bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombosis in Patients with Post-Polycythemia Vera Myelofibrosis: Incidence and Risk Factors
Authors: Teng Guangshuai , Zhang Yuhui , Gao Chao , Hu Naibo , Du Chenxiao , Bai Jie
Published: November 2021

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV). Post PV myelofibrosis (MF) is the advanced phase in the natural progression of PV. To explore the risk factors for thrombosis in post-PV MF, clinical characteristics, laboratory characteristics, the incidence of thrombosis and survival were retrospectively analyzed in a cohort of 163 Chinese patients with post-PV MF. The Kaplan-Meier method and multivariate Cox analysis were used to identify the risk factors and a risk model for thrombosis was established. Among the 163 patients, the median follow-up duration was 6 (1-18) years. During follow-up, 84 (51.5%) patients developed thrombosis, 11 (6.7%) patients progressed to acute leukemia, and 35 (21.5%) patients died (20% of whom died due to thrombosis). The 5-year, 10-year, and 15-year thrombosis-free survival (TFS) rates were 59.8%, 28.2%, and 9%, respectively. The TFS time of the post-PV MF patients was significantly lower than that of the age- and sex-matched PV patients (P<0.001). The incidence of venous thrombosis was significantly higher after the diagnosis of post-PV MF than before or at the time of the diagnosis, and the proportions of patients with JAK 2 V617F allele burden ≥75% or absolute monocyte count ≥1.5×10 9/L was significantly higher in the venous thrombosis group than in the group without venous thrombosis (P<0.05). Multivariate analysis showed that palpable splenomegaly (P=0.008, HR=3.284, 95% CI [1.373,7.855]), age ≥60 years (P=0.048, HR=1.604, 95% CI [1.004,2.56]), and a history of thrombosis (P<0.001, HR=2.767, 95% CI [1.735, 4.412]) were risk factors for thrombosis in post-PV MF patients, then a risk model for thrombosis was established according to these data. The median TFS durations in patients in the extremely high-risk group, high-risk group, intermediate-risk group, and low-risk group were 2 years, 4 years, 9 years, and 13 years, respectively. In summary, post-PV MF patients have a higher incidence of thrombosis. Reducing the volume of the spleen and the allele burden of JAK2 V617F is critical to prevent thrombosis in post-PV MF patients.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Mesenchymal Stromal Cell-Derived S100A8 Promotes Acute Myeloid Leukemia Progression Via ROS Signaling
Authors: Wu Jinxian , Liu Xiaoyan , Zhou Fuling
Published: November 2021

Introduction: Mesenchymal stromal cell (MSC) is an important cell component in the bone marrow microenvironment. MSC-derived inflammatory factors regulate the progression of acute myeloid leukemia (AML) by regulating the signaling pathways in hematopoietic cells. S100A8 is an inflammatory factor which belong to the calcium-binding protein S100 family. In vivo animals experiments showed that increased expression of S100A8 in MSC was accompanied by increased proliferative MSCs, and decreased mature osteoblasts. MSC-derived S100A8 can also cause mitochondrial dysfunction in hematopoietic stem progenitor cells, induce oxidative stress response and DNA damage repair, that promotes the progression of myeloid dysplastic syndromes (MDS). However, whether MSC-derived S100A8 involved in AML development have not been reported. In this study, we attempted to elucidate the regulation of MSC-derived S100A8 on MSC itself as well as leukemia cells.

Methods: Human MSCs were isolated from AML patients samples by whole bone marrow adherent culture, and the third to fifth passage cells were collected for analysis. The lentivirus vector carrying cDNA of S100A8 gene and the empty lentivirus vector were constructed and infected into MSCs,respectively. Cell cycle and apoptosis of MSCs were analysed by flow cytometry. Acute myeloid leukemia cell line Kasumi-1 was co-cultured with the two groups of mesenchymal stem cells in vitro for 3 days, respectively.cell cycle and apoptosis were analysed, and the cell proliferation was detected by Edu. The ROS levels of co-cultured Kasumi-1 cells were detected by flow cytometry. The apoptosis of kasumi-1 co-cultured cells treated with VP-16 for 48 hour was detected by flow cytometry.

Results: The rate of G0 phase cell in S100A8-overexpressed MSCs was higher than in control group.The proliferation rate of Kasumi-1 cells was significantly increased S100A8 overexpressed group than in control after 72-h co-culture, while the apoptosis rate of Kasumi-1 cells was significantly decreased in S100A8 overexpressed group. Futhermore, the apoptosis rate of Kasumi-1 cells co-cultured with S100A8-overexpressed MSCs was markedly lower than in control group after exposed in vp-16 for 48 hour.The ROS level of Kasumi-1 cells co-cultured with S100A8-overexpressed MSCs were significantly increased than those of the control group.

Conclusion: S100A8 derived from MSCs plays a critical role in progression and drug resistance of acute myeloid leukemia, by increasing the ROS levels of AML cells, that indicates S100A8 may serve as a potential novel therapeutic target in AML.

Disclosures

No relevant conflicts of interest to declare.
Sex Differences in EBV Viremia after Haplo-HSCT Imply Sex Bias during Immune Reconstitution
Authors: Wei Rong , Xu Lanping , Huang Xiaojun
Published: November 2021

Objective: Posttransplant infection is common and tough to deal, patients after HSCT rely on immune reconstitution for protection. We desperately need a deeper understanding of how the system works to help the patients overcome the infection.

Method: This study analyzed the disease course of EBV viremia after haplo-HSCT, as well as the laboratory testing data. The sex bias during immune reconstitution was manifested by comparing the outcomes between male and female patients,

Results: 236 patients received haplo-HSCT in 2013 in our center, at a median follow up of 5 years, among whom 78 patients underwent EBV infection. The incidence of EBV viremia after transplantation is 33.1% in total, with a significant difference between men and women (40.0% and 26.7% respectively, p=0.034). Men tended to have earlier onset time (14-434d after HSCT) and longer duration (7-70d) than women (17-592d after HSCT, 7-30d). Both the initial and peak viral load were higher in men than in women (initial viral load＞10 4/ml: men 6.52% vs. women 3.13%, peak viral load＞10 5/ml: men 8.70% vs. women 3.13%). To explain this phenomenon, we analyzed the laboratory testing data on 30d and 60d after HSCT. And we found that male patients had higher plasma levels of immunoglobulin M on 60d after HSCT if infected by EBV, referring to more robust induction of innate immune (p=0.033). By contrast, female patients had significantly increased CD4+ T cell during EBV infection, representing more robust activation of adaptive immune (p=0.019).

Conclusion: These findings provide a possible explanation for the observed sex biases in EBV viremia after haplo-HSCT, and provide an important basis for the recognition of immune reconstitution, furthermore, raise concern of the development of a sex-based approach to the treatment and care of male and female patients with infection after HSCT.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
FISH-Guided Evaluation of Hyperdiploidy and Other Cytogenetic Abnormalities in Childhood Burkitt Lymphoma
Authors: Avgerinou Georgia , Filippidou Maria , Kostopoulos Ioannis V , Exarchos Athanasios , Stefanaki Kalliopi , Binenbaum Ilona , Liapis Konstantinos , Kossiva Lydia , Katsibardi Katerina , Polychronopoulou Sophia , Mantzourani Marina , Kattamis Antonis , Papadhimitriou Stefanos
Published: November 2021

Background: Burkitt lymphoma (BL) is the most common lymphoma in childhood. Apart from MYC rearrangement, considered the hallmark of the disease, BL often presents with additional chromosome aberrations, the biological and clinical significance of which is not fully understood. Materials and methods: The study included 72 children (55 boys, 17 girls), aged 2-16 years (median 9), with BL diagnosed on the basis of histopathology and a demonstrable MYC rearrangement. Touch imprints from the diagnostic biopsy samples were investigated with i-FISH for MYC, BCL2, BCL6, IGH, IGK and IGL rearrangements genes and copy number aberrations involving 1q21/1p32, 7cen/7q31, 9cen/9p21, 13q14/13q34 and 17cen/17p13. Deviations from the diploid status were further investigated for aneusomies of the carrier chromosome with the use of appropriate chromosome enumeration probes. Results: MYC gene was demonstrated in all cases with MYC/IGH fusion in 83.3% (60/72). 47 cases (65.3%) were found with least one additional aberration, most commonly with 1q gain (29.2%), 7q gain (19.4%), 13q deletion (19.4%), hemizygous 9p loss (8.3%) and hyperdiploidy (8.3%). Advanced clinical stage (IV), 7q gain (but not trisomy 7) and -9/9p- were significantly associated with shorter overall survival. There was no instance of relapse or death among the hyperdiploid cases. Conclusions: This extensive FISH investigation on imprints of affected tissue provides clinically meaningful information on the genetic profile of BL and may prove valuable in the management of patients with no karyotype available. In particular, the demonstration of hyperdiploidy through the use of chromosome enumeration probes could offer the means for the delineation of clonal evolution pathways and the recognition of a subgroup of children with excellent prognosis who could be cured with low-intensity chemotherapy regimens.

Disclosures

Kattamis: VIFOR: Consultancy; CRISPR/Vertex: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; BMS/Celgene: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy.
IKZF1deletions Coupled with CD20 Expression Represents a Novel High-Risk Subtype in Adult B-Cell Progenitor Acute Lymphoblastic Leukemia
Authors: Tang Bingqing , Wang Zhixiang , Lin Dainan , He Xianjun , Cai Zihong , Huang Kangyu , Zhou Xuan , Lin Ren , Xiaoli Liu , Xu Na , Huang Fen , Sun Jing , Liu Qifa , Zhou Hongsheng
Published: November 2021

Genetic deletions of IKZF1 are associated with poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Here we investigated the effect of IKZF1 deletions (IKZF1 del) plus with immunotype in adult B-ALL in PDT-ALL-2016 cohort. This cohort study involved 161 patients with B-ALL from 2016 to 2019, with detailed information about IKZF1 del and CD20 expression. Validation cohort consists N= patients from TARGET cohort. IKZF1 del was detected in 36.0% of patients with 3-year event-free survival (EFS) of 37.2±6.7% and overall survival (OS) of 51.1±7.3%, compared to IKZF1 wild-type (IKZF1 wt) with EFS 55.4±5.1% (P<0.01) and OS 74.6±4.5% (P<0.05), respectively. CD20 expression was also associated with inferior EFS than CD20-negative group (P<0.05). Furthermore, IKZF1 del coupled with CD20 expression, termed as IKZF1 del/CD20+, comprised 12.4% of patients with 3-year EFS of 25.0±9.7% compared with IKZF1 wt (P<0.05 ) and IKZF1 del/CD20- (P<0.05 ) groups, respectively. Multivariable analyses demonstrated independence of IKZF1 del/CD20+ with highest hazard ratio for EFS and OS. Furthermore, the prognostic strength of IKZF1 del/CD20+ was confirmed in TARGET validation cohort. Eighty-one patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notably, neither IKZF1 del(P=0.6288), CD20 (P=0.0705) or IKZF1 del/CD20 (P=0.3410) groups were identified as poor outcome in allo-HSCT cohort. Collectively, our data demonstrate that IKZF1 del/CD20+ represents a very high-risk subtype in adult B-ALL; and particularly, allo-HSCT could overcome the poor outcome of IKZF1 del and IKZF1 del/CD20+.

Disclosures

No relevant conflicts of interest to declare.
Second Malignant Neoplasms (SMN) in Myeloma Patients Post Stem Cell Transplant (SCT)
Authors: Kulkarni Samar , Murray John , Cavet Jim , Dennis Mike , Bloor Adrian , Patel Amit , Castleton Anna , Tomlins Joanna
Published: November 2021

Introduction: Recent developments in management of patients with myeloma have resulted in longer survival. Availability of newer class of agents for treatment has prolonged survival, improved quality of life and achieved better disease control. Use of SCT, either autologous (AutoSCT) and to a lesser extent allogeneic (AlloSCT) still forms an important aspect of myeloma treatment pathway. Improved survivorship mandates evaluation of long term consequences and risk of SMN is one of the most important long-term consequences affecting overall outcome.

Aim: Estimate the risk of SMN post SCT in patients with Myeloma.

Methods and Materials: Analysis includes 779 patients who received SCT for myeloma from January 2002 to December 2019. Data was collected using case records, electronic patient records, transplant database and information from referring hospitals. Follow-up was updated to June 2020.

Results: Analysis includes 779 patients with myeloma (M: 488, F:291; median age:59yr, range: 26-75) receiving AutoSCT (n=716) or AlloSCT (n=63). Conditioning for AutoSCT was high dose melphalan in majority (n=714, 99.7%). AlloSCT conditioning was RIC (n=40/63, 63.5%) or MAC (n=23/63, 36.5%). TBI was part of conditioning in 51/779 (6.5%). There was no difference in demographics between two groups.

Results: Median follow-up was 46 mo (range: 0.2-220). Second malignancy was identified in 48 of 779 cases (6.0%). SMN developed in 6/63 (10%) AlloSCT and 42/716 (6%) AutoSCT patents (p=0.25). SMN types were haematological (n=21), lymphoma (n=6) and solid tumours (n=21). MDS was the only haematological SMN in this series. Secondary MDS developed in 20/21 of AutoSCT as compared to 1/63 in AlloSCT (p=0.01). Non-haematological SMN were breast (n=3), upper GI (n=3), lower GI (n=2), hepato-billiary (n=2), prostate (n=3), skin (n=5), and unknown primary (n=1). SMN incidence was higher with increasing follow-up (2002-2014, 8%; 2015-2017, 2.8%, 2018-2019, 0%, p=0.002). There was no association with development of SMN and gender, age at transplant, type of stem cell source or transplant conditioning. Incidence of SMN was significantly higher for all sites as compared to general population. Cumulative incidence of SMN was 5% at 5 yr, and 15% at 10 yr for AutoSCT patients.

Conclusion: Myeloma patients are at increased risk of SMN and need monitoring for long term side effects. Development of MDS post AutoSCT is the commonest SMN post AutoSCT but there is increased incidence of solid tumours as well. Impact of new modalities of treatment needs long term monitoring.

Disclosures

Bloor: Novartis: Honoraria; Kite, a Gilead Company: Honoraria.
The diversity among the species Tetragenococcus halophilus including new isolates from a lupine seed fermentation
Authors: Link Tobias , Vogel Rudi F. , Ehrmann Matthias A.
Published: November 2021

Background

Tetragenococcus (T.) halophilus can be isolated from a variety of fermented foods, such as soy sauce, different soy pastes, salted fish sauce and from cheese brine or degraded sugar beet thick juice. This species contributes by the formation of short chain acids to the flavor of the product. Recently, T. halophilus has been identified as a dominant species in a seasoning sauce fermentation based on koji made with lupine seeds.

Results

In this study we characterized six strains of T. halophilus isolated from lupine moromi fermentations in terms of their adaptation towards this fermentation environment, salt tolerance and production of biogenic amines. Phylogenic and genomic analysis revealed three distinctive lineages within the species T. halophilus with no relation to their isolation source, besides the lineage of T. halophilus subsp. flandriensis. All isolated strains from lupine moromi belong to one lineage in that any of the type strains are absent. The strains form lupine moromi could not convincingly be assigned to one of the current subspecies. Taken together with strain specific differences in the carbohydrate metabolism (arabinose, mannitol, melibiose, gluconate, galactonate) and amino acid degradation pathways such as arginine deiminase pathway (ADI) and the agmatine deiminase pathway (AgDI) the biodiversity in the species of T. halophilus is greater than expected. Among the new strains, some strains have a favorable combination of traits wanted in a starter culture.

Conclusions

Our study characterized T. halophilus strains that were isolated from lupine fermentation. The lupine moromi environment appears to select strains with specific traits as all of the strains are phylogenetically closely related, which potentially can be used as a starter culture for lupine moromi. We also found that the strains can be clearly distinguished phylogenetically and phenotypically from the type strains of both subspecies T. halophilus subsp. halophilus and T. halophilus subsp. flandriensis.
A NAC transcription factor OsNAC3 positively regulates ABA response and salt tolerance in rice
Authors: Zhang Xiang , Long Yan , Chen Xingxiang , Zhang Baolei , Xin Yafeng , Li Longying , Cao Shuling , Liu Fuhang , Wang Zhigang , Huang Hao , Zhou Degui , Xia Jixing
Published: November 2021

Background

NAC (NAM, ATAF and CUC) transcription factors (TFs) play vital roles in plant development and abiotic stress tolerance. Salt stress is one of the most limiting factors for rice growth and production. However, the mechanism underlying salt tolerance in rice is still poorly understood.

Results

In this study, we functionally characterized a rice NAC TF OsNAC3 for its involvement in ABA response and salt tolerance. ABA and NaCl treatment induced OsNAC3 expression in roots. Immunostaining showed that OsNAC3 was localized in all root cells. OsNAC3 knockout decreased rice plants’ sensitivity to ABA but increased salt stress sensitivity, while OsNAC3 overexpression showed an opposite effect. Loss of OsNAC3 also induced Na+ accumulation in the shoots. Furthermore, qRT-PCR and transcriptomic analysis were performed to identify the key OsNAC3 regulated genes related to ABA response and salt tolerance, such as OsHKT1;4, OsHKT1;5, OsLEA3–1, OsPM-1, OsPP2C68, and OsRAB-21.

Conclusions

This study shows that rice OsNAC3 is an important regulatory factor in ABA signal response and salt tolerance.
Diagnostic performance of a wearing dynamic ECG recorder for atrial fibrillation screening: the HUAMI heart study
Authors: Fu Wenxia , Li Ruogu
Published: November 2021

Background

Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia with high morbidity and mortality rate. Evidence shows that in every three patients with AF, one is asymptomatic. The asymptomatic and paroxysmal nature of AF is the reason for unsatisfactory and delayed detection using traditional instruments. Research indicates that wearing a dynamic electrocardiogram (ECG) recorder can guide accurate and safe analysis, interpretation, and distinction of AF from normal sinus rhythm. This is also achievable in an upright position and after exercises, assisted by an artificial intelligence (AI) algorithm.

Methods

This study enrolled 114 participants from the outpatient registry of our institution from June 24, 2020 to July 24, 2020. Participants were tested with a wearable dynamic ECG recorder and 12-lead ECG in a supine, an upright position and after exercises for 60 s.

Results

Of the 114 subjects enrolled in the study, 61 had normal sinus rhythm and 53 had AF. The number of cases that could not be determined by the wristband of dynamic ECG recorder was two, one and one respectively. Case results that were not clinically objective were defined as false-negative or false-positive. Results for diagnostic accuracy, sensitivity, and specificity tested by wearable dynamic ECG recorders in a supine position were 94.74% (95% CI% 88.76–97.80%), 88.68% (95% CI 77.06–95.07%), and 100% (95% CI 92.91–100%), respectively. Meanwhile, the diagnostic accuracy, sensitivity and specificity in an upright position were 97.37% (95% CI 92.21–99.44%), 94.34% (95% CI 84.03–98.65%), and 100% (95% CI 92.91–100%), respectively. Similar results as those of the upright position were obtained after exercise.

Conclusion

The widely accessible wearable dynamic ECG recorder integrated with an AI algorithm can efficiently detect AF in different postures and after exercises. As such, this tool holds great promise as a useful and user-friendly screening method for timely AF diagnosis in at-risk individuals.
Age is the only predictor for upper gastrointestinal malignancy in Chinese patients with uncomplicated dyspepsia: a prospective investigation of endoscopic findings
Authors: Huang Yu , Gui Qian , Li Huiyi , Long Xiaohua , Liang Xiao , Lu Hong
Published: November 2021

Background

Dyspepsia is a common cause of physician visits. If and when endoscopy should be performed depend on the regions and the populations. This study aimed to identify the current risk factors predictive of upper gastrointestinal malignancy or peptic ulcer in China with high prevalence of gastric cancer.

Methods

A questionnaire was conducted among consecutive outpatients undergoing their first esophagogastroduodenoscopy for dyspepsia. Symptoms other than alarm symptoms in this study were defined as uncomplicated dyspepsia.

Results

4310 outpatients (mean age 44, median 42, range 14–86) were included in the final analyses. Significant pathology was found in 13.8% (595/4310) patients including peptic ulcer (12.3%) and upper gastrointestinal malignancy (1.5%). Age, male sex and alarm symptoms were significantly associated with malignancy. The age cut-off identified for upper gastrointestinal malignancy was 56 years among patients with uncomplicated dyspepsia, which was similar to the combined cutoff of age and gender.

Conclusions

Age should be considered as the primary predictor for upper gastrointestinal malignancy in Chinese patients with uncomplicated dyspepsia. 56 could probably be the optimal age to identify those lesions in this population. Trial registration: Chictr.org (ChiCTR2000040775).
Expert-based medication reviews to reduce polypharmacy in older patients in primary care: a northern-Italian cluster-randomised controlled trial
Authors: Mahlknecht Angelika , Wiedermann Christian J. , Sandri Marco , Engl Adolf , Valentini Martina , Vögele Anna , Schmid Sara , Deflorian Felix , Montalbano Carmelo , Koper Dara , Bellmann Romuald , Sönnichsen Andreas , Piccoliori Giuliano
Published: November 2021

Background

Evidence regarding clinically relevant effects of interventions aiming at reducing polypharmacy is weak, especially for the primary care setting. This study was initiated with the objective to achieve clinical benefits for older patients (aged 75+) by means of evidence-based reduction of polypharmacy (defined as ≥8 prescribed drugs) and inappropriate prescribing in general practice.

Methods

The cluster-randomised controlled trial involved general practitioners and patients in a northern-Italian region. The intervention consisted of a review of patient’s medication regimens by three experts who gave specific recommendations for drug discontinuation.

Main outcome measures were non-elective hospital admissions or death within 24 months (composite primary endpoint). Secondary outcomes were drug numbers, hospital admissions, mortality, falls, fractures, quality of life, affective status, cognitive function.

Results

Twenty-two GPs/307 patients participated in the intervention group, 21 GPs/272 patients in the control group. One hundred twenty-five patients (40.7%) experienced the primary outcome in the intervention group, 87 patients (32.0%) in the control group. The adjusted rates of occurrence of the primary outcome did not differ significantly between the study groups (intention-to-treat analysis: adjusted odds ratio 1.46, 95%CI 0.99–2.18,p = 0.06; per-protocol analysis: adjusted OR 1.33, 95%CI 0.87–2.04,p = 0.2).

Hospitalisations as single endpoint occurred more frequently in the intervention group according to the unadjusted analysis (OR 1.61, 95%CI 1.03–2.51,p = 0.04) but not in the adjusted analysis (OR 1.39, 95%CI 0.95–2.03,p = 0.09). Falls occurred less frequently in the intervention group (adjusted OR 0.55, 95%CI 0.31–0.98; p = 0.04). No significant differences were found regarding the other outcomes.

Definitive discontinuation was obtained for 67 (16.0%) of 419 drugs rated as inappropriate.

About 6% of the prescribed drugs were PIMs.

Conclusions

No conclusive effects were found regarding mortality and non-elective hospitalisations as composite respectively single endpoints. Falls were significantly reduced in the intervention group, although definitive discontinuation was achieved for only one out of six inappropriate drugs. These results indicate that (1) even a modest reduction of inappropriate medications may entail positive clinical effects, and that (2) focusing on evidence-based new drug prescriptions and prevention of polypharmacy may be more effective than deprescribing.

Trial registration

Current Controlled Trials (ID ISRCTN: 38449870), date: 11/09/2013.
High dose intravenous vitamin C treatment in Sepsis: associations with acute kidney injury and mortality
Authors: McCune Thomas R. , Toepp Angela J. , Sheehan Brynn E. , Sherani Muhammad Shaheer K. , Petr Stephen T. , Dodani Sunita
Published: November 2021

Background

The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients.

Methods

Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU.

Results

Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46–2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003–2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09–2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48–1.31]).

Conclusion

Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.
Assessing the effectiveness of an app-based child unintentional injury prevention intervention for caregivers of rural Chinese preschoolers: protocol for a cluster randomized controlled trial
Authors: He Jieyi , Wang Wanhui , Ning Peishan , Cheng Peixia , Li Jie , Zheng Ming , Yuan Shujuan , Yang Lei , Wu Youyou , Zong Huiying , Schwebel David C. , Yang Yang , Hu Guoqing
Published: November 2021

Background

Compared to urban children, children living in rural areas of most countries, including China, are at higher risk of suffering unintentional injuries. Most proven injury prevention interventions, however, are rarely implemented in rural China due to lack of resources. Mobile health interventions are low-cost and easy-to-implement, facilitating implementing injury prevention in resource-limited areas (e.g., rural areas). This study is designed and implemented to examine the effectiveness of an app-based intervention for unintentional injury prevention among rural preschoolers in China.

Methods

A single-blind, 18-month, parallel-group cluster randomized controlled trial with 1:1 allocation ratio will be implemented in 2 rural areas of China (Yang County, Shaanxi Province, and Shicheng County, Jiangxi Province). In total, at least 3508 rural caregivers of preschoolers aged 3–6 years old who own a smartphone will be recruited from 24 preschools. Clusters will be randomized at the preschool level and allocated to the control group (receiving routine school-based education plus app-based parenting education excluding unintentional injury prevention) or the intervention group (receiving routine school-based education plus app-based parenting education including unintentional injury prevention). External support strategies will be adopted by local partners to minimize user fatigue, non-compliance, and attrition. Data collection will be conducted at baseline and then every 3 months during the 18-month follow-up time period. Intention-to-treat data analysis will be implemented. Missing values will be imputed by using the Expectation Maximization algorithm. Generalized estimating equation will test the overall effectiveness of the app-based intervention. A per-protocol sensitivity analysis will be conducted to test the robustness of results. Subgroup analyses will follow the strategies for primary analyses. The primary outcome measure is the incidence rate of unintentional injury among preschoolers during the study period. Secondary outcome measures comprise longitudinal changes in caregiver’s attitudes, caregiver-reported supervision behaviors, and caregiver-assessed home environment safety surrounding child unintentional injury prevention in the last week using a standardized audit instrument.

Discussion

The app-based intervention is expected to be feasible and effective over the 18-month intervention period. If the app is demonstrated effective as hypothesized, we will initiate processes to generalize and popularize it broadly to rural child caregivers across China.

Trial registration

ChiCTR2000037606, registered on August 29, 2020.
Model difference in the effect of cilostazol on the development of experimental pulmonary hypertension in rats
Authors: Ito Toshikazu , Zhang Erquan , Omori Ayaka , Kabwe Jane , Kawai Masako , Maruyama Junko , Okada Amphone , Yokochi Ayumu , Sawada Hirofumi , Mitani Yoshihide , Maruyama Kazuo
Published: November 2021

Background

Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats.

Methods

Fifty-one male Sprague–Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60 mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. The mean pulmonary artery pressure (mPAP), the right ventricle weight-to-left ventricle + septum weight ratio (RV/LV + S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed. Levels of the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB proteins in lung tissue were measured using Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed.

Results

mPAP [35.1 ± 1.7 mmHg (MCT) (n = 9) vs. 16.6 ± 0.7 (control) (n = 9) (P < 0.05); 29.1 ± 1.5 mmHg (CH) (n = 10) vs. 17.5 ± 0.5 (control) (n = 10) (P < 0.05)], RV/LV + S [0.40 ± 0.01 (MCT) (n = 18) vs. 0.24 ± 0.01 (control) (n = 10) (P < 0.05); 0.41 ± 0.03 (CH) (n = 13) vs. 0.27 ± 0.06 (control) (n = 10) (P < 0.05)], and %Muscularization and %MWT were increased by MCT injection and CH exposure. CLZ significantly attenuated these changes in the MCT model [mPAP 25.1 ± 1.1 mmHg (n = 11) (P < 0.05), RV/LV + S 0.30 ± 0.01 (n = 14) (P < 0.05)]. In contrast, these CLZ effects were not observed in the CH model. Lung eNOS protein expression was unchanged in the MCT model and increased in the CH model. Lung protein expression of AKT, phosphorylated AKT, and IκB was downregulated by MCT, which was attenuated by CLZ; the CH model did not change these proteins. Lung MCP-1 mRNA levels were increased in MCT rats but not CH rats.

Conclusions

We found model differences in the effect of CLZ on PH development. CLZ might exert a preventive effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might depend on the PH etiology.
Surgical antimicrobial prophylaxis in open reduction internal fixation procedures at a metropolitan hospital in Australia: a retrospective audit
Authors: Hassan Sarah , Chan Vincent , Stevens Julie , Stupans Ieva , Gentle Juliette
Published: November 2021

Background

Open reduction internal fixation (ORIF) of closed fractures is a required indication for surgical antimicrobial prophylaxis (SAP). Guidelines contain recommendations on how best to prescribe SAP, however, adherence to SAP guidelines remains suboptimal. The Australian Therapeutic Guidelines: Antibiotic v16 (updated April 2019) advocates for single dose prophylaxis for ORIF procedures. There is a paucity of information on how SAP is prescribed for ORIF of closed fractures in Australian hospitals. The aim of this study was to identify prescribing practice and to evaluate guideline adherence pre- and post-guideline update.

Methods

A retrospective audit was conducted for patients undergoing an ORIF of closed fractures at a metropolitan teaching hospital in a 6-month period during 2018 (pre-guideline update) and 2019 (post-guideline update). Data were collected on prescribing practice (perioperative antibiotics prescribed, dose, time and route of administration and duration of prophylaxis) and compared to SAP recommendations in Therapeutic Guidelines: Antibiotic v15 (2018) and v16 (2019). Descriptive statistics and Chi square tests were used to report categorical variables. Binary logistic regression was used to identify factors associated with guideline adherence. A p-value < 0.05 was deemed statistically significant.

Results

Data were collected for a total of 390 patients (n = 185, 2018; n = 205, 2019). Cefazolin was the most commonly prescribed antibiotic as per guideline recommendations, with variable, yet appropriate doses observed across the two audit periods. While 78.3% of patients received SAP for the correct duration in 2018, only 20.4% of patients received single dose prophylaxis in 2019. Overall adherence to guidelines was 63.2% in the 2018, and 18.0% in the 2019 audit periods respectively. Patient age was significantly associated with an increase in overall guideline adherence, while lower limb fractures, an American Society of Anesthesiologists (ASA) score of 3 and emergency admissions were associated with decreased overall adherence to SAP guidelines.

Conclusion

Adherence to guidelines was greater with v15 (2018) compared with v16 (2019). Patient factors, including limb fracture site and ASA score, had little impact on guideline adherence. Further research is required to understand what influences guideline adherence in the orthopaedic setting.
Validity and reliability of the Persian version of the oropharyngeal Mucositis quality of life scale
Authors: Hasheminasab Fatemeh Sadat , Pourpasha Mona , Dehghan Azizallah , Galousalari Mahboubeh Yari , Hashemi Seyed Mehdi , Setayesh Mohammad
Published: November 2021

Background

Oral mucositis is one of the serious complications of chemotherapy and/or radiotherapy that significantly affects the quality of patients’ life. The Oropharyngeal Mucositis-Specific Quality-of-Life questionnaire (OMQoL) is an acceptable instrument for measuring the quality of life in these patients. The aim of this study was to evaluate the validity and reliability of the Persian version of OMQoL questionnaire.

Methods

This study was a cross-sectional and multi-centric research. After translation from English to Persian, back translation, and cultural adaptation, the Persian version of the questionnaire was prepared. One hundred forty-four patients suffering from oral mucositis referred to three different university affiliated hospitals related to Zahedan, Kerman and Tehran Universities of Medical Sciences, were participated in this study. Then the questionnaire was completed by trained interviewers. The reliability was assessed by Cronbach’s alpha coefficient, and validity was measured through factor analysis, and construct validity (including discriminant validity, and convergent validity) methods.

Results

Cronbach's alpha in all dimensions was higher than 0.9 that indicated a perfect internal consistency. The results of factor analysis indicated that the dimensions specified in the Persian version were the same as the original version (Factor loading of all items > 0.4). The correlation coefficient for all items was more than 0.75, and the convergence validity was 100% in all dimensions.

Conclusion

The results of this study showed that the reliability, and validity of Persian version of OMQoL were acceptable, which can be used to measure the quality of life in patients with oral mucositis.
Construct validity for the self-reported competency and sub-construct associated characteristics of Romanian physicians in autism spectrum disorder
Authors: Rahbar Mohammad H. , Dobrescu Iuliana , Gillani Shezeen , Hessabi Manouchehr , Kim Sori , Stancu Mihaela , Rad Florina
Published: November 2021

Background

Lack of physicians’ knowledge regarding mental health, including Autism Spectrum Disorder (ASD) could have adverse effects on affected individuals’ health and quality of life. The purpose of this study was to provide construct validity for a modified questionnaire in order to determine the self-reported competency for underlying sub-constructs in ASD, make inferences on perceived competence in ASD based on a sample of Romanian physicians, and identify physicians’ characteristics associated with these sub-domains of competency.

Methods

For this survey, we modified a questionnaire that was used in Pakistan and Turkey, and administered it to a sample of 383 practicing physicians in Romania to assess their perceived competency regarding ASD. Exploratory factor analysis on 12 knowledge questions revealed five sub-domains: stigma, potential causes, children’s behavior, misconceptions, and educational needs associated with ASD knowledge. Using General Linear Models, we determined physicians’ characteristics that predict the total competency score and various competency sub-scores.

Results

Seventy-five percent of the responding physicians were female and 30% had over 30 years practicing medicine. The majority (73–94%) of physicians have correctly responded to some basic questions regarding knowledge about ASD. We also found that younger physicians were more knowledgeable about potential causes of ASD than older physicians (Adjusted Mean Score (AMS): 2.90 vs. 2.18, P < 0.01), while older physicians knew more about the behavior of children with ASD (AMS: 0.64 vs. 0.37, P = 0.02). We found a significant interaction (P < 0.01) between television as source of ASD knowledge and city where the clinic is located in relation to knowledge of the physicians regarding stigma related to ASD. However, the total score was not associated with the variables associated with sub-domains.

Conclusion

Using factor analysis, we demonstrated construct validity of five sub-domains related to Romanian physicians’ knowledge about ASD that include stigma, potential causes, behavior in ASD children, special education needs, and misconceptions related to ASD. The lack of significant association of the knowledge of physicians on ASD neither with the Psychiatry nor the Pediatric ward rotations at medical school may support the need for improving the curriculum on ASD in Romanian medical schools.
The moderating effect of emotional competence on job satisfaction and organisational commitment of healthcare professionals
Authors: Stamouli Elena , Gerbeth Sebastian
Published: November 2021

Background

Healthcare organisations, such as hospitals, are largely seen as task-oriented, width different people expected to work in interdependent teams. The objective of this study was to investigate the relevance of individual factors (job satisfaction) and individual competences (emotional competence) for organisational commitment in a sample of healthcare professionals.

Methods

A cross-sectional survey was conducted among 96 healthcare professionals from March to June 2018 in the catchment area of five clinics in Bavaria, Germany. The present research examined the moderating role of emotional competence on the relationship between job satisfaction and organisational commitment using moderated regression analysis and simple slope analysis.

Results

Multiple regression analysis indicated that emotional competence moderated the relationship between satisfaction with the job and commitment to the job. The results showed that healthcare professionals with high emotional competence are able to deal more effectively with dissatisfaction in the workplace so that organisational commitment remains unaffected.

Conclusions

Based on the findings of this study emotional competence of healthcare professionals is important for increasing job satisfaction and commitment to the job. Especially for healthcare professionals whose job satisfaction is low, a high level of emotional competence enables them to maintain a high level of organisational commitment. The findings of the study are discussed at the theoretical level for researchers and practical level for hospital managers interested in fostering emotional competence and improving healthcare professionals’ job satisfaction and their organisational commitment, which ultimately may lead to effective performance.
“Time is of the essence”: relationship between hospital staff perceptions of time, safety attitudes and staff wellbeing
Authors: Ellis Louise A. , Tran Yvonne , Pomare Chiara , Long Janet C. , Churruca Kate , Mahmoud Zeyad , Liauw Winston , Braithwaite Jeffrey
Published: November 2021

Background

Hospitals are perceived as fast-paced and complex environments in which a missed or incorrect diagnosis or misread chart has the potential to lead to patient harm. However, to date, limited attention has been paid to studying how hospital sociotemporal norms may be associated with staff wellbeing or patient safety. The aim of this study was to use novel network analysis, in conjunction with well-established statistical methods, to investigate and untangle the complex interplay of relationships between hospital staff perceived sociotemporal structures, staff safety attitudes and work-related well-being.

Method

Cross-sectional survey data of hospital staff (n = 314) was collected from four major hospitals in Australia. The survey included subscales from the Organizational Temporality Scale (OTS), two previously established scales of safety attitudes (teamwork climate and safety climate) and measures of staff-related wellbeing (job satisfaction, emotional exhaustion, depersonalisation).

Results

Using confirmatory factor analysis, we first tested a 19-item version of the OTS for use in future studies of hospital temporality (the OTS-H). Novel psychological network analysis techniques were then employed, which identified that “pace” (the tempo or rate of hospital activity) occupies the central position in understanding the complex relationship between temporality, safety attitudes and staff wellbeing. Using a path analysis approach, serial mediation further identified that pace has an indirect relationship with safety attitudes through wellbeing factors, that is, pace impacts on staff wellbeing, which in turn affects hospital safety attitudes.

Conclusions

The findings of this study are important in revealing that staff wellbeing and safety attitudes can be significantly improved by placing more focus on temporal norms, and in particular hospital pace. There are implications for increasing levels of trust and providing staff with opportunities to exercise greater levels of control over their work.
Evaluating implementation outcomes (acceptability, adoption, and feasibility) of two initiatives to improve the medication prior authorization process
Authors: Jones Laney K. , Ladd Ilene G. , Gregor Christina , Evans Michael A. , Graham Jove , Gionfriddo Michael R.
Published: November 2021

Background

Processes such as prior authorization (PA) for medications, implemented by health insurance companies to ensure that safe, appropriate, cost-effective, and evidence-based care is provided to all members, have created inefficiencies within healthcare systems. Thus, healthcare systems have implemented supplemental processes to reduce burden and ensure efficiency, timeliness, and appropriate care.

Objective

Evaluate implementation outcomes of two initiatives related to PA for medications: a common record that records all PA-related information that was integrated into the health record and an auto-routing of specialty prescriptions to a hospital-owned specialty pharmacy.

Methods

We conducted semi-structured interviews with medical staff to understand their experience, acceptability, adoption, and feasibility of these initiatives guided by Proctor’s Framework for Implementation Outcomes. Transcripts were analyzed using consensus coding.

Results

Eleven medical staff participated in semi-structured interviews. The two initiatives were analyzed together because the findings were similar across both for our outcomes of acceptability, adoption, and feasibility. Participants found the implemented initiatives to be acceptable and beneficial but felt there were still challenges with the new workflow. The initiatives were fully adopted by only one clinic site within the healthcare system, but limitations arose when adopting to another site. Individuals felt the initiatives were feasible and improved workflow, communication, and transparency. However, participants described future adaptations that would help improve this process including improved standardization, automation, and transparency.

Conclusion

The acceptability, adoption, and feasibility of two initiatives to improve the PA process within the one clinical site were well received but issues of generalizability limited the initiatives adoption system wide.
Involvement of immune system and Epithelial–Mesenchymal-Transition in increased invasiveness of clustered circulatory tumor cells in breast cancer
Authors: Khoshbakht Samane , Azimzadeh Jamalkandi Sadegh , Masudi-Nejad Ali
Published: November 2021

Background

Circulating tumor cells (CTCs) are the critical initiators of distant metastasis formation. In which, the reciprocal interplay among different metastatic pathways and their metastasis driver genes which promote survival of CTCs is not well introduced using network approaches.

Methods

Here, to investigate the unknown pathways of single/cluster CTCs, the co-expression network was reconstructed, using WGCNA (Weighted Correlation Network Analysis) method. Having used the hierarchical clustering, we detected the Immune-response and EMT subnetworks. The metastatic potential of genes was assessed and validated through the support vector machine (SVM), neural network, and decision tree methods on two external datasets. To identify the active signaling pathways in CTCs, we reconstructed a casual network. The Log-Rank test and Kaplan–Meier curve were applied to detect prognostic gene signatures for distant metastasis-free survival (DMFS). Finally, a predictive model was developed for metastasis risk of patients using VIF-stepwise feature selection.

Results

Our results showed the crosstalk among EMT, the immune system, menstrual cycles, and the stemness pathway in CTCs. In which, fluctuation of menstrual cycles is a new detected pathway in breast cancer CTCs. The reciprocal association between immune responses and EMT was identified in CTCs. The SVM model indicated a high metastatic potential of EMT subnetwork (accuracy, sensitivity, and specificity scores were 87%). The DMFS model was identified to predict patients’ metastasis risks. (c-index = 0.7). Finally, novel metastatic biomarkers of KRT18 and KRT19 were detected in breast cancer CTCs.

Conclusions

In conclusion, the reciprocal interplay among critical unknown pathways in CTCs manifests both their survival in blood and metastatic potentials. Such findings may help to develop more precise predictive metastatic-risk models or detect pivotal metastatic biomarkers.