bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment
Authors: Yang Yang , Liu Qilong , Cao Lei , Sun Wei , Gu Xiaowei , Liu Bin , Xiao Na , Teng Fei , Li Xiaoli , Chen Meiji , Yu Weiguang , Lin Huanyi , Xu Guixing 
Published: May 2021

Abstract
Background
The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment.

Methods
Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified from our medical institution during 2016–2018 and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results
The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39–0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1–14.8] for OSI vs 9.6 months [95% CI, 8.4–10.2] for AFA). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41–0.91; p = 0.014; median, 4.5 months [95% CI, 3.5–5.7] vs 3.9 months [95% CI, 3.1–4.8]). The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%).

Conclusions
In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.
Cryoneurolysis’ outcome on pain experience (COPE) in patients with low-back pain: study protocol for a single-blinded randomized controlled trial
Authors: Truong K. , Meier K. , Nikolajsen L. , van Tulder M. W. , Sørensen J. C.H , Rasmussen M. M 
Published: May 2021

Abstract
Background
Low-back pain, including facet joint pain, accounts for up to 20 % of all sick leaves in DenmarkA proposed treatment option is cryoneurolysis. This study aims to investigate the effect of cryoneurolysis in lumbar facet joint pain syndrome.

Methods
A single-center randomized controlled trial (RCT) is performed including 120 participants with chronic facet joint pain syndrome, referred to the Department of Neurosurgery, Aarhus University Hospital. Eligible patients receive a diagnostic anesthetic block, where a reduction of pain intensity ≥ 50 % on a numerical rating scale (NRS) is required to be enrolled. Participants are randomized into three groups to undergo either one treatment of cryoneurolysis, radiofrequency ablation or placebo. Fluoroscopy and sensory stimulation is used to identify the intended target nerve prior to administrating the above-mentioned treatments. All groups receive physiotherapy for 6 weeks, starting 4 weeks after treatment. The primary outcome is the patients’ impression of change in pain after intervention (Patient Global Impression of Change (PGIC)) at 4 weeks follow-up, prior to physiotherapy. Secondary outcomes are a reduction in low-back pain intensity (numeric rating scale) and quality of life (EQ-5D, SF-36) and level of function (Oswestry Disability Index), psychological perception of pain (Pain Catastrophizing Scale) and depression status (Major Depression Inventory).
Data will be assessed at baseline (T0), randomization (T1), day one (T2), 4 weeks (T3), 3 (T4), 6 (T5) and 12 months (T6).

Discussion
This study will provide information on the effectiveness of cryoneurolysis vs. the effectiveness of radiofrequency ablation or placebo for patients with facet joint pain, and help to establish whether cryoneurolysis should be implemented in clinical practice for this patient population.

Trial registration
The trial is approved by the ethical committee of Central Jutland Denmark with registration number 1-10-72-27-19 and the Danish Data Protection Agency with registration number 666,852. The study is registered at Clinicaltrial.gov with the ID number NCT04786145.
Strategies for managing the destruction of calcar femorale
Authors: Mei Jin , Pang Lili , Jiang Zhongchao 
Published: May 2021

AbstractBackgroundThe calcar femorale was identified long ago. However, our current understanding of the calcar is insufficient, and its related concepts are sometimes confused. The calcar femoral is an important anatomical structure of the proximal femur, and its function can be overlooked. In trauma, tumors, or other diseases, the calcar femorale can be destroyed or changed pathologically. As a result, the mechanical structure of the proximal femur becomes destroyed, causing pathological fractures. How to address the destruction of the calcar femorale or the damage to the calcar femorale is discussed in this article.Main textDestruction of the calcar femorale is accompanied by many conditions, including trauma, tumors, and other diseases. The types of hip fractures caused by trauma include femoral neck fractures and intertrochanteric fractures. Dynamic hip screws, proximal femoral nail anti-rotation, and multiple parallel cannulate pins can be used in different conditions. When metastatic and primary bone tumors involve the calcar femorale, endoprostheses are widely used. Other diseases, such as fibrous dysplasia and aneurysmal bone cyst are treated differently.ConclusionsThe calcar femorale can redistribute stresses and the destruction of the calcar femorale can lead to an increase in posterior medial stress. Many factors need to be considered when deciding whether to reconstruct the calcar femorale. Effective treatment strategies for managing the destruction of calcar femorale will need first establishing the precise mechanism of the destruction of the calcar and then designing therapies towards these mechanisms. Further investigation to the calcar needs to be carried out.
Augmented reality in the operating room: a clinical feasibility study
Authors: Dennler Cyrill , Bauer David E. , Scheibler Anne-Gita , Spirig José , Götschi Tobias , Fürnstahl Philipp , Farshad Mazda 
Published: May 2021

Abstract
Background
Augmented Reality (AR) is a rapidly emerging technology finding growing acceptance and application in different fields of surgery. Various studies have been performed evaluating the precision and accuracy of AR guided navigation. This study investigates the feasibility of a commercially available AR head mounted device during orthopedic surgery.

Methods
Thirteen orthopedic surgeons from a Swiss university clinic performed 25 orthopedic surgical procedures wearing a holographic AR headset (HoloLens, Microsoft, Redmond, WA, USA) providing complementary three-dimensional, patient specific anatomic information. The surgeon’s experience of using the device during surgery was recorded using a standardized 58-item questionnaire grading different aspects on a 100-point scale with anchor statements.

Results
Surgeons were generally satisfied with image quality (85 ± 17 points) and accuracy of the virtual objects (84 ± 19 point). Wearing the AR device was rated as fairly comfortable (79 ± 13 points). Functionality of voice commands (68 ± 20 points) and gestures (66 ± 20 points) provided less favorable results. The greatest potential in the use of the AR device was found for surgical correction of deformities (87 ± 15 points). Overall, surgeons were satisfied with the application of this novel technology (78 ± 20 points) and future access to it was demanded (75 ± 22 points).

Conclusion
AR is a rapidly evolving technology with large potential in different surgical settings, offering the opportunity to provide a compact, low cost alternative requiring a minimum of infrastructure compared to conventional navigation systems. While surgeons where generally satisfied with image quality of the here tested head mounted AR device, some technical and ergonomic shortcomings were pointed out. This study serves as a proof of concept for the use of an AR head mounted device in a real-world sterile setting in orthopedic surgery.
Comparison of hamstring and quadriceps strength after anatomical versus non-anatomical anterior cruciate ligament reconstruction: a retrospective cohort study
Authors: Jiang Hai , Zhang Lei , Zhang Rui-Ying , Zheng Qiu-Jian , Li Meng-Yuan 
Published: May 2021

Abstract
Background
Strength recovery of injured knee is an important parameter for patients who want to return to sport after anterior cruciate ligament reconstruction (ACLR). Comparison of muscle strength between anatomical and non-anatomical ACLR has not been reported.

Purpose
To evaluate the difference between anatomical and non-anatomical single-bundle ACLR in hamstring and quadriceps strength and clinical outcomes.

Methods
Patients received unilateral primary single-bundle hamstring ACLR between January 2017 to January 2018 were recruited in this study. Patients were divided into anatomical reconstruction group (AR group) and non-anatomical reconstruction group (NAR group) according to femoral tunnel aperture position. The hamstring and quadriceps isokinetic strength including peak extension torque, peak flexion torque and H/Q ratio were measured at an angular velocity of 180°/s and 60°/s using an isokinetic dynamometer. The isometric extension and flexion torques were also measured. Hamstring and quadriceps strength were measured preoperatively and at 3, 6, and 12 months after surgery. Knee stability including Lachman test, pivot-shift test, and KT-1000 measurement and subjective knee function including International Knee Documentation Committee (IKDC) and Lysholm scores were evaluated during the follow-up.

Results
Seventy-two patients with an average follow-up of 30.4 months (range, 24–35 months) were included in this study. Thirty-three were in AR group and 39 in NAR group. The peak knee flexion torque was significant higher in AR group at 180°/s and 60°/s (P < 0.05 for both velocity) at 6 months postoperatively and showed no difference between the two groups at 12 months postoperatively. The isometric knee extension torque was significant higher in AR group at 6 months postoperatively (P < 0.05) and showed no difference between the two groups at 12 months postoperatively. No significant differences between AR group and NAR group were found regarding knee stability and subjective knee function evaluations at follow-up.

Conclusions
Compared with non-anatomical ACLR, anatomical ACLR showed a better recovery of hamstring and quadriceps strength at 6 months postoperatively. However, the discrepancy on hamstring and quadriceps strength between the two groups vanished at 1 year postoperatively.
Long-term follow-up of prophylactic mesh reinforcement after emergency laparotomy. A retrospective controlled study
Authors: Bravo-Salva A. , Argudo-Aguirre N. , González-Castillo A. M. , Membrilla-Fernandez E. , Sancho-Insenser J. J. , Grande-Posa L. , Pera-Román M. , Pereira-Rodríguez J. A. 
Published: May 2021

Abstract
Background
Prevention of incisional hernias with a prophylactic mesh in emergency surgery is controversial. The present study aimed to analyze the long-term results of prophylactic mesh used for preventing incisional hernia after emergency midline laparotomies.

Methods
This study was a registered (NCT04578561) retrospective analysis of patients who underwent an emergency midline laparotomy between January 2009 and July 2010 with a follow-up period of longer than 2 years. Long-term outcomes and risk factors for the development of incisional hernias between patients who received a prophylactic reinforcement mesh (Group M) and suture (Group S) were compared.

Results
From an initial 266 emergency midline laparotomies, 187 patients were included. The median follow-up time was 64.4 months (SD 35). Both groups had similar characteristics, except for a higher rate of previous operations (62 vs. 43.2%; P = 0.01) and operation due to a revision laparotomy (32.5 vs.13%; P = 0.02) in the M group. During follow-up, 29.9% of patients developed an incisional hernia (Group S 36.6% vs. Group M 14.3%; P = 0.002). Chronic mesh infections were diagnosed in 2 patients, but no mesh explants were needed, and no patient in the M group developed chronic pain. Long-term risk factors for incisional hernia were as follows: smoking (HR = 2.47; 95% CI 1.318–4.624; P = 0.05), contaminated surgery (HR = 2.98; 95% CI 1.142–7.8; P = 0.02), surgical site infection (SSI; HR = 3.83; 95% CI 1.86–7.86; P = 0.001), and no use of prophylactic mesh (HR = 5.09; 95% CI 2.1–12.2; P = 0.001).

Conclusion
Incidence of incisional hernias after emergency midline laparotomies is high and increases with time. High-risk patients, contaminated surgery, and surgical site infection (SSI) benefit from mesh reinforcement. Prophylactic mesh use is safe and feasible in emergencies with a low long-term complication rate.
Trial registration: NCT04578561. www.clinicaltrials.gov
Safety profile of preoperative administration of low-molecular-weight heparin on minimally invasive lung cancer surgery: a randomized controlled trial
Authors: A-Lai Gu-Ha , Zhuo Ze-Guo , Li Gang , Song Tie-Niu , Xu Zhi-Jie , Shen Xu , Yao Peng , Lin Yi-Dan 
Published: May 2021

Abstract
Background
Venous thromboembolism remains a common but preventable complication for cancerous lung surgical patients. Current guidelines recommend thromboprophylaxis for lung patients at high risk of thrombosis, while a consensus about specific administration time is not reached. This study was designed to investigate the safety profile of preoperative administration of low-molecular-weight-heparin (LMWH) for lung cancer patients.

Methods
From July 2017 to June 2018, patients prepared to undergo lung cancer surgery were randomly divided into the preoperative LMWH-administration group (PRL) for 4000 IU per day and the postoperative LMWH-administration group (POL) with same dosage, all the patients received thromboprophylaxis until discharge. Baseline characteristics including demographics and preoperative coagulation parameters were analyzed, while the endpoints included postoperative coagulation parameters, postoperative drainage data, hematologic data, intraoperative bleeding volume and reoperation rate.

Results
A total of 246 patients were collected in this RCT, 34 patients were excluded according to exclusion criterion, 101 patients were assigned to PRL group and 111 patients belonged to POL group for analysis finally. The baseline characteristic and preoperative coagulation parameters were all comparable except the PRL group cost more operation time (p = 0.008) and preoperative administration duration was significantly longer (p < 0.001). The endpoints including postoperative day 1 coagulation parameters, mean and total drainage volume, drainage duration, intraoperative bleeding volume and reoperation rate were all similar between the two groups. Moreover, coagulation parameters for postoperative day 3 between the two groups demonstrated no difference.

Conclusion
Preoperative administration of low-molecular-weight-heparin demonstrated safety and feasibility for lung cancer patients intended to receive minimally invasive surgery.
Trial registration: ChiCTR2000040547 (www.chictr.org.cn), 2020/12/1, retrospectively registered.
Salidroside protects endothelial cells against LPS-induced inflammatory injury by inhibiting NLRP3 and enhancing autophagy
Authors: You Lijiao , Zhang Di , Geng Huan , Sun Fangyuan , Lei Ming 
Published: May 2021

AbstractBackgroundSalidroside (SAL) is a bioactive compound extracted fromRhodiola roseawith various biological properties. This study was designed to explore the functions of SAL on the endothelial damage induced by lipopolysaccharide (LPS) and its related mechanisms.MethodsHuman umbilical vein endothelial cells (HUVECs) were pretreated with SAL (0, 10, 25, 50, 100 μM), and then incubated with LPS (10 μg/mL). Cell viability was evaluated by MTT assay, cell injury by lactate dehydrogenase (LDH) release, and inflammatory cytokines release by ELISA assay. Oxidative stress was evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) in cell lysate. Apoptosis was detected by flow cytometry and caspase-3 activity. Western blot were performed to determine expression levels of autophagy and NOD-like receptor protein 3 (NLRP3) related proteins.ResultsSAL at 50 μM concentration showed no toxicity on HUVECs, but attenuated LPS-induced injury, as evidenced by increased cell viability, reduction in LDH level and inflammatory cytokines in culture media. SAL also reduced MDA level and increased SOD activity in HUVECs, and inhibited apoptosis rate and caspase-3 activity. (P < 0.05). Moreover, LPS enhanced HUVECs autophagy, and SAL pretreatment further enhanced autophagy, with increased Beclin-1 protein and decreased P62 protein. SAL also attenuated LPS-induced activation of NLRP3 inflammasome, reduced the protein expression of NLRP3-related proteins, including ASC and caspase-1. Autophagy inhibition by 3-MA markedly reversed SAL-modulated changes in cell viability and NLRP3 expression in LPS-stimulated HUVECs.ConclusionSAL protects endothelial cells against LPS-induced injury through inhibition of NLRP3 pathways and enhancing autophagy.
A new family with spastic paraplegia type 51 and novel mutations in AP4E1
Authors: Winkler Izabela , Miotła Paweł , Lejman Monika , Pietrzyk Aleksandra , Kacprzak Magdalena , Kubiak Marcin , Sobczyńska-Tomaszewska Agnieszka , Skrzypczak Maciej , Jaszczuk Ilona 
Published: May 2021

Abstract
Background
Autosomal recessive mutations in the AP-4 (adaptor protein complex 4) complex subunit ϵ − 1 (AP-4E1) gene on chromosome 15q21.2 are known to cause spastic paraplegia 51 (SPG51). The exact phenotype of SPG51 remains poorly characterized, because only a few families have been reported as carriers of the mutation. In addition, a previous study identified an autosomal dominant mutation in the AP4E1 gene as being associated with persistent stuttering. The aim of the current study was to characterize the phenotype of a paediatric patient with an identified novel AP4E1 mutation presenting with significant psychomotor retardation, intellectual disability and paraplegia.

Methods
Magnetic resonance imaging was used to identify hypoplasia of the corpus callosum. The DNA sample was tested using multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). In addition, next-generation sequencing (NGS) was performed using the patient’s DNA, and Sanger sequencing was performed using that of his family members.

Results
The phenotype was identified to be associated with a novel pathogenic variant c.942_943 + 3delinsCC in the AP4E1 gene. The patient manifested severely delayed psychomotor development, impaired global physical development and general illness. Movement disorders were evident during the neonatal period.

Conclusions
The present study identifies a previously unknown disease-inducing AP4E1 gene mutation.
Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug
Authors: Nesti Lorenzo , Tricò Domenico , Mengozzi Alessandro , Natali Andrea 
Published: May 2021

AbstractSince 1985, the thiazolidinedione pioglitazone has been widely used as an insulin sensitizer drug for type 2 diabetes mellitus (T2DM). Although fluid retention was early recognized as a safety concern, data from clinical trials have not provided conclusive evidence for a benefit or a harm on cardiac function, leaving the question unanswered. We reviewed the available evidence encompassing both in vitro and in vivo studies in tissues, isolated organs, animals and humans, including the evidence generated by major clinical trials. Despite the increased risk of hospitalization for heart failure due to fluid retention, pioglitazone is consistently associated with reduced risk of myocardial infarction and ischemic stroke both in primary and secondary prevention, without any proven direct harm on the myocardium. Moreover, it reduces atherosclerosis progression, in-stent restenosis after coronary stent implantation, progression rate from persistent to permanent atrial fibrillation, and reablation rate in diabetic patients with paroxysmal atrial fibrillation after catheter ablation. In fact, human and animal studies consistently report direct beneficial effects on cardiomyocytes electrophysiology, energetic metabolism, ischemia–reperfusion injury, cardiac remodeling, neurohormonal activation, pulmonary circulation and biventricular systo-diastolic functions. The mechanisms involved may rely either on anti-remodeling properties (endothelium protective, inflammation-modulating, anti-proliferative and anti-fibrotic properties) and/or on metabolic (adipose tissue metabolism, increased HDL cholesterol) and neurohormonal (renin–angiotensin–aldosterone system, sympathetic nervous system, and adiponectin) modulation of the cardiovascular system. With appropriate prescription and titration, pioglitazone remains a useful tool in the arsenal of the clinical diabetologist.