bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the usefulness of red blood cell distribution width in critically ill pediatric patients
Authors: Kim Da Hyun , Ha Eun Ju , Park Seong Jong , Jhang Won Kyoung 
Published: September 2020

Abstract
Red blood cell distribution width (RDW) is a component of routine complete blood count, which reflects variability in the size of circulating erythrocytes. Recently, there have been many reports about RDW as a strong prognostic marker in various disease conditions in the adult population. However, only a few studies have been performed in children. This study aimed to investigate the association between RDW and pediatric intensive care unit (PICU) mortality in critically ill children. This study includes 960 patients admitted to the PICU from November 2012 to May 2018. We evaluated the associations between RDW and clinical parameters including PICU mortality outcomes. The median age of the study population was 15.5 (interquartile range, 4.8–54.5) months. The mean RDW was 15.6% ± 3.3%. The overall PICU mortality was 8.8%. As we categorized patients into 3 groups with respect to RDW values (Group 1: ≤14.5%; Group 2: 14.5%–16.5%; and Group 3: >16.5%) and compared clinical parameters, the higher RDW groups (Groups 2 and 3) showed more use of vasoactive-inotropic drugs, mechanical ventilator support, higher severity scores, including pediatric risk of mortality III, pediatric sequential organ failure assessment, pediatric logistic organ dysfunction-2 (PELOD-2), and pediatric multiple organ dysfunction syndrome scores, and higher PICU mortality than the lower RDW group (Group 1) (P < .05). Based on multivariate logistic regression analysis adjusted for age and sex, higher RDW value (≥14.5%) was an independent risk factor of PICU mortality. Moreover, adding RDW improved the performance of the PELOD-2 score in predicting PICU mortality (category-free net reclassification index 0.357, 95% confidence interval 0.153–0.562, P = .001). In conclusion, higher RDW value was significantly associated with worse clinical parameters including PICU mortality. RDW was an independent risk factor of PICU mortality and the addition of RDW significantly improved the performance of PELOD-2 score in predicting PICU mortality. Thus, RDW could be a promising prognostic factor with advantages of simple and easy measurement in critically ill pediatric patients.
Operative Trauma and Blood Loss — Impact on Tumor Growth and Recurrence
Authors: Pretzsch Elise , Bösch Florian , Renz Bernhard , Werner Jens , Angele Martin , Chaudry Irshad H. 
Published: September 2020

ABSTRACT
In cancer patients, surgical removal of the primary tumor is one of the major steps within a multimodal therapy concept toward eliminating the disease and limiting further progression. In this respect, surgical trauma can have potent effects on the patient's immune system. Intraoperative blood loss associated with major surgical trauma leads to reduced blood flow, regional hypoxia, metabolic, and microenvironmental alterations stimulating an inflammatory response characterized by the release of pro-inflammatory cytokines (i.e., TNF-α, IL-6) and acute-phase proteins. The inflammatory state is accompanied by and intertwined with a counter-regulatory anti-inflammatory response reflected in the rise of anti-inflammatory cytokines (i.e., transforming growth factor-β) and prostaglandins (i.e., prostaglandin E2) which can lead to a depression of cell-mediated immunity and systemic immunosuppression. This results in a highly vulnerable state with concurrent expression of pro- and anti-inflammatory cytokines alternately predominating. The immunosuppressive state is characterized by a reduced antigen-presentation capacity of macrophages, alterations in lymphocyte proliferation, and activation as well as a shift of the Th1/Th2 (T helper cells 1 and 2) balance toward Th2 and a decrease in natural killer cell activity. The severity of the immunosuppression thereby correlates with the extent and the duration of the surgical procedure. Growing evidence suggests that the immunosuppressive state following hemorrhage and surgical trauma might not only be a risk factor for postoperative complications but also facilitate tumor proliferation, metastatic growth, and recurrence. This article provides an overview of the cascade of events and underlying mechanisms resulting in immunosuppression and describes the impact of hemorrhage and major surgical trauma on tumor growth and recurrence. Attempts to control for perioperative inflammation thereby reducing the adverse effects of postoperative immunosuppression could have positive effects on tumor growth, metastasis formation, and recurrence.
Childhood Mortality After Fluid Bolus With Septic or Severe Infection Shock: A Systematic Review and Meta-Analysis
Authors: Yue Jing , Zheng Ronghao , Wei Huiping , Li Jie , Wu Jiannan , Wang Ping , Zhao Hui 
Published: September 2020

ABSTRACT

Background:
A considerable debate on whether fluid bolus could decrease childhood mortality in pediatric patients with septic or severe infection shock is still unresolved. A systematic review and meta-analysis was conducted to investigate the mortality rates after fluid bolus among children with septic or severe infection shock.

Methods:
A systematic electronic search of PubMed, MEDLINE, Cochrane Library, and EMBASE databases was conducted to identify relevant published studies till March 30, 2020.

Results:
A total of 19 studies with 9,321 severe sepsis or septic shock pediatric patients were included and exhibited an acceptable quality. Of the 17 studies that reported mortality at 48 h, no bolus group decreased the mortality rate when compared with bolus group with a risk ratio (RR) of 0.74 [95% confidence interval (CI) = 0.62–0.88, P < 0.01], and showed no heterogeneity (I
2 = 0%). Similar results were observed on colloids and crystalloids solution in malaria shock cases with a RR of 0.79 (95% CI = 0.62–1.02). For the subgroup of general shock patients, no significant difference was shown with an RR of 0.79 (95% CI = 0.62–1.02, P = 0.07) and no significant heterogeneity (I
2 = 0%). Two studies reported mortality at week 4 and pooled results indicated that no bolus group was protective against mortality when compared with bolus group with RR of 0.71 (95% CI = 0.57–0.88, I
2 = 0%).

Conclusion:
For the mortality at 48 h, the no bolus group showed decreased mortality when compared with the bolus group, especially in the malaria group. Similar results were found in the colloids and crystalloids solution in patients with malaria shock. Meta-analysis studies with long-term follow-up period and larger sample size are warranted to address the conclusion in the future.
High Versus Low Volume Fluid Resuscitation Strategies in a Porcine Model (Sus scrofa) of Combined Thermal and Traumatic Brain Injury
Authors: Guenther Timothy M. , Spruce Marguerite W. , Bach Lindsey M. , Caples Connor M. , Beyer Carl A. , Grayson John K. , Meyers Frederick J. , Palmieri Tina L. , Brown Ian E. 
Published: September 2020

ABSTRACT

Background:
Combined burn and traumatic brain injury (TBI) treatment priorities may not align due to opposing fluid resuscitation paradigms used in treating burns and TBI. We developed a porcine model of combined thermal injury/TBI and compared an “aggressive” fluid resuscitation strategy using the Parkland formula and a “restrictive” resuscitation strategy using the modified Brooke formula.

Methods:
Twenty-eight swine were deeply anesthetized and received a 40% total body surface area full-thickness burn injury and TBI. Swine were then randomized to receive restrictive or aggressive resuscitation for 8 h after which time animals were euthanized and necropsy was performed. Volume of brain injury was assessed after analyzing segmental slices of brain tissue.

Results:
There were no differences between the restrictive and aggressive resuscitation groups in blood pressure, heart rate, central venous pressure, intra-cranial pressure (ICP), or serum lactate levels after 8 h of resuscitation. Urine output was higher in the aggressive resuscitation group. The restrictive group had a significantly higher serum blood urea nitrogen (BUN) compared with baseline and compared with the aggressive group. There was no significant difference in size of brain injury between groups.

Conclusions:
Both restrictive and aggressive resuscitation demonstrated adequate resuscitation at 8 h postinjury. Increased serum BUN in the restrictive group may be an indicator of early acute kidney injury, despite adequate urine output. Resuscitation strategy did not appear to affect ICP or the size of brain injury.
Transfer Language Space with Similar Domain Adaptation: A Case Study with Hepatocellular Carcinoma
Authors: Balthazar Patricia , Lee Scott Jeffery , Desser Terry , Rubin Daniel L. , Gichoya Judy Wawira , Banerjee Imon 
Published: September 2020

AbstractTransfer learning is a common practice in image classification with deep learning where the available data is often limited for training a complex model with millions of parameters. However, transferring language models requires special attention since cross-domain vocabularies (e.g. between news articles and radiology reports) do not always overlap as the pixel intensity range overlaps mostly for images. We present a concept of similar domain adaptation where we transfer an inter-institutional language model between two different modalities (ultrasound to MRI) to capture liver abnormalities. Our experiments show that such transfer is more effective for performing shared targeted task than generic language space transfer. We use MRI screening exam reports for hepatocellular carcinoma as the use-case and apply the transfer language space strategy to automatically label thousands of imaging exams.
Potential reduction in transmission of COVID-19 by digital contact tracing systems: a modelling study
Authors: Plank Michael J. , James Alex , Lustig Audrey , Steyn Nicholas , Binny Rachelle N , Hendy Shaun C. 
Published: September 2020

AbstractBackgroundDigital tools are being developed to support contact tracing as part of the global effort to control the spread of COVID-19. These include smartphone apps, Bluetooth-based proximity detection, location tracking, and automatic exposure notification features. Evidence on the effectiveness of alternative approaches to digital contact tracing is so far limited.MethodsWe use an age-structured branching process model of the transmission of COVID-19 in different settings to estimate the potential of manual contact tracing and digital tracing systems to help control the epidemic. We investigate the effect of the uptake rate and proportion of contacts recorded by the digital system on key model outputs: the effective reproduction number, the mean outbreak size after 30 days, and the probability of elimination.ResultsEffective manual contact tracing can reduce the effective reproduction number from 2.4 to around 1.5. The addition of a digital tracing system with a high uptake rate over 75% could further reduce the effective reproduction number to around 1.1. Fully automated digital tracing without manual contact tracing is predicted to be much less effective.ConclusionsFor digital tracing systems to make a significant contribution to the control of COVID-19, they need be designed in close conjunction with public health agencies to support and complement manual contact tracing by trained professionals.
Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China
Authors: Yang Juan , Chen Xinhua , Deng Xiaowei , Chen Zhiyuan , Gong Hui , Yan Han , Wu Qianhui , Shi Huilin , Lai Shengjie , Ajelli Marco , Viboud Cecile , Yu Hongjie 
Published: September 2020

AbstractThe pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, where a first wave of intense community transmission was cut short by interventions. Using multiple data source, we estimated the disease burden and clinical severity of COVID-19 by age in Wuhan from December 1, 2019 to March 31, 2020. We adjusted estimates for sensitivity of laboratory assays and accounted for prospective community screenings and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95%CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had higher burden than the 2009 influenza pandemic or seasonal influenza, and that clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.
Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile
Authors: Law Jaclyn C. , Koh Wan Hon , Budylowski Patrick , Lin Jonah , Yue FengYun , Abe Kento T. , Rathod Bhavisha , Girard Melanie , Li Zhijie , Rini James M. , Mubareka Samira , McGeer Allison , Chan Adrienne K. , Gingras Anne-Claude , Watts Tania H. , Ostrowski Mario 
Published: September 2020

AbstractThere is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-γ to TNF-α ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-γg+ CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.
Integration of multi-omics data improves prediction of cervicovaginal microenvironment in cervical cancer
Authors: Bokulich Nicholas A. , Łaniewski Paweł , Chase Dana M. , Caporaso J. Gregory , Herbst-Kralovetz Melissa M. 
Published: September 2020

AbstractEmerging evidence suggests that a complex interplay between human papillomavirus (HPV), microbiota, and the cervicovaginal microenvironment contribute to HPV persistence and carcinogenesis. Integration of multiple omics datasets is predicted to provide unique insight into HPV infection and cervical cancer progression. Cervicovaginal specimens were collected from a cohort (n=100) of Arizonan women with cervical cancer, cervical dysplasia, as well as HPV-positive and HPV-negative controls. Microbiome, immunoproteome and metabolome analyses were performed using 16S rRNA gene sequencing, multiplex cytometric bead arrays, and liquid chromatography-mass spectrometry, respectively. Multi-omics integration methods, including neural networks (mmvec) and Random Forest supervised learning, were utilized to explore potential interactions and develop predictive models. Our integrated bioinformatic analyses revealed that cancer biomarker concentrations were reliably predicted by Random Forest regressors trained on microbiome and metabolome features, suggesting close correspondence between the vaginal microbiome, metabolome, and genital inflammation involved in cervical carcinogenesis. Furthermore, we show that features of the microbiome and host microenvironment, including metabolites, microbial taxa, and immune biomarkers are predictive of genital inflammation status, but only weakly to moderately predictive of cervical cancer state. Different feature classes were important for prediction of different phenotypes. Lipids (e.g. sphingolipids and long-chain unsaturated fatty acids) were strong predictors of genital inflammation, whereas predictions of vaginal microbiota and vaginal pH relied mostly on alterations in amino acid metabolism. Finally, we identified key immune biomarkers associated with the vaginal microbiota composition and vaginal pH (MIF and TNFα), as well as genital inflammation (IL-6, IL-10, leptin and VEGF). Integration of multiple different microbiome “omics” data types resulted in modest increases in classifier performance over classifiers trained on the best performing individual omics data type. However, since the most predictive features cannot be known a priori, a multi-omics approach can still yield insights that might not be possible with a single data type. Additionally, integrating multiple omics datasets provided insight into different features of the cervicovaginal microenvironment and host response. Multi-omics is therefore likely to remain essential for realizing the advances promised by microbiome research.
Implementation and validation of a pooling strategy for a sustainable screening campaign for the presence of SARS-CoV-2
Authors: Cesselli Daniela , Bulfoni Michela , Marzinotto Stefania , Marcon Barbara , Cmet Sara , Cussigh Anna Rosa , Migotti Angelica , Martinella Romina , Pipan Corrado , Beltrami Antonio Paolo , Curcio Francesco 
Published: September 2020

AbstractMass screening aimed at detecting, in asymptomatic subjects, the presence of SARS-CoV-2 is considered a strategic measure for the control of the present pandemic. It allows virus carriers to be identified and quarantined, thus preventing local spread and protecting vulnerable individuals. Although the screening strategy should be determined by the epidemiological situation, the size of the population that can be screened is indeed limited by the availability of resources. Here we present the implementation of an 8-sample pool strategy that relies on protocols, reagents and equipment currently used in clinical diagnostics. The method permitted to identify, with 100% sensitivity, specificity and accuracy, samples with low viral load, being the limit of detection of 11 viral copies extracted from the equivalent of 133μl of nasopharyngeal sample-pool. When the protocol has been applied, as a proof of principle, in a real population of 3592 consecutive nasopharyngeal swabs collected by healthcare providers in asymptomatic subjects, 20 positive pools were detected and in 100% of cases the positive specimens identified. Considering these performances, the 8-sample pool will allow, in populations with an expected positive rate of less than 1%, reducing costs by at least 80%, being a suitable method for a sustainable mass screening strategy in a population of asymptomatic subjects.
Does Clinical Nihilism affect the diagnostic approach for patients with undiagnosed adult coeliac disease? A UK Multicentre study
Authors: Blanshard RJ , Naylor G , Taylor MA , Penny HA , Mooney PD , Sanders DS 
Published: September 2020

AbstractBackgroundAdult coeliac disease (CD) has delays in diagnosis but the reasons for this have not been explored.MethodsGroup 1) Time from primary care presentation to diagnostic endoscopy was prospectively quantified in 151 adult patients with a positive endomysial antibody test and compared with the diagnostic pathway of 92 adult patients with suspected inflammatory bowel disease (IBD). Group 2) Across 4 hospitals over a 3-month period, duodenal biopsy reports for suspected CD were reviewed (n=1423). Group 3) 50 gastroenterologists completed questionnaires concerning their viewpoints on CD.ResultsGroup 1) Suspected coeliac patients waited significantly longer for diagnostic endoscopy following referral (48.5 [28-89] days) than suspected IBD patients (34.5 [18-70] days; p=0.003). Group 2) Of the 1423 patients that underwent diagnostic endoscopy for possible CD, 40.0% met the guidelines to take at least 4 biopsies. Diagnosis of CD was more likely if these guidelines were followed (10.1% vs 4.6% p<0.0001). 12.4% of newly diagnosed CD patients had at least 1 non-diagnostic gastroscopy in the 5 years prior to diagnosis. Group 3) 32.0% (16) of gastroenterologists failed to identify that CD has greater prevalence in adults than IBD. Moreover, 36.0% (18) of gastroenterologists felt that doctors were not required for the management of CD.ConclusionProlonged waiting times for endoscopy and inadequacies in biopsy technique suggest clinical inertia towards CD. This is exemplified by the nihilistic approach to the condition demonstrated in our qualitative data. This is the first study to demonstrate clinical inertia towards CD.Main messagesCD patients face greater delays at all wait intervals from referral to diagnostic endoscopy compared to inflammatory bowel disease (IBD) patients.The majority of endoscopists do not follow guidelines for diagnostic endoscopy for CD. This reduced diagnosis rates by over 50%.Questionnaire findings presented a nihilistic attitude towards CD alone and in comparison to IBD.This is the first study to fully represent how clinical inertia towards CD directly leads to increased diagnostic delay and likely missed diagnoses.What is already known on the subjectDiagnostic delay is a key issue facing modern management of coeliac disease (CD) whilst only 1 in 4 cases are estimated to be diagnosed.Delayed diagnosis of CD is associated with an increased risk of complications from the disease and a worse quality of life.
Clinical, cerebrospinal fluid and neuroimaging findings in COVID-19 encephalopathy: a case series
Authors: Tuma Raphael , Guedes Bruno , Carra Rafael , Iepsen Bruno , Rodrigues Júlia , Camelo-Filho Antonio Edvan , Kubota Gabriel , Ferrari Maíra , Neto Adalberto Studart , Oku Mariana Hiromi Manoel , Terrim Sara , Lopes Cesar Castello Branco , Passos Neto Carlos E. B. , Fiorentino Matheus D. , Souza Julia C. C. , Baima José Pedro S. , Silva Tomás , Perissinotti Iago , Martin Maria da Graça M. , Gonçalves Marcia , Fortini Ida , Smid Jerusa , Adoni Tarso , Lucato Leandro , Nitrini Ricardo , Gomes Helio , Castro Luiz H 
Published: September 2020

AbstractObjectiveTo describe the clinical, neurological, neuroimaging and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center.MethodsWe retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020.ResultsFifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2) or severe (3), p<0.001).ConclusionIn our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.