Cardiovascular Disease as a Consequence or a Cause of Cancer: Potential Role of Extracellular Vesicles.

Both cardiovascular disease and cancer continue to be causes of morbidity and mortality all over the world. Preventing and treating heart disease in patients undergoing cancer treatment remain an important and ongoing challenge for improving the lives of cancer patients, but also for their survival. Despite ongoing efforts to improve patient survival, minimal advances have been made in the early detection of cardiovascular disease in patients suffering from cancer. Understanding the communication between cancer and cardiovascular disease can be based on a deeper knowledge of the molecular mechanisms that define the profile of the bilateral network and establish disease-specific biomarkers and therapeutic targets. The role of exosomes, microvesicles, and apoptotic bodies, together defined as extracellular vesicles (EVs), in cross talk between cardiovascular disease and cancer is in an incipient form of research. Here, we will discuss the preclinical evidence on the bilateral connection between cancer and cardiovascular disease (especially early cardiac changes) through some specific mediators such as EVs. Investigating EV-based biomarkers and therapies may uncover the responsible mechanisms, detect the early stages of cardiovascular damage and elucidate novel therapeutic approaches. The ultimate goal is to reduce the burden of cardiovascular diseases by improving the standard of care in oncological patients treated with anticancer drugs or radiotherapy.

Bone Regeneration and Oxidative Stress: An Updated Overview.

Bone tissue engineering is a complex domain that requires further investigation and benefits from data obtained over past decades. The models are increasing in complexity as they reveal new data from co-culturing and microfluidics applications. The in vitro models now focus on the 3D medium co-culturing of osteoblasts, osteoclasts, and osteocytes utilizing collagen for separation; this type of research allows for controlled medium and in-depth data analysis. Oxidative stress takes a toll on the domain, being beneficial as well as destructive. Reactive oxygen species (ROS) are molecules that influence the differentiation of osteoclasts, but over time their increasing presence can affect patients and aid the appearance of diseases such as osteoporosis. Oxidative stress can be limited by using antioxidants such as vitamin K and N-acetyl cysteine (NAC). Scaffolds and biocompatible coatings such as hydroxyapatite and bioactive glass are required to isolate the implant, protect the zone from the metallic, ionic exchange, and enhance the bone regeneration by mimicking the composition and structure of the body, thus enhancing cell proliferation. The materials can be further functionalized with growth factors that create a better response and higher chances of success for clinical use. This review highlights the vast majority of newly obtained information regarding bone tissue engineering, such as new co-culturing models, implant coatings, scaffolds, biomolecules, and the techniques utilized to obtain them.

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review.

In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives.

Fractionated Irradiation in Photobiomodulation Therapy of Ankle Sprain.

OBJECTIVE: The aim of this study was to test whether fractionated irradiation in photobiomodulation therapy enhances short-term recovery in patients with moderate severity ankle sprain. DESIGN: Nineteen patients were randomly assigned to one of two groups: one group receiving photobiomodulation therapy combined with the standard rest, icing, compression, and elevation treatment, or a group receiving only standard treatment. Group 1 patients were irradiated using a laser system (635 nm, 15 mW) according to a double-fractionated irradiation scheme consisting of two sessions (4.5 and 9 J/cm) separated by a 30-min time interval. Short-term outcomes (reflectance, pain, and clinical outcomes) were assessed at baseline, 10 days, and 6 wks after treatment. RESULTS: Reflectance data analysis showed significant changes in group 1 (P = 0.027). There was also an ankle function score improvement more in group 1 than in group 2, with a significant short-term effect (P = 0.011) but without significant long-term effects (P = 0.178). Compared with group 2, group 1 had an immediate effect on pain reduction, but no long-term effect (P = 0.074). CONCLUSIONS: Combined with standard treatment, fractionated irradiation photobiomodulation therapy has been shown to have favorable short-term effects on the recovery of patients with ankle sprains, but its long-term effects should be improved.

Aneurysmal bone cyst--clinical and morphological aspects.

AIM: To assess the results of surgical treatment in aneurysmal bone cysts. MATERIALS AND METHODS: 31 patients with aneurysmal bone cysts underwent surgical treatment in our department. In almost half of cases, the lesion was located in the femur. In 12 cases, a pathological bone fracture was the first clinical sign. The treatment consisted in curettage, abrasion of the cavity inner walls using a motorized burr and filling with morsellized bone grafts (autografts ± allografts) or bone substitutes (four cases). Microscopically, the diagnosis relies on cystic spaces filled with blood, divided by fibrous septae consisting in immature bone trabeculae, hemosiderin filled macrophages and fibroblasts. We performed multiple bioptic probes from different levels of the lesion. RESULTS: Macroscopically, the osseous lesion appeared as a multi-loculated blood-filled cavity (cavities separated by septa) in 30 (96.77%) cases and as a solid tumor in one (3.23%) case. At 12 months after surgery, grafts osteointegration was present in 24 cases. At an average follow-up time of six years and four months, refilling with bone grafts was necessary in two cases and no local recurrence was observed. CONCLUSIONS: Aneurysmal bone cyst is most frequent in the second decade of age. Its prevalence in female gender is double compared to the male gender. The positive diagnosis relies on the histopathological examination. Because of the strong relationship with a number of precursor lesions (giant cell tumor, fibrous dysplasia, non-ossifying fibroma, chondroblastoma, osteoblastoma) multiple bioptic probings are mandatory, in order to diagnose, if possible, a primary lesion, which may modify the therapeutic attitude. Treatment by curettage, abrasion of the cavity inner walls and filling with morsellized grafts has very good results. The risk of recurrence is very low.

Immunohistochemistry in diagnosis and surgical treatment of femoral bone metastasis.

BACKGROUND: When the primary tumor is unknown, the biopsy and the histopathological examination (associated with immunohistochemistry and molecular profiling) will identify the type and subtype of the tumor and, if possible, the site of origin. The classification in type and subtype will allow to assess the prognosis and to indicate the most appropriate therapeutic approach. AIM: Identification of the unknown primary tumor by biopsy and immunohistochemistry from the femoral bone metastasis, the clinical results and the survival rate after osteosynthesis ± cement stabilization of the lesion. PATIENTS AND METHODS: 52 patients with femoral metastasis were included in a prospective study. The gender ratio was 30 women/22 men (average age - 64 years and six months; range: 33-82 years). Thirty-three patients had pathologic bone fracture, while 19 had osteolytic lesions without fracture. The mean follow-up for survivors was 34 months (range: 17-56 months). Surgical treatment consisted in hemiarthroplasty, osteosynthesis with DHS (Dynamic Hip Screw), proximal femoral nail, locked centromedullary nail or DCS (Dynamic Condylar Screw) ± cement. In 19 (36.54%) cases, the primary tumor was not known. In these cases, biopsy and histological examination with immunochemistry were performed. Twenty-three (52.27%) patients underwent chemotherapy. Clinical and radiological check-ups were performed every three months in the first year and every six months after that. RESULTS: Pain was ameliorated in all cases. Deambulation was achieved in 45 out of 52 (86.54%) patients. Survival rate was 76.92% (40/52) at six months and 59.61% (31/52) at 12 months. At the end of the follow-up period, 18 (34.61%) patients were alive, 24 (46.15%) were deceased and 10 (19.23%) were lost to follow-up. After eliminating the patients lost to follow-up, the survival rate was 33.33% (9/27) in the pathologic fracture group and 60% (9/15) in the osteolytic lesion without fracture group. CONCLUSIONS: Most of the patients (86%) could be mobilized immediately after surgery. The expected survival rate one year after surgery is around 60%. The goals of osteosynthesis are the same, regardless the location of the lesion and the implant used: pain amelioration, appropriate stability for immediate full weight bearing, durability for patient's life expectancy. All extended osteolytic lesions must be reinforced at the time of the surgical procedure. The presence of a pathologic fracture is a negative prognosis factor for the medium term survival rate.

Osteosynthesis in fractures of the distal third of humeral diaphysis.

OBJECTIVES: To compare the clinical results of osteosynthesis with plate and screws versus anterograde locked intramedullary nail in fractures of the distal third of humeral diaphysis. MATERIAL AND METHODS: 184 patients with fractures of the distal third of humeral diaphysis were included in a prospective study. 82 patients underwent open reduction and internal fixation with plate and screws (Group 1), while in 102 cases, closed reduction and osteosynthesis with locked intramedullary nail was performed (Group 2). The 2 groups were similar in terms of age and gender distribution and pattern of fractures. The function of shoulder and elbow were assessed using the Oxford Shoulder Score (OSS) and Oxford Elbow Score (OES). Operating time, duration of hospital stay, complications and moment of union were recorded. OUTCOMES: 6 months after surgery the average OSS was 44.42 in Group I and 40.23 in Group II, while the mean OES was 40.88 in Group I and 46.54 in Group II. The average duration of the surgical procedure was 87 min in Group1 and 43 min in the nail group (p<0.001).The mean duration of hospital stay was 2.6 days in Group 1 and 1.8 days in Group 2 (p<0.05). The rate of non-unions was 3.66% in the plate group and 2.94% in the retrograde nail group (p>0.05). CONCLUSIONS: The clinical results of the 2 methods of osteosynthesis were similar, but the operating time and the duration of hospital stay were longer after plate osteosynthesis. Shoulder function was slightly impaired in the nail group but not statistically significant.

Extended exposure in difficult total knee arthroplasty using tibial tubercle osteotomy.

OBJECTIVES: In some total knee arthroplasty cases, the usual medial parapatellar approach does not allow the appropriate patellar eversion and the desired exposure of the knee joint. Partial disinsertion of the patellar tendon doesn't substantially improve the surgical exposure and can lead to extensor apparatus weakening and complete secondary ruptures, while the V-Y quadricipital plasty leads to post-op immobilization of the knee, which delays the functional rehabilitation, with negative impact on the range of motion. The tibial tubercle osteotomy, however, allows an extension of the approach in total knee arthroplasty, without endangering the quadricipital extensor apparatus. MATERIAL AND METHODS: In this study we analysed the post-operative results of 11 cases of primary total knee arthroplasty in which a frontal plane osteotomy of the tibial tubercle was performed in addition to the standard medial parapatellar approach, as a result of the patients associated conditions, like rheumatoid arthritis with an extension deficit higher than 150, previous knee synovectomy by arthrotomy, progressive genu varum with more than 150 deviation, varus deviation of the lower limb with previous closing wedge proximal tibial osteotomy or patellar fractures with vicious consolidation. OUTCOMES: Overall, the results were more than satisfactory with a significant increase in the patients mean range of motion and Knee Society Score. There were some post-op issues in some of the patients, but they were adressed accordingly, having no long-term impact on the results. CONCLUSIONS: . We could thus conclude that, in special cases, the frontal plane tibial tubercle osteotomy is an effective technique which can provide a wide approach with appropriate protection of the knee extensor apparatus.

Platelet reactivity in chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common medical problem that may result in significant morbidity and mortality. Platelets are key players in haemostasis and thrombosis, but their role in the development of venous thrombosis is more controversial. AIM: The purpose of this study was to investigate platelet properties in CVI and their interaction with the venular endothelium. METHODS: Human peripheral venules were explanted during leg surgery of patients with CVI and of healthy subjects (C); concurrently, the platelets were isolated from blood samples collected. The techniques used were: fluorescence and electron microscopy and Western-blotting. RESULTS: Compared with the C group, the platelets of patients with CVI are activated, as demonstrated by: (i) cellular modifications, such as alteration of the discoidal shape by the development of extended cytoplasmic filopodia and changes of the cells normal ultrastructure, (ii) biochemical modifications, such as the enhanced protein levels of FAK, p85 PI3K, Akt and src, accounting for activation of alphaIIbbeta3 outside-in signaling, and (iii) apparent higher adhesion to the venular endothelium. We demonstrate in addition, that CVI is accompanied by severe modifications of the ultrastructure of the cells within the venular wall. CONCLUSIONS: In CVI, platelets circulate in an activated state and may contribute to the altered dysfunctional response of the venous wall and to the development of this pathology.

Arthroscopical and histological study of cartilaginous lesions treated by mosaicplasty.

AIM: The aim of our study was to assess macro- and microscopically the knee cartilaginous lesions outcome treated by mosaicplasty. MATERIAL AND METHOD: Our study included 32 patients who underwent mosaicplasty for nondegenerative cartilaginous lesions of the knee and a second look arthroscopy. In 21 patients, minibiopsies from the repaired lesion were performed under arthroscopic control (from the cartilaginous region of the transplanted osteocartilaginous grafts and from the spaces between grafts). All repaired lesions were carefully examined during arthroscopy and all harvested minifragments were studied by optical microscopy (staining method - hematoxylin eosin). RESULTS: Macroscopically, the articular surface of the repaired cartilaginous lesions was smooth and congruent to the adjacent surfaces. The aspect and resistance to compression of grafted area was similar to those of the normal surrounding cartilage. The transferred cartilage maintained its height, being at the level of the neighboring cartilage. One year postoperatively, the limits of the cartilaginous autografts were still visible. Two years postoperatively, these limits were no longer visible. Microscopically, the region of the former lesion was constituted mainly by viable hyaline cartilage. Fibrous cartilaginous tissue was visualized in the spaces between the grafts. CONCLUSIONS: The second look arthroscopy showed that after mosaicplasty the repaired articular surface was smooth, leveled, homogenous and congruent to adjacent cartilage. The spaces between grafts are progressively covered by fibrous cartilaginous tissue with a more textured and uneven surface. Mosaicplasty is a biological surgical technique, which restores the normal osteocartilaginous architecture of the most part of the grafted area. The transplanted osteocartilaginous cylindrical grafts maintain its viability and mechanical properties.