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Journal of Clinical Medicine Jun 2024Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events....
Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 - 0.402 × age + 4.560 × 10 × age2 - 2.621 × 10 × age2 × MBP + 3.176 × 10 × age × MBP - 1.832 × 10 × MBP. MBP= (DBP) + 0.4(SBP - DBP). At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; < 0.029; HR 3.03, 95% CI 1.118-8.211). In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.
PubMed: 38929906
DOI: 10.3390/jcm13123377 -
Journal of Personalized Medicine Jun 2024Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a...
BACKGROUND
Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses. Herein, we investigated whether clinical or US assessment of joints and entheses can predict the progression of joint destruction in Japanese patients with PsA.
METHODS
Thirty joints and 14 entheses in 47 patients were assessed using US and clinical examination. The US greyscale (GS) and power Doppler (PD) scores at the ultrasonographic synovitis, the US active enthesitis count, and the clinical tender joint/entheses count were assessed. Additionally, the yearly radiographic progression of the Sharp-van der Heijde scoring method for PsA was assessed. Their correlations were investigated.
RESULTS
About half of the patients with PsA experienced joint destruction during a follow-up period of 20.4 months. Progression of joint destruction in patients with PsA only correlated with joint GS and PD scores, reflecting the severity of ultrasonographic synovitis, not with the tender joint/entheses count.
CONCLUSIONS
US examinations are essential for preventing joint destruction and physical impairment in patients with PsA.
PubMed: 38929851
DOI: 10.3390/jpm14060630 -
Journal of Personalized Medicine Jun 2024Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and...
Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and dysfunction that culminate in progressive articular cartilage loss. We present our experience in the management of hip and knee OA by means of the intra-articular injection of fat micrograft, describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft on damaged tissue, as well as its natural lubricating effect on the joints. Inclusion criteria were as follows: men and women, aged 20 to 80 years, that referred articular pain of the hips and/or knees, showing initial-stage degenerative OA. From October 2018 to July 2023, a total of 250 patients underwent treatment with the Sefficare device (SEFFILINE srl, Bologna, Italy). The Superficial Enhanced Fluid Fat Injection device was used to perform autologous regenerative treatments in a safe, standardized, easy, and effective way on 160 women, 64%, and 90 men, 36%. A total of 190 procedures (76%) involved the knees, with 20 patients who were bilaterally treated, while 60 procedures, all unilateral, involved the hips (24%). The mean age at treatment was 52.4 years. Before treatment, each patient had undergone X-rays and Magnetic Resonance Imaging (MRI) of the painful hip/knee to evaluate and grade the articular OA. Postoperatively, each patient was assessed after one, three, six, and twelve months. The donor site postoperative course was uneventful other than minimal discomfort. Clinically, the ROM (range of motion) of the treated knee/hip increased an average of 10 degrees 3 months after treatment, but the stiffness was reduced, as reported by the patients. The VAS (Visual Analog Scale) was submitted at 3, 6, and 12 months, demonstrating a progressive reduction of pain, with the best score obtained at six months postoperatively. In total, 85% of patients were satisfied one year after treatment, with a considerable improvement in pain and quality of life. The satisfactory outcome of this minimally invasive procedure indicates that the intra-articular injection of fat micrograft can replace or considerably delay the need for the classical major joint replacement surgery, thanks to its impact on the quality of life of patients and financial cost.
PubMed: 38929825
DOI: 10.3390/jpm14060604 -
Life (Basel, Switzerland) May 2024The escalating prevalence of retinal diseases-notably, age-related macular degeneration and hereditary retinal disorders-poses an intimidating challenge to ophthalmic... (Review)
Review
The escalating prevalence of retinal diseases-notably, age-related macular degeneration and hereditary retinal disorders-poses an intimidating challenge to ophthalmic medicine, often culminating in irreversible vision loss. Current treatments are limited and often fail to address the underlying loss of retinal cells. This paper explores the potential of stem-cell-based therapies as a promising avenue for retinal regeneration. We review the latest advancements in stem cell technology, focusing on embryonic stem cells (ESCs), pluripotent stem cells (PSCs), and mesenchymal stem cells (MSCs), and their ability to differentiate into retinal cell types. We discuss the challenges in stem cell transplantation, such as immune rejection, integration into the host retina, and functional recovery. Previous and ongoing clinical trials are examined to highlight the therapeutic efficacy and safety of these novel treatments. Additionally, we address the ethical considerations and regulatory frameworks governing stem cell research. Our analysis suggests that while stem-cell-based therapies offer a groundbreaking approach to treating retinal diseases, further research is needed to ensure long-term safety and to optimize therapeutic outcomes. This review summarizes the clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt's disease.
PubMed: 38929652
DOI: 10.3390/life14060668 -
Life (Basel, Switzerland) May 2024Together, lower back and neck pain are among the leading causes of acquired disability worldwide and have experienced a marked increase over the past 25 years.... (Review)
Review
Together, lower back and neck pain are among the leading causes of acquired disability worldwide and have experienced a marked increase over the past 25 years. Paralleled with the increasing aging population and the rise in chronic disease, this trend is only predicted to contribute to the growing global burden. In the context of cervical neck pain, this symptom is most often a manifestation of cervical degenerative disc disease (DDD). Traditionally, multilevel neck pain related to DDD that is recalcitrant to both physical and medical therapy can be treated with a procedure known as cervical corpectomy. Presently, there are many flavors of cervical corpectomy; however, the overarching goal is the removal of the pain-generating disc via the employment of the modern anterior approach. In this review, we will briefly detail the pathophysiological mechanism behind DDD, overview the development of the anterior approach, and discuss the current state of treatment options for said pathology. Furthermore, this review will also add to the current body of literature surrounding updated indications, surgical techniques, and patient outcomes related to cervical corpectomy. Finally, our discussion ends with highlighting the future direction of cervical corpectomy through the introduction of the "skip corpectomy" and distractable mesh cages.
PubMed: 38929635
DOI: 10.3390/life14060651 -
Medicina (Kaunas, Lithuania) Jun 2024: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral...
: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral disc herniation, degenerative changes, or trauma. While conservative treatments are initially preferred, persistent or severe cases may require surgical intervention. Ultrasound-guided selective nerve root block (SNRB) has emerged as a promising intervention for alleviating symptoms and potentially obviating the need for surgery. This study evaluates the therapeutic efficacy of ultrasound-guided SNRB in managing chronic CR, aiming to determine its potential in symptom relief and delaying or avoiding surgical procedures. : A retrospective analysis was conducted on 720 outpatients treated for CR between October 2019 and March 2022. After excluding patients with traumatic CR, previous surgeries, malignancies, progressive neurological symptoms requiring immediate surgery, or inadequate conservative treatment, 92 patients who had experienced cervical radicular pain for more than three months and had failed to improve after more than six weeks of conservative treatment with VAS scores ≥ 5 were included. The patients underwent single or multiple ultrasound-guided SNRB procedures, involving the injection of dexamethasone and lidocaine under real-time ultrasound guidance. Symptom severity was assessed at the baseline, and at 4, 8, and 12 weeks post-procedure using the Visual Analog Scale (VAS). The data collected included age, sex, presence of neck and/or radicular pain, physical examination findings, recurrence of symptoms, improvement in symptoms, and whether surgical intervention was ultimately required. Statistical analyses were performed to identify the factors associated with symptom improvement or recurrence. : Significant symptom improvement was observed in 69 (75.0%) participants post-SNRB, with 55 (79.7%) showing improvement at 4 weeks, 11 (15.9%) at 8 weeks, and 3 (4.4%) at 12 weeks. Symptom recurrence, defined by an increase in VAS score accompanied by a pain flare lasting at least 24 h after a pain-free interval of at least one month, was noted in 48 (52.2%) patients. The presence of combined neck and radicular pain was a significant predictor of recurrence ( = 0.008). No significant associations were found between symptom relief and factors such as age, gender, initial pain severity, or MRI findings. : Ultrasound-guided SNRB effectively manages chronic CR, providing substantial symptom relief and potentially reducing the need for surgical intervention. This technique offers a promising conservative treatment option, especially given its real-time visualization advantages and minimal radiation exposure.
Topics: Humans; Female; Male; Middle Aged; Radiculopathy; Retrospective Studies; Nerve Block; Ultrasonography, Interventional; Adult; Treatment Outcome; Pain Measurement; Aged; Lidocaine; Chronic Disease; Dexamethasone
PubMed: 38929619
DOI: 10.3390/medicina60061002 -
Animals : An Open Access Journal From... Jun 2024The increase in the canine geriatric population means that veterinarians are more often confronted with diseases that are more prevalent in patients in this age group.... (Review)
Review
The increase in the canine geriatric population means that veterinarians are more often confronted with diseases that are more prevalent in patients in this age group. As in other organ systems, degenerative, neoplastic, and vascular diseases are the most prevalent neurologic disorders in older dogs. A neurological disease in an older dog poses a challenge for the clinician due to the presence of concomitant diseases and age-related changes that make it difficult to interpret the neurological examination. In addition, given the age of the patients, some owners do not allow advanced imaging tests, and it is necessary to establish the most likely presumptive diagnosis to initiate treatment. Although many of these diseases can cause clinical signs that can be very upsetting, some of them can be managed with symptomatic therapy and have a good prognosis, such as idiopathic vestibular syndrome. Moreover, advances in and the greater availability of therapeutic options such as surgery and radiation therapy may increase survival and quality of life in diseases with a more serious prognosis, such as tumours. The aim of this review is to summarize the clinical presentation, diagnosis, and treatment of the more frequent diseases affecting the central nervous systems of geriatric dogs.
PubMed: 38929372
DOI: 10.3390/ani14121753 -
International Journal of Molecular... Jun 2024MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important...
MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle.
Topics: MicroRNAs; Tissue Engineering; Humans; Tissue Scaffolds; Cell Differentiation; Adipose Tissue; Blood Vessels; Gene Expression Regulation; Neovascularization, Physiologic; Stem Cells; Cell Proliferation; Signal Transduction
PubMed: 38928467
DOI: 10.3390/ijms25126762 -
International Journal of Molecular... Jun 2024Pericytes are multipotent cells embedded within the vascular system, primarily surrounding capillaries and microvessels where they closely interact with endothelial... (Review)
Review
Pericytes are multipotent cells embedded within the vascular system, primarily surrounding capillaries and microvessels where they closely interact with endothelial cells. These cells are known for their intriguing properties due to their heterogeneity in tissue distribution, origin, and multifunctional capabilities. Specifically, pericytes are essential in regulating blood flow, promoting angiogenesis, and supporting tissue homeostasis and regeneration. These multifaceted roles draw on pericytes' remarkable ability to respond to biochemical cues, interact with neighboring cells, and adapt to changing environmental conditions. This review aims to summarize existing knowledge on pericytes, emphasizing their versatility and involvement in vascular integrity and tissue health. In particular, a comprehensive view of the major signaling pathways, such as PDGFβ/ PDGFRβ, TGF-β, FOXO and VEGF, along with their downstream targets, which coordinate the behavior of pericytes in preserving vascular integrity and promoting tissue regeneration, will be discussed. In this light, a deeper understanding of the complex signaling networks defining the phenotype of pericytes in healthy tissues is crucial for the development of targeted therapies in vascular and degenerative diseases.
Topics: Pericytes; Humans; Signal Transduction; Homeostasis; Animals; Neovascularization, Physiologic; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38928298
DOI: 10.3390/ijms25126592 -
International Journal of Molecular... Jun 2024Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim... (Review)
Review
Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim of this systematic review is to investigate the therapeutic potential of fluoxetine in cognitive decline in AD, focusing on its anti-degenerative mechanisms of action and clinical implications. According to PRISMA, we searched MEDLINE, up to 1 April 2024, for animal and human studies examining the efficacy of fluoxetine with regard to the recovery of cognitive function in AD. Methodological quality was evaluated using the ARRIVE tool for animal AD studies and the Cochrane tool for clinical trials. In total, 22 studies were analyzed (19 animal AD studies and 3 clinical studies). Fluoxetine promoted neurogenesis and enhanced synaptic plasticity in preclinical models of AD, through a decrease in Aβ pathology and increase in BDNF, by activating diverse pathways (such as the DAF-16-mediated, TGF-beta1, ILK-AKT-GSK3beta, and CREB/p-CREB/BDNF). In addition, fluoxetine has anti-inflammatory properties/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome. Only three clinical studies showed that fluoxetine ameliorated the cognitive performance of people with AD; however, several methodological issues limited the generalizability of these results. Overall, the high-quality preclinical evidence suggests that fluoxetine may have neuroprotective, antioxidant, and anti-inflammatory effects in AD animal models. While more high-quality clinical research is needed to fully understand the mechanisms underlying these effects, fluoxetine is a promising potential treatment for AD patients. If future clinical trials confirm its anti-degenerative and neuroprotective effects, fluoxetine could offer a new therapeutic approach for slowing down the progression of AD.
Topics: Fluoxetine; Alzheimer Disease; Humans; Animals; Cognitive Dysfunction; Disease Models, Animal; Neurogenesis; Neuronal Plasticity
PubMed: 38928248
DOI: 10.3390/ijms25126542