bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral silymarin formulation efficacy in management of AC-T protocol induced hepatotoxicity in breast cancer patients: A randomized, triple blind, placebo-controlled clinical trial
Authors: Moezian Ghazal Sadat Askarpour , Javadinia Seyed Alireza , Sales Soodabeh Shahid , Fanipakdel Azar , Elyasi Sepideh , Karimi Gholamreza 
Published: April 2021

Background Chemotherapeutic agents, with or without other drugs and radiation, may cause indirect or direct hepatotoxicity. Doxorubicin-induced hepatotoxicity (DIH) is a major health concern in cancer patients receiving this cytotoxic drug that is mostly resulted from the production of reactive oxygen species leading to transient or permanent liver damages. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. Purpose This study aimed to investigate the clinical efficacy of systemic administration of silymarin in management of chemotherapy induced hepatotoxicity in patients with non-metastatic breast cancer who received doxorubicin/cyclophosphamide-paclitaxel (AC-T) regimen. Material: In this randomized, triple blind, placebo-controlled clinical trial, 30 patients who received AC-T who fulfilled the inclusion criteria were randomly allocated to silymarin (n = 15) or placebo (n = 15) groups to receive oral silymarin 140 mg three times a day or placebo tablets, respectively. Fatty liver severity was assessed by liver ultrasound imaging and FibroScan® and also measurement of liver function tests before and after the intervention. Results There was a non-significant trend toward more severe liver involvement in placebo group comparing to the silymarin group after intervention based on ultrasonography (p = 0.083). Besides, in silymarin group, hepatic involvement grade based on ultrasonography considerably reduced after intervention (p = 0.012). However, no difference was found between two groups based on FibroScan and liver function tests. Conclusion Oral administration of silymarin could significantly reduce hepatotoxicity severity after 1 month of treatment in non-metastatic breast cancer patients treated with AC-T regimen.
A prospective sonographic evaluation of peripheral intravenous catheter associated thrombophlebitis
Authors: Mielke Nicholas , Johnson Steven , Karabon Patrick , Bahl Amit 
Published: April 2021

Objective: Thrombophlebitis associated with peripheral intravenous catheters (PIVCs) is a poorly described complication in the literature. Given limited accuracy of current assessment tools and poor documentation in the medical record, the true incidence and relevance of this complication is misrepresented. We aimed to identify risk factors in the development of thrombophlebitis using an objective methodology coupling serial diagnostic ultrasound and clinical assessment. Methods: We conducted a single-site, prospective observational cohort study. Adult patients presenting to the emergency department that underwent traditionally placed PIVC insertion and were being hospitalized with an anticipated length of stay greater than 2 days were eligible participants. Using serial, daily ultrasound evaluations and clinical assessments via the phlebitis scale, we identified patients with asymptomatic and symptomatic thrombosis. The primary goal was to identify demographic, clinical, and IV related risk factors associated with thrombophlebitis. Univariate and multivariate analyses were employed to identify risk factors for thrombophlebitis. Results: A total of 62 PIVCs were included between July and August 2020. About 54 (87.10%) developed catheter-related thrombosis with 22 (40.74%) of the thrombosed catheters were characterized as symptomatic. Multivariate cox regression demonstrated that catheter diameter relative to vein diameter greater than one-third [AHR = 5.41 (1.91, 15.4) p = 0.0015] and angle of distal tip of catheter against vein wall ⩾5° [AHR = 4.39 (1.39, 13.8) p = 0.0116] were associated with increased likelihood of thrombophlebitis. Conclusions: Our study found that the increased proportion of catheter relative to vein size and steeper catheter tip angle increased the risk of thrombophlebitis. Catheter size relative to vein size is a modifiable factor that should be considered when inserting PIVCs. Additional larger prospective investigations using objective methodologies are needed to further characterize complications in PIVCs.
Aerobic exercise for adolescent outpatients with persistent major depression: Feasibility and acceptability of moderate to vigorous group exercise in a clinically referred sample
Authors: Jarbin Håkan , Höglund Kristina , Skarphedinsson Gudmundur , Bremander Ann 
Published: April 2021

Aims: To assess feasibility and acceptability of exercise in clinically referred adolescents with major depression. Methods: Outpatients12 to 17 years with mild to moderate persistent depression participated in a supervised, pulse monitored, 14-week aerobic exercise but without control group. Primary outcome was adherence and secondary was clinician-rated Quick Inventory of Depressive Symptomatology – Adolescent (QIDS-A17-C), aerobic capacity, functioning, and well-being. Results: Twenty-one (66%) of 32 eligible adolescents with major depression with disease duration 2.4 (1.1–5.3) years and comorbid ADHD (71%) and anxiety disorders (62%) consented. Estimated maximum heart rate above 70% was achieved for mean 31.6 minutes, indicating that the intensity and duration of the exercise intervention was well received. Fourteen patients (67%) participated throughout the program and attended a median of 29 (81%, range 20–35) supporting satisfaction with the intervention by most patients. QIDS-A17-C score decreased compared to baseline at 15 weeks ( p < .001) and further at 1 year ( p < .001). Aerobic capacity improved during the intervention but was not maintained, while functioning improved and after 1 year also well-being. Conclusion: This 14 week moderate to vigorous aerobic exercise intervention was feasible and well accepted by most adolescents with persistent depression and extensive comorbidities.
Phase III randomized study of carboplatin pemetrexed with or without bevacizumab with initial versus “at progression” cerebral radiotherapy in advanced non squamous non-small cell lung cancer with asymptomatic brain metastasis
Authors: Monnet Isabelle , Vergnenègre Alain , Robinet Gilles , Berard Henri , Lamy Regine , Falchero Lionel , Vieillot Sabine , Schott Roland , Ricordel Charles , Chouabe Stephane , Thomas Pascal , Gervais Radj , Madroszyk Anne , Abdiche Samir , Chiappa Anne Marie , Greillier Laurent , Decroisette Chantal , Auliac Jean Bernard. , Chouaïd Christos ,   the GFPC 02-13 (METAL2) investigators
Published: April 2021

Background: The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM. Methods: This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin–pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537]. Results: The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p < 0.001); there were no significant differences between BR and ChT arms for median PFS: 4.7, 95% confidence interval (CI):3.4–7.5 versus 4.8, 95% CI: 2.4–6.5 months, for median OS: 8.5, 95% CI:.6–11.1 versus 8.3, 95% CI:4.5–11.5 months, cerebral and extra-cerebral ORR (27% versus 13%, p = 0.064, and 30% versus 41%, p = 0.245, respectively). The ChT arm had more grade 3/4 neutropenia than the BR arm (13% versus 6%, p = 0.045); others toxicities were comparable. Conclusion: The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR.
Return-to-Play Outcomes in Elite Athletes After Cervical Spine Surgery: A Systematic Review
Authors: Leider Joseph , Piche Joshua David , Khan Moin , Aleem Ilyas 
Published: April 2021

Context: Return-to-play (RTP) outcomes in elite athletes after cervical spine surgery are currently unknown. Objective: To systematically review RTP outcomes in elite athletes after anterior cervical discectomy and fusion (ACDF), cervical disc replacement (CDR), or posterior foraminotomy (PF) surgery. Data Sources: EMBASE, PubMed, Cochrane, and Medline databases from inception until April 2020. Keywords included elite athletes, return to play, ACDF, foraminotomy, and cervical disc replacement. Study Selection: Eligible studies included those that reported RTP outcomes in elite athletes after cervical spine surgery. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Data were extracted by 2 independent reviewers. Results: The primary outcomes of interest were rates and timing of RTP. Secondary outcomes included performance on RTP. A total of 1720 studies were initially screened. After inclusion criteria were applied, 13 studies with a total of 349 patients were included. A total of 262 (75%) played football, 37 (11%) played baseball, 19 (5%) played rugby, 10 (3%) played basketball, 10 (3%) played hockey, 9 (3%) were wresters, and 2 (1%) played soccer. ACDF was reported in 13 studies, PF in 3 studies, and CDR in 2 studies. The majority of studies suggest that RTP after surgical management is safe in elite athletes who are asymptomatic after their procedure and may lead to higher rates and earlier times of RTP. There is limited evidence regarding RTP or outcomes after CDR or multilevel surgery. Conclusion: The management and RTP in elite athletes after cervical spine injury is a highly complex and multifactorial topic. The overall evidence in this review suggests that RTP in asymptomatic athletes after both ACDF and PF is safe, and there is little evidence for decreased performance postoperatively. Surgical management results in a higher RTP rate compared with athletes managed conservatively.
Improving the effectiveness of a paediatric handbook for new house officers
Authors: Wee Justin Liang Yi , Ting Chun Yi , Cheng Duo-Tong , Kan Sheau Yun , Kang Zhi Lin , Loo Benny Kai Guo 
Published: April 2021

Background and objectives: To help house officers adjust quickly to their new responsibilities, a departmental handbook is provided. As this had not been updated recently and was underutilised, a quality improvement project was undertaken to improve this resource. Methods: The handbook was updated and new material added based on feedback from house officers and senior medical staff. Subsequently, house officers were surveyed on their utilization rate of the new handbook and its usefulness in various clinical scenarios. An open-book clinical quiz was administered to gauge their clinical competency. Results: There was a 26.8% increase in the proportion of house officers who used the handbook more than once every 2–3 days compared to pre-intervention. There was a significant improvement in quiz scores from 26.7/40 to 31.1/40 between the pre-intervention ( n=19) and post-intervention ( n=37) groups ( p<0.001), as well as perceived usefulness of the handbook in various clinical scenarios as measured on a 10-point Likert scale. Conclusions: We find that improvement in the quality of a handbook for paediatric house officers is associated with increase in its utilization and benefits to their clinical competency and confidence level, especially on call. To increase the utilization rate of the handbook, both the user interface and content need to be improved.
A Quantifiable Risk Factor for ACL Injury: Applied Mathematics to Model the Posterolateral Tibial Plateau Surface Geometry
Authors: Tat Jimmy , Crapser Drew , Alaqeel Motaz , Schupbach Justin , Lee-Howes Jacob , Tamimi Iskandar , Burman Mark , Martineau Paul A. 
Published: April 2021

Background: The mechanism for traumatic ruptures of the native anterior cruciate ligament (ACL) is frequently a noncontact injury involving a valgus moment with internal rotation of the tibia. The abnormal rotation and translation of the lateral femoral condyle posteroinferiorly relative to the lateral tibial plateau is thought to be related to the geometry of the tibial plateau. Purpose/Hypothesis: The purpose of the study was to mathematically model the posterior tibial plateau geometry in patients with ACL injuries and compare it with that of matched controls. The hypothesis was that increased convexity and steepness of the posterior aspect of the lateral plateau would subject knees to higher forces, leading to a potentially higher risk of ACL injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We mathematically modeled the posterior curvature of the lateral tibial plateau in 64 patients with ACL injuries and 68 matched controls. Using sagittal magnetic resonance imaging scans of the knee, points on the articular cartilage of the posterolateral tibial plateau were selected and curve-fitted to a power function ( y = a × xn). For coefficient a and coefficient n, both variables modulated the shape of the curve, where a larger magnitude represented an increase in slope steepness. Groups were compared using a Mann-Whitney test and α < .05. Results: There was a significant difference in surface geometry between the patients with ACL injuries and matched controls. The equation coefficients were significantly larger in the patients with ACL injuries: coefficient a (ACL injury, 0.9 vs control, 0.68; P < .0001) and coefficient n (ACL injury, 0.34 vs control, 0.30; P = .07). For coefficient a, there was a 78.9% sensitivity, 77.5% specificity, and odds ratio of 12.6 (95% CI, 5.5-29.0) for ACL injury using a cutoff coefficient a = .78. Conclusion: Patients with ACL injuries had a significantly greater posterolateral plateau slope. The steeper drop off may play a role in higher anterior translation forces, coupled with internal rotation torques on the knee in noncontact injury, which could increase ACL strain and predispose to ACL injury.
Impact of obstructive sleep apnoea and intermittent hypoxia on blood rheology: a translational study
Authors: Waltz Xavier , Beaudin Andrew E. , Belaidi Elise , Raneri Jill , Pépin Jean-Louis , Pialoux Vincent , Hanly Patrick J. , Verges Samuel , Poulin Marc J. 
Published: April 2021

BackgroundHaemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterationsviaoxidative stress.MethodsWistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidantt-butyl hydroperoxide (TBHP).ResultsIn rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength.ConclusionsIH and OSAper sedo not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.
Association between the renin–angiotensin system and chronic lung allograft dysfunction
Authors: Berra Gregory , Farkona Sofia , Mohammed-Ali Zahraa , Kotlyar Max , Levy Liran , Clotet-Freixas Sergi , Ly Phillip , Renaud-Picard Benjamin , Zehong Guan , Daigneault Tina , Duong Allen , Batruch Ihor , Jurisica Igor , Konvalinka Ana , Martinu Tereza 
Published: April 2021

Chronic lung allograft dysfunction (CLAD) is the major cause of death after lung transplantation. Angiotensin II (AngII), the main effector of the renin–angiotensin system, elicits fibrosis in both kidney and lung. We identified six AngII-regulated proteins (Ras homolog family member B (RHOB), bone marrow stromal cell antigen 1 (BST1), lysophospholipase 1 (LYPA1), glutamine synthetase (GLNA), thrombospondin 1 (TSP1) and laminin subunit β2 (LAMB2)) that were increased in urine of patients with kidney allograft fibrosis. We hypothesised that the renin–angiotensin system is active in CLAD and that AngII-regulated proteins are increased in bronchoalveolar lavage fluid (BAL) of CLAD patients.We performed immunostaining of AngII receptors (AGTR1 and AGTR2), TSP1 and GLNA in 10 CLAD lungs and five controls. Using mass spectrometry, we quantified peptides corresponding to AngII-regulated proteins in BAL of 40 lung transplant recipients (stable, acute lung allograft dysfunction (ALAD) and CLAD). Machine learning algorithms were developed to predict CLAD based on BAL peptide concentrations.Immunostaining demonstrated significantly more AGTR1+cells in CLADversuscontrol lungs (p=0.02). TSP1 and GLNA immunostaining positively correlated with the degree of lung fibrosis (R2=0.42 and 0.57, respectively). In BAL, we noted a trend towards higher concentrations of AngII-regulated peptides in patients with CLAD at the time of bronchoscopy, and significantly higher concentrations of BST1, GLNA and RHOB peptides in patients that developed CLAD at follow-up (p<0.05). The support vector machine classifier discriminated CLAD from stable and ALAD patients at the time of bronchoscopy (area under the curve (AUC) 0.86) and accurately predicted subsequent CLAD development (AUC 0.97).Proteins involved in the renin–angiotensin system are increased in CLAD lungs and BAL. AngII-regulated peptides measured in BAL may accurately identify patients with CLAD and predict subsequent CLAD development.
The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories
Authors: Marcon Alessandro , Locatelli Francesca , Dharmage Shyamali C. , Svanes Cecilie , Heinrich Joachim , Leynaert Bénédicte , Burney Peter , Corsico Angelo , Caliskan Gulser , Calciano Lucia , Gislason Thorarinn , Janson Christer , Jarvis Deborah , Jõgi Rain , Lytras Theodore , Malinovschi Andrei , Probst-Hensch Nicole , Toren Kjell , Casas Lidia , Verlato Giuseppe , Garcia-Aymerich Judith , Accordini Simone 
Published: April 2021

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991–1993, 1999–2002 and 2010–2013. Disease status was classified in 2010–2013, when the subjects were aged 40–68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.