bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous IL-6 Inhibitor Sarilumab vs. Standard Care in Hospitalized Patients With Moderate-To-Severe COVID-19: An Open Label Randomized Clinical Trial
Authors: García-Vicuña Rosario , Rodriguez-García Sebastián C. , Abad-Santos Francisco , Bautista Hernández Azucena , García-Fraile Lucio , Barrios Blandino Ana , Gutiérrez Liarte Angela , Alonso-Pérez Tamara , Cardeñoso Laura , Alfranca Aránzazu , Mejía-Abril Gina , Sanz Sanz Jesús , González-Alvaro Isidoro 
Published: February 2022

BackgroundThe use of IL-6 blockers in COVID-19 hospitalized patients has been associated with a reduction in mortality compared to standard care. However, many uncertainties remain pertaining to optimal intervention time, administration schedule, and predictors of response. To date, data on the use of subcutaneous sarilumab is limited and no randomized trial results are available.MethodsOpen label randomized controlled trial at a single center in Spain. We included adult patients admitted with microbiology documented COVID-19 infection, imaging confirmed pneumonia, fever and/or laboratory evidence of inflammatory phenotype, and no need for invasive ventilation. Participants were randomly assigned to receive sarilumab, a single 400 mg dose in two 200 mg subcutaneous injections, added to standard care or standard care, in a 2:1 proportion. Primary endpoints included 30-day mortality, mean change in clinical status at day 7 scored in a 7-category ordinal scale ranging from death (category 1) to discharge (category 7), and duration of hospitalization. The primary efficacy analysis was conducted on the intention-to-treat population.ResultsA total of 30 patients underwent randomization: 20 to sarilumab and 10 to standard care. Most patients were male (20/30, 67%) with a median (interquartile range) age of 61.5 years (56–72). At day 30, 2/20 (10%) patients died in the sarilumab arm vs. none (0/10) in standard care (Log HR 15.11, SE 22.64; p = 0.54). At day 7, no significant differences were observed in the median change in clinical status (2 [0–3]) vs. 3 [0–3], p = 0.32). Median time to discharge (days) was similar (7 [6–11] vs. 6 [4–12]; HR 0.65, SE 0.26; p = 0.27). No significant differences were detected in the rate of progression to invasive and noninvasive mechanical ventilation.Conclusions and RelevanceOur pragmatic pilot study has failed to demonstrate the benefit of adding subcutaneous sarilumab to standard care for mortality by 30 days, functional status at day 7, or hospital stay. Findings herein do not exclude a potential effect of sarilumab in severe COVID-19 but adequately powered blinded randomized phase III trials are warranted to assess the impact of the subcutaneous route and a more selected target population.Trial Registrationwww.ClinicalTrials.gov, Identifier: NCT04357808.
Role of Intensified Lung Physiotherapy Bundle on the Occurrence of Pneumonia After Cardiac Surgery
Authors: Cheng Wei , Chen Jianwei , Sun Jianhua , Zhang Jiahui , Li Dongkai , Wang Hao , Li Zunzhu , Cui Na 
Published: February 2022

ObjectiveThe role of intensified lung physiotherapy bundle after cardiac surgery was investigated.MethodsA before- and after-surgery comparison was conducted between the study from January 1, 2018 to December 31, 2019 (control group), when traditional lung physiotherapy bundle was used, and from January 1, 2020 to May 1, 2021 (study group), when the intensified bundle was used. The baseline data, clinical features, incidence of postoperative pneumonia, and prognoses of all the enrolled cardiac surgery patients were analyzed.ResultsIn accordance with the study criteria, 358 patients were enrolled. The incidence rate of postoperative pneumonia was significantly lower in the study group than in the control group (14.2 vs. 22.7%, P = 0.037), as was in-hospital mortality (1.5 vs. 5.2%, P = 0.043). Patients receiving the intensified lung physiotherapy bundle had much shorter mechanical ventilation time (92 vs. 144 h, P &lt; 0.0001), much shorter intensive care unit (ICU) stay (5 vs. 7 days, P &lt; 0.001), and much shorter hospital stay (17 vs. 18.5 days, P = 0.022). The intensified lung physiotherapy bundle was an independent protective factor enabling the reduced occurrence of pneumonia (P = 0.007). On univariate analysis, this bundle significantly improved in-hospital mortality (P = 0.043).ConclusionsOur intensified lung physiotherapy bundle potentially reduces the rate of postoperative pneumonia after cardiac surgery. This bundle might also be adopted as a suitable reference guide for the prevention of other postoperative pulmonary complications.
Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice
Authors: Gu Jinxin , Chen Lixue , Sun Ran , Wang Jie-Li , Wang Juntao , Lin Yingjun , Lei Shuwen , Zhang Yang , Lv Dan , Jiang Faqin , Deng Yuru , Collman James P. , Fu Lei 
Published: February 2022

Neurodegeneration is a pathological condition in which nervous system or neuron losses its structure, function, or both leading to progressive neural degeneration. Growing evidence strongly suggests that reduction of plasmalogens (Pls), one of the key brain lipids, might be associated with multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Plasmalogens are abundant members of ether-phospholipids. Approximately 1 in 5 phospholipids are plasmalogens in human tissue where they are particularly enriched in brain, heart and immune cells. In this study, we employed a scheme of 2-months Pls intragastric administration to aged female C57BL/6J mice, starting at the age of 16 months old. Noticeably, the aged Pls-fed mice exhibited a better cognitive performance, thicker and glossier body hair in appearance than that of aged control mice. The transmission electron microscopic (TEM) data showed that 2-months Pls supplementations surprisingly alleviate age-associated hippocampal synaptic loss and also promote synaptogenesis and synaptic vesicles formation in aged murine brain. Further RNA-sequencing, immunoblotting and immunofluorescence analyses confirmed that plasmalogens remarkably enhanced both the synaptic plasticity and neurogenesis in aged murine hippocampus. In addition, we have demonstrated that Pls treatment inhibited the age-related microglia activation and attenuated the neuroinflammation in the murine brain. These findings suggest for the first time that Pls administration might be a potential intervention strategy for halting neurodegeneration and promoting neuroregeneration.
Treatment of Third Branch Trigeminal Neuralgia With a Balloon Inflated in the Foramen Ovale
Authors: Lu Zhangfan , Wang Jiadong , Cao Yang , Sun Chenglong , Du Quan , Shen Yongfeng , Yu Wenhua , Du Yuanfeng 
Published: February 2022

ObjectiveTo investigate the efficacy of modified percutaneous balloon compression for simple third branch pain and its postoperative complications.MethodsClinical data and surgical records of 132 patients with third branch pain treated with percutaneous balloon compression from March 2015 to May 2019 were retrospectively analyzed, of which 81 cases were in the modified group and 51 cases were in the classic group. The modified technique was to compress again at the foramen ovale to enhance the compression in V3 after compression of the Gasserian ganglion.ResultsIn the modified group, the overall therapeutic efficiency was 96.3%, with 77 patients (95.1%) having immediate postoperative pain relief and one patient (1.2%) having occasional pain without the need for medication. In the classic group, immediate postoperative pain relief was seen in 43 cases (84.3%), and two patients (3.9%) had occasional pain with no need for medication. The rate of complete pain relief was significantly higher in the modified group than in the classic group (P &lt; 0.05). Postoperative follow-up ranged from 14 to 48 months. The pain-free rates were 77.8 and 54.9% in the modified and classic groups, respectively. The incidence of facial numbness in the region of the first branch was significantly lower than in the classic group (P &lt; 0.001).ConclusionThe modified procedure has significant advantages over the classic procedure in improving surgical efficacy, reducing postoperative recurrence rate, and decreasing postoperative numbness in the region, and can be used to treat simple trigeminal neuralgia in the third branch.
Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis
Authors: Xu Song-Song , Zhang Xiu-Ling , Liu Sha-Sha , Feng Shu-Tang , Xiang Guang-Ming , Xu Chang-Jiang , Fan Zi-Yao , Xu Kui , Wang Nan , Wang Yue , Che Jing-Jing , Liu Zhi-Guo , Mu Yu-Lian , Li Kui 
Published: February 2022

BackgroundThe diet-induced gut microbiota dysbiosis has been suggested as a major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood.MethodsWe established a long-term excessive-energy diet-induced metabolic syndrome (MetS) inbred Wuzhishan minipig model, which is characterized by its genetic stability, small size, and human-like physiology. The metabolic parameters, atherosclerotic lesions, gut microbiome, and host transcriptome were analyzed. Metabolomics profiling revealed a linkage between gut microbiota and atherothrombosis.ResultsWe showed that white atheromatous plaque was clearly visible on abdominal aorta in the MetS model. Furthermore, using metagenome and metatranscriptome sequencing, we discovered that the long-term excessive energy intake altered the local intestinal microbiota composition and transcriptional profile, which was most dramatically illustrated by the reduced abundance of SCFAs-producing bacteria including Bacteroides, Lachnospiraceae, and Ruminococcaceae in the MetS model. Liver and abdominal aorta transcriptomes in the MetS model indicate that the diet-induced gut microbiota dysbiosis activated host chronic inflammatory responses and significantly upregulated the expression of genes related to arachidonic acid-dependent signaling pathways. Notably, metabolomics profiling further revealed an intimate linkage between arachidonic acid metabolism and atherothrombosis in the host-gut microbial metabolism axis.ConclusionsThese findings provide new insights into the relationship between atherothrombosis and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of cardiovascular diseases in MetS.
Prevalence and Prognostic Significance of Malnutrition in Hypertensive Patients in a Community Setting
Authors: Yang Zhi-wen , Wei Xue-biao , Fu Bing-qi , Chen Ji-yan , Yu Dan-qing 
Published: February 2022

BackgroundMalnutrition is a significantly poor prognostic factor for a variety of cardiovascular diseases. However, its prevalence and prognostic value in hypertensive patients is still unclear. The present study sought to determine the prevalence and prognostic value of malnutrition in hypertensive patients in a community setting.MethodsWe included 9,949 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) (2005–2014). The Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Naples Prognostic Score (NPS) were applied to assess the nutritional status of participants. A Cox regression model was established to examine the association between malnutrition and cardiovascular and all-cause mortality.ResultsIn all, 19.9, 3.9, and 82.9% hypertensive patients were considered to have malnutrition as evaluated by the CONUT, NRI, and NPS, respectively. Malnutrition assessed by CONUT and NRI was independently associated with cardiovascular mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.41 (1.04–1.91) and 5.79 (2.34–14.29) for CONUT; 2.60 (1.34–5.07) and 3.30 (1.66–6.56) for NRI (all P &lt; 0.05), and for all-cause mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.48 (1.30–1.70) and 4.87 (3.40–6.98) for CONUT; 1.72 (1.24–2.39) and 2.60 (1.96–3.44) for NRI (all P &lt; 0.01). Naples Prognostic Score could only independently predict all-cause mortality.ConclusionsMalnutrition was common among hypertensive patients and was closely associated with both long-term cardiovascular and all-cause mortality.
Association Between Egg Consumption and Dementia Risk in the EPIC-Spain Dementia Cohort
Authors: Margara-Escudero Hernando J. , Zamora-Ros Raul , de Villasante Izar , Crous-Bou Marta , Chirlaque María-Dolores , Amiano Pilar , Mar Javier , Barricarte Aurelio , Ardanaz Eva , Huerta José María 
Published: February 2022

BackgroundCurrent evidence suggests that egg composition might have potential neuroprotective effects. Our aim was to determine the association between egg consumption and the risk of dementia in a Mediterranean population.MethodsThis study was carried out in 3 centers from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort, i.e., 25,015 participants aged 30–70 years, recruited in 1992–1996, and followed up for a mean of 21.5 years.ResultsA total of 774 incident dementia cases were diagnosed and validated, of which 518 were Alzheimer's disease (AD). Data on egg consumption were estimated using a validated dietary history questionnaire at recruitment. Cox proportional hazards models, adjusted for confounders, were used in the analyses. No association was observed between egg consumption and either total dementia [hazard ratio between extreme quartiles (HRQ4vs.Q1: 1.05; 95% CI 0.85–1.31; p-trend = 0.93)] or AD (HRQ4vs.Q1 0.93; 95% CI 0.72–1.21; p-trend = 0.50) risks. After dividing the population by adherence to the relative Mediterranean diet (rMED) score, a borderline inverse association was found between egg intake and both total dementia (HRQ4vs.Q1: 0.52; 95% CI 0.30–0.90; p-trend = 0.10) and AD (HRQ4vs.Q1: 0.52; 95% CI 0.27–1.01; p-trend = 0.13) risks within participants with low adherence to rMED score. However, no association was observed in participants with medium and high adherence to rMED score.ConclusionThis prospective study suggests that egg consumption is associated with a reduced risk of dementia, and specifically of AD, in the adult population with low adherence to rMED score; whereas it has no impact in subjects with moderate and high MD adherence.
Establishing a Macrophage Phenotypic Switch-Associated Signature-Based Risk Model for Predicting the Prognoses of Lung Adenocarcinoma
Authors: Chen Jun , Zhou Chao , Liu Ying 
Published: February 2022

BackgroundTumor-associated macrophages are important components of the tumor microenvironment, and the macrophage phenotypic switch has been shown to correlate with tumor development. However, the use of a macrophage phenotypic switch-related gene (MRG)-based prognosis signature for lung adenocarcinoma (LADC) has not yet been investigated.MethodsIn total, 1,114 LADC cases from two different databases were collected. The samples from TCGA were used as the training set (N = 490), whereas two independent datasets (GSE31210 and GSE72094) from the GEO database were used as the validation sets (N = 624). A robust MRG signature that predicted clinical outcomes of LADC patients was identified through multivariate COX and Lasso regression analysis. Gene set enrichment analysis was applied to analyze molecular pathways associated with the MRG signature. Moreover, the fractions of 22 immune cells were estimated using CIBERSORT algorithm.ResultsAn eight MRG-based signature comprising CTSL, ECT2, HCFC2, HNRNPK, LRIG1, OSBPL5, P4HA1, and TUBA4A was used to estimate the LADC patients’ overall survival. The MRG model was capable of distinguishing high-risk patients from low-risk patients and accurately predict survival in both the training and validation cohorts. Subsequently, the eight MRG-based signature and other features were used to construct a nomogram to better predict the survival of LADC patients. Calibration plots and decision curve analysis exhibited good consistency between the nomogram predictions and actual observation. ROC curves displayed that the signature had good robustness to predict LADC patients’ prognostic outcome.ConclusionsWe identified a phenotypic switch-related signature for predicting the survival of patients with LADC.
Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules
Authors: Xie Shaonan , Li Shaoteng , Deng Huiyan , Han Yaqing , Liu Guangjie , Liu Qingyi 
Published: February 2022

BackgroundSynchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis.MethodsSMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients’ need to undergo whole-body PET/CT and brain MRI examination.ResultsA total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted.ConclusionFor SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.
A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis
Authors: Leite Carlos Heli Bezerra , Lopes Carlos Diego Holanda , Leite Caio Abner Vitorino Gonçalves , Terceiro Dulce Andrade , Lima Gabriel Silva , Freitas Jéssica Andrade , Cunha Fernando Queiroz , Almeida Paulo Roberto Carvalho , Wong Deysi Viviana Tenazoa , Lima-Júnior Roberto César Pereira 
Published: February 2022

BackgroundRadiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.ObjectiveThe present study then aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis.Material/MethodsC57BL/6 male mice were subjected to HDR (radiation source: iridium-192 [Ir-192]) through a cylindrical propylene tube inserted 2 cm far from the anal verge into the rectum. The animals received radiation doses once a day for three consecutive days (fractions of 9.5 Grays [Gy]), 3.0 mm far from the applicator surface. The sham group received only the applicator with no radiation source. The survival rate was recorded, and a colonoscopy was performed to confirm the tissue lesion development. Following euthanasia, samples of the rectum were collected for histopathology, cytokines dosage (IL-6 and KC), and immunohistochemical analysis (TNF-α and COX-2).ResultsHDR significantly reduced animals’ survival ten days post first radiation exposure (14% survival vs. 100% in the non-irradiated group). Day seven was then used for further investigation. Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P &lt; 0.05 vs. the control group). The tissue damage was accompanied by an inflammatory response, marked by increased KC and IL-6 tissue levels, and immunostaining for TNF-α and COX-2 (P &lt; 0.05 vs. control group).ConclusionsWe established a novel animal model of actinic proctitis induced by HDR brachytherapy, marked by inflammatory damage and low animal mortality.
A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects
Authors: Ferini Gianluca , Castorina Paolo , Valenti Vito , Illari Salvatore Ivan , Sachpazidis Ilias , Castorina Luigi , Marrale Maurizio , Pergolizzi Stefano 
Published: February 2022

IntroductionMetastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit–risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models.MethodsWe treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed.ResultsWe observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system.ConclusionsPET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system’s role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.