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Injury Jul 2024Atrophic pseudoarthrosis is a serious complication with an incidence of 5-10 % of bone fractures located in the diaphysis of long bones. Standard treatments involve... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Treatment of non-hypertrophic pseudoarthrosis of long bones with a Tissue Engineered Product loaded with autologous bone marrow-derived Mesenchymal Stromal Cells: Results from a phase IIa, prospective, randomized, parallel, pilot clinical trial comparing to iliac crest autograft.
BACKGROUND
Atrophic pseudoarthrosis is a serious complication with an incidence of 5-10 % of bone fractures located in the diaphysis of long bones. Standard treatments involve aggressive surgical procedures and re-interventions requiring the use of autografts from the iliac crest as a source of bone-forming biological activity (Standard of Care, SoC). In this context, regenerative ex vivo expanded osteogenic cell-based medicines could be of interest. Particularly, Mesenchymal Stromal Cells (MSC) offer new prospects to promote bone tissue repair in pseudoarthrosis by providing biological activity in an osteoconductive and osteoinductive environment.
METHODS
We conducted a phase IIa, prospective, randomised, parallel, two-arms, open-label with blinded assessor pilot clinical trial to compare SoC vs. a tissue-engineered product (TEP), composed of autologous bone marrow (BM)-derived MSCs loaded onto allogeneic decellularised, lyophilised spongy bone cubes, in a cohort of 20 patients with non-hypertrophic pseudoarthrosis of long bones. Patients were followed up for 12 months. Radiological bone healing was evaluated by standard X-ray and computed tomography (CT) scanning. Quality of life was measured using the EUROQOL-5D questionnaire.
RESULTS
Ten patients were randomized to TEP and 10 to SoC with iliac crest autograft. Manufacturing of TEP was feasible and reproducibly achieved. TEP implantation in the bone defect was successful in all cases and none of the 36 adverse events (AE) reported were related to the treatment. Efficacy analyses were performed in the Full Analysis Set (FAS) population, which included 17 patients after 3 patients withdrew from the study. The degree of consolidation, estimated by measuring Hounsfield units (HU) on CT, showed no significant differences between the two treatment groups at 12 months post treatment (main efficacy variable) (p = 0.4835) or at 6 months.
CONCLUSIONS
Although only a small number of patients were included in our study, it is notable that no significant differences were observed between the experimental treatment and SoC, thus suggesting TEP as an alternative where autograft is not available or contraindicated.
Topics: Humans; Pseudarthrosis; Male; Female; Pilot Projects; Mesenchymal Stem Cell Transplantation; Middle Aged; Prospective Studies; Ilium; Transplantation, Autologous; Tissue Engineering; Treatment Outcome; Adult; Mesenchymal Stem Cells; Aged; Bone Transplantation; Quality of Life; Autografts
PubMed: 38797000
DOI: 10.1016/j.injury.2024.111596 -
Cancers May 2024The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT).... (Review)
Review
The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT). Particularly, pelvic bone marrow dose exposure has been identified as a contributing factor to this hematologic toxicity. Chemotherapy further increases bone marrow suppression, often necessitating treatment interruptions or dose reductions. A systematic search for original articles published between 1 January 2006 and 7 January 2024 that reported on chemoradiotherapy for locally advanced cervical cancer and hematologic toxicities was conducted. Twenty-four articles comprising 1539 patients were included in the final analysis. HT of grade 2 and higher was observed across all studies and frequently exceeded 50%. When correlating active pelvic bone marrow and HT, significant correlations were found for volumes between 10 and 45 Gy and HT of grade 3 and higher. Several dose recommendations for pelvic bone and pelvic bone marrow sparing to reduce HT were established, including V10 < 90-95%, V20 < 65-86.6% and V40 < 22.8-40%. Applying dose constraints to the pelvic bone/bone marrow is a promising approach for reducing HT, and thus reliable implementation of therapy. However, prospective randomized controlled trials are needed to define precise dose constraints and optimize clinical strategies.
PubMed: 38791920
DOI: 10.3390/cancers16101842 -
International Journal of Molecular... May 2024Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental...
Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia.
Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.
Topics: Humans; Mesenchymal Stem Cells; Female; Male; Osteoarthritis, Hip; Middle Aged; Aged; Acetabulum; Developmental Dysplasia of the Hip; Adult; Biomarkers; Femur; Immunophenotyping
PubMed: 38791213
DOI: 10.3390/ijms25105173 -
Children (Basel, Switzerland) May 2024Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The standard and most effective treatment is wide resection of the tumor...
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The standard and most effective treatment is wide resection of the tumor combined with neoadjuvant chemotherapy. Adolescent idiopathic scoliosis (AIS) is a genetically determined three-dimensional spinal deformity, which occurs in teenage patients and is mostly progressive. The basic management strategy is surgical treatment when the curve exceeds 50 degrees. However, the indications are different in oncologic patients. The aim of this study was to describe a case of adolescent scoliosis with osteosarcoma of the pelvis. The authors conducted a scoping review using PubMed and Embase to analyze the state of knowledge. The presented paper is the first report of pelvis osteosarcoma coexisting with adolescent idiopathic scoliosis. Treatment for this complex case finished with very good results, with no recurrence observed during the nine-year follow-up.
PubMed: 38790602
DOI: 10.3390/children11050607 -
Bioengineering (Basel, Switzerland) May 2024Spinal alignment intricately influences functional independence, particularly in older women with osteopenia experiencing mild neck and back pain. This study elucidates...
Spinal alignment intricately influences functional independence, particularly in older women with osteopenia experiencing mild neck and back pain. This study elucidates the interplay between spinal alignment, bone mineral density (BMD), and muscle strength in elderly women presenting with mild neck and back pain. Focusing on a cohort of 189 older women, we examined the associations among global tilt (GT), coronal and sagittal alignment, BMD, grip strength, and functional independence as gauged by the Barthel index. Our findings indicate significant associations between functional capacity and grip strength, bone density, GT, and pelvic tilt (PT). Elderly women with a Barthel Index above 80 demonstrated higher grip strength and better bone quality, reflected by less negative average T scores. These individuals also exhibited lower values of GT and PT, suggesting a better sagittal alignment compared to those with a Barthel index of 80 or below. The results highlight that deviations in GT and PT are significantly associated with decreased functional independence. These insights emphasize the importance of maintaining optimal spinal alignment and muscle strength to support functional independence in elderly women. This study underscores the potential for targeted interventions that improve postural stability and manage pain effectively in this vulnerable population.
PubMed: 38790360
DOI: 10.3390/bioengineering11050493 -
Journal of Orthopaedic Case Reports May 2024Pelvic apophyseal avulsion fractures are uncommon injuries that frequently affect adolescents while participating in sports. This occurs because the enthesis cannot...
INTRODUCTION
Pelvic apophyseal avulsion fractures are uncommon injuries that frequently affect adolescents while participating in sports. This occurs because the enthesis cannot withstand the tractional force applied because the apophysis has not yet fully fused. Due to its complex muscular structure, being the origin of several muscles that cross two lower extremity joints, the pelvis has an increased risk for such injuries. The diagnosis of pelvic avulsion injuries depends heavily on imaging. The best way to detect soft-tissue changes, including tendon or muscle strain, bone marrow edema, hematomas, and soft tissue avulsion injuries, is with an magnetic resonance imaging . It is also the best at showing tendon retraction and can help the clinician spot patients who might benefit from surgical treatment.
CASE REPORT
We report six cases of adolescents professional footballers that suffered avulsion injuries while playing football. The patients had painfully restricted hip range of motion and were unable to bear weight. Some of them on physical examination felt pain at the palpation of the injured area. Magnetic resonance revealed apophysis growth plate avulsion with or without displaced bone fragments that were treated conservatively with an excellent clinical and radiological outcome.
CONCLUSION
For an accurate diagnosis of pelvic avulsion injuries and clinical management, it is important that everyone caring for this patient population is aware of the common injury mechanisms, radiographic findings, and available treatments.
PubMed: 38784877
DOI: 10.13107/jocr.2024.v14.i05.4466 -
BMC Women's Health May 2024Radiotherapy (RT)-induced pelvic insufficiency fractures (PIF) are prevalent in patients with cervical cancer. Inconclusive studies on PIF after cervical irradiation... (Review)
Review Comparative Study
BACKGROUND
Radiotherapy (RT)-induced pelvic insufficiency fractures (PIF) are prevalent in patients with cervical cancer. Inconclusive studies on PIF after cervical irradiation create uncertainty. This review examined PIF after RT in cervical patients, including its pathobiology, likely locations of fractures, incidence, clinical symptoms, and predisposing factors. We further discussed study limitations and therapeutic possibilities of PIF.
METHODS
The following online resources were searched for relevant articles: Google Scholar and PubMed. The keywords 'pelvic insufficiency fractures', 'cervical carcinoma' and 'cervical cancer', as well as 'chemoradiotherapy', 'chemoradiation', and 'radiotherapy', were some of the terms that were used during the search.
RESULTS
Patients with PIF report pelvic pain after radiation treatment for cervical cancer; the incidence of PIF ranges from 1.7 to 45.2%. Evidence also supports that among all patients treated with pelvic radiation, those who experienced pelvic insufficiency fractures invariably had at least one sacral fracture, making it the most frequently fractured bone in the body. Menopausal status, weight, BMI, age, and treatments and diagnosis modalities can influence PIF during radiotherapy.
CONCLUSIONS
In conclusion, our comparative review of the literature highlights significant heterogeneity in various aspects of PIF following radiation for patients with cervical cancer. This diversity encompasses prevalence rates, associated risk factors, symptoms, severity, diagnosis methods, preventive interventions, and follow-up periods. Such diversity underscores the complexity of PIF in this population and emphasizes the critical need for further research to elucidate optimal management strategies and improve patient outcomes.
Topics: Humans; Uterine Cervical Neoplasms; Female; Fractures, Stress; Pelvic Bones; Radiation Injuries; Risk Factors; Radiotherapy
PubMed: 38783273
DOI: 10.1186/s12905-024-03099-8 -
International Journal of Surgery Case... Jun 2024Bone hydatidosis is a rare parasitic infection caused by Echinococcus granulosus, with a frequency of 1-2 %, it has a high morbidity and mortality rate due to its long...
INTRODUCTION AND IMPORTANCE
Bone hydatidosis is a rare parasitic infection caused by Echinococcus granulosus, with a frequency of 1-2 %, it has a high morbidity and mortality rate due to its long clinical latency and lack of symptomatic specificity. This often leads to delayed diagnosis and discovery, usually at the stage of complications.
CASE PRESENTATION
We present a case of sacral hydatidosis in a 71-year-old patient with no prior medical history. The symptomatology was a pelvic pain that had been ongoing for 5 months with constipation and difficulty with defecation. The clinical and radiological findings initially suggested a primary or metastatic malignant tumour. The biopsy revealed a multivesicular cystic lesion, indicating a hydatid cyst of the sacrum, confirmed later by anatomopathological examination. The lesion was almost completely removed, drainage was performed and the patient was put on anti-parasitic treatment.
CLINICAL DISCUSSION
The clinical presentation of bone hydatidosis is poor and its course is insidious, which often leads to a delay in diagnosis. Medical imaging can provide a precise assessment of the lesion, allowing for extensive surgical resection to be planned. However, therapeutic methods and health education in endemic countries are still the best measures for limiting the considerable damage caused by this parasite.
CONCLUSION
Hydatid osteopathy is a slow and progressive disease that can be difficult to diagnose early, which can compromise the quality of treatment. Therefore, it is important to focus on preventive measures to eradicate this parasitic infection.
PubMed: 38772245
DOI: 10.1016/j.ijscr.2024.109772 -
Journal of Cancer Research and Clinical... May 2024Ewing's sarcoma (ES) is an aggressive cancer of bone and soft tissue, most of which tend to occur in the bone. Extraosseous Ewing's sarcoma (EES) of the cervix is... (Review)
Review
BACKGROUND
Ewing's sarcoma (ES) is an aggressive cancer of bone and soft tissue, most of which tend to occur in the bone. Extraosseous Ewing's sarcoma (EES) of the cervix is extremely rare.
CASE PRESENTATION
In the present work, we reported a 39-year-old cervical EES patient with a 2.5*2.1*1.8 cm tumor mass. According to previous literatures, our case is the smallest tumor found in primary cervical ES ever. The patient initially came to our hospital due to vaginal bleeding, and then the gynecological examination found a neoplasm between the cervical canal and partially in the external cervical orifice. The diagnosis of EES was confirmed below: Hematoxylin & Eosin staining (H&E) revealed small round blue malignant cells in biopsy specimens. Immunohistochemistry (IHC) showed the positive staining for CD99, NKX2.2, and FLI1. Disruption of EWSR1 gene was found by fluorescence in situ hybridization (FISH), and the EWSR1-FLI1 gene fusion was determined by next-generation sequencing (NGS). The patient received laparoscopic wide hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, and postoperative adjuvant chemotherapy and remained disease free with regular follow-up for 1 year.
CONCLUSIONS
Through a systematic review of previously reported cervical ES and this case, we highlighted the importance of FISH and NGS for the accuracy of ESS diagnosis, which could assist on the optimal treatment strategy. However, due to the rarity of the disease, there is no standard treatment schemes. Investigation on molecular pathological diagnosis and standardization of treatment regimens for cervical ES are critical to patients' prognosis.
Topics: Humans; Female; Sarcoma, Ewing; Uterine Cervical Neoplasms; Adult; Oncogene Proteins, Fusion; Homeobox Protein Nkx-2.2; RNA-Binding Protein EWS; In Situ Hybridization, Fluorescence; Transcription Factors; Proto-Oncogene Protein c-fli-1; Nuclear Proteins; Homeodomain Proteins
PubMed: 38769118
DOI: 10.1007/s00432-024-05698-2 -
Journal of the American Academy of... May 2024Diabetes mellitus (DM) is a risk factor of infection. Although DM has been associated with worse functional outcomes after acetabular fracture, literature regarding the...
INTRODUCTION
Diabetes mellitus (DM) is a risk factor of infection. Although DM has been associated with worse functional outcomes after acetabular fracture, literature regarding the effect of DM on surgical site infection and other early complications is lacking.
METHODS
A 20-year registry from a level 1 trauma center was queried to identify 134 patients with DM and 345 nondiabetic patients with acetabular fractures.
RESULTS
The diabetic patient population was older (57.2 versus 43.2; P < 0.001) and had higher average body mass index (33.6 versus 29.5; P < 0.001). Eighty-three patients with DM and 270 nondiabetics were treated surgically (62% versus 78%; P < 0.001). Diabetic patients who were younger (54.6 versus 61.4; P = 0.01) with fewer comorbidities (1.7 versus 2.2; P = 0.04) were more frequently managed surgically. On univariate analysis, patients with DM more commonly developed any early infection (28.4% versus 21%; P = 0.049) but were no more likely to develop surgical site infection, or other postoperative complications. Older patient age, length of stay, baseline pulmonary disease, and concurrent abdominal injury were independent predictors of postoperative infection other than surgical site infection. Diabetics that developed infection had more comorbidities (2.4 versus 1.5; P < 0.001) and higher Injury Severity Score (24.1 versus 15.8; P = 0.003), and were more frequently insulin-dependent (72.7% versus 41%; P = 0.01).
DISCUSSION
Independent of management strategy, diabetic patients were more likely to develop an infection after acetabular fracture. Insulin dependence was associated with postoperative infection on univariate analysis. Optimal selection of surgical candidates among patients with DM may limit postoperative infections.
Topics: Humans; Male; Female; Middle Aged; Registries; Trauma Centers; Adult; Fractures, Bone; Surgical Wound Infection; Acetabulum; Aged; Diabetes Mellitus; Retrospective Studies; Risk Factors; Diabetes Complications
PubMed: 38768051
DOI: 10.5435/JAAOSGlobal-D-23-00166