Klotho as an Early Marker of Acute Kidney Injury Following Cardiac Surgery: A Systematic Review.

Acute kidney injury is a common complication following cardiac surgery (CSA-AKI). Serum creatinine levels require a minimum of 24-48 h to indicate renal injury. Nevertheless, early diagnosis remains critical for improving patient outcomes. A PRISMA-compliant systematic review of the PubMed and CENTRAL databases was performed to assess the role of Klotho as a predictive biomarker for CSA-AKI (end-of-search date: 17 February 2024). An evidence quality assessment of the four included studies was performed with the Newcastle-Ottawa scale. Among the 234 patients studied, 119 (50.8%) developed CSA-AKI postoperatively. Serum Klotho levels above 120 U/L immediately postoperatively correlated with an area under the curve (AUC) of 0.806 and 90% sensitivity. Additionally, a postoperative serum creatinine to Klotho ratio above 0.695 showed 94.7% sensitivity and 87.5% specificity, with an AUC of 92.4%, maintaining its prognostic validity for up to three days. Urinary Klotho immunoreactivity was better maintained in samples obtained via direct catheterization rather than indwelling catheter collection bags. Storage at -80 °C was necessary for delayed testing. Optimal timing for both serum and urine Klotho measurements was from the end of cardiopulmonary bypass to the time of the first ICU lab tests. In conclusion, Klotho could be a promising biomarker for the early diagnosis of CSA-AKI. Standardization of measurement protocols and larger studies are needed to validate these findings.

Myocardial Expression of Pluripotency, Longevity, and Proinflammatory Genes in the Context of Hypercholesterolemia and Statin Treatment.

Background: This study sought to assess the effect of statin therapy on myocardial inflammation in a White New Zealand rabbit model of atherogenesis. Methods: The mRNA expression levels of pro-inflammatory, pluripotency, and aging-related markers were quantified following a controlled feeding protocol and statin treatments. Results: Following high-cholesterol diet induction, we observed significant upregulation in the myocardial mRNA levels of MYD88, NF-κB, chemokines (CCL4, CCL20, and CCR2), IFN-γ, interleukins (IL-1ß, IL-2, IL-4, IL-8, IL-10, and IL-18), and novel markers (klotho, KFL4, NANOG, and HIF1α). In contrast, HOXA5 expression was diminished following a hyperlipidemic diet. Both statin treatments significantly influenced the markers studied. Nevertheless, rosuvastatin administration resulted in a greater reduction in MYD88, NF-kB, chemokines (CCL4, CCL20, and CCR2), and interleukins IL-1ß, IL-8, KLF4, NANOG, and HIF1α than fluvastatin. Fluvastatin, on the other hand, led to a stronger decrease in IL-4. Downregulation of IL-2 and IL-18 and upregulation of IFNß and HOXA5 were comparable between the two statins. Notably, rosuvastatin had a stronger effect on the upregulation of klotho and IL-10. Conclusion: Overall, statin therapy significantly attenuated inflammatory, pluripotency, and klotho expression in myocardial tissue under atherogenic conditions. Our findings also highlight the differential efficacy of rosuvastatin over fluvastatin in curtailing proatherogenic inflammation, which could have profound implications for the clinical management of cardiovascular disease.

Raw data were not disclosed in 95% of PubMed-indexed heart failure meta-analyses in 2021: A systematic analysis of transparency.

BACKGROUND: The rising concern of irreproducible and non-transparent studies poses a significant challenge in modern medical literature. The impact of this issue on cardiology, particularly in the subfield of heart failure, remains poorly understood. To address this knowledge gap, we assessed the quality of evidence presented in recent heart failure meta-analyses by exploring several crucial transparency indicators. METHODS: We conducted a cross-sectional study and searched PubMed for meta - analyses themed around heart failure. We included the 100 most recent publications from 2021 and investigated the presence of several indices that are associated with transparency and reproducibility. RESULTS: The vast majority of the papers did not include their raw data (95/100, 95%) nor their analytic code (99/100, 99%). Less than half (42/100, 42%) preregistered their protocol, while only 65/100 (65%) adhered to a reporting guidelines method. Bias calculation for the respective studies included in each meta - analysis was present in 83/100 (83%) papers and publication bias was measured in approximately half (56/100, 56%). CONCLUSIONS: Our study indicates that meta-analyses in the field of heart failure present important information of transparency infrequently. Therefore, reproduction and validation of their findings seems to be practically impossible.

Multivisceral Resection for Locally Advanced Gastric Cancer: A Systematic Review and Evidence Quality Assessment.

Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease control. The aim of the present study was to systematically review all available literature on the postoperative and long-term outcomes of MVR for gastric cancer. The PubMed database was systematically searched by two independent investigators for studies concerning MVR for LAGC. In total, 30 original studies with 3362 patients met our inclusion criteria. R0 resection was achieved in 67.77% (95% CI, 65.75-69.73%) of patients. The spleen, colon and pancreas comprised the most frequently resected organs in the context of MVR. Pancreatic fistulae (10.08%, 95% CI, 7.99-12.63%), intraabdominal abscesses (9.92%, 95% CI, 7.85-12.46%) and anastomotic leaks (8.09%, 95% CI, 6.23-10.45%) constituted the most common postoperative complications. Using the available data, we estimated the mean 1-year survival at 62.2%, 3-year survival at 33.05%, and 5-year survival at 30.21% for the entire cohort. The survival rates were mainly correlated with lymphatic invasion, tumor size and patient age. Therefore, gastrectomy, together with MVR, is feasible and may offer a survival advantage compared to gastrectomy alone or no other surgical treatment in a selected group of patients. Consequently, both patient and tumor characteristics should be carefully assessed to optimize candidate selection.

Transfection of Vein Grafts with Early Growth Response Factor-1 Oligodeoxynucleotide Decoy: Effects on Stem-Cell Genes and Toll-like Receptor-Mediated Inflammation.

The long-term patency of vein grafts is challenged by intimal hyperplasia. We sought to explore the intricate relationships between the transcription factor Egr-1, toll-like receptors (TLRs), and stem cell genes and also assessed oligodeoxynucleotide decoys (ODNs) as a strategy to prevent vein graft failures. A total of 42 New Zealand white rabbits were fed hyperlipidemic chow and classified into three groups. A double-stranded Egr-1 ODN was synthesized and infused in vein grafts prior to anastomosis with the common carotid artery. All vein grafts were retrieved at the conclusion of the predefined experimental period. Real-time quantitative polymerase chain reaction was performed to estimate expression patterns for several genes of interest. MYD88, TLR2-4, TLR8, NF-kB, TNF-α, IFNß, and IFNγ; chemokines CCL4, CCL20, CCR2; numerous interleukins; and stem cell genes KFL4, NANOG, HOXA5, and HIF1α were universally downregulated in the ODN arm compared with the controls. By understanding these multifaceted interactions, our study offers actionable insights that may pave the way for innovative interventions in vascular reconstructions.

Endovascular Treatment of Type A Aortic Dissection: A Systematic Review and Meta-Analysis Using Reconstructed Time-to-Event Data.

OBJECTIVE: The undisputed gold standard of treatment for type A aortic dissections (TAAD) is open surgery. Anecdotal reports have assessed thoracic endovascular aortic repair (TEVAR) as a last resort for highly selected candidates. The present study aims to evaluate endovascular outcomes in TAAD patients who are unsuitable for open surgery whilst having TEVAR-compatible aortic anatomy. METHODS: A PRISMA-compliant systematic search of the PubMed, Scopus, and Cochrane databases was performed up to 19 May 2022. Time-to-event data were reconstructed using Kaplan-Meier curves from the source literature. RESULTS: In 20 eligible studies, 311 patients underwent TEVAR for acute, subacute, or chronic TAAD. Mean age at the time of the operation was 60.70 ± 8.00 years and 75.48% (95% Confidence Interval [CI], 60.33-88.46%) of the included patients were males. Mean operative time was 169.40 ± 30.70 min. Overall, 0.44% (95% CI, 0.00-4.83%) of the cases were converted to salvage open surgery. Technical failure, stroke, and endoleaks occurred in 0.22%, 0.1%, and 8.52% of the cohort, respectively. Thirty-day postoperative complication rate was 7.08% (95% CI, 1.52-14.97%), whereas late complications developed in 16.89% (95% CI, 7.75-27.88%) of the patients. One-, three-, and five-year survival rates were estimated at 87.15%, 82.52% and 82.31%, respectively. Reintervention was required in 8.38% of the cohort over a mean follow-up of 32.40 ± 24.40 months. CONCLUSIONS: TEVAR seems to be feasible in highly selected patients with TAAD who cannot tolerate open surgery. Overcoming technical limitations and acquiring long-term data are warranted to safely define the place of endovascular treatment in the armamentarium of TAAD repair.

Bioprosthetic Valves for Lifetime Management of Aortic Stenosis: Pearls and Pitfalls.

This review explores the use of bioprosthetic valves for the lifetime management of patients with aortic stenosis, considering recent advancements in surgical (SAV) and transcatheter bioprostheses (TAV). We examine the strengths and challenges of each approach and their long-term implications. We highlight differences among surgical bioprostheses regarding durability and consider novel surgical valves such as the Inspiris Resilia, Intuity rapid deployment, and Perceval sutureless bioprostheses. The impact of hemodynamics on the performance and durability of these prostheses is discussed, as well as the benefits and considerations of aortic root enlargement during Surgical Aortic Valve Replacement (SAVR). Alternative surgical methods like the Ross procedure and the Ozaki technique are also considered. Addressing bioprosthesis failure, we compare TAV-in-SAV with redo SAVR. Challenges with TAVR, such as TAV explantation and considerations for coronary circulation, are outlined. Finally, we explore the potential challenges and limitations of several clinical strategies, including the TAVR-first approach, in the context of aortic stenosis lifetime management. This concise review provides a snapshot of the current landscape in aortic bioprostheses for physicians and surgeons.

Differences between Lower Extremity Arterial Occlusion vs. Stenosis and Predictors of Successful Endovascular Interventions.

Background and Objectives: In patients with peripheral artery disease, there is insufficient understanding of characteristics that predict successful revascularization of the lower extremity (LE) chronic total occlusions (CTOs) and baseline differences in demographic, clinical, and angiographic characteristics in patients with LE CTO vs. non-CTO. We aim to explore these differences and predictors of successful revascularization among CTO patients. Materials and Methods: Two vascular centers enrolled LE-CTO patients who underwent endovascular revascularization. Data on demographics, clinical, angiographic, and interventional characteristics were collected. LE non-CTO arterial stenosis patients were compared. A total of 256 patients with LE revascularization procedures were studied; among them, 120 had CTOs and 136 had LE stenosis but no CTOs. Results: Aspirin use (Odds ratio, OR: 3.43; CI 1.32-8.88; p = 0.011) was a positive predictor whereas a history of malignancy (OR: 0.27; CI 0.09-0.80; p = 0.018) was a negative predictor of successful crossing in the CTO group. The CTO group had a higher history of myocardial infarction (29.2 vs. 18.3%, p = 0.05), end-stage renal disease (19.2 vs. 9.6%, p = 0.03), and chronic limb-threatening ischemia as the reason for revascularization (64.2 vs. 22.8%, p < 0.001). They were more likely to have advanced TransAtlantic Inter-Society Consensus (TASC) stages, multi-vessel revascularization procedures, longer lesions, and urgent treatment. Conclusions: The use of aspirin is a positive predictor whereas a history of malignancy is a negative predictor for successful crossing in CTO lesions. Additionally, LE-CTO patients have a higher incidence of comorbidities, which is expected given their higher disease burden. Successful endovascular re-vascularization can be associated with baseline clinical variables.

Mitral valve surgery in octogenarians: Identifying factors that can guide clinical decision-making.

BACKGROUND: Mitral valve surgery in octogenarians is a clinical challenge due to the impact of inherent, age-related comorbidities. Within the context of an aging population, the number of mitral surgery candidates over 80 has been gradually increasing. We sought to evaluate our institutional experience with mitral valve surgery in octogenarians to identify factors that may prove useful during the process of clinical decision-making. METHODS: We retrospectively reviewed our institutional database for all patients over 80 years of age who underwent mitral valve surgery in our department from October 2002 up to February 2021. The primary endpoints of our study were 30-day all-cause mortality and long-term survival after the first postoperative month. RESULTS: In total, 99 octogenarians underwent mitral valve surgery for various types of mitral pathology. In particular, 70 patients underwent mitral valve replacement with or without concomitant procedures and 29 underwent mitral valve repair with or without concomitant procedures. There was no difference between the two approaches in terms of 30-day mortality and long-term survival. Chronic kidney disease and total operative time were independent predicting factors for 30-day mortality. Etiology of mitral valve pathology and EuroSCORE II was independent predicting factors for long-term survival. CONCLUSIONS: The type of mitral valve surgery did not affect 30-day and long-term mortality rates in our study. Renal impairment and EuroSCORE II were independent predictors of 30-day mortality and long-term prognosis, respectively. Rheumatic valve disease was also associated with a poorer prognosis.

The effectiveness of blood flow restriction training in cardiovascular disease patients: A scoping review.

Therapeutic exercise is integral to the comprehensive rehabilitation of patients with cardiovascular disease and, as such, is recommended by the American Heart Association as a valuable and effective treatment method for such patients. The type of exercise applied to these patients is aerobic and resistance exercise with mild intensities and loads to avoid overloading the cardiovascular system. Blood flow restriction exercise is a novel exercise modality in clinical settings that has in many studies a similar effect on muscle hypertrophy, strength, and cardiovascular response to training at a 70% strength level without blood flow restriction. Since this exercise mode does not require high-intensity loads, it can be a safe method for improving muscle strength, cardiovascular endurance, and functionality in cardiovascular patients. Given that, the objective of this review is to assess and summarize existing evidence for the use of blood flow restriction in cardiovascular patients. A scoping review of existing clinical trials was conducted. Eleven studies were examined that suggested the use of blood flow restrictions in cardiovascular patients to achieve improvements in muscle strength, functionality, and cardiovascular parameters such as blood pressure decrease.

MYD88 and Proinflammatory Chemokines in Aortic Atheromatosis: Exploring Novel Statin Effects.

Atherosclerosis is driven by a diverse range of cellular and molecular processes. In the present study, we sought to better understand how statins mitigate proatherogenic inflammation. 48 male New Zealand rabbits were divided into eight groups, each including 6 animals. The control groups received normal chow for 90 and 120 days. Three groups underwent a hypercholesterolemic diet (HCD) for 30, 60, and 90 days. Another three groups underwent HCD for 3 months, followed by normal chow for one month, with or without rosuvastatin or fluvastatin. The cytokine and chemokine expressions were assessed in the samples of thoracic and abdominal aorta. Rosuvastatin significantly reduced MYD88, CCL4, CCL20, CCR2, TNF-α, IFN-ß, IL-1b, IL-2, IL-4, IL-8, and IL-10, both in the thoracic and abdominal aorta. Fluvastatin also downregulated MYD88, CCR2, IFN-ß, IFN-γ, IL-1b, IL-2, IL-4, and IL-10 in both aortic segments. Rosuvastatin curtailed the expression of CCL4, IFN-ß, IL-2, IL-4, and IL-10 more effectively than fluvastatin in both types of tissue. MYD88, TNF-α, IL-1b, and IL-8 showed a stronger downregulation with rosuvastatin compared to fluvastatin only in the thoracic aorta. The CCL20 and CCR2 levels reduced more extensively with rosuvastatin treatment only in abdominal aortic tissue. In conclusion, statin therapy can halt proatherogenic inflammation in hyperlipidemic animals. Rosuvastatin may be more effective in downregulating MYD88 in atherosclerotic thoracic aortas.

Risk of sarcopenia, fear of COVID-19, anxiety, depression and physical activity levels: Associations across patients on hemodialysis within Greece.

Objectives: The purpose of this multicenter cross-sectional study was to investigate the association between SARC-F, fear of COVID 19, anxiety, depression and physical activity in patients undergoing hemodialysis. Methods: This study was conducted in 3 hemodialysis centers in Greece during the period of the COVID-19 pandemic. Sarcopenia risk was assessed using the Greek version of SARC-F (≥4). Demographic and medical history were collected from the patient's medical charts. The participants were also asked to fill the Fear of COVID-19 Scale (FCV-19S), the Hospital Anxiety and Depression Scale (HADS), and the International Physical Activity Questionnaire (IPAQ) questionnaire. Results: A hundred and thirty-two (132) patients on hemodialysis (92 men, 70.75±13.14 years) were enrolled. Sarcopenia risk (utilizing the SARC-F) was found in 41.7% of patients on hemodialysis. The average duration of hemodialysis was 3.94±4.58 years. The mean score values for SARC-F, FCV-19S and HADS were 3.9±2.57, 21.08±5.32, and 15.02±6.69, respectively. The majority of patients were physically inactive. The SARC-F scores were strongly associated with age (r=56; p<0.001), HADS (r=0.55; p<0.001), levels of physical activity (r=0.5; p<0.001), but not with FCV-19S (r=0.27; p<0.001). Conclusion: A statistically significant relationship was recorded between sarcopenia risk and age, anxiety/depression and levels of physical inactivity in patients on hemodialysis. Future studies are necessary in order to evaluate the association of specific characteristics of patients.

Updates on the Global Prevalence and Etiology of Constrictive Pericarditis: A Systematic Review.

Constrictive pericarditis is a rare disease with poorly understood epidemiology. A systematic literature search was adopted to assess the region- and period-specific traits of constrictive pericarditis through Pubmed, EMBASE, and Scopus. Case reports and studies including less than 20 patients were excluded. The risk of bias was assessed through the Study Quality Assessment Tools developed by the National Heart Lung Blood Institute by 4 reviewers. Patient demographics, disease etiology, and mortality were the primary assessed outcomes. One hundred thirty studies with 11,325 patients have been included in this systematic review and meta-analysis. The age at diagnosis of constrictive pericarditis has markedly increased after 1990. Patients from Africa and Asia are considerably younger compared with those from Europe and North America. Moreover, there are differences in etiology, as tuberculosis remains the dominant cause of constrictive pericarditis in Africa and Asia but has been surpassed by history of previous chest surgery in North America and Europe. The human immunodeficiency virus affects 29.1% of patients from Africa diagnosed with constrictive pericarditis, a feature that is not observed on any other continent. The early mortality rate after hospitalization has improved. The variances of age at diagnosis and etiology of constrictive pericarditis should be considered by the clinician during the work-up of cardiac and pericardial diseases. An underlying human immunodeficiency virus infection complicates a significant portion of constrictive pericarditis cases in Africa. Early mortality has improved across the world but remains high.

Aortic valve neocuspidization using the Ozaki technique: A meta-analysis of reconstructed patient-level data.

BACKGROUND: Aortic valve neocuspidization using the Ozaki technique has shown promising results both in adults and children. METHODS: A systematic search of the PubMed and Cochrane databases was performed up to November 13, 2021. Individual patient data were reconstructed and analyzed from the Kaplan-Meier curves of all eligible studies for time-to-event outcomes. RESULTS: We included a total of 22 studies reporting on 1,891 patients that underwent Ozaki reconstruction. Mean age at the time of surgery was 43.2 ± 24.5 years (65 ± 12.3 years for adult patients and 12.3 ± 3.8 years for pediatric patients). The most common indication was aortic stenosis (46.4%, 95% CI 34.1-58.6). Mean cross-clamp and cardiopulmonary bypass duration were 106.8 ± 24.8 minutes and 135.2 ± 35.1 minutes, respectively. Permanent pacemaker was implanted in 0.7% (95% CI 0.4-1.2) of the patients. At discharge, mean effective orifice area was 2.1 ± 0.5 cm2/m2. At latest follow-up, peak gradient was 15.7 ± 7.4 mm Hg and only 0.25% (95% CI 0-2.3) had moderate aortic insufficiency. In-hospital mortality was 0.7% (95% CI 0.1-1.7). Late mortality was 1.9% during a mean follow-up of 38.1 ± 23.8 months. One-year, 3-year, and 5-year freedom from reoperation rates were 98.0 %, 97.0 % and 96.5%, respectively. More than half of the reoperations were due to infective endocarditis (51.5%, 95% CI 18.3-84.0). In our cohort, the risk of endocarditis per patient per year was 0.5%. CONCLUSIONS: The midterm outcomes of the Ozaki procedure are excellent in terms of hemodynamics, survival, and freedom from reoperation. Acquiring long-term follow-up will help solidify this technique in the cardiac surgery armamentarium.

The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.

Gastrectomy for Cancer: A 15-Year Analysis of Real-World Data from the University of Athens.

Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06-4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11-1.65) and recurrence (HR: 2.87; 95% CI: 1.32-6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer.

Neuromuscular control of the lower extremities can be better enhanced by applying ankle taping and kinesiological taping rather than elastic bandaging: a randomized control study in amateur soccer players.

[Purpose] This study evaluated the effects of ankle elastic bandaging, taping, and kinesiology taping on the neuromuscular control of the lower extremities before and after their application and after exercise in soccer athletes. [Participants and Methods] Fifty-five amateur soccer players were randomly divided into four research sub-groups either receiving bandaging (n=15), taping (n=15), and kinesiology taping (n=15) on their ankle or serving as controls (n=10). The dynamic stability of the non-dominant limb was assessed through the star excursion balance test (SEBT) in three research conditions: a) before sports taping application, b) after the application, and c) after a 15 min laboratory simulation of soccer activities. [Results] Taping and kinesiology taping improved the dynamic stabilization of the lower limb more statistically significantly than bandaging. The addition of exercise significantly improved the SEBT results in the taping and kinesiology taping more than the bandaging and control groups. [Conclusion] Exercise activates the proprioceptive mechanisms of the lower limb and improves its neuromuscular control. This functional improvement of the lower limb appears to be enhanced after ankle taping and kinesiology taping compared with elastic bandaging and controls.

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens.

AIMS: Inflammatory dysregulation of mechanosensitive developmental genes may be central to atherogenesis. In the present seven-week model, we utilized colchicine regimens to curtail aortic atherogenesis in New Zealand White rabbits. We also explored the effect of colchicine regimens on atheroprotective (Klotho, HOXA5, NOTCH1, and OCT4) and proatherogenic (HIF1a, SOX2, BMP4, and NANOG) genes. METHODS: The control (n = 6) and group A (n = 6) received standard and cholesterol-enriched chow, respectively. Groups B (n = 8) and C (n = 8) were fed hypercholesterolemic diet and were treated with colchicine plus fenofibrate or N-acetylcysteine (NAC), respectively. RESULTS: Group A developed significantly greater thoracic and abdominal aortic atherosclerosis compared to groups B (p < 0.001) and C (p < 0.001). Combining colchicine with NAC resulted in stronger atheroprotection both in the thoracic and the abdominal aorta. In group A thoracic aortas, Klotho was downregulated compared to controls (95% CI: 1.82-15.76). Both colchicine regimens upregulated Klotho back to baseline levels (p < 0.001). Colchicine/fenofibrate also significantly upregulated thoracic NOTCH1 compared to controls (95% CI: -8.09 to -0.48). Colchicine/NAC significantly reduced thoracic NANOG expression compared to hyperlipidemic diet alone (95% CI: 0.37-8.29). In the abdominal aorta, hypercholesterolemic diet resulted in significant downregulation of HOXA5 (95% CI: 0.03-2.74) which was reversed with colchicine/NAC back to baseline (95% CI: -1.19 to 1.51). Colchicine/fenofibrate downregulated HIF1a compared to baseline (95% CI: 0.83-6.44). No significant differences were noted in terms of BMP4, SOX2, and OCT4. CONCLUSIONS: Overall, the aortic expression pattern of mechanosensitive genes seems to be spatially influenced by a hyperlipidemic diet and can be modified using colchicine-based therapy.

Stem cell genes in atheromatosis: The role of Klotho, HIF1α, OCT4, and BMP4.

During fetal development, shear stress regulates several aspects of vascular development. Alterations in signaling pathways due to disturbed flow in atheroprone regions closely mirror phenomena seen during embryogenesis. This flow-dependent dysregulation of developmental genes appears to promote atherogenesis by mediating inflammatory phenomena, cell cycle progression, apoptosis, cell migration, and oxidative stress. Indeed, several stem cell genes have been implicated in vascular health and atheromatosis. Klotho is key in maintaining endothelial integrity, reducing oxidative stress, and sustaining endothelial nitric oxide production. In atherosclerotic lesions, OCT4 mediates the conversion of vascular smooth muscle cells from contractile to a de-dedifferentiated proliferative phenotype with phagocytic ability. HIF1α drives atherosclerotic plaque progression by promoting intraplaque angiogenesis. BMP4 promotes osteochondrogenic development and arterial calcification. Strategic extracellular matrix changes are also seen during the various phases of atherosclerosis. The aforementioned conceptual framework explains how proatherogenic inflammation develops in response to low shear stress. In the present review, we explored the effect of cardinal atheroprotective (Klotho, OCT4) and proatherogenic (HIF1α, BMP4) genes in mediating proatherogenic inflammation.

Reliability and Validity of Non-radiographic Methods of Forward Head Posture Measurement: A Systematic Review.

Forward head posture measurement can be conducted using various methods and instruments. The selection of the appropriate method requires the factors of validity and reliability to be considered. This systematic review reports on the reliability and validity of the non-radiographic methods examined for measuring forward head posture. The review identified relevant studies following a systematic search of electronic databases. The studies were assessed for quality by two independent reviewers using a critical appraisal tool. The studies' data were extracted and assessed, and the results were synthesized qualitatively using a level of evidence approach. Twenty-one studies met the eligibility criteria and were included in the review. Both reliability and validity were investigated for five studies, whereas reliability only was investigated for 17 studies. In total, 11 methods of forward head posture measurement were evaluated in the retrieved studies. The validity of the methods ranged from low to very high. The reliability of the methods ranged from moderate to excellent. The strongest levels of evidence for reliability support the use of classic photogrammetry. For validity, the evidence is not conclusive. Further studies are required to strengthen the level of evidence on the reliability and validity of the remaining methods. It is recommended that this point be addressed in future research.