were reported., Methods: The medical records of patients who underwent single-port 3D E-NSM for breast cancer from August 2018 to September 2020 were analyzed, and the preliminary outcome of this procedure as well as the patient-reported aesthetic results are described in this article., Results: The study enrolled 70 patients who received 80 procedures of single-port 3D E-NSM. The mean operation time was 158 ± 36 min, and the mean blood loss was 41 ± 26 ml. Three procedures (3.8 %) associated with delayed axillary wound-healing, eight cases of transient nipple ischemia (10 %), three cases of partial nipple ischemia/necrosis (3.7 %), and one case of total nipple-areolar complex (NAC) necrosis (1.3 %) were observed. No patient had margin involvement. Satisfaction rates of approximately 90 % were observed in terms of postoperative scar appearance, location, and length. Most of the patients (87.8 %) reported that they would choose the same operation again if given the chance to do so. The overall cost of a single-port 3D E-NSM was 7522 ± 470 U.S. dollars. According to cumulative sum (CUSUM) plot analysis, about 14 cases were needed for surgeons to familiarize themselves with single-port 3D E-NSM and immediate gel implant reconstruction and to decrease their operation time significantly in the initial learning phase., Conclusion: Single-port 3D E-NSM, a safe, efficient, lower-cost procedure, is associated with a good aesthetic result. It is a promising new technique for breast cancer patients indicated for mastectomy, but long-term oncologic safety follow-up evaluation still is needed., (© 2021. Society of Surgical Oncology.)

Background: The optimal axillary lymph node (ALN) management strategy in patients diagnosed with ductal carcinoma in situ (DCIS) preoperatively remains controversial. The value of breast magnetic resonance imaging (MRI) to predict ALN metastasis pre-operative DCIS patients was evaluated., Methods: Patients with primary DCIS with or without pre-operative breast MRI evaluation and underwent breast surgery were recruited from single institution. The value of breast MRI for ALN evaluation, predictors of breast and ALN surgeries, upgrade from DCIS to invasive cancer, and ALN metastasis were analyzed., Results: A total of 682 cases with pre-operative diagnosis of DCIS were enrolled in current study. The rate of upgrade to invasive cancer were found in 34.2% of specimen, and this upgrade rate is 23% for patients who received breast conserving surgery and 40.7% for mastectomy (p < 0.01). Large pre-operative imaging tumor size and post-operative invasive component were risk factors to ALN metastasis. Breast MRI had 53.8% sensitivity, 77.8% specificity, 14.9% positive predictive value, 95.9% negative predictive value (NPV), and 76.2% accuracy to predict ALN metastasis in pre-OP DCIS patients. In MRI node-negative breast cancer patients with MRI tumor size < 3 cm, the NPV was 96.4%, and all these false-negative cases were N1. Pre-OP diagnosed DCIS patients with MRI tumor size < 3 cm and node negative suitable for BCS could safely omit SLNB if whole breast radiotherapy is to be performed., Conclusion: Breast MRI had high NPV to predict ALN metastasis in pre-OP DCIS patients, which is useful and could be provided as shared decision-making reference., (© 2021. The Author(s).)

Rationale: Gynecomastia is a common benign breast disorder in men. Surgical management of gynecomastia includes that of a subcutaneous mastectomy with or without concurrent liposuction. Herein, the authors presented a case of complicated gynecomastia (gynecomastia with concurrent foreign body injection) which was successfully managed with an innovative technique that offered acceptable operative time, minimal complications, good recovery and satisfactory aesthetic outcome., Patient Concerns: A 39-year-old Taiwanese man who developed gynecomastia along with self-injection of foreign body (salad oil) over the past 10 years for breast enlargement presented as symptomatic bilateral breast lumps., Diagnosis: Bedside sonography revealed multiple large droplets of oil in the subcutaneous tissue bilaterally, resembling cystic lesions., Intervention: Bilateral single-port 3-dimensional videoscope-assisted endoscopic subcutaneous mastectomy was performed after bilateral breast liposuction. Operative findings include bilateral gynecomastia and previous bilateral breast foreign body material. The total weight of lipoaspirate was 400 grams and 300 grams for right and left side respectively. Subcutaneous mastectomy specimen weight was 820 grams and 661 grams for right and left breast tissue., Outcomes: Operative duration was 315 minutes and intraoperative blood loss at 150 ml. Patient was discharged 2 days after the operation, and subsequent follow up ultrasound showed complete removal of foreign bodies and fibrotic breast tissue. Patient was satisfied with the post-operative aesthetic outcomes., Lessons: Single-port 3-dimensional videoscope-assisted endoscopic subcutaneous mastectomy with concurrent liposuction is a promising and safe surgical option for patient with complicated gynecomastia and severe fibrosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives : Despite the high prevalence of gallstone disease (GSD), the shared risk factors of GSD and osteoporosis, and the known association between hip fracture and hepatobiliary diseases, the association between hip fracture and GSD is not currently clear. Therefore, we performed a nationwide population-based study to investigate the association between GSD and hip fracture to determine the impact of cholecystectomy on the risk of fracture. Methods : In this study, we assessed all subjects in the longitudinal health insurance database (LHID) between 2000 and 2011, excluding those subjects aged >20 years old and those with a previous history of hip fracture (ICD-9-CM 820). Among those that were included, subjects with at least two or more outpatient visits or with one record of hospitalization under the coding of GSD (ICD-9-CM code: 574) were allocated to the GSD cohort. The remaining subjects were designated to the control cohort. All participants were followed till the onset of hip fracture, withdrawal from the NHI, or the end of 2013. Results : We found that the cumulative incidence of hip fracture was higher in the GSD cohort than in the control cohort (log-rank test: p-value < 0.01). After adjustment, the GSD patients had a 1.21-fold risk of hip fracture compared to control subjects (aHR = 1.21, 95% CI = 1.21-1.30). Comparison between those subjects without GSD and those without cholecystectomy revealed that the risk of hip fracture was higher among GSD patients that had not undergone cholecystectomy (aHR = 1.17, 95% CI = 1.06-1.29) or those that had undergone cholecystectomy (aHR = 1.22, 95% CI = 1.06-1.41). Conclusion : Based upon these results, we concluded that GSD was associated with an increased risk of hip fracture regardless of whether the patient had undergone cholecystectomy.

Platelet-rich plasma (PRP) is widely utilized in the treatment of sports injuries. However, potential systemic effects after localized PRP injection are unclear at present. In this prospective randomized study, 24 Taiwanese male athletes with tendinopathy were randomized into a PRP group (n = 13) or a saline group (n = 11). The concentrations of serum and urine biomarkers were quantified by enzyme-linked immunosorbent assay assessment as well as gas chromatographic and mass spectrometric analysis, respectively. The results showed no significant differences in serum levels of growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein 3, vascular endothelial growth factor, platelet-derived growth factor-BB, or serum substance P(SP) between the two groups before intervention, nor at 1, 2, or 7 days after intervention. However, a significant decrease in the serum SP level 1 and 7 days after PRP injection was observed. Regarding urinary concentrations of metabolites of anabolic androgenic steroids (AAS), no between-group differences before intervention, nor at 1, 2, or 7 days after intervention, were observed. Our study failed to observe significant surge of serum anabolic molecules and urinary excretion of anabolic AAS metabolites after PRP injection., Competing Interests: None

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1β, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1β and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1β in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA., (© 2020 Federation of American Societies for Experimental Biology.)

Background: Endoscopic assisted breast surgery was associated with small and inconspicuous scar and endoscopic assisted breast conserving surgery (E-BCS) for breast cancer was increasingly performed as well. The clinical outcomes, learning curve analysis and patient reported cosmetic result of E-BCS for breast cancer were reported along with a review of the current literature., Methods: A retrospective study analyzing the outcomes of E-BCS for breast cancer patients through an endoscopic breast surgery database in a single institution from June 2009 to May 2019 was performed and a literature review through Pubmed and Medline was conducted as well., Results: 100 consecutive breast cancer patients who underwent E-BCS were analyzed. The mean age of patients was 52.5 years old. Furthermore, the mean pathologic tumor size was 1.6 cm and majority of patients had early stage (13% stage 0, 56% stage I, and 30% stage II) breast cancer. The mean operation time of E-BCS in the current study was 133 ± 50 min and in learning curve analysis, after accumulation of 15 consecutive cases the operation time significantly decreased. The morbidities of E-BCS were minor and most of them were skin flap related. The margin involvement rate was 4%. About 98% of patients surveyed were satisfied with the incision length, location and scar appearance of E-BCS whereas all of them were satisfied with E-BCS in general. With a mean follow-up of 29.2 ± 24.4 months, 3% of patients developed locoregional recurrences, 3% had distant metastasis and there were 2 mortalities observed., Conclusion: In our preliminary experience, E-BCS is a promising surgical technique for selected early breast cancer patients with low morbidity, acceptable oncological outcomes and high patient satisfaction., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest or financial ties to disclose., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Robotic nipple sparing mastectomy (R-NSM), which uses the da Vinci surgical platform, could perform NSM and immediate breast reconstruction through a small and inconspicuous extra-mammary axillary or lateral chest incision. R-NSM was reported with extremely low nipple areolar complex (NAC) necrosis rate, good cosmetic results, and high patient satisfaction. However, there was little evidence available comparing the effectiveness and safety of R-NSM and conventional NSM (C-NSM) in the management of breast cancer., Methods: A case control comparison study was conducted for patients with breast cancer who underwent R-NSM or C-NSM with immediate gel implant breast reconstruction (IGBR) from July 2011 to September 2019 at a single institution to compare the clinical outcomes, patient-reported esthetic results, and medical cost., Results: According to the study design, 54 procedures of R-NSM were compared with 62 procedures of C-NSM in the surgical management of breast cancer combined with IGBR. Compared with C-NSM, R-NSM was associated with higher overall satisfaction (92% excellent and 8% good versus 75.6% excellent and 24.4% good, P = 0.046), and wound/scar related outcome in patient-reported esthetic results. The NAC ischemia/necrosis risk, overall complication rate, and blood loss were not significantly different between R-NSM and C-NSM groups. However, longer operation time and higher overall medical cost (10,877 ± 796 versus 5,702 ± 661 US Dollars, P<0.01) was observed in R-NSM group., Conclusion: Compared with C-NSM, R-NSM showed comparable clinical outcomes and favorable patients' satisfaction with the esthetic results, but at the price of longer operation time and higher cost., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: New surgical innovations of nipple-sparing mastectomy (NSM), such as endoscopic NSM (E-NSM) or robotic NSM (R-NSM), were emerging. However, there was a lack of evidence comparing the effectiveness and safety in the management of breast cancer., Methods: A case-control comparison study was conducted for patients with breast cancer underwent E-NSM or R-NSM with immediate prosthesis breast reconstruction (IPBR) from July 2010 to February 2019 at a single institution to compare the clinical outcomes, learning curve, patient-reported cosmetic results, and medical cost., Results: A total of 91 E-NSM and 40 R-NSM procedures were retrieved and analyzed. The surgical margin involvement rate in both R-NSM (2.5%) and E-NSM (4.4%) procedures were relatively low (P = 0.52). The R-NSM group was associated with higher satisfaction rates in terms of scar appearance, scar length, and surgical wound position compared with the E-NSM group. Compared with E-NSM, the R-NSM operation time took longer (241 ± 61 vs. 215 ± 70 min, P = 0.01), less blood loss (32 ± 29 vs. 79 ± 62 ml, P < 0.01), and higher medical cost (10,587 ± 554 vs. 6855 ± 936 U.S. dollars, P < 0.01). There was no statistically significant difference in nipple ischemia/necrosis or overall complication between R-NSM and E-NSM. In the learning curve analysis, it took the 27th procedure in E-NSM and 10th procedure in R-NSM to decrease operation time significantly., Conclusions: R-NSM was associated with higher wound-related satisfaction, lesser blood loss, and shorter learning curve compared with E-NSM, however, at the price of longer operation time and higher medical cost.

[This corrects the article DOI: 10.1155/2020/5901962.]., (Copyright © 2020 Chieh-Cheng Hsu et al.)

Objective: Chronic osteomyelitis (COM) can induce systemic inflammation, and systemic inflammation may be associated with suicide tendency. However, no studies have investigated the correlation between COM and suicide tendency., Methods: The aim of this population-based study was to determine the epidemiology of fatal/non-fatal suicide among COM patients. Subjects with at least two outpatient visits or one course of inpatient care diagnosed with COM were recruited into a COM cohort. The control/COM subject ratio was approximately 4:1 matched by age, sex, major depression coding and index year (COM patients). Subjects with suicide attempts before COM diagnosis and subjects aged <20 years were excluded., Results: COM patients had 1.93 (95% confidence interval [CI]: 1.11-3.36) times the risk of fatal/non-fatal suicide as control subjects. Considering death as the competing event of fatal/non-fatal suicide, COM patients had 1.76 (95% CI: 1.03-3.01) times the risk of fatal/non-fatal suicide (competing risk regression model). The effect of COM on fatal/non-fatal suicide was more prominent among diabetic patients. COM severity also correlated with the risk of fatal/non-fatal suicide., Conclusions: More attention must be paid to suicide tendency among COM patients.

The development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resistin is known to promote the release of inflammatory cytokines during OA progression. In this study, we identified significantly higher levels of resistin and CD68 (a monocyte surface marker) expression in human OA tissue compared with in healthy control tissue. We also found that resistin enhances VCAM-1 expression in human OASFs and facilitates the adhesion of monocytes to OASFs. These effects were attenuated by inhibitors of PKCα, p38, and JNK; their respective siRNAs; and by a microRNA-381 (miR-381) mimic. In our anterior cruciate ligament transection (ACLT) rat model of OA, the inhibition of resistin activity prevented ACLT-induced damage to the OA rat cartilage and pathological changes in resistin and monocyte expression. We also found that resistin affects VCAM-1 expression and monocyte adhesion in human OASFs by inhibiting miR-381 synthesis via the PKCα, p38, and JNK signaling pathways. Our clarification of the crucial role played by resistin in the pathogenesis of OA may lead to more effective therapy that reduces OA inflammation.

Much data suggests intersecting activities between the adipokine apelin (APLN) and the pathologic processes of obesity and osteoarthritis (OA), with APLN modulating cartilage, synovium, bone, and various immune cell activities. The synovium plays an important role in the pathogenesis of OA. We investigated the crosstalk between APLN, a major OA-related adipokine, and interleukin 1 beta (IL-1β), a major proinflammatory cytokine, in human OA synovial fibroblasts (OASFs). We showed that APLN stimulated the synthesis of IL-1β in a concentration- and time-dependent manner, which was mitigated by blockade of the PI3K and ERK pathway. We also showed that APLN inhibited the expression of miRNA-144-3p, which blocks IL-1β transcription; this suppression activity was reversed via blockade of the PI3K and ERK pathway. Moreover, pathologic changes in OA cartilage were rescued when APLN was silenced by shAPLN transfection both in vitro and in vivo . Our evidence is the first to show that APLN stimulates the expression of IL-1β by activating the PI3K and ERK pathway and suppressing downstream expression of miRNA-144-3p in OASFs. We also demonstrate that knockdown of APLN expression by shAPLN transfection ameliorated changes in OA cartilage severity. These results shed light on OA pathogenesis and suggest a novel treatment pathway.

Aim: We wish to investigate the therapeutic potential of a single-session high-energy extracorporeal shock wave therapy (ESWT) on the rotator cuff lesions with shoulder stiffness. Patients and Methods . Thirty-seven patients afflicted with rotator cuff lesions with shoulder stiffness were randomized to receive either shockwave or sham treatment based on statistical randomization. In the shockwave group, we used Orthospec™ Extracorporeal Shock Wave Therapy 3000 impulse 24 kV (0.32 mJ/mm 2 ) focused at two points as one session. The sham intervention entailed the use of the device in which the silicone pad was removed from the stand-off device. The visual analogue scale (VAS), muscle power of the shoulder, Constant and Murley score (CMS), and range of motion (ROM) of the shoulder were assessed for all patients. Ten milliliters of peripheral venous blood was obtained from every participant for the measurements of markers for inflammation, tissue regeneration, angiogenesis, and substance P before and at 1 week and 4 weeks after intervention., Results: The ESWT group has significantly better VAS, muscle power, CMS, and ROM at 6 and 12 months after intervention. No between-group differences were observed before as well as 1 and 4 weeks after intervention in the selected biomarkers., Conclusion: ESWT may be a good adjuvant for the treatment of rotator cuff lesions with shoulder stiffness., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Jih-Yang Ko et al.)

Synovium-induced angiogenesis is central to osteoarthritis (OA) pathogenesis and thus a promising therapeutic target. The adipokine apelin (APLN) is involved in both OA pathogenesis and angiogenesis. We examined the role of APLN in synovium-induced angiogenesis by investigating the crosstalk between APLN and vascular endothelial growth factor (VEGF) expression in human OA synovial fibroblasts (OASFs). We found higher levels of APLN and VEGF expression in OA samples compared with normal samples. APLN-induced stimulation of VEGF expression and VEGF-dependent angiogenesis in OASFs was mitigated by FAK/Src/Akt signaling. APLN also inhibited levels of microRNA-150-5p (miR-150-5p), which represses VEGF production and angiogenesis. Analyses of an OA animal model showed that shAPLN transfection of OASFs rescued pathologic changes in OA cartilage and histology. Here, we found APLN enhances VEGF expression and angiogenesis via FAK/Src/Akt cascade and via downstream suppression of miR-150-5p expression. These findings help to clarify the pathogenesis of adipokine-induced angiogenesis in OA synovium.

Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07-1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00-1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0-26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2-67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42-5.56). Preventive measures for hip fracture might be warranted for PLA patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Chieh-Cheng Hsu et al.)

Background: Osteoporosis and fragility fracture are the major complications after liver transplantation (LT). The aim of the study was to determine the incidence and risk factors of hip fracture after LT., Methods: We conducted a retrospective population-based cohort study, enrolling the patients receiving LT between January 1999 and December 2010. Control subjects were randomly matched to every recipient by age and sex by 1 : 10 ratios., Results: During the follow-up period, 17 recipients (0.77%) and 70 (0.32%) control subjects suffered from hip fractures. The incident rates (per 10000 person-years) were 21.49 for recipients and 7.52 for controls (adjusted hazard ratio = 2.71; 95% confidence interval = 1.21-6.05). The cumulative incidence of hip fracture was significantly higher among the recipients ( p < 0.0001). Among the recipients, the subjects aged >65 years at transplantation and with pretransplant steroid use are more susceptible to posttransplant hip fracture. Immunosuppressive agents did not significantly affect the risk of hip fracture among recipients., Conclusions: Liver transplantation is a risk factor for hip fractures. Aged >65 years at transplantation and pretransplant steroid use are risk factors for posttransplant hip fractures among the recipients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Yung-Cheng Chiu et al.)

Introduction: Tranexamic acid (TXA) is an effective blood salvage agent that reduces perioperative blood loss in conventional total knee arthroplasty (TKA). As computer-assisted surgery for TKA (CAS-TKA) results in a lower perioperative blood loss than conventional TKA, the additional effect of blood conservation by TXA might be mitigated. This study aimed to evaluate the efficacy of TXA in CAS-TKA., Methods: We retrospectively reviewed 222 consecutive patients who underwent CAS-TKA. Intravenous TXA was administered in 103 patients (TXA group) at a dosage of 20 mg/kg 15 min before deflation of the tourniquet. The other 119 patients did not receive TXA (control group). Patient demographic data including age, gender, BMI, DM, and hypertension were collected. The primary outcomes were the estimated total blood loss (ETBL) and perioperative data, including tourniquet duration, preoperative and postoperative day 1 (POD1) and day 3 (POD3) serum D-dimer, CRP, hemoglobin (Hb), and hematocrit (Hct) levels. Secondary outcomes including transfusion rate and 90-day complications were recorded., Results: The ETBL was lower in the TXA group on both POD1 (404.34 ± 234.77 vs. 595.47 ± 279.04, p < 0.001) and POD3 (761.39 ± 260.88 vs. 987.79 ± 326.58, p < 0.001). The TXA group also demonstrated a lower level of CRP on POD1 ( p =0.02) and lower levels of CRP and serum D-dimer on POD3 ( p =0.008 and p < 0.001). Consumption of fibrinogen was higher in the control group on both POD1 ( p =0.013) and POD3 ( p < 0.001). Length of hospital stay was lower in the TXA group (5.42 ± 1.21 vs. 6.25 ± 1.49, p < 0.001). The transfusion rate and perioperative complications were not significantly different between the two groups., Conclusion: Administration of TXA is not only effective in reducing perioperative blood loss and length of hospital stay but also exerts an anti-inflammatory effect following CAS-TKA without causing major complications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Kuan-Ting Wu et al.)

This study genotyped blood samples from 214 patients with rheumatoid arthritis (RA) and 293 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, rs1689334 and rs62514004. We want to investigate whether the SNPs in the WNT1-inducible signaling pathway protein 1 (WISP-1) gene may increase the risk of developing RA. We showed that RA disease was more likely with the AA genotype compared with the AG genotype of SNP rs2977537 (adjusted odds ratio [AOR]: 0.54; 95% confidence interval [CI]: 0.34-0.84), and with the TT genotype (AOR: 0.24; 95% CI: 0.13-0.39) or the GG genotype (AOR: 0.05; 95% CI: 0.03-0.10) compared with the GT genotype of rs2929973, and with the AA genotype (AOR: 0.34; 95% CI: 0.22-0.54) or GG genotype (AOR: 0.52; 95% CI: 0.31 to 0.87) vs the AG genotype of rs2977530. Rheumatoid factor positivity was more likely with the AA genotype than with the AG genotype of the rs2977537 polymorphism (AOR: 0.16; 95% CI: 0.16-0.94). High CRP (>8 mg/L) was more likely with the non-AG genotype (AA + GG) than the AG genotype of rs2977537 (AOR: 1.84; 95% CI: 1.05-3.21) and with the AA genotype vs the AG genotype of rs2977530 (AOR: 2.62; 95% CI: 1.35-5.09). Compared with the AG genotype, the AA genotype of rs2929970 was more likely to require prednisolone (AOR: 0.49; 95% CI: 0.27-0.88), while the AG genotype was more likely than the AA genotype of SNP rs2977530 to require TNF-α inhibitors (AOR: 2.07; 95% CI: 1.08 to 3.98). WISP-1 may be a diagnostic marker and therapeutic target for RA therapy.

Background: Venous thromboembolism (VTE) is a major sequela after total knee arthroplasty (TKA). We prospectively compared the differences in the perioperative plasma D-dimer and fibrinogen levels between the individuals undergoing TKA via computer-assisted navigation and via a conventional method as the surrogate comparison for VTE. There were 174 patients fulfilling the inclusion criteria and providing valid informed consent between September 2011 and November 2013. There were 69 females and 20 males in the navigation-assisted group (median age: 71.00 years), while the conventional group was composed of 59 females and 26 males (median age: 69.00 years). Blood samples were obtained prior to and at 24 and 72 h after surgery for measurement of the levels of plasma D-dimer and fibrinogen., Results: A significantly lower plasma D-dimer level 24 h after TKA (p = 0.001) and a milder postoperative surge 24 h after TKA (p = 0.002) were observed in patients undergoing navigation-assisted TKA. The proportions of subjects exceeding the plasma D-dimer cut-off values of 7.5, 8.6 and 10 mg/L 24 h after TKA were all significantly higher in the conventional group than in the navigation-assisted group (p = 0.024, 0.004, and 0.004, respectively)., Conclusions: A lower plasma D-dimer level and a milder surge in the plasma D-dimer level were observed in patients undergoing navigation-assisted TKA in comparison with patients undergoing conventional TKA 24 h after surgery. These findings may supplement the known advantages of navigation-assisted TKA.

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction : Human chondrosarcomas (CS; a malignant cartilage-forming bone tumor) respond poorly to chemotherapy and radiation treatment, resulting in high morbidity and mortality rates. Expanded treatment options are urgently needed. Areas covered : This article updates our 2014 review, in which we evaluated the CS treatments available at that time and potential treatment options under investigation. Since then, advances in research findings, particularly from Chinese herbal medicines, may be bringing us closer to more effective therapies for CS. In particular, promising findings have been reported from research targeting platelet-derived growth factor receptor. Expert opinion : Few treatment options exist for CS; chemotherapy is not even an option for unresectable disease, in which 5-year survival rates are just 2%. New information about the multitude of genes and signaling pathways that encourage CS growth, invasion and metastasis are clarifying how certain signaling pathways and plant-derived active compounds, especially molecularly-targeted therapies that inhibit the PDGF receptor, interfering with these biological processes. This review summarizes discoveries from the last 5 years and discusses how these findings are fueling ongoing work into effectively dealing with the disease process and improving the treatment of CS.

The preliminary experience and results of an innovative surgical technique that incorporated a single-port and 3-dimensional (3D) videoscope system for endoscopic nipple-sparing mastectomy (E-NSM) were reported. The medical records of patients who underwent single-port 3D E-NSM for breast cancer during the period of August 2018 to October 2018 in a single institution were collected prospectively and analyzed. Patients' reported cosmetic outcome results were also obtained. During the study period, 11 patients received 15 procedures of single-port 3D E-NSM. The mean operation time for single-port 3D E-NSM and immediate prosthesis breast reconstruction was 181.8 ± 32.4 minutes. The mean blood loss was 38.3 ± 45.3 ml (15-60). In the postoperative morbidity evaluation, 1 patient (6.7%) had delayed axillary wound healing and 2 (13.4%) had transient nipple ischemia, but there were no cases of total nipple areolar complex necrosis and implant loss observed. In addition, there were no cases with margin involvement or locoregional recurrence during the follow-up period. In patient-reported cosmetic outcomes, high (93.3%) satisfaction rates were observed in terms of postoperative scar appearance, location, and length. All patients who had received 3D E-NSM and immediate prosthesis breast reconstruction reported that they would choose the same operation again if given the chance to do so. From our preliminary experience, single-port 3D E-NSM is a feasible and safe procedure with good cosmetic results. Hence, this technique could be a promising new technique for patients with breast cancer indicated for nipple-sparing mastectomy., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Osteoarthritis (OA) is an age-related disease marked by synovial inflammation and cartilage destruction arising from synovitis, joint swelling and pain. OA therapy that targets the synovium is a promising strategy for mitigating the symptoms and disease progression. Altered activity of the transforming growth factor-β1 isoform (TGF-β1) during aging underlies OA progression. Notably, aberrant forkhead box class O 3 (FOXO3) activity is implicated in the pathogenesis of various age-related diseases, including OA. This study explored the interaction and cross-talk of TGF-β1 and FOXO3 in human osteoarthritis synovial fibroblasts (OASFs). TGF-β1 stimulated FOXO3 synthesis in OASFs, which was mitigated by blocking adenosine monophosphate-activated protein kinase (AMPK) and p38 activity. TGF-β1 also inhibited the expression of miR-92a, which suppresses FOXO3 transcription. The suppression of miR-92a was effectively reversed with the blockade of the AMPK and p38 pathways. Our study showed that TGF-β1 promotes anti-inflammatory FOXO3 expression by stimulating the phosphorylation of AMPK and p38 and suppressing the downstream expression of miR-92a. These results may help to clarify OA pathogenesis and lead to better targeted treatment.

Secretion from adipose tissue of adipokines or adipocytokines, comprising of bioactive peptides or proteins, immune molecules and inflammatory mediators, exert critical roles in inflammatory arthritis and obesity. This review considers the evidence generated over the last decade regarding the effects of several adipokines including leptin, adiponectin, visfatin, resistin, chemerin and apelin, in cartilage and bone homeostasis in the pathogenesis of rheumatoid arthritis and osteoarthritis, which has important implications for obesity.

Background: The preliminary experience and learning curve of robotic nipple sparing mastectomy (R-NSM) in the management of breast cancer were analyzed and reported., Methods: The medical records of patients who underwent R-NSM for breast cancer during the period of March 2017 to June 2018 were collected from the same surgeon in a single institute. Data on clinicopathologic characteristics, type of surgery, method of breast reconstruction, and operation time were prospective collected. Learning curve of R-NSM was evaluated and analyzed by the cumulative sum (CUSUM) plot method., Results: A total of 39 consecutive R-NSM procedures from 35 patients were analyzed. The time needed for "docking", "R-NSM", and "R-NSM and immediate prosthesis breast reconstruction (IPBR)" decreased after cases experience accumulated, and in mature phase procedures could finished within 10 min, 100mins, and 240 min, separately. In CUSUM plots analysis of learning curve, the cases needed to decrease operation time for "docking", "R-NSM", and "total time for R-NSM and IPBR" were 13th, 13th, and 12th procedures separately. Mastectomy weight and lymph node metastasis were factors related to operation time. The rate of total nipple areolar complex necrosis for R-NSM was 0%. One (2.9%, 1/35) R-NSM procedure was found to have positive margin involved in the final pathologic check-up. No implant loss, or local recurrence was observed during a mean follow-up of 8.6 ± 4.5 (1.3-16.7) months., Conclusion: From our preliminary experience, R-NSM and IPBR (or R-NSM alone) is a safe procedure, and the operation time needed significantly decrease after cases experience accumulated., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disease resulting from the misfolding and accumulation of a pathogenic protein, causing cerebellar dysfunction, and this disease currently has no effective treatments. Far-infrared radiation (FIR) has been found to protect the viability of SCA3 cells by preventing mutant ataxin-3 protein aggregation and promoting autophagy. However, this possible treatment still lacks in vivo evidence. This study assessed the effect of FIR therapy on SCA3 in vivo by using a mouse model over 28 weeks. Control mice carried a healthy wild-type ATXN3 allele that had a polyglutamine tract with 15 CAG repeats (15Q), whereas SCA3 transgenic mice possessed an allele with a pathological polyglutamine tract with expanded 84 CAG (84Q) repeats. The results showed that the 84Q SCA3 mice displayed impaired motor coordination, balance abilities, and gait performance, along with the associated loss of Purkinje cells in the cerebellum, compared with the normal 15Q controls; nevertheless, FIR treatment was sufficient to prevent those defects. FIR significantly improved performance in terms of maximal contact area, stride length, and base support in the forepaws, hindpaws, or both. Moreover, FIR treatment supported the survival of Purkinje cells in the cerebellum and promoted the autophagy, as reflected by the induction of autophagic markers, LC3II and Beclin-1, concomitant with the reduction of p62 and ataxin-3 accumulation in cerebellar Purkinje cells, which might partially contribute to the rescue mechanism. In summary, our results reveal that FIR confers therapeutic effects in an SCA3 transgenic animal model and therefore has considerable potential for future clinical use.