bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dependency in Activities of Daily Living During the First Year After Stroke
Authors: E. Wurzinger Hannah , Abzhandadze Tamar , Rafsten Lena , Sunnerhagen Katharina S. 
Published: November 2021

Background: Dependency in personal activities of daily living (ADL) is a common short-term and long-term consequence of stroke and requires targeted rehabilitation. As the duration of hospital stay has become shorter in recent decades, early identification of patients who require rehabilitation has become vital. To our knowledge, no study has investigated whether ADL dependency in the very early stages after admission to the stroke unit can explain ADL dependency 3 and 12 months later. This knowledge would facilitate planning for very early discharge and patient-centered rehabilitation.Objective: This study evaluated whether ADL dependency within 2 days after stroke could explain ADL dependency at 3 and 12 months after stroke.Methods: This longitudinal cohort study included patients with stroke who were treated at a stroke unit in the Sahlgrenska University Hospital (Gothenburg, Sweden) between May 2011 and March 2016. The primary independent variable was ADL dependency at 36–48 h after admission to the stroke unit, which was assessed using a Barthel Index (BI) score of ≤90. The dependent variables were self-reported personal ADL dependency at 3 and 12 months after stroke. Binary logistic regression analyses were performed.Results: Of 366 eligible patients (58% male; median age 71 years), a majority (76%) had mild stroke and 60% were ADL dependent 36–48 h after stroke. Univariable and multivariable logistic regression analyses showed that patients who were dependent within the first 2 days after stroke had higher odds for being dependent 3 months as well as 12 months after stroke.Conclusion: The results indicated that dependency in personal ADL during the first 2 days can explain dependency at 3- and 12-month post-stroke. Therefore, early ADL assessments post-stroke can be used for understanding rehabilitation needs after stroke.
Reduced Programming Time and Strong Symptom Control Even in Chronic Course Through Imaging-Based DBS Programming
Authors: Lange Florian , Steigerwald Frank , Malzacher Tobias , Brandt Gregor Alexander , Odorfer Thorsten Michael , Roothans Jonas , Reich Martin M. , Fricke Patrick , Volkmann Jens , Matthies Cordula , Capetian Philipp D. 
Published: November 2021

Objectives: Deep brain stimulation (DBS) programming is based on clinical response testing. Our clinical pilot trial assessed the feasibility of image-guided programing using software depicting the lead location in a patient-specific anatomical model.Methods: Parkinson's disease patients with subthalamic nucleus-DBS were randomly assigned to standard clinical-based programming (CBP) or anatomical-based (imaging-guided) programming (ABP) in an 8-week crossover trial. Programming characteristics and clinical outcomes were evaluated.Results: In 10 patients, both programs led to similar motor symptom control (MDS-UPDRS III) after 4 weeks (medicationOFF/stimulationON; CPB: 18.27 ± 9.23; ABP: 18.37 ± 6.66). Stimulation settings were not significantly different, apart from higher frequency in the baseline program than CBP (p = 0.01) or ABP (p = 0.003). Time spent in a program was not significantly different (CBP: 86.1 ± 29.82%, ABP: 88.6 ± 29.0%). Programing time was significantly shorter (p = 0.039) with ABP (19.78 ± 5.86 min) than CBP (45.22 ± 18.32).Conclusion: Image-guided DBS programming in PD patients drastically reduces programming time without compromising symptom control and patient satisfaction in this small feasibility trial.
Case Report: Dual Target Deep Brain Stimulation With Externalized Programming for Post-traumatic Complex Movement Disorder
Authors: Gadot Ron , Shofty Ben , Najera Ricardo A. , Anand Adrish , Banks Garrett , Khan Abdul Basit , LoPresti Melissa A. , Vanegas Arroyave Nora , Sheth Sameer A. 
Published: November 2021

Introduction: Movement disorders can be common, persistent, and debilitating sequelae of severe traumatic brain injury. Post-traumatic movement disorders are usually complex in nature, involving multiple phenomenological manifestations, and can be difficult to control with medical management alone. Deep brain stimulation (DBS) has been used to treat these challenging cases, but distorted brain anatomy secondary to trauma can complicate effective targeting. In such cases, use of diffusion tractography imaging and inpatient testing with externalized DBS leads can be beneficial in optimizing outcomes.Case Description: We present the case of a 42-year-old man with severe, disabling post-traumatic tremor who underwent bilateral, dual target DBS to the globus pallidus internus (GPi) and a combined ventral intermediate nucleus of the thalamus (Vim)/dentato-rubro-thalamic tracts (DRTT) target. DRTT fiber tracts were reconstructed preoperatively to assist in surgical targeting given the patient’s distorted anatomy. Externalization and survey of the four leads extra-operatively with inpatient testing allowed for internalization of the leads that demonstrated benefit. Six months after surgery, the patient’s tremor and dystonic burden had decreased by 67% in the performance sub-score of The Essential Tremor Rating Scale (TETRAS).Conclusion: A patient-tailored approach including target selection guided by individualized anatomy and tractography as well as extra-operative externalized lead interrogation was shown to be effective in optimizing clinical outcome in a patient with refractory post-traumatic tremor.
The Effects of L-Carnitine, Acetyl-L-Carnitine, and Propionyl-L-Carnitine on Body Mass in Type 2 Diabetes Mellitus Patients
Authors: Wang Dong-Dong , Wang Tian-Yun , Yang Yang , He Su-Mei , Wang You-Mei 
Published: November 2021

Purpose: The study aimed to explore the effects of l-carnitine, acetyl-l-carnitine, and propionyl-l-carnitine on Body Mass in type 2 diabetes mellitus (T2DM) patients.Methods: Randomized controlled trial (RCT) studies of l-carnitine, acetyl-l-carnitine, and propionyl-l-carnitine in T2DM patients were searched. The change rates of Body Mass index (BMI) from baseline values were used as an evaluation indicator. The maximal effect (Emax) model by non-linear mixed-effect modeling (NONMEM) was used as the evaluation method.Results: A total of 10 RCT studies, 1239 T2DM patients were included for analysis, including eight studies of l-carnitine, one study of acetyl-l-carnitine, and one study of propionyl-l-carnitine. The study found that l-carnitine could reduce the Body Mass of T2DM patients. Based on only one study each for acetyl-l-carnitine and propionyl-l-carnitine, no significant effects were found in acetyl-l-carnitine or propionyl-l-carnitine. In addition, in order to achieve a plateau of efficacy (80% Emax), 2 g/day l-carnitine was required for at least 2 weeks.Conclusions: Two g/day l-carnitine was required for at least 2 weeks to affect Body Mass in T2DM patients, and no significant effects were found in acetyl-l-carnitine or propionyl-l-carnitine.
Efficacy and Safety of First-Line Treatment Strategies for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis
Authors: Peng Ling , Lu Dafeng , Xia Yang , Hong Shaodong , Selvaggi Giovanni , Stebbing Justin , Sun Yilan , Liang Fei 
Published: November 2021

BackgroundTargeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance.MethodsPubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration’s tool.ResultsNine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs.ConclusionsLorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly.
Risk Factor and Surgical Outcome of Petersen’s Hernia After Gastrectomy in Gastric Cancer
Authors: Liu Song , Hu Qiongyuan , Song Peng , Tao Liang , Ai Shichao , Miao Ji , Wang Feng , Kang Xing , Shen Xiaofei , Sun Feng , Xia Xuefeng , Wang Meng , Lu Xiaofeng , Guan Wenxian 
Published: November 2021

BackgroundPetersen’s hernia is a life-threatening complication after gastrectomy. This study is dedicated to identify risk factors for Petersen’s hernia and compare clinical outcomes between patients receiving early or delayed surgical interventions.MethodsData from all patients who received gastrectomy due to gastric cancer were collected. Clinical characteristics were compared between Petersen and non-Petersen groups, bowel necrosis and non-necrotic groups. Propensity score matching (PSM) was conducted to generate two comparative groups. Univariate analysis and multivariate logistic regression were performed for risk factor evaluation.ResultsA total of 24 cases of Petersen’s hernia were identified from 1,481 cases of gastrectomy. PSM demonstrated that lower body mass index [BMI; odds ratio (OR) = 0.2, p &lt; 0.01] and distal gastrectomy (OR = 6.2, p = 0.011) were risk factors for Petersen’s hernia. Longer time interval from emergence visit to laparotomy (p = 0.042) and elevated preoperative procalcitonin (p = 0.033) and C-reactive protein (CRP; p = 0.012) were associated with higher risk of bowel necrosis in Petersen’s hernia. Early surgical intervention resulted in less bowel necrosis rate (p = 0.012) and shorter length of necrotic bowel (p = 0.0041).ConclusionsLow BMI and distal gastrectomy are independent risk factor for Petersen’s hernia after gastrectomy. Curtailing observing time and executing prompt surgery are associated with bowel viability and better outcome in patients with Petersen’s hernia.
Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study
Authors: Ogiwara Toshiki , Kawazoe Hitoshi , Egami Saeka , Hashimoto Hironobu , Saito Yoshimasa , Sakiyama Naomi , Ohe Yuichiro , Yamaguchi Masakazu , Furukawa Tetsuya , Hara Azusa , Hiraga Yui , Jibiki Aya , Yokoyama Yuta , Suzuki Sayo , Nakamura Tomonori 
Published: November 2021

BackgroundNivolumab and pembrolizumab are the standard treatments for patients with advanced non-small-cell lung cancer (NSCLC). While there are reports on several inflammatory indices and the prognosis of patients with cancer, no study has combined baseline medication with the neutrophil-to-lymphocyte ratio (NLR) to predict clinical outcomes. This study investigated the efficacy of baseline medications plus NLR to predict the effectiveness of nivolumab and pembrolizumab in a real-world clinical setting.MethodsWe conducted a single-center retrospective observational study of consecutive patients with advanced NSCLC who received nivolumab or pembrolizumab as first-line, second-line, or beyond treatment between December 2015 and November 2018 at the National Cancer Center Hospital in Japan. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The drug-based prognostic score for baseline medications plus NLR was weighed based on the regression β coefficients. The multivariable Cox proportional hazard model was used to assess the association between the prognostic score-stratified groups and survival outcomes.ResultsIn total, 259 patients were evaluated in this study. A prognostic score calculated from the baseline medications plus NLR was used to categorize the patients into good (score 0), intermediate (scores 1–2), and poor (scores 3–6) -prognosis groups. The multivariable Cox proportional hazard model revealed a significant association between the poor-prognosis group and reduced OS. The hazard ratio of OS was 1.75 (95% confidence interval: 1.07–2.99; P = 0.031). In contrast, no association between these prognosis groups and PFS was observed.ConclusionsThe findings suggest that the baseline medications with nivolumab or pembrolizumab plus NLR could lead to progressively shorter survival outcomes in patients with advanced NSCLC and could be used as a prognostic index for poor outcomes. However, to ascertain the clinical application of these findings, these concomitant medications need further validation in a large-scale multicenter study.
Characteristics of the Gut Microbiome and IL-13/TGF-β1 Mediated Fibrosis in Post-Kasai Cholangitis of Biliary Atresia
Authors: Meng Lingdu , Liu Jia , Wang Junfeng , Du Min , Zhang Shouhua , Huang Yanlei , Shen Zhen , Dong Rui , Chen Gong , Zheng Shan 
Published: November 2021

Aims:Cholangitis in biliary atresia (BA), which accelerates liver fibrosis progression, is among the most common serious complications after Kasai surgery; however, its etiology remains elusive. Gut microbiome migration may contribute to post-Kasai cholangitis. Further, there is no appropriate model of BA post-Kasai cholangitis for use in investigation of its pathogenesis.Methods:We explored the characteristics of gut microbiome in patients with BA before and after Kasai procedure based on 16S rDNA sequencing. We isolated the dominant strain from patient stool samples and established anin vitromodel by infecting patient-derived liver organoids. Bulk RNA-seq was performed, and we conducted qPCR, ELISA, and western blot to explore the mechanism of fibrosis.Results:Gut microbiome diversity was lower in patients after, relative to before, Kasai procedure, while the relative abundance ofKlebsiellawas higher. Patients who developed cholangitis within 1 month after discharge tended to have simpler gut microbiome composition, dominated byKlebsiella.Klebsiella pneumoniae(KPN) was isolated and used for modeling. RNA-seq showed that BA liver organoids expressed markers of hepatic progenitor cells (KRT19, KRT7, EPCAM, etc.) and that organoids were more stable and less heterogeneous among individuals than liver tissues. After infection with KPN, gene expression patterns in BA liver organoids were enriched in pathways related to infection, apoptosis, and fibrosis. Preliminary experiments indicated the presence of IL-13/TGF-β1-mediated fibrosis in post-Kasai cholangitis.Conclusions:Our findings using a newly-developed model, demonstrate a key role forKlebsiella, and a potential mechanism underlying fibrosis in post-Kasai cholangitis, mediated by the IL-13/TGF-β1 pathway.
Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
Authors: Feng Burong , Zhao Xiuye , Zhao Wei , Jiang Huiwei , Ren Zijing , Chen Yingfu , Yuan Ye , Du Zhimin 
Published: November 2021

Aloe-emodin widely possesses antibacterial, anti-inflammatory, antioxidant, antiviral, and anti-infectious properties. This study investigated the effect of ethyl 2-succinate-anthraquinone (Luhui derivative, LHD) on inflammation. In vitro, a THP-1 macrophage inflammation model, made by 100 ng/ml phorbol-12-myristate-13-acetate (PMA) and 1 μg/ml LPS for 24 h, was constructed. The LHD group (6.25 μmol/L, 12.5 μmol/L, 25 μmol/L, 50 μmol/L) had no effect on THP-1 cell activity, and the expression of IL-6 mRNA was down-regulated in a concentration-dependent manner, of which the 25 μmol/L group had the best inhibitory effect. The migration of THP-1 macrophages induced by LPS was decreased by the LHD. Moreover, the LHD suppressed ROS fluorescence expression by inhibiting MDA expression and increasing SOD activity. In vivo, we revealed that the LHD, in different doses (6.25 mg/kg, 12.5 mg/kg, 25 mg/kg, 50 mg/kg), has a protective effect on stress physiological responses by assessing the body temperature of mice. Interestingly, acute lung injury (e.g., the structure of the alveoli disappeared and capillaries in the alveolar wall were dilated and congested) and liver damage (e.g., hepatocyte swelling, neutrophil infiltration, and hepatocyte apoptosis) were obviously improved at the same condition. Furthermore, we initially confirmed that the LHD can down-regulate the expression of NLRP3, IL-1β, and caspase-1 proteins, thereby mediating the NLRP3 inflammasome signaling pathway to produce anti-inflammatory effects. In conclusion, our results indicate that the LHD exerts anti-inflammatory activity via regulating the NLRP3 signaling pathway, inhibition of oxidative stress, and THP-1 macrophage migration.
Clinical Effects of Korean Red Ginseng in Postmenopausal Women With Hand Osteoarthritis: A Double-Blind, Randomized Controlled Trial
Authors: Kim Hye In , Chon Seung Joo , Seon Ki Eun , Seo Seok Kyo , Choi Yun-Rak 
Published: November 2021

Background: Although many menopausal Asian women use herbal remedies for joint pain, there are no studies evaluating the efficacy of Korean red ginseng on osteoarthritis symptoms in postmenopausal women. The purpose of this study is to analyze antioxidant enzyme activity, oxidative stress markers, and pain scores before and after red ginseng consumption, to assess its effect in postmenopausal women. Methods. This prospective, double-blind, randomized controlled trial enrolled 52 postmenopausal women who presented with hand edema and/or pain and were diagnosed as degenerative arthritis of the hand. Patients were randomly assigned to the red ginseng (RG) group (supplemented with 3 g/d of RG for 12 weeks) or the placebo group. Changes in pain and Disability of the Arm, Shoulder, and Hand (DASH) scores, antioxidant enzyme, oxidative stress markers, serum estradiol levels, and endometrial thickness were analyzed. Results. The pain score and DASH score were significantly improved in the RG group (both p &lt; 0.05). The improvement of pain score at rest, during work or sport, and DASH score was significant compared to that of the placebo group. The superoxide dismutase level increased (p &lt; 0.05) and the malondialdehyde level decreased (p &lt; 0.05) significantly in the RG group, while none of the antioxidative factors showed a significant change in the placebo group. Serum estradiol levels and endometrial thickness were not affected by RG supplementation. Conclusion. RG may be an effective dietary supplement for postmenopausal women with degenerative osteoarthritis of the hand. It may relieve pain and improve antioxidative activity without the risk of endometrial thickening.
A Comparative Analysis of Pricing and Reimbursement of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Europe
Authors: Abdallah Khadidja , De Boeck Kris , Dooms Marc , Simoens Steven 
Published: November 2021

Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor), have substantially improved patients’ lives yet significantly burden healthcare budgets. This analysis aims to compare pricing and reimbursement of aforementioned cystic fibrosis medicines, across European countries.Methods: Clinical trial registries, national databases, health technology assessment reports and grey literature of Austria, Belgium, Denmark, France, Germany, Ireland, Poland, Spain, Sweden, Switzerland, Netherlands, the United Kingdom were consulted. Publicly available prices, reimbursement statuses, economic evaluations, budget impact analyses and managed entry agreements of CFTR modulators were examined. Results: In Belgium, lowest list prices were observed for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €417 per defined daily dose (DDD) and €372 per average daily dose (ADD), respectively. Whereas, Switzerland had the lowest price for Orkambi® (lumacaftor/ivacaftor) listed at €309 per DDD. Spain had the highest prices for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €850 per DDD and €761 per ADD, whereas Orkambi® (lumacaftor/ivacaftor) was most expensive in Poland at €983 per DDD. However, list prices were subject to confidential discounts and likely varied from actual costs. In all countries, these treatments were deemed not to be cost-effective. The annual budget impact of the CFTR modulators varied between countries and depended on factors such as local product prices, size of target population, scope of costs and discounting. However, all modulators were fully reimbursed in ten of the evaluated countries except for Sweden and Poland that, respectively, granted reimbursement to one and none of the therapies. Managed entry agreements were confidential but commonly adopted to address financial uncertainties.Conclusion: Discrepancies concerning prices, reimbursement and access were detected for Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor) across European countries.