bluuebunny/crossref_metadata_2025 huggingface dataset:
The combination of intraoperative CT navigation and C-arm fluoroscopy for INFIX and percutaneous TITS screw placement in the treatment of pelvic ring injury: technical note
Authors: Hiyama Akihiko , Ukai Taku , Nomura Satoshi , Watanabe Masahiko
Published: January 2022

Background

The subcutaneous screw rod system, commonly known as the internal pelvic fixator (INFIX), is useful in managing unstable pelvic ring fractures. Conventional INFIX and transiliac–transsacral (TITS) screw techniques are performed using C-arm fluoroscopy. There have been problems with medical exposure and screw insertion accuracy with these techniques. This work describes new INFIX and TITS techniques using intraoperative computed tomography (CT) navigation and C-arm fluoroscopy for pelvic ring fracture.

Methods

A typical case is presented in this study. An 86-year-old woman suffered from an unstable pelvic ring fracture due to a fall from a height. INFIX and TITS screw fixation with intraoperative CT navigation were selected to optimize surgical invasiveness and proper implant placement.

Results

The patient was placed in a supine position on a Jackson table. An intraoperative CT navigation was imaged, and screws were inserted under the navigation. Postoperative X-rays and CT confirmed that the screw was inserted correctly. This technique was less invasive to the patient and had little radiation exposure to the surgeon. Rehabilitation of walking practice was started early after the surgery, and she was able to walk with the assistance of a walker by the time of transfer.

Conclusions

The technique employed in our case study has the cumulative advantages of safety, accuracy, and reduced radiation exposure, together with the inherent advantages of functional outcomes of previously reported INFIX and TITS screw techniques. Further experience with this approach will refine this technique to overcome its limitations and facilitate its wider use.
Low filling ratio of the distal nail segment to the medullary canal is a risk factor for loss of anteromedial cortical support: a case control study
Authors: Song Hui , Chang Shi-Min , Hu Sun-Jun , Du Shou-Chao
Published: January 2022

Background

Anteromedial cortical support apposition (positive and/or neutral cortical relations) is crucial for surgical stability reconstruction in the treatment of trochanteric femur fractures. However, the loss of fracture reduction is frequent in follow-ups after cephalomedullary nail fixation. This paper aimed to investigate the possible predictive risk factors for postoperative loss of anteromedial cortex buttress after nail fixation.

Methods

A retrospective analysis of 122 patients with AO/OTA 31A1 and A2 trochanteric femur fractures treated with cephalomedullary nails between January 2017 and December 2019 was performed. The patients were classified into two groups according to the postoperative status of the anteromedial cortical apposition in 3D CT images: Group 1 with contact “yes” (positive or anatomic) and Group 2 with contact “No” (negative, loss of contact). The fracture reduction quality score, tip-apex distance (TAD), calcar-referenced TAD (Cal-TAD), Parker ratio, neck-shaft angle (NSA), and the filling ratio of the distal nail segment to medullary canal diameter in anteroposterior (AP) and lateral fluoroscopies (taken immediately after the operation) were examined in univariate and multivariate analyses. Mechanical complications were measured and compared in follow-up radiographs.

Results

According to the postoperative 3D CT, 84 individuals (69%) were categorized into Group 1, and 38 individuals (31%) were classified as Group 2. The multivariate logistic regression analysis showed that the poor fracture reduction quality score (P < 0.001) and decreasing filling ratio in the lateral view (P < 0.001) were significant risk factors for the loss of anteromedial cortical contact. The threshold value for the distal nail filling ratio in lateral fluoroscopy predicting fracture reduction re-displacement was found to be 53%, with 89.3% sensitivity and 78.9% specificity. The mechanical complication (varus and over lateral sliding) rate was higher in Group 2.

Conclusions

The fracture reduction quality score and the decreasing filling ratio of the distal nail to the medullary canal in the lateral view (a novel parameter causing pendulum-like movement of the nail) were possible risk factors for postoperative loss of anteromedial cortical support.
Effect analysis of iliac bone autografting for Hepple V osteochondral lesions of the talus
Authors: Wang Xin , Zhang Dong , Zhang Fengqi , Jin Lin , Shi Donglin , Hou Zhiyong
Published: January 2022

Background

Talar cartilage injury is a kind of disease that causes long-term and chronic pain of ankle joint. Autologous osteochondral transplantation has been viewed as an alternative choice for treating these lesions, but donor-site morbidity has limited its application. This study aimed to analyze the efficacy of iliac bone autografting for Hepple V osteochondral lesions of the talus.

Methods

This retrospective study included 32 patients surgically treated for Hepple V osteochondral lesions of the talus from January 2015 to January 2020. All patients underwent open surgery. Ipsilateral iliac bone grafts were taken and filled with talar cartilage injury area. The improvement of postoperative ankle pain was evaluated by Visual Analogue Scale (VAS), and the improvement of ankle function was evaluated by the American Orthopaedic Foot & Ankle Society (AOFAS). During the postoperative follow-up, X-ray examination of the front and side of the ankle joint and CT of the ankle joint were performed to evaluate the bone cartilage healing in the graft area.

Results

Thirty-two patients (32 ankles) (100%) returned for clinical and radiologic follow-up at an average of 28 (range 24–36) months postoperatively. At 3 months postoperatively and at the last follow-up, the AOFAS scores were (80.4 ± 3.6) and (89.2 ± 6.4), respectively, which were significantly improved compared with the preoperative score (49.7 ± 8.1), and the difference was statistically significant (P < 0.05). The VAS scores were (2.1 ± 0.9) and (1.5 ± 0.8), respectively, which were significantly better than the preoperative score (6.2 ± 1.7), and the difference was statistically significant (P < 0.05). Re-examination of the front and side of the ankle joint X-rays and CT showed that the bone healing at the osteotomy of medial malleolus and osteochondral transplantation area. All patients had no pain at the donor site. No complications occurred in 32 patients at the last follow-up.

Conclusions

With iliac bone autografting for Hepple V osteochondral lesions of the talus can effectively relieve ankle joint pain and significantly improved ankle function.

Level of evidence

Level III, Retrospective series.
Does the critical shoulder angle decrease after acromioplasty? A systematic review and meta-analysis
Authors: Zhang Mingtao , Yang Zhitao , Zhang Borong , Liu Tao , Jiang Jin , Yun Xiangdong
Published: January 2022

Background

Rotator cuff tears are one of the most common shoulder injuries in the older population. This study aimed to determine whether acromioplasty reliably decreases the critical shoulder angle (CSA) and describe any associated complications.

Methods

A systematic literature review was performed according to PRISMA guidelines using PubMed, EMBASE, Web of Science, and Cochrane Library Database. Two reviewers independently screened the titles and abstracts using prespecified criteria. Studies where the acromioplasty was performed as a surgical procedure were included. Patient characteristics and degree of CSA reduction were collected from each individual study. All statistical analyses were performed using Review Manager (RevMan) 5.4.1 software. A random-effects model was used for meta-analysis.

Results

A total of 9 studies involving 1236 patients were included in the meta-analysis. The age of patients ranged from 23 to 82 years. The follow-up period ranged from 12 to 30 months. Of the 9 studies, 8 (88.9%) were retrospective, 1 (11.1%) was prospective, 5 were comparative, and 4 were case series. The mean CSA was significantly reduced from 36.1° ± 4.6° to 33.7° ± 4.2 (p < 0.05). The meta-analysis showed an overall best estimate of the mean difference in pre- and postoperative CSA equal to 2.63° (95% confidence interval: 2.15, 3.11] (p < 0.00001).

Conclusions

Acromioplasty can significantly reduce CSA, notably in cases of high preoperative CSA. In addition, the effect of lateral acromioplasty on the CSA was more significant compared to anterolateral acromioplasty. Acromioplasty was not associated with complications during the short-term follow-up.
Nuss procedure for combined pectus excavatum and carinatum in a patient with a history of congenital esophageal atresia repair surgery
Authors: Yoo Gyeol , Jeong Jin Yong
Published: January 2022

Cardiothoracic surgery usually causes tissue adhesion on the operation site which increases the risk of complications in the subsequent thoracic surgery including Nuss procedure. Disorders that require cardiothoracic surgery include chest wall deformities such as pectus excavatum, congenital heart diseases, lung diseases such as congenital cystic adenomatiod malformation and bronchopulmonary dysplasia, and congenital diaphragmatic hernia. Recently, we encountered a rare case of combined pectus excavatum and carinatum in a patient with a history of congenital esophageal atresia repair surgery. Commendably, despite tissue adhesion from the previous surgery, a modified Nuss procedure was performed successfully with no complications. We agree that the Nuss procedure is feasible for thoracic deformities in patients with a surgical history of cardiothoracic surgery.
A review on the applications of Traditional Chinese medicine polysaccharides in drug delivery systems
Authors: Wang Bei , Wang Xianfeng , Xiong Zhiwei , Lu Guanzheng , Ma Weikun , Lv Qinglin , Wang Long , Jia Xiaobin , Feng Liang
Published: January 2022

Traditional Chinese medicine polysaccharides (TCMPs) are plentiful and renewable resources with properties such as biocompatibility, hydrophilicity, biodegradability, and low cytotoxicity. Because the polysaccharide molecular chain contains a variety of active groups, different polysaccharide derivatives can be easily produced through chemical modification. They have been increasingly used in drug delivery systems (DDS). However, the potential of polysaccharides is usually ignored due to their structural complexity, poor stability or ambiguity of mechanisms of actions. This review summarized the applications of TCMPs in DDS around four main aspects. The general characteristics of TCMPs as drug delivery carriers, as well as the relationships between structure and function of them were summarized. Meanwhile, the direction of preparing multifunctional drug delivery materials with synergistic effect by using TCMPs was discussed. This review aims to become a reference for further research of TCMPs and their derivatives, especially applications of them as carriers in pharmaceutical preparation industry.
Macrophages-aPKCɩ-CCL5 Feedback Loop Modulates the Progression and Chemoresistance in Cholangiocarcinoma
Authors: Yang Tao , Deng Zhengdong , Xu Lei , Li Xiangyu , Yang Tan , Qian Yawei , Lu Yun , Tian Li , Yao Wei , Wang Jianming
Published: January 2022

Background

Recent data indicated that macrophages may mutually interact with cancer cells to promote tumor progression and chemoresistance, but the interaction in cholangiocarcinoma (CCA) is obscure.

Methods

10x Genomics single-cell sequencing technology was used to identified the role of macrophages in CCA. Then, we measured the expression and prognostic role of macrophage markers and aPKCɩ in 70 human CCA tissues. Moreover, we constructed monocyte-derived macrophages (MDMs) generated from peripheral blood monocytes (PBMCs) and polarized them into M1/M2 macrophages. A co-culture assay of the human CCA cell lines (TFK-1, EGI-1) and differentiated PBMCs-macrophages was established, and functional studies in vitro and in vivo was performed to explore the interaction between cancer cells and M2 macrophages. Furthermore, we established the cationic liposome-mediated co-delivery of gemcitabine and aPKCɩ-siRNA and detect the antitumor effects in CCA.

Results

M2 macrophage showed tumor-promoting properties in CCA. High levels of aPKCɩ expression and M2 macrophage infiltration were associated with metastasis and poor prognosis in CCA patients. Moreover, CCA patients with low M2 macrophages infiltration or low aPKCɩ expression benefited from postoperative gemcitabine-based chemotherapy. Further studies showed that M2 macrophages-derived TGFβ1 induced epithelial-mesenchymal transition (EMT) and gemcitabine resistance in CCA cells through aPKCɩ-mediated NF-κB signaling pathway. Reciprocally, CCL5 was secreted more by CCA cells undergoing aPKCɩ-induced EMT and consequently modulated macrophage recruitment and polarization. Furthermore, the cationic liposome-mediated co-delivery of GEM and aPKCɩ-siRNA significantly inhibited macrophages infiltration and CCA progression.

Conclusion

our study demonstrates the role of Macrophages-aPKCɩ-CCL5 Feedback Loop in CCA, and proposes a novel therapeutic strategy of aPKCɩ-siRNA and GEM co-delivered by liposomes for CCA.
Genome-wide CRISPR/Cas9 library screen identifies PCMT1 as a critical driver of ovarian cancer metastasis
Authors: Zhang Jingjing , Li Yun , Liu Hua , Zhang Jiahui , Wang Jie , Xia Jia , Zhang Yu , Yu Xiang , Ma Jinyan , Huang Masha , Wang Jiahui , Wang Liangzhe , Li Qian , Cui Rutao , Yang Wen , Xu Yingjie , Feng Weiwei
Published: January 2022

Background

The development of lethal cancer metastasis depends on the dynamic interactions between cancer cells and the tumor microenvironment, both of which are embedded in the extracellular matrix (ECM). The acquisition of resistance to detachment-induced apoptosis, also known as anoikis, is a critical step in the metastatic cascade. Thus, a more in-depth and systematic analysis is needed to identify the key drivers of anoikis resistance.

Methods

Genome-wide CRISPR/Cas9 knockout screen was used to identify critical drivers of anoikis resistance using SKOV3 cell line and found protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) as a candidate. Quantitative real-time PCR (qRT-PCR) and immune-histochemistry (IHC) were used to measure differentially expressed PCMT1 in primary tissues and metastatic cancer tissues. PCMT1 knockdown/knockout and overexpression were performed to investigate the functional role of PCMT1 in vitro and in vivo. The expression and regulation of PCMT1 and integrin-FAK-Src pathway were evaluated using immunoprecipitation followed by mass spectrometry (IP-MS), western blot analysis and live cell imaging.

Results

We found that PCMT1 enhanced cell migration, adhesion, and spheroid formation in vitro. Interestingly, PCMT1 was released from ovarian cancer cells, and interacted with the ECM protein LAMB3, which binds to integrin and activates FAK-Src signaling to promote cancer progression. Strikingly, treatment with an antibody against extracellular PCMT1 effectively reduced ovarian cancer cell invasion and adhesion. Our in vivo results indicated that overexpression of PCMT1 led to increased ascites formation and distant metastasis, whereas knockout of PCMT1 had the opposite effect. Importantly, PCMT1 was highly expressed in late-stage metastatic tumors compared to early-stage primary tumors.

Conclusions

Through systematically identifying the drivers of anoikis resistance, we uncovered the contribution of PCMT1 to focal adhesion (FA) dynamics as well as cancer metastasis. Our study suggested that PCMT1 has the potential to be a therapeutic target in metastatic ovarian cancer.
A prognostic model based on immune-related long noncoding RNAs for patients with epithelial ovarian cancer
Authors: Peng Yao , Wang Hui , Huang Qi , Wu Jingjing , Zhang Mingjun
Published: January 2022

Background

Long noncoding RNAs (lncRNAs) are important regulators of gene expression and can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNAs play an important role in the tumour immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumour patients. Epithelial ovarian cancer (EOC) is characterized by a high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on immune-related lncRNAs associated with survival in EOC.

Methods

We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database and identified differentially expressed genes through differential expression analysis. Immune-related lncRNAs were obtained through intersection and coexpression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into a training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were performed to construct an immune-related lncRNA signature. Kaplan–Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were performed for verification in the training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GSEA) and the Timer data portal.

Results

An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature was used to divide patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group and was verified to be robust in both the validation set and the combination set. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.).

Conclusions

We identified and established a prognostic signature of immune-related lncRNAs in EOC, which will be of great value in predicting the prognosis of clinical patients and may provide a new perspective for immunological research and individualized treatment in EOC.
Optimal cardiopulmonary resuscitation duration for favorable neurological outcomes after out-of-hospital cardiac arrest
Authors: Park SungJoon , Lee Sung Woo , Han Kap Su , Lee Eui Jung , Jang Dong-Hyun , Lee Si Jin , Lee Ji Sung , Kim Su Jin ,   for the Korean Cardiac Arrest Research Consortium (KoCARC) Investigators
Published: January 2022

Background

A favorable neurological outcome is closely related to patient characteristics and total cardiopulmonary resuscitation (CPR) duration. The total CPR duration consists of pre-hospital and in-hospital durations. To date, consensus is lacking on the optimal total CPR duration. Therefore, this study aimed to determine the upper limit of total CPR duration, the optimal cut-off time at the pre-hospital level, and the time to switch from conventional CPR to alternative CPR such as extracorporeal CPR.

Methods

We conducted a retrospective observational study using prospective, multi-center registry of out-of-hospital cardiac arrest (OHCA) patients between October 2015 and June 2019. Emergency medical service–assessed adult patients (aged ≥ 18 years) with non-traumatic OHCA were included. The primary endpoint was a favorable neurological outcome at hospital discharge.

Results

Among 7914 patients with OHCA, 577 had favorable neurological outcomes. The optimal cut-off for pre-hospital CPR duration in patients with OHCA was 12 min regardless of the initial rhythm. The optimal cut-offs for total CPR duration that transitioned from conventional CPR to an alternative CPR method were 25 and 21 min in patients with initial shockable and non-shockable rhythms, respectively. In the two groups, the upper limits of total CPR duration for achieving a probability of favorable neurological outcomes < 1% were 55–62 and 24–34 min, respectively, while those for a cumulative proportion of favorable neurological outcome > 99% were 43–53 and 45–71 min, respectively.

Conclusions

Herein, we identified the optimal cut-off time for transitioning from pre-hospital to in-hospital settings and from conventional CPR to alternative resuscitation. Although there is an upper limit of CPR duration, favorable neurological outcomes can be expected according to each patient’s resuscitation-related factors, despite prolonged CPR duration.
Effect of nutritional education on anthropometric deficits among pre-school aged children in south West Ethiopia: quasi-experimental study
Authors: Bidira Kebebe , Tamiru Dessalegn , Belachew Tefera
Published: January 2022

Background

Under-nutrition is a global problem and one of the most serious public health issues. Globally, 156 million under-five children were stunted, and 50 million were wasted in 2016. Malnutrition among preschool-age children is caused by low socioeconomic status, food insecurity, poor feeding practices, and infectious diseases. This intervention aimed to evaluate the effect of nutrition education delivered through trained health professionals in improving the nutritional status of preschool -aged children.

Methods

A quasi-experimental design among 588 preschool –aged children was used. A multistage sampling technique followed by a systematic random sampling technique was used to identify caregivers with preschool-aged children. Structured questionnaires were used to collect data. The baseline difference in demographic and socioeconomic characteristics between the two groups was examined using a chi-square test and an independent sample t-test was used to determine the mean difference in under-nutrition between the intervention and control groups. Generalized estimating equations (GEE) were used to determine the change in the difference in outcome between the intervention and control groups as well as the association of predictors with under-nutrition in children. The Adjusted odds ratio (AOR) with the corresponding 95% confidence intervals was reported to show the strength of the association. Variables with a p-value of less than 0.05 were considered statistically significant in multivariable analysis.

Results

In this study, the nutritional status of preschool age children was significantly associated with nutrition education intervention [AOR = 0.566, 95% CI: (0.347, 0.923)], place of delivery [AOR = 0.724, 95% CI: (0.551, 0.951)], ARI in the last 2 weeks [AOR = 1.823, 95% CI: (1.226, 2.710)], source of drinking water [AOR = 0.624, 95% CI: (0.484, 0.805)] and household food security [AOR = 1.311, 95% CI: (1.030, 1.669)] .

Conclusions

Findings of this study showed that nutrition education can effectively reduce the magnitude of under-nutrition among preschool children. Under-nutrition was e significantly associated with nutritional education, place of delivery, ARI in the last 2 weeks, source of drinking water, and food security. Therefore, both government and non-government should consider the impacts of nutrition education to alleviate under-nutrition and improve the health status of preschool-age children.
The adolescent with obesity: what perspectives for treatment?
Authors: Nicolucci Antonio , Maffeis Claudio
Published: January 2022

The dramatic increase in overweight and obesity among children and adolescents has become a major public health problem. Obesity in children and young adults is associated with an increased prevalence of cardiometabolic risk factors. Obesity during adolescence represents a strong predictor of obesity and higher mortality in adulthood. Due to the serious implications of obesity in adolescents, effective treatments are urgently needed. Lifestyle interventions represent the recommended therapy. Nevertheless, real world data show that the majority of adolescents do not achieve weight loss in the long term, and are reluctant to participate in lifestyle interventions. Pharmacological treatment is recommended if a formal lifestyle modification program fails to limit weight gain or to improve comorbidities. However, until 2020 the European Medicines Agency (EMA) had not approved any pharmacotherapeutic agents for obesity in pediatric patients. On April 2021, EMA has authorized the use of Liraglutide, a glucagon-like peptide (GLP)-1 analog, for the treatment of obesity in adolescents (12–17 years). The efficacy and safety of Liraglutide were demonstrated in a randomized, double-blind trial, enrolling 251 adolescents. After 56 weeks, a reduction in BMI of at least 5% was observed in 43.3% of participants in the liraglutide group vs. 18.7% in the placebo group, and a reduction in BMI of at least 10% was observed in 26.1 and 8.1%, respectively. Gastrointestinal events were the events most frequently reported with liraglutide. Bariatric surgery represents another effective treatment for adolescents with severe obesity, with sustained benefits on weight loss and cardiometabolic risk factors. However, long-term safety and effectiveness data in adolescents are still scarce. Risks of bariatric surgery include the need for additional abdominal surgical procedures and specific micronutrient deficiencies. Hopefully, new pharmacological treatments in addition to lifestyle interventions will offer more chances of success.
Design and rationale for a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy (OVOID) trial: study protocol for a randomized controlled trial
Authors: Jo Sua , Moon Hyeyeon , Park Kyungil , Sohn Chang-Bae , Kim Jeonghwan , Kwon Yong-Seop , Kim Su Hong
Published: January 2022

Background

Dilated cardiomyopathy (DCMP) is characterized by ventricular chamber enlargement and systolic dysfunction which may cause heart failure. Patients with DCMP have overactivation of the renin-angiotensin-aldosterone systems, which can also adversely affect myocardial metabolism in heart failure. The impairment of myocardial metabolism can contribute to the progression of left ventricular remodeling and contractile dysfunction in heart failure. Although angiotensin II receptor blockers (ARBs) have been used to treat patients with DCMP, there has been no direct comparison of the efficacy of these agents. The objective of this study is to compare the effects of olmesartan and valsartan on myocardial metabolism in patients with DCMP.

Methods/design

The OVOID study (a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy) is designed as a non-blinded, open-label, parallel-group, prospective, randomized, controlled, multicenter clinical trial. A total of 40 DCMP patients aged between 20 and 85 years will be randomly allocated into the olmesartan or the valsartan group. 18F-fluoro-2-deoxyglucose (FDG) cardiac positron emission tomography (PET) will be performed at baseline and six months after receiving the study agent. The primary endpoint is myocardial glucose consumption per square meter, measured using 18F-FDG PET 6 months after receiving the study agent.

Discussion

The purpose of this trial is to compare the efficacy between olmesartan and valsartan in improving myocardial metabolism in DCMP patients. This will be the first randomized comparative study investigating the differential effects of ARBs on heart failure.

Trial registration

ClinicalTrials.govNCT04174456. Registered on 18 November 2019
Effects of Bushen-Jiangya granules on blood pressure and pharmacogenomic evaluation in low-to-medium-risk hypertensive patients: study protocol for a randomized double-blind controlled trial
Authors: Yang Xiaochen , Liu Lanping , Xiong Xingjiang , Zhang Yun , Liu Yongmei , Li Hongzheng , Yao Kuiwu , Wang Jie
Published: January 2022

Introduction

Hypertension is one of the most important risk factors for cardiovascular disease, and its control rates remain low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) could suppress ventricular hypertrophy and inflammatory responses, lower blood pressure, and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension.

Methods and analysis

This trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experimental group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is the change in 24-h average systolic and diastolic blood pressure. The secondary outcomes include heart rate variability, pharmacogenomic evaluation, improvement in TCM syndrome, and serum pro-inflammatory/anti-inflammatory cytokines between the two groups. The safety of medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0.

Ethics and dissemination

This study has been approved by the Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial, and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences.

Discussion

We hypothesize that patients with low-to-medium-risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians.

Trial registration

Chinese Clinical Trial Registry ChiMCTR1900002876. Registered in November 2019
Outcome selection for tissue-agnostic drug trials for immune-mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance
Authors: Aiyegbusi Olalekan Lee , di Ruffano Lavinia Ferrante , Retzer Ameeta , Newsome Philip N. , Buckley Christopher D. , Calvert Melanie J.
Published: January 2022

Background

Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to:

Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies.

Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences.

Methods

The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared.

Results

Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS.

Conclusions

The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS.

Trial registration

Not registered.
Association between blood glucose levels and Glasgow Outcome Score in patients with traumatic brain injury: secondary analysis of a randomized trial
Authors: Yuan Tao , He Hongyu , Liu Yuepeng , Wang Jianwei , Kang Xin , Fu Guanghui , Xie Fangfang , Li Aimin , Chen Jun , Wang Wenxue
Published: January 2022

Background

Blood glucose levels that are too high or too low after traumatic brain injury (TBI) negatively affect patient prognosis. This study aimed to demonstrate the relationship between blood glucose levels and the Glasgow Outcome Score (GOS) in TBI patients.

Methods

This study was based on a randomized, dual-center, open-label clinical trial. A total of 208 patients who participated in the randomized controlled trial were followed up for 5 years. Information on the disease, laboratory examination, insulin therapy, and surgery for patients with TBI was collected as candidate variables according to clinical importance. Additionally, data on 5-year and 6-month GOS were collected as primary and secondary outcomes, respectively. For multivariate analysis, a generalized additive model (GAM) was used to investigate relationships between blood glucose levels and GOS. The results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). We further applied a two- piecewise linear regression model to examine the threshold effect of blood glucose level and GOS.

Results

A total of 182 patients were included in the final analysis. Multivariate GAM analysis revealed that a bell-shaped relationship existed between average blood glucose level and 5-year GOS score or 6-month GOS score. The inflection points of the average blood glucose level were 8.81 (95% CI: 7.43–9.48) mmol/L considering 5-year GOS as the outcome and were 8.88 (95% CI 7.43−9.74) mmol/L considering 6-month GOS score as the outcome. The same analysis revealed that there was also a bell relationship between average blood glucose levels and the favorable outcome group (GOS score ≥ 4) at 5 years or 6 months.

Conclusion

In a population of patients with traumatic brain injury, blood glucose levels were associated with the GOS. There was also a threshold effect between blood glucose levels and the GOS. A blood glucose level that is either too high or too low conveys a poor prognosis.

Trial registration

ClinicalTrials.gov NCT02161055. Registered on 11 June 2014.
Metabarcoding reveals low prevalence of microsporidian infections in castor bean tick (Ixodes ricinus)
Authors: Trzebny Artur , Liberska Justyna , Slodkowicz-Kowalska Anna , Dabert Miroslawa
Published: January 2022

Background

Microsporidia is a large group of eukaryotic obligate intracellular spore-forming parasites, of which 17 species can cause microsporidiosis in humans. Most human-infecting microsporidians belong to the generaEnterocytozoonandEncephalitozoon. To date, only five microsporidian species, includingEncephalitozoon-like, have been found in hard ticks (Ixodidae) using microscopic methods, but no sequence data are available for them. Furthermore, no widespread screening for microsporidian-infected ticks based on DNA analysis has been carried out to date. Thus, in this study, we applied a recently developed DNA metabarcoding method for efficient microsporidian DNA identification to assess the role of ticks as potential vectors of microsporidian species causing diseases in humans.

Methods

In total, 1070 (493 juvenile and 577 adult) unfed host-seekingIxodes ricinusticks collected at urban parks in the city of Poznan, Poland, and 94 engorged tick females fed on dogs and cats were screened for microsporidian DNA. Microsporidians were detected by PCR amplification and sequencing of the hypervariable V5 region of 18S rRNA gene (18S profiling) using the microsporidian-specific primer set. Tick species were identified morphologically and confirmed by amplification and sequencing of the shortened fragment of cytochromecoxidase subunit I gene (mini-COI).

Results

All collected ticks were unambiguously assigned toI. ricinus. Potentially zoonoticEncephalitozoon intestinaliswas identified in three fed ticks (3.2%) collected from three different dogs. In eight unfed host-seeking ticks (0.8%), including three males (1.1%), two females (0.7%) and three nymphs (0.7%), the new microsporidian sequence representing a species belonging to the genusEndoreticulatuswas identified.

Conclusions

The lack of zoonotic microsporidians in host-seeking ticks suggests thatI.ricinusis not involved in transmission of human-infecting microsporidians. Moreover, a very low occurrence of the other microsporidian species in both fed and host-seeking ticks implies that mechanisms exist to defend ticks against infection with these parasites.

Graphical abstract
Creatinine-to-body weight ratio is a predictor of incident diabetes: a population-based retrospective cohort study
Authors: He Jiacheng
Published: January 2022

Purpose

Creatinine to body weight (Cre/BW) ratio is considered the independent risk factor for incident type 2 diabetes mellitus (T2DM), but research on this relationship is limited. The relationship between the Cre/BW ratio and T2DM among Chinse individuals is still ambiguous. This study aimed to evaluate the correlation between the Cre/BW ratio and the risk of T2DM in the Chinese population.

Methods

This is a retrospective cohort study from a prospectively collected database. We included a total of 200,658 adults free of T2DM at baseline. The risk of incident T2DM according to Cre/BW ratio was estimated using multivariable Cox proportional hazards models, and a two-piece wise linear regression model was developed to find out the threshold effect.

Results

With a median follow-up of 3.13 ± 0.94 years, a total of 4001 (1.99%) participants developed T2DM. Overall, there was an L-shaped relation of Cre/BW ratio with the risk of incident T2DM (P for non-linearity < 0.001). When the Cre/BW ratio (× 100) was less than 0.86, the risk of T2DM decreased significantly as the Cre/BW ratio increased [0.01 (0.00, 0.10), P < 0.001]. When the Cre/BW ratio (× 100) was between 0.86 and 1.36, the reduction in the risk of developing T2DM was not as significant as before [0.22 (0.12, 0.38), P < 0.001]. In contrast, when the Cre/BW ratio (× 100) was greater than 1.36, the reduction in T2DM incidence became significantly flatter than before [0.73 (0.29,1.8), P = 0.49].

Conclusion

There was an L-shaped relation of Cre/BW ratio with incidence of T2DM in general Chinese adults. A negative curvilinear association between Cre/BW ratio and incident T2DM was present, with a saturation effect predicted at 0.86 and 1.36 of Cre/BW ratio (× 100).
Association of metabolic syndrome traits with urinary biomarkers in Japanese adults
Authors: Kabasawa Keiko , Hosojima Michihiro , Ito Yumi , Matsushima Kazuo , Tanaka Junta , Hara Masanori , Nakamura Kazutoshi , Narita Ichiei , Saito Akihiko
Published: January 2022

Background

Although metabolic syndrome traits are risk factors for chronic kidney disease, few studies have examined their association with urinary biomarkers.

Methods

Urinary biomarkers, including A-megalin, C-megalin, podocalyxin, albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase, were cross-sectionally assessed in 347 individuals (52.7% men) with a urine albumin-to-creatinine ratio (ACR)  < 300 mg/g in a health checkup. Metabolic syndrome traits were adopted from the National Cholesterol Education Program (third revision) of the Adult Treatment Panel criteria modified for Asians.

Results

Participants had a mean body mass index, estimated glomerular filtration rate (eGFR), and median ACR of 23.0 kg/m2, 74.8 mL/min/1.73 m2, and 7.5 mg/g, respectively. In age- and sex-adjusted logistic regression analysis, A-megalin and albumin were significantly associated with the clustering number of metabolic syndrome traits (3 or more). After further adjustment with eGFR, higher quartiles of A-megalin and albumin were each independently associated with the clustering number of metabolic syndrome traits (adjusted odds ratio for A-megalin: 1.30 per quartile, 95% CI 1.03–1.64; albumin: 1.42 per quartile, 95% CI 1.12–1.79).

Conclusions

Both urinary A-megalin and albumin are associated with the clustering number of metabolic syndrome traits. Further research on urinary A-megalin is warranted to examine its role as a potential marker of kidney damage from metabolic risk factors.
AK098656: a new biomarker of coronary stenosis severity in hypertensive and coronary heart disease patients
Authors: Wang Xin , Wu Ya-li , Zhang Yuan-yuan , Ke Jing , Wang Zong-wei , Zhang Bao-yu , Ma Yan , Yang Long-yan , Zhao Dong
Published: January 2022

Background

AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications.

Methods

A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation.

Results

AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006).

Conclusion

AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.
Effect of six-week traditional resistance and functional training on functional performance in female netball players
Authors: Kovac Dimitrije , Krkeljas Zarko , Venter Ranel
Published: January 2022

Background

Improving the quality of functional movements in athletes generally requires additional training targeting specific functional deficiencies. However, well-rounded, traditional strength and conditioning program should also improve player’s movement quality. Therefore, the primary aim of this study was to compare the effect of two different six-week interventions on the functional score of female netball players.

Methods

In a randomized controlled study, players were divided into control and intervention group. Both groups completed identical six-week strength and conditioning program, with the intervention group also completing additional corrective exercises three sessions per week during the same period.

Results

The FMS® score was significantly higher in the intervention group after 6-week program (f = 9.85, p = 0.004). However, the differences in total score may be attributed mainly to differences between groups in active straight leg raise (p = 0.004) and trunk stability push-up test (p = 0.02), as other individual tests demonstrated similar time and group effect.

Conclusion

These results indicate that although FMS® based intervention may improve overall functional movement score, the athletes in both groups have demonstrated similar improvements in most of the individual tests. Hence, a well-rounded strength and conditioning program incorporating athlete-specific exercises based on limitations identified in the functional movement screen, may result in a balanced training strategy and reduce the need for supplementary functional training sessions.
CT angiography for the assessment of EVAR complications: a pictorial review
Authors: Gozzo Cecilia , Caruana Giovanni , Cannella Roberto , Farina Arduino , Giambelluca Dario , Dinoto Ettore , Vernuccio Federica , Basile Antonio , Midiri Massimo
Published: January 2022

Endovascular aneurysm repair (EVAR) is a minimally invasive treatment proposed as an alternative to open repair in patients with abdominal aortic aneurysms. EVAR consists in a stent-graft placement within the aorta in order to exclude the aneurysm from arterial circulation and reduce the risk of rupture. Knowledge of the various types of devices is mandatory because some stents/grafts are more frequently associated with complications. CT angiography is the gold standard diagnostic technique for preprocedural planning and postprocedural surveillance. EVAR needs long-term follow-up due to the high rate of complications. Complications can be divided in endograft device-related and systemic complications. The purpose of this article is to review the CT imaging findings of EVAR complications and the key features for the diagnosis.