bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention
Authors: Zhu Mingrui , Huang Xinqi , Shan Haiyan , Zhang Mingyang
Published: January 2022

Traumatic brain injury (TBI) contributes to death, and disability worldwide more than any other traumatic insult and damage to cellular components including mitochondria leads to the impairment of cellular functions and brain function. In neurons, mitophagy, autophagy-mediated degradation of damaged mitochondria, is a key process in cellular quality control including mitochondrial homeostasis and energy supply and plays a fundamental role in neuronal survival and health. Conversely, defective mitophagy leads to the accumulation of damaged mitochondria and cellular dysfunction, contributing to inflammation, oxidative stress, and neuronal cell death. Therefore, an extensive characterization of mitophagy-related protective mechanisms, taking into account the complex mechanisms by which each molecular player is connected to the others, may provide a rationale for the development of new therapeutic strategies in TBI patients. Here, we discuss the contribution of defective mitophagy in TBI, and the underlying molecular mechanisms of mitophagy in inflammation, oxidative stress, and neuronal cell death highlight novel therapeutics based on newly discovered mitophagy-inducing strategies.
Real-Time Dance Posture Tracking Method Based on Lightweight Network
Authors: Wang Zhigang
Published: January 2022

Video analysis of human motion has been widely used in intelligent monitoring, sports analysis, and virtual reality as a research hotspot in computer vision. It is necessary to decompose and track the movements in the process of movement in order to improve the training quality in dance training. The traditional motion tracking decomposition method, on the other hand, is unable to calculate the visual changes of adjacent key nodes, and the contour of 3D visual motion tracking remains ambiguous. This paper applies the human posture estimation algorithm in computer vision to the detection of key points of rectangular objects and obtains the heat map of key points of rectangular objects by adding a lightweight feature extraction network and a feature pyramid layer integrating multilayer semantic information, on the basis of summarizing and analyzing related research work at home and abroad. Because of the fusion of multilayer information, the network’s design not only reduces the amount of calculation and parameters but also improves the accuracy of the final detection result. The test results show that the proposed algorithm’s recognition accuracy has improved.
Coresidence of Older Parents and Adult Children Increases Older Adults’ Self-Reported Psychological Well-Being
Authors: Lee Soohyoung Rain , Kim Laurie S.
Published: January 2022

A multigenerational household is no longer a rare phenomenon in contemporary society. However, relevant literature has focused on elderly parents receiving support from their adult child, thereby coresiding. This is potentially problematic, as both generations could benefit from living together, and little is known about the benefit of living with adult children from older adults’ perspectives compared to the risk of this living situation. Previous research suggests a significant negative effect of living alone, e.g., low psychological well-being, and it becomes more salient among single parents, such as widowed or divorced. The current paper utilizes the National Health Measurement Study with a sample of age 55 and over. Their SF-36 Mental Health and Physical Health Component and self-acceptance scores were measured. Path analysis reveals that both physical and mental health and self-acceptance scores are lower among single older adults at the time of the survey (e.g., divorced and widowed) than among those who are nonsingle and living with their adult child. A complete mediation effect of living with an adult child on older adults’ mental health and self-acceptance was observed in both White and non-White minority older adults. This suggests that living with an adult child possibly serves as a protective factor for the negative relationship between living alone and their well-being. The current study seeks to stimulate ideas that might generate the following answer to community-based care in our contemporary aging society.
Discrete Dynamic Modeling Analysis of Engineering Management and Quality Optimization Innovation Mode Based on Big Data Intelligent Algorithm
Authors: Zhuang Xiaowen , Wu Chuanbao
Published: January 2022

With the advent of the big data era, information technology and intelligent algorithms are more and more widely used. In the engineering project management industry, big data technology and dynamic modeling have achieved good results. Enterprises attach great importance to the innovation of engineering project management. The establishment of engineering management and quality optimization innovation model can improve the management efficiency of engineering project process and enable enterprises to obtain great advantages in market competition. The use of big data technology can make project management and quality innovation more information‐based and intelligent. Based on the above situation, this paper puts forward the research on discrete dynamic modeling of engineering management and optimization innovation mode based on big data intelligent algorithm. It mainly uses big data technology to collect and classify the obtained data information and uses discrete dynamic modeling technology to optimize the management system, focus on the management and innovation of green engineering, use big data dynamic modeling technology to build engineering management model, and improve the balance of project model through intelligent planning algorithm. The experimental results show that the big data intelligent algorithm combined with discrete dynamic modeling technology increases the applicability and feasibility of the system. The accurate data after big data analysis can be used for quality supervision and detection, which not only improves the project quality problems but also improves the management efficiency of the project.
Effect of Polyethylene Cover for Preventing Corneal Injury in Critically Ill Patients: A Meta-Analysis
Authors: Li Tao , Zhou Huijuan
Published: January 2022

Objective. Polyethylene cover has been proved to be an effective method in protecting corneal, but its advantage compared to other conventional methods is still unclear. Our study is aimed at assessing clinical effects of polyethylene cover versus other methods in the prevention of corneal injury for critically ill patients. Methods. We searched randomized controlled trials comparing polyethylene cover versus other methods for critically ill patients through the databases of PubMed, Embase, Web of Science, and China National Knowledge database. Forest plots and funnel plots were also performed on the included articles. Results were expressed as risk ratio (RR) with 95% confidence intervals. Results. Eight studies were eventually identified. The incidence of corneal injury in the polyethylene cover group was lower than that in the eye drops group (RR=0.24, 95% CI (0.12, 0.45),P<0.0001) but had no significant difference when compared to the eye gel group (RR=0.42, 95% CI (0.13, 1.34),P=0.14) and the eye ointment group (RR=−0.61, 95% CI (0.23, 1.59),P=0.31). Conclusion. This study showed that polyethylene cover, eye gel, and eye ointment had an equal effect for preventing corneal injury in critically ill patients, and the effect of eye drops was relatively low. However, there were other intervention methods that had not been compared due to the small number of articles; further studies should be performed to assess which method was the best practice method.
Impact of Material and Lens Design on Repositioning Surgery of Toric Intraocular Lenses: A Single-Arm Meta-Analysis
Authors: Wu Jing , Yang Changping , Yin Yan , Liu Linlin , Wang Hui
Published: January 2022

Aim. To analyze the pooled incidence rate in repositioning surgery by considering different materials and designs. Methods. All published studies investigating the repositioning surgery of toric intraocular lenses (IOLs) before September 1, 2020, were searched and evaluated. The R3.5.2 software was used to extract the data, and a single arm meta-analysis was performed. Results. 19 cases from 18 published studies articles were included in the meta-analysis. The pooled incidence rate in repositioning surgery was 2% (I2 = 53%, Pheterogeneity<0.01). Plate and silicone IOLs had significantly higher incidence rates (6% for each) than loop (2%) and hydrophobic acrylate (2%). Incidence rates of Acrysof, Staar, TECNIS, PhysIOL SA, T-flex 623T, and Microsil 6116TU groups were 1% (95% CI [1%–2%]), 6% (95% CI [4%–9%]), 3% (95% CI [2%–4%]), 1.40% (1/71), 3.03% (1/33), and 4.76% (1/21), respectively. Conclusions. The pooled incidence rate of repositioning surgery in IOLs was 2%. Materials and designs would be risk factors for the rotational stability of the toric IOLs. Pooled incidence rates of the hydrophobic acrylate and loop group were lower than those of the silicone and plate group. Product identity is the main driver of heterogeneity.
Digital Twin‐Based Modeling of Complex Systems for Smart Aging
Authors: Deng Yiyi
Published: January 2022

In this paper, we use digital twin technology to conduct in‐depth analysis and research on the modeling of complex systems for smart aging. The solution of the digital twin model based on a big data platform is proposed, and the problem of asynchronous and incomplete digital twin real‐time monitoring data is solved, and the algorithm is applied to the digital twin model based on the big data platform for data preprocessing to achieve better results. To improve the real‐time data transmission, the OPCUA information modeling method is optimized by using node merging and adaptive compression, which statutes the system data and achieves the effect of information fusion. The Web protocol is also used to unify the digital twin information interaction form. After experimental testing, the effectiveness of the information modeling scheme designed in this paper is verified. The fall detection results based on the digital twin selected thresholds are significantly better than the experimental results of the manually set threshold method; the thresholds set by the digital twin can more accurately identify daily behaviors, especially the more violent daily behaviors such as lying down, and the accurate alarm rate of the falling behavior reaches 92.5%. In contrast, the artificially set thresholds have a lower overall recognition rate for human behaviors and are prone to misclassification, with a misclassification rate of 3.8%. Therefore, it can be determined that using the digital twin method to set feature thresholds is better than the manual setting threshold method in terms of detection accuracy, and the digital twin method is chosen to select the thresholds for each stage of the fall process in this project. The validation results demonstrate the system’s excellence in information interaction, optimization of numerical analysis, and display of results for smart aging.
Removal of Cr(VI) from Aqueous Solutions Using Biowastes: Tella Residue and Pea (Pisum sativum) Seed Shell
Authors: Kebede Abayneh , Kedir Kassim , Melak Fekadu , Asere Tsegaye Girma
Published: January 2022

The wide use of chromium (Cr) in different industries led to the release of a considerable amount of Cr(VI) into water bodies. Exposure to Cr(VI) can cause diseases in humans and animals. Therefore, low-cost technology for Cr(VI) removal is required. In this study, the biowastes, “Tella” residue (TR) and Pea (Pisum sativum) seed shell (PSS), were evaluated for their Cr(VI) removal efficiency from aqueous solutions. The physicochemical properties of adsorbents were studied, and the adsorbents were further characterized using FTIR and XRD. Batch adsorption experiments have shown that the Cr(VI) uptake was pH-dependent and found to be effective in a wide range of pH values (pH 1 to 10) for PSS. The kinetics of Cr(VI) removal by the adsorbents was well expressed by the pseudo-second-order model. The experimental equilibrium adsorption data fitted well with Freundlich isotherm indicating multilayers adsorption. The estimated Cr(VI) adsorption capacities of TR and PSS were 15.6 mg/g and 8.5 mg/g, respectively. On top of this, the possibility of reusing adsorbents indicates the potential applicability of TR and PSS for the treatment of Cr(VI) contaminated water. Further study on the evaluation of the efficiency of the adsorbents using real chromium-contaminated wastewater is recommended.
Some Fixed Point Theorems for Boyd and Wong Type Contraction Mapping in Ordered Partial Metric Spaces with an Application
Authors: Kumar Santosh , Nziku Faustine
Published: January 2022

This paper establishes and proves a fixed point theorem for Boyd and Wong type contraction in ordered partial metric spaces. In doing so, we have extended several existing results into ordered complete partial metric spaces. An illustrative example is given to demonstrate the validity of our results. Finally, the existence of the solution of nonlinear integral equation is discussed as an application of the main result.
Identification of Driver Genes and Interaction Networks Related to Brain Metastasis in Breast Cancer Patients
Authors: Zhang Haojie , Wang Xiaohong , Hou Changran , Yang Zhenlin
Published: January 2022

Brain metastasis is a common complication of breast cancer (BC); however, the interaction networks and driver genes that lead to brain metastasis in BC patients are still unknown. In this study, we employed bioinformatics analyses to discover hub genes and long noncoding RNA- (lncRNA-) protein-coding gene (PCG) networks related to BC brain metastasis (BCBM). Firstly, we screened differentially expressed PCGs and lncRNAs in normal and BCBM samples using the GSE52604 dataset. Subsequently, differentially expressed genes (DEGs) and overall interaction networks were constructed, and topological degrees were analyzed to identify potential driver genes. After identifying the hub pathogenic module by weighted gene coexpression network analysis (WGCNA), the genes in the hub module were evaluated for functional enrichment. Finally, we constructed multiple interaction networks associated with BCBM and identified seven potential driver genes, out of which MYBPC1 was the only overlapping gene in the adopted analytical methods. It is worth mentioning that we validated the prognostic value of the identified hub genes in TCGA database and evaluated the prediction ability of MYBPC1 in the GSE38057 dataset. In addition, the CIBERSORT algorithm revealed changes in the immune microenvironment. In conclusion, the driver PCGs and lncRNAs in the interaction networks can be utilized as a promising therapeutic strategy for the treatment of brain metastasis in BC patients.
Evaluation of Zebrafish Toxicology and Biomedical Potential of Aeromonas hydrophila Mediated Copper Sulfide Nanoparticles
Authors: Rajeshkumar S. , Santhoshkumar J. , Vanaja M. , Sivaperumal P. , Ponnanikajamideen M. , Ali Daoud , Arunachalam Kalirajan
Published: January 2022

The present study deals with extracellular synthesis and characterization of copper sulfide (CuS) nanoparticles using Aeromonas hydrophila, and the biological applications of the synthesized CuS like antibacterial, anti-inflammatory, and antioxidant activity were reported. Further, the toxicological effects of the CuS were evaluated using zebrafish as an animal model. The primary step of the synthesis was carried out by adding the precursor copper sulfates to the culture supernatant of Aeromonas hydrophila. The UV-visible spectrophotometer was used to characterize the synthesized nanoparticles, and the peak was obtained at 307 nm through the reduction process. Fourier transform infrared spectroscopy (FTIR) was involved to find out the functional groups (carboxylic acid, alcohols, alkanes, and nitro compounds) associated with copper sulfide nanoparticles (CuS-NPs). Atomic force microscopy (AFM) was used to characterize the CuS topographically, and a scanning electron microscope (SEM) revealed about 200 nm sized CuS nanoparticles with agglomerated structures. Overall, the characterized nanoparticles can be considered as a potential candidate with therapeutic proficiencies as antibacterial, antioxidant, and anti-inflammatory mediator/agents.
Design of Data Classification and Classification Management System for Big Data of Hydropower Enterprises Based on Data Standards
Authors: Luo Wei , Xu Jian , Zhou Ziqi
Published: January 2022

The advent of the era of big data has had a great impact on traditional management methods, and companies have also begun to make changes. The management approach has changed from initially focusing on business development to now focusing on user experience and putting people first. The data standard classification management system is a system for management and analysis based on the database. Therefore, this article is based on data standards, taking hydropower companies as an example, to design and research the data classification management system to promote the operation and safety of hydropower companies. This article mainly uses the experimental method, data collection method, and algorithm analysis method to thoroughly understand and explore the content of this article. The experimental results show that the testability of this article can basically reach the general level, and the delay time of the system does not exceed 10 seconds, which can be applied to the company.
The Change of Soluble Programmed Death Ligand 1 (sPD-L1) in Plasma of Small Cell Lung Cancer and Its Clinical Significance
Authors: Lu Feijie , Dong Yongquan , Li Qianjun , Wang Mingming
Published: January 2022

Background soluble programmed death-ligand 1 (sPD-L1) expression in lung squamous cell carcinoma and lung adenocarcinoma is associated with disease progression, and sPD-L1 expression in small cell lung cancer (SCLC) may have similar manifestations and become a potential marker for treatment. The purpose of this study was to observe the changes of plasma sPD-L1 expression in SCLC patients. Methods. 90 patients diagnosed with SCLC from January 2019 to November 2020 were selected as the test group, including 72 males and 18 women,

58.7
±
6.6

years; 30 healthy subjects were selected from the physical examination center, including 18 males, 12 females, and

60.3
±
7.0

years. There were no statistical difference in sex and age factors between the trial and control groups (

p
>
0.05

). Selected SCLC used chemotherapy regimen:

cisplatin
+
etoposide

(EP),

carboplatin
+
etoposide

(CE), and SCLC group were divided into three subgroups of disease progression group, partial remission group, and disease stability group according to the treatment effect. Comparison of the differences in sPD-L1 expression content between the experimental and control populations. Plasma sPD-L1 levels were dynamically monitored pre- and posttreatment in 90 patients with small-cell lung cancer and were associated with efficacy among subgroups. Meanwhile, the risk factors for patient sPD-L1 expression content were analyzed by logistic regression. Results. Plasma sPD-L1 levels were higher in the SCLC group than in the healthy people group (

t
=
7.40

,

p
<
0.01

). In the disease progression group of the SCLC group, sPD-L1 levels were decreased in the SCLC group, sPD-L1 in some remission group was increased after treatment, and sPD-L1 levels in the disease-stable group (

p
>
0.05

). Multivariate logistic regression analysis showed that factors promoting increased sPD-L1 expression in SCLC patients included increased smoking, brain metastasis, and ProGRP expression (both

p

values < 0.05). Conclusion. (1) Higher peripheral sPD-L1 expression in SCLC patients than in healthy patients, and the expression levels were closely related to efficacy. (2) Dynamic changes in s PD-L1 were correlated with clinical efficacy. (3) The progression of sPD-L1 and ProGRP in SCLC patients showed the same extent during remission and stabilization, suggesting the effect of s PD-L1 in the evaluation of SCLC tumors and the reflection of the tumor marker ProGRP.
Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer
Authors: Blum Joanne L. , Laird A. Douglas , Litton Jennifer K. , Rugo Hope S. , Ettl Johannes , Hurvitz Sara A. , Martin Miguel , Roché Henri H. , Lee Kyung-Hun , Goodwin Annabel , Chen Ying , Lanzalone Silvana , Chelliserry Jijumon , Czibere Akos , Hopkins Julia F. , Albacker Lee A. , Mina Lida A.
Published: January 2022

Purpose:

PARP inhibitors (PARPi) have demonstrated efficacy in tumors with germline breast cancer susceptibility genes (gBRCA) 1 and 2 mutations, but further factors influencing response to PARPi are poorly understood.

Experimental Design:

Breast cancer tumor tissue from patients with gBRCA1/2 mutations from the phase III EMBRACA trial of the PARPi talazoparib versus chemotherapy was sequenced using FoundationOne CDx.

Results:

In the evaluable intent-to-treat population, 96.1% (296/308) had ≥1 tumor BRCA (tBRCA) mutation and there was strong concordance (95.3%) between tBRCA and gBRCA mutational status. Genetic/genomic characteristics including BRCA loss of heterozygosity (LOH; identified in 82.6% of evaluable patients), DNA damage response (DDR) gene mutational burden, and tumor homologous recombination deficiency [assessed by genomic LOH (gLOH)] demonstrated no association with talazoparib efficacy.

Conclusions:

Overall, BRCA LOH status, DDR gene mutational burden, and gLOH were not associated with talazoparib efficacy; however, these conclusions are qualified by population heterogeneity and low patient numbers in some subgroups. Further investigation in larger patient populations is warranted.
Late-Life Depression, Cognitive Impairment, and Relationship with Alzheimer’s Disease
Authors: Invernizzi Sandra , Simoes Loureiro Isabelle , Kandana Arachchige Kendra G. , Lefebvre Laurent
Published: January 2022

This narrative review aimed to explore the existing knowledge in order to examine the multiple forms of late-life depression (LLD) within a non-neurodegenerative or a neurodegenerative context, in particular Alzheimer’s disease (AD). This review will first provide information about different pathogenic hypotheses proposed to describe LLD when it is not linked to a neurodegenerative context. Within the presentation of these syndromes, the literature reports thymic and cognitive specific features and highlights a common preponderance of cognitive impairment, and particularly executive. This review will also report data from research works that have addressed the role of depressive symptoms (DSs) in incidence of AD and mild cognitive impairment (MCI) conversion to AD. These findings support the claim that the relationship between DS (or LLD) and the cognitive decline encountered in AD can be of 2 types: (1) risk factor or (2) prodrome. They also support the hypothesis that the effect of DS on the incidence of AD can be identified between specific characteristics of these symptoms such as a very first apparition late in life, an increasing severity of DS, and a poor response to medical treatment. Finally, longitudinal and cross-sectional research will be presented, aiming to identify the predictive value of DS (or LLD) on AD incidence and/or conversion of MCI (and specifically amnestic MCI). This final section shows that specific features of LLD, such as being of early- or late-onset, can be considered as indices of AD incidence.
Post-Progression Survival Highly Influences Overall Survival in Driver Gene Mutation/Translocation Negative or Unknown Type of Non-Small Cell Lung Cancer
Authors: Imai Hisao , Onozato Ryoichi , Kaira Kyoichi , Kawashima Sayaka , Masubuchi Ken , Tajima Kohei , Minato Koichi
Published: January 2022

Introduction: In stage I–III non-small cell lung cancer (NSCLC), which is considered operable, surgical resection is the most efficacious treatment and is considered to provide a cure. However, after complete surgical resection, approximately 50% of patients with stage I–IIIA NSCLC experience recurrence and death. Once postoperative recurrence of NSCLC occurs, the prognosis is significantly poor, and the course of treatment after recurrence may influence overall survival (OS). Consequently, we investigated the relationship between relapse-free survival (RFS), post-progression survival (PPS), and OS in patients with postoperative recurrence of NSCLC with driver gene mutation/translocation negative or unknown status. Methods: Between January 2007 and September 2019, 101 patients with driver gene mutation/translocation negative or unknown status of NSCLC who underwent complete resection and in whom recurrence occurred were analyzed. The associations between RFS, PPS, and OS were analyzed at the individual patient level. Results: Linear regression and Spearman rank correlation analyses revealed that PPS was strongly associated with OS (r = 0.83, p < 0.0001, R2 = 0.71), whereas RFS was moderately correlated with OS (r = 0.65, p < 0.0001, R2 = 0.48). In the multivariate analysis, performance status at relapse, administration of immune checkpoint inhibitors, and radiotherapy for oligo-recurrences were significantly associated with PPS (p < 0.001). Conclusion: Current analysis of individual-level data of patients who underwent complete resection implied that PPS had a higher impact on OS than RFS in patients with postoperative recurrence of driver gene mutation/translocation negative or unknown status of NSCLC. Additionally, current perceptions indicate that treatment beyond progression after complete surgical resection might strongly affect OS.
Multiple Clinical Manifestations of Lichenoid Spectrum: A Patient with Frontal Fibrosing Alopecia, Lichen Planus Pigmentosus, and Nail Lichen Planus
Authors: Sarikaya Solak Sezgi , Sezer Burak Emre , Anzerlioglu Mete , Tokmak Zeynep , Topuz Canberk
Published: January 2022

Introduction: Frontal fibrosing alopecia (FFA) is characterized by irreversible, symmetrical band-like hair loss in the frontotemporal region. Lichen planus pigmentosus (LPP) is a variant of lichen planus (LP) that presents with hyperpigmented macules and patches predominantly in sun-exposed areas. Nail LP is a subtype of LP that can be present alone or with other forms of LP. Case Report: We report a rare case of a 59-year-old woman presenting with symmetrical, gray-brown, hyperpigmented lesions on her neck and face, band-like alopecia in the frontotemporal region, severe onycholysis in two fingernails, and prominent longitudinal ridging in all fingernails. Clinical, dermoscopic, and histological findings established a diagnosis of FFA associated with LPP and nail LP was established. Discussion/Conclusion: In recent years, it has been established that FFA can be associated with LPP and it is thought to be a variant of lichen planopilaris. Nail involvement is rarely reported in FFA or LPP. To our knowledge, the presence of the three conditions in the same patient has not been previously reported. Although rare we would like to emphasize the importance of a careful examination of the nails in patients with FFA and/or LPP to prevent irreversible nail changes.
Erste EULAR-Empfehlungen (Points to Consider) für rheumatische Nebenwirkungen von Checkpoint-Inhibitoren
Authors: Aringer Martin
Published: January 2022

Background: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management. Methods: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed. Results: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies. Conclusion: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.
Erhöhen Glukokortikoide auch kurzfristig das kardiovaskuläre Risiko? Eine Studie in Glukokortikoid-naiven Patienten mit rheumatoider Arthritis
Authors: Mihai Carina
Published: January 2022

Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals. Methods: Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year. Results: 19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5–9 mg 1.56 (1.18–2.06) and ≥10 mg 1.91 (1.31–2.79), without increased risk at 0–4 mg 1.04 (0.55–1.59). Cumulative dose over preceding 6 months showed increased aHR at 751–1100 mg 1.43 (1.04–1.98) and >1100 mg 2.05 (1.42–2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08–2.32), without increased risk at shorter durations. One-year analyses were consistent. Conclusions:Over preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.
COVID-19: Una enfermedad multiorgánica
Authors: Sánchez-Ríos Carla Paola
Published: January 2022

Background: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (COVID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology. Methods: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22–89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests. Results: Severe pulmonary endothelitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either. Conclusions: Extensive pulmonary endothelitis and multi-organ involvement are characteristic autopsy features in fatal COVID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.
Period-Dependent Survival Benefit of Percutaneous Microwave Ablation for Hepatocellular Carcinoma: A 12-Year Real-World, Multicentric Experience
Authors: Yu Jie , Cheng Zhi-Gang , Han Zhi-Yu , Liu Fang-Yi , Zheng Rong-Qin , Cheng Wen , Wei Qiang , Yu Song-Yuan , Li Qin-ying , He Guang-zhi , Luo Yan-chun , Yu Xiao-Ling , Liang Ping
Published: January 2022

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown. Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit. Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients. Recurrence and survival were analyzed using the Kaplan-Meier method with time-period stratification. Results: A total of 5,326 HCCs (mean diameter, 2.9 cm ± 1.2) underwent 4,051 sessions of MWA with a median follow-up of 61.3 (0.6–169.5 range) months during 3 periods (2007–2010, 2011–2014, and 2015–2018). Technical success was achieved in 5,194 (97.5%) tumors with significant improvement over time, especially for >3.0-cm HCC (p < 0.001). Local tumor progression (LTP) showed no period-dependent advance, with >3.0-cm HCC and perivascular location being the risk factors for LTP. The median intrahepatic metastasis time was 27.6 (95% confidence interval [CI]: 25.2–28.8) months, with 5- and 10-year occurrence rates of 68.8% and 79.4%, respectively. The 5- and 10-year overall survivals were 63.9% and 41.1%, respectively, and BCLC stage 0, A, and all B patients showed an observable survival improvement over time (p < 0.001). The median disease-free survival time increased from 19.4 (95% CI: 16.5–22.6) months in 2007–2010 to 28.1 (95% CI: 25.9–32.3) months in 2015–2018. The improved survival for early recurrent (≤2 years) patients was period-dependent, as verified by Cox regression analyses. The major complications rate per procedure was 3.0% (122/4,051). Conclusions: These real-world data show that MWA provided an upward trend in survival for HCC patients with BCLC stage 0–B over a 12-year follow-up period. An encouraging clear survival benefit in early recurrent patients was also observed.
Telemedizinische Versorgung von Wundpatienten: Echtzeit-Feedback verbessert Qualität von Wundbildern
Authors: Kirsten Natalia
Published: January 2022

Background: Travel to clinics for chronic wound management is burdensome to patients. Remote assessment and management of wounds using mobile and telehealth approaches can reduce this burden and improve patient outcomes. An essential step in wound documentation is the capture of wound images, but poor image quality can have a negative influence on the reliability of the assessment. To date, no study has investigated the quality of remotely acquired wound images and whether these are suitable for wound self-management and telemedical interpretation of wound status. Objective: Our goal was to develop a mobile health (mHealth) tool for the remote self-assessment of digital ulcers (DUs) in patients with systemic sclerosis (SSc). We aimed to define and validate objective measures for assessing the image quality, evaluate whether an automated feedback feature based on real-time assessment of image quality improves the overall quality of acquired wound images, and evaluate the feasibility of deploying the mHealth tool for home-based chronic wound self-monitoring by patients with SSc. Methods: We developed an mHealth tool composed of a wound imaging and management app, a custom color reference sticker, and a smartphone holder. We introduced 2 objective image quality parameters based on the sharpness and presence of the color checker to assess the quality of the image during acquisition and enable a quality feedback mechanism in an advanced version of the app. We randomly assigned patients with SSc and DU to the 2 device groups (basic and feedback) to self-document their DU at home over 8 weeks. The color checker detection ratio (CCDR) and color checker sharpness (CCS) were compared between the 2 groups. We evaluated the feasibility of the mHealth tool by analyzing the usability feedback from questionnaires, user behavior and timings, and the overall quality of the wound images. Results: A total of 21 patients were enrolled, of which 15 patients were included in the image quality analysis. The average CCDR was 0.96 (191/199) in the feedback group and 0.86 (158/183) in the basic group. The feedback group showed significantly higher (P<.001) CCS compared to the basic group. The usability questionnaire results showed that the majority of patients were satisfied with the tool, but could benefit from disease-specific adaptations. The median assessment duration was <50 seconds in all patients, indicating the mHealth tool was efficient to use and could be integrated into the daily routine of patients. Conclusions: We developed an mHealth tool that enables patients with SSc to acquire good-quality DU images and demonstrated that it is feasible to deploy such an app in this patient group. The feedback mechanism improved the overall image quality. The introduced technical solutions consist of a further step towards reliable and trustworthy digital health for home-based self-management of wounds.
Kutane T-Zell-Lymphome: Low-dose Gemcitabin in der Therapie fortgeschrittener CTCL
Authors: Assaf Chalid , Blazejak Christoph
Published: January 2022

Background: Gemcitabine is an effective single-agent chemotherapy used in advanced stages of cutaneous T-cell lymphoma (CTCL). However, gemcitabine used in the current standard regimen is frequently associated with adverse events (AE), such as an increased risk for myelosuppression and severe infections. Objectives: We investigated in this retrospective study the effect of low-dose gemcitabine in pretreated advanced-stage CTCL and in blastic plasmacytoid dendritic cell neoplasia (BPDCN) regarding overall response (OR), progression-free survival (PFS), and AE. Material and Methods: A retrospective, multicenter study was conducted on 64 CTCL and BPDCN patients treated with gemcitabine in average absolute dosage of 1,800 mg/m2 per cycle, which is 50% lower compared to standard dosage of 3,600 mg/m2 per cycle (1,200 mg/m2 day 1, 8, 15). Evaluation of response to therapy and AE was done 4–6 weeks after the sixth cycle. Results: OR was 62% with 11% demonstrating a complete response. The median time of PFS was 12 months and median time to next treatment was 7 months. Only 3/63 patients showed serious side effects, e.g., port infection or acute renal failure. Almost 73% of the patients experienced minor to moderate side effects (CTCAE grade 0–2). Fatigue (27.2%), fever (22.7%), and mild blood count alteration (18.2%) were the most common AE. Conclusions: This retrospective analysis supports the use of low-dose gemcitabine therapy in CTCL, demonstrating with 62% OR and PFS of 12 months an almost identical response rate and survival as compared to the standard dose therapy reported in previous studies but with a significantly improved safety profile and tolerability.
An Exploratory Study of the Effects of the pH of Synthetic Urine on Skin Integrity in Healthy Participants
Authors: Koudounas Sofoklis , Bader Dan L. , Voegeli David
Published: January 2022

Background: Incontinence-associated dermatitis (IAD) develops from prolonged exposure of skin to urine and/or stool and represents a common complication in older adults, reducing the quality of life. Increased pH is an important etiologic factor of IAD; however, the relationship between urinary pH and skin barrier disruption remains unclear. Objective: The aim of this study is to examine the effects of synthetic urine (s-urine) at various pHs on transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH. Methods: S-urine solutions (pH 5.0–9.0) were applied to the volar forearms of 15 healthy participants for 2 h, with another site serving as the untreated control. Measurements of TEWL, SCH, and skin surface pH were obtained at baseline (BL) and after each challenge. Skin buffering capacity was also examined in 5 volunteers by recording skin pH at BL, after 2 h exposure and every 5 min for 40 min. Results: TEWL and SCH were increased following exposure to s-urine compared to BL values. Although there was a tendency for pH to increase after exposure, further investigation showed that changes are only temporal as pH value is restored to BL within 5 mins. There were no significant differences between solutions. Conclusions: This study revealed that urine disrupts healthy skin integrity; however, its effects are not pH dependent. Transient changes were observed on the acid mantle of the skin due to its innate buffering capacity. Future studies need to examine the effects of urine combined with bacteria responsible for pH elevation in patients with urinary incontinence.
Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy
Authors: Piers Sebastiaan R. , Androulakis Alexander F. , Yim Kevin S. , van Rein Nienke , Venlet Jeroen , Kapel Gijsbert F. , Siebelink Hans-Marc , Lamb Hildo J. , Cannegieter Suzanne C. , Man Sum-Che , Zeppenfeld Katja
Published: January 2022

Background:

Spontaneous nonsustained ventricular tachycardia (NSVT) on Holter, VT inducibility during electrophysiology study, and late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) have been associated with sustained ventricular arrhythmias (SVAs) in nonischemic dilated cardiomyopathy (DCM). This study aimed to analyze whether these parameters carry independent prognostic value for spontaneous SVA in DCM.

Methods:

Between 2011 and 2018, patients with the DCM clinical spectrum and documented SVA, suspected SVA, or considered to be at intermediate or high risk for SVA were enrolled in the prospective Leiden Nonischemic Cardiomyopathy Study. Patients underwent a comprehensive evaluation including 24-hour Holter, LGE-CMR, and electrophysiology study. Holters were assessed for the presence of NSVT (≥3 beats; rate, ≥120 bpm; lasting <30 s) and NSVT characteristics (coupling interval, duration, cycle length, morphology, regularity). Patients were followed at 6 to 12 monthly intervals.

Results:

Of all 115 patients (age, 59±12 years; 77% men; left ventricular ejection fraction, 33±13%; history of SVA, 36%; LGE in 63%; median LGE mass, 13 g; interquartile range, 8–23 g), 62 (54%) had NSVT on Holter, and sustained monomorphic VT was inducible in 34 of 114 patients (30%). NSVT was not associated with LGE on CMR or VT inducibility during electrophysiology study nor were its features (all
P
>0.05). During 4.0±1.8 years of follow-up, SVA occurred in 39 patients (34%). NSVT (HR, 4.47 [95% CI, 1.87–10.72];
P
=0.001) and VT inducibility (HR, 3.08 [95% CI, 1.08–8.81];
P
=0.036) were independently associated with SVA during follow-up. A bivariable model including only noninvasively acquired parameters also allowed identification of a high-risk subgroup (ie, those with both NSVT and LGE on CMR). The findings remained similar when only patients without prior SVA were included.

Conclusions:

In patients with DCM, NSVT on Holter and VT inducibility during electrophysiology study predict SVA during follow-up independent of LGE on CMR. NSVTs may serve as an initiator, and sustained VT inducibility indicates the presence of the substrate for SVA in DCM.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01940081.
Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Bosman Laurens P. , Wang Weijia , Lie Øyvind H. , van Lint Freyja H.M. , Rootwelt-Norberg Christine , Murray Brittney , Tichnell Crystal , Cadrin-Tourigny Julia , van Tintelen J. Peter , Asselbergs Folkert W. , Calkins Hugh , te Riele Anneline S.J.M. , Haugaa Kristina H. , James Cynthia A.
Published: January 2022

Background:

Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (
arvcrisk.com
). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise.

Methods:

We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models.

Results:

We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7–9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53–2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71–0.84) and showed no significant improvement (Akaike information criterion change, <2).

Conclusions:

Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification.