Identification of biomarkers for essential hypertension based on metabolomics

AimEssential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases.Data synthesisThis review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0.Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development.ConclusionsThis study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.     

Evaluation of the incorporation of an IOTA-ADNEX model in the discrimination of adnexal masses in our third-level hospital centre,taking into account the menopausal status of patients. Five years of experience

ObjectiveThe objectives were to estimate the performance of the IOTA-ADNEX model test after its incorporation into the ultrasound tests of our third-grade hospital gynecology service, as well as to assess whether its capacity of accuracy is modified when taking into account the patient's menopausal status.MethodsA cross-sectional study was conducted to clinically evaluate the diagnostic performance of the IOTA-ADNEX model test, which was performed between January 2016 and December 2021. The study included 573 women with an adnexal injury who underwent surgical excision within 180 days after ultrasound diagnosis and histological confirmation (gold standard). After the ultrasound exam, the injuries were classified using the ADNEX model. The study estimated the area under the receiver-operating-characteristics curve (AUC) of the ADNEX model for classifying between benign and malignant adnexal masses and compared the performance by menopausal state. Sensitivity and specificity were determined for different cut-off points.ResultsOut of the 573 women, 183 (31.9%) had a malignant tumor. The AUC of the ADNEX model for differentiating between benign and malignant adnexal masses at the time of ultrasound examination was 0.92 and the best malignancy threshold, detected by Youden index, was 22.5%. At this cut-off, the sensitivity of the ADNEX model was 91.8% and the specificity was 76.4%. However, it varies according to menopausal status: in the group of pre-menopausal patient, sensitivity was 86.1% (95% CI, 85.4%–86.8%) and specificity was 81.3% (95% CI, 85.4%–86.8%). In the postmenopausal group, sensitivity was 96.1% (95% CI, 95.6%–96.7%) and specificity was 68.5% (95% CI, 68.1%–68.8%).ConclusionsThe IOTA-ADNEX model is a reliable diagnostic tool to discard ovarian cancer. However, the accuracy of the test, at the same cut-off point, varies according to the menopausal state of the patient so it may be important to take it into account when taking decisions in clinical practice.     

The percutaneous learning curve of 3rd generation minimally-invasive Chevron and Akin osteotomy (MICA)

BackgroundMinimally-invasive Chevron and Akin osteotomy (MICA) represents the third-generation percutaneous hallux valgus surgery which is characterized by an extra-articular osteotomy, stable internal fixation and a high potential for correction. Compared to other percutaneous techniques of the foot, MICA is generally regarded as an advanced and demanding surgical procedure with a flat learning curve. The aim of this study is to analyze a single-surgeons experience with his first 50 consecutive MICA procedures.MethodsBetween May 2018 and February 2021, 50 consecutive MICA procedures performed by the author with the "K-wires-First technique" were prospectively analyzed focusing on surgery duration, number of fluoroscopies, correction results and surgery-associated complications. A modification of the original MICA technique as described by its inaugurators Redfern and Vernois allows the use of a standard-sized C-arm and aims to reduce revison rates and conversion to open surgery by placing the guidewires prior to performing the osteotomy.ResultsThe average surgery time for all MICA procedures was 46.8 min (SD 12.1, range 31–90 min). The average amount of fluoro shots required to perform MICA was n = 126.6 (SD 40.8, range 65–231). Comparing the preoperative and 6-week postoperative radiographs, the IMA decreased after MICA by a mean of 10.8° from 16.2° to 5.4° and the HVA by a mean of 22.1° from 30.6° to 8.5°. One case required intraoperative conversion to open hallux correction. There were 4 feet in three patients with secondary screw removal of the Chevron fixation due to prominent proximal screw tips.ConclusionsAlthough the learning curve of 3rd generation MICA is flat and requires specific training and intensive practice, the rate of complications is not elevated compared to other percutaneous hallux valgus techniques. Strict adherence to the principles of 3rd generation MICA with stable fixation and meticulous intraoperative control of each surgical step helps to reduce surgery-associated complications. The learning curve showed a continous improvement in regard to surgery time and use of fluoroscopy. After 40 procedures, the surgery time consistently dropped under 45 min and required less than 100 fluoro-shots. The modified surgical technique may help reduce Chevron screw mal-positioning when using large C-arm fluoroscopy for this procedure.     

Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial

BackgroundPretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients.MethodsWe created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups.ResultsIn 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p ?< ?0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p ?< ?0.001), and using 0, 1–100 and ?> ?100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p ?= ?0.06). Similar results were found in all subanalyses.ConclusionCalcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.     

多重荧光PCR-熔解曲线法同时检测常见病原真菌方法学的建立及诊断价值

目的建立多重荧光PCR-熔解曲线法，并评价其同时检测假丝酵母菌、曲霉菌及新型隐球菌的诊断价值。 方法建立多重荧光PCR-熔解曲线法并对其检测体系进行优化。收集临床高度怀疑为侵袭性真菌感染（IFI）的各类临床样本179例，其中血液65例、深部痰液35例、尿液30例、脑脊液18例、胸腹水12例、肺泡灌洗液10例、新鲜肺组织9例。通过敏感性、特异性、重复性实验验证多重荧光PCR-熔解曲线法的检测性能，并应用受试者工作特征（ROC）曲线评价该方法的诊断效能。 结果建立的多重荧光PCR-熔解曲线法可同时检测8种常见病原真菌，包括4种假丝酵母菌（白假丝酵母菌、热带假丝酵母菌、光滑假丝酵母菌、克柔假丝酵母菌）、3种曲霉菌（烟曲霉、黄曲霉、黑曲霉）和新型隐球菌。其最低检测限为1 × 10⁴ cfu/mL，且常见细菌无扩增反应，重复性实验解链温度波动小于0.5 ℃。179例临床样本中，以培养法、镜检法、病理诊断等"金标准"方法诊断IFI阳性为112例，多重荧光PCR-熔解曲线法检测阳性为96例。多重荧光PCR-熔解曲线法同时检测假丝酵母菌、曲霉菌及新型隐球菌的敏感度为0.857，特异度为0.970，阳性预测值为0.980，阴性预测值为0.802，ROC曲线下面积为0.914，95%置信区间为0.868 ~ 0.959，P < 0.001。 结论本研究建立的多重荧光PCR-熔解曲线法可快速、准确、高通量同时检测假丝酵母菌、曲霉菌及新型隐球菌，对于IFI的早期诊断具有重要意义。     

Reliability and validity of the Japanese version of the Biological Rhythms Interview of assessment in neuropsychiatry-self report for delayed sleep-wake phase disorder

ObjectiveThe Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) might be applicable for assessing delayed sleep-wake phase disorder (DSWPD). We aimed to investigate the reliability and validity of the Japanese version of the BRIAN self-report (J-BRIAN-SR) in DSWPD patients and determine a cutoff score to identify the presence of the disorder.MethodsWe enrolled 60 newly diagnosed DSWPD outpatients and 64 age-matched healthy controls. We used Cronbach's alpha for internal reliability to evaluate J-BRIAN-SR. We confirmed the reliability of the A test and re-test using Pearson's correlation coefficient in the controls. We used confirmatory factor analysis to evaluate the factor structure of J-BRIAN-SR and referenced the Morningness-Eveningness Questionnaire (MEQ) to check concurrent validity. We analyzed the receiver operating characteristic curve (ROC) to determine the J-BRIAN-SR cutoff point for the presence of DSWPD.ResultsThe 18-component scores of the J-BRIAN-SR had an overall reliability coefficient (Cronbach's alpha) of 0.82. We confirmed a high test-retest reliability using an intraclass correlation coefficient (r = 0.84). The correlation between J-BRIAN-SR and MEQ was 0.38 (p = 0.003). The J-BRIAN-SR that we extracted by exploratory factor analysis consisted of three factors. A score of 40 points provided a sensitivity of 80.0% and a specificity of 75.6% for the positivity of DSWPD.ConclusionsThe results of the present study revealed that J-BRIAN-SR is a valid and reliable instrument for screening and evaluating the severity of DSWPD. Our findings will be useful to physicians and patients in Japan and those in clinical settings.     

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging

1. Download : Download high-res image (252KB)
2. Download : Download full-size image

     

Functional outcomes and complications after treatment of distal radius fracture in patients sixty years and over: A systematic review and network meta-analysis

AimThis network meta-analysis aims to compare functional outcomes and complications between conservative treatment and surgery for distal radius fractures in patients aged 60 years and over.MethodsWe searched the PubMed, EMBASE, and Web of Science databases for randomized controlled trials (RCTs) assessing the effect of conservative treatment and surgery for distal radius fractures in patients aged 60 years and over. Primary outcomes included grip strength and overall complications. Secondary outcomes included Disabilities of the Arm, Shoulder, and Hand (DASH) scores, Patient-Rated Wrist Evaluation (PRWE) scores, wrist range of motion and forearm rotation, and radiographic assessment. All continuous outcomes were assessed using standardized mean differences (SMDs) with 95% confidence intervals (CIs), and binary outcomes were assessed using odds ratio (OR) with 95% CIs. The surface under the cumulative ranking curve (SUCRA) was used to determine a hierarchy of treatments. Cluster analysis was performed for grouping treatments based on the SUCRA values of primary outcomes.ResultsFourteen RCTs were included to compare conservative treatment, volar lockedplate (VLP), K-wires fixation, and external-fixation. VLP outperformed conservative treatment for 1-year and minimum 2-year grip strength (SMD; 0.28 [0.07 to 0.48] and 0.27 [0.02 to 0.53], respectively). VLP yielded the optimal grip strength at 1-year and minimum 2-year follow-up (SUCRA; 89.8% and 86.7%, respectively). In a subgroup analysis of patients aged 60 to 80 years old, VLP outperformed conservative treatment in DASH and PRWE scores (SMD, 0.33 [0.10, 0.56] and 0.23 [0.01, 0.45], respectively). In addition, VLP had the fewest complications (SUCRA = 84.3%). Cluster analysis suggested that VLP and K-wire fixation were more effective treatment groups.ConclusionEvidence to date demonstrates that VLP provides measurable benefits in grip strength and fewer complications to those 60 years of age and over, and that benefit is not reflected in current practice guidelines. There is a subgroup of patients where K-wire fixation outcomes are similar to those of VLP; defining this subgroup may yield substantial societal benefits.