bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent BMI and Early-Onset Type 2 Diabetes Among Ethiopian Immigrants and Their Descendants: A Nationwide Study.
Authors: Simchoni Maya , Hamiel Uri , Pinhas-Hamiel Orit , Zucker Inbar , Cukierman-Yaffe Tali , Lutski Miri , Derazne Estela , Beer Zivan , Behar Doron , Keinan-Boker Lital , Mosenzon Ofri , Tzur Dorit , Afek Arnon , Tirosh Amir , Raz Itamar , Twig Gilad
Published: August 2020

Background: We assessed in a nationwide cohort the association between adolescent BMI and early-onset (<40 years) type 2 diabetes among Israelis of Ethiopian origin.Methods: Normoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. Results: 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI.Conclusions: Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.
Interplay between Male Testosterone Levels and the Risk for Subsequent Invasive Respiratory Assistance among COVID-19 Patients at Hospital Admission
Authors: Salciccia Stefano , Gentile Vincenzo , Mastroianni Claudio M. , Pasculli Patrizia , Lascio Giovanni Di , Ciardi Maria Rosa , Sperduti Isabella , Maggi Martina , De Berardinis Ettore , Giudice Francesco Del , Eisenberg Michael L. , Sciarra Alessandro
Published: August 2020

Purpose: to evaluate the prognostic value of male serum total testosterone (TT) levels among COVID-19 patients requiring an invasive respiratory assistance at hospital admission.Methods: 29 men with full haemato-chemical blood sample panel at hospital admission for COVID-19 related respiratory syndrome were retrospectively reviewed. Multivariable logistic regression model was implemented to test the predictive role of TT levels and subsequent risk for invasive oxygenation after adjusting for age, comorbidities and life-style related confounders. Results: higher serum TT levels (ng/mL) were found independently associated with a lower odd of invasive oxygenation (Odds ratio [OR]: 0.43, 95%CI: 0.23-0.85; p=0.016). Significant negative correlation was found between TT and C-reactive protein, pH, Interleukine-6 and D-Dimer while positive correlation was established among TT levels and Monocytes (x109/L).Conclusion: low testosterone levels may play a relevant role in the natural history of COVID-19 respiratory syndrome by making a patient with comorbidities and higher baseline levels of pro-inflammatory cytokines more susceptible to a potentially fatal clinical course at the moment of infection progression.
Short-term effects of ambient temperature and relative humidity on the risk of COVID-19 and SARS in Guangzhou, China: A time-series analysis
Authors: Wang Hui , Chen Chun , Lin Qiaoxuan , Li Tiegang
Published: August 2020

Coronavirus infection has exerted a severe disease burden on the world, especially the newly emerged SARS-CoV-2 that has caused worldwide pandemic. It is possible meteorological factors can influence the transmission of coronavirus. The aim of this study was to evaluate the effect of meteorological factors on COVID-19 and SARS, and to provide evidence for disease control and prevention. Data of COVID-19 and SARS cases and daily mean temperature, relative humidity and other meteorological factors in Guangzhou in 2003 and 2020 were collected. Using a distributed lag non-linear model approach, we assessed the relationship between ambient temperature, relative humidity and the risks of COVID-19 and SARS. The numbers of cases for COVID-19 and SARS during the study period were 347 and 1072, respectively. There was a dome-shaped relation between mean temperature and COVID-19, with a threshold of 14.50°C (RR=1.48, 95%CI: 1.01, 2.16) and the optimal range was 12.40-16.40°C. A similar association was found between mean temperature and SARS occurrence, with a threshold of 18.40°C (RR=1.02, 95%CI: 1.00, 1.04), and the optimal range was 15.30-19.30°C. Besides, there were non-linear negative relationships between both RH and COVID-19, SARS. In addition, the largest overall effect of RH on COVID-19 and SARS were obtained at 52% and 45%, yielding relative risk of 7.47 (95%CI: 1.66, 33.55) and 47.56 (95%CI: 11.49, 196.95), respectively. The optimal ranges were below 77.00% and below 82.70%, respectively. Meteorological parameters should be taken into consideration while developing early warning systems and risk strategies for controlling and preventing coronavirus infection.
The Preventive Efficacy of Vitamin B Supplement on the Cognitive Decline of Elderly Adults: a Systematic Review and Meta-analysis
Authors: li shufeng , Guo Yuchen , Men Jie , Fu Hanlin , Xu Ting
Published: August 2020

Background
The irreversibility of cognitive impairment of Alzheimer’s disease (AD) prompts that preventing or delaying the onset of AD should be a public health priority. Vitamin B supplement can lower the serum homocysteine (Hcy) level, but whether it can prevent cognitive decline or not remains unclear. We aimed to evaluate the preventive efficacy of vitamin B supplement on the cognitive decline of elderly adults.
Methods
We searched PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, Science Direct, PsycINFO from inception to December 1, 2019, and then updated the retrieved results on June 1, 2020. The randomized controlled trials (RCTs) which evaluated the efficacy of vitamin B in mild cognitive impairment (MCI) patients or elderly adults without cognitive impairment were selected. Standardized mean difference (SMD) or mean difference (MD) as well as their 95% confidence interval (CI) were calculated by performing random effects models or fixed effects models.
Results
A total of 21 RCTs involving 7571 participants were included for meta-analysis. The forest plots showed that there is significant effect in global cognitive function (15 RCTs, SMD: 0.36; 95% CI: 0.18 to 0.54, P < 0.01) and Hcy (11 RCTs, MD: -4.59; 95%CI: -5.51 to -3.67, P < 0.01), but there is no effect in information processing speed (10 RCTs, SMD: 0.06; 95% CI: -0.12 to 0.25, P = 0.49), episodic memory (15 RCTs, SMD: 0.10; 95% CI: -0.04 to 0.25, P = 0.16), executive function (11 RCTs, SMD: -0.21; 95% CI: -0.49 to 0.06, P = 0.13). The value of effect size and heterogeneity did not vary apparently when excluding the low-quality studies, so we could believe that the results of meta-analysis were robust.
Conclusions
Vitamin B supplement might delay or maintain the cognitive decline of elderly adults. We can recommend that the vitamin B supplement should be considered as a preventive medication to MCI patients or elderly adults without cognitive impairment. More well-designed RCTs with large sample sizes were required to clarify the preventive efficacy in the future.
Predictors for HIV testing among Chinese workers in infrastructure construction enterprises in Kenya
Authors: Zhou Wenjuan , Deng Wenyu , Luo Junfei , Bai Yin , He Zeyi , Wang Honghong
Published: August 2020

Background: There are more and more Chinese migrants in sub-Saharan Africa currently. Most of them engaged in infrastructure construction. Their risk of infection with high-incidence diseases in sub-Saharan Africa, such as the risk of HIV infection, is not researched among them by now. This study aimed to describe recent HIV test behaviour and related factors among those Chinese workers in Kenya.Methods: A cross-sectional survey was conducted among 110 male Chinese workers from six different Chinese infrastructure construction enterprises in Kenya. And a two-stage cluster random sampling method was used to select participants. We used a structured questionnaire that includes HIV testing behavior in the recent one year, demographic and socioeconomic characteristics, HIV-related knowledge and cognition, HIV-related perceptions and attitudes, utilization of HIV testing. Logistic regression was used to explore the predictors of recent HIV test behaviour among Chinese construction workers in Kenya.Result: Of the 110 participants, 30 (27.27%) were tested for HIV in the recent one year. All participants were male, and the majority were married (73.2%). The mean age was 37.49 years (SD=9.725; range: 23 to 63), and a considerable proportion refused to answer questions about transactional sexual behaviors (83.6%) in recent one year. Most were able to obtain HIV-related information (91.8%) and exposed to HIV related information in recent one year (68.2%), but only 47.6% had sufficient HIV knowledge. More than one-fifth of participants held positive attitudes toward paying for sex, and nearly one-fifth believed that selling sex was acceptable. Multiple logistic regression analysis indicated that participants who said they were acceptable to pay for sex (OR: 4.51; 95% CI: 1.18, 17.34) and exposed to HIV related information (OR: 3.82; 95% CI: 1.28, 11.41) in the recent one year were more likely to test for HIV in the past one year.Conclusion: Higher recent HIV test rates were associated with the open sexual attitude towards paying for sex and exposed to HIV related information in the recent one year among Chinese workers in Kenya. More specific attention about HIV should be offered to this unique population to increase the rate of HIV testing among them.
Clinical Values of two Novel Estrogen Receptor Signaling Targeted lncRNAs in Invasive ductal breast carcinoma
Authors: ilbeigi shahrzad , Farahani Mostafa Davood Abadi , Monjezi Mohammad Rafiee , Farahani Farahnaz , Daraei Abdolreza , Dastsooz Hassan , Moradi Sepide , Amirghofran Zahra , Mansoori Yaser , Tabei Seyed Mohammad Bgher
Published: August 2020

Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of new data regarding the molecular heterogeneity of invasive cancers is quickly emerging; far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in heterogeneity feature of the BC. In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues (ANCTs). And finally, bioinformatic evaluation has been done.The qPCR results showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P= 0.0085 and P= 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P= 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with age at menarche <14 compared to patients with age at menarche ≥14 (P= 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P= 0.047). And finally, using bioinformatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA Zinc Finger and BTB Domain Containing 10 (ZBTB10).Altogether, our findings suggest that these lncRNAs with potential oncogenic roles involved in pathogenesis of IDC with clinical significance, and thus, they may serve as novel markers for diagnosis and treatment of IDC.
Proficiencies of Military Medical Officers in Intubating Difficult Airways
Authors: Lim Jonathan Zhao Min , Chew Shi Hao , Chin Benjamin Zhao Bin , Siew Raymond Chern Hwee
Published: August 2020

Introduction This study shed light on the proficiency of military medical officers who had received between 2-3 years of post-graduate training, in the handling of the difficult airway in a trauma manikin simulator using direct and video laryngoscopes.Method133 doctors from the Singapore Armed Forces Medical Officer Cadet Course were assessed using high-fidelity simulator models with standardised difficult airways (simulator with tongue-swelling and cervical collar). They used the Macintosh direct laryngoscope (DL), King Vision channelled-blade laryngoscope (KVC), King Vision non-channelled blade laryngoscope (KVNC), and the McGrath (MG) laryngoscope on the same model in a randomised sequence. The intubation success rates and time to intubation were recorded and analysed for the study.ResultsThe medical officers had a 71.4% intubation success rate with the DL on the difficult airway trauma simulator model and the mean time to intubation of 40.1s. With the KVC, the success rate is 86.5% with mean intubation time of 40.4s. The KVNC produced 24.8% success rate, with mean time to intubation of 53.2s. The MG laryngoscope produced 85.0% success rate, with a mean time of intubation of 37.4s.ConclusionMilitary medical officers with 2-3 years of post-graduate training had a success rate of 71.4% success rate intubating a simulated difficult airway in a trauma setting using a DL. Success rates were improved with the use of KVC and the MG laryngoscope, but was worse with the KVNC.
Diminished Adherence of Biomphalaria Glabrata Embryonic Cell Line to Sporocysts of Schistosoma Mansoni Following Programmed Knockout of the Allograft Inflammatory Factor
Authors: Coelho Fernanda Sales , Rodpai Rutchanee , Miller Andre , Karinshak Shannon E , Mann Victoria H , Carvalho Omar dos Santos , Cladeira Roberta Lima , Mourao Marina de Moraes , Brindley Paul J , Ittiprasert Wannaporn
Published: August 2020

The development of the larval stage of Schistosoma mansoni in an intermediate host snail of the genus Biomphalaria is an obligatory component of the life cycle. Enhanced understanding of the mechanism(s) of host defense in the snail may hasten the development of tools that block transmission of schistosomiasis. The B. glabrata embryonic cell line, termed the Bge line, is a versatile resource for investigation of the snail-schistosome relationship. A key attribute of the Bge cell is the hemocyte-like phenotype, given the central role of the snail hemocyte in innate and cellular immunity. The allograft inflammatory factor 1, AIF, is evolutionarily conserved, typically is expressed in phagocytes and granular leukocytes, is a marker of macrophage activation in mammals and in invertebrates, and enhances cell proliferation and migration. AIF is highly expressed in strains of B. glabrata resistant S. mansoni infection in comparison with susceptible strains of the snail. We hypothesized that BgAIF may play a role in hemocyte proliferation, adhesion and/or migration after exposure of the snail to schistosomes. CRISPR/Cas gene knockout of the BgAIF gene in Bge cells was undertaken to investigate the hypothesis. Gene knockout manipulation induced gene-disrupting indels, frequently 1–2 bp insertions and/or 8–30 bp deletions, at the programmed target site; a range from 9 to 17% of BgAIF genes were mutated during 12 replicate experiments, and transcript levels for BgAIF were significantly reduced by up to 73% (range, 26 to 73%, mean 49.5 ± 20.2% S.D, n = 12) when monitored for up to nine days following the gene-editing manipulation. The adherence to sporocyst of BgAIF gene-edited (ΔBgAIF) Bge cells was significantly diminished in comparison to wild type cells, even though cell morphology did not differ between ΔBgAIF treatment and control groups of Bge cells. A Bge cell adherence index (CAI) to individual sporocysts was observed at 2.66 ± 0.10 for control and 2.30 ± 0.22 in ΔBgAIF cells (P < 0.05), revealing that ΔBgAIF cells were significantly less adherent than wild type Bge cells to primary sporocysts. The findings supported the hypothesis that BgAIF plays a role in the adherence of B. glabrata hemocytes to sporocysts during schistosome infection.
Epidemiology, Clinical Characteristics, and Prognostic Factors of Atopic Children Hospitalised for Adenovirus Infection: A Single Institutional Study in Shenyang, China
Authors: Li Miao , Han Xiao-Hua , Liu Li-Yun , Yao Hui-Sheng , Yi Li-Li
Published: August 2020

Background: Atopy may be associated with the severity of disease and poor prognosis after adenovirus (Adv) infection in children. Our aim was to observe the clinical characteristics and pulmonary radiological changes in atopic children with Adv pneumonia in China.Methods: Children hospitalised for Adv pneumonia from June 2018 to Dec 2019 were analysed. All children were divided into three groups: atopic with Adv, non-atopic with Adv, and atopic without Adv infection. Each group was further divided into mild or severe infection groups according to disease severity. Standard treatment was initiated after admission and regular follow-up evaluations were conducted at 1 month after discharge. Baseline and clinical characteristics, and pulmonary radiological changes of atopic and non-atopic children were collected. Risk factors associated with small airway diseases in Adv pneumonia patients were analyzed.Results: Compared with non-atopic children with Adv infection, the cases of eosinophilic granulocyte count were significantly higher in atopic children than non-atopic children (P<0.05). Among children with mild and severe infection, the number of patients with wheezing and small airway disease as observed by high-resolution computed tomography (HRCT) was significantly higher in atopic children than non-atopic children (P<0.05). Furthermore, coughing was more severe in atopic children than non-atopic children (P<0.05). A family history of asthma (OR 2.1 [95% CI 1.8–3.0]), personal history of asthma (OR 2.7 [95% CI 2.1–3.1]), atopy (OR 2.1 [95% CI 1.8–3.2]), severe infection (OR 1.9 [95% CI 1.0–2.7]), and Adv infection (OR 1.4, [95% CI 0.9–2.0]) were independent factors associated with the development of small airway disease, both after admission and a month after discharge. Conclusions: Atopic children with Adv infection experience more severe coughing during hospitalisation and are prone to wheezing and small airway disease on the HRCT. Family and personal history of asthma, atopy, severe infection, and Adv infection were independent factors associated with the development of small airway disease on the chest HRCT scan.
Daidzein Supplementation Enhances Embryos Survival by Improving Hormones, Antioxidant Capacity, and Metabolic Profiles of Amniotic Fluid in Sows
Authors: Xie Kunhong , Li Yan , Chen Daiwen , Yu Bing , Luo Yuheng , Mao Xiangbing , Huang Zhiqing , Yu Jie , Luo Junqiu , Zheng Ping , Yan Hui , He Jun
Published: August 2020

Background: Daidzein (DAI) is a kind of natural isoflavonic phytoestrogen with estrogenic activity. However, little is known about its influence on early fetal growth in mammalian animals. In this study, we investigated the effects dietary DAI supplementation on early fetal development in sows. To explore the potential mechanisms, the metabolic profiles of amniotic ﬂuid collected at 35 days of gestation (dg) was determined by using metabolomics. Results: Results show that DAI supplementation at a dose of 200 mg/kg significantly enhanced the number of viable embryos at the early gestation stage (P < 0.05). DAI significantly elevated the concentrations of estrogen (E) and insulin-like growth factor-I (IGF-I) in the amniotic fluid (P < 0.05). Moreover, DAI tended to increase the concentration of progesterone, but decrease the concentration of tumor necrosis factor α (TNF-α) in the amniotic ﬂuid (0.05<P<0.10). Interestingly, the activity of glutathione peroxidase (GSH-Px) was higher in the DAI group than in the CON group (P < 0.05). An 1H NMR-based metabolomics analysis identified a number of metabolites in the amniotic fluid, and some critical metabolites such as arginine, creatine, and citrate were found to be significantly elevated upon DAI supplementation (P < 0.05). Importantly, the metabolic pathways involved in arginine and proline metabolisms were found to be significantly affected by DAI. Conclusions: These findings suggested that dietary DAI supplementation may improve embryos survival by improving hormones, antioxidant capacity, and metabolic profiles in the maternal amniotic ﬂuid.
A Novel ALK Fusion Gene (NSF-ALK) Identified in a Patient With Recurrent Spindle Cell Sarcoma Respond to Crizotinib: A Case Report
Authors: Jin Shuiling , Weng Lanling , Zhong Qian , Cui Chi , Tang Wenxue , Zong Hong , Ma Wang , Li Zhi
Published: August 2020

Background: Spindle cell sarcoma (SCS) is a rare malignant tumor which relapses quickly and has poor prognosis.Case presentation: We report a case of SCS deriving from the left side of chestpossessed a novel unreported ALK fusion gene named NSF-ALK found by Next Generation Sequencing (NGS) technology. Despite receiving three surgical resections, local recurrence occurred rapidly and distant brain metastasis was eventually observed in this patient. The subsequent administration of crizotinib1, an oral anaplastic lymphoma kinase inhibitor, resulted in dramatic tumor shrinkage and the patient entered a remission period that has been ongoing for more than 10 months.Conclusions: In summary, this study is the first to describe a novel NSF-ALK fusion in spindle cell sarcoma which has promising efficacy by crizotinib treatment. More importantly, the case also shows that next generation sequencing provids more information of mutation to guide treatment in clinical decisions by presenting molecular changes.
Value of Serum Macrophage Migration Inhibitory Factor (Mif), Adiponectin, and Other Adipokines as Markers of Proteinuria and Renal Dysfunctionin Lupus Nephritis: A Cross-sectional Study.
Authors: Gamez-Nava Jorge Ivan , Diaz-Rizo Valeria , Perez-Guerrero Edsaul Emilio , Muñoz-Valle Jose Francisco , Saldaña-Cruz Ana Miriam , Fajardo-Robledo Nicte Selene , Jacobo-Cuevas Heriberto , Nava-Valdivia Cesar Arturo , Alcaraz-Lopez Miriam Fabiola , Trujillo Xochitl , Huerta Miguel , Cardona-Muñoz Ernesto German , Gonzalez-Lopez Laura
Published: August 2020

BackgroundTo date, there is controverted the association between serum macrophage migration inhibitory factor (MIF) and serum adipokines with Lupus Nephrites.ObjectiveTo investigate the value of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritisMethodsDesign: cross-sectional. We included 196 Systemic Lupus Erythematosus (SLE) and 52 controls (HC). In SLE, disease activity was assessed by SLEDAI. Renal involvement was investigated by Renal-SLEDAI: a) Renal-SLE involvement (n=43) and b) Non-Renal-SLE (n=153). MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed correlations of MIF, adipokines and renal involvement parameters [proteinuria (g/day), serum creatinine and other]. Multivariable linear regression was used for investigating factors associated with the intensity of proteinuria. ResultsSLE patients had higher MIF (p=0.02) and adiponectin levels (p<0.001) than HC. In renal-SLE involvement there were higher adiponectin levels (19.0 vs 13.3 µg/mL, p=0.002) and resistin levels (10.7 vs 8.9 ng/mL, p=0.01), compared with non-Renal-SLE. Proteinuria correlated with high adiponectin (rs=0.19, p<0.009) and resistin levels (rs=26, p<0.001). MIF (rs=0.27, p=0.04) and resistin (rs= 0.18; p=0.02) correlated with increased creatinine. High Renal activity correlated with adiponectin (rs=0.21, p=0.004). Multiple linear regression identified that elevated adiponectin (p=0.02), younger age (p=0.04) and low MIF (p=0.02) were associated with intensity of proteinuria. Low MIF and high adiponectin levels have interaction for intensity of proteinuria (R2=0.41). ConclusionsHigh adiponectin combined with low MIF concentrations interacts for increase proteinuria in renal-SLE, and MIF and resistin levels are associated with renal dysfunction. These findings highlight the relevance of including the assessment of MIF and adipokines as clinical markers in the evaluation of LN.
Multi-tiered External Facilitation: The Role of Feedback Loops and Tailored Interventions in Supporting Change in a Stepped-Wedge Implementation Trial
Authors: Penney Lauren S , Damush Teresa M. , Rattray Nicholas A. , Miech Edward J. , Baird Sean A. , Homoya Barbara J. , Myers Laura J. , Bravata Dawn M.
Published: August 2020

Background Facilitation is a complex, relational implementation strategy that guides change processes. Facilitators engage in multiple activities and tailor efforts to local contexts. The contextual factors that prompt facilitators to tailor activities have not been well-described. Methods We conducted a mixed methods evaluation of a trial to improve the quality of transient ischemic attack care. Six sites in the Veterans Health Administration received external facilitation (EF) before and during a 1-year active implementation period. We examined how EF was employed, perceived, and activated. Data analysis included prospective logs of facilitator correspondence with sites (160 site-directed episodes), stakeholder interviews (n=78), and collaborative call debriefs (n=22). Logs were descriptively analyzed across facilitators, sites, time periods, and activity types. Interview transcripts were coded for content related to EF and themes were identified. Debriefs were reviewed to identify instances of and utilization of EF during site critical junctures. Results Multi-tiered EF was supported by two groups (site-facing quality improvement [QI] facilitators and the implementation support team) that were connected by feedback loops. Each site received an average of 24 episodes of site-directed EF; most of the EF was delivered by the QI nurse. For each site, site-directed EF frequently involved networking (45%), preparation and planning (44%), process monitoring (44%), and/or education (36%). EF less commonly involved audit and feedback (20%), brainstorming solutions (16%), and/or stakeholder engagement (5%). However, site-directed EF varied widely across sites and time periods in terms of these facilitation types. Site participants recognized the responsiveness of the QI nurse, and valued her problem-solving, feedback, and accountability support. External facilitators used monitoring and dialogue to intervene by facilitating redirection during challenging periods of uncertainty about project direction and feasibility for sites. External facilitators, in collaboration with the implementation support team, successfully used strategies tailored to diverse local contexts, including networking, providing data, and brainstorming solutions. Conclusions Multi-tiered facilitation capitalizing on feedback loops allowed for tailored, site-directed facilitation that aligned with the types of supports that local participants valued. Critical juncture cases illustrate the complexity of EF and the need to often try multiple strategies in combination to facilitate implementation progress.
Nanoparticles in 472 Human Cerebrospinal Fluid: Changes in Extracellular Vesicle Concentration and miR-21 Expression as a Biomarker for Leptomeningeal metastasis
Authors: Lee Kyue-Yim , Im Ji Hye , Lin Weiwei , Gwak Ho-Shin , Kim Jong Heon , Yoo Byong Chul , Kim Tae Hoon , Park Jong Bae , Park Hyeon Jin , Kim Ho-Jin , Kwon Ji-Woong , Shin Sang Hoon , Yoo Heon , Lee Changjin
Published: August 2020

Background: Leptomeningeal metastasis (LM) has a poor prognosis and is difficult to diagnose and predict the response of treatment. In this study, we suggest that the monitoring of changes in the concentration of extracellular vesicles in cerebrospinal fluid could help to diagnose or predict outcomes for LM.Methods: We measured nanoparticles in 472 human CSF from controls and patients including LM with both Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) after two-step centrifugations.Results: NTA revealed nanoparticles distributed at a median 193 nm in size, and 1.74 × 108 /ml in concentration, and those were significantly higher in LM compared to other groups (211 nm vs. 188 nm, p < 0.001 and 2.80 × 108 /ml vs. 1.49 × 108 /ml, p < 0.01, respectively). Changes in NTA-measured nanoparticles (EV from here) concentration after intra-CSF chemotherapy were further examined in non-small cell lung cancer patients with LM (n=33). Overall survival was longer for patients with increased EV than the others (442 vs. 165 days, p < 0.001). Exosome surface markers (CD9/CD63/CD81) significantly decreased in the EV-decreased group (ratio 0.64, p<0.0001). MicroRNA-21 expression decreased in this favorable prognostic group, whereas increased in the EV-decreased group (p = 0.003). Conclusions: The elevated concentration of extracellular vesicles in cerebrospinal fluid in patients with LM can be a diagnostic marker. Moreover, EV changes combined with microRNA-21 might be a biomarker for monitoring intracranial chemotherapy of LM.
Association between plasma complement factor H concentration and clinical outcomes in patients with sepsis
Authors: Shimizu Junji , Fujino Kazunori , Sawai Toshihiro , Tsujita Yasuyuki , Tabata Takahisa , Eguchi Yutaka
Published: August 2020

Background The complement system is important for defending against pathogens; however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway.This study aimed to investigate the association between plasma CFH levels on admission to the ICU and 90-day mortality and organ dysfunction, in patients with sepsis. Methods This is a single-center prospective observational study conducted from July 2016 to March 2019. Logistic regression analysis and correlation analysis were performed to assess the relationship between the plasma CFH on admission to the ICU and 90-day mortality, and organ dysfunction. Results This analysis included 62 patients. The plasma CFH levels were significantly lower in 90 day non survivors than those in survivors (70.0 μg/ml [interquartile range (IQR) 51.2 - 97.6] vs 104.8 μg/ml [IQR 66.8 - 124.2] , P=0.006) . The plasma CFH levels were associated with 90 day mortality (OR 0.977 95% CI 0.957 – 0.994, p = 0.01). Correlation analysis showed that the plasma CFH levels were negatively correlated with the Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score 2 (SAPS 2) (r= -0.35, P=0.005; r=-0.28, P=0.026; r=-0.30, P=0.019, respectively). Regarding the SOFA scores for each organ, those for the coagulation and neurological components were negatively correlated with the CFH concentration (r=-0.33, P=0.010; r=-0.25, P=0.046, respectively).Conclusion Lower plasma levels of CFH were associated with sepsis severity and mortality and were correlated with the coagulation and neurological components of the SOFA score in patients with sepsis on admission to the ICU.
A key role of gut microbiota-vagus nerve axis and gut microbiota-spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration
Authors: Zhang Yujing , Xie Bing , Lv Zheng , Qi Hong , Zhang Jiancheng , Yuan Shiying
Published: August 2020

Background: Sleep deprivation (SD) is shown to be correlated with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. Methods: In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) followed by 3 consecutive days of SD. The subdiaphragmatic vagotomy (SDV) was performed 2 weeks before LPS injection. The pseudo germ-free mouse model was created by administering antibiotics for 14 consecutive days, and then fecal microbiota transplant (FMT) was performed by gavaging supernatant from fecal suspension of septic mice with or without SD into pseudo germ-free mice with or without SDV or splenectomy. Splenectomy was performed 14 days prior to antibiotics administration.Results: We found that SD after LPS administration increased the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma leve, increased spleen weight, and promoted pathological injury and IL-6 expression in lung, liver and kidney. Post-septic sleep deprivation had no effects on the diversity of gut microbiota. However, the relative abundance of Proteobacteria and its subgroups were increased in septic mice received SD. Pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors do. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, Splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Conclusions: Taken together, our results suggest that gut microbiota-vagus nerve axis and gut microbiota-spleen axis could play key roles in modulating systemic inflammation induced by SD after LPS administration.
Prevalence, Risk Factors and Outcomes of Platelet Transfusion Refractoriness in Critically Ill Patients: A Retrospective Cohort Study
Authors: Arabi Saeed , Almahayni Abdullah O , Alomair Abdulrahman , Masuadi Emad M , Damlaj Moussab , Al-Dorzi Hasan
Published: August 2020

Background: Refractoriness to platelet transfusion is an understudied phenomenon in critically ill patients. Our objective was to evaluate the prevalence, risk factors and clinical outcomes of platelet refractoriness among patients in a tertiary-care intensive care unit (ICU).Methods: A retrospective cohort study included all patients (age >14 years) who were admitted to a tertiary-care medical-surgical ICU between 2011 and 2016 and received ≥2 platelet transfusions during their ICU stay. We calculated platelet increment (PI) and corrected count increment (CCI). Results: A total of 267 patients were enrolled in the study, collectively receiving 1357 transfusions with a median of 3 (interquartile range: 2-6) transfusions per patient. The median pretransfusion platelet count was 31.0 x109/L (interquartile range: 16.0, 50.0) with a median PI of 6 x109/L (interquartile range: -5, 24). The prevalence of platelet transfusion refractoriness was 54.8% based on PI and 57.0% based on CCI. The two methods had excellent concordance in diagnosing refractoriness (kappa coefficient: 0.939). Refractoriness was more common in patients admitted by Hepatology, Liver Transplant, and Hematology services (69.7%, 69.2%, and 55.6%, respectively). On multivariable logistic regression, younger age was the only significant predictor of refractoriness (odds ratio per year increment: 0.975, 95% CI: 0.951-0.999). Finally, refractoriness was associated with increased length of stay in the ICU (p=0.02), but not with mortality.Conclusions: We demonstrated excellent concordance between PI and CCI for the diagnosis of platelet transfusion refractoriness. Platelet transfusion refractoriness was highly (>50%) prevalent in critically ill patients. However, it was not associated with increased mortality.
Argatroban anticoagulation for adult Extracorporeal Membrane Oxygenation: A systematic review
Authors: Geli Janos , Capoccia Massimo , Maybauer Dirk M , Maybauer Marc O
Published: August 2020

Background: Extracorporeal Membrane Oxygenation (ECMO) is an established method of circulatory support in critically ill patients. Heparin is the widely used anti-coagulation treatment for patients on ECMO in view of its features. Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin III (AT-III) deficiency may lead to sub-therapeutic anticoagulation with potentially serious consequences. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban and bivalirudin as main agents. We aimed to review the evidence supporting the effectiveness and safety of argatroban as a potential definitive alternative to heparin in the adult patient population undergoing ECMO support. Methods: A web based systematic literature search was performed in Medline (PubMed) and Embase from inception until June 18th 2020. Results: The search identified 13 publications relevant to the target (4 cohort studies and 9 case series). Case reports and case series with less than 3 cases were not included in the qualitative synthesis. The aggregate number of argatroban treated patients on Extra Corporeal Life Support (ECLS) was n = 317. In the majority of studies argatroban was used as a continuous infusion without loading dose. Starting doses on ECMO varied between 0.05 and 2 μg/kg/min and were titrated to achieve the chosen therapeutic target range. The activated partial thormboplastin time (aPTT) was the anticoagulation parameter used for monitoring purposes in most studies, whereas some utilized the activated clotting time (ACT). Optimal therapeutic targets varied between 43-70 to 60-100 seconds for aPTT and 150-210 to 180-230 seconds for ACT. Bleeding and thromboembolic complication rates were comparable to patients treated with unfractionated heparin (UFH). Conclusions: Argatroban infusion rates and anticoagulation target ranges showed substantial variations. The rational for divergent dosing and monitoring approaches are discussed in this paper. Argatroban appears to be a safe and viable alternative to UFH in patients requiring ECLS. To establish an ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted.
An SDF-1α Gene-activated Collagen Scaffold Restores Pro-angiogenic Wound Healing Features in Human Diabetic Adipose-derived Stem Cells
Authors: Laiva Ashang Luwang , O’Brien Fergal J. , Keogh Michael B.
Published: August 2020

Background: Diabetic foot ulcer is one of the leading causes of leg amputation and mortality in diabetic patients. Autologous stem cell therapy holds some potential to be a solution to this problem, however diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen-chondroitin sulfate (coll-CS) scaffold functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold) can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). Methods: Gene-activated scaffolds were first prepared by soak-loading polyethyleneimine nanoparticles carrying the plasmid encoding for SDF-1α gene into a freeze-dried coll-CS scaffold. ADSCs from healthy and diabetic donors were then seeded on the gene-activated scaffold. The response of the ADSCs in the gene-activated scaffold was then compared against those of the healthy ADSCs cultured on the gene-free scaffold over 2 weeks period. Functional response in the ADSCs such as the activation of SDF-1α mediated signaling, production of bioactive factors, pro-angiogenic bioactivity of secreted factors, matrix deposition and remodeling was determined using proteome profiling, Matrigel assay, qRT-PCR and immunofluorescence.Results: Overall, we found that SDF-1α gene-activated scaffold could restore pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the SDF-1α gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream signaling of β-arrestin as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also effectively stimulated angiogenesis in endothelial cells while undergoing matrix remodeling characterized by reduction in deposition of fibronectin matrix and increase in the expression of basement membrane protein collagen IV. The SDF-1α gene-activated scaffold also induced a controlled pro- healing response in the healthy ADSCs by disabling the signaling of early developmental factors while promoting the expression of tissue remodeling components.Conclusion: We show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs paving the way for autologous patient stem cell therapies in combination with novel biomaterials to treat diabetic foot ulcers.
Changes in Left Ventricular Electromechanical Relations During Targeted Hypothermia
Authors: Wisløff-Aase Kristin , Kerans Viesturs , Haugaa Kristina , Halvorsen Per Steinar , Skulstad Helge , Espinoza Andreas
Published: August 2020

Background: Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of mechanical and electrical systole are correlated to ventricular arrhythmias. The electromechanical window (EMW) becomes negative when electrical systole outlasts the mechanical systole. Prolonged electrical systole is also associated with electrical and mechanical dispersion, both predisposing for arrhythmias. The electromechanical relations during targeted hypothermia are unknown, but treatment after cardiac arrest has not demonstrated increased incidence of ventricular arrhythmic events.We wanted to explore the electromechanical relations during hypothermia at 33 °C. We hypothesized that targeted hypothermia would increase electrical and mechanical systolic duration without an increase in electromechanical negativity, nor an increase in electrical and mechanical dispersion. Methods: In a porcine model (n = 14) we registered electrocardiogram (ECG) and echocardiographic recordings during 38 °C and 33 °C, at spontaneous and atrial paced heart rate 100 beats/min. EMW was calculated by subtracting electrical systole, QT interval, from the corresponding mechanical systole, recorded from onset QRS to aortic valve closure. Electrical dispersion was measured as time from peak to end of the ECG T wave. Mechanical dispersion was calculated by strain echocardiography as standard deviation of time to peak strain. Results:Electrical systole increased during hypothermia at spontaneous heart rate (p < 0.001) and heart rate 100 beats/min (p = 0.005). Mechanical systolic duration was prolonged and outlasted electrical systole independently of heart rate (p < 0.001). EMW changed from negative to positive value (-20 ± 19 to 27 ± 34 ms, p = 0.001). The positivity was even more pronounced at heart rate 100 beats/min (-25 ± 26 to 41 ± 18 ms, p < 0.001). Electrical dispersion decreased (p = 0.027 and p = 0.003), while mechanical dispersion did not differ (p = 0.078 and p = 0.297).Conclusion: Targeted hypothermia increased electrical and mechanical systolic duration, the electromechanical window became positive, electrical dispersion was reduced and mechanical dispersion was unchanged. These alterations may have clinical importance. Further clinical studies are required to clarify whether corresponding electromechanical alterations are accommodating in humans.
Corticosteroid therapy for corona virus disease 2019-related acute respiratory distress syndrome: a cohort study with propensity score analysis
Authors: Wu Chaomin , Hou Dongni , Du Chunling , Cai Yanping , Zheng Junhua , Xu Jie , Chen Xiaoyan , Chen Cuicui , Hu Xianglin , Zhang Yuye , Song Juan , Wang Lu , Chao Yen-cheng , Feng Yun , Xiong Weining , Chen Dechang , Zhong Ming , Hu Jie , Jiang Jinjun , Bai Chunxue , Zhou Xin , Xu Jinfu , Gong Fengyun , Song Yuanlin
Published: August 2020

Background
The impact of corticosteroid therapy on outcomes of patients with Coronavirus disease-2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without.
Methods
In this single-centre retrospective observational study, patients with ARDS caused by COVID-19 between 24 December 2019 and 24 February 2020 were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality.
Results
A total of 382 patients including 226 (59.2%) patients who received systemic corticosteroids and 156 (40.8%) patients with standard treatment were analyzed. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days (HR, 0.48; 95% CI, 0.25, 0.93; p = 0.0285). The association remained significantly after adjusting for age, sex, Sequential Organ Failure Assessment score at hospital admission, propensity score of corticosteroid treatment, and comorbidities (HR: 0.51; CI: 0.27, 0.99; p = 0.0471). Corticosteroids were not associated with delayed viral RNA clearance in our cohort.
Conclusion
In this clinical practice setting, low-to-moderate dose corticosteroid treatment was associated with reduced risk of death in COVID-19 patients who developed ARDS.
Culture-negative and culture-positive septic shock: characteristics and clinical outcomes
Authors: Kim June-sung , Kim Youn-Jung , Kim Won Young
Published: August 2020

Background We evaluated the characteristics and outcomes of culture-negative septic shock versus culture-positive septic shock.Methods We performed a retrospective observational study of data from a prospective registry from 2014 to 2018. A total of 2,499 adult patients with septic shock were enrolled. The primary outcome was 90-day mortality, and the secondary outcomes were the length of hospital stay, a requirement for mechanical ventilation or renal replacement therapy, and in-hospital mortality.Results Of 1,718 patients with septic shock, 1,012 (58.9%) patients were culture-positive (blood 803, urine 302, sputum 102, others 204) and the median pathogen detection time was 9.5 hours (aerobic 10.2 hours and anaerobic 9.0 hours). The most common site of infection among the culture-positive was the hepatobiliary tract (39.5%), while for the culture-negative was the lower respiratory tract (38.2%). The culture-negative group had a lower mean body temperature (37.3 vs 37.7 ℃), lactate (2.5 vs. 3.2 mmol/L), C-reactive protein (11.1 vs 11.9 mg/dL), and sequential organ failure assessment score (7.0 vs. 8.0) than that of the culture-positive group. However, 90-day mortality between the groups was not significantly different (32.7 vs 32.2%, p = 0.83), and the other clinical outcomes also did not differ significantly. Moreover, a shorter culture detection time was correlated with a higher sequential organ failure assessment score but not with mortality.Conclusion Patients with septic shock are frequently culture-negative, especially in cases where the infection focus is in the lower respiratory tract. Although culture-negative was associated with degree of organ dysfunction, it was not an independent predictor of death.