bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Neutrophil-to-Lymphocyte Ratio at Admission Predicts the 6-monthss Outcome in Acute Traumatic Cervical Spinal Cord Injury Patients: A Retrospective Study
Authors: Zhao Jian-Lan , Lai Song-Tao , Du Zhuo-Ying , Sun Yi-Rui , Yuan Qiang , Wu Xing , Li Zhi-Qi , Hu Jin , Xie Rong
Published: January 2020

Background: The prognostic value of Neutrophil-to-Lymphocyte Ratio (NLR) for the outcome of acute cervical traumatic spinal cord injury (tSCI) patients has rarely been studied by now throughout the world. Methods: We performed a single-center retrospective cohort study to evaluate the prognostic value of NLR from peripheral whole blood count in patients with acute cervical tSCI. Patients within 6 hours of acute cervical tSCI treated between Dec 2008 and May 2018 in Huashan Hospital of Fudan University were enrolled. Outcomes of patients with tSCI were assessed using American spinal injury association Impairment Scale (AIS). 6-month outcomes were dichotomized into poor outcome group (AIS A to C) and good outcome group (AIS D and E). Uni- and multivariate analyses were performed to assess the independent predictors of 6-month outcome. Two prediction models based on admission characteristics were built to evaluate the prognostic value of NLR. The discriminative ability of predictive models was evaluated using the area under the curve (AUC). Results: A total of 377 patients were identified from our single center in China PR. Multivariate analysis showed that age, AIS grade at admission, NLR (p<0.001) and coagulopathy (p = 0.003) were independent predictors of the 6-months outcome for acute cervical tSCI patients. The model combing NLR and standard variables (AUC=0.944; 95% CI, 0.923-0.964) showed a more favorable prognostic value than that without NLR (AUC=0.841; 95% CI, 0.798-0.885) in terms of 6-month outcome. Conclusions: NLR is firstly identified as an independent predictor of the 6-month outcome in acute cervical tSCI patients worldwide. The prognostic value of NLR is favorable, and a high NLR is associated with poor outcome in patients with acute cervical tSCI.
Detection of fractures of hand and forearm in whole-body CT for suspected polytrauma in intubated patients
Authors: Münn Friederike , Laun Reinhold A , Asmus Ariane , Bülow Robin , Bakir Sinan , Haralambiev Lyubomir , Eisenschenk Andreas , Kim Simon
Published: January 2020

Background: The aim of this study was to evaluate the potential of whole-body CT for diagnosis of hand and forearm fractures in intubated patients with suspected polytrauma. Methods: We performed a retrospective analysis on data collected from two trauma centres in Germany, including demographics, ISS, clinical symptoms, depiction in whole-body CT, and time to diagnosis. Results: Out of 426 patients included in the study, 66 (15.5%) suffered a hand or forearm fracture. The total number of fractures was 132. The WBCT report mentioned 98 (74.2 %). 16 (12,1 %) fractures of 12 patients were diagnosed later than 24 hrs after admission. Late diagnoses of fractures of the hand occurred more often if the hand was not fully included in the CT scan field. The sensitivity of WBCT for cases with fractures of hand and/or forearm with full inclusion of the corresponding area in the scan field was 80.2 %. Conclusions: This study shows that WBCT is a valuable diagnostic tool for hand fractures in polytrauma patients. Hands should be evaluated regardless of clinical presentation in intubated patients after suspected polytrauma if they are included in the whole-body CT.
Genetic structure characteristics and treatment for Listeria monocytogenes infections
Authors: Yu Wei , Huang Yicheng , Guo Lihua , Zhang Jiajie , Zhan Yaqiong , Zhang Li , Qiu Yunqing
Published: January 2020

Background: Invasive Listeria monocytogenes (Lm) carry a high mortality despite antibiotic treatment. The aim of this study was to investigate the mechanism of pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated as well. Methods: Three Lm isolates were collected and 15 antibiotics susceptibility tests were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Furthermore, the effect of meropenem, linezolid, benzylpenicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay.Results: Two sequence types (STs) were identified for isolate 23949 (ST87), 26530 (ST3), 34096 (ST87), respectively. All isolates were resistant to fosfomycin and daptomycin. The resistant genes fosX, mprF, norB and vgaALC were identified in all isolates. Furthermore, 80 virulence genes were detected and 72 genes were found in all three isolates. There were 26 virulent genes associated with the structure, biosynthesis, motor switch of flagellum. And other virulent genes were involved in chemotaxis, protease, internalin and metabolism. It is of note that 8 genes (inlJ, llsB, llsD, llsG, llsH, llsP, llsX, llsY) were only found in 26530 isolated from cerebrospinal fluid (CSF), 7 of which were associated with haemolysin. Further in vitro time-kill assay found trimethoprim/sulfamethoxazole at serum or CSF concentrations had bactericidal effect (>3.5 log10 CFU/ml) against three tested Lm strains at 24 h. Conclusions: The involved virulence factors were mainly associated with bacterial pathogenicity. Notably, trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm bloodstream infection or intracranial infection.
A Critical Realist Evaluation of an Integrated Care Project for Vulnerable Families in Sydney, Australia
Authors: Tennant Elaine , Miller Erin , Costantino Kathryn , De Souza Denise , Coupland Heidi , Fotheringham Penelope , Eastwood John
Published: January 2020

Background Healthy Homes and Neighbourhoods (HHAN) Integrated Care Initiative was established to improve the care of families with complex health and social needs who reside in Sydney Local Health District. HHAN seeks to provide long-term multi-disciplinary care coordination as well as enhance capacity building and promotion of integrated care. We describe the qualitative component of a critical realist pilot case study aimed at exploring, explaining and refining emerging HHAN programme theories in relation to care coordination. Methods Semi-structured qualitative interviews with HHAN clients (n=12), HHAN staff and other stakeholders (n=21). Emerging themes informed the development of Context-Mechanism-Outcome configurations aimed at evaluating HHAN’s effectiveness and refining the programme theory. Results HHAN’s effectiveness was based on two process mechanisms: Engagement of vulnerable clients and integration of services. The relational mechanisms underpinning effective engagement of clients by care coordinators included: building trust, leveraging other family, social and organisational relationships, meeting clients on their own terms, demonstrating staff effectiveness as quickly as possible, and client empowerment. Operational mechanisms for enhancing care integration included knowledge transfer activities and shared learning among collaborators, structural and cultural changes, enhancing mutual respect, co-location of multidisciplinary and/or interagency staff and cultivating faith in positive change among staff. Conclusions Use of a critical realism case study approach served to elucidate the varied influences of contexts and mechanisms on programme outcomes, to highlight what works for whom and in what context. Findings supported the initial programme theory that engagement and trust building with clients, alongside enhanced collaboration and integration of services, improved outcomes for vulnerable families with complex needs. Further research is needed to explore the cost-effectiveness of integrated care initiatives, in view of the long term nature of service provision and the risk of staff burnout.
Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017
Authors: Aas Christer frode , Vold Jørn Henrik , Skurtveit Svetlana , Odsbu Ingvild , Chalabianloo Fatemeh , Johansson Kjell Arne , Fadnes Lars Thore
Published: January 2020

Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate cumulative frequency of HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were adjusted for age, gender, and OAT medications and studied in a logistic regression model. Results In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV treatment uptake increased in both countries, giving a cumulative frequency of around one-third in both countries at the end of the study period. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients during the introduction period of new direct-acting treatment regimens. However, a further scale-up is crucial to be able to control and eliminate the HCV endemic among OAT patients.
Classification of muscle-invasive bladder cancer based on tumor stromal compartment
Authors: Wei Kang-Lai , Shi Lin , Liang Zhi-Jie , Liang Hai-wei , Guo Yi-Nan , Liu Yu , Zhu Dan-Dan , Wu Fang-Xiao , Yi Xiao-Lin , Mo Steven , Qi Zhong-Quan , Li Hongmian
Published: January 2020

Purpose There has been a resurgence of interest in the tumor stroma in recent years. Whether the relative abundance of various stromal cells can be used as a classification system for muscle-invasive bladder cancer (MIBC) remain elusive.Methods We applied single-cell RNA-sequence (scRNA-seq) data from two MIBCs to identify stromal cell (CD45 negative cells) clusters and the marker gene set of each cell cluster. The single sample gene set enrichment analysis method is used to estimate the relative abundance of the cell clusters in each MIBC sample from The Cancer Genome Atlas. Subsequently, k-means clustering was performed to cluster the MIBCs. Prognosis, oncogenic pathway enrichment score, epithelial-mesenchymal transition (EMT) score, gene mutation frequency, and tumor infiltrating lymphocytes (TILs) were compared among the stromal component-based types of MIBC.ResultsIn the scRNA-seq analysis, a total of nine cell clusters mainly composed of four types of cells were identified. Cell clusters 0, 1, 2, 3, 4, and 7 were considered as bladder epithelial cells, the cells in clusters 5 and 8 were mainly recognized as stem cells and fibroblasts, and the cell cluster 6 was recognized were endothelial cells. The 408 MIBC samples were classified into three types. Type 1 and 3, the “stromal-sufficient” type I and II with higher stromal cells, and Type 2, the “stromal-desert” type with lower stromal cells. The stromal-desert type had significantly better overall survival. As the tumor progresses, the stromal component of the stromal-desert type increases and change into the stromal-sufficient type. Increased stromal cells may come from EMT. The enrichment scores of multiple oncogenic pathways in stromal-sufficient types were significantly higher than those in stromal-desert type. More TILs were found in stromal-sufficient type, but their function may be inhibited by stromal cells. In addition, the three stromal types of MIBC may have specific gene mutation characteristics.Conclusions We proposed a novel stromal component-based classification system to divided into MIBC three phenotype. The three types of MIBC differ in various biological characteristics. The progress of MIBC may be summarized as the process of gradually increasing stromal components and constructing a microenvironment suitable for cancer cells.
Capturing complex vaccine-immune-disease relationships for free-ranging koalas: IL17 production is an important intermediate factor against chlamydial disease
Authors: Lizárraga David , Timms Peter , Quigley Bonnie L , Hanger Jon , Carver Scott
Published: January 2020

Background Disease is a major factor negatively affecting koala populations. Vaccination is a promising treatment option that would result in immune-mediated protection against disease. Measuring and assessing vaccine efficacy can be challenging owing to both direct and indirect interactions caused by vaccination. In this study, we investigate vaccine-immune-chlamydial load-disease relationships from MOMP (major outer membrane protein) vaccine trials to protect healthy free-ranging koalas against Chlamydia -related diseases. Methods We created a priori hypotheses based on data sources and perceived direct and indirect interactions from koalas vaccinated six months prior. Each hypothesis was tested as a structural equation model to evaluate possible causality among measured variables. Model averaging was used as multiple models fit the data, and the strength of relationships were examined through averaged coefficients and the raw data. Results Despite multiple potential sources of variation owing to the koalas in this study being free-ranging, our analyses provide unique insights into the effects of vaccinating against Chlamydia . We found more relationships in urogenital models with interleukin 17 (IL17) production compared to models with interferon gamma (IFNγ) production. In the averaged model with IL17, urogenital chlamydial load was positively associated with disease and negatively associated with IL17 production. MOMP vaccination had a trending effect for reducing chlamydial load and also had a strong effect on increasing IL17 production. This indicated a link between MOMP vaccination, reduction of urogenital chlamydial load, and increased production of IL17. Not surprisingly, urogenital chlamydial load was a positive predictor for the development of urogenital disease at six months post-vaccination. Conclusions Using structural equation modelling, this study has helped illuminate that the immune cytokine IL17 may be an important intermediate factor linking MOMP vaccination with chlamydial pathogenesis and protection, enhancing previous investigations. Going beyond univariate statistics, the methods used in this study can be applied to other preclinical vaccination experiments to identify important direct and indirect factors underpinning the effects of a vaccine.
Comparison of Choriocapillary Flow Density Between Fellow eyes of Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration
Authors: Luo Mingyue , Yuan Mingzhen , Yang Jingyuan , Zhao Nan , Dai Rongping , Chen Youxin
Published: January 2020

Background To compare the choriocapillary flow density (CFD) among the contralateral eyes of polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD) and healthy controls with spectral-domain optical coherence angiography tomography (SD-OCTA).Methods This is a cross-sectional study. 36 eyes of 36 PCV patients, 35 eyes of nAMD patients and 34 control eyes were included. All sujects underwent the HD Angio Retina 6.0 mm scan pattern of OCTA (RTVue XR Avanti AngioVue; Optovue, Inc., Fremont, CA, USA). Circles with radius of 1.00, 1.50 and 3.00 mm were manually selected in choriocapillaries (CC) slab, and CFD was calculated as the percentage of flow area to the whole selected area as CFD-1.00, 1.50, 3.00 respectively. Multivariate linear regression analysis was performed to evaluate the differences of CFD among the three groups after adjusting for age, gender and the existence of drusen.Results Mean CFD-1.00, 1.50, 3.00 of nAMD group were 61.09, 62.65 and 65.67, significantly lower than PCV group (65.80, 66.75, 67.86, P= 0.000, 0.000, 0.022) and control (66.17, 66.45, 68.08, P= 0.000, 0.001, 0.025), while no difference were detected between PCV group and control ( P= 0.507, 0.798, 0.575).Conclusions CFD of nAMD fellow eyes were significantly lower than that of PCV and control eyes, while no difference was detected between PCV and control group, indicating different role of CC loss in early pathogenesis of nAMD and PCV.
Isolation and characterization of bacteriaophages against virulent Aeromonas hydrophila
Authors: Liu Jin , Gao Shanshan , Dong Yuhao , Lu Chengping , Liu Yongjie
Published: January 2020

Background: Aeromonas hydrophila is an important water-borne pathogen that leads to a great economic loss in aquaculture. Along with the abuse of antibiotics, drug-resistant strains rise rapidly. In addition, the biofilms formed by this bacterium limited the antibacterial effect of antibiotics. Bacteriaophages have been attracted increasing attention as a potential alternative to antibiotics against bacterial infections. Results: Five phages against pathogenic A. hydrophila, named N21, W3, G65, Y71 and Y81, were isolated. Morphological analysis by transmission electron microscopy revealed that phages N21, W3 and G65 belong to the family Myoviridae, while Y71 and Y81 belong to the Podoviridae. These phages were found to have broad host spectra, although their burst sizes were varied per infected host cell at their optimal multiplicity of infection. They were sensitive to high temperature but had a wide adaptability to the pH. In addition, the phages G65 and Y81 showed considerable effect on growth and biofilm inhibition of A. hydrophila; and the phages G65, W3 and N21 were able to scavenge mature biofilm effectively. Phage treatments applied to the pathogenic A. hydrophila in mice model resulted in a significantly decreased bacterial loads in tissues. Conclusions: Five A. hydrophila phages were isolated with broad host ranges, low latent periods, and wide pH and thermal tolerance. And the phages exhibited varying abilities in controlling A. hydrophila infection. This work presents promising data supporting the future use of phage therapy.
Clinical and microbiological characteristics of Cryptococcus gattii isolated from China
Authors: Jin Liang , Cao Jingrong , Xue Xinying , Wu Hua , Wang Lifeng , Guo Ling , Shen Dingxia
Published: January 2020

Background: Infection, even outbreak, caused by Cryptococcus gattii (C. gattii ) has been reported in Canada and the United States, but there were sparsely-reported cases of C. gattii in China. Our interest in occurrence, clinical manifestation, laboratory identification and molecular characterization of Chinese C. gattii strains leads us to this research. Methods: A total of 254 clinical isolates primarily identified as Cryptococcus neoformans (C. neoformans ) were collected. VITEK 2 compact, canavanine glycine bromothymol blue (CGB) agar and Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used for strain identification. Multi-locus sequence typing (MLST) was performed for genotyping. Antifungal susceptibility test was carried out with commercial kits of both ATB fungus 3 and Yeast one. Clinical information of patients was reviewed retrospectively. Label-free proteome technique was used to quantitatively analyze the differential proteins of C. gattii. Results: Out of 254 clinical isolates, we identified eight strains as C. gattii. MLST showed genotype VGI accounted for the most (6 / 8), the other two strains were genotype VGII（VGIIa and VGIIb respectively）with 3 specific spectra of molecular weight about 4342, 8686, 9611 Dalton by MALDI-TOF MS. The minimal inhibitory concentrations (MICs) of Fluconazole with Yeast one was 2～4 times higher than that with ATB fungus 3. Higher MICs of antifungal agents were exhibited against VGII strains than against VGI strains. C. gattii genotype VGII and VGI possessed 418 and 774 specific proteins respectively. Comparative proteome analysis showed that 180 proteins were highly expressed in C. gattii VGII and 329 proteins were highly expressed in C. gattii VGI. The enrichment of differentially expressed proteins between VGII and VGI was directed to Golgi complex.Conclusions: Infection by C. gattii in China might have been underestimated because of initial mis-identification. Genotype VGI was predominant but VGII was more resistant to antifungal agents. There was significant difference in protein expression profile between VGII and VGI C. gattii.
A novel gene expression system for Ralstonia eutropha based on the T7 promoter
Authors: Bi Changhao , Xiong Bin , Hu Muzi , Li Zhongkang , Liu Li , Li Siwei , Zhang Chunzhi , Zhang Xueli
Published: January 2020

Background: Ralstonia eutropha (syn. Cupriavidus necator) is a model microorganism for the metabolism of polyhydroxyalkanoates (PHAs) and a potential chassis for protein expression. Although current plasmid systems for R. eutropha provide a basic platform for gene expression, the performance of the induction systems is still limited. In addition, the sizes of the cloned genes is limited due to the large sizes of the plasmid backbones.Results: In this study, an R. eutropha T7 expression system was established by integrating a T7 RNA polymerase gene driven by the PBAD promoter into genome of R. eutropha, and cloning the T7 promoter into a pBBR1-derived plasmid for gene expression. In addition, the essential sequence necessary for pBBR1 plasmid replication was identified, and the redundant parts were deleted, reducing the expression plasmid size to 3392 bp, and the electroporation efficiency was improved 4 times. As a result, the highest expression level of Rfp was enhanced slightly, and the L-arabinose concentration necessary for induction was decreased 20 times. Conclusions: R. eutropha with the T7 expression system provides an efficient platform for protein expression and synthetic biology applications.
Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center
Authors: Masri Hiba EL , Hollingworth Samantha , Driel Mieke van , Benham Helen , McGuire Treasure
Published: January 2020

BackgroundDisease modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm be a barrier to use.MethodsIn a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes.ResultsThere were 1,547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling.ConclusionConsumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.
Mean Platelet Volume (MPV): New diagnostic indices for co-morbidity of Tuberculosis and Diabetes Mellitus
Authors: Qin Yongwei , qu shengyan , xu feifan , Wang lin
Published: January 2020

Background: Tuberculosis (TB) and type 2 diabetes mellitus (DM) are global health diseases with high morbidity and lethality . Few studies had focus on the platelet indices in TB-DM co-morbidity patients. The objective of this work was to analyze the platelet indices in TB, DM and TB+DM to assess the predictive value of platelet index for the risk of these diseases. Methods: In total, 246 patients were distribute d into three groups (113 TB, 59 DM and 74 TB+DM) admitted in our hospital along with 133 healthy controls (HC). Platelet indices namely platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW) were compared among the four groups and explored the relationship with inflammatory markers by using statistical software. Results: Our study discovered that MPV and PCT were significantly down-expressed in TB+DM patients (9.95±1.25fL, 0.20±0.05%, P <0.0001, P =0.0121, separately ) than those in DM individuals (10.92±1.17fL, 0.22±0.04%). Moreover, on comparison of TB (9.42±1.01fL), the changes of MPV were significantly higher in TB+DM patients (9.95±1.25fL, P =0.0041). No differences were found in PLT and PDW among the four groups ( P >0.05). The sensitivity and specificity of MPV in differential diagnosis of DM patients vs TB+DM patients were defined as 64.9% and 66.1% ( P <0.0001), as well as 60.8% and 66.4% of MPV in differ from TB patients and TB+DM patients ( P =0.003). MPV improved the diagnosis sensitivity when combined with clinical golden parameters as fasting blood glucose in DM and mycobacterium tuberculosis culture result in TB. In addition, the sensitivity and specificity of PCT in the differential diagnosis of DM patients vs TB+DM patients were defined as 69.5% and 59.4% ( P =0.008). PCT improved the diagnosis sensitivity when combined with fasting blood glucose in DM (72.9% vs 64.9%, P =0.004). In addition, MPV was connected with CRP and ESR in the TB+DM patients rather than PCT. Conclusions: Our research shows that MPV and PCT might be the clinical laboratory markers distinguished TB+DM patients from TB or DM individuals, thus providing support for earlier clinical diagnosis, prevention, and therapy.
Meta-analysis of serum and/or plasma D-dimer in the diagnosis of periprosthetic joint infection
Authors: Li Cheng , Margaryan Donara , Ojeda-Thies Cristina , Perka Carsten , Trampuz Andrej
Published: January 2020

Background The purpose of this meta-analysis was to evaluate the diagnostic value of D-dimer in detecting periprosthetic joint infection (PJI). Methods A systematic search and screen of relevant studies was performed in the PubMed, Web of Science and Embase databases using the following medical subject headings (MeSH) or keywords: “arthroplasty or joint prosthesis or joint replacement or periprosthetic joint or prosthetic joint”, “infection or infectious or infected”, and “D-dimer or serum D-dimer or plasma D-dimer or fibrin degradation products”. Then, the data were analysed and processed by Meta-Disc software. Results A total of 7 studies with 1285 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.75 (95% confidence interval [CI]: 0.70 to 0.79), 0.69 (95% CI: 0.66 to 0.72), 3.01 (95% CI: 1.84 to 4.93), 0.32 (95% CI: 0.19 to 0.53) and 10.20 (95% CI: 3.63 to 28.64), respectively. Subgroup analyses showed that use of serum D-dimer had better sensitivity and specificity than plasma D-dimer for the diagnosis of PJI (0.86, 0.84 vs. 0.67, 0.60, respectively). Conclusion Serum D-dimer had a better diagnostic value than plasma D-dimer for the diagnosis of PJI.
El Niño Southern Oscillation as an early warning tool for dengue outbreak in India
Authors: Pramanik Malay K. , Singh Poonam , Kumar Gaurav , Ojha Vijay Prakash , Dhiman Ramesh C.
Published: January 2020

Background Dengue is rapidly expanding climate-sensitive mosquito-borne disease worldwide. Outbreaks of dengue occur in various parts of India as well but there is no tool to provide early warning. The current study was, therefore, undertaken to find out the link between El Niño, precipitation, and dengue cases, which could help in early preparedness for control of dengue.Methods Data on Oceanic Niño Index was extracted from CPC-IRI (USA) while the data on monthly rainfall was procured from India Meteorological Department. Data on annual dengue cases was taken from the website of National Vector Borne Disease Control Programme (NVBDCP). Correlation analysis was used to analyse the relationship between seasonal +ONI, ‘rainfall index’ and ‘dengue case index’ based on past 20 years state-level data. The ‘dengue case index’ representing ‘relative deviation from mean’ was correlated to the 3 months average Oceanic Niño Index (ONI). The computed r values of ‘dengue case index’ and ‘+ONI’ were further interpreted using GIS software to generate spatial correlation map. The short-term (1 year) prediction of dengue probability map has been prepared based on phase-wise (El Niño, La Niña, and Neutral) 20 years averaged ONI.Results A high correlation between +ONI and dengue incidence was found, particularly in the states of Arunachal Pradesh, Chhattisgarh, Haryana, Uttarakhand, Andaman and Nicobar Islands, Delhi, Daman and Diu. On the other hand, the states like Assam, Himachal Pradesh, Meghalaya, Manipur, Mizoram, Jammu & Kashmir, Uttar Pradesh, Orissa, and Andhra Pradesh shown negative correlation between summer El Niño and dengue incidence.Conclusion The generated map signifies the spatial correlation between +ONI and ‘dengue case index’, indicating positive correlation in the central part, while negative correlation in some coastal, northern, and north-eastern part of India. For improvement of results, a study at micro-scale (district level) month-wise association with Indian Ocean Dipole and local weather variables is desirable for better exploration of dengue outbreaks in the states with ‘no association’. The findings offer reliable tool for national programme for early preparedness for undertaking intervention measures on the basis of the forecast of El Niño Southern Oscillation (ENSO).
An investigation of an anthrax outbreak in Makoni District Ward 22 and 23 in Zimbabwe
Authors: Makurumidze Richard , Tafara Gombe Notion , Tapuwa Magure , Tshimanga Mufuta
Published: January 2020

Background : The first official clinical case of human anthrax case was made at Makoni District Medical Office on the 19 th of December 2013. This followed cattle deaths which were confirmed in the laboratory to be due to anthrax. We report the clinical characteristics, distribution of anthrax cases (place and time), risk factors for contracting the disease, environmental assessment, district preparedness and response and outbreak prevention and control measures. Methods: We conducted an outbreak investigation with the design of a 1:1 unmatched case-control study. Data were collected using a structured questionnaire. Environmental assessment, district preparedness and response and outbreak prevention and control measures were assessed using checklists through observations and key informant interviews. Data were analyzed using Stata-16. Bivariate analysis was performed to identify risk factors for contracting anthrax. Results: Thirty-seven cases (37) and 37 controls were interviewed. All the cases had cutaneous anthrax with commonest site of eschar being the hand (43%). Most of the cases (89%) were managed according to national guidelines. Eating meat from a from a cattle slaughtered due unknown illness or died alone [OR = 7.00 , 95%CI(2.06-23.82], skinning [OR = 5.04, 95%CI(1.77-14.36)], cutting meat [OR = 5.32, 95%CI(1.91-14.77)], cooking meat [OR = 3.42, 95%CI(1.32-8.91.)], source of from other villagers [vs butchery, OR = 14.85, 95%CI(2.79-79.06)], cuts during cutting meat or skinning cattle [OR = 3.50, 95% CI(1.18-10.51)], belonging to a religion which permits eating meat from a from a cattle slaughtered due unknown illness or died alone [OR = 6.29, 95%CI(1.85-21.39)] were associated with contracting anthrax. Having heard of anthrax before was protective against contracting anthrax [OR = 0.35, 95%CI (0.13-0.93)]. The district was ill-equipped and delay to respond to the outbreak. Conclusion: The anthrax outbreak resulted from contact with and consumption of infected cattle meat. The district delayed and was not prepared to control the outbreak. However, the outbreak was controlled through cattle vaccination; health education and awareness campaigns. The district should strengthen its emergence preparedness and response capacity, revive zoonotic committees, conduct awareness campaign during the high-risk period and improve the surveillance of anthrax during high risk periods.
The effect of multimorbidity patterns, and the impact of comorbid anxiety and depression, on primary health service use: the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study
Authors: Ng Shu Kay , Martin Sean A , Adams Robert J , O'Loughlin Peter , Wittert Gary A
Published: January 2020

Background: Multimorbidity has been identified as a serious challenge on global health system, closely associated with lower quality of life, poorer health outcomes, and higher utilisation of health services. However, there are major gaps in our knowledge around multimorbidity, especially its effect on primary care services and the burden of comorbid mental health conditions on multimorbidity patterns. This study sought to determine patterns of multimorbidity and quantify their impact on use of primary health services in the presence and absence of anxiety and depression among a cohort of urban community-dwelling men. Methods: This was a prospective cohort study with Australian population. The study population consisted of 2,039 men aged ≥40, who were enrolled either in the Florey Adelaide Male Ageing Study (FAMAS) Stage 2 between 2007-2010 or in the North-West Adelaide Health Study (NWAHS) Stage 3 between 2008-2010. Data have been collected on the prevalence of 8 chronic conditions and linked Medicare data about individual health service utilization information on annual GP visits. Multinomial logistic regression was adopted to quantify the impact of anxiety and depression on the frequencies of GP visits, with adjustment for participant’s demographic and lifestyle characteristics. Results: Obesity and cardiovascular disease (CVD) were associated with the highest number of comorbid conditions. Two non-random multimorbidity “clusters” emerged: (CVD, Obesity, Diabetes) and (CVD, Obesity, Osteoarthritis). Participants with conditions comorbid with CVD were more likely to have 10 or more annual GP visits, compared to multimorbidity involving other conditions. Comparing to participants without CVD, the presence of CVD increased the chance of having 10 or more annual GP visits (adjusted risk ratio: 3.7; 95% CI: 2.8-4.8). When CVD was comorbid with anxiety and depression having 10 or more annual GP visits was more common (adjusted risk ratio: 1.8; 95% CI: 1.2-2.5). Conclusions: In Australian, community-dwelling men, multimorbidity is associated with a high use of GP services; especially for multimorbidity that includes CVD with comorbid anxiety and depression. Multimorbidity patterns involving CVD should be considered in developing clinical trials to better inform medical decision making and care for patients with CVD and comorbid conditions.
Hypophosphataemia after ferric carboxymaltose is unrelated to symptoms, intestinal inflammation or vitamin D status
Authors: Fang Wendy , Kenny Rachel , Rizvi Qurat-ul-Ain , McMahon Lawrence P. , Garg Mayur
Published: January 2020

Background and aims Intravenous iron replacement is recommended for iron-deficient patients with inflammatory bowel disease (IBD), but may be associated with hypophosphataemia, predisposing to osteomalacia and fractures. This study aimed to evaluate the incidence and risk factors for hypophosphataemia following intravenous ferric carboxymaltose (FCM) in patients with IBD. Methods This prospective observational study of patients with and without IBD evaluated serum phosphate for 28 days following intravenous FCM, and assessed associations with symptoms, markers of inflammation and vitamin D status. Results 24 patients with IBD (11 with Crohn’s disease [CD], 13 with ulcerative colitis [UC], mean age 45 years [range 19-90], 7 female), and 20 patients without IBD (mean age 56 [22-88]y, 11 female), were included. Overall, serum phosphate declined by a mean of 36% at Day 7, with a mean fall of 42% (SD 19%) at some time point over 28 days (p<0.001). Twenty-four of 44 (55%) patients developed moderate to severe hypophosphataemia (serum phosphate <0.6 mmol/L). No differences between patients with and without IBD were seen, but patients with CD had greater decline in phosphate than those with UC. There was no association between hypophosphataemia and symptomatic adverse events, faecal calprotectin, C-reactive protein, albumin, platelet count, 25(OH) vitamin D, or 1,25(di-OH) vitamin D. Intact fibroblast growth factor levels increased by mean 84% (p=0.004), within 2 days of infusion. Serum phosphate <1.05mmol/L on Day 2 predicted susceptibility to moderate-severe hypophosphataemia (OR 7.0). Conclusions Hypophosphataemia following FCM is common, unrelated to symptomatic adverse events, baseline intestinal or systemic inflammation, or vitamin D status.
Association between NAFLD and risk of prevalent chronic kidney disease: Why there is a difference between East and West?
Authors: Zhang Min , Lin Su , Wang Mingfang , Huang Jiaofeng , Liu Shiying , Wu Sumei , Zhang Haoyang , Wu Zimu , Liu Wenyue , Zhang Dongchu , Hao Chuanming , Zhu Yueyong , Zheng Minghua , Wang Xiaozhong
Published: January 2020

Background: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. Methods: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m 2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. Results: A total of 60965 participants were analyzed, including 11844 from the US and 51229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p<0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. Conclusion: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.
Case report on a swift shift in uropathogen from Shigella Flexneri to Escherichia Coli: A thin line between bacterial persistence and reinfection
Authors: Tufon Kukwah Anthony , Yolande Fokam Djike Puepi , Kouanou Youmbi Sylvain , Meriki Henry Dilonga
Published: January 2020

Background Urinary tract infections (UTI) are mostly caused by bacteria. Urine cultures are usually a definitive measure to select the appropriate antibiotics for the elimination of a uropathogen and recovery from the infection. However, the preferred antibiotics as determined by urine culture and sensitivity may still not eliminate the infection and would require further examination to ascertain the cause of treatment failure which could be unresolved bacteriuria, bacterial persistence, immediate reinfection with a different uropathogen or misdiagnosis. Case presentation A 2-year-old female was admitted in the Regional hospital of Buea following persistent fever. An auto medication with amoxicillin was reported. Urinalysis was done on the first day and the sediment of the cloudy urine revealed many bacteria and few pus cells. Ceftriaxone was prescribed as empirical treatment and a request for urine and blood culture was made. Three days after admission, the temperature and CRP were 39.0°c and 96 mg/l respectively. The urine culture results (>10 5 CFU/ml of Shigella flexneri sensitive to ofloxacin) were presented to the doctor on the 4 th day of admission. Patient was put on ofloxacin. Three days after, the temperature (38.5°c) and CRP (24mg/l) were still elevated. The blood culture result came out negative. A second urine culture was requested which came back positive (>10 5 CFU/ml of Escherichia coli resistant to second generation fluoroquinolones and susceptible to meropenem and amikacin). Ofloxacin was discontinued and the patient put on meropenem and amikacin. The third urine culture recorded no significant growth after 48 hours of incubation. The patient was discharged looking healthy once more with a normal body temperature. Conclusion Antibiotics tailored towards the elimination of a particular bacterial species may as well provide a favorable environment for other bacterial species that are resistant to it in the course of treating a UTI episode. This can imply overall treatment failure and may first of all require a second urine culture for confirmation rather than considering the possibilities of a misdiagnosis.
Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex
Authors: Koga Kohei , Yamada Akihiro , Song Qian , Li Xu-Hui , Chen Qi-Yu , Liu Ren-Hao , Ge Jun , Zhan Cheng , Furue Hidemasa , Zhuo Min , Chen Tao
Published: January 2020

Anterior cingulate cortex (ACC) plays important roles in sensory perception including pain and itch. Neurons in the ACC receive various neuromodulatory inputs from subcortical structures, including locus coeruleus noradrenaline (LC-NA) neurons. Few studies have been reported about synaptic and behavioral functions of LC-NA projections to the ACC. Using viral-genetic method (AAV-DIO-eYFP) on DBH-cre mice, we found that LC-NA formed synaptic connections to ACC pyramidal cells but not interneurons. This is further supported by the electron microscopic study showing NAergic fibers contact the presynaptic inputs and post-synaptic areas of the pyramidal cells. NA application produced both pre- and post-synaptic potentiation effects in ACC excitatory transmission in vivo and in vitro . Activation of LC-NA projection to the ACC by optogenetic method produced enhancement of excitatory transmission in vitro and induced scratching and behavioral sensitization for mechanical stimulation. Our results demonstrate that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.
Stress Ulcer Prophylaxis versus Placebo - a Blinded Randomized Control Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants with Congenital Heart Disease (SUPPRESS-CHD)
Authors: Mills Kimberly I. , Albert Ben D. , Bechard Lori J. , Duggan Christopher P. , Kaza Aditya , Rakoff-Nahoum Seth , Vlamakis Hera , Sleeper Lynn A. , Newburger Jane W. , Priebe Gregory P. , Mehta Nilesh
Published: January 2020

Background: Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit. Methods: A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 hours. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age <30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study. Discussion: Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of witholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population. Trial registration: NCT03667703; submitted September 12, 2018