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The Critical Role of the Adipocytokine NOV in Obstructive Sleep Apnea Induced Cardiometabolic Dysfunction: A Review
No full textObstructive sleep apnea (OSA) is highly prevalent and associated with oxidative stress, chronic inflammation, and adverse cardiovascular consequences. The comorbid condition of obesity remains epidemic. Both obesity and OSA are highly comorbid in patients with cardiovascular disease including atrial fibrillation, resistant hypertension, congestive heart failure, and coronary artery disease. Patients with these preexisting cardiovascular conditions should be screened for OSA with a low threshold to treat, even if OSA severity is mild. Nephroblastoma overexpressed (NOV/CCN3) protein has been identified in multiple chronic inflammatory states, most notably in obesity and more recently in OSA, even in the absence of obesity. As such, NOV may represent an important biomarker for oxidative stress in OSA and may lead to a deeper understanding of the relationship between OSA and its clinical sequelae
Postural Tachycardia Syndrome and COVID-19: Focus on Ivabradine Therapy
No full textIn this article we discuss the association of postural orthostatic tachycardia syndrome (POTS) with coronavirus-19 (COVID-19), ivabradine\u27s unique mechanism of action, and its use in POTS patients. We highlight the pathophysiology and common etiologies of POTS, including preceding viral infections, vaccines, trauma, surgeries, and other stressors. COVID-19, a viral illness, has been associated with POTS through a variety of mechanisms that are not yet well understood. The initial management strategy for POTS is largely nonpharmacological, focusing on increasing venous return to the heart through physical therapy or other exercise activities. Ivabradine is a selective inhibitor of the funny sodium channels within the sinoatrial node. This unique mechanism of action allows for the reduction of heart rate without any effect on the heart\u27s ionotropic activity. With an increase in the number of POTS cases, especially during the COVID pandemic, the importance of utilizing new medications and management strategies for POTS becomes imperative. Though ivabradine is currently only approved for the management of patients with coronary artery disease and heart failure by the Food and Drug Administration (FDA), it has also proven to be effective at reducing symptoms among patients with refractory POTS, and thus, should be considered for the management of patients who do not respond to initial treatment strategies
Splanchnic Nerve Block: An Emerging Treatment for Heart Failure
No full textHeart failure (HF) is a disease syndrome whose management is increasingly challenging given the aging population and efficacious management of acute cardiac events. The current treatment options within our armamentarium incompletely address the unmet needs of HF. Splanchnic nerve block (SNB) is a novel technique that targets the greater splanchnic nerve, a potential therapeutic target in HF. However, the technique confers potential adverse side effects and complications that warrant further investigations. In this review paper, we aim to discuss the inextricable role of splanchnic nerve in HF by highlighting their physiological interplay, clinical studies that have exhibited favorable hemodynamic parameters in the context of acute and chronic HF, and common side effects and possible complications from SNB
Repeated Mechanical Thrombectomy for Recurrent Large Vessel Occlusion: A Systematic Review and Meta-Analysis
No full textBackground: Mechanical thrombectomy (MT) is the standard treatment for acute large vessel occlusion (LVO). Recurrent LVO can still occur in patients who already underwent MT for the first LVO. This study aimed to evaluate the efficacy of repeating MT for recurrent LVO. Methods: This meta-analysis of the available literature was conducted to summarize the current evidence regarding repeated MT outcomes in patients with recurrent LVO. All studies with ≥ 1 outcomes of interest were included. The Newcastle-Ottawa Scale (NOS) was used for risk of bias assessment. Results: Twenty studies, 10 observational (n = 21,251 patients) and 10 case reports (n = 10 patients), were included. 266 patients (62.78% females) with recurrent LVO were identified, with an overall prevalence of 1.6% and a mean age of 65.67 ± 16.23 years. Cardio-embolism was the most common mechanism in both times, with a median of 15 days between the first and second LVOs. Compared with pre-intervention, the first and second MTs significantly reduced the National Institute of Health Stroke Scale (NIHSS) score, (mean difference (MD) = −8.91) and (MD = −5.97) respectively, with a significant difference (p = 0.001). The rate of favorable outcome (modified Rankin scale (mRS) score 0–3) was 82.6% and 59.2% after the first and second MTs respectively, with a significant difference (p \u3c 0.001). Conclusion: In properly selected recurrent LVO patients, repeated MT is efficacious and safe. A prior MT procedure should not discourage aggressive treatment as many patients may achieve favorable outcomes
A Tai Chi and Qigong Mind-Body Program for Low Back Pain: A Virtually Delivered Randomized Control Trial
No full textBackground: Mind-body treatments have the potential to manage pain, yet their effectiveness when delivered online for the treatment of low back pain (LBP) is unknown. We sought to evaluate whether a virtually delivered mind-body program integrating tai chi, qigong, and meditation (VDTQM) is effective for treating LBP. Methods: This randomized controlled trial compared VDTQM (n=175) to waitlist control (n=175). Eligible participants were at least 18 years old, had LBP for at least 6 weeks, were not pregnant, had not previously taken tai chi classes, and had not undergone spine surgery within 6 months. The treatment group received a 12-week VDTQM program in live online 60-minute twice-weekly group classes from September 2022 to December 2022. All participants continued their usual activities and care. Primary outcome was pain-related disability assessed by the Oswestry Disability Index (ODI) score. Secondary outcomes included pain intensity, sleep quality, and quality of life (QOL). Intent-to-treat analyses were conducted. Results: Of the 350 participants 278 (79%) were female, mean age was 58.8 years (range: 21–92), 244 (69.7%) completed the 8-week survey, 248 (70.9%) the 12-week, and 238 (68%) the 16 -week. No participants withdrew due to adverse treatment effects. Compared with control group, treatment group experienced statistically and clinically significant improvement in ODI score by −4.7 (95% CI: −6.24 to −3.16, p\u3c.01), −6.42 (95% CI: −7.96 to −4.88, p\u3c.01), and −8.14 (95% CI: −9.68 to −6.59, p\u3c.01) points at weeks 8, 12, and 16, respectively. Treatment group also experienced statistically significant improvement at all time points in the other outcomes. Conclusions: Among adults with LBP, VDTQM treatment resulted in small to moderate improvements in pain-related disability, pain intensity, sleep quality, and QOL. Improvements persisted 1 month after treatment concluded. These findings suggest VDTQM may be a viable treatment option for patients with LBP. Trial registration: clincaltrials.gov Identifier: NCT05801588
The Gut Microbiome and Cross-Reactivity of Food Allergens: Current Understanding, Insights, and Future Directions
No full textThis mini-review examines the emerging role of the gut microbiome in influencing food allergen cross-reactivity. It specifically focuses on how microbial diversity, antigens, and metabolites impact IgE-mediated allergic responses. Cross-reactivity occurs when structurally similar food and microbial antigens trigger hypersensitivities, affecting millions of people worldwide. Recent research underscores the significance of microbial diversity in early life for developing immune tolerance. Beneficial strains, such as Lactobacillus and Bifidobacterium, play a crucial role in supporting the functions of T regulatory cells (Tregs) and immunoglobulin A (IgA). Additionally, we discuss microbial metabolites, particularly short-chain fatty acids (SCFAs), which enhance immune tolerance by promoting Treg differentiation and maintaining gut barrier integrity, thereby reducing allergen entry. However, it is important to note that SCFAs can provoke inflammatory responses under certain conditions, highlighting the necessity for targeted research on their dual effects. Dysbiosis-related intestinal permeability, often referred to as “leaky gut,” can further worsen cross-reactivity. Microbial antigens like lipopolysaccharides (LPS) are known to influence Th2-dominant responses
The Role of Biomarkers Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Peptide (VIP) in Chronic and Episodic Migraines: A Meta-Analysis
No full textBackground. Migraine is a neurological disorder that results in disability accumulation, and there are no blood-based markers for indicating migraine susceptibility. Here, we aimed to evaluate the possible biomarker role of neuropeptides, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP) in chronic (CM) and episodic migraine (EM). Method. PubMed, medRxiv, and Google Scholar databases were searched up to the 7th of September 2022 using the search syntax to define all relevant articles addressing the plasma and serum levels of VIP and PACAP in migraineurs and controls. Concerning bias assessment, the risk of bias in nonrandomized studies-I (ROBINS-I) was assessed. Also, the standardized mean difference (SMD) was measured with a random effects model. Results. Five case-control studies with 503 migraine cases were included. CM patients had elevated VIP levels compared to controls (SMD=0.44, 95% CI 0.25-0.62, p\u3c0.00001). In contrast, PACAP levels were lower in EM patients (SMD=-0.30, 95% CI -0.48 to -0.11, p=0.002). Overall, migraine cases had higher VIP levels (SMD=0.25, 95% CI 0.11-0.39, p=0.0006) but lower PACAP levels (SMD=-0.16, 95% CI -0.30 to -0.03, p=0.020) than controls. Conclusion. The results support the role of VIP and PACAP neuropeptides in migraine pathophysiology. CM patients have significantly higher serum VIP levels, while EM patients have lower serum PACAP levels compared to controls. Further studies should confirm these findings
Botulinum Toxin Therapy in Parkinson Disease-Related Lower Limb Dystonia. an 8 Year Retrospective Review
No full textBackground: Lower extremity dystonia (LED) is a frequent complication of Parkinson disease (PD). Treatment with botulinum neurotoxinA (BoNTA) over 8 years was retrospectively reviewed. Cases 14 patients with LED received an average of 3.86 injections (1–8). Mean interval was 40 weeks (median of 25). Average dose was 182 units. Injections were well-tolerated. Using a 6 point scale, there was an average of 3.37 point improvement in disability after each session, with average duration of 28.56 weeks (median 11 weeks). After mean follow-up of 101 weeks, disabling dystonia was not present in 11 of 14 patients. Conclusions: Botulinum toxin is safe and effective in PD related LED. Good response to the first two injection sessions was significantly associated with greater likelihood of long-term response. Assertive BoNTA dosing may lead to sustained remission of symptoms. As natural history of LED in PD has not been reported, prospective placebo-controlled studies are needed
The CYP4/20-HETE/GPR75 Axis in the Progression Metabolic Dysfunction-Associated Steatosis Liver Disease (MASLD) to Chronic Liver Disease
No full textIntroduction: Metabolic-dysfunction-associated steatosis liver disease (MASLD) is a progressive liver disease from simple steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Chronic liver diseases (CLDs) can lead to portal hypertension, which is a major cause of complications of cirrhosis. CLDs cause structural alterations across the liver through increased contents of extracellular matrix (ECM), driving dysfunction of liver sinusoidal endothelial cells (LSECs) alongside hepatic stellate cells (HSCs) and activated resident or infiltrating immune cells. Bioactive arachidonic metabolites have diverse roles in the progression of MASLD. Both secreted levels of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acid (EET) are elevated in patients with liver cirrhosis. Methods: CLD samples were evaluated for changes in free fatty acids (FFA), cholesterol, bilirubin, bile acid, reactive oxygen species (ROD), lipid peroxidation, myeloperoxidase activity and hydroxyproline levels to evaluate the degrees of liver damage and fibrosis. To address the role of the CYP4/20-HETE/GPR75 axis, we measured the amount and the synthesis of 20-HETE in patients with CLD, specifically during the progression of MASLD. Additionally, we evaluated gene expression and protein levels of GPR75, a high-affinity receptor for 20-HETE across CLD patient samples. Results: We observed an increase in 20-HETE levels and synthesis during the progression of MASLD. Increased synthesis of 20-HETE correlated with the expression of CYP4A11 genes but not CYP4F2. These results were confirmed by increased P4504A11 protein levels and decreased P4504F2 protein levels during the development and progression of MASLD. The gene expression and protein levels of GPR75, the major receptor for 20-HETE, increased in the progression of MASLD. Interestingly, the CYP4A11 and GPR75 mRNA levels increased in steatohepatitis but dramatically dropped in cirrhosis and then increased in patients with HCC. Also, protein levels of P4504A11 and GPR75 mirrored their mRNA levels. Discussion: These results indicate that the CYP4A11 and subsequent GPR75 genes are coordinately regulated in the progression of MASLD and may have multiple roles, including 20-HETE activation of peroxisome proliferator-activated receptor α (PPARα) in steatosis and GPR75 in CLD through either increased cell proliferation or vasoconstriction in portal hypertension during cirrhosis. The abrupt reduction in CYP4A11 and GPR75 in patients with cirrhosis may also be due to increased 20-HETE, serving as a feedback mechanism via GPR75, leading to reduced CYP4A11 and GPR75 gene expression. This work illustrates key correlations associated with the CYP4/20-HETE/GPR75 axis and the progression of liver disease in humans
Atlantoaxial Subluxation and Down Syndrome: A Cross-Sectional Analysis
No full textBackground: Atlantoaxial subluxation (AAS) is a diagnosis describing misalignment of the C1 vertebra relative to C2. Excessive translation of this joint, located adjacent to the medullary brain stem, can lead to devastating neurological consequences. A higher prevalence of AAS within the Down syndrome (DS) population has been well‑established. This study aims to establish a prevalence rate of DS in patients hospitalized for AAS and compare outcomes between AAS patients with and without DS. Methods: This study utilized the National Inpatient Sample (NIS) provided by the Healthcare Cost and Utilization Project (HCUP). In accordance with HCUP 2023 Clinical Classifications Software Refined files, data were queried using the International Classification of Diseases 10th Edition codes for DS and AAS. Demographics, comorbidities, hospital course, and outcomes were examined and compared using binary and linear multivariate regression. IBM SPSS software was used for data analysis. Results: Of the 213,095 patients in the NIS database admitted between 2016 and 2020 with AAS as their primary diagnosis, 7.2% were DS patients. DS patients were significantly younger (26.56 ± 20.81 vs. 49.39 ± 27.63, P \u3c 0.01), less likely to be female (33.30% vs. 52.10%), and had fewer comorbidities (diabetes mellitus, hypertension, and hyperlipidemia) than non‑DS patients. There was no significant difference in likelihood to undergo surgical fusion between DS patients and non‑DS patients with AAS. Conclusion: This large‑scale study using NIS data determined that 7.2% of all patients admitted to hospitals for AAS are DS patients. The analysis of demographics, hospital course, and outcomes can influence the development of treatment protocols for AAS in the DS population