Ionized jet deposition of silver nanostructured coatings: Assessment of chemico-physical and biological behavior for application in orthopedics.

Infection is one of the main issues connected to implantation of biomedical devices and represents a very difficult issue to tackle, for clinicians and for patients. This study aimed at tackling infection through antibacterial nanostructured silver coatings manufactured by Ionized Jet Deposition (IJD) for application as new and advanced coating systems for medical devices. Films composition and morphology depending on deposition parameters were investigated and their performances evaluated by correlating these properties with the antibacterial and antibiofilm efficacy of the coatings, against Escherichia coli and Staphylococcus aureus strains and with their cytotoxicity towards human cell line fibroblasts. The biocompatibility of the coatings, the nanotoxicity, and the safety of the proposed approach were evaluated, for the first time, in vitro and in vivo by rat subcutaneous implant models. Different deposition times, corresponding to different thicknesses, were selected and compared. All silver coatings exhibited a highly homogeneous surface composed of nanosized spherical aggregates. All coatings having a thickness of 50 nm and above showed high antibacterial efficacy, while none of the tested options caused cytotoxicity when tested in vitro. Indeed, silver films impacted on bacterial strains viability and capability to adhere to the substrate, in a thickness-dependent manner. The nanostructure obtained by IJD permitted to mitigate the toxicity of silver, conferring strong antibacterial and anti-adhesive features, without affecting the coatings biocompatibility. At the explant, the coatings were still present although they showed signs of progressive dissolution, compatible with the release of silver, but no cracking, delamination or in vivo toxicity was observed.

Histological and histomorphometric analysis of bone tissue using customized titanium meshes with or without resorbable membranes: A randomized clinical trial.

OBJECTIVES: To date, no clinical studies have investigated the effect of using resorbable collagen membrane in conjunction with customized titanium mesh to promote bone formation in guided bone regeneration. Therefore, a non-inferiority analysis (one-sided 95% CI approach) was designed to compare the augmented bone gained using meshes with and without collagen membranes, through histological and histomorphometric investigations. MATERIALS AND METHODS: Thirty patients undergoing bone augmentation procedures at both maxillary and mandible sites were randomly treated with customized titanium meshes alone (M-, n = 15) or covered with resorbable membrane (M+, n = 15), in both cases filled with autogenous bone and xenograft. After 6 months of healing, bone tissue biopsies were taken from the augmented region. The bone tissue (B.Ar), grafting material (G.Ar), and non-mineralized tissue (NMT.Ar) areas were quantified through histomorphometric analysis, as were the osteoid area (O.Ar) and its width. RESULTS: Collagen membrane did not appear to significantly influence the investigated parameters: B.Ar, G.Ar, NMT.Ar, and O.Ar were similar between Group M- (34.3%, 11.5%, 54.1%, 1.95 µm2 , respectively) and Group M+ (35.3%, 14.6%, 50.2%, and 1.75 µm2 , respectively). Considering the overall population, significantly higher rates of newly formed bone were obtained in mandibular sites, while non-mineralized and dense connective tissue rates were higher in the maxilla (p < .05). CONCLUSIONS: The application of collagen membrane over titanium mesh did not lead to significant results. Bone formation appeared significantly different in the maxilla compared with the mandible. Additional studies are required to further investigate the issues observed.

Availability of medical and endovascular therapies for venous thromboembolism: a global survey for World Thrombosis Day.

BACKGROUND: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE). OBJECTIVES: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation. METHODS: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE. Furthermore, we collected information by accessing or contacting national or continental medicines agencies, manufacturers or distributors, and online drug repositories. RESULTS: We obtained data from a total of 69 countries: 33 countries in Europe, 19 in Asia, 7 in the Americas, 9 in Africa, and 1 in Oceania. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists were available in almost all countries, but shortages were recorded in 13%, 19%, and 15% of them, respectively. Direct oral anticoagulants were available in approximately three-quarters of the surveyed countries. At least one parenteral medication for heparin-induced thrombocytopenia was available in 57% of countries and a shortage was reported in 9% of these. Shortage of thrombolytics was recorded in 50% of countries. Overall, at least one type of catheter-directed therapy system was approved for use in 77% of countries and available in 23% of surveyed institutions. Our findings revealed notable geographic disparities in the worldwide availability of VTE therapies, the access to which appeared to be limited by economic and geopolitical factors. CONCLUSION: We anticipate that this comprehensive information will play a pivotal role in highlighting the shortcomings of VTE therapies and the lack of homogeneous availability globally.

Structural and functional validation of a highly specific Smurf2 inhibitor.

Smurf1 and Smurf2 are two closely related member of the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase family and play important roles in the regulation of various cellular processes. Both were initially identified to regulate transforming growth factor-ß and bone morphogenetic protein signaling pathways through regulating Smad protein stability and are now implicated in various pathological processes. Generally, E3 ligases, of which over 800 exist in humans, are ideal targets for inhibition as they determine substrate specificity; however, there are few inhibitors with the ability to precisely target a particular E3 ligase of interest. In this work, we explored a panel of ubiquitin variants (UbVs) that were previously identified to bind Smurf1 or Smurf2. In vitro binding and ubiquitination assays identified a highly specific Smurf2 inhibitor, UbV S2.4, which was able to inhibit ligase activity with high potency in the low nanomolar range. Orthologous cellular assays further demonstrated high specificity of UbV S2.4 toward Smurf2 and no cross-reactivity toward Smurf1. Structural analysis of UbV S2.4 in complex with Smurf2 revealed its mechanism of inhibition was through targeting the E2 binding site. In summary, we investigated several protein-based inhibitors of Smurf1 and Smurf2 and identified a highly specific Smurf2 inhibitor that disrupts the E2-E3 protein interaction interface.

Bactericidal Activity of Silver-Doped Chitosan Coatings via Electrophoretic Deposition on Ti6Al4V Additively Manufactured Substrates.

Prosthetic reconstruction can serve as a feasible alternative, delivering both functional and aesthetic benefits to individuals with hand and finger injuries, frequent causes of emergency room visits. Implant-related infections pose significant challenges in arthroplasty and osteosynthesis procedures, contributing to surgical failures. As a potential solution to this challenge, this study developed a new class of silver (Ag)-doped chitosan (CS) coatings via electrophoretic deposition (EPD) on osseointegrated prostheses for infection therapy. These coatings were successfully applied to additively manufactured Ti6Al4V ELI samples. In the initial phase, the feasibility of the composite coating was assessed using the Thermogravimetric Analysis (TGA) and Attenuated Total Reflection (ATR) techniques. The optimized structures exhibited impressive water uptake in the range of 300-360%. Codeposition with an antibacterial agent proved effective, and scanning electron microscopy (SEM) was used to examine the coating morphology. Biologically, CS coatings demonstrated cytocompatibility when in direct contact with a fibroblast cell line (L929) after 72 h. When exposed to the Staphylococcus epidermidis strain (ATCC 12228), these coatings inhibited bacterial growth and biofilm formation within 24 h. These findings underscore the significant potential of this approach for various applications, including endoprostheses like hip implants, internal medical devices, and transcutaneous prostheses such as osseointegrated limb prosthetics for upper and lower extremities.

Intake and digestibility of two diets for nine-banded armadillos (Dasypus novemcinctus: Linnaeus, 1758) kept under human care.

The study aimed to evaluate metabolic parameters, nutrient intake, and absorption of two diets formulated for Dasypus novemcinctus armadillos under human care. Were studied two diets: D1-a diet with dry dog food, ground beef, and boiled chicken egg with shells; D2-a diet with the same ingredients as D1, with added banana and papaya. Both are mixed in water. The parameters analyzed were body weight (BW), weight gain (WG), maintenance energy requirement (MER), Lee index, biometrics, body condition score, glucose, triglycerides, total cholesterol, and cholesterol fractions for eight male armadillos. Dietary intake (DI) and efficiency, nutrient intake, metabolizable energy, and digestibility coefficient for the diets were evaluated in six male armadillos. The diet that included fruits showed higher BW, WG, MER, Lee index, and better glucose metabolism. Both diets promoted increases in WG and Lee Index, as well as improvements in glucose metabolism. The diet without fruit improved the lipid profile of the animals. D2 presented the highest DI, better dietary efficiency, and higher energy intake but also a lower crude fiber intake. However, it showed the best utilization of gross fiber and all other nutrients. In conclusion, the diets constituted an adequate nutritional option for captive armadillos and can be used in malnutrition and pathological processes recovery. Although both diets were adequate, the nonfruit diet was preferable due to the improved lipid profile.

POMONA: a multiplatform software for modeling seed physiology.

Seed physiology is related to functional and metabolic traits of the seed-seedling transition. In this sense, modeling the kinetics, uniformity and capacity of a seed sample plays a central role in designing strategies for trade, food, and environmental security. Thus, POMONA is presented as an easy-to-use multiplatform software designed to bring several logistic and linearized models into a single package, allowing for convenient and fast assessment of seed germination and or longevity, even if the data has a non-Normal distribution. POMONA is implemented in JavaScript using the Quasar framework and can run in the Microsoft Windows operating system, GNU/Linux, and Android-powered mobile hardware or on a web server as a service. The capabilities of POMONA are showcased through a series of examples with diaspores of corn and soybean, evidencing its robustness, accuracy, and performance. POMONA can be the first step for the creation of an automatic multiplatform that will benefit laboratory users, including those focused on image analysis.

Gender-Specific Differences in Human Vertebral Bone Marrow Clot.

Recently, our group described the application of vertebral bone marrow (vBMA) clot as a cell therapy strategy for spinal fusion. Its beneficial effects were confirmed in aging-associated processes, but the influence of gender is unknown. In this study, we compared the biological properties of vBMA clots and derived vertebral mesenchymal stem cells (MSCs) from female and male patients undergoing spinal fusion procedures and treated with vBMA clot. We analyzed the expression of growth factors (GFs) in vBMA clots and MSCs as well as morphology, viability, doubling time, markers expression, clonogenicity, differentiation ability, senescence factors, Klotho expression, and HOX and TALE gene profiles from female and male donors. Our findings indicate that vBMA clots and derived MSCs from males had higher expression of GFs and greater osteogenic and chondrogenic potential compared to female patients. Additionally, vBMA-clot-derived MSCs from female and male donors exhibited distinct levels of HOX and TALE gene expression. Specifically, HOXA1, HOXB8, HOXD9, HOXA11, and PBX1 genes were upregulated in MSCs derived from clotted vBMA from male donors. These results demonstrate that vBMA clots can be effectively used for spinal fusion procedures; however, gender-related differences should be taken into consideration when utilizing vBMA-clot-based studies to optimize the design and implementation of this cell therapy strategy in clinical trials.

Impact of Care Interventions on the Survival of Patients with Cardiac Chest Pain.

BACKGROUND: Chest pain is considered the second most frequent complaint among patients seeking emergency services. However, there is limited information in the literature about how the care provided to patients with chest pain, when being attended to in the emergency room, influences their clinical outcomes. AIMS: To assess the relationship between care interventions performed on patients with cardiac chest pain and their immediate and late clinical outcomes and to identify which care interventions were essential to survival. METHODS: In this retrospective study. We analyzed 153 medical records of patients presenting with chest pain at an emergency service center, São Paulo, Brazil. Participants were divided into two groups: (G1) remained hospitalized for a maximum of 24 h and (G2) remained hospitalized for between 25 h and 30 days. RESULTS: Most of the participants were male 99 (64.7%), with a mean age of 63.2 years. The interventions central venous catheter, non-invasive blood pressure monitoring, pulse oximetry, and monitoring peripheral perfusion were commonly associated with survival at 24 h and 30 days. Advanced cardiovascular life support and basic support life (p = 0.0145; OR = 8053; 95% CI = 1385-46,833), blood transfusion (p < 0.0077; OR = 34,367; 95% CI = 6489-182,106), central venous catheter (p < 0.0001; OR = 7.69: 95% CI 1853-31,905), and monitoring peripheral perfusion (p < 0.0001; OR = 6835; 95% CI 1349-34,634) were independently associated with survival at 30 days by Cox Regression. CONCLUSIONS: Even though there have been many technological advances over the past decades, this study demonstrated that immediate and long-term survival depended on interventions received in an emergency room for many patients.

Effects of dietary copper and zinc hydroxychloride supplementation on bone development, skin quality and hematological parameters of broilers chickens.

This study was carried out to evaluate the effects of supplementation with different levels of copper (Cu) and zinc (Zn), using two mineral sources (sulphate and hydroxy forms), on the bone characteristics, skin strength/elasticity, and haematological parameters of broilers. A total of 1792 1-day-old male Cobb-500 broiler chickens were randomly distributed among eight dietary treatments, using Cu sulphate (CSM) or hydroxychloride (CHC), and Zn sulphate (ZSM) or hydroxychloride (ZHC). The dietary treatments were as follows: (1) low-CSM/high-ZSM, (2) high-CSM/high-ZSM, (3) low-CHC/low-ZHC, (4) low-CHC/medium-ZHC, (5) low-CHC/high-ZHC, (6) high-CHC/low-ZHC, (7) high-CHC/medium-ZHC, and (8) high-CHC/high-ZHC. On Day 42, blood samples were collected from one bird/pen to analyze the haematological parameters. Finally, two birds/pen were slaughtered, and the tibia and femur were collected to analyze the quality of bone and skin. The means were subjected to ANOVA and, when significant, compared by Tukey's test (p < 0.05) or Dunnett's (p < 0.05) test. The haematological parameters were not influenced by mineral supplementation. However, the inclusion of low ZHC enhanced the skin strength compared to high ZHC (p = 0.046). Furthermore, the bone mineral density of the tibia proximal epiphysis, tibia ash and tibia mineral content were positively improved with supplementation of low-CHC/medium-ZHC compared to high-CHC/medium-ZHC. This study demonstrated that hydroxy compounds are potential alternatives for replacing sulphate supplements in broiler diets. Moreover, among the Cu and Zn levels, the low CHC (15 mg/kg) and medium ZHC (100 mg/kg) improved bone development and skin integrity, suggesting that the combination of Cu and Zn can be a nutritional strategy to prevent the incidence of leg disorders in broilers.

The Effect of Magneto-Priming on the Physiological Quality of Soybean Seeds.

Microwaves have been applied to the drying of seeds of several species due to their maintenance of the quality of the seeds and reduction of time and costs. However, few is known about the effect of microwaves on the increase of the physiological quality of soybean seeds and especially their effects on longevity. Therefore, the use of microwaves as magneto-priming in soybean seeds was the object of study in this work. For this purpose, two soybean cultivars were selected and submitted to the ultra-high frequency (UHF) microwave exposure of 2.45 GHz, in the wavelength of 11 cm, and power of 0.2 W/g, for 15 min. The results showed that this condition of exposure to the microwave brought benefits in both cultivars after treatment. Incremental improvements were observed in the germinability indexes, the seedling length, the water absorption by the seeds, the fresh mass, dry mass, and longevity. The genes related to seed germination and longevity showed superior expression (HSFA3, HSP21, HSP17.6b, EXP, ABI3) with magneto-priming treatment. The data found ensure the use of the technique as a viable option for pre-treatment as magneto-priming in soybean seeds in order to improve seed quality.

Bone Regeneration Guided by a Magnetized Scaffold in an Ovine Defect Model.

The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous hydroxyapatite scaffold, incorporating superparamagnetic Fe3O4 nanoparticles (MNPs), was implanted in a critical bone defect realized in sheep metatarsus. Superparamagnetic nanoparticles functionalized with hyperbranched poly(epsilon-Lysine) peptides and physically complexed with vascular endothelial growth factor (VEGF) where injected in situ to penetrate the magnetic scaffold. The scaffold was fixed with cylindrical permanent NdFeB magnets implanted proximally, and the magnetic forces generated by the magnets enabled the capture of the injected nanoparticles forming a VEGF gradient in its porosity. After 16 weeks, histomorphometric measurements were performed to quantify bone growth and bone-to-implant contact, while the mechanical properties of regenerated bone via an atomic force microscopy (AFM) analysis were investigated. The results showed increased bone regeneration at the magnetized interface; this regeneration was higher in the VEGF-MNP-treated group, while the nanomechanical behavior of the tissue was similar to the pattern of the magnetic field distribution. This new approach provides insights into the ability of magnetic technologies to stimulate bone formation, improving bone/scaffold interaction.

Vertebral Bone Marrow Clot towards the Routine Clinical Scenario in Spine Surgeries: What about the Antimicrobial Properties?

Exploring innovative techniques and treatments to improve spinal fusion procedures is a global challenge. Here, we provide a scientific opinion on the ability of a vertebral bone marrow (vBM) clot to provide a local combined delivery system not only of stem cells, signaling biomolecules and anti-inflammatory factors but also of molecules and proteins endowed with antimicrobial properties. This opinion is based on the evaluation of the intrinsic basic properties of the vBM, that contains mesenchymal stem cells (MSCs), and on the coagulation process that led to the conversion of fibrinogen into fibrin fibers that enmesh cells, plasma but above all platelets, to form the clot. We emphasize that vBM clot, being a powerful source of MSCs and platelets, would allow the release of antimicrobial proteins and molecules, mainly cathelicidin LL- 37, hepcidin, kinocidins and cationic host defense peptides, that are per se gifted with direct and/or indirect antimicrobial effects. We additionally highlight that further studies are needed to deepen this knowledge and to propose vBM clot as multifunctional bioscaffold able to target all the main key challenges for spinal fusion surgery.

Safety and efficacy of autologous bone marrow clot as a multifunctional bioscaffold for instrumental posterior lumbar fusion: a 1-year follow-up pilot study.

Background: Bone marrow aspirate (BMA), when combined with graft substitutes, has long been introduced as a promising alternative to iliac crest bone graft in spinal fusion. However, the use of BMA is limited by the absence of a standardized procedure, a structural texture, and the potential for diffusion away from the implant site. Recently, the potential use of a new formulation of BMA, named BMA clot, has been preclinically described. In this report, we present the results of a prospective pilot clinical study aimed at evaluating the safety and efficacy of autologous vertebral BMA (vBMA) clot as a three-dimensional and multifunctional bioscaffold in instrumented posterior lumbar fusion. Methods: Ten consecutive patients with an indication of multilevel (≤5) posterior spinal fusion due to lumbar spine degenerative diseases were included in the study and treated with vBMA. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and EuroQoL-5L (EQ-5L) preoperatively and at 3 months and 12 months after spinal fusion. Bone fusion quality was evaluated at the 12-month follow-up using the Brantigan classification on radiography (XR) imaging. Bone density was measured on computed tomography (CT) scans at 6 and 12 months of follow-up visits at the intervertebral arches and intervertebral joint areas and expressed in Hounsfield unit (HU). Results: The results indicate a successful posterolateral fusion rate of approximately 100% (considering levels with C, D, and E grades according to the Brantigan classification) at the 12-month follow-up, along with an increase in bone density from 6 to 12 months of follow-up. An improvement in the quality of life and health status following surgery, as assessed by clinical scores (ODI, VAS, and EQ-5L), was also observed as early as 3 months postsurgery. No adverse events related to the vBMA clot were reported. Conclusion: This prospective pilot study demonstrates the effectiveness and safety profile of vBMA clot as an advanced bioscaffold capable of achieving posterior lumbar fusion in the treatment of degenerative spine diseases. This lays the groundwork for a larger randomized clinical study.

Magnesium Alloys in Orthopedics: A Systematic Review on Approaches, Coatings and Strategies to Improve Biocompatibility, Osteogenic Properties and Osteointegration Capabilities.

There is increasing interest in using magnesium (Mg) alloy orthopedic devices because of their mechanical properties and bioresorption potential. Concerns related to their rapid degradation have been issued by developing biodegradable micro- and nanostructured coatings to enhance corrosion resistance and limit the release of hydrogen during degradation. This systematic review based on four databases (PubMed®, Embase, Web of Science™ and ScienceDirect®) aims to present state-of-the-art strategies, approaches and materials used to address the critical factors currently impeding the utilization of Mg alloy devices. Forty studies were selected according to PRISMA guidelines and specific PECO criteria. Risk of bias assessment was conducted using OHAT and SYRCLE tools for in vitro and in vivo studies, respectively. Despite limitations associated with identified bias, the review provides a comprehensive analysis of preclinical in vitro and in vivo studies focused on manufacturing and application of Mg alloys in orthopedics. This attests to the continuous evolution of research related to Mg alloy modifications (e.g., AZ91, LAE442 and WE43) and micro- and nanocoatings (e.g., MAO and MgF2), which are developed to improve the degradation rate required for long-term mechanical resistance to loading and excellent osseointegration with bone tissue, thereby promoting functional bone regeneration. Further research is required to deeply verify the safety and efficacy of Mg alloys.

Complications in Spinal Fusion Surgery: A Systematic Review of Clinically Used Cages.

Spinal fusion (SF) comprises surgical procedures for several pathologies that affect different spinal levels, and different cages are employed in SF surgery. Few clinical studies highlight the role of cages in complications beyond the outcomes. The aim of this systematic review is to collect the last 10 years' worth of clinical studies that include cages in SF surgery, focusing on complications. Three databases are employed, and 21 clinical studies are included. The most-performed SF procedure was anterior cervical discectomy and fusion (ACDF), followed by lumbar SF. The polyetheretherketone (PEEK) cage was the most-used, and it was usually associated with autograft or calcium phosphate ceramics (hydroxyapatite (HA) and tricalcium phosphate (ßTCP)). For lumbar SF procedures, the highest percentages of subsidence and pseudoarthrosis were observed with PEEK filled with bone morphogenetic protein 2 (BMP2) and ßTCP. For ACDF procedures, PEEK filled with autograft showed the highest percentages of subsidence and pseudoarthrosis. Most studies highlighted the role of surgical techniques in patient complications. There are many interacting events that contextually affect the rate of clinical success or failure. Therefore, in future clinical studies, attention should focus on cages to improve knowledge of chemical, biological and topographical characteristics to improve bone growth and to counteract complications such as cage loosening or breaking and infections.

Food preference of nine-banded armadillo (Dasypus novemcinctus, Linnaeus, 1758) under human care.

This study aims to evaluate the food preference of nine banded armadillos kept in captivity, exposed to four different diets: Diet 1 (D1) - dry dog food and ground beef; Diet 2 (D2) - dry dog food, ground beef, and chicken eggs; Diet 3 (D3) - dog food, ground beef, bananas, and papaya; Diet 4 (D4) - dog food, ground beef, chicken eggs, banana, and papaya. To this end, an experiment was carried out for five weeks, the first four of which were for preliminary management and the fifth week for data collection. Frequency of consumption, total intake for each diet, and intake ratio were evaluated. The dietary preference was higher for the diets with a higher protein percentage (D1 and D2), mainly D2, which presented increased demand and intake starting on the fourth day of observation. In second day of observation, D1 presented the higher intake ratio, but D2 gradually replaced it. The diet containing the lowest protein rate (D3) was the least favored on all observation days and evaluations. In conclusion, the food preference of ex-situ armadillos seems to be related to the inclusion of greater amounts of protein, particularly that of animal origin, with eggs being the most appreciated ingredient in this study.

Antiosteoporotic Nanohydroxyapatite Zoledronate Scaffold Seeded with Bone Marrow Mesenchymal Stromal Cells for Bone Regeneration: A 3D In Vitro Model.

BACKGROUND: Bisphosphonates are widely employed drugs for the treatment of pathologies with high bone resorption, such as osteoporosis, and display a great affinity for calcium ions and apatitic substrates. Here, we aimed to investigate the potentiality of zoledronate functionalized hydroxyapatite nanocrystals (HAZOL) to promote bone regeneration by stimulating adhesion, viability, metabolic activity and osteogenic commitment of human bone marrow derived mesenchymal stromal cells (hMSCs). METHODS: we adopted an advanced three-dimensional (3D) in vitro fracture healing model to study porous scaffolds: hMSCs were seeded onto the scaffolds that, after three days, were cut in halves and unseeded scaffolds were placed between the two halves. Scaffold characterization by X-ray diffraction, transmission and scanning electron microscopy analyses and cell morphology, viability, osteogenic differentiation and extracellular matrix deposition were evaluated after 3, 7 and 10 days of culture. RESULTS: Electron microscopy showed a porous and interconnected structure and a uniform cell layer spread onto scaffolds. Scaffolds were able to support cell growth and cells progressively colonized the whole inserts in absence of cytotoxic effects. Osteogenic commitment and gene expression of hMSCs were enhanced with higher expressions of ALPL, COL1A1, BGLAP, RUNX2 and Osterix genes. CONCLUSION: Although some limitations affect the present study (e.g., the lack of longer experimental times, of mechanical stimulus or pathological microenvironment), the obtained results with the adopted experimental setup suggested that zoledronate functionalized scaffolds (GHAZOL) might sustain not only cell proliferation, but positively influence osteogenic differentiation and activity if employed in bone fracture healing.

Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.