bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of Xiaoaiping injection for breast cancer
Authors: Hou Daorui , Xiong Jian , Peng Yahui , Li Ya , Xiong Lu
Published: August 2020

Background:

Xiaoaiping injection, extracted from the Chinese herb Marsdenia tenacissima (Roxb.) Wight et Arn., is a broad-spectrum anti-tumor drug and has been widely used for the treatment of breast cancer in China. The aim of this study is to systematically investigate the efficacy and safety of Xiaoaiping injection for the treatment of breast cancer.

Methods:

We will perform the comprehensive literature search in the following databases from their inceptions to August 2020 for data extraction: PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system.

Results:

The results of our research will be published in a peer-reviewed journal.

Conclusion:

The conclusion of this study will provide evidence to show whether Xiaoaiping injection is an effective intervention for patient with breast cancer.

OSF registration number:

10.17605/OSF.IO/4ZUXC
Evaluation of H-type hypertension prevalence and its influence on the risk of increased carotid intima-media thickness among a high-risk stroke population in Hainan Province, China
Authors: Zhou Feng , Hou Dan , Wang Yukai , Yu Dan
Published: August 2020

H-type hypertension, defined as a combination of hypertension and hyperhomocysteinemia (Hhcy), is associated with atherosclerosis and, therefore, increased stroke risk. However, the role of hypertension and Hhcy in high-risk stroke populations has not been studied. The present study investigated the prevalence of H-type hypertension in a high-risk stroke population of Hainan Province, China and to assess possible joint effects between hypertension and Hhcy for increased carotid intima-media thickness (CIMT). In this community-based cross-sectional study, 959 high-risk stroke subjects (age, 65.8 ± 10.8 years; 46.6% men) were recruited from Hainan Province, China. The demographic and clinical characteristics were collected, and blood samples were obtained. Analysis of variance or chi-square tests were performed to compare variates among groups based on both homocysteine levels and blood pressure status. The associations of hypertension and Hhcy with increased CIMT were evaluated through logistic regression. The prevalence of H-type hypertension was 34.8% in this population, with a higher ratio of H-type hypertension in men than in women. Compared with the normotension and normal homocysteine subgroup, the risk of increased CIMT was significantly higher in the subgroup with hypertension and Hhcy (odds ratio [OR] = 2.639; 95% confidence interval [CI], 1.690–4.091) after adjusting for age and sex. Increased CIMT was affected by an additive synergetic interaction between Hhcy and hypertension (synergy index = 1.105). It emphasized the clinical importance of anti-hypertension and lowering Hhcy in the high-risk stroke population.
Efficacy and safety of Ginkgo biloba for patients with early diabetic nephropathy
Authors: Wang Hongyun , Yuan Meilin , Zou Xinrong
Published: August 2020

Background:

Diabetic nephropathy (DN) is not only an important microvascular complication of diabetes but also the main cause of end-stage renal disease. Ginkgo biloba has a variety of biological activities and has been widely used in China to treat kidney diseases such as DN. This article aimed to evaluate the efficacy and safety of G biloba in patients affected with DN in the early stage.

Methods:

This protocol follows the preferred reporting items for systematic review and meta-analysis protocols and the recommendations of the Cochrane Collaboration Handbook. Seven electronic databases will be searched from inception to July 31, 2020. Two investigators will independently identify relevant randomized controlled trials, fetch data, and assess the risk of bias with tools provided by Cochrane. A comprehensive meta-analysis will be conducted with the Cochrane Collaboration software (Review Manager 5.3) for eligible and appropriate studies. Further, the evidence will be assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results:

The results will be published in academic peer-reviewed journals, and the evidence gathered by this project will be dedicated to assessing the efficacy and safety of G biloba for DN patients in the early stage.

Conclusion:

This systematic review and meta-analysis will synthesize the available evidence to demonstrate the efficacy of G biloba in delaying the progression of patients with early DN.

Trial registration number:

PROSPERO CRD42020166805.
Comparison of high ligation of great saphenous vein using pneumatic tourniquets and conventional method for great saphenous vein varicosis
Authors: Chen Ping , Chen Hui , Yang Mu
Published: August 2020

To investigate the efficiency of high ligation, great saphenous vein stripping and subfascial perforator vein surgery for treating great saphenous vein varicosis under the assistance of sterilized electric pneumatic tourniquet and Esmarchs bandage.

In total, 274 patients confirmed with primary varicosis between January 2014 and November 2017 were included in this study. Patients were divided into

After surgery, the affected limbs in both groups were wrapped up using the elastic bandage for 2 weeks, followed by wearing elastic stocking for 6 months. Then we analyzed the intraoperative bleeding, surgery time, subcutaneous hemorrhage after surgery and postoperative pains.

The surgical time in the treatment group was significantly lower than that of control group (58.62 ± 7.47 minutes vs 76.35 ± 9.24 minutes, P < .01). The intraoperative bleeding in the treatment group was significantly lower than that of the control group (17.56 ± 3.52 ml vs 49.87 ± 8.78 ml, P < .01).

High ligation, great saphenous vein stripping, and subfascial perforator vein surgery under the assistance of sterilized electric pneumatic tourniquet and Esmarch's bandage was effective for the treatment of varicosis in lower limbs featured by reduced surgery time and less bleeding.
Evaluation of the efficacy of Conbercept in the treatment of diabetic macular edema based on OCTA
Authors: Ba Teer , Zhou Lili , Zhang Han , Zhang Xiaoguang , Guo Shixuan , Li Huixia , Tian Haiyan , Caihan Qiqige , Bai Gang , Zhou Jing , Qi Lao , Zhang Xueyan , Zhang Guisen
Published: August 2020

Background:

Diabetic macular edema (DME) can cause severe vision impairments for patients with diabetes. Recently, Conbercept has shown efficacy on DME with 3-monthly loading dose injection and pro re nata (PRN, 3+PRN) thereafter in retrospectivetrials. Furthermore, there are some other approaches have been recommended such as 2mg bimonthly (2q8) after 5 initial doses, or Conbercept 0.5mg treat-and-extend, however, some patients still have recurrence of the disease after treatment. Therefore, in order to identify more efficacy and safety approach on Conbercept inpatients with DME, a randomized controlled trial will be performed with 6-monthly loading dose injection and PRN (6+PRN) compared with 3+PRN treatments.

Methods:

This study is a multicenter, randomized control trial of Conbecept treating DME in China. Patients with type 2 diabetes suffered from DEM who already planned to receive Conbercept treatment will be recruited. All subjects will be randomized divided into either a study agent treatment group (6+PRN) or a control group (3+PRN), and observes the subjects for 48 weeks after initiation of treatment.

Results:

This study will provide a new powerful evidence of the efficacy and safety of Conbecept treating DME.

Discussion:

This RTC study will determine whether multiple treatments of Conbercept provide better effectiveness in patients with DME.

Trial registration number:

ChiCTR2000032728
Efficacy and safety of Xiaoaiping injection for liver cancer
Authors: Hou Daorui , Xiong Jian , Li Ya , Peng Yahui , Xiong Lu
Published: August 2020

Background:

Xiaoaiping injection, extracted from the Chinese herb Marsdenia tenacissima (Roxb.) Wight et Arn., is a broad-spectrum anti-tumor drug and has been widely used for the treatment of liver cancer in China. The aim of this study is to systematically investigate the efficacy and safety of Xiaoaiping injection for the treatment of liver cancer.

Methods and analysis:

Seven electronic databases including the Cochrane Library, PubMed, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Scientific Journal Database, and Wanfang Database will be systematically retrieved for data extraction from their inceptions to August 2020. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I

2
tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Eggers test. The quality of evidence will be assessed by the GRADE system.

Results:

The results of our research will be published in a peer-reviewed journal.

Conclusion:

The conclusion of this study will provide helpful evidence of the effect and safety of Xiaoaiping injection for the treatment of liver cancer in clinical practice.

OSF registration number:

10.17605/OSF.IO/9BD6A.
The efficacy and safety of Tanreqing injection combined with western medicine for severe pneumonia
Authors: Wang Lei , Fan Yihua , Xu Jingyu , Deng Huaihan , Geng Chen , Jia Bo
Published: August 2020

Background:

Tanreqing injection, as a kind of traditional Chinese medicine injection widely used in clinic, has the effects of clearing heat, reducing phlegm and detoxifying, and avoids the problems of slow effect and complicated decocting of traditional Chinese medicine. Severe pneumonia is a critical disease of the respiratory system, with symptoms such as dyspnea, shortness of breath, high fever, and coma. Clinical studies have found that Tanreqing injection combined with Western medicine has a good effect in the treatment of severe pneumonia. In order to explore the efficacy and safety of Tanreqing injection combined with antibiotics in the treatment of severe pneumonia, we plan to conduct a systematic evaluation and meta-analysis.

Methods:

Randomized controlled trials (RCTs) on the treatment of severe pneumonia with Tanreqing injection combined with western medicine were collected by searching PubMed, The Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, Weipu Database, and China Biomedical Literature Service System (CBM) by computer with the retrieval time from establishment of database to July 2020. Two researchers independently screened and extracted the literature, and finally evaluated the bias risk of the included study, and meta-analysis was conducted using RevMan5.3 software.

Results:

The study evaluated the efficacy and safety of Tanreqing injection combined with Western medicine in the treatment of severe pneumonia in terms of total response rate, CURB-65 score, white blood cell count (WBC), antipyretic time (AT), adverse reaction incidence, etc.

Conclusions:

This study will provide a reliable evidence-based basis for the clinical application of Tanreqing injection in the treatment of severe pneumonia.

Ethics and dissemination:

The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/SQDMG.
Comparison of total disc arthroplasty and fusion in treatment of lumbar disc disease
Authors: Wang Yi , Bai Yunting , Ma Haoguang , Wang Shaolei
Published: August 2020

Background:

In recent years, the clinical efficacy of spinal fusion (SF) or total disc arthroplasty (TDA) in the treatment of the degenerative lumbar disc disease is still controversial. The objective of this retrospective clinical trial was to investigate whether TDA was superior to the SF in the complication rates and clinical outcome scores.

Methods:

This retrospective research was based on the Strengthening the Reporting of Observational studies in Epidemiology checklist. Internal clinical data sets for 2014 to 2018 were acquired and consolidated with the approval of the Institutional Review Committee of Shaoxing Hospital of Zhejiang University. Inclusion criteria in this present research included: low back pain without or with the leg pain for more than one year; failure of conservative treatment planned for more than three months; age was 25 to 60 years old; followed up for at least one year. The main outcome measure was disability and pain measured via the Norwegian version of Oswestry disability index 2.0. The other clinical outcomes included Short-Form Health Survey, reoperations, duration of surgery, complications, hospital stay length, as well as the blood loss. The significance was set at 0.05 level with the confidence intervals of 95%. The software package of SPSS (version 21.0; SPSS Inc, Chicago, IL, USA) was applied for all the analyses of statistics.

Results:

The null hypothesis is that there is no significant difference in outcomes between TDA and SF in the treatment of degenerative lumbar disc disease.

Trial registration:

This study protocol was registered in Research Registry (researchregistry5847).
Fecal microbiota transplantation therapy for Parkinson's disease
Authors: Xue Liu-Jun , Yang Xiao-Zhong , Tong Qiang , Shen Peng , Ma Shi-Jie , Wu Shang-Nong , Zheng Jin-Long , Wang Hong-Gang
Published: August 2020

Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.
Identification of the hub genes and pathways involved in acute myeloid leukemia using bioinformatics analysis
Authors: Tan Youping , Zheng Liling , Du Yuanyuan , Zhong Qi , Zhu Yangmin , Liu Zhi , Liu Shuang , Zhang Qing
Published: August 2020

Background:

We identified the hub genes and pathways dysregulated in acute myeloid leukemia and the potential molecular mechanisms involved.

Methods:

We downloaded the GSE15061 gene expression dataset from the Gene Expression Omnibus database and used weighted gene co-expression network analysis to identify hub genes. Differential expression of the genes was evaluated using the limma package in R software. Subsequently, we built a protein–protein interaction network followed by functional enrichment analysis. Then, the prognostic significance of gene expression was explored in terms of overall survival. Finally, transcription factor-mRNA (ribonucleic acid) and microRNA-mRNA interaction analysis was also explored.

Results:

We identified 100 differentially expressed hub genes. Functional enrichment analysis indicated that the genes were principally involved in immune system regulation, host defense, and negative regulation of apoptosis and myeloid cell differentiation. We identified 4 hub genes, the expression of which was significantly correlated with overall survival. Finally, 26 key regulators for hub genes and 38 microRNA-mRNA interactions were identified.

Conclusion:

We performed a comprehensive bioinformatics analysis of hub genes potentially involved in acute myeloid leukemia development. Further molecular biological experiments are required to confirm the roles played by these genes.
Prognostic value of serum albumin-to-creatinine ratio in patients with acute myocardial infarction
Authors: Liu Hong , Zhang Jianna , Yu Jing , Li Dongze , Jia Yu , Cheng Yisong , Zhang Qin , Liao Xiaoyang , Liu Yanmei , Wu Jiang , Zeng Zhi , Cao Yu , Zeng Rui , Wan Zhi , Gao Yongli
Published: August 2020

The long-term association between serum albumin-to-creatinine ratio (sACR) and poor patient outcomes in acute myocardial infarction (AMI) remains unclear. This study aimed to determine whether sACR was a predictor of poor long-term survival in patients with AMI.

This was a study of patients with AMI in the emergency department (ED) from the retrospective multicenter study for early evaluation of acute chest pain (REACP) study. The patients were categorized into tertiles (T1, T2, and T3) based on the admission sACR (0.445 and 0.584 g/μmol). Baseline sACR at admission to the ED was predictive of adverse outcomes. The primary outcome was all-cause mortality within the follow-up period. Cox proportional hazards models were performed to investigate the association between sACR and all-cause mortality in patients with AMI.

A total of 2250 patients with AMI were enrolled, of whom 229 (10.2%) died within the median follow-up period of 10.7 (7.2–14.6) months. Patients with a lower sACR had higher all-cause mortality and adverse outcomes rates than patients with a higher sACR. Kaplan–Meier survival analysis showed that patients with a higher sACR had a higher cumulative survival rate (P < .001). Cox regression analysis showed that a decreased sACR was an independent predictor of all-cause mortality [T2 vs T1: hazard ratio (HR); 0.550, 95% confidence interval (95% CI), 0.348–0.867; P = .010 and T3 vs T1: HR, 0.305; 95% CI, 0.165–0.561; P < .001] and cardiac mortality (T2 vs T1: HR, 0.536; 95% CI, 0.332–0.866; P = .011 and T3 vs T1: HR, 0.309; 95% CI, 0.164–0.582, P < .001).

The sACR at admission to ED was independently associated with adverse outcomes, indicating that baseline sACR was a useful biomarker to identify high-risk patients with AMI at an early phase in ED.
Gemtuzumab ozogamicin monotherapy prior to stem cell infusion induces sustained remission in a relapsed acute myeloid leukemia patient after allogeneic stem cell transplantation
Authors: Sumiyoshi Ritsu , Tashiro Haruko , Saito Sumiko , Matsuo Takuji , Yamamoto Tadashi , Matsumoto Kensuke , Ooi Jun , Shirafuji Naoki
Published: August 2020

Rationale:

Patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have poor prognosis. Many patients are not eligible for 2nd HSCT due to organ dysfunction or other complications that prevent them from tolerating conditioning chemotherapy. In those ineligible patients for 2nd HSCT with myeloablative conditioning regimen, reduced intensity conditioning (RIC) are often used. RIC regimens are less toxic but has a less direct anti-tumor efficacy so that RIC regimens are not suitable for the patients with high tumor burden. To overcome this dilemma, Gemtuzumab Ozogamicin (GO) has been used as a part of RIC regimens to add anti-tumor efficacy. We report here a relapsed AML patient who was treated with GO monotherapy followed by stem cell infusion.

Patient concerns:

A 25-year-old male with AML experienced relapse 9 months after allo-HSCT.

Diagnosis:

Since he had mild renal and cardiac dysfunction and his AML did not progress rapidly, we decided not to give him an intensive chemotherapy. However, after azacitidine (AZA) and donor lymphocyte infusion therapy, his leukemic blasts did not decrease.

Interventions:

Originally, we had planned to proceed with a 2nd allo-HSCT with RIC regimen that consisted of fludarabine, melphalan and fractionated GO (3 mg/m2/dose) on day -21, -18, and -15. However, the patient developed appendicitis after the last dose of GO when his neutrophil was 0 cells/μl. Based on his medical acuity, we terminated the rest of the patients conditioning regimen and the patient did not receive any further chemotherapeutics. The patient was still infused with peripheral blood stem cells from the donor on day 0.

Outcomes:

His appendicitis was resolved by antibiotics without surgery. His AML has been in CR more than 18 months under AZA maintenance therapy.

Lessons:

GO monotherapy could be a conditioning regimen of 2nd allo HSCT from the same donor as the first HSCT for relapsed AML patients.
Survival outcomes and rate of missed upper gastrointestinal cancers at routine endoscopy: a single centre retrospective cohort study
Authors: Gavric Aleksandar , Hanzel Jurij , Zagar Tina , Zadnik Vesna , Plut Samo , Stabuc Borut
Published: August 2020

Objectives

Data on the long-term survival outcome of patients with missed upper gastrointestinal cancers (MUGC) is lacking. Retrospective studies have found no difference in 1- and 2-year survival among patients with missed gastric and oesophageal cancers; we thus aimed to assess 3-year survival of patients with MUGC at oesophagogastroduodenoscopy.

Methods

This was a retrospective cohort study conducted at a single tertiary endoscopy centre. All oesophagogastroduodenoscopies performed between January 2007 and December 2015 were included in the study. The endoscopy database was cross-matched with the Slovenian Cancer Registry database. Missed cancers were defined as those diagnosed within 36 months after a negative oesophagogastroduodenoscopy.

Results

During the study period, 29 617 oesophagogastroduodenoscopies were performed. In total, 422 upper gastrointestinal cancers were diagnosed and the rate of missed gastric cancers was 7.3% (95% CI, 4.9–10.6%) (26/354), and 4.4% (95% CI, 0.9–12.4%) for oesophageal cancers (3/68). Three-year survival of patients with MUGC was shorter than that of those with non-MUGC, being 12% (95% CI, 1–25%) vs. 31% (95% CI, 26–36%) (P = 0.043) for gastric and 0 vs. 9% (95% CI, 1–17%) (P = 0.121) for oesophageal cancer.

Conclusion

Missed gastric cancer during oesophagogastroduodenoscopy may be associated with shorter 3-year survival compared to patients whose gastric cancer was diagnosed at index oesophagogastroduodenoscopy.
Orthognathic Hardware Complications in the Era of Patient-Specific Implants
Authors: Kalmar Christopher L. , Humphries Laura S. , Zimmerman Carrie E. , Vu Giap H. , Swanson Jordan W. , Bartlett Scott P. , Taylor Jesse A.
Published: August 2020

Background:

Patients undergoing orthognathic skeletal correction present with a variety of comorbidities that may affect surgical outcomes. The purpose of this study was to determine how patient risk factors and operative technique contribute to complication rates after orthognathic surgery in the era of patient-specific implants.

Methods:

Retrospective cohort analysis was conducted of pediatric patients undergoing Le Fort I osteotomy, bilateral sagittal split osteotomy, and/or genioplasty from 2014 to 2018. Patient risk factors, operative characteristics, and postoperative outcomes were gathered and compared with appropriate statistics.

Results:

Ninety-four patients met inclusion criteria, with an overall 1-year complication rate of 11.7 percent (11 of 94). Patient-specific mandibular plates are significantly associated with infection (p = 0.009; OR, 8.8), occurrence of any complication (p = 0.003; OR, 8.3), readmission (p < 0.001; OR, 11.1), and reoperation (p < 0.001; OR, 11.4). In patients with syndromes or history of cleft lip/palate, patient-specific mandibular plates are associated with infection (p = 0.006; OR, 10.3), readmission (p < 0.001; OR, 21.6), and reoperation (p < 0.001; OR, 22.9). In multivariate regression controlling for age, sex, syndrome status, and orofacial cleft history, use of patient-specific mandibular plates was associated with infection (p = 0.017; adjusted OR, 12.5), any complication (p = 0.007; adjusted OR, 11.8), readmission (p = 0.001; adjusted OR, 17.9), and reoperation (p = 0.001; adjusted OR, 18.9).

Conclusions:

In the era of patient-specific orthognathic surgery, syndromic status and use of patient-specific mandibular plates are associated with increased infection, readmission, and reoperation because of hardware-related complications. The authors’ data support increased caution and counseling with use of patient-specific mandibular implants in patients with syndromic status, history of orofacial cleft, and history of previous maxillomandibular surgery given increased risk of hardware-related complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Correlation between Venous Thromboembolism Risk and Venous Congestion in Microvascular Reconstruction of the Lower Extremity
Authors: Parham Christopher S. , Shen Chan , Pennock Michael M. , Henderson Stacy R. , Kulaylat Audrey S. , Johnson Timothy S.
Published: August 2020

Background:

Risk for venous thromboembolism formation and the relationship to postoperative free flap venous congestion and flap failure have not been adequately evaluated in a trauma population. The authors aim to use the Caprini Risk Assessment Model to evaluate the association between venous thromboembolism risk and postoperative flap venous congestion following lower extremity free tissue transfer.

Methods:

A retrospective analysis was conducted of all patients who underwent lower extremity free flap reconstruction of traumatic defects at a single institution between 2007 and 2016. A Wilcoxon rank sum test was used for nonparametric analysis of aggregate Caprini Risk Assessment Model scores and flap outcomes. Flap venous congestion and failure rates as associated with the categorical variables underlying the Caprini Risk Assessment Model were further studied. Logistic regression was used to evaluate each of these outcomes and other flap-related covariates relative to the Caprini Risk Assessment Model categorical variables that had the greatest effect on our patient sample.

Results:

One hundred twelve patients underwent lower extremity free flap reconstruction. One hundred eight free flaps were analyzed. Eight patients were excluded. The majority of patients were male (75.9 percent) and required reconstruction because of acute trauma (68.1 percent versus 31.9 percent for chronic wounds). There was no statistically significant association found between age, body mass index, or timing of trauma versus venous congestion, flap failure, or other flap-related covariates.

Conclusion:

In patients with significantly elevated Caprini Risk Assessment Model scores, there was no significant association between venous thromboembolism risk and flap failure following free tissue reconstruction of lower extremities.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
COVID-19 and its Mimics
Authors: Hanfi Sameer H. , Lalani Tasneem K. , Saghir Amina , McIntosh Lacey J. , Lo Hao S. , Kotecha Hemang M.
Published: August 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current outbreak of Coronavirus disease 2019 (COVID-19). Although imaging should not be used for first-line screening or diagnosis, radiologists need to be aware of its imaging features, and those of common conditions that may mimic COVID-19 pneumonia. In this Pictorial Essay, we review frequently encountered conditions with imaging features that overlap with those that are typical of COVID-19 (including other viral pneumonias, chronic eosinophilic pneumonia, and organizing pneumonia), and those with features that are indeterminate for COVID-19 (including hypersensitivity pneumonitis, pneumocystis pneumonia, diffuse alveolar hemorrhage, pulmonary edema, and pulmonary alveolar proteinosis).
Clinical Significance of Papillary Muscles on Left Ventricular Mass Quantification Using Cardiac Magnetic Resonance Imaging
Authors: Al-Arnawoot Amna , O’Brien Ciara , Karur Gauri R. , Nguyen Elsie T. , Wasim Syed , Iwanochko Robert M. , Morel Chantal F. , Hanneman Kate
Published: August 2020

Purpose:

Accurate and reproducible assessment of left ventricular mass (LVM) is important in Fabry disease. However, it is unclear whether papillary muscles should be included in LVM assessed by cardiac magnetic resonance imaging (MRI). The purpose of this study was to evaluate the reproducibility and predictive value of LVM in patients with Fabry disease using different analysis approaches.

Materials and Methods:

A total of 92 patients (44±15 y, 61 women) with confirmed Fabry disease who had undergone cardiac MRI at a single tertiary referral hospital were included in this retrospective study. LVM was assessed at end-diastole using 2 analysis approaches, including and excluding papillary muscles. Adverse cardiac events were assessed as a composite end point, defined as ventricular tachycardia, bradycardia requiring device implantation, severe heart failure, and cardiac death. Statistical analysis included Cox proportional hazard models, Akaike information criterion, intraclass correlation coefficients, and Bland-Altman analysis.

Results:

Left ventricular end-diastolic volume, end-systolic volume, ejection fraction, and LVM all differed significantly between analysis approaches. LVM was significantly higher when papillary muscles were included versus excluded (157±71 vs. 141±62 g, P<0.001). Mean papillary mass was 16±11 g, accounting for 10%±3% of total LVM. LVM with pap illary muscles excluded had slightly better predictive value for the composite end point compared with LVM with papillary muscles included based on the model goodness-of-fit (Akaike information criterion 140 vs. 142). Interobserver agreement was slightly better for LVM with papillary muscles excluded compared with included (intraclass correlation coefficient 0.993 [95% confidence interval: 0.985, 0.996] vs. 0.989 [95% confidence interval: 0.975, 0.995]) with less bias and narrower limits of agreement.

Conclusions:

Inclusion or exclusion of papillary muscles has a significant effect on LVM quantified by cardiac MRI, and therefore, a standardized analysis approach should be used for follow-up. Exclusion of papillary muscles from LVM is a reasonable approach in patients with Fabry disease given slightly better predictive value and reproducibility.
microRNA-145 Inhibition Upregulates SIRT1 and Attenuates Autophagy in a Mouse Model of Lung Ischemia/Reperfusion Injury via NF-κB-dependent Beclin 1
Authors: Dai Shao-Hua , Chen Lu-Jie , Qi Wang-Hong , Ye Chun-Lin , Zou Guo-Wen , Liu Wei-Cheng , Yu Ben-Tong , Tang Jian
Published: August 2020

Background.

MicroRNA-145 (miR-145) has been shown to play a critical role in ischemia/reperfusion (I/R) injury; however, the expression and function of miR-145 in lung I/R injury have not been reported yet. This study aimed to elucidate the potential effects of miR-145 in lung I/R injury.

Methods.

Lung I/R mice models and hypoxia/reoxygenation (H/R) pulmonary microvascular endothelial cell models were established. The expression of miR-145 and sirtuin 1 (SIRT1) was measured with reverse transcription-quantitative polymerase chain reaction and Western blot analysis in mouse lung tissue and cells. Artificial modulation of miR-145 and SIRT1 (downregulation) was done in I/R mice and H/R cells. Additionally, Pao
2/FiO2 ratio, wet weight-to-dry weight ratio, and cell apoptosis in mouse lung tissues were determined by blood gas analyzer, electronic balance, and deoxyuridine triphosphate-biotin nick end-labeling assay, respectively. Autophagy marker Beclin 1 and LC3 expression, NF-κB acetylation levels, and autophagy bodies were detected in cell H/R and mouse I/R models by Western blot analysis. pulmonary microvascular endothelial cell apoptosis was detected with flow cytometry.

Results.

miR-145 was abundantly expressed in the lung tissue of mice and PMVECs following I/R injury. In addition, miR-145 directly targeted SIRT1, which led to significantly decreased Pao
2/FiO2 ratio and increased wet weight-to-dry weight ratio, elevated acetylation levels and transcriptional activity of NF-κB, upregulated expressions of tumor necrosis factor-α, interleukins-6, and Beclin 1, autophagy bodies, cell apoptosis, as well as LC3-II/LC3I ratio.

Conclusions.

In summary, miR-145 enhances autophagy and aggravates lung I/R injury by promoting NF-κB transcriptional activity via SIRT1 expression.
Predation of the giant Miocene caiman
Purussaurus
on a mylodontid ground sloth in the wetlands of proto-Amazonia
Authors: Pujos François , Salas-Gismondi Rodolfo
Published: August 2020

Thirteen million years ago in South America, the Pebas Mega-Wetland System sheltered multi-taxon crocodylian assemblages, with the giant caiman
Purussaurus
as the top predator. In these Miocene swamps where reptiles and mammals coexisted, evidence of their agonistic interactions is extremely rare. Here, we report a tibia of the mylodontid sloth
Pseudoprepotherium
bearing 46 predation tooth marks. The combination of round and bisected, shallow pits and large punctures that collapsed extensive portions of cortical bone points to a young or sub-adult
Purussaurus
(approx. 4 m in total length) as the perpetrator. Other known crocodylians of the Pebas System were either too small at adulthood or had discordant feeding anatomy to be considered. The pattern of tooth marks suggests that the perpetrator attacked and captured the ground sloth from the lower hind limb, yet an attempt of dismembering cannot be ruled out. This discovery from the Peruvian Amazonia provides an unusual snapshot of the dietary preferences of
Purussaurus
and reveals that prior to reaching its giant size, young individuals might have fed upon terrestrial mammals of about the size of a capybara.
Coordinated crawling via reinforcement learning
Authors: Mishra Shruti , van Rees Wim M. , Mahadevan L.
Published: August 2020

Rectilinear crawling locomotion is a primitive and common mode of locomotion in slender soft-bodied animals. It requires coordinated contractions that propagate along a body that interacts frictionally with its environment. We propose a simple approach to understand how this coordination arises in a neuromechanical model of a segmented, soft-bodied crawler via an iterative process that might have both biological antecedents and technological relevance. Using a simple reinforcement learning algorithm, we show that an initial all-to-all neural coupling converges to a simple nearest-neighbour neural wiring that allows the crawler to move forward using a localized wave of contraction that is qualitatively similar to what is observed in
Drosophila melanogaster
larvae and used in many biomimetic solutions. The resulting solution is a function of how we weight gait regularization in the reward, with a trade-off between speed and robustness to proprioceptive noise. Overall, our results, which embed the brain–body–environment triad in a learning scheme, have relevance for soft robotics while shedding light on the evolution and development of locomotion.
Visualizing mineralization processes and fossil anatomy using synchronous synchrotron X-ray fluorescence and X-ray diffraction mapping
Authors: Gueriau Pierre , Réguer Solenn , Leclercq Nicolas , Cupello Camila , Brito Paulo M. , Jauvion Clément , Morel Séverin , Charbonnier Sylvain , Thiaudière Dominique , Mocuta Cristian
Published: August 2020

Fossils, including those that occasionally preserve decay-prone soft tissues, are mostly made of minerals. Accessing their chemical composition provides unique insight into their past biology and/or the mechanisms by which they preserve, leading to a series of developments in chemical and elemental imaging. However, the mineral composition of fossils, particularly where soft tissues are preserved, is often only inferred indirectly from elemental data, while X-ray diffraction that specifically provides phase identification received little attention. Here, we show the use of synchrotron radiation to generate not only X-ray fluorescence elemental maps of a fossil, but also mineralogical maps in transmission geometry using a two-dimensional area detector placed behind the fossil. This innovative approach was applied to millimetre-thick cross-sections prepared through three-dimensionally preserved fossils, as well as to compressed fossils. It identifies and maps mineral phases and their distribution at the microscale over centimetre-sized areas, benefitting from the elemental information collected synchronously, and further informs on texture (preferential orientation), crystallite size and local strain. Probing such crystallographic information is instrumental in defining mineralization sequences, reconstructing the fossilization environment and constraining preservation biases. Similarly, this approach could potentially provide new knowledge on other (bio)mineralization processes in environmental sciences. We also illustrate that mineralogical contrasts between fossil tissues and/or the encasing sedimentary matrix can be used to visualize hidden anatomies in fossils.
Symbionts shape host innate immunity in honeybees
Authors: Horak Richard D. , Leonard Sean P. , Moran Nancy A.
Published: August 2020

The gut microbiome plays a critical role in the health of many animals. Honeybees are no exception, as they host a core microbiome that affects their nutrition and immune function. However, the relationship between the honeybee immune system and its gut symbionts is poorly understood. Here, we explore how the beneficial symbiont
Snodgrassella alvi
affects honeybee immune gene expression. We show that both live and heat-killed
S. alvi
protect honeybees from the opportunistic pathogen
Serratia marcescens
and lead to the expression of host antimicrobial peptides
.
Honeybee immune genes respond differently to live
S. alvi
compared to heat-killed
S. alvi,
the latter causing a more extensive immune expression response. We show a preference for Toll pathway upregulation over the Imd pathway in the presence of both live and heat-killed
S. alvi
. Finally, we find that live
S. alvi
aids in clearance of
S. marcescens
from the honeybee gut, supporting a potential role for the symbiont in colonization resistance. Our results show that colonization by the beneficial symbiont
S. alvi
triggers a replicable honeybee immune response. These responses may benefit the host and the symbiont, by helping to regulate gut microbial members and preventing overgrowth or invasion by opportunists.
Negative mood affects the expression of negative but not positive emotions in mice
Authors: Clarkson Jasmine M. , Leach Matthew C. , Flecknell Paul A. , Rowe Candy
Published: August 2020

Whether and to what extent animals experience emotions is crucial for understanding their decisions and behaviour, and underpins a range of scientific fields, including animal behaviour, neuroscience, evolutionary biology and animal welfare science. However, research has predominantly focused on alleviating negative emotions in animals, with the expression of positive emotions left largely unexplored. Therefore, little is known about positive emotions in animals and how their expression is mediated. We used tail handling to induce a negative mood in laboratory mice and found that while being more anxious and depressed increased their expression of a discrete negative emotion (disappointment), meaning that they were less resilient to negative events, their capacity to express a discrete positive emotion (elation) was unaffected relative to control mice. Therefore, we show not only that mice have discrete positive emotions, but that they do so regardless of their current mood state. Our findings are the first to suggest that the expression of discrete positive and negative emotions in animals is not equally affected by long-term mood state. Our results also demonstrate that repeated negative events can have a cumulative effect to reduce resilience in laboratory animals, which has significant implications for animal welfare.
Actinomadura rubteroloni sp. nov. and Actinomadura macrotermitis sp. nov., isolated from the gut of the fungus growing-termite Macrotermes natalensis
Authors: Benndorf René , Martin Karin , Küfner Michelle , de Beer Z. Wilhelm , Vollmers John , Kaster Anne-Kristin , Beemelmanns Christine
Published: August 2020

The taxonomic positions of two novel aerobic, Gram-positive actinobacteria, designated strains RB29T and RB68T, were determined using a polyphasic approach. Based on 16S rRNA gene sequence analysis, the closest phylogenetic neighbours of RB29T were identified as

Actinomadura rayongensis

DSM 102126T (99.2 % similarity) and

Actinomadura atramentaria

DSM 43919T (98.7 %), and for strain RB68T was

Actinomadura hibisca

DSM 44148T (98.3 %). Digital DNA–DNA hybridization (dDDH) between RB29T and its closest phylogenetic neighbours,

A. rayongensis

DSM 102126T and

A. atramentaria

DSM 43919T, resulted in similarity values of 53.2 % (50.6–55.9 %) and 26.4 % (24.1–28.9 %), respectively. Additionally, the average nucleotide identity (ANI) was 93.2 % (94.0 %) for

A. rayongensis

DSM 102126T and 82.3 % (78.9 %) for

A. atramentaria

DSM 43919T. dDDH analysis between strain RB68T and

A. hibisca

DSM 44148T gave a similarity value of 24.5 % (22.2–27.0 %). Both strains, RB29T and RB68T, revealed morphological characteristics and chemotaxonomic features typical for the genus

Actinomadura

, such as the presence of meso-diaminopimelic acid in the cell wall, galactose and glucose as major sugar components within whole-cell hydrolysates and the absence of mycolic acids. The major phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside. Predominant menaquinones were MK-9(H6) and MK-9(H8) for RB29T and MK-9(H4) and MK-9(H6) for RB68T. The main fatty acids were identified as 10-methyloctadecanoic acid (10-methyl C18:0), 14-methylpentadecanoic acid (iso-C16:0), hexadecanoic acid (C16:0) and cis-9-octadecanoic acid (C18 : 1 ω9c). Here, we propose two novel species of the genus

Actinomadura

: Actinomadura rubteroloni sp. nov. with the type strain RB29T (=CCUG 72668T=NRRL B-65537T) and Actinomadura macrotermitis sp. nov. with the type strain RB68T (=CCUG 72669T=NRRL B-65538T).
Clinical Outcomes in Hospitalized Patients with COVID-19 on Therapeutic Anticoagulants
Authors: Patel Niti G. , Bhasin Ajay , Feinglass Joseph M. , Belknap Steven M. , Angarone Michael P. , Cohen Elaine R. , Barsuk Jeffrey H.
Published: August 2020

Background

COVID-19 is associated with hypercoagulability and an increased incidence of thrombosis. We evaluated the clinical outcomes of adults hospitalized with COVID-19 who either continued therapeutic anticoagulants previously prescribed or who were newly started on anticoagulants during hospitalization.

Methods

We performed an observational study of adult inpatients’ with COVID-19 at 10 hospitals affiliated with Northwestern Medicine in the Chicagoland area from March 9 to June 26, 2020. We evaluated clinical outcomes of subjects with COVID-19 who were continued on their outpatient therapeutic anticoagulation during hospitalization and those who were newly started on these medications compared to those who were on prophylactic doses of these medications based on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement. The primary outcome was overall death while secondary outcomes were critical illness (WHO score ≥5), need for mechanical ventilation, and death among those subjects who first had critical illness adjusted for age, sex, race, body mass index (BMI), Charlson score, glucose on admission, and use of antiplatelet agents.

Results

1,716 subjects with COVID-19 were included in the analysis. 171 subjects (10.0%) were continued on their outpatient therapeutic anticoagulation and 201(11.7%) were started on new therapeutic anticoagulation during hospitalization. In subjects continued on home therapeutic anticoagulation, there were no differences in overall death, critical illness, mechanical ventilation, or death among subjects with critical illness compared to subjects on prophylactic anticoagulation. Subjects receiving new therapeutic anticoagulation for COVID-19 were more likely to die (OR 5.93; 95% CI 3.71-9.47), have critical illness (OR 14.51; 95% CI 7.43-28.31), need mechanical ventilation (OR 11.22; 95% CI 6.67-18.86), and die after first having critical illness. (OR 5.51; 95% CI 2.80 −10.87).

Conclusions

Continuation of outpatient prescribed anticoagulant was not associated with improved clinical outcomes. Therapeutic anticoagulation for COVID-19 in absence of other indications was associated with worse clinical outcomes.
Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts
Authors: Fabbri Chiara , Hagenaars Saskia P. , John Catherine , Williams Alexander T. , Shrine Nick , Moles Louise , Hanscombe Ken B. , Serretti Alessandro , Shepherd David J. , Free Robert S. , Wain Louise V. , Tobin Martin D. , Lewis Cathryn M.
Published: August 2020

Treatment-resistant depression (TRD) is a major contributor to the disability caused by major depressive disorder (MDD). Using primary care electronic health records from UK Biobank and EXCEED studies, we defined MDD and TRD, providing an easily accessible approach to investigate their clinical and genetic characteristics.

MDD defined from primary care records was compared with other measures of depression and validated using the MDD polygenic risk score (PRS). Using prescribing records, TRD was defined from at least two switches between antidepressant drugs, each prescribed for at least six weeks. Clinical-demographic characteristics, SNP-heritability and genetic overlap with psychiatric and non-psychiatric traits were compared in TRD and non-TRD MDD cases.

In 230,096 and 8,926 UKB and EXCEED participants with primary care data, respectively, the prevalence of MDD was 8.7% and 14.2%, of which 13.2% and 13.5% was TRD (2,430 and 159 cases), respectively. In both cohorts, MDD defined from primary care records was strongly associated with MDD PRS, and in UKB it showed overlap of 72%-88% with other MDD definitions. In UKB, TRD and non-TRD heritability was comparable (h2SNP = 0.25 [SE=0.04] and 0.19 [SE=0.02], respectively). TRD was positively associated with the polygenic risk score (PRS) of attention deficit hyperactivity disorder and negatively associated with the PRS of intelligence compared to non-TRD. It was more strongly associated with unfavourable clinical-demographic variables than non-TRD.

This study demonstrated that MDD and TRD can be reliably defined using primary care records and provides the first large scale population assessment of the genetic, clinical and demographic characteristics of TRD.