Cross-Cultural Adaptation and Validation of the Romanian Musculoskeletal Tumor Society Scoring System for Patients with Extremity Bone Sarcomas.

Background and Objectives: Primary malignant bone tumors are rare lesions, and their complex treatment can lead to functional impairment. It is important to have a postoperative assessment tool for patients' functional outcomes to be evaluated and to consequently adapt future treatments in the pursuit of a continuous improvement of their quality of life. The Musculoskeletal Tumor Society Score (MSTS) is a validated specific system score that is used frequently in the follow-up of these patients. We found no information about a valid translated Romanian version of this score neither for the upper limb nor for the lower limb. We proposed in this study to translate the original version of the MSTS Score into Romanian and to perform validation analysis of the Romanian-language MSTS Score. Materials and Methods: We selected 48 patients who underwent limb-salvage surgery after resection of bone sarcomas. Patients were interrogated twice according to the translated Romanian version of the MSTS Score during their follow-up. The translation was performed according to the recommended guidelines. A total number of 96 questionnaires were valid for statistical analysis. Results: Internal consistency and reliability were good for both sets of questionnaires' analytic measurements, with Cronbach's alpha values of 0.848 (test) and 0.802 (retest). The test-retest evaluation proved to be statistically strong for reproducibility and validity with Spearman's rho = 0.9 (p < 0.01, 95% CI). Conclusions: This study permitted the translation of this score and the validation of psychometric data. Our results showed that the Romanian version of the MSTS is a reliable means of assessment of the functional outcome of patients who received limb-salvage surgery for the upper and lower extremities.

Low-Molecular-Weight Heparins (LMWH) and Synthetic Factor X Inhibitors Can Impair the Osseointegration Process of a Titanium Implant in an Interventional Animal Study.

Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 µm and 86.9 µm) at the peri-implant area, compared to control (43.2 µm and 39.2 µm), enoxaparin (39.6 µm and 24 µm), and fondaparinux (36.2 µm and 32.7 µm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation.

Clinical outcomes after arthroscopically assisted talus fracture fixation.

PURPOSE: The purpose of this article is to describe the novel technique of arthroscopic-assisted reduction and internal fixation (ARIF) of talar neck fractures, presenting also the outcomes of this treatment method in a series of four patients. METHODS: Between 2011 and 2019, we have treated in our service a number of four patients with talar neck fractures, by the arthroscopic technique. The surgical intervention consists in arthroscopic exploration of tibiotalar and subtalar joints, arthroscopic lavage and debridement, reduction, and osteosynthesis with two cannulated screws under both arthroscopic and fluoroscopic control. Post-operative care consists in non-weightbearing immobilization for 6 weeks, followed by partial loading under the protection of a walking brace for the next six weeks and ROM exercises. The patients were followed up at three  months, when a CT scan was performed, and at one year, when X-ray images showed the consolidation of fractures. RESULTS: Normal or slightly reduced ROM of the ankle and hindfoot was noted in three out of four patients, absence of any pain, or disability (3 patients). The AOFAS' Ankle-Hindfoot scale showed good and excellent results; mean score was 92.75 points (86-98p) at one year after the surgery. CONCLUSION: Arthroscopic-assisted management of talar fractures offers the advantages of minimally invasive surgery combined with good visualization of the fracture, good control of anatomic reduction, and the possibility to treat associated lesions. Main disadvantages of the method are technical difficulties, requires a prolonged learning curve, and offers limited fixation alternatives.

Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model.

OBJECTIVES: The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement. MATERIALS AND METHODS: Eighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro-CT, mechanical pull-out test, histology, and bone serum markers. RESULTS: Peri-implant micro-CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri-implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull-out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant. CONCLUSION: The hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.

The impact of proton pump inhibitors on bone regeneration and implant osseointegration.

Proton pump inhibitors (PPIs) have become known for the treatment of gastric-acid related disorders. Similar to any other drugs, PPIs have possible adverse reactions, being associated with bone fractures, infections, kidney disease, mineral deficiency, dementia, and pneumonia. Multiple analyses have stated that PPIs therapy may affect bone regeneration and osseointegration process, causing an increased risk of bone fracture, deterioration of bone metabolism and impaired bone healing. In this review, we emphasized the current literature regarding the influence of proton pump inhibitors in the bone regeneration process. Results from the studies suggest a link between PPIs intake and bone regeneration, but several concerns are raised regarding inadequate recipient bone, surgical trauma, limitations on the titanium surface, comorbidities or interference with other pharmacological agents. Further studies are needed to determine whether the impaired bone regeneration process is due to PPI or coexisting factors.

Cannabinoids and bone regeneration.

Bone is a complex tissue with unique properties such as high strength and regeneration capabilities while carrying out multiple functions. Bone regeneration occurs both in physiological situations (bone turnover) and in pathological situations (e.g. fractures), being performed by osteoblasts and osteoclasts. If this process is inadequate, fracture nonunion or aseptic loosening of implants occurs and requires a complex treatment. Exogenous factors are currently used to increase bone regeneration process when needed, such as bisphosphonates and vitamin D, but limitations do exist. Cannabinoid system has been shown to have positive effects on bone metabolism. Cannabinoids at bone level mainly act on two receptors called CB-1 and CB-2, but GPR55, GPR119, TPRV1, TPRV4 receptors may also be involved. The CB-2 receptors are found in bone cells at higher levels compared to other receptors. Endocannabinods represented by anandamide and 2-arachidonoylglycerol, can stimulate osteoblast formation, bone formation and osteoclast activity. CB-2 agonists including HU-308, HU-433, JWH133, and JWH015 can stimulate osteoblast proliferation and activity, while CB-2 antagonists such as AM630 and SR144528 can inhibit osteoclast differentiation and function. CB-1 antagonist AM251 has been shown to inhibit osteoclast differentiation and activity, while GPR55 antagonist cannabidiol increases osteoblast activity and decreases osteoclast function. An optimal correlation of dose, duration, moment of action, and affinity can lead to an increased bone regeneration capacity, with important benefits in many pathological situations which involve bone tissue. As adverse reactions of cannabinoids have not been described in patients under controlled medication, cannabinoids can represent future treatment for bone regeneration.

Systemic drugs with impact on osteoarthritis.

Articular cartilage has a complex structure and metabolism which allow for a proper movement within joints. Nevertheless, several systemically administered pharmacological agents have been proved to improve the anabolic response in the case of cartilage lesions. Alendronate, glucosamine, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, vitamin C, vitamin D, aspirin and strontium ranelate have shown positive results in clinical trials. On the other hand, calcitonin, risedronate, doxycycline, and celecoxib did not slow the progression of cartilage lesions in clinical trials. Other systemic drugs or supplements such as teriparatide, leptin, zoledronic acid, bevacizumab, atorvastatin, omega-3 fatty acid, naringin, MSM, selenium, zinc, magnesium, resveratrol, donepezil, naproxen, etodolac, ursodeoxycholic acid (UDCA), lithium chloride, and rebamipide showed positive results in in vitro and animal studies but clinical trials are needed to confirm the positive impact on cartilage repair. A number of molecules, not currently available on the market, have also shown promising results in cartilage healing, such as licofelone, sclerostin, cyclopamine, cyclodextrin polysulfate, AG-041R, osteoprotegerin, rhMK, ß-cryptoxanthine, NF-κb essential modulator binding domain (NBD), TGF-ß-neutralizing antibody, osteogenic protein-1 (BMP-7), fibroblast growth factor 2 (FGF2), and RhBMP-2. Currently available systemic drugs that impair cartilage healing are represented by corticosteroids, vitamin A, and fluoroquinolones.

Comparing the Effect of Tourniquet vs Tourniquet-Less in Simultaneous Bilateral Total Knee Arthroplasties.

BACKGROUND: Total knee arthroplasty (TKA) is a commonly performed procedure worldwide for the treatment of knee joint disease. Tourniquet is frequently used during the entire procedure to reduce blood loss and increase surgical comfort. On the other hand, tourniquet-related complications exist, and there are still controversies whether benefits outweigh the risks. METHODS: Patients undergoing simultaneous TKAs had one knee assigned to group A (use of tourniquet during the entire procedure) and the other knee assigned to group B (use of tourniquet only during cementation). Blood loss, intraoperative complications, implant alignment, soft tissue swelling, pain score, and range of motion were analyzed. RESULTS: Fifty-four patients undergoing 108 TKAs were included in the study. Total blood loss was almost 2 times higher in group B knees compared with group A. No difference was observed between groups in implant alignment, soft tissue swelling, pain, range of motion, or other early postoperative complications. CONCLUSION: Tourniquet use in TKAs during the entire surgical procedure reduces total blood loss, without an increase in early postoperative complications.

Systemic drugs that influence titanium implant osseointegration.

Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, innovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments. Anabolic bone-acting agents include parathyroid hormone (PTH) peptides, simvastatin, prostaglandin EP4 receptor antagonist, vitamin D and strontium ranelate; anti-catabolic bone-acting agents include compounds like calcitonin, biphosphonates, RANK/RANKL/OPG system and selective estrogen receptor modulators (SERM). Examples of the new therapies include DKK1- and anti-sclerostin antibodies. All classes of treatments have proven to possess positive impacts such as an increase in bone mineral density and on osseointegration. In order to prevent complications from occurring after surgery, some post-operative systemic drugs are administered; these can show an impairment in the osseointegration process. These include nonsteroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors. The effects of aspirin, acetaminophen, opioids, adjuvants, anticoagulants and antibiotics in implant fixations are not fully understood, but studies are being carried out to investigate potential ramifications. It is currently accepted that systemic pharmacological agents can either enhance or impair implant osseointegration; therefore, proper drug selection is essential. This review aims to discuss the varying effects of three different classes of treatments on improving this process.

Distal Rotational Metatarsal Osteotomy (DROMO) for the treatment of hallux valgus associated with first metatarsal pronation: Surgical technique and initial results.

BACKGROUND: Hallux valgus (HV) is a very common deformity worldwide. Most of the surgical techniques used in the treatment of HV only correct these deformities in two planes, that is sagittal and transverse planes. The importance of the first metatarsal pronation as an etiological factor of hallux valgus is validated by numerous authors and it is usually unaddressed. Few surgical techniques have focused on the correction of rotational deformity of the hallux valgus. We aim to first report a detailed technique and a case series using the Distal Rotational Metatarsal Osteotomy (DROMO) surgical technique, which is less invasive and can address the pronation deformation. METHODS: The inclusion period was 6 months finishing in April 2021. The study analyzed the following x-ray parameters: preoperative and postoperative intermetatarsal angle (IMA), preoperative and postoperative hallux valgus angle (HVA), preoperative and postoperative coronal rotation of the first metatarsal according Hardy and Clapham's classification as described by Kim et al., preoperative and postoperative shape of the first metatarsal head as described by Ono et al. RESULTS: 33 patients matched our inclusion and exclusion criteria. Most patients underwent the surgery for the left foot (n = 18), compared to the right foot (n = 15). We found statistically significant differences between preoperative and postoperative IMA (p < 0.001), preoperative and postoperative HVA (p < 0.001). Preoperative and postoperative coronal rotation of the first metatarsal as classified by Hardy and Clapham was significantly different (p < 0.001), as well as preoperative and postoperative shape of the first metatarsal head (p < 0.01). CONCLUSIONS: DROMO can correct the metatarsal rotation through minimal invasive surgery. From our perspective, DROMO technique should be another alternative for HV correction technique which in time can be associated as a local anesthetic technique, DROMO results are attractive for an ambulatory procedure.

Custom-Made 3D-Printed Prosthesis after Resection of a Voluminous Giant Cell Tumour Recurrence in Pelvis.

Giant-cell tumours are benign aggressive bone lesions that can affect any part of the skeleton. In early stages, curettage is preferred, but in case of local recurrence or voluminous lesions in the periacetabular region, wide resection and reconstruction are recommended. The purpose of this article is to increase clinicians' awareness of the importance of the follow-up of these patients and to describe a case of a voluminous recurrence of a giant-cell tumour in the pelvis. We present a 25-year-old female who underwent internal hemipelvectomy assisted by 3D cutting-guides and reconstruction with a custom-made 3D-printed pelvic prosthesis, hip arthroplasty and ilio-sacral arthrodesis. No postoperative complications occurred and, at long-term follow-up, the patient had a stable and painless hip joint, good bone-implant osteointegration, with an excellent functional outcome. In spite of all available reconstructive techniques, in well-selected patients with voluminous pelvic resections, custom-made 3D-printed implants allow patients to have a good mechanical outcome.

Finite Element Analysis of Different Osseocartilaginous Reconstruction Techniques in Animal Model Knees.

Lesions of the articular cartilage are frequent in all age populations and lead to functional impairment. Multiple surgical techniques have failed to provide an effective method for cartilage repair. The aim of our research was to evaluate the effect of two different compression forces on three types of cartilage repair using finite element analysis (FEA). Initially, an in vivo study was performed on sheep. The in vivo study was prepared as following: Case 0-control group, without cartilage lesion; Case 1-cartilage lesion treated with macro-porous collagen implants; Case 2-cartilage lesion treated with collagen implants impregnated with bone marrow concentrate (BMC); Case 3-cartilage lesion treated with collagen implants impregnated with adipose-derived stem cells (ASC). Using the computed tomography (CT) data, virtual femur-cartilage-tibia joints were created for each Case. The study showed better results in bone changes when using porous collagen implants impregnated with BMC or ASC stem cells for the treatment of osseocartilaginous defects compared with untreated macro-porous implant. After 7 months postoperative, the presence of un-resorbed collagen influences the von Mises stress distribution, total deformation, and displacement on the Z axis. The BMC treatment was superior to ASC cells in bone tissue morphology, resembling the biomechanics of the control group in all FEA simulations.

Causes of revision after total hip arthroplasty in an orthopedics and traumatology regional center.

Background and aim: Despite the great success of primary total hip arthroplasty (THA), the number of revisions has significantly increased over the past years. The objectives of the study were to investigate the main causes that lead to revision of THA, the time interval between primary THA and revision, and the results of the revision surgery. We also assessed whether there was any correlation between the patients' age, BMI, diagnosis for primary THA and the cause of failure. Methods: This paper retrospectively analyzed 189 patients with THA revision surgery performed over a six-year period, between 2015 and 2020. Patients' charts were reviewed to collect data on patient's demographics, patient's primary THA and revision procedures, and the time interval between primary THA and revision surgery. Patients were divided into 3 groups according to the time interval THA-revision: group I (<5 years), group II (5-10 years) and group III (>10 years). Results: The patients' mean age (82 men/107 women) was 69.59±7.85 years (range 31-92 years). The most frequent revision cause was aseptic loosening (52%), followed by periprosthetic fractures (18%), infection (17%) and persistent hip instability (12%). Patients' age (r=0.43) and BMI (r=-0.4) had low correlation with the time interval between THA and revision. Conclusions: The main causes for revision THA within less than five years are infection and instability, while revision for aseptic loosening is performed especially after five years from the primary THA. Osteonecrosis, post-traumatic osteoarthritis and femoral neck fracture are correlated with a higher incidence of revision at less than five years from the primary THA.

Gradual Drug Release Membranes and Films Used for the Treatment of Periodontal Disease.

Periodontitis is an inflammatory disease that, if not treated, can cause a lot of harm to the oral cavity, to the patients' quality of life, and to the entire community. There is no predictable standardized treatment for periodontitis, but there have been many attempts, using antibiotics, tissue regeneration techniques, dental scaling, or root planning. Due to the limits of the above-mentioned treatment, the future seems to be local drug delivery systems, which could gradually release antibiotics and tissue regeneration inducers at the same time. Local gradual release of antibiotics proved to be more efficient than systemic administration. In this review, we have made a literature search to identify the articles related to this topic and to find out which carriers have been tested for drug release as an adjuvant in the treatment of periodontitis. Considering the inclusion and exclusion criteria, 12 articles were chosen to be part of this review. The selected articles indicated that the drug-releasing carriers in periodontitis treatment were membranes and films fabricated from different types of materials and through various methods. Some of the drugs released by the films and membranes in the selected articles include doxycycline, tetracycline, metronidazole, levofloxacin, and minocycline, all used with good outcome regarding their bactericide effect; BMP-2, Zinc-hydroxyapatite nanoparticles with regenerative effect. The conclusion derived from the selected studies was that gradual drug release in the periodontal pockets is a promising strategy as an adjuvant for the treatment of periodontal disease.

Assessment and Care of Oral Lesions for Patients Who Undergo Radioiodine Treatment for Thyroid Cancer.

Patients with differentiated thyroid cancer who undergo radioiodine treatment often present oral complications with a significant impact on their oral cavity function. Any potential sources of systemic infections like periodontal disease, unfitted dentures, orthodontic appliances, deficient/rough fillings, or traumatic dentition must be treated by the dental practitioner, because they represent the main source of spread and dissemination. Any systemic complication of a dental foci may result from improper dental preparation of the patient before radioiodine therapy and inadequate post-radioiodine therapy oral care. Therefore, all patients proceeding into radioiodine treatment should be addressed by the oncological team to undergo thorough dental check-up and receive appropriate treatment in due time.

Current therapeutic approaches in the management of hemophilia-a consensus view by the Romanian Society of Hematology.

Hemophilia A (HA) and hemophilia B (HB) are rare disorders, being caused by the total lack or under-expression of two factors from the coagulation cascade coded by genes of the X chromosome. Thus, in hemophilic patients, the blood does not clot properly. This results in spontaneous bleeding episodes after an injury or surgical intervention. A patient-centered regimen is considered optimal. Age, pharmacokinetics, bleeding phenotype, joint status, adherence, physical activity, personal goals are all factors that should be considered when individualizing therapy. In the past 10 years, many innovations in the diagnostic and treatment options were presented as being either approved or in development, thus helping clinicians to improve the standard-of-care for patients with hemophilia. Recombinant factors still remain the standard of care in hemophilia, however they pose a challenge to treatment adherence because they have short half-life, which where the extended half-life (EHL) factors come with the solution, increasing the half-life to 96 hours. Gene therapies have a promising future with proven beneficial effects in clinical trials. We present and critically analyze in the current manuscript the pros and cons of all the major discoveries in the diagnosis and treatment of HA and HB, as well as identify key areas of hemophilia research where improvements are needed.

Pediatric Thyroid Cancer in Europe: An Overdiagnosed Condition? A Literature Review.

Thyroid neoplastic pathology is the most common form of cancer associated with radiation exposure. The most common histopathological type of thyroid carcinoma is the differentiated thyroid cancer (these include papillary and follicular type), which represents over 90% of all cases, especially affecting girls rather than boys. Although patients are diagnosed in advanced stages as compared to adults, the prognosis of the disease is very good, with a 30-year survival rate of over 95% but post-therapeutic morbidity remains quite high. The treatment is based in particular on the therapeutic guidelines for adults, but as children have some histopathological and genetic characteristics of thyroid cancer, as well as different initial clinical presentations, we decided to review the literature on this pathology among the pediatric population, focusing on cases in Europe. The major interest is the impact of the Chernobyl accident.

Disorders of Dental Hard Tissues Induced by Radioiodine-131 (I-131) Therapy Used in Differentiated Thyroid Cancer: An In Vitro Study.

This study aimed to evaluate, in vitro, the effects of I-131 on enamel and dentin in healthy human incisive permanent maxillary teeth. Our in vitro model analogue with the in vivo conditions of differentiated thyroid carcinoma patients treated with I-131, consisted in a solution of I-131 dissolved in artificial saliva. A total of 48 teeth were divided into eight groups (n = 6): control, irradiation groups at 3, 6, 12, 24, 36, 48, and 192 h, respectively. At the end of radiation exposure, radioiodine activity of specimens was assessed. Fine microstructure, nanostructure, surface roughness, and hidroxyapatite (HAP) crystallite diameter were investigated by atomic force microscopy (AFM) to both enamel and dentin structures. There is a constant increase of radioactivity in dental structures at 3, 6, 12, 24 h, due to progressive retention and I-131 migration, with a maximum at 36 h. Enamel showed notable alterations, which was correlated with the increase of the treatment time. A relevant visible distance between the HAP prisms was observed after 24 h. The surface suffered a loss in its compact structure. I-131 acts in the same way on HAP crystallites in dentin as in those in enamel. It was noticed that their morpho-dimensional changes occurred only after 12 h of treatment. Radioiodine-131 determines degradation of enamel and dentin by starting from the alteration of the crystalline network of HAP prisms, transforming them from compact materials into an agglomeration of rocky submicron structures.