bluuebunny/crossref_metadata_2025 huggingface dataset:
Inspiratory Muscle Training in Children: Moderate Loads (60%) Are Safe and Promote an Increase in PIMAX
Authors: Nascimento Milena Siciliano , Prado Cristiane do , Ejzenberg Fernanda , Kushida Simone Sayuri , Fontes Amanda , Almeida João Fernando , Medeiros Daniela Nasu
Published: September 2020

Background: Weaning failure are complex outcomes as it involves some aspects including weakness of the respiratory muscles. Ventilator-induced diaphragmatic dysfunction has been described as one of the main complications of IMV. Inspiratory muscle training with moderate loads was described in adults as having excellent results in terms of disconnection from the IMV literature. On pediatric population there is still a scarcity of and most of it consists of descriptions of isolated case reports. Methods: This study aims at evaluating whether muscle training using moderate loads will cause an increase in maximal inspiratory pressure (PIMAX) in patients dependent on mechanical ventilation. This is a retrospective study conducted in 2 Pediatric Intensive Care Units from January 2016 to December 2017. All patients who underwent muscle training during the period of the study were included. PIMAX was measured using a manovacuometer. Three measurements were made with an occlusion time of 15 seconds and a recovery interval of 2 minutes between them. Muscle training was performed following the institutional protocol (4 sets of 6 repetitions with a load equivalent to 60% of PIMAX) 1x/day, 6 days a week, excluding the day of the measurement of PIMAX. Results: Six patients undergoing prolonged mechanical ventilation (average time of mechanical ventilation of 9647 hours) who underwent muscle training to disconnect mechanical ventilation were included. The measurements of PIMAX pre-training were compared to weeks 1 to 4. A significant difference on PIMAX was observed after the second week of training (p <0.001). Five patients progressed to IMV disconnection. Conclusion: Our study supports the performance of IMT using moderate loads (60%), with no risk of muscle fatigue as it resulted in a significant increase in PIMAX after 2 weeks of training, with positive outcomes regarding weaning from mechanical ventilation.
A Randomized Trial of Albumin Infusion to Prevent Intradialytic Hypotension in Hypoalbuminemic Patients
Authors: Macedo Etienne , Karl Bethany , Lee Euyhyun , Mehta Ravindra L.
Published: September 2020

Background: Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia 1. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients. Methods: A randomized, crossover trial was performed in 65 AKI or ESRD patients with hypoalbuminemia (albumin<3g/dl) who required HD during hospitalization. Patients were randomized to receive 100ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to 6 sessions. Patients’ vital signs and ultrafiltration removal rate were recorded every 15 to 30 minutes during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded. Results: 65 patients were submitted to 249 sessions; mean age was 58 (+/-12), 46 (70%) were male with a mean weight of 76 (+/-18) kg. Presence of IDH was lower during albumin sessions based on all definitions. The risk of hypotension was significantly decreased based on the Kidney Disease Outcomes Quality Initiative (KDOQI) definition; (15% with NS vs. 7% with albumin, p=0.002). Lowest intradialytic SBP was significantly worse in patients that received 0.9% sodium chloride in comparison to albumin (NS 83 vs. Albumin 90 mmHg,p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies (NS -8.25 ml/kg/h (-11.18 -5.80) vs. 8.27ml/kg/h (-12.22 - 5.53) with albumin, p =0.011). Conclusion: In hypoalbuminemic patients who need HD, administration of albumin before dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve safety of HD and achievement of fluid balance in these high-risk patients.ClinicalTrials.gov Identifier: NCT04522635Retrospectively registered in August 21, 2020
Early Corticosteroids Decrease Mortality in Critically Ill Patients with COVID-19: A Cohort Study
Authors: Monedero Pablo , Gea Alfredo , Castro Pedro , Candela-Toha Angel M. , Hernández-Sanz María L. , Arruti Egoitz , Villar Jesús , Ferrando Carlos
Published: September 2020

Background: Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose. Methods: This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from March 12th to June 29th, 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48h of ICU admission) with those who did not receive early corticosteroids or any corticosteroids at all. Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications. Results: A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n=485) had a lower ICU mortality (30.3% vs 40.6%, HR 0.71, 95% CI 0.57-0.89) and higher number of ventilator-free days (mean difference 2.5 days, 95% CI 1.3-3.8) compared to non-early treated patients. There were no differences in 7-day mortality (HR 0.76, 95% CI 0.48-1.2), medical complications (OR 2.18, 95% CI 0.91-5.25) or secondary infections (OR 0.88, 95% CI 0.67-1.15) between both groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens. Conclusion: Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality (10.3% absolute risk reduction) and shorter duration of mechanical ventilation.
Do Primary Care Clinicians Incorporate Comorbidities and Concurrent Medications When Prescribing Opioids for Low Back Pain? A Retrospective Cross-Sectional Analysis
Authors: Keller Michelle Sophie , Truong Lyna , Mays Allison Moser , Needleman Jack , Heilemann MarySue V. , Nuckols Teryl K
Published: September 2020

Background Given the risks of opioid therapy, clinicians are under growing pressure to treat pain with non-opioid medications. Yet non-opioid analgesics such as non-steroidal anti-inflammatory drugs have their own risks; patients with kidney disease or gastrointestinal diseases can experience serious adverse events. We examined how primary care clinicians balance patient comorbidities and concurrent medications when prescribing opioids. Methods We used a retrospective cross-sectional study design and data from one health system. We identified office visits for low back pain from 2012-2017 and sampled the first visit per patient per year (N= 24,543 visits). We created indicators reflecting contraindications for NSAIDs (kidney, liver, cardiovascular/cerebrovascular, and gastrointestinal diseases; concurrent use of anticoagulants/antiplatelets) and opioids (depression, anxiety, substance use and bipolar disorders, chronic corticosteroid use, and concurrent benzodiazepines) and estimated four logistic regression models, with the first model including all patient visits and then stratifying for previous opioid use. Results Patients received an opioid prescription at 4% of visits. Among all patients, kidney disease (marginal effect [ME]: 3%; 95%CI: 1%-4%) or chronic/concurrent anticoagulant/antiplatelet prescriptions (ME: 2%, 95%CI: 1%-3%) were associated with a higher probability of receiving an opioid prescription. Concurrent benzodiazepines (ME: 7%, 95%CI: 5%-9%) and substance use diagnoses (ME: 1%, 95%CI: 0%-3%) were also associated with a higher probability of opioid prescription receipt. Among patients with long-term opioid use, contraindications for NSAIDs were not associated with a higher probability of opioid prescription receipt, while the probability of opioid receipt among those with concurrent benzodiazepines was substantially higher (ME: 10%, 95%CI: 14%-53%).Conclusions Among our entire sample, patients with kidney disease were 75% more likely to receive an opioid prescription for low back pain. Among patients with long-term opioid use, we did not find the same association. Patients with long-term use were likely started on opioids when opioid prescribing was more liberal; discussions regarding non-opioid options would be worthwhile for this population. Patients with concurrent benzodiazepines were 175% more likely to receive an opioid prescription; among patients with long-term opioid use, they were 250% more likely to receive opioids. These findings are troubling, as this combination is dangerous and can lead to overdose.
Use of Health Information Exchange in The Continuity of Care as Viewed by Patients and Nurses: A Cross Sectional Study
Authors: Itzhaki Michal , Koren Ella , Hussien Khaled Abu , Levy Liron , Gantz Irit , Barnoy Sivia
Published: September 2020

Background: Patients' attitudes towards sharing their personal health information are critical for implementation of Health Information Exchange (HIE). Nurses contribute significantly to information sharing within the care continuum in hospitals and community. The purpose of this study was to examine the awareness and readiness of chronic ill patients and nurses to use HIE.Methods: A cross sectional study among 312 inpatients with a chronic illness, 110 nurses working in internal wards, and 55 contact nurses working in a large Health Maintenance Organization. Multiple linear regressions were performed to assess the associations between knowledge, attitudes, socio-demographics, and both the readiness and intention to use HIE. Results: Mean levels of awareness were low across all three groups. The readiness to share information with medical healthcare providers was higher than the readiness to share information with agents not involved in direct care. Contact nurses expressed more positive attitudes than internal ward nurses or patients (F=11.25; p=.0001) and were more willing than patients to share information with health care workers (F=16.786; p=0001). All nurses (Internal ward and contact) were more willing to share information with medical agents not involved in direct care as compared to patients (F=8.072; p=.0001). Contact nurses expressed a significantly greater intention to use HIE than did internal ward nurses or patients (F=9.825; p=.0001), Knowledge, attitudes and being a nurse predicted the intention to share information on HIE with medical health care providers (F=29.91), and with agents not involved in direct care (F=19.65).Conclusions: Before implementation of an HIE system, it is important to raise awareness, readiness, and intention to use HIE among the general public, nurses, and other medical staff. Policy makers should organize national campaigns under the auspices of the Ministry of Health, in order to present the advantages of HIE and provide detailed information about the systems.
Study on Income for the Workforce of Public Health Institutions in Beijing Between 2011 and 2016
Authors: Qiu Wuqi , Yang Yujie , Meng Yueli , Mao Ayan
Published: September 2020

Background: This article analyses the average annual incomes of the workforce of municipal and district level public health institutions in Beijing between 2011 and 2016, and provides a useful reference for strengthening of public health services in China. Methods: This investigation combined quantitative analysis with qualitative investigation through a questionnaire survey and interviews with key informant. Results: Remuneration was relatively high for staff of the Municipal Maternal and Child Health Care Hospital and the staff of the Mental Health Institution, who had the highest annual average income among municipal specialized public health institutions between 2011 and 2016. The average annual incomes of the Municipal CDC, HSI, TCI, Municipal Emergency Medical Centre and Red Cross Blood Centre were all lower than the average annual income of the workers in the city's health industry (157,200 yuan). The average annual income of staff in the public health institutions at district level in Beijing is generally lower than that for staff in municipal institutions, especially those with high professional positions. Conclusions: The average income of public health workers in Beijing is generally lower than that of other health workers in the whole city. The result is a lack of professional attractiveness, which affects the stability and development of Beijing public health personnel.
Elevated ILC3s-related Inflammatory Factors may Promote Tendinopathy
Authors: Xu Peng , Yue Jiawei , Xu Xu , Wu Yumin
Published: September 2020

Background: The prevalence of tendinopathy has risen dramatically over the last few decades and has become a common and serious orthopedic problem in sports injury and elderly populations. Immune cells have been shown to be associated with tendinopathy, with the percentage of Group 3 Innate Lymphoid Cells (ILC3s) having been shown to be upregulated in tendon tissue compared with peripheral blood. Methods: We used flow cytometry to investigate the percentage of circulating ILC3s in patients with tendinopathy and controls patients; Realtime-PCR was performed to detect the mRNA levels of ILC3s surface markers, CD45, IL-23R, ICOS and ILC3s-related inflammatory factors and transcription factors IL-17A, IL-22 and RORC in tendon samples. Results: Our results showed that the proportion of ILC3s in the peripheral blood circulation of patients with tendinopathy has no significant difference from that of controls by flow cytometry for Lin‑IL-2R+IL-23R + cells; however, the surface marker of ILC3s was upregulated in tendon tissue. In addition, IL-23, a characteristic activating factor of ILC3s, was also upregulated. Relative mRNA expression levels of IL-17A and IL-22 were also upregulated in tendinopathy tendon tissue compared to control patients. Conclusions: These results suggest that ILC3s may be a potential immune factor for tendinopathy.
Blood Eosinophils and Mortality in Patients With Acute Respiratory Distress Syndrome: A Propensity Score Matching Analysis
Authors: Chen Haotian , Mao Yue , Xu Jianfeng , Huang Xiaoxia , Zhou Niya , Wang Yongkui
Published: September 2020

Background: The effect of blood eosinophils on mortality in acute respiratory distress syndrome (ARDS) patients and whether this effect is impacted by corticosteroids are unclear. This study explored the relationship between blood eosinophils and 28-day mortality in ARDS patients and investigated whether the relationship varied according to corticosteroid use.Methods: The Medical Information Mart for Intensive Care III database was employed to extract data. Patients with ARDS who were 16 years or older, used mechanical ventilation during the ICU stay and stayed in the ICU for at least 48 consecutive hours were screened for inclusion. Cox regression models using the stepwise backward method and propensity score matching (PSM) were employed to assess the relationship between blood eosinophil counts and 28-day mortality.Result: A total of 3372 patients were included, and the 28-day mortality rate was 24.23% (817/3372). The crude 28-day mortality was significantly lower in patients with eosinophil count ≥2% (105/574 vs. 712/2798, p< 0.001) than in those with eosinophil count <2%. In the Cox regression model, the eosinophil count ≥2% showed a significant association with decreased 28-day mortality (hazard ratio (HR) 0.761; 95% confidence interval (CI) =0.620-0.935, p=0.009). In a subgroup analysis, we detected an interactive effect of eosinophils and corticosteroids use (p value for interaction, p=0.006). In the corticosteroid non-use subgroup, eosinophil counts ≥2% were significantly related to decreased 28-day mortality (HR=0.730, 95% CI =0.577-0.923), but the result was non-significant in the corticosteroid non-use subgroup model (p=0.231). A total of 574 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the eosinophil count ≥2% group than in the eosinophil count <2% group (105/574 vs 136/574, p=0.025).Conclusions: Higher eosinophil counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.
Altered Spontaneous Brain Activity in Somatic Symptom Disorder: A Resting-state fMRI Study
Authors: Cui Yangyang , Liang Huai-Bin , Zhu Qian , Qin Zhaoxia , Hu Yue , Liu Yi-Sheng , Zhao Rong , Qiao Yuan , Tang Wei , Gao Tingting , Liu Jian-Ren , Du Xiaoxia
Published: September 2020

Background: Somatic symptom disorders (SSDs) are common medical disorders characterized by various biological, social, and psychological pathogenic factors. Little is known about the neural correlations of SSD. Methods: In this study, we evaluated the dysfunction in 45 patients with SSD and in 43 controls by combining the regional homogeneity (ReHo) amplitudes of low-frequency fluctuation (ALFF) methods based on resting-state functional magnetic resonance imaging. Results: Compared to the controls, the patients with SSD exhibited significantly greater ReHo in the right cingulate gyrus and smaller ReHo in the right precuneus, left inferior and temporal gyrus extending to the left middle temporal gyrus and left parahippocampal gyrus, and right pons. The SSD patients showed higher ALFF values in the cingulate gyrus extending to the left medial frontal gyrus, right insula extending to the right inferior frontal gyrus, and left medial frontal gyrus extending to the left anterior cingulate cortex. Conclusions: These dysfunction areas seem to have a particular importance for the occurrence of SSD, which may result in dysfunction in self-relevant processes, emotional processing, multimodal integration, arousal, interoception, and body perception.
Reconfiguration of Multistable 3D Ferromagnetic Mesostructures
Guided by Energy Landscape Surveys
Authors: Li Yi , Avis Sam , Chen Junbo , Wu Guangfu , Zhang Teng , Kusumaatmaja Halim , WANG XUEJU
Published: September 2020

Reconfigurable three-dimensional (3D) structures that can reversibly change their geometries and thereby their functionalities are promising for a wide range of applications. Despite intensive studies, the lack of fundamental understanding of the highly nonlinear multistable states existing in these structures has significantly hindered the development of reconfigurable systems that can realize rapid, well-controlled shape change. Herein we present a systematic, integrated experimental and computational study to control and tailor the multistable states of 3D structures and their reconfiguration paths. Our energy landscape analysis using a discrete shell model and minimum energy pathway methods leads to design maps for a controlled number of stable states by varying geometry and material parameters, and energy-efficient reconfiguration paths among the multistable states. Concurrently, our experiments show that 3D structures assembled from ferromagnetic composite thin films of diverse geometries can be rapidly reconfigured among their multistable states, with the number of stable states and reconfigurable paths in excellent agreement with computational predictions. In addition, we demonstrate a wide breadth of applications including reconfigurable 3D light emitting systems, remotely- controlled release of particles/drugs from a reconfigurable structure, and 3D structure arrays that can form desired patterns following the written path of a magnetic “pen”. Our results represent a critical step towards the rational design and development of well-controlled, rapidly and remotely reconfigurable structures for many applications.
Epidemiology of Clinically Suspected and Laboratory-Confirmed Bloodstream Infections at A South African Neonatal Unit
Authors: Dramowski Angela , Bekker A , Cotton M F , Whitelaw A C , Coffin S
Published: September 2020

Background: Data from Africa reporting the epidemiology of infection in hospitalised neonates are limited. Methods: We conducted a cross-sectional study with convenience sampling to characterise neonates investigated with blood culture/s for suspected infection at a 124-bed neonatal unit in Cape Town, South Africa (1 February-31 October 2018). Enrolled neonates were classified as having proven bloodstream infection (BSI) (blood culture-positive with a pathogen) or presumed infection (clinically suspected but blood culture-negative) or potentially at risk of infection (maternal risk factors at birth). Results: Of 1299 hospitalised neonates with >1 blood culture sampling episode, 712 (55%) were enrolled: 126 (17.7%) had proven BSI; 299 (42%) had presumed infection and 287 (40.3%) were potentially at risk of infection. Neonates with proven BSI had lower birth weight and higher rates of co-existing surgical conditions versus the presumed/potential infection groups (p<0.001). Median onset of proven BSI versus presumed infection was at 8 (IQR 5-13) and 1 (IQR 0-5) days respectively (p<0.001). Most proven BSI were healthcare-associated (114/126; 90.5%), with Klebsiella pneumoniae (80.6% extended-spectrum β-lactamase producers) and Staphylococcus aureus (66.7% methicillin-resistant) predominating. Mortality from proven BSI (34/126; 27%) was substantially higher than that observed in presumed (8/299; 2.7%) and potential infections (3/287; 1.0%) (p<0.001). The odds of death from proven BSI was 3-fold higher for Gram-negatives than for Gram-positive/fungal pathogens (OR 3.23; 95%CI 1.17-8.92). Conclusion: Proven BSI episodes were predominantly healthcare-associated and associated with a high case fatality rate. Most neonates with presumed infection or at potential risk of infection had favourable 30-day outcomes.
Research of Magnetic Particle Imaging Reconstruction based on the Elastic Net Regularization
Authors: Chen Xiaojun , Han Xiao , Wang Xiaolin , Tang Xiaoying
Published: September 2020

The authors have requested that this preprint be withdrawn due to author disagreement.
Comparison of Cognitive and Other Developmental Functions in Children With Stunting and Malnutrition
Authors: Handryastuti Setyo , Pusponegoro Hardiono D. , Nurdadi Surastuti , Chandra Anita , Pramita Feka A. , Soebadi Amanda , Widjaja Ivan R. , Rafli Achmad
Published: September 2020

Background. Stunting is the impairment of growth and development due to malnutrition and/or chronic disease/infection. According to the Indonesia Basic National Health Survey 2013, prevalence of stunting in Indonesia reached 37.2%. Various studies have shown that impaired cognitive development may be found in children with stunting and malnutrition. This research has purpose to determine cognitive development in stunted children and malnourished children, using Bayley Scale of Infant Development III (Bayley-III). Methods. A cross-sectional study in 51 children aged 6 month to 3 year old who fullfiled the inclusion criteria at the Outpatient Clinic of Dr.Cipto Mangunkusumo National General Hospital from June 2017 until January 2018. Cognitive development was assessed using the Bayley Scale of Infant Development Third Edition (Bayley-III). Results. Twenty six children with stunting and 25 children with malnutrition without stunting with age of subjects were 11.0 month (2.0-34.0) and 16.0 month (7.0-25.6) respectively. Bayley-III percentile in cognitive scale were 12.5 (0.1-75) and 16.0 (0.1-99.9) with P (p-value)=0.55. Conclusions: Stunted children showed lower cognitive scores compared to the children with malnutrition. Although it was not significant, but it showed that Bayley-III scores group of stunting and malnutrition groups of children with normal stature far below the 50 percentile (P50). This showed that both children with stunting and malnutrition possible to have decreased cognitive function. Further research is needed with a larger sample to get comprehensive conclusions. Early detection and intervention also should be aimed at children who are experienced growth faltering to prevent developmental problems, especially cognitive function.
Safety of Allogenic Human Cord Blood Derived Mononuclear Cells for Extreme Preterms Infants at High Risk of Death: A Descriptive Study
Authors: Chen Jia , Mei Yabo , Du Xue , Li Qiuping , Wang Zizhen , Zhang Xing , Chen Yuhan , Zhang Yanping , Feng Zhichun
Published: September 2020

Backgroud Extreme preterm infants are at a high risk for developing preterm complications and death. Despite advances in medical care, many survivors face a lifetime of disability. Objective To assess the short term safety of and four-year follow-up outcomes of allogenic, human umbilical cord blood (hUCB) derived mononuclear cells(MNCs) infusion to extreme preterm infants with high risk potential of death. Method This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of allogenic, hUCB-MNCs infusion for extreme preterm infants with high risk potential of death. HUCB MNCs characteristics, pre- and postinfusion vital signs and laboratory investigations were recorded. Temporal proﬁles of cytokines and growth factors from blood were test. Clinical data including mortality rates, preterm complications and follow-up outcomes were recorded. Results After processing, relatively MNCs mean (1.9±0.8) ×106/kg; volume mean (11.25±2.12)ml/kg were infused to 10 extremely preterm infants with high risk of death. No adverse effects were noticed during treatment. 40% received extubation and weaned to nasal CPAP successfully; 30% received lower FiO2; no infants suffered from late onset sepsis; 30% received poor response to MNCs infusion. 40% infants suffered from ROP and only one infant needed laser surgery. No patients suffered from NEC after MNCs infusion. All ten infants who received hUCB MNCs infusion survived inhospital and prevent deterioration of clinical features, but 4 infants discharged against the advice of the doctor by their parents and lost connection. Regarding the rest 6 infants, no home oxygen therapy and rehospitalization, no suffered from other long-term respiratory complications at visit 1～visit 3. One infant showed cerebral palsy at visit 1, no clinical evidence associated this with MNCs infusion. Blood level of HGF signiﬁcantly increased, but MMP-9, IL-6, IL-8, TNF-α and TGF-β levels were significantly lower at 24h post infusion compared with baseline (P < 0.05).Conclusions Collection, preparation, and infusion of allogenic hUCB MNCs to extreme preterm infants is feasible and safe. Trial registration The study was registered on Chinese Clinical Trials.gov (NO. ChiCTR–OPN - 15006932). Registered 17 August 2015, http://www.chictr.org.cn/edit.aspx?pid=11662&htm=4.
Identification Of The Molecular Targets And Immunophenotype Of Gastric Cancer By Bioinformatics Analysis
Authors: Yang Tao , Zhang KeGang , Xu Rui , You Junhao , Li Fang
Published: September 2020

Background: Gastric cancer (GC) is the most lethal tumor of gastrointestinal tract worldwide. Despite advances in various therapies, the prognosis of GC remains poor. Moreover, only a small fraction of GC patients benefit from immunotherapy. Therefore, it is urgent to deeply understand the molecular characteristics and immunophenotype of GC. Methods: We analyzed the gene expression profile of GSE118916 from GEO database, including the mRNA expression profiles of 15 pairs of GC tumor and adjacent non-tumor tissues. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online website DAVID. And then the survival prediction values of the top 10 up-regulated genes were analyzed using Kaplan–Meier plotter database. Finally, the immune cells infiltration was analyzed using CIBERSORT online tool.Results: A total of 1156 DEGs were identified, including 633 up-regulated genes and 523 down-regulated genes. The up-regulated genes were mainly enriched in cell adhesion, proliferation, migration and inflammation response. In addition, the up-regulated genes were significantly enriched in acid metabolism, complement and coagulation cascades, cell adhesion and p53 signaling pathway, which were all significant in tumor progression, relapse and metastasis. In addition, the up-regulated genes CTSL and PIEZO1 were associated with poor prognosis in GC patients. Moreover, a unique immune-suppressive microenvironment was identified in GC tissues. Conclusions: CTSL and PIEZO1 might be potential biomarkers and therapeutic targets in GC patients.
3D Printed Models Improve Surgical Planning for Correction of Severe Postburn Ankle Contracture With External Fixator
Authors: Chen Youbai , Niu Zehao , Jiang Weiqian , Lei Yonghong , Guo Lingli , Xia Wensen , Song Baoqiang , Huang Luyu , Zhang Qixu , Han Yan
Published: September 2020

Background: Gradual distraction with external fixators such as Ilizarov frame has been widely used for the treatment of severe postburn ankle contracture (PAC). However, the application of external fixator is complex and conventional surgical planning based on 2D imaging is compromised due to a lack of spatial geometry and tactile feedback. The purpose of this study was to evaluate the surgical planning with patient-specific 3D-printed models (3DPM) for the treatment of PAC with external fixators. Methods: A two-centered retrospective cohort study, composed of consecutive patients who underwent external fixation for the treatment of severe PAC, was implemented. Patients were divided into two cohorts (3DPM group vs. Control group) according to whether 3DPM was used for preoperative surgical planning. The primary outcome variable was operation duration. Other outcome variables included improvement in metatarsal-tibial angle (MTA), range of motion (ROM), American Orthopedic Foot and Ankle Society (AOFAS) scores, and complications. Results: Between January 2008 and June 2018, ten patients with an average age of 23.8±14.1 yeas were treated for PAC at two centers. 3DPM were used for surgical planning in 5 patients. 3DPM group had significantly shorter operation duration than the control group (2±0.3 hours vs. 3.2±0.3 hours, p=0.0001). The comparison of preoperative, after removal of external fixator, and follow-up MTA, ROM, and AOFAS between the 3DPM and control group showed no significant differences. A plantigrade foot was achieved and gait was substantially improved in all patients at the final follow-up. Pin-tract infections occurred in 2 patients (one in each group) during distraction and were treated with wound care and oral antibiotics. Conclusion: The results of this study show that surgical planning using patient-specific 3DPM significantly reduced the operation duration while providing similar improvements in MTA, ROM, and AOFAS scores compared to traditional surgical planning for the correction of severe PAC with external fixators.
Effect of a Low-fodmap Diet for the Management of Functional Abdominal Pain Disorders in Children: A Study Protocol for a Randomized Controlled Trial
Authors: Stróżyk Agata , Horvath Andrea , Muir Jane , Szajewska Hania
Published: September 2020

Background Evidence from studies in adults documents that fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may be triggers of symptoms in individuals with functional abdominal pain disorders (FAPDs). However, in children, the evidence is very limited. We aim to assess the effects of a low-FODMAP diet compared with a regular diet for the management of children with FAPDs. Methods We will perform a randomized, quadruple-blinded, controlled trial. Seventy-four children aged 8 to 18 years with a FAPD (Irritable Bowel Syndrome or Functional Abdominal Pain-Not Otherwise Specified), diagnosed according to the Rome IV criteria, will be randomly allocated to receive either a low-FODMAP diet or a regular diet for 4 weeks. The primary outcome will be the percentage of the responders, defined as the participants who have at least 30% improvement in abdominal pain intensity on a Visual Analogue Scale (VAS) during the last week of the trial compared with baseline, that is at least equal to the Reliable Change Index (≥ 25 mm change on VAS). Other outcomes will include changes in stool consistency, abdominal pain frequency, total scores on the Gastrointestinal Symptom Rating Scale, KIDSCREEN-10 Index and World Health Organization Five Well-Being Index, child’s school attendance and parents’ work absenteeism, and BMI-for-age z-score. Compliance, tolerability of the low-FODMAP diet, and adverse events also will be evaluated. Each FAPD subtype will be assessed separately.DiscussionThere is a need for high-quality evidence regarding the dietary management of children with FAPDs. This randomized controlled trial (RCT) of rigorous methodological design will help to establish the effectiveness, if any, of a low-FODMAP diet for the management of FAPDs in the pediatric population. The findings of this RCT will assist with the development of guidelines and influence the direction of further research. Trial registration: NCT04528914
Effects of Intravenous Immunoglobulin on the Course of Severe COVID-19: Results From a Retrospective Data Analysis of a Patient Cohort in Turkey Treated With or Without Octagam®
Authors: Esen Figen , Özcan Perihan E. , Orhun Günseli , Polat Özlem , Anaklı İlkay , Alay Gülçin , Tuna Verda , Çeliksoy Emre , Kılıç Mehmet , Mercan Mutlu , Tukek Tufan
Published: September 2020

Background: There is some evidence from case reports and a few studies in China that critically ill COVID-19 patients may benefit from treatment with intravenous immunoglobulins (IVIG). We compared clinical outcomes and biomarkers in a Turkish cohort of patients with severe COVID-19 who were treated with the institution's standard of care (SOC), either alone or in combination with IVIG.Methods: Data from COVID-19 patients treated in two intensive care units at the University hospital of Istanbul was analyzed retrospectively. Patients received preliminary SOC according to the institution's treatment algorithm, to which Octagam 5% at 30 g/day for 5 days was added in one of the two wards. Both groups were compared regarding baseline characteristics, survival, and changes in inflammation markers (C-reactive protein=CRP, ferritin, procalcitonin, interleukin-6, D‑dimer, leukocytes). Imbalance in baseline APACHE II scores was addressed by propensity-score-matching; otherwise Kaplan-Meier and multiple logistic regression models were used.Results: Data from 93 patients was analyzed, 51 had received IVIG and 42 had not. About 75% of patients were male and both groups had comparable body mass index (BMI) and blood group distribution. IVIG-treated patients were younger (means 65 vs. 71 years) and had slightly lower baseline disease scores (APACHE II: 20.6 vs. 22.4; SOFA: 5.0 vs. 7.0). Overall survival (OS) was 61% in the IVIG and 38% in the control group. After controlling for imbalances at baseline, there was still a trend for better OS (OR: 2.2, 95%CI: 0.9-5.4, p=0.091) and a significantly longer median survival time with IVIG (68 vs. 18 days, p=0.014). IVIG significantly reduced CRP levels, but had no relevant effect on other inflammation markers.Conclusion: Adjunct treatment with IVIG might add to the COVID-19 armamentarium, but results need to be confirmed in a randomized, controlled trial.
Right Ventricular-Arterial Uncoupling Independently Predicts Survival in COVID-19 ARDS
Authors: D'Alto Michele , Marra Alberto , Severino Sergio , Salzano Andrea , Romeo Emanuele , De Rosa Rosanna C , Stagnaro Francesca , Pagnano Gianpiero , Verde Raffaele , Murino Patrizia , Farro Andrea , Ciccarelli Giovanni , Vargas Maria , Fiorentino Giuseppe , Servillo Giuseppe , Gentile Ivan , Corcione Antonio , Cittadini Antonio , Naeije Robert , Golino Paolo
Published: September 2020

Aim. To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an acute respiratory distress syndrome (ARDS).Methods. Ninety-four consecutive patients (mean age 64 yrs) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio Results. The majority of patients needed ventilatory support, which was non-invasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62±13 vs 68±12 years, p=0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270±104 vs 117±57 mmHg, p<0.001). In the non-survivors, PASP was increased (42±12 vs 30±7 mmHg, p<0.001), while TAPSE was decreased (19±4 vs 25±4 mm, p<0.001). Accordingly the TAPSE/PASP ratio was lower than in the survivors (0.51±0.22 vs 0.89±0.29 mm/mmHg, p<0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR:0.026; 95%CI:0.01-0.579; p:0.019) and PaO2/FIO2 (HR:0.988; 95%CI:0.988-0.998; p:0.018) ratios were the only independent predictors of mortality, with ROC-determined cut-off values of 159 mmHg and 0.635 mm/mmHg respectively.Conclusions. COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.
Unexpected central-memory CD8+ T cell reduction hampers the antitumor efficacy of mogamulizumab (anti-CC chemokine receptor 4 mAb) treatment
Authors: Maeda Yuka , Wada Hisashi , Saito Takuro , Sugiyama Daisuke , Irie Takuma , Minoura Kodai , Suzuki Susumu , Kojima Takashi , Kakimi Kazuhiro , Nakajima Jun , Funakoshi Takeru , Iida Shinsuke , Oka Mikio , Shimamura Teppei , Doi Toshihiko , Doki Yuichiro , Nakayama Eiichi , Ueda Ryuzo , Nishikawa Hiroyoshi
Published: September 2020

Developing Treg cell-targeted therapies is an important aspect in cancer immunotherapy. Here, we investigate anti-CCR4 mAb (mogamulizumab) with solid cancer patients in phase 1b clinical trial based on the predominant detection of CCR4-expressing eTreg cells in tumors. While eTreg cells in peripheral blood were significantly decreased after mogamulizumab administration in all patients, clinical responses were hardly detected. Comprehensive immune-monitoring revealed that concomitant reduction of central-memory CD8+ T cells with CCR4 expression, that reportedly play an important role in antitumor activity. This reduction was subsided in long survivors in whom central-memory CD8+ T cells possessed lower CCR4 expression and/or NK cells exhibited an exhausted phenotype. Thus, excess doses of mogamulizumab harboring enhanced antibody-dependent cellular cytotoxicity could unexpectedly deplete central-memory CD8+ T cells with CCR4 expression. We therefore need to carefully determine the optimal dose of mogamulizumab for successful clinical application as cancer immunotherapy to avoid unexpected depletion of effector components.
Mesenchymal Stem Cells Regulate IL8 and TGFA Expression in a Novel Leucocytes Depleted Platelet-Rich Plasma-Skin Equivalent in a Preliminary in vitro Study of Chronic Wound Healing
Authors: Seria Elisa , Galea George , Grech Gabriella , Tagliaferro Sarah Samut , Felice Alexander
Published: September 2020

Background: Chronic leg ulcerations are associated with Haemoglobin disorders, Type 2 Diabetes Mellitus, and long-term venous insufficiency. Mesenchymal stem cells (MSCs) ability to modulate the inflammatory response represents the fundamental requisite for their applicability as a treatment of chronic wounds.Methods: This study aimed to develop a novel bioactive platelet-rich plasma (PRP)-leukocytes-depleted scaffold to reproduce typical clinical wound of patients with poor chronic skin perfusion and low leucocytes infiltration. After scratching the wound model to mimic injury three conditions were compared; an untreated condition, a condition treated with recombinant TNF to mimic an inflammatory state and a condition treated with TNF and also with MSCs to evaluate how the latter’s immunomodulatory properties affect the therapeutic outcomes in an inflammatory state. Gene expression of IL8 and TGFA were analysed in biological triplicates of the three conditions. Statistical analysis was done through a paired student t-test and a p <0.05 was considered significant.Results: We set up a skin model that consisted of a leukocyte-depleted, platelet-rich plasma scaffold, with embedded fibroblasts as dermal equivalent and seeded keratinocytes on it as multi-layered epidermidis. IL8 expression increased upon scratching (p=0.014) and continued to increase up to day 1 (p=0.048). IL8 expression decreased upon administration of TNF (p=0.005) but then increased again. IL8 expression decreased in the untreated condition after day 1 as the natural healing process took place and was lower than in treated conditions in day 8 (p=0.048). TGFA expression decreased upon scratching (p=0.006) and increased again in day 1, more so in the untreated than in the treated conditions (p=0.02). TGFA expression decreased again in day 4 in the study group before increasing sharply (p=0.027) in day 8 to reach pre-scratch levels. Conclusion: This study found that a leukocyte-depleted PRP-based skin equivalent can be useful in the study of treatments of chronic wounds. This study also indicates that MSCs appear to modulate the expression of IL8 by switching from an immunosuppressive phenotype to a pro-inflammatory phenotype. These results indicate that the administration of MSCs could offer a potential therapeutic approach for the treatment of leg ulcers in patients with poor skin perfusion.
Association of Serum Antibodies Against the Mycobacterium Avium Complex and Hemoptysis: A Cross-Sectional Study
Authors: Ogata Hiroaki , Moriwaki Atsushi , Nakagawa Taisuke , Sakoda Soichiro , Ishimatsu Akiko , Taguchi Kazuhito , Aso Hiroshi , Nogami Hiroko , Kadowaki Masako , Tateshi Yuko , Yoshida Makoto
Published: September 2020

Background: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. Methods: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥ 20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. Results: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2% and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15–7.44)). Conclusions: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. MAC patients who tested positive for the MAC-Ab should be carefully followed up for the potential development of hemoptysis.
“This is My Boy’s Health! Talk Straight to Me!” Perspectives on Accessible and Culturally Safe Care Among Aboriginal and Torres Strait Islander Patients of Clinical Genetics Services
Authors: Dalach Philippa , Savarirayan Ravi , Baynam Gareth , McGaughran Julie , Kowal Emma , Massey Libby , Jenkins Misty , Paradies Yin , Kelaher Margaret
Published: September 2020

BackgroundAboriginal and Torres Strait Islander people do not enjoy equal access to specialist health services that adequately meet their needs. Clinical genetics services are at the vanguard of realising the health benefits of genomic medicine. As the field continues to expand in clinical utility and implementation it is critical that Aboriginal and Torres Strait Islander people are able to participate and benefit equally to avoid further widening of the existing health gap. This is the first study to explore barriers to accessing clinical genetics services among Aboriginal and Torres Strait Islander people, which has been acknowledged as a key strategic priority in Australian genomic health policy.MethodsA participatory design process engaged a majority-Aboriginal Project Reference Group and Aboriginal End-User Group. 63 semi-structured interviews were conducted with Aboriginal and/or Torres Strait Islander people who had accessed the government-funded clinical genetics service in Western Australia, Queensland or the Northern Territory between 2014-2018. The sample included patients, parents and carers. Participants were asked to recount their ‘patient journey’, from referral through to post-appointment and reflect on their perceptions of genetics and its implications for the health of themselves and their families. Analysis tracked chronological service engagement, followed by an inductive thematic approach. ResultsBarriers to access and engagement were present at each stage of the patient journey. These included challenges in obtaining a referral, long waiting periods, limited genetic literacy, absence of Aboriginal support services, communication challenges and lack of adequate psychosocial support and follow-up after attendance. Participants’ overall experiences of attending a genetic health service were varied, with positive perceptions tied closely to a diagnosis being achieved. The experience of (and expectation for) recognition of cultural identity and provision of culturally safe care was low among participants. Unaddressed concerns continued to cause significant distress in some people years after their appointment took place.ConclusionsThere is significant scope for improving the care provided to Aboriginal and Torres Strait Islander people at clinical genetics services. Immediate attention to minimising logistical barriers, developing relationships with Aboriginal Community Controlled Health Services and providing practical and specific cultural safety training for practitioners is required at the service-level. Our findings strongly support the development of guidelines or policies recognising the collective cultural needs of Aboriginal and Torres Strait Islander people in relation to genomic health care.