Meniscal Repair with ArthroZheal® an Autologous Bioactive Fibrin Scaffold. A New Technique and Treatment Option.

Injuries of the meniscus often lead to changes in joint biomechanics, which affect the load distribution and contact stresses. The menisci consist of a peripheral vascular region (red zone) and an inner avascular region (white zone). The blood supply plays an important role in the healing of meniscal tears. Surgical treatment of such lesions includes meniscectomy/meniscoplasty and repair, depending on the type of injury, where "meniscoplasty" refers to the treatment modality that occurs under coblation. The application of Autologous Bioactive Matrix (ABM) has been shown to promote healing in such lesions. In addition, a special type of PRF (ArthroZheal®, Vivostat A/S, Allerød, Denmark) has been demonstrated to have healing effects in extracellular matrix synthesis and cell proliferation, as well as regenerative and remodeling effects. This autologous product can be applied directly at the meniscal repair site. We performed a prospective study on meniscus repair with ArthroZheal® alone (plus meniscoplasty) and ArthroZheal® together with an all-inside suturing technique using the STAR AccurFix Meniscal Repair Device system (STAR Sports Medicine, Beijing, China), depending on the type and the site of the lesion. One hundred twenty knees (110 patients) were identified through the use of clinical examination and MRI scan. The study took place between January 2023 and August 2023. Two groups were created: GROUP A was treated only with ArthroZheal®(plus meniscoplasty) and GROUP B was treated with a combination of ArthroZheal® and an all-inside suturing technique (STAR AccurFix). Pre- and postoperative grading was performed with the International Knee Documentation Committee (IKDC) score and the Tegner Activity Level Scale (Tegner Score). The results with both treatment methods were excellent and meniscus restoration has been documented on MRIs conducted 6 months post-op. In 15 patients, 2nd-look arthroscopy was performed through a nanoscope on an outpatient basis, and showed meniscal healing and remodeling. Tegner scores and IKDC scores in both groups showed significant improvement. Meniscal repair should be performed at all costs to maintain meniscal integrity and prevent long-term degenerative changes. New treatment methods include orthobiologics and all-inside suturing techniques. The main idea is to apply an autologous biological scaffold which is able to carry cells into the meniscal lesion and to allow their differentiation, proliferation, and extracellular matrix synthesis to produce a meniscal-like tissue. Our results suggest that the application of autologous ABM (ArthroZheal®) for the treatment of such lesions by means of dry arthroscopy results in better MRI, pain management and functional results at 3 months post-op, and these improvements can persist for up to 6 months.

A Rare Case of an Intertrochanteric Hip Fracture Combined with an Ipsilateral Incomplete Atypical Femoral Fracture Treated with a Long Gamma Intramedullary Nail.

Introduction: Osteoporotic hip fractures can occur at the femoral neck and intertrochanteric area, with the peritrochanteric fracture being responsible for half of these fractures in the geriatric population. Atypical femoral fractures have been associated in the literature with long-term use of bisphosphonates or denosumab. However, few cases with the characteristics of these fractures have been reported in the past in patients not receiving antiresorptive drugs. To date, no combination of an intertrochanteric fracture with an impending incomplete atypical fracture of the ipsilateral femoral diaphysis has been previously reported in the literature. Case Report: We present a rare case of a 97-year-old female patient with an intertrochanteric femoral fracture, with a preexisting focal cortical thickening along the lateral aspect of the ipsilateral proximal femoral diaphysis which is a warning sing for an incomplete atypical femoral fracture. A long gamma nail was used to fix the intertrochanteric fracture and simultaneously to stabilize and protect the area of the atypical femoral fracture. Conclusion: Any patient with a peritrochanteric hip fracture who was under long-term treatment with antiresorptive agents against osteoporosis, or has other risk factors predisposing to atypical femoral fracture, should undergo a thorough radiological examination of the ipsilateral femur, to exclude the possibility of simultaneous presence of both of the above pathologies. In any such case, the use of a long hip cephalomedullary nail seems to be the best treatment option, because it can treat both fractures at the same time.

Atypical Femoral Fracture in a Patient without Bisphosphonate or Denosumab Exposure-A Case Report.

Introduction: Atypical femoral fractures (AFF) are associated with the use of bisphosphonates (BPs) or denosumab. However, few cases that meet the characteristics of these fractures, as established by the American Society of Bone and Mineral Research, have occurred in patients who have never used antiresorptive drugs. Case Report: We report a case of AFF in a 67-year-old woman who had never used antiresorptive medications. The history and comorbidities of the patient, the characteristics of the fracture, and the subsequent treatment are presented. Conclusion: AFFs may occur even in patients who have never been exposed to BPs or denosumab. The absence of antiresorptive osteoporosis therapy and the lack of radiographic focal periosteal reaction in the lateral femoral cortex, as in our case, can make it difficult to detect and prevent the disorder. Prolonged use of proton pump inhibitors and Vitamin D deficiency-related osteomalacia may contribute to the occurrence of these fractures. Further studies are required to accurately understand all inciting factors contributing to the development of AFFs.

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients.

BACKGROUND: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). METHODS: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. RESULTS: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. CONCLUSION: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

Prognostic significance of arterial stiffness and osteoprotegerin in patients with stable coronary artery disease.

BACKGROUND: Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question. MATERIALS AND METHODS: We randomly enrolled 262 patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave velocity (PWV) was measured as a well-established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52 months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes. RESULTS: During the follow-up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45 ± 2.19 m/s vs 8.73 ± 2.07 m/s, P = .04) and OPG levels (4.21 ± 2.19 pmol/L vs 3.18 ± 1.74 pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1 m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%. CONCLUSIONS: These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI.

High platelet reactivity is associated with vascular function in patients after percutaneous coronary intervention receiving clopidogrel.

BACKGROUND: In the present study, we evaluated the association of platelet reactivity with vascular function in patients after percutaneous coronary intervention receiving clopidogrel treatment. METHODS: We enrolled 150 patients with stable CAD receiving clopidogrel regimen (75 mg/d), 1 month after percutaneous coronary intervention. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. High on treatment platelet reactivity (HPR) was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU), and the diagnostic cutoff value is 230 PRU. Patients were evaluated prospectively up to 24 months. The primary end point was a composite of death from cardiovascular causes, nonfatal major cardiovascular events and hospitalization for cardiovascular causes. RESULTS: There was no difference in the basic clinical and demographic characteristics between subjects with HPR and non-HPR. Subjects with high on treatment platelet reactivity and PRU>230 had significantly increased PWV (8.81 ± 2.25 m/s vs. 7.69 ± 1.95 m/s, p = 0.001) and AIx (25.27 ± 8.67% vs. 20.87 ± 10.57%, p = 0.04) compared to subjects with PRU≤230. PWV was also associated with PRU (r = 0.23, p = 0.02). HPR was associated with significantly increased risk of primary end point [HR = 5.38, 95%CI:(1.15, 26.04), p = 0.03]. CONCLUSIONS: Increased platelet reactivity is associated with impaired arterial stiffness in patients after percutaneous coronary intervention receiving clopidogrel treatment, highlighting another clinical factor implicated in individual platelet response to antiplatelet therapy. Moreover, increased platelet reactivity is associated with adverse outcome in these patients.

Vitamin D3, D2 and arterial wall properties in coronary artery disease.

OBJECTIVES: There are two major forms of vitamin D, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). We studied the effect of the different vitamin D fractions (D3/D2) on arterial wall properties in coronary artery disease (CAD) patients. METHODS: We included 252 subjects with CAD. Endothelial function was evaluated by flow mediated dilation (FMD). Carotid femoral pulse wave velocity (PWV) was measured as an index of arterial stiffness and augmentation index (AI) as a measure of reflected waves. Measures for 25(OH)D2 and 25(OH)D3 were performed using Liquid Chromatography Mass Spectrometry technology. RESULTS: From the study population, 155(62%), 66(26%) and 31(12%) were categorized as having vitamin D deficiency, insufficiency and sufficiency respectively. There was no difference between subjects with vitamin D deficiency, insufficiency and sufficiency in FMD, AI and PWV (p=NS for all). Subjects with vitamin D insufficiency/deficiency had significantly higher D2 to D ratio compared to subjects with vitamin D sufficiency. Interestingly, FMD was positively associated with D2 to D ratio (rho=0.13, p=0.02) and subjects with D2 levels<0.3ng/ml had impaired FMD compared to those with increased D2 levels (p=0.048). CONCLUSION: Vitamin D insufficiency/deficiency is highly prevalent in CAD subjects. Vitamin D2 concentrations are positively associated with endothelial function. These findings may suggest a beneficial role of vitamin D2 levels in vascular health.

Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MetS) is associated with adverse cardiovascular events, and impaired vascular function. In this study we evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on vascular function, inflammatory and fibrinolytic process in subjects with MetS. METHODS: We studied the effect of a 12 weeks oral treatment with 2 g/day of omega-3 PUFAs in 29 (15 male) subjects (mean age 44 ± 12 years) with MetS on three occasions (day0: baseline, day 28 and day 84). The study was carried out on two separate arms (PUFAs and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. The diagnosis of MetS was based on the guidelines of Adult Treatment Panel III definition. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Serum levels of interleukin-6(IL-6) and plasminogen activator inhibitor-1(PAI-1) were measured by ELISA. RESULTS: Treatment with PUFAs resulted in a significant improvement from day 0 to 28 and 84 in FMD and PWV (p < 0.001 for all). Nevertheless, treatment with placebo resulted in no significant changes in FMD (p = 0.63) and PWV (p = 0.17). Moreover, PUFAs treatment, compared to placebo, decreased IL-6 levels (p = 0.03) and increased PAI-1 levels (p = 0.03). Finally, treatment with PUFAs resulted in a significant decrease in fasting triglyceride levels from day 0 to 28 and 84 (p < 0.001) and in serum total cholesterol levels (p < 0.001). CONCLUSIONS: In subjects with MetS, treatment with omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect.

Favorable effects of concord grape juice on endothelial function and arterial stiffness in healthy smokers.

BACKGROUND: Smoking is associated with impaired vascular function. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. Endothelial function and arterial stiffness are surrogate markers of arterial health. We examined the impact of CGJ on arterial wall properties in healthy smokers. METHODS: We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on 3 occasions (day 0 (baseline), day 7, and day 14) in a randomized, placebo-controlled, double-blind, crossover study. Measurements were taken before (pSm), immediately after (Sm0), and 20 minutes after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. RESULTS: Compared with placebo, treatment with CGJ resulted in a significant improvement in pSm values of FMD (P = 0.02) and PWV (P = 0.04). At baseline, smoking decreased FMD in both the CGJ group (P < 0.001) and the placebo group (P < 0.001). Compared with placebo, CGJ treatment prevented the acute smoking-induced decrease in FMD on day 7 (P = 0.02) and day 14 (P < 0.001). Moreover, at baseline, smoking induced a significant elevation in PWV in both the CGJ group (P = 0.02) and the placebo group (P = 0.04). Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 (P = 0.003) and day 14 (P < 0.001). CONCLUSIONS: CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties.

Dose-dependent effects of short term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure.

OBJECTIVES: Statins, beyond their lipid lowering role, exert beneficial effect on endothelial function in patients with atherosclerosis. Aim of the present study was to examine the short term pleiotropic effects of different doses of atorvastatin treatment, on endothelial function, arterial stiffness and indices of left ventricular remodeling in heart failure (HF) patients. METHODS: We studied the effect of 4 weeks administration of atorvastatin in 22 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery and arterial stiffness by augmentation index (AIx). Serum levels of matrix metalloproteinase-9 (MMP-9) and intracellular adhesion molecule-1 (sICAM-1) were measured as biomarkers of left ventricular remodeling and endothelial function, respectively, while, b-type natriuretic peptide (BNP) was measured as a marker of left ventricular function. RESULTS: Compared to baseline, atorvastatin 40 mg/d significantly improved FMD values (3.18 ± 3.03% vs. 5.98 ± 2.49%, p = 0.001) and AIx values (25.98 ± 8.55% vs. 23.09 ± 8.87%, p = 0.046). In addition, compared to baseline measurements, treatment with atorvastatin 40 mg/d resulted in significantly decreased levels of serum logMMP-9 levels (2.47 ± 0.23 ng/ml vs. 2.39 ± 0.24 ng/ml, p = 0.04) and of logICAM-1 levels (2.46 ± 0.13 ng/ml vs. 2.37 ± 0.16 ng/ml, p < 0.001). No significant changes were found after treatment with atorvastatin 10 mg/d in the aforementioned parameters. CONCLUSIONS: Short term treatment with 40 mg/d of atorvastatin exerts beneficial impact on arterial wall properties and on indices of left ventricle remodeling in heart failure patients.

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease.

BACKGROUND: Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients. METHODS: The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD. RESULTS: CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p<0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p<0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p=0.006). Furthermore, PWV was associated with serum OPG levels (r=0.19, p<0.001) and with serum logOPN levels (r=0.10, p=0.049). Multivariate linear regression analysis revealed that increased OPG (p=0.013) and logOPN (p=0.006) levels are associated with 3-vessel CAD and Gensini score (p=0.04 for OPG and p=0.09 for OPN), independently of other known cardiovascular risk factors. CONCLUSION: The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.

Effects of Ω-3 fatty acids on endothelial function, arterial wall properties, inflammatory and fibrinolytic status in smokers: a cross over study.

BACKGROUND: Smoking is associated with endothelial dysfunction and arterial stiffness. Supplementation of Ω-3 PUFAs is associated with better prognosis. Aim of this study was to evaluate the effects of Ω-3 polyunsaturated fatty acids (PUFAs) supplementation on smoking-induced impairment of arterial function. METHODS: We studied the effect of a 12 weeks oral treatment with 2gr/day of Ω-3 PUFAs in 20 healthy smokers on three occasions (day 0:baseline, day 28 and day 84). The study was carried out on two separate arms (Ω-3 fatty acids and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm), immediately and 20min after cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Circulating levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) were measured. RESULTS: Compared with placebo, Ω-3 PUFAs treatment resulted in a significant improvement in pSm values of FMD (p<0.05), AIx (p<0.001) and PWV (p<0.01). Although, acute cigarette smoking decreased FMD and caused an increase in AIx and PWV, Ω-3 PUFAs treatment blunted the acute smoking-induced impairment of FMD (p<0.001), AIx (p<0.05) and PWV (p<0.05) and significantly decreased levels of TNFα (p<0.05) and IL-6 (p=0.01) and increased levels of PAI-1 (p=0.05). CONCLUSIONS: Ω-3 PUFAs improved endothelial function and the elastic properties of the arterial tree in healthy smokers, with a parallel anti-inflammatory effect.