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Europace : European Pacing,... Jun 2024Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are...
Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.
AIMS
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA.
METHODS AND RESULTS
A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA.
CONCLUSION
The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.
Topics: Humans; Catheter Ablation; Male; Atrial Flutter; Female; Atrial Fibrillation; Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Treatment Outcome; Middle Aged; Recurrence; Tachycardia, Supraventricular; Retrospective Studies; Prealbumin
PubMed: 38934242
DOI: 10.1093/europace/euae155 -
Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Frontiers in Pharmacology 2024Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are...
Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia. We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture. Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir Medium dried flowers (NC1) and Cannabixir THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%-89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values. Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.
PubMed: 38933665
DOI: 10.3389/fphar.2024.1395951 -
Journal of Diabetes and Metabolic... Jun 2024Diabetes mellitus is a common chronic metabolic disorder that is characterized by increased levels of glucose for prolonged periods of time. Incessant hyperglycemia... (Review)
Review
BACKGROUND
Diabetes mellitus is a common chronic metabolic disorder that is characterized by increased levels of glucose for prolonged periods of time. Incessant hyperglycemia leads to diabetic complications such as retinopathy, nephropathy, and neuropathy, and cardiovascular complications such as ischemic heart disease, peripheral vascular disease, diabetic cardiomyopathy, stroke, etc. There are many studies that suggest that various polyphenols affect glucose homeostasis and can help to attenuate the complications associated with diabetes.
OBJECTIVE
This review focuses on the possible role of various dietary polyphenols in palliating diabetes-induced cardiovascular complications. This review also aims to give an overview of the interrelationship among ROS production (due to diabetes), inflammation, glycoxidative stress, and cardiovascular complications as well as the anti-hyperglycemic effects of dietary polyphenols.
METHODS
Various scientific databases including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and Wiley Online Library were used for searching articles that complied with the inclusion and exclusion criteria.
RESULTS
This review lists several polyphenols based on various pre-clinical and clinical studies that have anti-hyperglycemic potential as well as a protective function against cardiovascular complications.
CONCLUSION
Several pre-clinical and clinical studies suggest that various dietary polyphenols can be a promising intervention for the attenuation of diabetes-associated cardiovascular complications.
PubMed: 38932901
DOI: 10.1007/s40200-023-01326-x -
Journal of Diabetes and Metabolic... Jun 2024This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence... (Review)
Review
OBJECTIVE
This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence specific genes in various cell types, including those involved in diabetes complications.
SIGNIFICANCE
Diabetes, a prevalent and severe condition, poses life-threatening risks due to elevated blood glucose levels. It results from inadequate insulin production by the pancreas or ineffective insulin utilization by the body. Recent research suggests siRNA could hold promise in addressing diabetes complications.
METHODS
In this review, we discussed several subjects, including diabetes; its function, and common treatment options. An in-depth analysis of gene silencing method for siRNA and role of siRNA in diabetes, focusing on its impact on glucose homeostasis, diabetic retinopathy, wound healing, diabetic nephropathy and peripheral neuropathy, diabetic foot ulcers, diabetic atherosclerosis, and diabetic cardiomyopathy.
RESULT
siRNA-based treatment has the potential to target specific genes without disrupting several other endogenous pathways, which decreases the risk of off-target effects. In addition, siRNA has the capability to provide long-term efficacy with a single dose which will reduce treatment options and enhance patient compliance.
CONCLUSION
In the context of diabetic complications, siRNA has been explored as a potential therapeutic tool to modulate the expression of genes involved in various processes associated with diabetes-related issues such as Diabetic Retinopathy, Neuropathy, Nephropathy, wound healing. The use of siRNA in these contexts is still largely experimental, and challenges such as delivery to specific tissues, potential off-target effects, and long-term safety need to be addressed. Additionally, the development of siRNA-based therapies for clinical use in diabetic complications is an active area of research.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01405-7.
PubMed: 38932822
DOI: 10.1007/s40200-024-01405-7 -
Clinical and Translational Science Jun 2024Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of...
Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1 miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1 and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1 miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1 miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.
Topics: Animals; Neurofibromatosis 1; Disease Models, Animal; Mice; Neurofibromin 1; Behavior, Animal; Male; Hippocampus; Cognitive Dysfunction; Oligodendroglia; Humans; Astrocytes; Female
PubMed: 38932491
DOI: 10.1111/cts.13858 -
Pharmaceutics May 2024Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach...
Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach and delivery system. Ciprofloxacin (CIP) is used as a drug of choice for many bacterial infections; however, long-term therapy and off-site drug accumulation lead to an increased risk of tendinitis and peripheral neuropathy. To overcome this issue, nanotechnology is being exploited to encapsulate antibiotics within polymeric structures, which not only facilitates dose maintenance at the infection site but also limits off-site side effects. Here, sodium alginate (SA) and thiol-anchored chitosan (TC) were used to encapsulate CIP via a calcium chloride (CaCl) cross-linker. For this purpose, the B-390 encapsulator was employed in the preparation of nanobeads using a simple technique. The hydrogel-like sample was then freeze-dried, using trehalose or mannitol as a lyoprotectant, to obtain a fine dry powder. Design of Experiment (DoE) was utilized to optimize the nanobead production, in which the influence of different independent variables was studied for their outcome on the polydispersity index (PDI), particle size, zeta potential, and percentage encapsulation efficiency (% EE). In vitro dissolution studies were performed in simulated saliva fluid, simulated gastric fluid, and simulated intestinal fluid. Antibacterial and anti-inflammatory studies were also performed along with cytotoxicity profiling. By and large, the study presented positive outcomes, proving the advantage of using nanotechnology in fabricating new delivery approaches using already available antibiotics.
PubMed: 38931815
DOI: 10.3390/pharmaceutics16060691 -
Nutrients Jun 2024Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there...
Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.
Topics: Humans; Carpal Tunnel Syndrome; Vitamin D; Female; Vitamin D Deficiency; Male; Middle Aged; Electromyography; Adult; Treatment Outcome; Dietary Supplements; Adrenal Cortex Hormones; Median Nerve; Aged
PubMed: 38931299
DOI: 10.3390/nu16121947 -
Journal of Clinical Medicine Jun 2024: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes.... (Review)
Review
: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. : The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. : Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). : The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.
PubMed: 38930142
DOI: 10.3390/jcm13123604 -
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