bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase
Authors: Ringel Jens , Ramlow Anja , Bock Christopher , Sheriff Ahmed 
Published: August 2021

BackgroundPlasma levels of C-reactive protein (CRP), induced by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) triggering COVID-19, can rise surprisingly high. The increase of the CRP concentration as well as a certain threshold concentration of CRP are indicative of clinical deterioration to artificial ventilation. In COVID-19, virus-induced lung injury and the subsequent massive onset of inflammation often drives pulmonary fibrosis. Fibrosis of the lung usually proceeds as sequela to a severe course of COVID-19 and its consequences only show months later. CRP-mediated complement- and macrophage activation is suspected to be the main driver of pulmonary fibrosis and subsequent organ failure in COVID-19. Recently, CRP apheresis was introduced to selectively remove CRP from human blood plasma.Case ReportA 53-year-old, SARS-CoV-2 positive, male patient with the risk factor diabetes type 2 was referred with dyspnea, fever and fulminant increase of CRP. The patient’s lungs already showed a pattern enhancement as an early sign of incipient pneumonia. The oxygen saturation of the blood was ≤ 89%. CRP apheresis using the selective CRP adsorber (PentraSorb® CRP) was started immediately. CRP apheresis was performed via peripheral venous access on 4 successive days. CRP concentrations before CRP apheresis ranged from 47 to 133 mg/l. The removal of CRP was very effective with up to 79% depletion within one apheresis session and 1.2 to 2.14 plasma volumes were processed in each session. No apheresis-associated side effects were observed. It was at no point necessary to transfer the patient to the Intensive Care Unit or to intubate him due to respiratory failure. 10 days after the first positive SARS-CoV-2 test, CRP levels stayed below 20 mg/l and the patient no longer exhibited fever. Fourteen days after the first positive SARS-CoV-2 test, the lungs showed no sign of pneumonia on X-ray.ConclusionThis is the first report on CRP apheresis in an early COVID-19 patient with fulminant CRP increase. Despite a poor prognosis due to his diabetes and biomarker profile, the patient was not ventilated, and the onset of pneumonia was reverted.
The Optimal Second-Line Systemic Treatment Model for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: A Bayesian Network Meta-Analysis
Authors: Zhan Ze-Jiang , Yao Wen-Yu , Zhang Fang , Qiu Wen-Ze , Liao Kai- , Feng Jian-Hui , Tan Jin-Yun , Liu Hui , Yuan Tai-Ze , Zheng Rong-Hui , Yuan Ya-Wei 
Published: August 2021

BackgroundThe optimal second-line systemic treatment model for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains controversial. A Bayesian network meta-analysis (NMA) was performed to address this issue with regard to efficacy and toxicity.MethodsBy searching MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science, we extracted eligible studies. Efficacy, represented as overall survival (OS) and progression-free survival (PFS), and overall toxicity, represented as ≥ grade 3 severe acute events (sAE), were assessed to compare the following 7 treatment models through an NMA: standard-of-care therapy (SoC), single targeted therapy different from SoC (ST), double targeted therapy (DT), targeted therapy combined with chemotherapy (T+C), single immune checkpoint inhibitor therapy (SI), double immune checkpoint inhibitor therapy (DI) and single chemotherapy different from SoC (SC). Rank probabilities according to the values of the surface under the cumulative ranking curve (SUCRA) were separately determined for efficacy and toxicity.ResultsIn total, 5285 patients from 24 eligible studies were ultimately screened, with 5184, 4532 and 4026 involved in the NMA of OS, PFS and sAE, respectively. All qualifying studies were absent from first-line immune checkpoint inhibitor therapy. In terms of OS, SI was superior to the other treatments, followed by DI, ST, T+C, SoC, DT and SC. Other than SI and SC, all treatments tended to be consistent, with hazard ratios (HRs) close to 1 between groups. For PFS, ST ranked first, while DT ranked last. For the toxicity profiles, compared with the other models, SI resulted in the lowest incidences of sAE, with statistical significance over SoC (odds ratio [OR] 0.31, 95% credible interval [CrI] 0.11 to 0.90), ST (OR 0.23, 95% CrI 0.06 to 0.86) and DT (OR 0.11, 95% CrI 0.02 to 0.53), while DT was the worst. When the SUCRA values of OS and sAE were combined, a cluster plot illustrated the superiority of SI, which demonstrated the best OS and tolerability toward sAE.ConclusionFor R/M HNSCC patients without immune checkpoint inhibitors in the first-line setting, SI may serve as the optimal second-line systemic treatment model, demonstrating the best OS and least sAE.
Developing Machine Learning Algorithms to Predict Pulmonary Complications After Emergency Gastrointestinal Surgery
Authors: Xue Qiong , Wen Duan , Ji Mu-Huo , Tong Jianhua , Yang Jian-Jun , Zhou Cheng-Mao 
Published: August 2021

Objective: Investigate whether machine learning can predict pulmonary complications (PPCs) after emergency gastrointestinal surgery in patients with acute diffuse peritonitis.Methods: This is a secondary data analysis study. We use five machine learning algorithms (Logistic regression, DecisionTree, GradientBoosting, Xgbc, and gbm) to predict postoperative pulmonary complications.Results: Nine hundred and twenty-six cases were included in this study; 187 cases (20.19%) had PPCs. The five most important variables for the postoperative weight were preoperative albumin, cholesterol on the 3rd day after surgery, albumin on the day of surgery, platelet count on the 1st day after surgery and cholesterol count on the 1st day after surgery for pulmonary complications. In the test group: the logistic regression model shows AUC = 0.808, accuracy = 0.824 and precision = 0.621; Decision tree shows AUC = 0.702, accuracy = 0.795 and precision = 0.486; The GradientBoosting model shows AUC = 0.788, accuracy = 0.827 and precision = 1.000; The Xgbc model shows AUC = 0.784, accuracy = 0.806 and precision = 0.583. The Gbm model shows AUC = 0.814, accuracy = 0.806 and precision = 0.750.Conclusion: Machine learning algorithms can predict patients' PPCs with acute diffuse peritonitis. Moreover, the results of the importance matrix for the Gbdt algorithm model show that albumin, cholesterol, age, and platelets are the main variables that account for the highest pulmonary complication weights.
Patient Preferences for Lung Cancer Treatments: A Study Protocol for a Preference Survey Using Discrete Choice Experiment and Swing Weighting
Authors: Monzani Dario , Petrocchi Serena , Oliveri Serena , Veldwijk Jorien , Janssens Rosanne , Bailo Luca , Smith Meredith Y. , Smith Ian , Schoefs Elise , Nackaerts Kristiaan , Vandevelde Marie , Louis Evelyne , Decaluwé Herbert , De Leyn Paul , Declerck Hanne , Katz Eva G. , Petrella Francesco , Casiraghi Monica , Durosini Ilaria , Galli Giulia , Garassino Marina Chiara , de Wit G. Ardine , Pravettoni Gabriella , Huys Isabelle 
Published: August 2021

Background: Advanced treatment options for non-small cell lung cancer (NSCLC) consist of immunotherapy, chemotherapy, or a combination of both. Decisions surrounding NSCLC can be considered as preference-sensitive because multiple treatments exist that vary in terms of mode of administration, treatment schedules, and benefit–risk profiles. As part of the IMI PREFER project, we developed a protocol for an online preference survey for NSCLC patients exploring differences in preferences according to patient characteristics (preference heterogeneity). Moreover, this study will evaluate and compare the use of two different preference elicitation methods, the discrete choice experiment (DCE) and the swing weighting (SW) task. Finally, the study explores how demographic (i.e., age, gender, and educational level) and clinical (i.e., cancer stage and line of treatment) information, health literacy, health locus of control, and quality of life may influence or explain patient preferences and the usefulness of a digital interactive tool in providing information on preference elicitation tasks according to patients.Methods: An online survey will be implemented with the aim to recruit 510 NSCLC patients in Belgium and Italy. Participants will be randomized 50:50 to first receive either the DCE or the SW. The survey will also collect information on participants' disease-related status, health locus of control, health literacy, quality of life, and perception of the educational tool.Discussion: This protocol outlines methodological and practical steps to quantitatively elicit and study patient preferences for NSCLC treatment alternatives. Results from this study will increase the understanding of which treatment aspects are most valued by NSCLC patients to inform decision-making in drug development, regulatory approval, and reimbursement. Methodologically, the comparison between the DCE and the SW task will be valuable to gain information on how these preference methods perform against each other in eliciting patient preferences. Overall, this protocol may assist researchers, drug developers, and decision-makers in designing quantitative patient preferences into decision-making along the medical product life cycle.
Neural Conduction Along Postretinal Visual Pathways in Glaucoma
Authors: Parisi Vincenzo , Ziccardi Lucia , Tanga Lucia , Roberti Gloria , Barbano Lucilla , Carnevale Carmela , Manni Gianluca , Oddone Francesco 
Published: August 2021

Purpose: This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes.Methods: Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24–2 Humphrey mean deviation (MD) between −2.5 and −20 dB and IOP &lt;21 mmHg on pharmacological treatment (OAG group) and 20 age-matched controls (control group) were enrolled. In both groups, simultaneous pattern electroretinograms (PERG) and visual evoked potentials (VEP), in response to checks stimulating macular or extramacular areas (the check edge subtended 15′ and 60′ of visual arc, respectively), and RNFL-T (measured in superior, inferior, nasal, and temporal quadrants) were assessed.Results: In the OAG group, a significant (ANOVA, p &lt; 0.01) reduction of 60′ and 15′ PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60′ and 15′ PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly (p &lt; 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson’s test, p &lt; 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation (p &lt; 0.01) with RNFL-T (overall or temporal) values was detected.Conclusions: In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60′ and 15′ RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction.
White Matter Integrity Underlies the Physical-Cognitive Correlations in Subjective Cognitive Decline
Authors: Wei Yi-Chia , Hsu Chih-Chin Heather , Huang Wen-Yi , Chen Yao-Liang , Lin Chemin , Chen Chih-Ken , Lin Chen , Shyu Yu-Chiau , Lin Ching-Po 
Published: August 2021

Objective: Although previous studies postulated that physical and cognitive decline codeveloped in preclinical dementia, the interconnected relationship among subjective cognitive complaints (SCCs), objective cognitive performance, and physical activity remained hazy. We investigated the mediating roles of physical activity between subjective and objective cognition. Diffusion tensor imaging (DTI) was utilized to test our hypothesis that brain white matter microstructural changes underlie the physical-cognitive decline in subjective cognitive decline (SCD).Methods: We enrolled cognitively normal older adults aged &gt; 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital during 2017–2020. Regression models analyzed mediation effects of physical activity between subjective and objective cognition. The self-reported AD8 questionnaire assessed SCCs. The SCD group, defined by AD8 score ≥ 2, further underwent diffusion MRI scans. Those who agreed to record actigraphy also wore the SOMNOwatch™ for 72 h. Spearman's correlation coefficients evaluated the associations of diffusion indices with physical activity and cognitive performance.Results: In 95 cognitively normal older adults, the AD8 score and the Montreal Cognitive Assessment (MoCA) score were mediated partially by the metabolic equivalent of the International Physical Activity Questionnaire-Short Form (IPAQ-SF MET) and fully by the sarcopenia score SARC-F. That is, the relation between SCCs and poorer cognitive performance was mediated by physical inactivity. The DTI analysis of 31 SCD participants found that the MoCA score correlated with mean diffusivity at bilateral inferior cerebellar peduncles and the pyramids segment of right corticospinal tract [p &lt; 0.05, false discovery rate (FDR) corrected]. The IPAQ-SF MET was associated with fractional anisotropy (FA) at the right posterior corona radiata (PCR) (p &lt; 0.05, FDR corrected). In 15 SCD participants who completed actigraphy recording, the patterns of physical activity in terms of intradaily variability and interdaily stability highly correlated with FA of bilateral PCR and left superior corona radiata (p &lt; 0.05, FDR corrected).Conclusions: This study addressed the role of physical activity in preclinical dementia. Physical inactivity mediated the relation between higher SCCs and poorer cognitive performance. The degeneration of specific white matter tracts underlay the co-development process of physical-cognitive decline in SCD.
Stroke Care During the First and the Second Waves of the COVID-19 Pandemic in a Community Hospital
Authors: Sobolewski Piotr , Szczuchniak Wiktor , Grzesiak-Witek Danuta , Wilczyński Jacek , Paciura Karol , Antecki Mateusz , Frańczak-Prochowski Tadeusz , Kos Marek , Kozera Grzegorz 
Published: August 2021

Objective: The coronavirus disease 2019 (COVID-19) infection may alter a stroke course; thus, we compared stroke course during subsequent pandemic waves in a stroke unit (SU) from a hospital located in a rural area.Methods: A retrospective study included all patients consecutively admitted to the SU between March 15 and May 31, 2020 (“first wave”), and between September 15 and November 30, 2020 (“second wave”). We compared demographic and clinical data, treatments, and outcomes of patients between the first and the second waves of the pandemic and between subjects with and without COVID-19.Results: During the “first wave,” 1.4% of 71 patients were hospitalized due to stroke/TIA, and 41.8% of 91 during the “second wave” were infected with SARS-CoV-2 (p &lt; 0.001). During the “second wave,” more SU staff members were infected with COVID-19 than during the “first wave” (45.6 vs. 8.7%, p &lt; 0.001). Nevertheless, more patients underwent intravenous thrombolysis (26.4 vs. 9.9%, p &lt; 0.008) and endovascular thrombectomy (5.3 vs. 0.0%, p &lt; 0.001) during the second than the first wave. Large vessel occlusion (LVO) (OR 8.74; 95% CI 1.60–47.82; p = 0.012) and higher 30-day mortality (OR 6.01; 95% CI 1.04–34.78; p = 0.045) were associated with patients infected with COVID-19. No differences regarding proportions between ischemic and hemorrhagic strokes and TIAs between both waves or subgroups with and without COVID-19 existed.Conclusion: Despite the greater COVID-19 infection rate among both SU patients and staff during the “second wave” of the pandemic, a higher percentage of reperfusion procedures has been performed then. COVID-19 infection was associated with a higher rate of the LVO and 30-day mortality.
Serum Metabolites Differentiate Amnestic Mild Cognitive Impairment From Healthy Controls and Predict Early Alzheimer's Disease via Untargeted Lipidomics Analysis
Authors: Zhang Lumi , Li Lingxiao , Meng Fanxia , Yu Jie , He Fangping , Lin Yajie , Su Yujie , Hu Mengjie , Liu Xiaoyan , Liu Yang , Luo Benyan , Peng Guoping 
Published: August 2021

Background and Aim:Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD.Methods:We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC.Results:There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups.Conclusion:This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.
Radiomics-Based Texture Analysis of 68Ga-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With 177Lu-DOTATATE
Authors: Atkinson Charlotte , Ganeshan Balaji , Endozo Raymond , Wan Simon , Aldridge Matthew D. , Groves Ashley M. , Bomanji Jamshed B. , Gaze Mark N. 
Published: August 2021

PurposeNeuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value.MethodsThe pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis.ResultsMeasures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22–5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19–68.91, p=0.033) independently predicted OS.ConclusionThese preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients.
Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis
Authors: Hanafin Patrick O. , Sermet-Gaudelus Isabelle , Griese Matthias , Kappler Matthias , Ellemunter Helmut , Schwarz Carsten , Wilson John , Tan Marsha , Velkov Tony , Rao Gauri G. , Schneider-Futschik Elena K. 
Published: August 2021

Background: The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolutionised the treatment of cystic fibrosis (CF). However, due to the plethora of variances in disease manifestations in CF, there are inherent challenges in unified responses under CFTR modulator treatment arising from variability in patient outcomes. The pharmacokinetic (PK) data available for ivacaftor-lumacaftor cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drug combination is limited.Methods: Secondary objectives were to identify (1) patient characteristics and (2) the interactions between ivacaftor-lumacaftor responsible for interindividual variability (IIV).Results: Peak plasma concentrations (Cmax) of ivacaftor - lumacaftor were &gt;10 fold lower than expected compared to label information. The one-way ANOVA indicated that the patient site had an effect on Cmax values of ivacaftor metabolites ivacaftor-M1, ivacaftor-M6, and lumacaftor (p &lt; 0.001, p &lt; 0.001, and p &lt; 0.001, respectively). The Spearman’s rho test indicated that patient weight and age have an effect on the Cmax of lumacaftor (p = 0.003 and p &lt; 0.001, respectively) and ivacaftor metabolite M1 (p = 0.020 and p &lt; 0.001, respectively). Age (p &lt; 0.001) was found to effect on Cmax of ivacaftor M6 and on Tmax of ivacaftor M1 (p = 0.026). A large impact of patient characteristics on the IIV of PK parameters Cmax and Tmax, was observed among the CF patients.Conclusion: Understanding the many sources of variability can help reduce this individual patient variability and ensure consistent patient outcomes.