The Management and Clinical Outcome of the Charcot Foot

Osteoporoosilääkkeestä ei hyötyä diabeetikon jalkaongelmassa Diabeteksen esiintyvyys kasvaa kaikkialla maailmassa ja siihen liittyvät jalkaongelmat, kuten haavaumat, infektiot, kuoliot, Charcot n jalka ja amputaatiot ovat yksi merkittävimmistä diabetespotilaiden sairaalahoitoa aiheuttavista syistä. Charcot n jalka on invalidisoiva diabeteksen aiheuttama jalkaterän tai nilkan nivel- ja luusairaus. Tauti johtaa usein nopeasti etenevään jalkaterän tai nilkan luun tuhoutumiseen ja pysyviin virheasentoihin, joihin liittyy kohonnut amputaation riski. Väitöstutkimus osoitti, ettei osteoporoosilääkkeenäkin käytetty zoledronaatti nopeuttanut Charcot n jalan paranemista. Taudin toteaminen todettiin hankalaksi ja usein viiveet oikeaan diagnoosin olivat pitkiä. Mitä aiemmin oikeaan diagnoosiin päästiin, sitä parempi oli potilaiden pitkäaikaisennuste.Diabetes mellitus is an endemic disease affecting up to six percent of population worldwide. In Finland, over 300,000 patients have a diagnosis of diabetes and the number is exponentially increasing. Diabetic foot problems; such as ulceration, infection, gangrene, Charcot foot and amputation are a major source of morbidity and a leading cause of hospitalization for patients with diabetes. A non-infectious destruction of bones and joints in a neuropathic extremity was first described more than 100 years ago and has since come to be known by eponym Charcot foot. Today diabetes is the most common cause of Charcot foot, which is recognised as one of the most devastating and disabling complication of diabetes and among the most important risk factors for plantar ulcer formation and subsequent amputation. The understanding of the basic pathophysiological mechanisms of Charcot foot has gradually led to the development of new treatment strategies and the purpose of the present study was to investigate the effect of zoledronic acid (bisphosphonate) on the treatment of acute Charcot foot in a prospective, randomized controlled trial. In addition, the long-term effects of chronic Charcot foot on patient s clinical outcome and quality of life were investigated and a comprehensive analysis of historical patient series was conducted. The study population consisted of Charcot foot patients treated at the Tampere University Hospital Diabetic Foot Clinic during period 1994-2007. The first retrospective data was obtained from the patient records of the Diabetic Foot Clinic and was collated with the Hospital Discharge Register in order to assess the patient demographics and management details of a historical patient series with Charcot foot. The second data set consisted of prospectively enrolled patients (2002-2007) with acute midfoot Charcot foot and compared clinical resolution and bone mineral density changes during the treatment of acute Charcot foot with and without zoledronic acid. The fourth set data was also identified from the patient register of the Diabetic Foot Clinic and was a cross-sectional descriptive study assessing long-term clinical outcome and quality of life in patients with Charcot foot and at least five years of follow-up. The diagnosis of acute Charcot foot is demanding and significant delays in diagnosis were common. The average delay was 29 weeks and the most frequent incorrect diagnoses were erysipelas, deep venous thrombosis, gout, arthritis, fracture or osteomyelitis. The prospective study failed to show any clinical benefit (reduced immobilisation time) with zoledronic acid as an adjuvant in the treatment of acute midfoot Charcot foot. The median immobilisation time in the placebo group was 20 weeks, but this lengthy immobilisation did not lead to an obvious disuse osteoporosis of the hip in the Charcot foot affected side after six months of treatment. Management with zoledronic acid led to a significant increase of the hip bone mineral density in both sides compared to placebo, but the clinical significance of this was uncertain. In the long-term follow-up study 67% of patients had ulceration during follow-up and 40% were ulcerated more than once. Fifty percent of patients were managed surgically with an increase in surgery 4 years post diagnosis. Chronic Charcot foot was found to impair patient s physical functioning and general health but did not affect mental health. Long-term functional outcome of patients with Charcot foot is usually relatively good, mainly due to the absence of pain and if the correct diagnosis is reached early

Osteosarkooman diagnostiikka ja hoito

Teema : luukasvaimet. English summaryPeer reviewe

Osteosarkooman diagnostiikka ja hoito

Osteosarkooma on yleisin luusta lähtöisin oleva pahanlaatuinen kasvain, ja sen tavallisin esiintymispaikka on polven ympäristö. Osteosarkooma on pääosin lasten ja nuorten tauti, mutta sitä tavataan myös ikääntyvässä väestössä. Suomessa todetaan vuosittain vain noin 20 uutta osteosarkoomatapausta. Diagnostiikka ja hoito on keskitetty luukasvaimia hoitaviin yliopistosairaaloihin. Osteosarkoomat jaetaan matalan ja korkean graduksen (erilaistumis- eli pahanlaatuisuusasteen) kasvaimiin. Valtaosa osteosarkoomista on klassisia eli korkean graduksen luusarkoomia, joiden hoidossa yhdistelmäsolunsalpaajahoito on oleellinen. Matalan pahanlaatuisuusasteen esimerkiksi parosteaalinen osteosarkooma hoidetaan pelkällä leikkauksella. Suurin osa potilaista voidaan nykyään leikata raajaa säästävin tekniikoin ilman amputaatiota. Osteosarkoomapotilaiden ennuste on säilynyt melko lailla muuttumattomana 1990-luvun jälkeen, sillä viiden vuoden elossaolo-osuus on noin 60–70 %. Uusien hoitomuotojen kehittäminen on taudin harvinaisuuden vuoksi melko hidasta.</p

Tissue reconstructions after sacrectomies performed for primary sacral tumors

English abstrac

Modified Harrington's procedure for periacetabular metastases in 89 cases : a reliable method for cancer patients with good functional outcome, especially with long expected survival

Background and purpose - The pelvis is the 3rd most common site of skeletal metastases. In some cases, periacetabular lesions require palliative surgical management. We investigated functional outcome, complications, and implant and patient survival after a modified Harrington's procedure. Patients and methods - This retrospective cohort study included 89 cases of surgically treated periacetabular metastases. All patients were treated with the modified Harrington's procedure including a restoration ring. Lesions were classified according to Harrington. Functional outcome was assessed by Harris Hip Score (HHS) and Oxford Hip Score (OHS). Postoperative complications, and implant and patient survival are reported. Results - The overall postoperative functional outcome was good to fair (OHS 37 and HHS 76). Sex, age, survival > 6 and 12 months, and diagnosis of the primary tumor affected functional outcome. Overall implant survival was 96% (95% Cl 88-100) at 1 year, 2 years, and 5 years; only 1 acetabular implant required revision. Median patient survival was 8 months (0-125). 10/89 patients had postoperative complications: 6 major complications, leading to revision surgery, and 4 minor complications. Interpretation - Our modified Harrington's procedure with a restoration ring to achieve stable fixation, constrained acetabular cup to prevent dislocation, and antegrade iliac screws to prevent cranial protrusion is a reliable reconstruction for periacetabular metastases and results in a good functional outcome in patients with prolonged survival. A standardized procedure and low complication rate encourage the use of this method for all Harrington class defects.Peer reviewe

Total hip arthroplasty, combined with a reinforcement ring and posterior column plating for acetabular fractures in elderly patients : good outcome in 34 patients

Background and purpose Low-energy acetabulum fractures are uncommon, and mostly occur in elderly patients. Determining the optimal operative treatment for such fractures is challenging. Here we investigated whether acutely performed total hip arthroplasty plus posterior column plating (THA) reduced complications and reoperations compared with open reduction and internal fixation (ORIF) in elderly patients with acetabular fractures.Patients and methods We retrospectively reviewed the records of 59 patients, > 55 years of age, with complex acetabular fractures, caused by low-energy trauma, treated between January 2008 and September 2017. Of these patients, 34 underwent acute THA, and 25 ORIF alone. Patient and implant survival were compared between groups using Kaplan-Meier survival analysis and Cox multiple regression. Functional outcomes assessed by Oxford Hip Score (OHS) were compared between the THA patients and those 9 ORIF patients who underwent secondary THA due to posttraumatic hip osteoarthritis (OA) during follow-up.Results Overall patient survival was 90% (95% CI 82-98) at 12 months, and 64% (CI 47-81) at 5 years. Of 25 ORIF patients, 9 required secondary THA due to posttraumatic OA. Large fragments on the weight-bearing acetabular dome upon imaging predicted ORIF failure and secondary THA. The acute THA group and secondary THA group had similar 12-month OHS.Interpretation Acute THA including a reinforcement ring resulted in fewer reoperations than ORIF alone in elderly patients with acetabular fractures. These findings support acute THA as first-line treatment for complex acetabular fractures in elderly patients.Peer reviewe

Revision rate of reconstructions in surgically treated diaphyseal metastases of bone

Introduction: Skeletal metastases can weaken the bone, necessitating surgery, and surgical treatment options vary. The aim of this study was to investigate the revision rate of reconstructions in surgically treated diaphyseal skeletal metastases. Materials and methods: Between 2000 and 2018 at Helsinki and Tampere university hospitals in Finland, a total of 164 cases with diaphyseal skeletal metastases were identified from a prospectively maintained database. Tumor location was humerus, femur, and tibia in 106 (65%), 53 (32%), and 5 (3.0%) cases, respectively. A total of 82 (50%) cases were treated with intramedullary nailing (IMN), 73 (45%) with IMN and cementation, and 9 (5%) with another technique. Results: In the upper extremity, implant survival (IS) was 96.4% at 1, 2, and 5 years; in the lower extremity, it was 83.8%, 69.1%, and 57.6% at 1, 2, and 5 years, respectively. Lower extremity IS for impending lesions was 100% at 1, 2, and 5 years, and in cases operated for true pathologic fracture, it was 71.6%, 42.9%, and 21.5% at 1, 2, and 5 years, respectively. In IMN cases without cement, the complication rate was 16% (13/82) when compared to 6% (4/73) in IMN cases with cementation. Discussion: We would advocate for early intervention in patients with metastatic bone disease affecting the femur rather that watchful waiting with the risk for fracture and the need for urgent intervention. However, this choice must be balanced against the underlying risk of surgical intervention in a potentially fragile population with often limited prognoses.Peer reviewe

Clinical results and quality of life after reconstruction following sacrectomy for primary bone malignancy

Background: Sacrectomy is a rare and demanding surgical procedure that results in major soft tissue defects and spinopelvic discontinuity. No consensus is available on the optimal reconstruction algorithm. Therefore, the present study evaluated the results of sacrectomy reconstruction and its impact on patients' quality of life (QOL). Methods: A retrospective chart review was conducted for 21 patients who underwent sacrectomy for a primary bone tumour. Patients were divided into groups based on the timing of reconstruction as follows: no reconstruction, immediate reconstruction or delayed reconstruction. QOL was measured using the EQ-5D instrument before and after surgery in patients treated in the intensive care unit. Results: The mean patient age was 57 (range 22-81) years. The most common reconstruction was gluteal muscle flap (n =9) and gluteal fasciocutaneous flap (n = 4). Four patients required free-tissue transfer, three latissimus dorsi flaps and one vascular fibula bone transfer. No free flap losses were noted. The need for unplanned re-operations did not differ between groups (p =0.397), and no significant differences were found for pre- and post-operative QOL or any of its dimensions. Discussion: Free flap surgery is reliable for reconstructing the largest sacrectomy defects. Even in the most complex cases, surgery can be safely staged, and final reconstruction can be carried out within 1 week of resection surgery without increasing peri-operative complications. Sacrectomy does not have an immoderate effect on the measured QOL. (C) 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Chitosan/collagen/Mg, Se, Sr, Zn-substituted calcium phosphate scaffolds for bone tissue engineering applications : A growth factor free approach

According to the biomimetic bone scaffold design paradigm, a scaffold resembling natural bone tissue with molecular, structural and biological compatibility is needed to allow effective regeneration of bone tissue. Continuing our previous studies regarding scaffolds with chitosan matrix containing Mg, Se, Sr, Zn-substituted calcium phosphates (CaPs), the focus of this work was to further improve the properties of these growth factor-free scaffolds. By addition of collagen into the chitosan matrix at weight ratios of 100:0, 75:25, 50:50, 25:75 and 0:100, we aimed to better resemble natural bone tissue. Highly porous composite scaffolds based on chitosan and collagen, with 30 wt% of Mg, Se, Sr, Zn-substituted CaPs, were prepared by the freeze-gelation method. The scaffolds show a highly porous structure, with interconnected pores in the range of 20–350 μm and homogeneously dispersed CaPs. The added collagen further enhanced the stability measured during 28 days in simulated biological conditions. Live/dead and CyQUANT assays confirmed good viability and proliferation of human bone marrow-derived mesenchymal stem/stromal cells, while successful osteogenic differentiation was confirmed by alkaline phosphatase quantification and type I collagen immunocytochemical staining. Results indicated that the addition of collagen into the chitosan matrix containing Mg, Se, Sr, Zn-substituted CaPs improved the physicochemical and biological properties of the scaffolds.publishedVersionPeer reviewe

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide–drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome