Evaluation of Vitamin D-enriched Bone Graft in Surgically-induced Critical-sized Bone Defects: An Experimental Study.

BACKGROUND: Restoration of bone defects in the craniac vault may require the use of autografts, allografts, xenografts, or synthetic grafts. There are promising data that vitamin D may play a positive role in graft incorporation. The purpose of the present study is the evaluation of the impact of vitamin D addition to human-derived bone grafts in the healing of critical-sized bone defects in porcine skulls. MATERIALS AND METHODS: Four identical critical-sized defects were created in the calvaria of 8 adult Landrace Large White pigs. The first defect was left blank as control, the second defect was filled with human-derived bone graft, the third defect was filled with human-derived bone graft enriched with a low concentration of vitamin D (2 mg/mL), and the fourth defect was filled with human-derived bone graft enriched with a high concentration of vitamin D (10 mg/mL). The animals were sacrificed after 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation (bone volume/tissue volume) was quantitatively measured by histomorphometry. RESULTS: Signs of bone formation were evident in all bone sockets. Mean values of the bone volume/tissue volume of the 4 defects were 10.91%, 11.05%, 10.40% and 10.87% respectively, at 12 weeks. In 5 animals, high concentration of vitamin D caused a significant improvement in bone formation in relation to controls. In 3 animals, a high concentration of vitamin D was associated with decreased bone formation compared with controls. No statistical difference was observed in the graft healing among the 4 graft sites ( P > 0.05). CONCLUSIONS: The results of this study have shown that the addition of vitamin D to human-derived bone grafts does not have a significant effect on bone formation and graft incorporation in critical-sized bone defects of the porcine calvaria. Further high-quality studies are needed to fully elucidate the role of vitamin D in bone formation and bone graft union.

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.

COVID-19: A Greek Perspective.

Greece has managed to timely and properly implement a public health safety plan and contained the burden of the coronavirus disease (COVID-19) pandemic. On the contrary, COVID-19 has led to a national catastrophe in countries with superior infrastructures, such as Italy, Spain, France, and the United States. At a time when our nation's healthcare resources were insufficient to meet this unprecedented demand, it was necessary to prioritize needs in the hopes of maximizing lives saved. Although delaying definitive treatment of disorders presented a risk to specific individuals, countless others afforded life-saving resources necessary to overcome the most threatening manifestation of this illness. The cataclysm of COVID-19 offered an opportunity to reshape health care in ways that may not have seemed possible just a few months ago. To help scientists and clinicians across disciplines connect their strengths, so that together we can advance the state of the art in medicine and lead the way to a new era of computational medicine.

Association of postoperative fluid overload with adverse outcomes after congenital heart surgery: a systematic review and dose-response meta-analysis.

BACKGROUND: Pediatric cardiac surgery is commonly associated with acute kidney injury (AKI) and significant fluid retention, which complicate postoperative management and lead to increased rates of morbidity. This meta-analysis aimed to accumulate current literature evidence and evaluate the correlation of fluid overload degree with adverse outcome in patients undergoing congenital heart surgery. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar were systematically searched from inception. All studies reporting the effects of fluid overload on postoperative clinical outcomes were selected. A dose-response meta-analytic method using restricted cubic splines was implemented in R-3.6.1. RESULTS: Twelve studies were included, with a total of 3111 pediatric patients. Qualitative synthesis indicated that fluid overload was linked to significantly higher risk of mortality, AKI, prolonged hospital, and intensive care unit (ICU) stay, as well as with increased duration of mechanical ventilation, inotrope need, and infection rate. Meta-analysis demonstrated a linear correlation between fluid overload and the risk of mortality (χ2 = 6.22, p value = 0.01) and AKI (χ2 = 35.84, p value < 0.001), while a positive curvilinear relationship was estimated for the outcomes of hospital (χ2 = 18.84, p value = 0.0001) and ICU stay (χ2 = 63.69, p value = 0.0001). CONCLUSIONS: The present meta-analysis supports that postoperative fluid overload is significantly linked to elevated risk of prolonged hospital stay, AKI development, and mortality in pediatric patients undergoing cardiac surgery. These findings warrant replication by future prospective studies, which should define the optimal cutoff values and assess the effectiveness of therapeutic strategies to limit fluid overload in the postoperative setting.

Allopurinol Administration for the Prevention of Contrast-Induced Nephropathy: A Network Meta-analysis With Trial Sequential Analysis.

Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although the optimal one remains still unknown. The aim of the present meta-analysis is to accumulate current literature knowledge and evaluate the renoprotective effects of allopurinol administration before contrast medium exposure. To achieve this, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to November 8, 2018. Statistical meta-analysis was conducted with Review Manager 5.3, TSA 0.9.5.5 and R-3.4.3. Six studies were included with a total of 918 patients. Quantitative synthesis revealed that allopurinol leads to significantly reduced incidence of contrast-induced nephropathy compared with hydration alone [odds ratio: 0.29, 95% confidence interval: (0.09-0.90)]. Trial sequential analysis suggested that Z-curve crossed the O'Brien-Fleming significance boundaries, although required information size was not reached. Network meta-analysis indicated that allopurinol had the highest probability (81.2%) to rank as the most effective intervention compared with hydration and N-acetyl cysteine; however, significant overlap with the rest treatments was noted. In conclusion, the present meta-analysis suggests that allopurinol may represent a promising measure for the prevention of acute kidney injury after coronary angiography. Future large-scale randomized controlled trials should verify this finding, while combinations of allopurinol with other novel interventions should be evaluated to define the most effective strategy to be implemented in the clinical setting.

Pharmacological interventions for the prevention of acute kidney injury after pediatric cardiac surgery: a network meta-analysis.

BACKGROUND: Acute kidney injury constitutes a major complication of cardiac surgery in pediatric patients. The present meta-analysis aims to accumulate current literature and assess the efficacy of pharmacological interventions in preventing postoperative renal dysfunction after congenital heart surgery. METHODS: Literature search was conducted using Medline (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials CENTRAL (1999-2018), Clinicaltrials.gov (2008-2018), and Google Scholar (2004-2018) databases. Statistical analysis was performed with Review Manager 5.3 and R 3.4.3. RESULTS: Meta-analysis included 14 studies, with a total of 2,625 patients. AKI incidence was significantly lower in the dexmedetomidine (OR 0.49, 95% CI [0.28-0.87]) and acetaminophen (OR 0.43, 94% CI [0.28-0.67]) groups, while no difference was present in patients receiving corticosteroid (OR 1.16, 95% CI [0.69-1.95]), fenoldopam (OR 0.47, 95% CI [0.22-1.02]), or aminophylline (OR 0.98, 95% CI [0.29-3.34]). Network meta-analysis proposed that dexmedetomidine had the greatest probability (44.5%) to rank first, although significant overlap with the other treatments was observed. CONCLUSIONS: The present meta-analysis suggests that no firm evidence exists about the protective role of pharmacological interventions in the pediatric population. Future randomized controlled trials should clarify the effectiveness of dexmedetomidine and acetaminophen and indicate the optimal protocol to be applied, to protect renal function in the perioperative setting.

The Role of Tolvaptan Administration After Cardiac Surgery: A Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of tolvaptan in fluid management after cardiac surgery compared with conventional diuretic treatment. DESIGN: Systematic review of the literature with meta-analyses. SETTING: The Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to July 30, 2018. PARTICIPANTS: The study comprised 759 patients undergoing cardiac surgery. INTERVENTIONS: Tolvaptan administration (n = 397) or standard diuretic therapy (n = 398). MEASUREMENTS AND MAIN RESULTS: Ten studies were included in the present meta-analysis. Tolvaptan administration was associated with a significantly faster return to preoperative body weight (mean difference [MD)] -1.48 d, 95% confidence interval [CI] -1.92 to 1.03), shorter duration of hospital stay (MD -2.58 d, 95% CI -5.09 to -0.07), lower incidence of acute kidney injury (odds ratio 0.34, 95% CI 0.16-0.69), and greater urine output (MD 0.47 L/d, 95% CI 0.25-0.69) and sodium levels (MD 2.85 mEq/L, 95% CI 1.90-3.80). No significant differences were present regarding duration of intensive care unit stay (MD -0.09 d, 95% CI -0.33 to 0.15), arrhythmia incidence (odds ratio 0.58, 95% CI 0.33-1.02), and serum creatinine values (MD -0.08 mg/dL, 95% CI -0.20 to 0.04). CONCLUSIONS: The outcomes of the present meta-analysis suggest the promising role of tolvaptan administration in the management of fluid retention in patients after cardiac surgery. Future large-scale clinical trials should be conducted to fully elucidate its efficacy and to assess the optimal treatment protocol to be applied in the clinical setting.

Per os colchicine administration in cholesterol fed rabbits: Triglycerides lowering effects without affecting atherosclerosis progress.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease that is promoted, among others, by pro-inflammatory cytokines such as IL-1ß and IL-18 produced by NLRP 3 inflammasome. Development of atherosclerotic lesions is also affected by leptin. Furthermore, inflammasome's action is interfered with other inflammatory diseases, like diabetes. On the other hand, colchicine is reported to act as anti-inflammatory agent inhibiting inflammasome's action and stabilizing atherosclerotic lesions. The purpose of this study is to investigate the effect of per os colchicine on the de novo formation of atherosclerotic lesions and on the levels of IL-18, leptin and insulin in cholesterol-fed rabbits. METHODS: Twenty-three male, 2 months old New Zealand White rabbits, were seperated in 3 groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w and cholesterol 1% w/w plus colchicine 2 mg/kg body weight. Blood was collected for biochemical measurements and conduction of ELISA for leptin, IL-18 and insulin. Histologic examination of stained with eosin and hematoxylin aorta specimens was performed. Aortic intimal thickness was evaluated using image analysis. The statistical analysis included non-parametric tests: a) paired-sample Wilcoxon test, b) Spearman correlation coefficient and c) Kruscal-Wallis test. RESULTS: Triglerycide levels were decreased in cholesterol plus colchicine group in the end of the experiment (p < 0.05), whereas the cholesterol group had increased levels. No statistical differences were observed in the levels of IL-18, leptin and insulin between groups. Likewise, there was neither any correlation between IL-18, leptin and intima thickness nor between IL-18 and glucose and between leptin and weight. In cholesterol and colchicine group there was a strong positive correlation between IL-18 and insulin levels in the 4th week (r s = .66, n = 10, p < 0.05), whereas in the 7th week this correlation became strong negative (r s = -.86, n = 10, p < 0.05). Finally, intima thickness in the ascending and thoracic aorta of the cholesterol and colchicine group was significantly greater than that of the other groups (p < 0.05). CONCLUSIONS: Per os administration of colchicine did not influence atherosclerosis progression in cholesterol-fed rabbits, levels of IL-18, insulin and leptin. We encountered the attenuating role of colchicine on TG levels.

Anticoagulation in Patients with Atrial High-rate Episodes Detected by Cardiac Implantable Electronic Devices.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias that are identified by the use of continuous rhythm monitoring devices such as pacemakers, defibrillators, or implantable cardiac monitors. Nevertheless, the therapeutic implications of these rhythm disturbances remain uncertain. The presence of AHRE is associated with an increased risk of stroke as compared to patients who do not exhibit AHRE. The utilisation of oral anticoagulation has the ability to mitigate the likelihood of stroke occurrence in patients with AHRE. However, it is important to note that this treatment approach is also linked to a severe bleeding rate of approximately 2% per year. The stroke rate among individuals diagnosed with AHRE appears to be comparatively lower when compared to patients diagnosed with atrial fibrillation. The efficacy and safety of anticoagulation in patients with AHRE have yet to be definitively established. Further research is required to provide a comprehensive understanding of the effectiveness and safety of oral anticoagulation in individuals with AHRE.

Perceval-S over time. Clinical outcomes after ten years of usage.

BACKGROUND: Perceval-S has become a reliable and commonly used option in surgical aortic valve replacement (AVR) since its first implantation in humans 15 years ago. Despite the fact that this aortic valve has been proven efficient enough in the short and mid-term period, there is still lack of evidence for the long-term outcomes. MATERIALS AND METHODS: This is an observational retrospective study in a high-volume cardiovascular center. Pertinent data were collected for all the patients in whom Perceval-S was implanted from 2013 to 2020. RESULTS: The total number of patients was 205 with a mean age 76.4 years. Mean survival time was 5.5 years (SE = 0.26). The overall survival probability of patients undergoing aortic valve replacement with Perceval-S at 6 months was 91.0% (Standard Error SE = 2.0%), at one year 88.4% (SE = 2.3%) and at 5-years 64.8% (SE = 4.4%). A detrimental cardiac event leading to death was the probable cause of death in 35 patients (55.6%). The initiation of Transcatheter Aortic Valve Replacement (TAVR) program in our center in 2017 was associated with a decline in the number of very high-risk patients treated with sutureless bioprosthesis. This fact is demonstrated by the significant shift towards lower surgical risk cases, as median Euroscore II was reduced from 5,550 in 2016 to 3,390 in 2020. Mini sternotomy was implemented in 79,5% of cases favoring less invasive approach. Low incidence of reinterventions, patient prosthesis mismatch and structural valve degeneration was detected. CONCLUSIONS: The survival rate after aortic valve replacement with implantation of Perceval-S is satisfactory in the long-term follow-up. Cases of bioprosthesis dysfunction were limited. Mini sternotomy was used in the majority of cases. TAVR initiation program impacted on the proportion of patients treated with Perceval-S with reduction of high-risk patients submitted to surgery.

Residual strains in ascending thoracic aortic aneurysms: The effect of valve type, layer, and circumferential quadrant.

The stress distribution in ascending thoracic aortic aneurysms is determined by the mechanical properties, geometry, loading conditions, and zero-stress state of the aneurysmal aorta. Our objective was to fully characterize the zero-stress state of the aneurysmal aorta in twelve tricuspid aortic valve patients and eight (age/aortic diameter-matched) bicuspid aortic valve patients, for which little data are available. Opening angles and residual stretches were measured for the intact wall and individual layers according to quadrant and were similar in the two patient groups. The intact-wall and medial opening angles were comparable; their circumferential but not their axial ones peaked in the left lateral quadrant, with non-significant regional differences in the other layers. The intima's circumferential opening angles were the highest of all layers (∼300 deg) and the adventitia's the lowest (∼165 deg), with lesser layer differences in the axial opening angles. Upon radially cutting aortic rings, the released circumferential residual stretches were tensile (of large magnitude) externally and compressive (of small magnitude) internally, unlike the axial residual stretches released when cutting intact-wall strips, whose magnitude was small externally and large internally. Nevertheless, large circumferential compressive residual stretches were released in the adventitia upon layer dissection, counteracting the large circumferential tensile stretches of the intact wall externally. Moreover, the large axial tensile residual stretches of the intima counteracted the large axial compressive stretches of the intact wall internally. These layer-specific residual stretches may moderate the in-vivo stress gradients across wall thickness, serving as a protective mechanism against aortic dissection or rupture.

Tumor Markers and Their Diagnostic Significance in Ovarian Cancer.

Ovarian cancer (OC) is characterized by silent progression and late-stage diagnosis. It is critical to detect and accurately diagnose the disease early to improve survival rates. Tumor markers have emerged as valuable tools in the diagnosis and management of OC, offering non-invasive and cost-effective options for screening, monitoring, and prognosis. PURPOSE: This paper explores the diagnostic importance of various tumor markers including CA-125, CA15-3, CA 19-9, HE4,hCG, inhibin, AFP, and LDH, and their impact on disease monitoring and treatment response assessment. METHODS: Article searches were performed on PubMed, Scopus, and Google Scholar. Keywords used for the searching process were "Ovarian cancer", "Cancer biomarkers", "Early detection", "Cancer diagnosis", "CA-125","CA 15-3","CA 19-9", "HE4","hCG", "inhibin", "AFP", "LDH", and others. RESULTS: HE4, when combined with CA-125, shows improved sensitivity and specificity, particularly in early-stage detection. Additionally, hCG holds promise as a prognostic marker, aiding treatment response prediction and outcome assessment. Novel markers like microRNAs, DNA methylation patterns, and circulating tumor cells offer potential for enhanced diagnostic accuracy and personalized management. Integrating these markers into a comprehensive panel may improve sensitivity and specificity in ovarian cancer diagnosis. However, careful interpretation of tumor marker results is necessary, considering factors such as age, menopausal status, and comorbidities. Further research is needed to validate and refine diagnostic algorithms, optimizing the clinical significance of tumor markers in ovarian cancer management. In conclusion, tumor markers such as CA-125, CA15-3, CA 19-9, HE4, and hCG provide valuable insights into ovarian cancer diagnosis, monitoring, and prognosis, with the potential to enhance early detection.

The Role of MicroRNA-126 in Atherosclerotic Cardiovascular Diseases.

Atherosclerotic cardiovascular diseases remain the leading cause of morbidity and mortality worldwide despite all efforts made towards their management. Other than targeting the traditional risk factors for their development, scientific interest has been shifted towards epigenetic regulation, with microRNAs (miRs) being at the forefront. MiR-126, in particular, has been extensively studied in the context of cardiovascular diseases. Downregulated expression of this miR has been associated with highly prevalent cardiovascular risk factors such as arterial hypertension and diabetes mellitus. At the same time, its diagnostic and prognostic capability concerning coronary artery disease is still under investigation, with up-to-date data pointing towards a dysregulated expression in a stable disease state and acute myocardial infarction. Moreover, a lower expression of miR-126 may indicate a higher disease complexity, as well as an increased risk for future major adverse cardiac and cerebrovascular events. Ultimately, overexpression of miR-126 may emerge as a novel therapeutic target in atherosclerotic cardiovascular diseases due to its potential in promoting therapeutic angiogenesis and anti-inflammatory effects. However, the existing challenges in miR therapeutics need to be resolved before translation to clinical practice.

The Complex Relationship Between Diabetes and Cardiac Arrhythmias: Pathophysiology and Mechanisms.

Coronary artery disease, autonomic neuropathy, and diabetic cardiomyopathy are the most common cardiovascular complications of diabetes. However, emerging evidence demonstrates that diabetes also affects the heart's electrical conduction system, culminating in lethal arrhythmias and sudden cardiac death. Diabetes and rhythm disturbances have a complex relationship, and arrhythmias cannot only be attributed to ischemia and autonomic neuropathy. Hypoglycemia, hyperglycemia, and glucose fluctuations can potentially induce arrhythmias by activating various pathways. Structural remodeling can accelerate and exacerbate disease development. Mitochondrial dysfunction can also alter the structure and metabolism of cardiomyocytes and contribute to disease progression through oxidative stress and inflammation.

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.

Ascending aorta mechanics in bicuspid aortopathy: controversy or fact?

Bicuspid aortic valve is the most common congenital cardiovascular defect, often associated with proximal aortic dilatation, and the ideal management strategy is debated. The inconsistency in previous and present guideline recommendations emphasizes the insufficiency of the maximal diameter as the sole criterion for prophylactic repair. Our ability to guide clinical decisions may improve through an understanding of the mechanical properties of ascending thoracic aortic aneurysms in bicuspid compared to tricuspid aortic valve patients and non-aneurysmal aortas, because dissection and rupture are aortic wall mechanical failures. Such an understanding of the mechanical properties has been attempted by several authors, and this article addresses whether there is a controversy in the accumulated knowledge. The available mechanical studies are briefly reviewed, discussing factors such as age, sex, and the region of mechanical examination that may be responsible for the lack of unanimity in the reported findings. The rationale for acquiring layer-specific properties is presented along with the main results from our recent study. No mechanical vulnerability of ascending thoracic aortic aneurysms was evidenced in bicuspid aortic valve patients, corroborating present conservative guidelines concerning the management of bicuspid aortopathy. Weakening and additional vulnerability was evidenced in aged patients and those with coexisting valve pathology, aortic root dilatation, hypertension, and hyperlipidemia. Discussion of these results from age- and sex-matched subjects, accounting for the region- and layer-specific aortic heterogeneity, in relation to intact wall results and histologic confirmation, helps to reconcile previous findings and affords a universal interpretation of ascending aorta mechanics in bicuspid aortopathy.

Percutaneous Coronary Intervention With Drug Eluting Stents Versus Coronary Artery Bypass Graft Surgery in Patients With Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Το perform a systematic review and meta-analysis of the available literature comparing safety and efficacy outcomes between percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in patients with chronic kidney disease (CKD). Eligible studies included patients with eGFR < 60 mL/min/1.73 m2 that underwent revascularization. Subgroup analyses according to DES generation and dialysis status were performed. A total of 7157 and 8156 patients were included in the CABG and PCI arms respectively across 16 studies eligible studies. Weighted mean age was 68.6 and 63.8 years for the CABG and PCI arms, respectively. Mean follow-up time was 3.2 and 2.9 years respectively. Compared to CABG, PCI was associated with increased risk for all-cause mortality (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.13, 1.46; P < 0.01), cardiac mortality (HR: 1.59, 95% CI: 1.13, 2.23; P = 0.01), myocardial infarction (MI) (HR: 1.89, 95% CI: 1.43, 2.49; P < 0.01), and repeat revascularization (HR: 2.97, 95% CI: 2.20, 3.97; P < 0.01). Risk for stroke was lower (HR: 0.64, 95% CI: 0.50, 0,81; P < 0.01) in the PCI group. These results were unchanged when 1st or 2nd DES were used. A subgroup analysis showed no difference in all-cause mortality for DES PCI vs CABG in dialysis patients (HR: 1.11, 95% CI: 0.71, 1.73; P = 0.65). In patients with CKD, PCI is associated with higher risk of mortality, MI, and repeat revascularization compared with CABG and regardless of DES generation. Risk of stroke is higher with CABG. Type of revascularization had no impact on survival of dialysis patients.

Possible Roles of Vitamin D in Bone Grafting.

Bone grafting is one of the most commonly used options to treat large bone defects. Evidence has shown that vitamin D may affect osseointegration, a major component for successful bone grafting. In vitro studies have proved that implants coated with activated vitamin D stimulate bone production and reduce bone resorption around implants. Animal studies have noticed that oral administration of vitamin D may stimulate bone formation as well as strengthen and support the interaction between bone and implants. Vitamin D insufficiency may affect negatively the cortical peri-implant bone formation, suggesting a negative effect in graft incorporation. Few clinical studies have observed that vitamin D administration enhanced graft incorporation and bone formation, while severe vitamin D deficiency is associated with failed implant osseointegration. Even though there are encouraging results of vitamin D supplementation on graft incorporation in animal studies, the use of vitamin D as an adjuvant in bone grafting procedures cannot be fully supported at the moment. However, there is theoretical support in the use of vitamin D after surgery and the use of bone grafts to support the bone structure, relieve pain and increase graft absorption. Further experimental and clinical studies are required to support the administration of vitamin D and its analogues in such cases.

Contemporary ICD Use in Patients with Heart Failure.

Despite constant breakthroughs in heart failure (HF) therapy, the population of HF patients resume to grow and is linked to increased mortality and morbidity. Ventricular arrhythmias (VA) are one of the leading causes of mortality in HF subjects. Implantable cardioverter-defibrillators (ICDs) are currently the gold standard in treatment, preventing arrhythmic sudden cardiac death (SCD) episodes. However, the death rates related to HF remain elevated, as not all HF subjects benefit equally. Cardiac resynchronization therapy (CRT) has emerged as a novel approach for HF patients. These devices have been thoroughly investigated in major randomized controlled studies but continue to be underutilized in various countries. This review discusses the use of ICD in HF populations on top of treatments.

Captopril versus atenolol to prevent expansion rate of thoracic aortic aneurysms: rationale and design.

Thoracic aortic aneurysms are correlated with significant mortality and morbidity. No therapy, however, is effective at limiting aneurysm expansion and preventing rupture. Angiotensin-converting enzyme inhibitors can reduce the wall shear stress and inflammation, both of which play vital roles in the expansion of the aneurysm. A total of 636 patients will be randomized into one of three parallel arms, receiving captopril, atenolol or placebo. The primary end point will be the rate of change in the absolute diameter of the aortic root and ascending aorta on MRI of the aorta after 36 months. The trial will investigate the efficacy of angiotensin-converting enzyme inhibitors versus beta-blocker therapy in reducing the growth rate of thoracic aortic aneurysms and rupture. Trial registration number: NCT04224675.