Tag: pubmed

Vasc Med. 2022 Aug 24:1358863X221117608. doi: 10.1177/1358863X221117608. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aims to evaluate changes in the arterial spectral Doppler waveform in a canine artery stenosis model.

METHODS: Canine femoral artery stenosis models were established in 12 beagle dogs. Doppler waveforms were recorded in the femoral artery preoperatively and postoperatively in the femoral artery and at the ankle after formation of a 50%, 70%, and 90% stenosis or occlusion. Major descriptors for arterial Doppler waveform were used to analyse waveforms.

RESULTS: The proportion of multiphasic waveforms proximal to a moderate stenosis decreased compared to normal baseline, although the difference was not statistically significant, whereas the decreases at the stenosis, distal to the stenosis, and at the ankle were significant (p < 0.05). The decreases in arteries with a more severe stenosis or occlusion were significant at all locations (p < 0.05). The proportion of high resistive waveforms decreased significantly at the ankle in the arteries with a moderate stenosis (50%) (p = 0.002), but the decreases proximal to, at, and distal to the stenosis were not significant. The decreases were significant at all locations in the arteries with a more severe stenosis (p < 0.05). The decrease was significant at the ankle in the arteries with an occlusion (p < 0.001) but not significant pre, at, and post an occlusion.

CONCLUSIONS: Phasicity and resistance of Doppler waveforms alter in canine femoral arteries with a stenosis. Phasicity change seems more sensitive in response to an arterial stenosis than resistance change. Additional information on arterial resistance could be obtained using end-diastolic ratios, resistive indices, and potentially end-systolic notch velocity measurements.

PMID:36000474 | DOI:10.1177/1358863X221117608

J Am Heart Assoc. 2022 Aug 24:e025864. doi: 10.1161/JAHA.122.025864. Online ahead of print.

ABSTRACT

Background The systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small noncoding RNAs that have important roles in modulating protein levels and function of cells. Methods and Results We performed miRNA-sequencing on leukocytes isolated from neonatal patients with CPB (n=5) at 7 time points during the process of CPB, including before the initiation of bypass, during bypass, and at 3 time points during the first 24 hours after weaning from bypass. We identified significant differentially expressed miRNAs using generalized linear regression models, and miRNAs were defined as statistically significant using a false discovery rate-adjusted P<0.05. We identified gene targets of these miRNAs using the TargetScan database and identified significantly enriched biological pathways for these gene targets. We identified 54 miRNAs with differential expression during and after CPB. These miRNAs clustered into 3 groups, including miRNAs that were increased during and after CPB (3 miRNAs), miRNAs that decreased during and after CPB (10 miRNAs), and miRNAs that decreased during CPB but then increased 8 to 24 hours after CPB. A total of 38.9% of the target genes of these miRNAs were significantly differentially expressed in our previous study. miRNAs with altered expression levels are predicted to significantly modulate pathways related to inflammation and signal transduction. Conclusions The unbiased profiling of the miRNA changes that occur in the circulating leukocytes of patients with bypass provides deeper insight into the mechanisms that underpin the systemic inflammatory response that occurs in patients after exposure to CPB. These data will help the development of novel treatments and biomarkers for bypass-associated inflammation.

PMID:36000433 | DOI:10.1161/JAHA.122.025864

Bone Jt Open. 2022 Aug;3(8):656-665. doi: 10.1302/2633-1462.38.BJO-2021-0214.R1.

ABSTRACT

AIMS: The mid-term results of kinematic alignment (KA) for total knee arthroplasty (TKA) using image derived instrumentation (IDI) have not been reported in detail, and questions remain regarding ligamentous stability and revisions. This paper aims to address the following: 1) what is the distribution of alignment of KA TKAs using IDI; 2) is a TKA alignment category associated with increased risk of failure or poor patient outcomes; 3) does extending limb alignment lead to changes in soft-tissue laxity; and 4) what is the five-year survivorship and outcomes of KA TKA using IDI?

METHODS: A prospective, multicentre, trial enrolled 100 patients undergoing KA TKA using IDI, with follow-up to five years. Alignment measures were conducted pre- and postoperatively to assess constitutional alignment and final implant position. Patient-reported outcome measures (PROMs) of pain and function were also included. The Australian Orthopaedic Association National Joint Arthroplasty Registry was used to assess survivorship.

RESULTS: The postoperative HKA distribution varied from 9° varus to 11° valgus. All PROMs showed statistical improvements at one year (p < 0.001), with further improvements at five years for Knee Osteoarthritis Outcome Score symptoms (p = 0.041) and Forgotten Joint Score (p = 0.011). Correlation analysis showed no difference (p = 0.610) between the hip-knee-ankle and joint line congruence angle at one and five years. Sub-group analysis showed no difference in PROMs for patients placed within 3° of neutral compared to those placed > 3°. There were no revisions for tibial loosening; however, there were reports of a higher incidence of poor patella tracking and patellofemoral stiffness.

CONCLUSION: PROMs were not impacted by postoperative alignment category. Ligamentous stability was maintained at five years with joint line obliquity. There were no revisions for tibial loosening despite a significant portion of tibiae placed in varus; however, KA executed with IDI resulted in a higher than anticipated rate of patella complications.Cite this article: Bone Jt Open 2022;3(8):656-665.

PMID:36000465 | DOI:10.1302/2633-1462.38.BJO-2021-0214.R1

Zhonghua Yi Xue Za Zhi. 2022 Aug 23;102(31):2458-2464. doi: 10.3760/cma.j.cn112137-20220109-00060.

ABSTRACT

Objective: To compare the safety and efficacy of cryoablation(CYA) and radiofrequency ablation(RFA) for stageⅠnon-small cell lung cancer(NSCLC). Methods: From January 2014 to January 2019, 90 eligible patients [48 males, 42 females, age: 39-85(63.6±10.1)years] in the First Affiliated Hospital of Zhengzhou University met the inclusion criteria were retrospectively analyzed. They were divided into 2 groups according to different treatment methods(group CYA and group RFA). The duration of operation, intraoperative pain, local tumor progression rate and the incidence of complications were compared. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Results: The clinical data and tumor situation of the patients between two groups did not show significant differences. The mean duration of operation for group CYA was longer than that for group RFA [(73.5±17.2)min vs (51.4±18.7)min, P<0.001];the mean intraoperative visual analogue score(VAS)for group CYA was lower than that for group RFA (0.53±0.89 vs 3.44±2.44, P<0.001). The median follow-up period time were 53 months and 52 months for group CYA and RFA. At the end of the study, The local tumor progression rate was 31.6%(12/38) and 25.0%(13/52) for group CYA and group RFA, the difference were not statistically(P=0.491). There was no statistical difference for progress-free survival(PFS)between group CYA and group RFA[51(95%CI:40.3-55.0)months)vs 44(95%CI:37.2-54.1) months, P=0.649]. The median OS was not reached in both groups. The most common complications observed in the two groups were pneumothorax, hemorrhage and pleural effusion. There was no statistical difference in the incidence rates [42.1%(16/38) for group CYA vs 28.8% (15/52)for group RFA, P=0.191]. The incidence rate of pleural effusion for group CYA was higher than that for group RFA [26.3%(10/38)vs 5.8%(3/52), P=0.006]. The incidence rates of pneumothorax and hemorrhage had no statistical difference between the two groups [13.3%(5/38)vs 13.5% (7/52) and 15.8%(6/38) vs 9.6% (5/52), all P>0.05]. Conclusion: Compared with RFA,CYA shows no significant differences in the same efficacy and safety for treating patients with stage Ⅰ NSCLC, with less intraoperative pain but longer operative duration.

PMID:36000376 | DOI:10.3760/cma.j.cn112137-20220109-00060

Cardiol Young. 2022 Aug 24:1-8. doi: 10.1017/S104795112200261X. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine potentially modifiable risk factors for a complicated Glenn procedure (cGP) and whether a cGP predicted adverse neurodevelopmental and functional outcomes. A cGP was defined as post-operative death, heart transplant, extracorporeal life support, Glenn takedown, or prolonged ventilation.

METHODS: All 169 patients having a Glenn procedure from 2012 to 2017 were included. Neurodevelopmental assessments were performed at age 2 years in consenting survivors (n = 156/159 survivors). The Bayley Scales of Infant and Toddler Development-3^rd Edition (Bayley-III) and the Adaptive Behavior Assessment System-2^nd Edition (ABAS-II) were administered. Adaptive functional outcomes were determined by the General Adaptive Composite (GAC) score from the ABAS-II. Predictors of outcomes were determined using univariate and multiple variable linear or Cox regressions.

RESULTS: Of patients who had a Glenn procedure, 10/169 (6%) died by 2 years of age and 27/169 (16%) had a cGP. Variables statistically significantly associated with a cGP were the inotrope score on post-operative day 1 (HR 1.04, 95%CI 1.01, 1.06; p = 0.010) and use of inhaled nitric oxide post-operatively (HR 7.31, 95%CI 3.19, 16.76; p < 0.001). A cGP was independently statistically significantly associated with adverse Bayley-III Cognitive (ES -10.60, 95%CI -17.09, -4.11; p = 0.002) and Language (ES -11.43, 95%CI -19.25, -3.60; p = 0.004) scores and adverse GAC score (ES -14.89, 95%CI -22.86, -6.92; p < 0.001).

CONCLUSIONS: Higher inotrope score and inhaled nitric oxide used post-operatively were associated with a cGP. A cGP was independently associated with adverse 2-year neurodevelopmental and functional outcomes. Whether early recognition and intervention for risk of a cGP can prevent adverse outcomes warrants study.

PMID:36000320 | DOI:10.1017/S104795112200261X

J Phys Chem A. 2022 Aug 24. doi: 10.1021/acs.jpca.2c01309. Online ahead of print.

ABSTRACT

The relative abundances of singly deuterated methanol isotopologues, [CH₂DOH]/[CH₃OD], in star-forming regions deviate from the statistically expected ratio of 3. In Orion KL, the nearest high-mass star-forming region to Earth, the singly deuterated methanol ratio is about 1, and the cause for this observation has been explored through theory for nearly three decades. We present high-angular resolution observations of Orion KL using the Atacama Large Millimeter/submillimeter Array to map small-scale changes in CH₃OD column density across the nebula, which provide a new avenue to examine the deuterium chemistry during star and planet formation. By considering how CH₃OD column densities vary with temperature, we find evidence of chemical processes that can significantly alter the observed gas-phase column densities. The astronomical data are compared with existing theoretical work and support D-H exchange between CH₃OH and heavy water (i.e., HDO and D₂O) at methanol’s hydroxyl site in the icy mantles of dust grains. The enhanced CH₃OD column densities are localized to the Hot Core-SW region, a pattern that may be linked to the coupled evolution of ice mantle chemistry and star formation in giant molecular clouds. This work provides new perspectives on deuterated methanol chemistry in Orion KL and informs considerations that may guide future theoretical, experimental, and observational work.

PMID:36000316 | DOI:10.1021/acs.jpca.2c01309

Chron Respir Dis. 2022 Jan-Dec;19:14799731221104099. doi: 10.1177/14799731221104099.

ABSTRACT

Quality of life (QOL) in patients with Chronic obstructive pulmonary disease (COPD) is a major global concern in respiratory care with the specific instruments used rarely being developed using a modular approach. This paper is aimed to develop the COPD scale of the system of QOL Instruments for Chronic Diseases (QLICD-COPD) by the modular approach based on Classical Test Theory and Generalizability Theory (GT). 114 inpatients with COPD were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, and also GT analysis. The Results showed that Multi-trait scaling analysis, correlation and factor analyses confirmed good construct validity and criterion-related validity with almost all correlation coefficients or factor loadings being above 0.40. The internal consistency α and test-retest reliability coefficients (Pearson r and Intra-class correlations ICC) for all domains except for the social domain were larger than 0.70, ranging between 0.70-0.86 with r = 0.85 for the overall. The overall score and scores for physical and the specific domains had statistically significant changes after treatments with moderate effect size SRM (standardized response mean) ranging from 0.32 to 0.44. All G-coefficients and index of dependability were all greater than 0.80 exception of social domain (0.546 and 0.500 respectively), confirming the reliability of the scale further. It concluded that the QLICD-COPD has good validity, reliability, and moderate responsiveness, and can be used as the QOL instrument for patients with COPD.

PMID:36000309 | DOI:10.1177/14799731221104099

J Med Virol. 2022 Aug 24. doi: 10.1002/jmv.28085. Online ahead of print.

ABSTRACT

OBJECTIVES: To summarize the clinical characteristics and explore the role of treatment types in outcomes among psoriasis patients with Coronavirus Disease 2019 (COVID-19).

METHODS: The principal summary measures used were pooled prevalence and risk ratio (RR) with 95% confidential interval (CI). R statistic software was used for all the analysis.

RESULTS: A total of 19 studies including 4073 psoriasis patients with COVID-19 were eligible for the meta-analysis. The overall hospitalization rate is about 20.2% (95% CI, 12.7% – 28.7%), and changed to be 18.0 (95% CI, 9.9% – 27.6%) or 14.1 (95% CI, 5.9% – 24.6%) after systemic or biologic treatment. Moreover, the overall fatality rate is 1.5% (95% CI, 0.4% – 3.0%), and turned to be 0.7 (95% CI, 0 – 2.0%) or 0.5 (95% CI, 0 – 2.2%) after systemic or biologic therapy. Notably, a lower hospitalization risk ratio was found in patients receiving biologic therapy than those receiving other treatments (RR = 0.62, 95%CI, 0.42-0.94). The results were consistent after sensitivity analysis and trim-and-fill analysis.

CONCLUSIONS: Systemic, especially biologic therapy could lessen the clinical severity in psoriasis patients with COVID-19. Our finding will help to guide current recommendations and provide a reference for clinical decision-making. This article is protected by copyright. All rights reserved.

PMID:36000295 | DOI:10.1002/jmv.28085

Biostatistics. 2022 Aug 24:kxac036. doi: 10.1093/biostatistics/kxac036. Online ahead of print.

ABSTRACT

Set-based association tests are widely popular in genetic association settings for their ability to aggregate weak signals and reduce multiple testing burdens. In particular, a class of set-based tests including the Higher Criticism, Berk-Jones, and other statistics have recently been popularized for reaching a so-called detection boundary when signals are rare and weak. Such tests have been applied in two subtly different settings: (a) associating a genetic variant set with a single phenotype and (b) associating a single genetic variant with a phenotype set. A significant issue in practice is the choice of test, especially when deciding between innovated and generalized type methods for detection boundary tests. Conflicting guidance is present in the literature. This work describes how correlation structures generate marked differences in relative operating characteristics for settings (a) and (b). The implications for study design are significant. We also develop novel power bounds that facilitate the aforementioned calculations and allow for analysis of individual testing settings. In more concrete terms, our investigation is motivated by translational expression quantitative trait loci (eQTL) studies in lung cancer. These studies involve both testing for groups of variants associated with a single gene expression (multiple explanatory factors) and testing whether a single variant is associated with a group of gene expressions (multiple outcomes). Results are supported by a collection of simulation studies and illustrated through lung cancer eQTL examples.

PMID:36000269 | DOI:10.1093/biostatistics/kxac036

J Biopharm Stat. 2022 Jul 4;32(4):567-581. doi: 10.1080/10543406.2022.2080692. Epub 2022 Jun 15.

ABSTRACT

In oncology drug development, indication selection and optimal dose identification are the primary objectives for the early phase of clinical trials and could significantly impact the probability of success. Master protocols, e.g., basket trial, umbrella trial, and platform trial, have become popular in practice considering the connection of trial designs with multiple indications and treatment candidates. They also enable the optimization of operational resources and maximize the capability of data-driven decision-making. However, most of the available designs are developed with the efficacy endpoint only for treatment effect estimation and testing, without consideration of the safety end point. Thus, it often lacks a comprehensive quantitative framework to allow optimal treatment selection, which could put future development at risk. We propose an optimal Bayesian platform trial design with multiple end points (PMED) to characterize the overall benefit-risk profile. The design is further extended to allow treatment and indication selection within and across arms, with continuous monitoring on multiple interim analyses for futility. In addition, we propose dynamic borrowing across arms to increase the efficiency and accuracy of estimation given the level of similarity across arms. A hierarchical hypothesis structure is utilized to achieve optimal indication and treatment combination selection by controlling family-wise error. Through simulation studies, we show that PMED is a robust design under the studied scenarios with superb power and controlled family-wise error rate.

PMID:36000260 | DOI:10.1080/10543406.2022.2080692