Αρχειοθήκη ιστολογίου

Κυριακή 4 Απριλίου 2021

Does Familial Mediterranean Fever Provoke Atherosclerosis in Children? Evaluation of Arterial Stiffness and Serum Endocan Levels

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Abstract

Objectives

This study aimed to evaluate the risk for atherosclerosis by using echocardiographic arterial stiffness (AS) parameters and serum endocan levels, as a biomarker of endothelial dysfunction (ED) in children with FMF.

Methods

Seventy-nine children with FMF (12–18 years) and 41 healthy children were included, and clinical features (age at the first attack, age at the time of diagnosis, diagnosis delay time, colchicine dose, biological agent usage, MEFV mutations, and symptoms of attacks) of patients were noted. Arterial stiffness parameters were calculated by using echocardiographic aortic measurements with blood pressure monitoring. Hemogram parameters, acute phase reactants, blood glucose and lipid levels of 12 hours of fasting, and serum endocan levels were evaluated for all participants.

Results

There were no statistically significance regarding demographic features, acute phase reactants, and hemogram parameters. Blood glucose and lipid levels were similar, except for HDL (lower in FMF group, p=0.029). Serum endocan levels did not differ in two groups (p=0.906). Only stiffness of descending aorta was lower in FMF group (p=0.028), and the other AS parameters were similar between two groups (p>0.05 for each parameters).

Conclusion

Good disease control could be preventive for atherosclerosis in children with FMF. On the other hand, screening for cardiovascular diseases is essential, particularly for uncontrolled cases.

Graphical abstract

Distribution of MEFV gene mutations

Key points

• Exaggerated inflammation is the prominent feature of FMF attacks; moreover, it is shown that subclinical inflammation might also continue in attack-free periods.

• Chronic inflammation contributes to atherosclerotic process in almost all stages by activating endothelial cells, producing reactive oxygen species, and accelerating foam cell and atherosclerotic plaque formations.

• However, the results of this study showed that there was no difference in terms of atherosclerotic markers such as serum endocan levels and arterial stiffness parameters between pediatric FMF patients and healthy peers.

• Good disease control in pediatric FMF patients may prevent early atherosclerotic changes during childhood, which then may lead a probable decreased risk of subsequent CVD in adulthood.

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High Acuity Therapy Variation Across Pediatric Acute Care Cardiology Units: Results from the Pediatric Acute Care Cardiology Collaborative Hospital Surveys

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Abstract

We utilized the multicenter Pediatric Acute Care Cardiology Collaborative (PAC3) 2017 and 2019 surveys to describe practice variation in therapy availability and changes over a 2-year period. A high acuity therapies (ATs) score was derived (1 point per positive response) from 44 survey questions and scores were compared to center surgical volume. Of 31 centers that completed the 2017 survey, 26 also completed the 2019 survey. Scores ranged from 11 to 34 in 2017 and 11 to 35 in 2019. AT scores in 2019 were not statistically different from 2017 scores (29/44, IQR 27–32.5 vs. 29.5/44, IQR 27–31, p = 0.9). In 2019, more centers reported initiation of continuous positive airway pressure (CPAP) and Bi-level positive airway pressure (BiPAP) in Acute Care Cardiology Unit (ACCU) (19/26 vs. 4/26, p < 0.001) and permitting continuous CPAP/BiPAP (22/26 vs. 14/26, p = 0.034) compared to 2017. Scores in both survey years were significantly higher in the highest surgical volume group compared to the lowest, 33 ± 1.5 versus 25 ± 8.5, p = 0.046 and 32 ± 1.7 versus 23 ± 5.5, p = 0.009, respectively. Variation in therapy within the ACCUs participating in PAC3 presents an opportunity for shared learning across the collaborative. Experience with PAC3 was associated with increasing available respiratory therapies from 2017 to 2019. Whether AT scores impact the quality and outcomes of pediatric acute cardiac care will be the subject of further investigation using a comprehensive registry launched in early 2019.

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Heel fat pad involvement in rheumatoid arthritis: a review and case series

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting not only the synovial joints but also multiple extra-articular sites, including ankle and foot soft tissue. Hindfoot abnormalities usually follow those in the forefoot, with up to 4 out of 10 patients experiencing talalgia during their disease course. Enthesophytosis, retrocalcaneal bursitis, and plantar fasciitis are among the most common etiologies, while heel fat pad abnormalities like subcalcaneal bursitis are rare. Here, we report two cases of subcalcaneal bursitis, and the first case of heel fat pad and subcalcaneal bursa herniation in patients with established RA, along with a comprehensive literature review of subcalcaneal bursitis and other heel fat pad abnormalities in RA. Subcalcaneal bursitis, also referred to as panniculitis, inflammatory-edematous lesion, or adventitial (adventitious) bursitis has been reported in up to 10% of patients with RA. It appears as a compressi ble, heterogeneous, and hypoechoic subcalcaneal mass on ultrasound (US), with peripheral vascularization on Doppler US. Patients may present with heel discomfort. Ultrasonographic assessment is usually sufficient to confirm the presence of heel fat pad pathologies. Rest, analgesics, and mechanical aids with or without addition of disease-modifying antirheumatic drugs are usually employed, while intervention is rarely required.

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Periodontal disease and risk of mortality and kidney function decline in advanced chronic kidney disease: a nationwide population-based cohort study

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Abstract

Objectives

Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD.

Materials and methods

Taiwan's National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest.

Results

A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49–1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75–1.10), or MACE (aHR: 1.18, 95% CI: 0.91–1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures.

Conclusions

Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD.

Clinical relevance

These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD.

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Mucins reprogram stemness, metabolism and promote chemoresistance during cancer progression

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Abstract

Mucins are high-molecular-weight glycoproteins dysregulated in aggressive cancers. The role of mucins in disease progression, tumor proliferation, and chemotherapy resistance has been studied extensively. This article provides a comprehensive review of mucin's function as a physical barrier and the implication of mucin overexpression in impeded drug delivery to solid tumors. Mucins regulate the epithelial to mesenchymal transition (EMT) of cancer cells via several canonical and non-canonical oncogenic signaling pathways. Furthermore, mucins play an extensive role in enriching and maintaining the cancer stem cell (CSC) population, thereby sustaining the self-renewing and chemoresistant cellular pool in the bulk tumor. It has recently been demonstrated that mucins regulate the metabolic reprogramming during oncogenesis and cancer progression, which account for tumor cell survival, proliferation, and drug-resistance. This review article focuses on delineating muci n's role in oncogenic signaling and aberrant regulation of gene expressions, culminating in CSC maintenance, metabolic rewiring, and development of chemoresistance, tumor progression, and metastasis.

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Molten salt derived crystalline graphitic carbon nitride to enable selective photo-oxidation of benzyl alcohol

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Abstract

Graphitic carbon nitride with low cost was a fascinating metal-free photocatalyst for alcohol oxidation. However, pristine graphitic carbon nitride typically revealed fast charge recombination owing to incomplete polymerization. Therefore, increasing the degree of polymerization can be one of the effective ways to enhance its photocatalytic activity. Crystalline graphitic carbon nitride was prepared with the aim of modifying charge separation efficiency and increasing crystallinity for advancing catalytic performance by salt melting method. PTI owned a more positive valence band value (2.48 eV) than that of bulk g-C3N4, promising to enhance thermodynamic driving force toward photocatalytic oxidation reactions. In addition, PTI revealed effective adsorption ability for substrates by density functional theory (DFT) calculations. The optimal benzyl alcohol conversion efficiency was 59.3% with selectivity of > 99%. Meanwhile, the recycling experimental results demonstrated that PTI phtocatalyst owed an outstanding reusability and durability. The radical scavenging experiments and EPR analysis demonstrated that both •O2- and holes were the main reactive species in photocatalytic alcohol oxidation. This work might offer an avenue to conveniently prepare and bring a new opportunity to exploit photocatalysts with excellent photocatalytic alcohol oxidation performance.

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Local application reduces number of needed EPC for beneficial effects on wound healing compared to systemic treatment in mice

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Abstract

Introduction

Stem cell transplantation is one of the most promising strategies to improve healing in chronic wounds as systemic administration of endothelial progenitor cells (EPC) enhances healing by promoting neovascularization and homing though a high amount of cells is needed. In the following study, we analysed whether local application can reduce the number of EPC needed achieving the same beneficial effect on wound healing.

Material and Methods

Wound healing after local or systemic treatment with EPC was monitored in vivo by creating standardized wounds on the dorsum of hairless mice measuring wound closure every second day. Systemic group received 2 × 106 EPC i.v. and locally treated group 2 × 105 EPC, locally injected. As control PBS injection was performed the same way. Expression of CD31, VEGF, CD90 and, SDF-1α was analysed immunohistochemically for evaluation of neovascularisation and amelioration of homing.

Results

Local (7.1 ± 0.45 SD) as well as systemic (6.1 ± 0.23 SD) EPC transplantation led to a significant acceleration of wound closure compared to controls (PBS local: 9.7 ± 0.5 SD, PBS systemic 10.9 ± 0.38 SD). Systemic application enhanced CD31 expression on day 6 after wounding and local EPC on 6 and 9 in comparison to control. VEGF expression was not significantly affected. Systemic and local EPC treatment resulted in a significantly enhanced SDF-1α and CD90 expression on all days investigated.

Conclusion

Local as well as systemic EPC treatment enhances wound healing. Moreover, beneficial effects are obtained with a tenfold decrease number of EPC when applied locally. Thus, local EPC treatment might be more convenient way to enhance wound healing as number of progenitor cells is limited.

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Unusual cause of hypoxia due to incomplete removal of the closed suction catheter system during COVID-19 ventilation

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Comparison of Liver Recovery After Sleeve Gastrectomy and Roux-en-Y-Gastric Bypass

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Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is a common condition in patients with obesity. Bariatric surgery has often been proposed as a viable treatment option, but the ideal surgical procedure remains unclear. Inconsistently, reports on postoperative deterioration of liver function put further doubt on which technique to apply. Aim of this study was to assess the impact of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on the postoperative recovery of liver function.

Methods

A total of 175 patients with obesity that underwent bariatric surgery in our institution were included in this prospective cohort study. BMI, laboratory values, and liver function capacity (using LiMAx) were assessed preoperatively and at 6 and 12 months postoperatively. Generalized linear model (GLM) was performed to determine variables influencing liver function capacity after the operation.

Results

Prior to operations, 64% of patients presented with a diminished liver function capacity, as measured by LiMAx test. Liver function capacity significantly recovered after 12 months in the SG group (300 μg/kg/h preop vs. 367 μg/kg/h postop) but not in the RYGB group (306 μg/kg/h preop vs. 349 μg/kg/h). Preoperative factors impeding liver function recovery included type 2 diabetes mellitus (T2DM), weight, male sex, AST/thrombocyte ratio (APRI), and gamma-glutamyltransferase (GGT).

Conclusion

Bariatric surgery, especially sleeve gastrectomy, leads to an improvement of liver function. However, in some patients with T2DM, higher preoperative weight and male sex postoperative deterioration of liver function capacity may occur.

Graphical abstract

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Establishment and characterization of 38 novel patient-derived primary cancer cell lines using multi-region sampling revealing intra-tumor heterogeneity of gallbladder carcinoma

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Abstract

Gallbladder carcinoma (GBC) is a lethal biliary tract malignant neoplasm. Patient-derived primary cancer cell lines (PDPCs) are appropriate models to explore biological characteristics and potential therapeutics; however, there is a lack of PDPCs in GBC. In this study, we aimed to establish and characterize the GBC PDPCs, and further investigated the intra-tumor heterogeneity (ITH). Multi-region sampling (3–9 regions) of the operable tumor tissue samples was used to establish PDPCs. Short tandem repeat genotyping for cell authentication and karyotyping was performed, followed by whole-exome sequencing and RNA sequencing to assess the ITH at the genetic and transcriptional levels, respectively. Thirty-eight PDPCs were successfully established from seven GBC patients and characterized. ITH was observed with a median of 38.3% mutations being heterogeneous (range, 26.6–59.4%) across all patients. Similar with other tumor types, TP53 mutations were always truncal. In addition, there were three genes, KMT2C, CDKN2A, and ARID1A, with truncal mutations in at least two patients. A median of 370 differentially expressed genes (DEGs) was identified per patient. Distinct expression patterns were observed between major histocompatibility complex (MHC) class I and II genes. We found the expression of MHC class II genes in the PDPC samples was closely regulated by CIITA, while that of MHC class I genes were not correlated with CIITA expression. The PDPCs established from GBC patients can serve as novel in vitro models to identify the ITH, which may pave a crucial molecular foundation for enhanced understanding of tumorigenesis and progression.

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Geriatric assessment and medical preoperative screening (GrAMPS) program for older hernia patients

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Abstract

Purpose

The incidence of older adults undergoing inguinal and ventral hernia repairs is increasing. Older adults are disproportionately affected by age-related risk factors, which are often under-recognized and may adversely affect surgical outcomes. These age-related risk factors often termed "geriatric syndromes," include multimorbidity, frailty, cognitive impairment, depression, obesity, functional impairment, polypharmacy, and poor subjective health. The aim of this study was to identify the prevalence of age-related risk factors in older patients undergoing elective hernia repair.

Methods

Patients aged 60 years or older with a planned elective surgical repair of a ventral or inguinal hernia were prospectively enrolled in a clinic. Subjects completed several validated screening tools for geriatric syndromes.

Results

Seventy patients completed preoperative assessments (mean age: 68.5 years). In total, 24 (34.3%) screened positive for previously unrecognized objective cognitive impairment (Mini-Cog) and 33 (47.1%) for a subjective memory concern. Sixty patients (85.7%) met criteria for polypharmacy. Additionally, 48 (68.6%) screened positive for either pre-frailty (37, 52.9%) or frailty (11, 15.7%), and 66 (94.3%) had multimorbidity. Twenty-five (35.7%) patients self-rated their health as "poor" or "fair," and 18 (25.7%) patients endorsed some functional impairment.

Conclusions

There is a high prevalence of age-related risk factors in older patients undergoing elective hernia repair. Further, these factors are often unrecognized and underappreciated despite their potential to significantly impact informed consent and shared decision making. Additional study is required to define the impact of these age-related risk factors on surgical outcomes, which will inform preoperative risk assessment and optimization through modifiable risk reduction.

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