Clinical characteristics, treatment modalities, and potential contributing and prognostic factors in patients with bone metastases from gynecological cancers: A systematic review

The purpose of this study is to review the clinical characteristics, treatment modalities, and potential contributing and prognostic factors of bone metastases from gynecological cancers (GCs). A systematic literature search on PubMed, Scopus, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases was conducted. Thirty-one studies, all retrospective, were included in this review, for a total of 2880 patients with GC bone metastases. Primary tumors leading to bone metastases included endometrial cancer (EC), cervical cancer (CC), ovarian cancer (OC), uterine sarcoma (US) and vulvar cancer (VuC), mainly with an International Federation of Gynecology and Obstetrics (FIGO) Stage of III and IV. The main bone metastatic lesion site was the vertebral column, followed by the pelvic bone and lower extremity bones. The median survival rate after bone metastases diagnosis ranged from 3.0 to 45 months. The most frequent treatments were palliative and included radiotherapy and chemotherapy, followed by surgery. The findings of this review give a first dataset for a greater understanding of GC bone metastases that could help clinicians move toward a more “personalized” and thus more effective patient management

Design and characterization of a minimally invasive bipolar electrode for electroporation

Objective: To test a new bipolar electrode for electroporation consisting of a single minimally invasive needle. Methods: A theoretical study was performed by using Comsol Multiphysics® software. The prototypes of electrode have been tested on potatoes and pigs, adopting an irreversible electroporation protocol. Different applied voltages and different geometries of bipolar electrode prototype have been evaluated. Results: Simulations and pre-clinical tests have shown that the volume of ablated area is mainly influenced by applied voltage, while the diameter of the electrode had a lesser impact, making the goal of minimal-invasiveness possible. The conductive pole’s length determined an increase of electroporated volume, while the insulated pole length inversely affects the electroporated volume size and shape; when the insulated pole length decreases, a more regular shape of the electric field is obtained. Moreover, the geometry of the electrode determined a different shape of the electroporated volume. A parenchymal damage in the liver of pigs due to irreversible electroporation protocol was observed. Conclusion: The minimally invasive bipolar electrode is able to treat an electroporated volume of about 10 mm in diameter by using a single-needle electrode. Moreover, the geometry and the electric characteristics can be selected to produce ellipsoidal ablation volumes

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

The clinical strategies for tendon repair with biomaterials: A review on rotator cuff and Achilles tendons

Tendon repair is a complex process due to the low tenocyte density, metabolism, and vascularization. Tears of rotator cuff (RCT) and Achilles tendons ruptures have a major impact on healthcare costs and quality of life of patients. Scaffolds are used to improve the healing rate after surgery and long-term results. A systematic search was carried out to identify the different types of scaffolds used during RCT and Achilles tendon repair surgery in the last 10 years. A higher number of clinical studies were reported on RCT ruptures. Biological scaffolds were used more than synthetic ones, for both rotator cuff and Achilles tendons. Moreover, platelet-rich plasma (PRP)-based scaffolds were the most widely used in RCT. A different type of synthetic scaffold was used in each of the five studies found. Biological scaffolds either provide variable results, in particular PRP-based ones, or poor results, such as bovine equine pericardium. All the synthetic scaffolds demonstrated a significant increase in clinical and functional scores in biomechanics, and a significant decrease in pain and re-tear rate in comparison to conventional surgery. Despite the limited number of studies, further investigation in the clinical use of synthetic scaffolds should be carried out

Bone morphogenetic protein-2 signaling in the osteogenic differentiation of human bone marrow mesenchymal stem cells induced by pulsed electromagnetic fields

Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components

Pulsed Electromagnetic Fields Modulate miRNAs During Osteogenic Differentiation of Bone Mesenchymal Stem Cells: a Possible Role in the Osteogenic-angiogenic Coupling

Despite the high intrinsic ability of bone tissue to regenerate, bone healing fails in some pathological conditions and especially in the presence of large defects. Due to the strong relationship between bone development and vascularization during in vivo bone formation and repair, strategies promoting the osteogenic-angiogenic coupling are crucial for regenerative medicine. Increasing evidence shows that miRNAs play important roles in controlling osteogenesis and bone vascularization and are important tool in medical research although their clinical use still needs to optimize miRNA stability and delivery. Pulsed electromagnetic fields (PEMFs) have been successfully used to enhance bone repair and their clinical activity has been associated to their ability to promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study we investigated the potential ability of PEMF exposure to modulate selected miRNAs involved in the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). We show that, during in vitro hBMSC differentiation, PEMFs up-modulate the expression of miR-26a and miR-29b, which favor osteogenic differentiation, and decrease miR-125b which acts as an inhibitor miRNA. As PEMFs promote the expression and release of miRNAs also involved in angiogenesis, we conclude that PEMFs may represent a noninvasive and safe strategy to modulate miRNAs with relevant roles in bone repair and with the potential to regulate the osteogenic-angiogenic coupling

Effect of strontium substituted f-TCP associated to mesenchymal stem cells from bone marrow and adipose tissue on spinal fusion in healthy and ovariectomized rat

Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted beta-tricalcium phosphate (Sr-beta TCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham-operated (SHAM) Inbred rats. Both SHAM and OVX animals were divided into three groups: Sr-beta TCP, Sr-beta TCP+BMCSs, and Sr-beta TCP+ADSCs. Animals were euthanized 8 weeks after surgery and the spines evaluated by manual palpation, micro-CT, and histology. For both SHAM and OVX animals, the fusion tissue in the Sr-beta TCP+BMSCs group was more solid. This effect was significantly higher in OVX animals by comparing the Sr-beta TCP+BMCSs group with Sr-beta TCP+ADSCs. Radiographical score, based on micro-CT 2D image, highlighted that the Sr-beta TCP+BMCSs group presented a similar fusion to Sr-beta TCP and higher than Sr-beta TCP+ADSCs in both SHAM and OVX animals. Micro-CT 3D parameters did not show significant differences among groups. Histological score showed significantly higher fusion in Sr-beta TCP+BMSCs group than Sr-beta TCP and Sr-beta TCP+ADSCs, for both SHAM and OVX animals. In conclusion, our results suggest that addition of BMSCs to a Sr-beta TCP improve bone formation and fusion, both in osteoporotic and nonosteoporotic animal, whereas spinal fusion is not enhanced in rats treated with Sr-beta TCP+ADSCs. Thus, for conducting cells therapy in spinal surgery BMSCs still seems to be a better choice compared with ADSCs

New deployable expandable electrodes in the electroporation treatment in a pig model: A feasibility and usability preliminary study

The aim of the study is to evaluate the usability aspects of new deployable, expandable, electrode prototypes, in terms of suitability solutions for laparoscopic applications on the liver, endoscopic trans-oral and trans-anal procedures, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility of the electrode under instrumental guidance, compatibility of the electrode with laparoscopic/endoscopic accesses, surgical instruments, and procedural room and safety compatibility. The electroporation was performed on an animal model (Sus Scrofa Large White 60 kg) both in laparoscopy and endoscopy, under ultrasound guidance, and in open surgery. Electrodes without divergence, with needles coming out straight, parallel to each other, and electrodes with peripheral needles (four needles), diverging from the electrode shaft axis (electrode with non-zero divergence) have been tested. To cause an evaluable necrosis effect, the number of electrical pulses was increased to induce immediate liver cell death. Histological samples were analyzed by staining with Haematoxylin/Eosin or by immunohistochemical staining to confirm complete necrosis. The prototypes of expandable electrodes, tested in laparoscopy and endoscopy and in open surgery, respectively, are suitable in terms of usability, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility under instrumental guidance, compatibility with laparoscopic/endoscopic accesses, surgical instruments and procedural room safety, patient safety (no bleeding and/or perforation), and treatment efficacy (adequate ablated volume). Electroporation treatment using new deployable expandable electrode prototypes is safe and feasible. Moreover, electrode configurations allow for a gradual increase in the ablated area in consecutive steps, as confirmed by histology and immunohistochemistry