bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol use and poor sleep quality: a longitudinal twin study across 36 years
Authors: Helaakoski Viola , Kaprio Jaakko , Hublin Christer , Ollila Hanna M , Latvala Antti
Published: July 2022

Study Objectives

Poor sleep is one of the multiple health issues associated with heavy alcohol consumption. While acute effects of alcohol intake on sleep have been widely investigated, the longitudinal associations remain relatively underexplored. The objective of our research was to shed light on cross-sectional and longitudinal associations between alcohol use and poor sleep quality over time, and to elucidate the role of familial confounding factors in such associations.

Methods

Using self-report questionnaire data from the Older Finnish Twin Cohort (N = 13 851), we examined how alcohol consumption and binge drinking are associated with sleep quality during a period of 36 years.

Results

Cross-sectional logistic regression analyses revealed significant associations between poor sleep and alcohol misuse, including heavy and binge drinking, at all four time points (OR range = 1.61–3.37, p < .05), suggesting that higher alcohol intake is associated with poor sleep quality over the years. Longitudinal cross-lagged analyses indicated that moderate, heavy and binge drinking predict poor sleep quality (OR range = 1.25–1.76, p < .05), but not the reverse. Within-pair analyses suggested that the associations between heavy drinking and poor sleep quality were not fully explained by genetic and environmental influences shared by the co-twins.

Conclusions

In conclusion, our findings support previous literature in that alcohol use is associated with poor sleep quality, such that alcohol use predicts poor sleep quality later in life, but not vice versa, and that the association is not fully explained by familial factors.
Assessment of Absolute Substitution Model Fit Accommodating Time-Reversible and Non-Time-Reversible Evolutionary Processes
Authors: Goremykin Vadim
Published: July 2022

The loss of information accompanying assessment of absolute fit of substitution models to phylogenetic data negatively affects the discriminatory power of previous methods and can make them insensitive to lineage-specific changes in the substitution process. As an alternative, I propose evaluating absolute fit of substitution models based on a novel statistic which describes the observed data without information loss and which is unlikely to become zero-inflated with increasing numbers of taxa. This method can accommodate gaps and is sensitive to lineage-specific shifts in the substitution process. In simulation experiments, it exhibits greater discriminatory power than previous methods. The method can be implemented in both Bayesian and Maximum Likelihood phylogenetic analyses, and used to screen any set of models. Recently, it has been suggested that model selection may be an unnecessary step in phylogenetic inference. However, results presented here emphasize the importance of model fit assessment for reliable phylogenetic inference. [Absolute model fit; model misspecification; origin of plastids; phylogenomics.]
Tracking the trends of karyotype differentiation in the phylogenetic context of Gint, a scorpion genus endemic to the Horn of Africa (Scorpiones: Buthidae)
Authors: Just Pavel , Šťáhlavský František , Kovařík František , Štundlová Jana
Published: July 2022

To determine the mechanisms of karyotype differentiation in scorpions of the genus Gint, we employed an integrative approach, combining cytogenetic data and sequence-based phylogeny. We cytogenetically examined six species with emphasis on multivalent meiotic configurations, 18S rDNA and (TTAGG)n distribution and compared chromosomal data with genetic divergence based on analysis of 16S rRNA and COI gene markers. Our results show that Gint species exhibit substantial karyotype diversity (2n = 18–45) and a high incidence of chromosome heterozygosity. Meiotic chromosome chains formed by up to six elements were found in 85% of analysed individuals, causing intraspecific chromosome variation in three species. Fluorescence in situ hybridization revealed that the 18S rDNA distribution pattern differed in Gint species, including at the intrapopulation level, but the chromosomal localization of (TTAGG)n motif was stable across species. Conspicuous interspecific differences in chromosome counts broadly corresponded with genetic divergence among Gint species. Our findings indicate that Gint karyotypes have undergone dynamic reorganization through independent fusions, fissions and reciprocal translocations. Owing to present chromosomal polymorphism, such structural changes shaping the genome architecture appear to be still ongoing in the populations of some Gint species.
Polysubstance Use in Adults With Opioid Use Disorder Receiving Buprenorphine Maintenance
Authors: Elarabi Hesham Farouk , Radwan Doaa Nader , Adem Abdu , Marsden John , Lee Amanda J.
Published: July 2022

Introduction

Studying polysubstance use is a public health recommendation. In the United Arab Emirates, more than 80% of adults with opioid use disorder (OUD) use 2 or more nonopioid substances. This secondary analysis contrasts the characteristics of polysubstance users (OUD + ≥1 nonopioid) with OUD, explores the correlates and predictors of nonfatal overdose, and examines the impact of polysubstance use on OUD treatment outcomes using buprenorphine (BUP).

Methods

This analysis uses data from a 16-week outpatient randomized controlled trial of 141 adults with OUD allocated to BUP + incentivized adherence and abstinence monitoring (n = 70) and BUP in usual care (control, n = 71). Outcomes were nonfatal overdose events over the preceding 12 months, positive drug screens, and treatment retention. Participant characteristics were contrasted, and bivariate statistical tests were conducted for simple associations followed by logistic regression.

Results

Polysubstance use was reported by 117 participants (82.9%), the majority of whom used pregabalin 72.1% (n = 75). Compared with OUD, polysubstance users observed higher arrests (median, 1.0 [interquartile range, 0.0–3.0] vs 0.5 [interquartile range, 0.0–2.0]; P = 0.04]) and nonfatal overdose events (n = 33 [31.8%] vs 2 [10.8%], P = 0.003). Carisoprodol and injecting drug use independently predicted nonfatal overdose (adjusted odds ratio, 4.519 [95% confidence interval, 1.81–11.22] and 2.74 [95% confidence interval, 1.15–6.51], respectively). No significant difference was observed in opioid use and retention in treatment outcomes between groups.

Conclusion

Carisoprodol and injecting drug use increase the likelihood of nonfatal overdose in adults with OUD. Polysubstance use does not impact response to BUP treatment compared with OUD.
Relationship Between Sacroiliac Joint–related Pain and Spinopelvic Mobility
Authors: Tonosu Juichi , Oka Hiroyuki , Watanabe Kenichi , Abe Hiroaki , Higashikawa Akiro , Kawai Takuya , Yamada Koji , Nakarai Hiroyuki , Tanaka Sakae , Matsudaira Ko
Published: July 2022

Study Design.

A case-control study.

Objective.

To evaluate the relationship between sacroiliac joint–related pain (SIJ-RP) and spinopelvic mobility.

Summary of Background Data.

No specific radiological findings are available for the diagnosis of SIJ-RP. A previous study reported that a higher pelvic incidence and sacral slope (SS) values were significantly associated with sacroiliac joint pain. The concept of spinopelvic mobility, which is evaluated by the differences between SS in the standing and sitting positions, has been the focus of hip and spine surgeries in recent years.

Materials and Methods.

The SIJ-RP group comprised patients diagnosed with SIJ-RP based on physical findings and their response to analgesic injections. No other lumbar or hip joint diseases were observed. The non–SIJ-RP group comprised patients with lower back pain for reasons other than SIJ-RP. Radiographs of the lateral view of the pelvis in the standing and sitting positions were evaluated for all patients. We compared and analyzed the backgrounds, SS in the two positions, and difference in SS between the two positions in both groups.

Results.

In total, 245 patients were included in the study, with 49 and 196 patients in the SIJ-RP and non–SIJ-RP groups, respectively. More female patients experienced SIJ-RP than male patients (P=0.0361). There were significant differences between the groups for SS in standing (P=0.0076), sitting (P=0.0005), and those with a difference between sitting and standing of <5° (P=0.0278) in the univariate analyses. Logistic regression analyses, after adjustment for age and sex, revealed significant differences between the groups with an SS difference <5° (P=0.0088; 95% confidence interval, 1.280–5.519), with an odds ratio of 2.7.

Conclusion.

On evaluating spinopelvic mobility, we found that SIJ-RP was related to hypomobility of the sacrum, which could indicate the hypermobility of the sacroiliac joint.
Cost-utility Analysis of Neoadjuvant Teriparatide Therapy in Osteopenic Patients Undergoing Adult Spinal Deformity Surgery
Authors: Raad Micheal , Ortiz-Babilonia Carlos , Hassanzadeh Hamid , Puvanesarajah Varun , Kebaish Khaled , Jain Amit
Published: July 2022

Study Design.

A cost-utility analysis study.

Objective.

This study aims to evaluate the cost-utility of neoadjuvant teriparatide therapy in osteopenic patients undergoing adult spinal deformity (ASD) surgery.

Summary of Background Data.

There is increasing evidence supporting preoperative use of anabolic agents such as teriparatide for preoperative optimization of ASD patients with poor bone density. However, such treatments are associated with added costs. To our knowledge, the cost-utility of teriparatide in osteopenic patients undergoing ASD surgery has not been established.

Materials and Methods.

A decision-analysis model was developed for a hypothetical 68-year-old female patient with osteopenia (T score <−1.0) undergoing a T11 to pelvis instrumented spinal fusion for ASD. A comprehensive literature review was conducted to create estimates for event probabilities, costs, and quality adjusted life years at each node. Key model assumptions were that administration of a 4-month preoperative teriparatide course reduced 2-year postoperative reoperation rates [for pseudarthrosis from 5% to 2.5% and for proximal junctional failure (PJF) from 15% to 5%]. Monte Carlo simulations were used to calculate the mean incremental cost utility ratio and incremental net monetary benefits. One-way sensitivity analysis was used to estimate the contribution of individual parameters to uncertainty in the model.

Results.

Teriparatide was the favored strategy in 82% of the iterations. The mean incremental cost utility ratio for the teriparatide strategy was negative (higher net benefit, lower net cost), and lower than the willingness-to-pay threshold of $50,000 per quality adjusted life year. Teriparatide use was associated with a mean incremental net monetary benefit of $3,948. One-way sensitivity analysis demonstrated that the factors with the greatest impact on the model were the incidence of PJF in the no teriparatide group, the duration and monthly cost of treatment, and the cost of reoperation due to PJF.

Conclusions.

Neoadjuvant teriparatide is a cost-effective strategy to reduce postoperative complications in patients with osteopenia undergoing ASD surgery.
Brain Shock—Toward Pathophysiologic Phenotyping in Traumatic Brain Injury
Authors: Lazaridis Christos
Published: July 2022

Severe traumatic brain injury (TBI) is a heterogeneous pathophysiologic entity where multiple interacting mechanisms are operating. This viewpoint offers an emerging, clinically actionable understanding of the pathophysiologic heterogeneity and phenotypic diversity that comprise secondary brain injury based on multimodality neuromonitoring data. This pathophysiologic specification has direct implications for diagnostic, monitoring, and therapeutic planning. Cerebral shock can be helpfully subanalyzed into categories via an examination of the different types of brain tissue hypoxia and substrate failure: a) ischemic or flow dependent; b) flow-independent, which includes oxygen diffusion limitation, mitochondrial failure, and arteriovenous shunt; c) low extraction; and d) hypermetabolic. This approach could lead to an alternative treatment paradigm toward optimizing cerebral oxidative metabolism and energy crisis avoidance. Our bedside approach to TBI should respect the pathophysiologic diversity involved; operationalizing it in types of “brain shock” can be one such approach.
Onboarding in Health Care—Content Validity and Reliability of the Danish Onboarding Questionnaire (DOQ-34)
Authors: Muff Bech Line , Poetzsch Simone , Andersen Kamilla , Nørgaard Birgitte
Published: July 2022

Introduction:

During recent years, health care organizations have paid increasing attention to onboarding because of recruitment challenges. Organizational initiatives are frequently monitored and evaluated using questionnaire data, and to produce high-quality data, reliable instruments are paramount. We aimed to investigate the content validity and reliability of the Danish Onboarding Questionnaire, including cognitive interviewing and test–retest analyses.

Method:

We investigated content validity, including face validity and the content validity index, and reliability for the percentage of agreement. To analyze the cognitive interview data, thematic analysis was applied, followed by the question-and-answer model to categorize the problems revealed. To test reliability, the percentage of agreement was calculated with an accepted deviation of 1 on test–retest data.

Results:

Regarding the mental processes, multiple items were identified to be challenged regarding comprehension (clarification of concepts and understanding), judgment (ambiguity and relevance), and response (anonymity and personal information). The mental process retrieval was not represented. The subscale content validity index/Ave was found to be 0.935, representing a “good” level of content validity. With an accepted deviation of 1, the mean agreement was 97.7%.

Discussion:

Questionnaire items causing uncertainties or challenges are potential sources of deteriorated content validity and should be revised. We suggest that the Danish Onboarding Questionnaire-34 undergo an item reduction, which might increase its validity and reliability.
Necrotizing Infundibular Crystalline Folliculitis—A Case Report of a Rare Entity and Review of the Literature
Authors: Wiedemeyer Katharina , Brenn Thomas , Naert Karen
Published: July 2022

Necrotizing infundibular crystalline folliculitis (NICF) is a rare distinct entity that was introduced in 1999. It typically presents with numerous eruptive waxy papules on the forehead and/or the upper back in adults in their fifth to seventh decade of life. The pathogenesis is unknown to date, but yeast and bacterial infection of the follicular ostia seems to contribute to the development. More recently, NICF has occasionally been observed as a side effect of targeted antitumoral therapy. Histopathologically, NICF is characterized by dilated follicular ostia filled with pale filamentous and birefringent material enclosed by parakeratotic columns of the epidermis and accompanied by a mild superficial inflammatory infiltrate of the dermis. This case report is about a 58-year-old male patient presenting with multiple eruptive keratotic papules on his forehead. Histopathology revealed all classic features of NICF. The case represents a classic example of NICF and is compared with previously published cases that are comprehensively summarized in this article.
Autism Spectrum Disorder, Extremism, and the Role of Developmental-Behavioral Pediatric Clinicians
Authors: Soares Neelkamal , Allely Clare S. , Straub Frank , Penner Melanie
Published: July 2022

Extremism is a global phenomenon, with an increasing domestic and international presence. Extremists recruit persons to their causes through online forums that spread hate-filled narratives and promote violence. Individuals with autism spectrum disorder may be vulnerable to recruitment through these online forums, and clinicians who work with autistic adolescents, young adults, and their families should familiarize themselves with the risk and identify strategies based on a multidisciplinary approach in the early identification, holistic prevention, and care-based intervention strategies of at-risk adolescents. This special article, representing an international collaboration between developmental-behavioral pediatrics, law enforcement, and psychology, hopes to shed light on the issue for clinicians.
Evaluation of spin in the abstracts of systematic reviews and meta-analyses relating to postoperative nausea and vomiting
Authors: Bruns Matthew , Manojkumar Arvind , Ottwell Ryan , Hartwell Micah , Arthur Wade , Roberts Will , White Brad , Young Jeff , Martin Janet , Wright Drew N. , Chen Suhao , Miao Zhuqi , Vassar Matt
Published: July 2022

INTRODUCTION

Spin – the beautification of study results to emphasise benefits or minimise harms – is a deceptive reporting strategy with the potential to affect clinical decision-making adversely. Few studies have investigated the extent of spin in systematic reviews. Here, we sought to address this gap by evaluating the presence of the nine most severe forms of spin in the abstracts of systematic reviews on treatments for postoperative nausea and vomiting (PONV). PONV has the potential to increase hospital costs and patient burden, adversely affecting outcomes.

METHODS

We developed search strategies for MEDLINE and Embase to identify systematic reviews focused on PONV. Following title and abstract screening of the reviews identified during the initial search, those that met inclusion criteria were evaluated for the presence of spin and received a revised AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) appraisal by two investigators in a masked, duplicate manner. Study characteristics for each review were also extracted in duplicate.

RESULTS

Our systematic search returned 3513 studies, of which 130 systematic reviews and meta-analyses were eligible for data extraction. We found that 29.2% of included systematic reviews contained spin (38/130). Eight of the nine types of spin were identified, with spin type 3 ('selective reporting of or overemphasis on efficacy outcomes or analysis favouring the beneficial effect of the experimental intervention’) being the most common. Associations were found between spin and funding source. Spin was more likely in the abstracts of privately funded than nonfunded studies, odds ratio (OR) 2.81 [95% confidence interval (CI), 0.66 to 11.98]. In the abstracts of studies not mentioning funding spin was also more likely than in nonfunded studies, OR 2.30 (95% CI, 0.61 to 8.70). Neither of these results were statistically significant. Significance was found in the association between the presence of spin and AMSTAR-2 ratings: ‘low’ quality studies were less likely to contain spin than ‘high’ quality, OR 0.24 (95% CI, 0.07 to 0.88): ‘critically low’ studies were also less likely to contain spin than ‘high’ quality studies, OR 0.21 (95% CI, 0.07 to 0.65). There were no other associations between spin and the remaining extracted study characteristics or AMSTAR-2 ratings.

CONCLUSION

Spin was present in greater than 29% of abstracts of systematic reviews and meta-analyses regarding PONV. Various stakeholders must take steps to improve the reporting quality of abstracts on PONV.
Mild and moderate to severe early acute kidney injury following cardiac surgery among patients with heart failure and preserved vs. mid-range vs. reduced ejection fraction
Authors: Gao Yuchen , Wang Chunrong , Li Jun , Ji Bingyang , Wang Jianhui , Yan Fuxia , Wang Yuefu
Published: July 2022

BACKGROUND

Patients with heart failure who undergo cardiac surgery have increased long-term mortality in which acute kidney injury (AKI) plays a role. However, little is known about whether the incidence of AKI differs according to stratified left ventricular ejection fraction (LVEF).

OBJECTIVES

To assess the risks of mild AKI and moderate to severe AKI postcardiac surgery among patients with heart failure.

DESIGN

Retrospective cohort analysis of patient data. Ejection fractions were categorised as LVEF less than 40%, heart failure with reduced ejection fraction (HFrEF); LVEF 40 to 49%, heart failure with mid-range ejection fraction (HFmrEF); and LVEF at least 50%, heart failure with preserved ejection fraction (HFpEF).

PATIENTS AND SETTINGS

Patients who underwent cardiac surgery from 2012 to 2019 in Fuwai Hospital, Beijing, China, were consecutively enrolled.

MAIN OUTCOME MEASURES

The primary endpoint was postoperative AKI staged either as mild AKI or moderate to severe AKI. The secondary outcome was the peri-operative composite adverse event of dialysis support, tracheotomy, intrasurgical and postsurgical mechanical cardiac support and in-hospital mortality. This study also assessed chronic renal dysfunction at follow-up.

RESULTS

Of the 54 696 included patients, 18.9% presented with heart failure. Among these with HFpEF, HFmrEF and HFrEF, the incidence of postoperative mild AKI was 37.0, 33.4 and 37.6%, respectively. Patients with HFpEF and HFmrEF were characterised by numerically greater prevalence of moderate to severe AKI than HFrEF (8.5 vs. 9.1 vs. 5.8%). HFrEF and HFmrEF patients had comparable risks for mild AKI relative to HFpEF patients, odds ratio (OR) 0.885; 95% confidence interval CI 0.763 to 1.027 for HFmrEF vs. HFpEF; OR 1.083; 95% CI 0.933 to 1.256 for HFrEF vs. HFpEF. Patients with HFmrEF were more at risk for moderate to severe AKI than patients with HFpEF (OR, 1.368; 95% CI 1.066 to 1.742), but HFrEF and HFpEF did not differ significantly (OR 1.012; 95% CI 0.752 to 1.346). An increasing number of noncardiac comorbidities led to a higher risk of mild AKI and moderate to severe AKI in patients with heart failure; and its effect on AKI was almost equal among the three heart failure strata. The incidence of postoperative composite adverse outcome increased in a graded manner from HFpEF to HFmrEF to HFrEF. Information on the creatine concentrations at 3 months postoperatively and longer were retained for 5200 out of 10 347 (50.6%) heart failure patients in our charts.

The AKI severity and the presence of HFmrEF contributed substantially to the development of renal dysfunction over a median [IQR] follow-up of 10 months [4.0 to 21.0].

CONCLUSIONS

Initiative programmes aimed at patients with HFrEF to prevent moderate to severe AKI and chronic kidney dysfunction should also include patients with HFmrEF.
Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy
Authors: Bao Minghui , Song Yongjian , Wu Shouling , Li Jianping
Published: July 2022

Systemic chronic inflammation, represented by hypersensitive C-reactive protein (hsCRP), is an essential contributing factor to hypertension. However, the influence of hsCRP levels on the effect of antihypertensive pharmacological therapy remains unknown. We evaluated hsCRP levels in 3756 newly diagnosed, untreated hypertensive subjects. Participants were grouped by tertiles of hsCRP and were randomly treated with nitrendipine + captopril, nitrendipine + spironolactone hydrochlorothiazide + captopril, and hydrochlorothiazide + spironolactone. Blood pressure (BP) was recorded every 2 weeks. A multivariate mixed linear model was used to evaluate the impact of baseline hsCRP levels on the continuous antihypertensive effect. After 3, 6, 9, and 12 months of continuous antihypertensive treatment, no significant difference was observed in BP decline among the different hsCRP groups. We identified interactions between baseline hsCRP levels and follow-up time. After adjusting for conventional risk factors and the interactions between hsCRP and follow-up time, there was no significant association between baseline hsCRP level and antihypertensive effects at 0–6 months of follow-up. However, from 6 to 12 months, subjects with higher baseline hsCRP levels exhibited a more marked BP-lowering effect (P < 0.001 at 9 months, P = 0.002 at 12 months). Overall, there exist interaction effects between baseline hsCRP levels and follow-up time. Individuals with higher baseline hsCRP levels may exhibit a better response to antihypertensive therapy.
Dihydroartemisinin Attenuates Hypoxia-Induced Pulmonary Hypertension Through the ELAVL2/miR-503/PI3K/AKT Axis
Authors: Cai Haijian , Fan Shiqian , Cai Luqiong , Zhu Lin , Zhao Zhucheng , Li Yaozhe , Yao Yizhu , Huang Xiaoying , Wang Liangxing
Published: July 2022

Dihydroartemisinin (DHA) is an active form of artemisinin extracted from the traditional Chinese medicine Artemisia annua, which is used to treat malaria. Previous studies have shown that DHA has a therapeutic effect on pulmonary hypertension (PH), but its specific mechanism has not been fully elucidated. In this study, a hypoxia-induced PH mouse model was established and DHA was administered as a therapeutic intervention. We measured hemodynamics and right ventricular hypertrophy and observed hematoxylin and eosin staining of lung tissue sections, proving the therapeutic effect of DHA on PH. Furthermore, cell counting kit-8 and 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay kit were performed to examine cell proliferation of pulmonary artery smooth muscle cells cultured in hypoxia or in normoxia. Transwell migration chamber assay was performed to examine cell migration of the same cell model. Consistent with the therapeutic effect in vivo, DHA inhibited hypoxia-induced cell proliferation and migration. Through high-throughput sequencing of mouse lung tissue, we screened embryonic lethal abnormal vision-like 2 (ELAVL2) as a key RNA binding protein in PH. Mechanistically, DHA inhibited the proliferation and migration of pulmonary artery smooth muscle cells by promoting the expression of ELAVL2 and regulating the miR-503/PI3K/AKT pathway. The binding relationship between ELAVL2 and pre-miR-503 was verified by RNA binding protein immunoprecipitation assay. In conclusion, we first propose that DHA alleviates PH through the ELAVL2/miR-503/PI3K/AKT pathway, which may provide a basis for new therapeutic strategies of PH.
Fibrillin-1 Gene Polymorphisms (rs145233125, rs11070646, rs201170905) Are Associated With the Susceptibility and Clinical Prognosis of DeBakey Type III Aortic Dissection in Chinese Han Population
Authors: Sun Ling , Chang Yafei , Jiang Peipei , Wang Baozhu , Ma Yitong , Yuan Qinghua , Ma Xiang
Published: July 2022

We aim to investigate whether genetic variants of the Fibrillin-1 (FBN1) gene were associated with DeBakey type III aortic dissection (AD) and its clinical prognosis in Chinese Han population. Three single-nucleotide polymorphisms (SNPs) (rs145233125, rs11070646, rs201170905) in FBN1 were analyzed in patients with DeBakey type III AD (159) and healthy subjects (216). Gene–environment interactions were evaluated to use generalized multifactor dimensionality reduction. Haplotype analysis of the 3 SNPs in the FBN1 gene was performed by Haploview software. Patients were followed up for average 4 years. G carriers of rs11070646 and rs201170905 in FBN1 have an increased risk of DeBakey type III AD. The interaction of FBN1 and environmental factors facilitated to the increased risk of DeBakey type III AD (cross-validation consistency = 10/10, P = 0.001). One of the most common haplotypes revealed an increased risk of DeBakey type III AD (CGG, P = 0.009). Recessive models of rs145233125 CC genotype (P < 0.05) and rs201170905 GG genotype (P < 0.001) were associated with an increased risk of death and recurrent chest pain of DeBakey type III AD. In conclusions, FBN1 gene polymorphisms contribute to DeBakey type III AD susceptibility. The interactions of gene and environment are related with the risk of DeBakey type III AD. C carriers of rs145233125 and G carriers of rs201170905 may be the adverse prognostic indicators of death and recurrent chest pain in DeBakey type III AD.
Efficacy and Safety of Proton Pump Inhibitors in Patients With Coronary Artery Diseases Receiving Oral Antiplatelet Agents and/or Anticoagulants: A Systematic Review and Meta-Analysis
Authors: Shang Yao-Sheng , Zhong Peng-Yu , Ma Ying , Bai Nan , Niu Ying , Wang Zhi-Lu
Published: July 2022

The purpose of this meta-analysis was to evaluate the efficacy and safety of proton pump inhibitors (PPIs) plus antithrombotic strategy in patients with coronary artery diseases compared with antithrombotic strategy alone. We searched PubMed, EMBASE, Cochrane Library, and Chinese Biomedical Medical Literature databases to retrieve randomized controlled trials investigating PPIs combined with antithrombotic strategy in coronary artery diseases. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety outcome was gastrointestinal events. Secondary outcomes included all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, significant bleeding from gastroduodenal lesions, and gastroduodenal ulcer. Overall, 43,943 patients were enrolled from 19 trials. The incidence of MACCE [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96–1.15], all-cause death (RR 0.84; 95% CI 0.69–1.01), cardiovascular death (RR 0.88; 95% CI 0.69–1.12), myocardial infarction (RR 0.98; 95% CI 0.88–1.09), stent thrombosis (RR 1.01; 95% CI 0.76–1.34), and gastroduodenal ulcer (RR 0.40; 95% CI 0.13–1.29) did not increase significantly in patients receiving PPIs compared with patients without those. There were significant differences in the risk of gastrointestinal events (RR 0.34; 95% CI 0.21–0.54) and significant bleeding from gastroduodenal lesions (RR 0.09; 95% CI 0.03–0.28) between the 2 groups. In patients with coronary artery diseases, PPIs plus antithrombotic strategy could reduce the risk of gastrointestinal events and significant bleeding from gastroduodenal lesions but may not affect the incidence of MACCE, all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, and gastroduodenal ulcer (PROSPERO: CRD42021277899, date of registration October 10, 2021).
R-spondin 3 Inhibits High Glucose-Induced Endothelial Activation Through Leucine-Rich G Protein-Coupled Receptor 4/Wnt/β-catenin Pathway
Authors: Chen Chong , Qu Hang , Liu Fang , Yu Yu , Sun Kun , Chen Alex F.
Published: July 2022

High glucose-induced endothelial activation plays critical roles in the development of diabetic vascular complications. R-spondin 3 could inhibit inflammatory damage, and diabetic vascular inflammation is secondary to endothelial activation. In this article, we identify R-spondin 3 as a novel regulator of high glucose-induced endothelial activation. We found that the serum levels of R-spondin 3 were significantly reduced in type 2 diabetic patients and db/db mice. We observed that the increased expressions of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 (endothelial activation makers) in high glucose-stimulated human umbilical vein endothelial cell lines (HUVECs) could be inhibited by overexpressing R-spondin 3 or human R-spondin 3 recombinant protein. Subsequently, high glucose-induced adhesion and migration of human myeloid leukemia mononuclear cells (THP-1 cells) to HUVECs were markedly suppressed by the overexpression of R-spondin 3 in HUVECs. Moreover, the inhibitory effect of R-spondin 3 on the expressions of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in high glucose-treated HUVECs could be blocked by knockdown of leucine-rich G protein-coupled receptor 4 (R-spondin 3 receptor) or the specific inhibitor of Wnt/β-catenin pathway. Taken together, R-spondin 3 could suppress high glucose-induced endothelial activation through leucine-rich G protein-coupled receptor 4/Wnt/β-catenin pathway.
Subcellular β-Adrenergic Receptor Signaling in Cardiac Physiology and Disease
Authors: Wei Wenhui , Smrcka Alan V.
Published: July 2022

Adrenergic receptors are critical regulators of cardiac function with profound effects on cardiac output during sympathetic stimulation. Chronic stimulation of the adrenergic system of the heart under conditions of cardiac stress leads to cardiac dysfunction, hypertrophy, and ultimately failure. Emerging data have revealed that G protein–coupled receptors in intracellular compartments are functionally active and regulate distinct cellular processes from those at the cell surface. β2 adrenergic receptors internalize onto endosomes in various cell types where they have recently been shown to continue to stimulate cAMP production to selectively regulate gene expression. Other studies have identified β1 adrenergic receptors at the nuclear envelope and the Golgi apparatus. Here, we discuss data on signaling by β1 and β2 adrenergic receptors in the heart and the possible influence of their subcellular locations on their divergent physiological functions in cardiac myocytes and in cardiac pathology. Understanding the relative roles of these receptors at these locations could have a significant impact on pharmacological targeting of these receptors for the treatment of heart failure and cardiac diseases.
The Functional Effects of Visfatin on Human Left Internal Mammary Artery
Authors: Bayram Zeliha , Akcabag Esra , Ozbey Gul , Golbasi Ilhan , Ozdem Sadi S.
Published: July 2022

Visfatin may play a role in vascular dysfunction in metabolic disorders. Apart from its insulin-mimetic actions, it has divergent actions in the cardiovascular system with discordant results in the literature. Thus, we aimed to study the effects of visfatin on vascular responses of the human left internal mammary artery. Sections of redundant human left internal mammary artery were cut into 3-mm wide rings and hung in 20-mL organ baths containing physiologic salt solution and attached to an isometric force transducer connected to a computer-based data acquisition system. Removing endothelium caused an increase in pD2 values for visfatin-induced relaxation responses (10−12–10−7 M) (9.06 ± 0.21 and 11.08 ± 0.92, respectively). Nicotinamide phosphoribosyltransferase inhibitor FK866 (10 µM) reversed the visfatin-induced relaxations (10−12–10−7 M) (P = 0.024). Incubations with nitric oxide synthase inhibitor nitro-l-arginine methylester and guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) caused significant reductions in relaxation responses of visfatin (P = 0.011 and 0.008, respectively). Visfatin incubations decreased relaxation responses to acetylcholine but not to sodium nitroprusside. Incubations with visfatin did not change contractile responses to angiotensin II, endothelin-1, noradrenalin, and phenylephrine. In this study, visfatin caused endothelium-dependent relaxations mediated by nitric oxide–cyclic guanosine monophosphate pathway and nicotinamide phosphoribosyltransferase activity. Furthermore, visfatin-induced decreases in relaxation responses were also related to endothelium-derived nitric oxide.
Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation
Authors: Ialongo Cristiano , Sapio Maria , Angeloni Antonio
Published: July 2022

Background:

A new homogeneous affinity chrome-mediated immunoassay (ACMIA) “EVRO” from Siemens Healthcare was evaluated for therapeutic drug monitoring of everolimus (EVL) with automated sample pretreatment and compared with quantitative microsphere system (QMS) “EVER” from Thermo Fisher Scientific.

Methods:

Imprecision, inaccuracy, and limit of quantitation (LoQ) of ACMIA/EVRO were verified using both hemolysate quality control (QC) samples and pooled whole blood specimens. The interchangeability of methods and the agreement of results were analyzed using 72 specimens (from 38, 30, and 4 kidney, liver, and lung transplant recipients, respectively).

Results:

Within-run imprecision ranged within %CV = 2.81–2.53 with pooled whole blood specimens and within %CV = 2.88–2.53 with QCs; total imprecision with QCs was within %CV = 2.14–1.51. Inaccuracy with value assigned QC was %△ = 5.36 at the 5.6 ng/mL level and %△ = 5.56 at the 11.7 ng/mL level. LoQ was 0.93 ng/mL (%CV = 10). Passing–Bablok regression showed a constant bias of 0.679 ng/mL (95% CI: 0.216–1.026) and a proportional bias of 1.326 (95% CI: 1.240–1.425). Bland–Altman analysis showed 5/72 (6.9%) paired differences exceeding the limits of agreement and 1/72 (1.4%) paired differences exceeding 1.96 SD to a combined bias of 39.9% after detrending.

Conclusions:

ACMIA/EVRO shows satisfactory analytical performances that comply with recommendations, but it does not fulfill requirements for interchangeability with QMS/EVER. Particularly, this new assay using sirolimus-specific antibody shows a sizable proportional bias versus the more specific comparator, which may be because of EVL metabolites. This is supported by the lack of agreement for individual differences in most samples collected at the peak concentration (C2). Therefore, further evidence is needed to support the transition of EVL level monitoring from QMS/EVER to ACMIA/EVRO without making extensive changes to both reference interval and patient's baseline.
Endometrial microbiota from endometrial cancer and paired pericancer tissues in postmenopausal women: differences and clinical relevance
Authors: Wang Lili , Yang Jiaolin , Su Huancheng , Shi Liuming , Chen Bangtao , Zhang Sanyuan
Published: July 2022

Objective

The incidence of postmenopausal endometrial cancer (EC) is rising, and the uterine microbiota has recently been suggested to be an etiology of EC. However, the differences in microbiota profiles in paired EC and the adjacent non-EC endometrium, and the functional microbiota of clinical relevance remain largely unknown. Therefore, we examined the differences in microbiota profiles between EC and non-EC endometrium and investigated their clinical relevance to EC.

Methods

Twenty-eight EC-affected postmenopausal women undergoing hysterectomy were enrolled. Endometrial microbiome from paired EC and adjacent non-EC tissue samples were detected using 16S rRNA sequencing, and the data were analyzed using R language software.

Results

The α diversity and evenness of the endometrial bacterial community significantly increased in EC tissues than those in pericancer tissues (P < 0.05 for all variables). Lactobacillus and Gardnerella were the main bacterial genera present in both EC and adjacent non–EC-invading endometrium, whereas Prevotella, Atopobium, Anaerococcus, Dialister, Porphyromonas, and Peptoniphilus were more commonly enriched in the EC endometrium (corrected P < 0.05 for all variables). Finally, the abundance of some observed endometrial bacteria was associated with clinical aspects, particularly the vaginal pH, vaginal Lactobacillus abundance, and EC clinical stage.

Conclusions

Paired EC and adjacent non-EC endometrium harbor different endometrial microbiota, and the functional bacteria residing in the endometrium are clinically relevant but require further investigation.
VALIDATION OF AN AUTOMATED FLUID ALGORITHM ON REAL-WORLD DATA OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION OVER FIVE YEARS
Authors: Gerendas Bianca S. , Sadeghipour Amir , Michl Martin , Goldbach Felix , Mylonas Georgios , Gruber Anastasiia , Alten Thomas , Leingang Oliver , Sacu Stefan , Bogunovic Hrvoje , Schmidt-Erfurth Ursula
Published: July 2022

Background/Purpose:

To apply an automated deep learning automated fluid algorithm on data from real-world management of patients with neovascular age-related macular degeneration for quantification of intraretinal/subretinal fluid volumes in optical coherence tomography images.

Methods:

Data from the Vienna Imaging Biomarker Eye Study (VIBES, 2007–2018) were analyzed. Databases were filtered for treatment-naive neovascular age-related macular degeneration with a baseline optical coherence tomography and at least one follow-up and 1,127 eyes included. Visual acuity and optical coherence tomography at baseline, Months 1 to 3/Years 1 to 5, age, sex, and treatment number were included. Artificial intelligence and certified manual grading were compared in a subanalysis of 20%. Main outcome measures were fluid volumes.

Results:

Intraretinal/subretinal fluid volumes were maximum at baseline (intraretinal fluid: 21.5/76.6/107.1 nL; subretinal fluid 13.7/86/262.5 nL in the 1/3/6-mm area). Intraretinal fluid decreased to 5 nL at M1-M3 (1-mm) and increased to 11 nL (Y1) and 16 nL (Y5). Subretinal fluid decreased to a mean of 4 nL at M1-M3 (1-mm) and remained stable below 7 nL until Y5. Intraretinal fluid was the only variable that reflected VA change over time. Comparison with human expert readings confirmed an area under the curve of >0.9.

Conclusion:

The Vienna Fluid Monitor can precisely quantify fluid volumes in optical coherence tomography images from clinical routine over 5 years. Automated tools will introduce precision medicine based on fluid guidance into real-world management of exudative disease, improving clinical outcomes while saving resources.
ISOLATED RETINAL VASCULITIS
Authors: Silpa-archa Sukhum , Sapthanakorn Withawat , Foster C. Stephen
Published: July 2022

Purpose:

To identify prognostic factors for poor visual outcomes in patients with isolated retinal vasculitis and to elucidate the outcome of immunosuppressive treatment without the use of antituberculosis drugs for patients with retinal vasculitis associated with a positive QuantiFERON-TB Gold In-Tube (QFT) test.

Methods:

A retrospective chart review was performed of patients presenting with retinal vasculitis. After the diagnosis of active retinal vasculitis had been confirmed by fluorescein angiography and other possible causes of retinal vasculitis had been excluded, patients were categorized into two groups by their QFT result. Potential associated factors between the poor and good visual outcome groups were statistically analyzed by the chi-square test and logistic regression model with generalized estimating equations.

Results:

Seventy-three eyes (48 patients) were enrolled in this study. After univariate analysis, multivariate logistic regression analysis was performed and revealed that logMAR visual acuity at the initial visit (P = 0.01) and outer retinal disruption (P = 0.03) were the two factors significantly associated with poor visual outcomes. Systemic corticosteroids were administered without the use of antituberculosis drugs to all 16 cases of presumed tuberculous retinal vasculitis associated with positive QFT (26 eyes), 10 (63%) of whom were given nonsteroidal immunosuppressive drugs and achieved inflammatory control and treatment success.

Conclusion:

Risk factors leading to poor visual outcome in patients with isolated retinal vasculitis have been identified. Immunosuppressive treatment without antituberculosis drugs seems to be a promising regimen for selected patients with presumed tuberculous retinal vasculitis under vigilant care.
Agreement of infrared ear temperature with nasopharyngeal temperature and diagnostic performance on hypothermia in general anesthetized patients
Authors: Wan Li , Shen Pei-Ying , Zhang Shu-Xian , Wang Li-Zhong
Published: July 2022

Background:

Infrared ear thermometry is widely used in clinical practice due to its noninvasive, convenient, and quick sampling. However, its accuracy and feasibility in anesthetized patients have not yet been established.

Methods:

We conducted this cross-sectional study to evaluate the agreement between infrared ear temperature and nasopharyngeal temperature in general anesthetized patients and its performance in intraoperative hypothermia, defined as nasopharyngeal temperature <36°C. Adult female patients who underwent gynecological surgery under general anesthesia were enrolled in this study. Infrared ear temperature by Braun ThermoScan PRO 4000 (Braun GmbH, Kronberg, Germany) and nasopharyngeal temperature were measured simultaneously before, during, and after surgery. The agreement between the two temperatures was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The diagnostic performance of the infrared ear thermometer for hypothermia was evaluated using receiver operating characteristic (ROC) curve analysis.

Results:

Fifty-six patients with 168 pairs of simultaneous infrared ear and nasopharyngeal temperatures were included in this analysis. The mean infrared ear temperature was consistently higher than the nasopharyngeal temperature throughout surgery, but the differences were small (0.22, 0.13, and 0.06°C before, during, and after surgery, respectively). The ICC between the two temperatures before, during, and after surgery was 0.70, 0.75, and 0.80, respectively, and 93.5% of the differences fell within the 95% limits of agreement of ±0.5°C. An infrared ear thermometer had high diagnostic accuracy for hypothermia, with an area under the ROC curve of 0.95 (95% confidence interval [CI], 0.92-0.98). The cutoff of infrared ear temperature for hypothermia was 36.2°C with a sensitivity of 0.89 (95% CI, 0.71-0.98) and a specificity of 0.87 (95% CI, 0.81-0.92).

Conclusion:

The infrared ear temperature is in good agreement with the nasopharyngeal temperature in general anesthetized patients without hyperthermia and has high performance for detecting hypothermia. An infrared ear thermometer can be a diagnostic tool for intraoperative hypothermia.
Patient perceived needs and experiences of person-centered care in patients with inflammatory arthritis
Authors: van Slingerland Kim , Walter Margot J.M. , van der Stege Heleen A. , van Staa AnneLoes , van Pelt Philomine A. , de Jong Pascal H.P.
Published: July 2022

Background:

Health care is shifting toward a person-centered care (PCC) approach. For implementation of PCC, there may be a special role for nurse practitioners (NPs).

Purpose:

The aim of this study was to explore the patient-perceived levels of and needs for of PCC in inflammatory arthritis patients who visited the NP at the outpatient clinic of an academic hospital in the Netherlands.

Methods:

A cross-sectional study was performed. Disease characteristics were inventoried from the patient records. Patients filled out the PCCoc/rheum instrument, an instrument to measure patient perceived PCC, and a questionnaire based on the 14 life areas of the Self-Management Web, extended with areas including pain, fatigue, and night's rest. Participants were asked which life areas caused problems, and whether these problems were discussed. Mean values were calculated for normally distributed data and medians for nonnormally distributed data.

Results:

Most of the patients had well-controlled disease (86.1%). The mean score of the PCCoc/rheum was 55.3 (SD 8.1). Patients experienced most problems in life areas fatigue (37.3%) and pain (35.3%), these were also the life areas that were most often addressed at consultation. The life areas that gave problems and that were least addressed during consultation were intimate relationships & sexuality (66.7%) and household chores (58.8%).

Conclusions:

Despite an overall high level of patient perceived PCC delivered by NPs, patient with low disease activity frequently reported problems in life areas not addressed at consultation.

Implications for practice:

Implementation of the Self-Management Web and changing the focus of NP consultations may help to improve accommodating individual patient needs.