bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of innovative medical technologies in German inpatient care: patterns of utilization and evidence development
Authors: Dreger Marie , Eckhardt Helene , Felgner Susanne , Ermann Hanna , Lantzsch Hendrikje , Rombey Tanja , Busse Reinhard , Henschke Cornelia , Panteli Dimitra 
Published: October 2021

Abstract
Background
Innovative medical technologies are commonly associated with positive expectations. At the time of their introduction into care, there is often little evidence available regarding their benefits and harms. Accordingly, some innovative medical technologies with a lack of evidence are used widely until or even though findings of adverse events emerge, while others with study results supporting their safety and effectiveness remain underused. This study aims at examining the diffusion patterns of innovative medical technologies in German inpatient care between 2005 and 2017 while simultaneously considering evidence development.

Methods
Based on a qualitatively derived typology and a quantitative clustering of the adoption curves, a representative sample of 21 technologies was selected for further evaluation. Published scientific evidence on efficacy/effectiveness and safety of the technologies was identified and extracted in a systematic approach. Derived from a two-dimensional classification according to the degree of utilization and availability of supportive evidence, the diffusion patterns were then assigned to the categories “Success” (widespread/positive), “Hazard” (widespread/negative), “Overadoption” (widespread/limited or none), “Underadoption” (cautious/positive), “Vigilance” (cautious/negative), and “Prudence” (cautious/limited or none).

Results
Overall, we found limited evidence on the examined technologies regarding both the quantity and quality of published randomized controlled trials. Thus, the categories “Prudence” and “Overadoption” together account for nearly three-quarters of the years evaluated, followed by “Success” with 17%. Even when evidence is available, the transfer of knowledge into practice appears to be inhibited.

Conclusions
The successful implementation of safe and effective innovative medical technologies into practice requires substantial further efforts by policymakers to strengthen systematic knowledge generation and translation. Creating an environment that encourages the conduct of rigorous studies, promotes knowledge translation, and rewards innovative medical technologies according to their added value is a prerequisite for the diffusion of valuable health care.
Benefit of chemotherapy based on platinum with definitive radiotherapy in older patients with locally advanced esophageal squamous cell carcinoma
Authors: Wu Haishan , Yu Yilin , Zheng Qunhao , Liu Tianxiu , Wu Yahua , Wang Zhiping , Zheng Hongying , Liu Lingyun , Li Jiancheng 
Published: October 2021

Abstract
Objective
There is still no definitely therapeutic evidence of a beneficial effect of chemotherapy with radiotherapy for older patients with esophageal squamous cell carcinoma (ESCC). We aim to determine the influence of chemoradiotherapy (CRT) and radiotherapy (RT) alone in patients aged 65 years or older with locally advanced ESCC.

Methods
We retrospectively analyzed 581 ESCC patients who underwent CRT and RT alone. Univariate and multivariate Cox regression analysis was used to analyze the impact of clinical factors on long‐term overall survival (OS) and progression-free survival (PFS). Finally, we compared the toxicity rates of these patients.

Results
The median OS and PFS of the overall population were 23.2 months (2.0–162.6 months) and 18.6 months (1.1–159.6 months). Multivariate Cox regression analysis showed that chemotherapy (p < 0.05), tumor thickness (p < 0.01), and N stage (p < 0.05) were independent prognostic factors associated with both OS and PFS. In the chemotherapy subgroup, patients who received 2–8 cycles of chemotherapy had better OS than those who received 1 cycle (p = 0.015). The results also revealed that the CRT group has better OS and PFS than RT alone group for patients aged 65–74 years (both p < 0.01). However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone (both p > 0.05). Besides, higher staged ESCC has the inferior OS and PFS than lower staged ESCC for patients received RT alone and aged 65–74 years (both p < 0.05). Finally, there were significantly more severe hematologic toxicities in the CRT group than in those treated with RT alone in this study (p < 0.001).

Conclusions
The present study suggested that CRT for locally advanced ESCC in patients aged 65 years or older had a significant benefit over RT alone in terms of OS and PFS. However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone. CRT should be performed with special attention in patients aged 75 years or older.
Incidence and risk factors associated with human albumin administration following total joint arthroplasty: a multicenter retrospective study
Authors: Zhang Shaoyun , Si Haibo , Xie Jinwei , Wu Yuangang , Hu Qinsheng , Zeng Yi , Pei Fuxing , Shen Bin 
Published: October 2021

Abstract
Background
Enhanced recovery after surgery (ERAS) program advocates implementation of perioperative goal-directed fluid therapy and reduced application of colloidal fluids. It should be used reasonably selectively in high-risk patients despite the clear efficacy of human albumin (HA). Therefore, it is vital to identify the risk factors for the use of HA. This study aims to determine the incidence and risk factors of HA administration in patients undergoing total hip or knee arthroplasty (THA, TKA).

Methods
We identified patients undergoing THA or TKA in multiple institutions from 2014 to 2016 and collected patient demographics and perioperative variables. The criterion of HA administration was defined as a postoperative albumin level < 32 g/L or 32 to 35 g/L for at-risk patients. We compared 14 variables between patients who received HA administration and those who did not after stratification by the preoperative albumin (pre-ALB) level. Multivariable regressions identified the independent risk factors associated with HA administration.

Results
In total, 958 (20.3%) of 4713 patients undergoing THA and 410 (9.7%) of 4248 patients undergoing TKA received HA administration. In addition to pre-ALB < 35 g/L, preoperative anemia (odds ratio [OR] 2.12, P = 0.001; OR 1.39, P < 0.001) and drain use (OR 3.33, P = 0.001; OR 4.25, P < 0.001) were also independent risk factors for HA administration after THA regardless pre-ALB < 35 g/L or not, and patients undergoing TKA diagnosed of rheumatoid arthritis or ankylosing spondylitis tended to receive HA administration regardless pre-ALB < 35 g/L or not (OR 3.67, P = 0.002; OR 2.06, P < 0.001).

Conclusions
The incidence of HA administration was high in patients undergoing THA or TKA, and several variables were risk factors for HA administration. This finding may aid surgeons in preoperatively identifying patients requiring HA administration and optimizing perioperative managements.
Intra-articular injection of loaded sPL sustained-release microspheres inhibits osteoarthritis and promotes cartilaginous repairs
Authors: Li Jiyou , Liu Ning , Huang Zhipeng , Wang Wantao , Hou Donghua , Wang Wenbo 
Published: October 2021

Abstract
Background
Osteoarthritis is a chronic inflammatory disease of the joints associated with significant morbidity and lower quality of life. Current treatment strategies focus on reducing cartilage degeneration but fail to restore their proliferative ability. Super-activated platelet lysate (sPL) is an enhanced form of platelet-rich plasma that can be easily inactivated. The purpose of this study is to evaluate whether sPL-loaded PLGA/chitosan/gelatin microspheres can prevent and treat osteoarthritis.

Methods
Features of biological microspheres were detected by SEM and ELISA. Osteoarthritis chondrocytes were co-cultured with hydrogel loaded with sPL. The effect of biological microspheres on chondrocyte proliferation was evaluated using a CCK-8 cell proliferation test. Cell morphology and cell necrosis were measured with a microscope. The gene expression levels of cartilage-related markers type 2 collagen, aggrecan (ACAN), and SRY type high mobility group box-9 (SOX9) were determined by real-time quantitative polymerase chain reaction (Rt-PCR). A rat osteoarthritis model was established. Micro-CT was used to characterize cartilaginous changes after the injection of biological microspheres. Histopathological HE staining, Safranin-O Fast Green staining and staining scores, type II collagen staining, and proteoglycan staining were used to evaluate the degree of cartilaginous repair.

Results
Biological microspheres were able to continuously release biological factors. Exposure to loading sPL microspheres significantly increased chondrocyte proliferation, reduced cell necrosis, and increased the expression of cartilage markers type 2 collagen, ACAN, and SOX9 in osteoarthritic chondrocytes. In vivo experiments found that biological microspheres also smoothen cartilage surfaces, promote the expression of proteoglycan and type 2 collagen while also increasing cartilaginous integrity as evaluated using Safranin-O Fast Green staining.

Conclusions
PLGA/chitosan/gelatin hydrogel loaded with sPL is a promising tool for effective and non-invasive articular cartilage repair in osteoarthritis.

Graphic abstract
Biological microspheres loaded with sPL release various biological factors to promote chondrocyte proliferation and upregulate chondrocyte functionalization genes (SOX9, CoX II, ACAN), leading to an overall enhanced cartilaginous matrix.
Doxorubicin inhibits osteosarcoma progression by regulating circ_0000006/miR-646/ BDNF axis
Authors: Amuti Abulimiti , Liu Dehu , Maimaiti Ayiguli , Yu Yao , Yasen Yalikun , Ma Haoguang , Li Rui , Deng Shurong , Pang Fei , Tian Youliang 
Published: October 2021

Abstract
Background
Osteosarcoma (OS) is the most common aggressive bone tumor in children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This study aims to reveal the effects and underneath mechanism of DOX treatment in OS progression.

Methods
The expression of circular_0000006 (circ_0000006), microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein expression was determined by western blot. Cell proliferation was illustrated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were revealed by transwell migration and wound-healing assays and transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF was predicted by circRNA interactome and targetscan online database, respectively, and verified by dual-luciferase reporter assay. The effects of circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor formation assay.

Results
Circ_0000006 expression and the mRNA and protein levels of BDNF were dramatically upregulated, and miR-646 expression was effectively downregulated in OS tissues or cells compared with control groups. Circ_0000006 expression and BDNF protein expression were lower, and miR-646 expression was higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 knockdown repressed cell proliferation, migration and invasion, whereas promoted cell apoptosis under DOX treatment in OS cells; however, these effects were attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo.

Conclusion
Circ_0000006 knockdown promoted DOX-mediated effects on OS development by miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.
Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures
Authors: Zhang Kexin , Zhu Yanbin , Tian Yunxu , Tian Miao , Li Xiuting , Zhang Yingze 
Published: October 2021

Abstract
Objective
This study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures.

Methods
This was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein.

Results
There were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied.

Conclusions
We developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.
Investigation of the role of the miR17-92 cluster in BMP9-induced osteoblast lineage commitment
Authors: Zhang Yunyuan , Jing Xuran , Li Zhongzhu , Tian Qingwu , Wang Qing , Chen Xian 
Published: October 2021

Abstract
Background
Bone morphogenetic protein 9 (BMP9) has been identified as a crucial inducer of osteoblastic differentiation in mesenchymal stem cells (MSCs). Although microRNAs (miRNAs) are known to play a role in MSC osteogenesis, the mechanisms of action of miRNAs in BMP9-induced osteoblastic differentiation remain poorly understood.

Methods
In this study, we investigate the possible role of the miR17-92 cluster in the BMP9-induced osteogenic differentiation of MSCs by using both in vitro and in vivo bone formation assays.

Results
The results show that miR-17, a member of the miR17-92 cluster, significantly impairs BMP9-induced osteogenic differentiation. This impairment is effectively rescued by a miR-17 sponge, an antagomiR sequence against miR-17. Using TargetScan and the 3′-untranslated region luciferase reporter assays, we show that the direct target of miR-17 is the retinoblastoma gene (RB1), a gene that is pivotal to osteoblastic differentiation. We also confirm that RB1 is essential for the miR-17 effects on osteogenesis.

Conclusion
Our results indicate that miR-17 expression impairs normal osteogenesis by downregulating RB1 expression and significantly inhibiting the function of BMP9.
S2-alar-iliac screw and S1 pedicle screw fixation for the treatment of non-osteoporotic sacral fractures: a finite element study
Authors: Zheng Jianxiong , Feng Xiaoreng , Xiang Jie , Liu Fei , Leung Frankie K. L. , Chen Bin 
Published: October 2021

Abstract
Background
Five different sacral fracture fixation methods were compared using finite element (FE) analysis to study their biomechanical characteristics.

Methods
Denis type I sacral fractures were created by FE modeling. Five different fixation methods for the posterior pelvic ring were simulated: sacroiliac screw (SIS), lumbopelvic fixation (LPF), transiliac internal fixator (TIFI), S2-alar-iliac (S2AI) screw and S1 pedicle screw fixation (S2AI-S1) and S2AI screw and contralateral S1 pedicle screw fixation (S2AI-CS1). Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending and left twisting, respectively. Vertical stiffness, relative displacement and change in relative displacement were recorded and analyzed.

Results
As predicted by the FE model, the vertical stiffness of the five groups in descending order was S2AI-S1, SIS, S2AI-CS1, LPF and TIFI. In terms of relative displacement, groups S2AI-S1 and S2AI-CS1 displayed a lower mean relative displacement, although group S2AI-CS1 exhibited greater displacement in the upper sacrum than group S2AI-S1. Group SIS displayed a moderate mean relative displacement, although the displacement of the upper sacrum was smaller than the corresponding displacement in group S2AI-CS1, while groups LPF and TIFI displayed larger mean relative displacements. Finally, in terms of change in relative displacement, groups TIFI and LPF displayed the greatest fluctuations in their motion, while groups SIS, S2AI-S1 and S2AI-CS1 displayed smaller fluctuations.

Conclusion
Compared with SIS, unilateral LPF and TIFI, group S2AI-S1 displayed the greatest biomechanical stability of the Denis type I sacral fracture FE models. When the S1 pedicle screw insertion point on the affected side is damaged, S2AI-CS1 can be used as an appropriate alternative to S2AI-S1.
Four-branched graft inversion technique for the distal anastomosis in acute aortic dissection
Authors: Zou Yu , Teng Peng , Ma Liang 
Published: October 2021

Abstract
Background
Distal anastomosis bleeding is an issue during total arch replacement with the frozen elephant trunk technique. We used the 4-branched graft inversion technique for the distal anastomosis in acute aortic dissection. The aim was to evaluate the feasibility and benefits of the technique used during the frozen elephant trunk procedure for acute aortic dissection.

Methods
From January 2017 to July 2019, 109 patients underwent total arch replacement for type A acute aortic dissections. Patients were divided according to the technique used for the distal anastomosis as follows: group G (n = 57; 4-branched graft inversion technique) and group C (n = 52; conventional method with Teflon felt). The postoperative variables were analysed.

Results
The hospital mortality rate was 9.2% (10/109). The mean cardiopulmonary bypass, cardiac arrest, and circulatory arrest times were 234.95 ± 71.88 min, 168.25 ± 61.33 min, and 39.19 ± 9.45 min, respectively. The circulatory arrest and cardiac arrest times were shorter in the graft inversion group than in the conventional group (36.46 ± 7.88 min vs. 42.19 ± 10.17 min, P = 0.001 and 156.21 ± 55.99 min vs. 181.44 ± 64.68 min, P = 0.031, respectively). There were 7 cases of stroke (6.4%) and 5 cases of paraplegia (4.6%). Additionally, 13 patients (11.9%) required temporary continuous renal replacement therapy. Respiratory failure occurred in 19 patients (17.4%). There were no significant differences in postoperative complications between the two groups.

Conclusions
The 4-branched graft inversion technique provides effective and confirmed haemostasis during total aortic arch replacement using the frozen elephant trunk procedure.
Effect of ventilation strategy during cardiopulmonary bypass on postoperative pulmonary complications after cardiac surgery: a randomized clinical trial
Authors: Zhang Meng-Qiu , Liao Yu-Qi , Yu Hong , Li Xue-Fei , Shi Wei , Jing Wei-Wei , Wang Zai-Li , Xu Yi , Yu Hai 
Published: October 2021

Abstract
Background
To determine whether maintaining ventilation during cardiopulmonary bypass (CPB) with a different fraction of inspired oxygen (FiO2) had an impact on the occurrence of postoperative pulmonary complications (PPCs).

Methods
A total of 413 adult patients undergoing elective cardiac surgery with CPB were randomly assigned into three groups: 138 in the NoV group (received no mechanical ventilation during CPB), 138 in the LOV group (received a tidal volume (VT) of 3–4 ml/kg of ideal body weight with the respiratory rate of 10–12 bpm, and the positive end-expiratory pressure of 5–8 cmH2O during CPB; the FiO2 was 30%), and 137 in the HOV group (received the same ventilation parameters settings as the LOV group while the FiO2 was 80%).

Results
The primary outcomes were the incidence and severity of PPCs during hospitalization. The composite incidence of PPCs did not significantly differ between the NoV (63%), LOV (49%) and HOV (57%) groups (P = 0.069). And there was also no difference regarding the incidence of PPCs between the non-ventilation (NoV) and ventilation (the combination of LOV and HOV) groups. The LOV group was observed a lower proportion of moderate and severe pulmonary complications (grade ≥ 3) than the NoV group (23.1% vs. 44.2%, P = 0.001).

Conclusion
Maintaining ventilation during CPB did not reduce the incidence of PPCs in patients undergoing cardiac surgery.
Trial registration: Chinese Clinical Trial Registry ChiCTR1800015261. Prospectively registered 19 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25982
Risk factors for 30-day mortality in patients who received DeBakey type I aortic dissection repair surgery
Authors: Wang Zhigang , Chen Tao , Ge Pingping , Ge Min , Lu Lichong , Zhang Lifang , Wang Dongjin 
Published: October 2021

Abstract
Objective
This study aimed to identify risk factors for 30-day mortality in patients who received DeBakey type I aortic dissection (AD) repair surgery.

Methods
A total of 830 consecutive patients who received acute DeBakey type I AD surgery between 2014 and 2019 were included in the study. The associations between 30-day mortality and perioperative parameters were examined in order to identify risk factors.

Results
Our data suggested that the overall 30-day mortality rate of all enrolled patients was 11.7%. Unsurprisingly, non-survivors were older and more frequently accompanied with histories of cardiovascular diseases. For intraoperative parameters, the prevalence of coronary artery bypass grafting and cardiopulmonary bypass times were increased in non-survivors. In addition, acute kidney injury (AKI), dialysis, stroke, and deep sternal wound infection were more commonly seen among non-survivors. The multivariate logistic regression analysis suggested that cardiovascular disease history, preoperative D-dimer level, drainage volume 24 h after surgery, and postoperative AKI were independent risk factors for 30-day mortality after DeBakey type I aortic dissection repair surgery.

Conclusions
Our study demonstrated that cardiovascular disease history, preoperative D-dimer level, drainage volume 24 h after surgery as well as postoperative AKI were risk factors for 30-day mortality after DeBakey type I aortic dissection repair surgery.