bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive economic evaluation of enhanced recovery after surgery in hepatectomy
Authors: Dong Yihan , Zhang Yan , Jin Chengcheng
Published: November 2021

Background

Enhanced recovery after surgery (ERAS) is attracting extensive attention and being widely applied to reduce postoperative stress and accelerate recovery. However, the economic benefits of ERAS are less clarified at the social level. We aimed to assess the economic impact of ERAS in hepatectomy from the perspectives of patients, hospitals and society, as well as identify the approach to create the economic benefits of ERAS.

Methods

By combining the literature and national statistical data, the cost-effectiveness framework was clarified, and parameter values were determined. Cost-effectiveness analysis, cost–benefit analysis and cost-minimisation analysis were used to compare ERAS and conventional treatment from the perspectives of patients, hospitals and society. The capital flow diagram was used to analyse the change between them.

Results

ERAS significantly reduced the economic burden of disease on patients ($8935.02 vs $10,470.02). The hospital received an incremental benefit in ERAS (the incremental benefit cost ratio value is 1.09), and the total social cost was reduced ($5958.67 vs $6725.80). Capital flow diagram analysis demonstrated that the average daily cost per capita in the ERAS group increased ($669.51 vs $589.98), whereas the benefits depended on the reduction of hospital stay and productivity loss.

Conclusion

The mechanism by which ERAS works is to reduce the average length of stay, thereby reducing the economic burden and productivity loss on patients and promoting the hospital bed turnover rate. Therefore, ERAS should further focus on accelerating the rehabilitation process, and more economic support (such as subsidies) should be given to hospitals to carry out ERAS.
Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure
Authors: Zhang Yi , Wu Wei , Wang Yijie , Tong Lingjia , Hong Meng , Xia Qi , Chen Zhi
Published: November 2021

Objectives

Toll-like receptors (TLRs) on neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and potential signalling pathways. The aim of this study was to investigate alterations in TLR signalling pathways in neutrophils of ACLF patients.

Methods

Twenty-seven patients with compensated cirrhosis (n = 9), decompensated cirrhosis (n = 9) and ACLF (n = 9) were enrolled in the study. Neutrophils were isolated, and alterations in TLR signalling pathways were evaluated using an RT2 Profiler™ PCR Array. The fold change for each gene (2(−∆∆CT)) was compared among the groups. Genes with a fold change ratio of ≥ 2 or ≤ 0.5 along with a p value of < 0.05 were considered to be differentially expressed.

Results

A total of 17 genes were upregulated in neutrophils from patients with compensated cirrhosis and were mainly distributed in adaptors, TLR-interacting proteins and downstream pathways. Six genes were detected in patients with decompensated cirrhosis. A trend of downregulation of genes in the TLR signalling pathway was observed in neutrophils of patients with cirrhosis and ACLF. TLR3, IFNG, IL1B, TBK1, CCL2 and LTA were downregulated in neutrophils. Moreover, CD14 and IL10 were upregulated in neutrophils of ACLF patients.

Conclusions

TLR signalling pathway genes were differentially regulated in neutrophils between cirrhosis and ACLF. In ACLF patients, defective expression of TLR3 and IFN, along with enhanced CD14 and IL10 expression, was characterized by transcriptional alterations of neutrophils.
Home-based exercise program for adolescents with juvenile dermatomyositis quarantined during COVID-19 pandemic: a mixed methods study
Authors: Astley Camilla , Sieczkowska Sofia Mendes , Marques Isabela Gouveia , Ihara Bianca Pires , Lindoso Livia , Lavorato Sofia Simão Martins , Campos Lucia Maria Arruda , Pereira Rosa Maria Rodrigues , Elias Adriana Maluf , Aikawa Nadia Emi , Kozu Katia , Iraha Amanda Yuri , Franco Tathiane Christine , Roschel Hamilton , Queiroz Ligia Bruni , Polanczyk Guilherme Vanoni , Silva Clovis Artur , Gualano Bruno
Published: November 2021

Background

Exercise has been suggested to prevent deterioration of health-related quality of life (HRQL) and overall health in pediatric rheumatologic diseases during the COVID-19 pandemic. Herein we describe the effects of a 12-week, home-based, exercise program on overall health and quality of life among quarantined patients with juvenile dermatomyositis (JDM).

Method

This prospective, quasi-experimental, mixed methods (qualitative and quantitative) study was conducted between July and December 2020, during the most restricted period of COVID-19 pandemic in Brazil. The home-based exercise program consisted of a 12-week, three-times-a-week, aerobic and strengthening (bodyweight) training program. Qualitative data were systematically evaluated. Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory (PedsQOL) and Pittsburgh Sleep Quality Index (PSQI) evaluate symptoms of mental health disorder, HRQL, and quality of sleep.

Findings

11 patients (out of 27) met the inclusion criteria (91% female; mean ± SD age: 13.5 ± 3.2 years). Adherence to the intervention was 72.6%. Barriers to exercise involved poor internet connectivity, excessive weekly sessions, and other commitments. Even though not statistically significant, Self-report SDQ subscales Total Difficulties Score, Emotional Problems Score, and PedsQOL School Functioning Score improved after intervention (− 2.4; 95%confidence interval [CI] -5.1; 0.2, p = 0.06; − 1.0; 95%CI -2.2; 0.2, p = 0.09 and; 11.7; 95%CI -2.5; 25.8, p = 0.09, respectively). Remaining SDQ subscales were not altered. Six themes emerged from patients’ and parents’ comments (qualitative results). Patients engaged in exercise reported other health-related benefits including increased motivation, concentration and strength.

Interpretation

A home-based exercise program was associated with qualitative perceptions of improvements in overall health and HRQL by quarantined adolescents with JDM during COVID-19 pandemic. Lessons from this trial may help developing interventions focused on tackling physical inactivity in JDM.
Hypothermia modulates myeloid cell polarization in neonatal hypoxic–ischemic brain injury
Authors: Seitz Marina , Köster Christian , Dzietko Mark , Sabir Hemmen , Serdar Meray , Felderhoff-Müser Ursula , Bendix Ivo , Herz Josephine
Published: November 2021

Background

Neonatal encephalopathy due to hypoxia–ischemia (HI) is a leading cause of death and disability in term newborns. Therapeutic hypothermia (HT) is the only recommended therapy. However, 30% still suffer from neurological deficits. Inflammation is a major hallmark of HI pathophysiology with myeloid cells being key players, participating either in progression or in resolution of injury-induced inflammation. In the present study, we investigated the impact of HT on the temporal and spatial dynamics of microglia/macrophage polarization after neonatal HI in newborn mice.

Methods

Nine-day-old C57BL/6 mice were exposed to HI through occlusion of the right common carotid artery followed by 1 h hypoxia. Immediately after HI, animals were cooled for 4 h or kept at physiological body core temperature. Analyses were performed at 1, 3 and 7 days post HI. Brain injury, neuronal cell loss, apoptosis and microglia activation were assessed by immunohistochemistry. A broad set of typical genes associated with classical (M1) and alternative (M2) myeloid cell activation was analyzed by real time PCR in ex vivo isolated CD11b+ microglia/macrophages. Purity and composition of isolated cells was determined by flow cytometry.

Results

Immediate HT significantly reduced HI-induced brain injury and neuronal loss 7 days post HI, whereas only mild non-significant protection from HI-induced apoptosis and neuronal loss were observed 1 and 3 days after HI. Microglia activation, i.e., Iba-1 immunoreactivity peaked 3 days after HI and was not modulated by HT. However, ex vivo isolated CD11b+ cells revealed a strong upregulation of the majority of M1 but also M2 marker genes at day 1, which was significantly reduced by HT and rapidly declined at day 3. HI induced a significant increase in the frequency of peripheral macrophages in sorted CD11b+ cells at day 1, which deteriorated until day 7 and was significantly decreased by HT.

Conclusion

Our data demonstrate that HT-induced neuroprotection is preceded by acute suppression of HI-induced upregulation of inflammatory genes in myeloid cells and decreased infiltration of peripheral macrophages, both representing potential important effector mechanisms of HT.
Metabolic reprogramming mediates hippocampal microglial M1 polarization in response to surgical trauma causing perioperative neurocognitive disorders
Authors: Luo Gang , Wang Xiaofeng , Cui Yongchen , Cao Yue , Zhao Zhe , Zhang Junfeng
Published: November 2021

Background

Microglial polarization toward pro-inflammatory M1 phenotype are major contributors to the development of perioperative neurocognitive disorders (PNDs). Metabolic reprogramming plays an important role in regulating microglial polarization. We therefore hypothesized that surgical trauma can activate microglial M1 polarization by metabolic reprogramming to induce hippocampal neuroinflammation and subsequent postoperative cognitive impairment.

Methods

We used aged mice to establish a model of PNDs, and investigated whether surgical trauma induced metabolic reprograming in hippocampus using PET/CT and GC/TOF–MS based metabolomic analysis. We then determined the effect of the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) on hippocampal microglial M1 polarization, neuroinflammation, and cognitive function at 3 d after surgery.

Results

We found that surgery group had less context-related freezing time than either control or anesthesia group (P < 0.05) without significant difference in tone-related freezing time (P > 0.05). The level of Iba-1 fluorescence intensity in hippocampus were significantly increased in surgery group than that in control group (P < 0.05) accompanied by activated morphological changes of microglia and increased expression of iNOS/CD86 (M1 marker) in enriched microglia from hippocampus (P < 0.05). PET/CT and metabolomics analysis indicated that surgical trauma provoked the metabolic reprogramming from oxidative phosphorylation to glycolysis in hippocampus. Inhibition of glycolysis by 2-DG significantly alleviated the surgical trauma induced increase of M1 (CD86+CD206−) phenotype in enriched microglia from hippocampus and up-regulation of pro-inflammatory mediators (IL-1β and IL-6) expression in hippocampus. Furthermore, glycolytic inhibition by 2-DG ameliorated the hippocampus dependent cognitive deficit caused by surgical trauma.

Conclusions

Metabolic reprogramming is crucial for regulating hippocampal microglial M1 polarization and neuroinflammation in PNDs. Manipulating microglial metabolism might provide a valuable therapeutic strategy for treating PNDs.
Administration of anti-ERMAP antibody ameliorates Alzheimer’s disease in mice
Authors: Liu Haiyan , Zhao Jin , Lin Yujun , Su Min , Lai Laijun
Published: November 2021

Background

Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder and characterized by progressive loss of memory and cognitive functions, which are associated with amyloid-beta (Aβ) plaques. Immune cells play an important role in the clearance of Aβ deposits. Immune responses are regulated by immune regulators in which the B7 family members play a crucial role. We have recently identified erythroid membrane-associated protein (ERMAP) as a novel B7 family-related immune regulator and shown that ERMAP protein affects T cell and macrophage functions.

Methods

We produced a monoclonal antibody (mAb) against ERMAP protein and then determined the ability of the mAb to affect cognitive performance and AD pathology in mice.

Results

 We have shown that the anti-ERMAP mAb neutralizes the T cell inhibitory activity of ERMAP and enhances macrophages to phagocytose Aβ in vitro. Administration of the mAb into AD mice improves cognitive performance and reduces Aβ plaque load in the brain. This is related to increased proportion of T cells, especially IFNγ-producing T cells, in the spleen and the choroid plexus (CP), enhanced expression of immune cell trafficking molecules in the CP, and increased migration of monocyte-derived macrophages into the brain. Furthermore, the production of anti-Aβ antibodies in the serum and the macrophage phagocytosis of Aβ are enhanced in the anti-ERMAP mAb-treated AD mice.

Conclusions

Our results suggest that manipulating the ERMAP pathway has the potential to provide a novel approach to treat AD patients.
Postpartum intrauterine contraceptive device use and its associated factors in Ethiopia: systematic review and meta-analysis
Authors: Kassa Bekalu Getnet , Ayele Alemu Degu , Belay Habtamu Gebrehana , Tefera Adanech Getie , Tiruneh Gebrehiwot Ayalew , Ayenew Netsanet Temesgen , Mihiretie Gedefaye Nibret , Tenaw Lebeza Alemu , Semahegn Abenezer Melkie , Worku Mulugeta Dilie
Published: November 2021

Background

The intrauterine contraceptive device, a type of long-acting reversible contraception, is one of the most effective and safe contraceptive methods. In Ethiopia, intrauterine contraceptive device is little known and practised to delay pregnancy. Therefore, this study aimed to assess post-partum intrauterine contraceptive device utilisation and its associated factors among women in Ethiopia.

Method

In the current meta-analysis, variables were searched from different electronic database systems, including PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature. Data were extracted using a standardised data collection measurement tool. The data were also analysed by using STATA 16 statistical software. I2 tests assessed heterogeneity between the studies. A random-effect model was used to forecast the pooled utilisation of postpartum intrauterine contraceptive device.

Results

Twelve full-article studies were included. The pooled prevalence of post-partum intrauterine contraceptive device among women in Ethiopia was 21.63%. Occupation (OR = 4.44, 95% CI, 2.24–8.81), educational level of college and above (OR = 5.93, 95% CI, 2.55–13.8), antenatal care (OR = 2.09, 95% CI, 1.4–3.12), age (OR = 4.8, 95% CI, 2.3–10.04), good knowledge (OR = 4.16, 95% CI, 1.65–10.49), counseling (OR = 3.05, 95%CI, 1.41–6.63), husband support (OR = 11.48, 95% CI, 6.05–21.79) and awareness about IUCD (OR = 3.86, 95% CI, 1.46–10.2) were positively associated with utilization of postpartum intrauterine contraception device.

Conclusions

Utilisation of post-partum intrauterine contraceptive device was significantly low. Scaling up women’s educational status and ANC use has paramount importance in increasing post-partum IUD use, which further improves maternal and child health in general. This finding may be useful in both reproductive health promotion at an individual level and policy-making regarding this issue.
Development and validation of the reproductive health literacy questionnaire for Chinese unmarried youth
Authors: Ma Xuemei , Yang Yufan , Wei Qian , Jiang Hong , Shi Huijing
Published: November 2021

Objectives

This study aimed to develop and validate the reproductive health literacy questionnaire for Chinese unmarried youth aged 15–24.

Methods

We conducted a validity and reliability study of the questionnaire through a cross-sectional survey and test–retest analysis in four districts in Shanghai between April and June 2017. A total of 1587 participants completed a self-administered questionnaire anonymously on-site and the trained investigators conducted quality check afterwards. Sixty participants among them completed the test–retest assessment with 2 weeks interval. The reliability was determined by internal consistency, spilt-half reliability and test–retest reliability. The construct validity was assessed by confirmatory factor analysis.

Results

The 58-question reproductive health literacy questionnaire for Chinese unmarried youth demonstrated high internal consistency (Cronbach’s α = 0.919), spilt-half reliability (Guttman splitting coefficient = 0.846) and test–retest reliability (correlation coefficient = 0.720). The confirmatory factor analysis showed that the construct of the questionnaire fitted well with the hypothetical model. The reproductive health literacy scores in unmarried girls aged 15–24 were higher than boys (P < 0.05) and college students who lived in rural areas when they were middle and high school obtained lower score than those living in cities and suburbs (P < 0.01).

Conclusion

The reproductive health literacy questionnaire for Chinese unmarried youth demonstrated good reliability and validity, which could potentially be used as an effective evaluation instrument to assess reproductive health literacy among Chinese young people.
Unmet need for family planning and factors associated among women living with HIV in Oromia regional state, Ethiopia
Authors: Demissie Dereje Bayissa , Bulto Gizachew Abdissa , Mmusi-Phetoe Rose
Published: November 2021

Objectives

The purpose of this study was to determine the prevalence of the unmet need and identifying factors associated with the unmet need among women of reproductive age living with HIV in Oromia regional state, Ethiopia. One critical component of both a full range of contraceptives and satisfying demand for family planning with HIV services all women living with HIV is the appropriate model for HIV therapy, HIV prevention, and care with family planning services in a resource-limiting area like Ethiopia.

Methods

Health facility-based cross-sectional study design was conducted among women living with HIV attending ART clinics in the special zone of, Oromia regional state, by simple random sampling was used to select 654 respondents. Both bivariate and multivariable logistic regressions analysis was used to identify at adjusted odds ratio (AOR) with 95% CI in the final model.

Result

The study assessed the magnitude of demand for family planning among HIV-infected women and established that the demand was 630 (96.3%), of which 100 (16%) of women of reproductive age living with HIV had unmet needs for family planning while attending monthly ART clinic drug refilling and follow up. This study identified that factors found to be associated with met needs for family planning among women of reproductive age living with HIV attending ART/PMTC were discussions with healthcare providers (AOR = 4.33, 95% CI 2.56–7.32), previous pregnancy (AOR = 3.07, 95% CI 1.84–5.12); future fertility desire (AOR = 2.15, 95% CI 1.31–3.51); having sexual partners (AOR = 5.26, 95% CI 1.79–15.5) and the number of the sexual partner (one) (AOR = 7.24, 95% CI 1.82–28.74) were identified independent predictors of met needs for family planning.

Conclusion

The overall demand for family planning was 96% among the women living with HIV, and that 16% of women had an unmet need for family planning. The authors conducted a logistic regression and find various dependent variables that are associated with the met need for family planning services, such as having discussions with healthcare providers, having a partner and previous pregnancy; future fertility desire, the last pregnancy being intended. These results are interpreted to suggest that clear policy implications of family planning must be better integrated into ART clinics.
Improving postoperative radiographs for the parameter measurement of hexapod external fixator using an additional foot ring
Authors: Liu Yanshi , Liu Kai , Cai Feiyu , Zhang Tao , Yusufu Aihemaitijiang
Published: November 2021

Background

It is challenging to determine the orthogonality of radiographs in daily clinical practice. The purpose of this study was to show the usefulness of an additional foot ring which might determine the orthogonality of postoperative radiographs for the parameter measurement of hexapod external fixator.

Methods

We retrospectively analyzed 81 consecutive trauma patients with tibial shaft fractures treated by the hexapod external fixator at our institution from September 2014 to July 2019. Starting in March 2016, the postoperative radiographs for parameter measurement were obtained under the control of an additional foot ring. The final data consisted of 47 patients in traditional radiographs (Group I) and 34 patients under the control of foot ring during the radiographic process (Group II). The demographic data, original postoperative deformities, residual deformities after final correction, number of repeated radiographs after the first postoperative radiographs, time to the satisfactory reduction achieved, and external fixation time in all patients were documented and analyzed. The Johner–Wruhs criteria were used for the final clinical outcomes evaluation at the last clinical visit.

Results

Satisfactory reduction and bone union were achieved in all patients. There were no statistical significances between the two groups in the demographic data, original postoperative deformities, residual deformities after final correction, external fixation time, and the final clinical outcomes (P > 0.05). The mean number of repeated radiographs after the first radiographs (1.4 times) and mean time to the satisfactory reduction achieved (3.3 days) in patients with an additional foot ring used were all less than those without foot ring (2.4 times, 5.3 days) (P < 0.05).

Conclusions

The additional foot ring is a practical device to ensure the orthogonality of postoperative radiographs for the hexapod external fixator parameter measurement. Radiation exposure, duration of deformity correction, and cost for patients might be reduced due to the less repeated radiographs with the wrong position.
Comparison of preoperative trans-thoracic echocardiography with intraoperative findings in patients with congenital heart disease undergoing surgery: a prospective observational study
Authors: Njem Josiah Miner , Edwin Frank , Tettey Mark
Published: November 2021

Objective

To determine the diagnostic accuracy and safety of trans-thoracic echocardiography alone for indicating surgery by correlating preoperative trans-thoracic echocardiography with intra-operative findings in patients with congenital heart disease (CHD) in a low resource, low volume center.

Methodology

The pre-operative trans-thoracic echocardiography and intra-operative findings of two hundred and fifty patients with CHD, undergoing surgery at the National Cardiothoracic Centre (NCTC), Korle Bu Teaching Hospital, from 2012 to 2017 were prospectively compared. Included in this prospective study, were all patients with CHD who had trans-thoracic echocardiography alone at the NCTC. Excluded were patients who were operated at the NCTC based on echocardiography done elsewhere, those who had echocardiography at the NCTC but were operated elsewhere, as well as those whose operative decision were based on cardiac catheterization or CT angiography and patients with acquired heart defects. The analysis included profiling of patients on different demographic and clinical parameters. SPSS software was used for analysis.

Results

Of the 250 patients ages ranged from 2 months to 60 years. The mean was 4 years 95 days, median 1 year 180 days. The female sex accounted for 152 (60.6%). The preoperative trans-thoracic echocardiography correlated with intra-operative findings completely in 228 (91.2%) of patients, affirming the accuracy of this imaging modality. There were however, 19 (7.6%) false negatives and 3 (1.2%) false positive. Neither the false positive nor false negative errors resulted in complications or adversely affected the surgical outcome.

Conclusion

Based on the results of this study, preoperative transthoracic echocardiography done by cardiologists at the National Cardiothoracic Center, Korle Bu Teaching Hospital Accra, demonstrated a high correlation with intraoperative findings. Echocardiography also proved to be sensitive, accurate and safe for indicating surgery in patients with congenital heart disease.
Efficacy and safety of Chinese medicine JCM-16021 for diarrhea-predominant irritable bowel syndrome: study protocol for a multi-center, randomized, double-blind, placebo controlled clinical trial
Authors: Zheng Ya , Ching Jessica , Cheng Chung Wah , Lam Wai Ching , Chan Kam Leung , Zhang Xuan , Lam Pui Yan , Wu Xing Yao , Zhong Linda L. D. , Cao Pei Hua , Lo Cho Wing , Cheong Pui Kuan , Lin Zhixiu , Koh Matthew , Wu Justin , Bian Zhao Xiang
Published: November 2021

Background

Irritable bowel syndrome (IBS) is a common gastrointestinal functional disease. Adults with IBS may experience abdominal pain, change of bowel habits, and abnormal stool form without organic disease. IBS can seriously affect their work productivity and quality of life, especially diarrhea-predominant irritable bowel syndrome (IBS-D). The Chinese medicine JCM-16021 has been shown to be potentially effective in improving the symptoms of IBS-D based on a small scale clinical trial. Hence, a large scale clinical study is designed to further evaluate the efficacy and safety of the Chinese medicine JCM-16021 for IBS-D with traditional Chinese medicine (TCM) pattern of Liver Stagnation and Spleen Deficiency (LSSD).

Methods

This study is a multi-center, randomized, double-blind, placebo-controlled clinical trial. 392 eligible participants will be enrolled with 2-week run-in, 8-week treatment and 8-week follow-up. After run-in period, participants will be randomized to receive either the Chinese medicine JCM-16021 or placebo for 8 weeks, and will have post-treatment follow up for another 8 weeks. The primary outcome is the improvement rate on the global assessment of improvement (GAI) at week 10. The secondary outcomes consist of changes of IBS-D symptoms, TCM pattern improvement, IBS-Quality of Life (IBS-QoL), IBS-Symptom Severity Score (IBS-SSS), safety, etc.

Results

A standard protocol has been developed for the study. The protocol will provided a detailed procedure to conduct a clinical trial and verify if the Chinese medicine JCM-16021 would significantly improve the overall symptoms of IBS-D with LSSD pattern of TCM by relieving abdominal pain, reducing stool frequency, improving the stool consistency and improving quality of life. The consolidated evidence from the study can shed light on the treatment of IBS-D with Chinese medicine.

Conclusion

The protocol will provide details for investigators about the study following SPIRIT Statement. High-quality evidence on the efficacy and safety of Chinese medicine JCM-16021 for IBS-D will be provided through strict compliance with the protocol.

Trial registration: ClinicalTrial.gov identifier: NCT03457324. Registered 8 February 2018,https://clinicaltrials.gov/ct2/show/NCT03457324?term=NCT03457324&draw=2&rank=1
Safety and preliminary efficacy of the Gam-COVID-Vac vaccine and outcomes of SARS-CoV-2 infection in Russian patients with genitourinary malignancies
Authors: Tsimafeyeu Ilya , Volkova Maria , Alekseeva Galina , Berkut Maria , Nosov Alexander , Myslevtsev Igor , Andrianov Andrey , Semenov Andrey , Borisov Pavel , Zukov Ruslan , Goutnik Vadim , Savchuk Sergey , Dengina Natalia , Mitin Timur
Published: November 2021

Background

To our knowledge, there is no clinical data pertaining to COVID-19 outcomes and safety of COVID-19 vaccination in Russian patients with genitourinary (GU) malignancies. Aim of our analysis was to describe the characteristics of the COVID-19 infection course as well as preliminary safety and efficacy of Gam-COVID-Vac vaccine in patients with active GU malignancies.

Methods

Patients were retrospectively identified at nine cancer centers in different regions. Patients were included if COVID-19 was diagnosed by a polymerase chain reaction. Data from additional patients with GU cancers who had no positive SARS-CoV-2 RT-PCR test before vaccination and who received two doses of Gam-COVID-Vac (Sputnik V) between 11 February and 31 August 2021 were collected for safety assessment. Anonymized data were collected through an online registry covering demographics, treatments, and outcomes.

Results

The Gam-COVID-Vac vaccine was well tolerated; no grade 3–5 toxicities were reported in 112 vaccinated metastatic GU cancer patients. The most common grade 1 adverse events (81%) were injection site reactions (76%), flu-like illness (68%), and asthenia (49%). Five patients experienced grade 2 chills (4.5%) and 3 patients had grade 2 fever (2.7%). With median follow-up of 6.2 months, two COVID-19 cases were confirmed by RT-PCR test in the vaccine group (of 112 participants; 1.8%). Eighty-eight patients with COVID-19 disease were included in the analysis. The average age as of the study enrollment was 66 (range 39–81) and the majority of patients were male with renal cell carcinoma (RCC). Thirty-six patients (41%) had evidence of metastatic disease, of these 22 patients were receiving systemic therapy. More than half of patients required hospitalization. Fifty-four patients (61%) experienced complications. Sixteen patients who developed COVID-19 pneumonia required mechanical ventilator support. Sixteen patients (18%) died in a median of 23.5 days after the date of COVID-19 diagnosis was established. The 3-month survival rate was 82%. Clinical and/or radiographic progression of cancer during COVID-19 infection or the subsequent 3 months was observed in 10 patients (11.4%).

Conclusion

Patients with GU malignancies are at increased risk of mortality from COVID-19 infection when compared to the general population. Vaccination could be safe in GU cancer patients.

Trial registration: retrospectively registered.
A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
Authors: Xu Shilin , Zhang Meichen , Fang Xiaocui , Meng Jie , Xing Haiyan , Yan Doudou , Liu Jian , Yang Yanlian , Wen Tao , Zhang Weiqi , Wang Jianxiang , Wang Chen , Xu Haiyan
Published: November 2021

Acute myeloid leukemia (AML) is a common malignant heterogeneous hematopoietic disease with very low average 5-year survival rate due to the refractory feature and high rate of relapse. CD123 is highly expressed on multiple types of AML cells, especially leukemia stem cells, and closely associated with the poor prognosis of AML. Aiming to meet the urgent demand to targeted therapeutics for the refractory AML patients, herein we synthesize a CD123 antagonistic peptide (PO-6) loaded in nanomicelles (mPO-6), and investigated its therapeutic effect and pharmacokinetics on a lab-established refractory AML mice model (AE & CKITD816V). It is shown that the PO-6 can effectively bind to the CD123+ AML cells and the micellar formulation mPO-6 increases the dissolution stability and the specific binding capacity. When injected intravenously, mPO-6 significantly prolongs the survival of the refractory AML mice by interfering CD123/IL-3 axis, evidenced by the down regulation of phosphorylation of STAT5 and PI3K/AKT and the inhibition of activated NF-κB in the nucleus, as well as by the analysis results of next generation RNA-sequencing (RNA-seq) with the bone marrow of the AML mice. The antagonistic effect leads to the significantly reduction of AML cells infiltration in the bone marrow of the AML mice. In conclusion, mPO-6 could provide a potent antagonistic therapeutic approach for targeted treatment of AML.
RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
Authors: Wang Shengtan , Li Zaihong , Zhu Genhai , Hong Lan , Hu Chunyan , Wang Kang , Cui Kaiying , Hao Chunbo
Published: November 2021

Background

Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved.

Methods

Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells.

Results

Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability.

Conclusion

This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.
Identification and validation of objective triggers for initiation of resuscitation management of acutely ill non-trauma patients: the INITIATE IRON MAN study
Authors: Rovas Alexandros , Paracikoglu Efe , Michael Mark , Gries André , Dziegielewski Janina , Pavenstädt Hermann , Bernhard Michael , Kümpers Philipp
Published: November 2021

Background

While there are clear national resuscitation room admission guidelines for major trauma patients, there are no comparable alarm criteria for critically ill nontrauma (CINT) patients in the emergency department (ED). The aim of this study was to define and validate specific trigger factor cut-offs for identification of CINT patients in need of a structured resuscitation management protocol.

Methods

All CINT patients at a German university hospital ED for whom structured resuscitation management would have been deemed desirable were prospectively enrolled over a 6-week period (derivation cohort, n = 108). The performance of different thresholds and/or combinations of trigger factors immediately available during triage were compared with the National Early Warning Score (NEWS) and Quick Sequential Organ Failure Assessment (qSOFA) score. Identified combinations were then tested in a retrospective sample of consecutive nontrauma patients presenting at the ED during a 4-week period (n = 996), and two large external datasets of CINT patients treated in two German university hospital EDs (validation cohorts 1 [n = 357] and 2 [n = 187]).

Results

The any-of-the-following trigger factor iteration with the best performance in the derivation cohort included: systolic blood pressure < 90 mmHg, oxygen saturation < 90%, and Glasgow Coma Scale score < 15 points. This set of triggers identified > 80% of patients in the derivation cohort and performed better than NEWS and qSOFA scores in the internal validation cohort (sensitivity = 98.5%, specificity = 98.6%). When applied to the external validation cohorts, need for advanced resuscitation measures and hospital mortality (6.7 vs. 28.6%, p < 0.0001 and 2.7 vs. 20.0%, p < 0.012) were significantly lower in trigger factor-negative patients.

Conclusion

Our simple, any-of-the-following decision rule can serve as an objective trigger for initiating resuscitation room management of CINT patients in the ED.
Nasal spray live attenuated influenza vaccine: the first experience in Italy in children and adolescents during the 2020–21 season
Authors: Gasparini Chiara , Acunzo Miriam , Biuso Andrea , Roncaglia Stefania , Migliavacca Francesca , Borriello Catia R. , Bertolini Caterina , Allen Michaela R. , Orenti Annalisa , Boracchi Patrizia , Zuccotti Gian Vincenzo
Published: November 2021

Background

In Italy only recently, for the 2020–21 season, has the flu vaccination been extended to all children.

A quadrivalent live attenuated influenza vaccine (qLAIV) was administered to children aged 2–17 years for the first time.

We registered the number and severity of adverse reactions to (Fluenz Tetra™) and the factors influencing them, evaluated uniformity of access to care and assessed the degree of satisfaction with the vaccination of both parents and health care providers, in order to improve the 2021–22 vaccination program.

Methods

On vaccination day, a questionnaire was given out to collect information about the children and their parents. Between 1 and 3 months later, the parents were contacted to record any adverse reactions following (Fluenz Tetra™) and rate the degree of satisfaction.

Results

We received data of 3226 children from 2152 families.

Adverse events were reported in 24.8% of children: 80.6% mild, 18.1% moderate and 1.3% significant. The most common were rhinitis (52.5%) and fever (24.4%). Statistical analysis performed with a multiple regression model, showed that children aged 2–5 years have an increased risk of adverse events compared to both 6–10 years old (aRR 1.7, 95% CI 1.5–1.9, p < 0. 001) and 11–17 years old (aRR 1.5, 95% CI 1–2.2, p = 0.051).

Most families chose to vaccinate their children to protect them and because they were concerned about Covid19.

The main channel through which parents became aware of a new flu vaccination was word-of-mouth (39.8%), which occurred mostly among parents of the same school group, followed by information from the child’s doctor (30.6%), the Internet (26.9%), personal research (15%), newspapers (4%), telecommunications (7.5%) and other (2.6%).

Most parents (83.3%) were very satisfied and intend to vaccinate their children with qLAIV again (83.8%). The majority of operators (93%) considered the experience as excellent and are willing to repeat it (94.6%).

Conclusion

(Fluenz Tetra™) proved to be easy to administer and the degree of satisfaction was high among both health workers and parents. Considering its substantial safety profile especially in school-age children and adolescents, all these aspects make the nasal qLAIV optimal for widespread immunization.

Schools offer the best setting to reach more families and physicians should be actively involved.
Efficacy and safety of Chinese herbal medicine Wen Xin granules for the treatment of unstable angina pectoris with Yang deficiency and blood stasis syndrome: study protocol for a randomized controlled trial
Authors: Tian Pan-pan , Wu Qing-juan , Li Jun , Chen Heng-wen , Wu Ji , Deng Ya-wen , Xie Zi-cong , Zhao Wei , Tan Yu-qing
Published: November 2021

Introduction

Unstable angina pectoris (UAP) is the common type of coronary heart disease with the risk of developing into acute myocardial infarction (AMI). Currently, there are still numerous patients suffering from recurrent angina after revascularization or conventional medication due to the microvascular lesions, endothelial dysfunction, chronic inflammation, in-stent restenosis, and other factors. As an important part of China’s medical and health care system, traditional Chinese medicine (TCM) has rich clinical experience in the treatment of UAP. According to the theory of TCM, Yang deficiency and blood stasis syndrome is a common type of UAP. Wen Xin decoction, as a type of Chinese herbal medicine, has been used in the clinic for years and shown great efficacy in the treatment of UAP with Yang deficiency and blood stasis syndrome. This study aims to evaluate the efficacy and safety of Wen Xin granular in patients with UAP.

Methods and analysis

This is a double-blinded, randomized, placebo-controlled clinical trial. A total of 502 participants will be randomly allocated to the intervention group and the placebo group. Based on conventional medication, the intervention group will be treated with Wen Xin granular and the placebo group will be treated with Wen Xin granular placebo. The primary outcomes are major adverse cardiovascular events (MACE). Assessments will be performed 1 year after the treatment. The secondary outcomes include TCM symptom scale score, Seattle angina questionnaire, and thromboelastography. Assessments will be performed at baseline (before randomization) and 4 and 8 weeks after randomization.

Discussion

This trial will provide high-quality data on the benefits and risks of Wen Xin granular in patients with UAP.

Trial registration

ClinicalTrials.govNCT04661709. Registered on 30 November 2020
Multimodal cerebral imaging study on the effects of “Adjust Zang Dredge Meridian” electroacupuncture on cerebral central sensitization in PDPN patients: a study protocol for a sham-controlled, randomized trial
Authors: Li Mengyuan , Yao Lin , Huang Haipeng , Zhang Liying , Zheng Haizhu , Wang Guan , Zhong Zhen , Ma Shiqi , Yu Shuo , Wang Hongfeng
Published: November 2021

Background

Painful diabetic peripheral neuropathy (PDPN) has a great impact on an individual’s quality of life. The current researchers’ previous trial suggested that acupuncture was a promising adjunctive treatment for PDPN. However, the underlying mechanism of action of acupuncture treatment for PDPN is still unclear, especially its effects at the cerebral level. The aim of this trial will be to explore how acupuncture works in treating PDPN by using multimodal cerebral imaging.

Method and design

This will be a randomized controlled trial. A total of 150 participants will be recruited and assigned to one of three groups: the healthy group, the DM without PDPN group and the DM with PDPN group. Participants in the DM without PDPN and the DM with PDPN groups will each be further divided between an electroacupuncture group and a sham electroacupuncture group. Participants will receive six treatment sessions per week for 4 weeks. Multimodal cerebral imaging includes resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS); this neurophysiological testing will be the primary outcome measure. Subjective pain scales and blood analysis will be a secondary outcome measure and will be used to assess the clinical efficacy of the intervention. Multimodal cerebral imaging will be used to detect cerebral activity changes in each treatment group. The clinical data and fMRI data will be analysed for all the groups. Multiple correlation regression analyses will be used to assess the association between changes in cerebral functional activity and the improvement of clinical outcomes after acupuncture treatment.

Discussion

This study is based on the results of the researchers’ previous study, and using combined clinical and cerebral function changes, it will help evaluate the effects of acupuncture on PDPN. The investigation of acupuncture’s central mechanism of action will further expand the understanding of acupuncture treatment of PDPN.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900024109. Registered on 26 June 2019.
Visual attention and inhibitory control in children, teenagers and adults with autism without intellectual disability: results of oculomotor tasks from a 2-year longitudinal follow-up study (InFoR)
Authors: Amestoy Anouck , Guillaud Etienne , Bucchioni Giulia , Zalla Tiziana , Umbricht Daniel , Chatham Christopher , Murtagh Lorraine , Houenou Josselin , Delorme Richard , Moal Myriam Ly-Le , Leboyer Marion , Bouvard Manuel , Cazalets Jean-René
Published: November 2021

Background

Inhibitory control and attention processing atypicalities are implicated in various diseases, including autism spectrum disorders (ASD). These cognitive functions can be tested by using visually guided saccade-based paradigms in children, adolescents and adults to determine the time course of such disorders.

Methods

In this study, using Gap, Step, Overlap and Antisaccade tasks, we analyzed the oculomotor behavior of 82 children, teenagers and adults with high functioning ASD and their peer typically developing (TD) controls in a two-year follow-up study under the auspices of the InFoR-Autism project. Analysis of correlations between oculomotors task measurements and diagnostic assessment of attentional (ADHD-RS and ADHD comorbidity indices) and executive functioning (BRIEF scales) were conducted in order to evaluate their relationship with the oculomotor performance of participants with ASD.

Results

As indicated by the presence of a Gap and Overlap effects in all age groups, the oculomotor performances of ASD participants showed a preserved capability in overt attention switching. In contrast, the difference in performances of ASD participants in the Antisaccade task, compared to their TD peers, indicated an atypical development of inhibition and executive functions. From correlation analysis between our oculomotor data and ADHD comorbidity index, and scores of attention and executive function difficulties, our findings support the hypothesis that a specific dysfunction of inhibition skills occurs in ASD participants that is independent of the presence of ADHD comorbidity.

Limitations

These include the relatively small sample size of the ASD group over the study’s two-year period, the absence of an ADHD-only control group and the evaluation of a TD control group solely at the study’s inception.

Conclusions

Children and teenagers with ASD have greater difficulty in attention switching and inhibiting prepotent stimuli. Adults with ASD can overcome these difficulties, but, similar to teenagers and children with ASD, they make more erroneous and anticipatory saccades and display a greater trial-to-trial variability in all oculomotor tasks compared to their peers. Our results are indicative of a developmental delay in the maturation of executive and attentional functioning in ASD and of a specific impairment in inhibitory control.