Markevičiūtė, Vėtra

Background/Aim: Osteosarcoma (OS) treatment consists of chemotherapy with methotrexate, adriamycin (doxorubicin) and platinol (MAP) combined with intercalated surgery, resulting in a 5-year survival rate of 50–60%. We recently demonstrated that local delivery of doxorubicin via a microparticulate hydroxyapatite-based biomaterial (DASH) could efficiently impede tumor growth in subcutaneous OS; however, its effect in an orthotopic intraosseous OS remains unknown, particularly in conjunction with systemic MAP treatment. In this study, we performed two separate mouse model studies with the aim of (1) evaluating the effect of DASH in an orthotopic osteosarcoma model and (2) evaluating the efficacy and tolerability of DASH in conjunction with systemically administered MAP in a subcutaneous osteosarcoma model. Methods: In the first study, 56 mice were inoculated with human OS cells (i.e., h143B cells) in the proximal tibia. After 10 days, the mice were divided into seven treatment groups, of which group G2 (systemic DOX) was compared with groups G5–G7, which were treated with increasing doses of DOX delivered via DASH. The tumor-impeding response was evaluated via micro-CT (day 14), PET-CT (day 21) and tumor measurements (post-mortem). In the second study, 45 mice were inoculated subcutaneously with 143B cells and, 10 days later, groups G2–G5 were treated locally with increasing DASH doses, followed by two cycles of systemic MAP for all groups. On day 31, the animals underwent PET-CT examination followed by euthanasia and tumor measurements. Results: In both experiments, DASH treatment resulted in significantly lower tumor activity, tumor volume and weight. Micro-CT examination in the orthotopic model demonstrated that DASH treatment protected the bone from osteolysis. The subcutaneous study revealed that the mice were able to tolerate DASH, even in conjunction with systemically administered MAP. Conclusions: Intratumoral administration of DASH impeded OS growth in both animal models and protected bone against tumor-induced osteolysis. Furthermore, DASH was well-tolerated when administered in conjunction with systemic MAP therapy, indicating its potential therapeutic neo-adjuvant value in poor responders.

This study aims to evaluate the feasibility, safety, and peri-implant bone formation of augmenting a proximal femoral nail (PFN) helical blade with a calcium sulfate/hydroxyapatite (CaS/HA) biomaterial combined with systemic zoledronic acid (ZA).

Šio vadovėlio tikslas - pateikti šiuolaikinį požiūrį į politraumą (sin. dauginė trauma) patyrusio paciento radiologinę diagnostiką ir skirtas visiems radiologams ir kitų specialybių gydytojams, kurie klinikinėje praktikoje susiduria su politraumą patyrusiais pacientais. Visame pasaulyje garsiai kalbama apie poreikį politraumą patyrusius pacientus tirti ir gydyti vadovaujantis standartizuotais protokolais, nes esant kritinėms būklėms pirmosios valandos turi ypač didelę reikšmę tolesniam paciento tyrimui, gydymui ir išgyvenamumui. Todėl geros praktikos traumos komandos turi vadovautis principu, kad politraumą patyręs pacientas reikiamu metu atsidurtų reikiamoje vietoje reikalingam tyrimui ir gydymui gauti.

Introduction Giant cell tumor (GCT) of bone accounts for approximately 4-5% of primary bone tumors. It is intermediate, locally aggressive, and characterized by a high risk of recurrence, and a small but recognized risk of lung metastasis. GCT presents typically in the fourth decade of life, with a slight female predominance, and is often found in the meta-epiphyseal region of long bones, around major joints, where mechanical load and joint preservation are critical. The knee joint structures, particularly the distal femur and proximal tibia, are the most involved anatomical sites. The treatment typically adopted in case of GCT is intralesional curettage, resulting in a bone cavity that must be filled or reconstructed to restore the structural integrity and allow weight-bearing. Bone grafting, bone cement, and artificial bone substitutes are common options, and the choice depends on the extent of defect, location, size, the surgeon’s preference, as well as the main concerns. These points are reflected in the clinical presentation that follows. Case Presentation A 33-year-old woman presented to the department with an 8-month history of knee pain. Imaging revealed a distal femoral lesion. Giant cell tumor was suspected and confirmed by biopsy. No metastasis was detected. The patient underwent intralesional curettage followed by cementoplasty, bone grafting, and internal fixation of the distal femur. Discussion The distal femur is a high-load-bearing region, and after curettage, maintaining structural integrity is critical to reduce the risk of fracture. The sandwich technique, in which bone graft is interposed between cement and the articular surface, was employed. This approach may complicate radiologic follow-ups, but it facilitates safe reconstruction adjacent to the joint surface. Internal fixation was used considering both the volume and location of the cavity, providing adequate reinforcement. Follow-up imaging showed no evidence of recurrence, and chest CT excluded metastasis, confirming the treatment’s success. Regular monitoring is indicated due to the possibility of recurrence. Conclusions Curettage with sandwich cement reconstruction and internal fixation proved to be an effective and stable technique for the treatment of GCT of distal femur.

Background: Mortality rates between minor (e.g., removal of toes or part of the foot) and major (e.g., below- or above-the-knee) lower extremity amputations (LEA) vary significantly in diabetic patients. Other factors, including survival rates, rehabilitation outcomes, and healthcare burden, are also notably im-pacted by the type of amputation performed. Objective: This narrative review aims to analyze and compare mortality rates following minor and major LEA in diabetic patients, by highlighting key risk factors and their impact on patient outcomes. Methods: A narrative review of existing literature was conducted by using searches of PubMed and Google Scholar. Studies reporting mortality rates, risk factors, comorbidities, functional outcomes, and management strategies among diabetic patients undergoing minor and major LEA were included. Results: Major LEA is associated with significantly higher short- and long-term mortality rates, with five-year survival ranging from 10% to 48%, compared to 29% to 69% for minor LEA. The key risk factors for mortality include chronic renal disease, peripheral arterial disease, sepsis, and poor glycemic control. While minor LEA offers better survival rates, it carries a higher risk of progression to major amputation if diabetes-related complications persist. Conclusion: The findings highlight the critical importance of early intervention, strict glycemic control, and multidisciplinary care to improve the survival and quality of life in diabetic patients undergoing LEA. Limb preservation strategies should be prioritised whenever possible, as minor amputations lead to better long-term outcomes. Future research should focus on refining risk stratification and optimizing rehabilitation programs to enhance patient prognosis post-amputation.

Temos aktualumas Osteoporoze jau dabar serga daugiau nei 200 milijonų žmonių visame pasaulyje, o iki 2050 m. šis skaičius turėtų padvigubėti. Osteoporozės klasikiniai simptomai yra pastebimas kaulinio mineralinio tankio sumažėjimas ir trabekulinio kaulo poringumo padidėjimas, ko pasekoje lūžių fiksavimo konstrukcijoms sunku įsitvirtinti trapiame akytajame kaule. Darbo tikslas (-ai) Šio darbo tikslas yra sukurti metodą, kaip pagerinti mechaninį konstrukcijų tvirtinimąsi ir pagerinti kaulo formavimąsi aplink jas, pacientams patyrusiems lūžius klubo srityje. Tyrimo metodai Ikiklinikiniai ekspermentiniai tyrimai atlikti Lundo Universitetinės ligoninės Biomedicininių tyrimų cente. Klinikinis tyrimas FAME indekso vertinimui ir validizacijai atlikti Gazi universiteto Medicinos fakulteto Ortopedijos ir traumatologijos klinikoje, Antalijoje, Turkikoje ir Lietuvos sveikatos mokslų univesiteto ligoninėje, Kauno klinikose, Ortopedijos ir traumatologijos skyriuje. Klinikinis randomizuotas tyrimas atliktas Lietuvos sveikatos mokslų universiteto ligoninėje, Kauno klinikose, Ortopedijos ir traumatologijos skyriuje. Ikiklinikiniai ir klinikiniai tyrimai vykdyti 2018– 2023 metų laikotarpyje. Tyrimai atlikti gavus Švedijos žemės ūkio valdybos komiteto leidimą (leidimo nr: 152888/2019.). Kauno universitetinės ligoninės etikos komiteto leidimą, (leidimo numeris: P1 BE–2–76/2019). Tyrimų protokolai parengti vadovaujantis Pasaulio medicinos asociacijos etikos kodeksu (Helsinkio deklaracija). Visi tiriamieji pasirašė informuoto asmens sutikimo formą daly vauti tyrime. Tyrimuose su gyvūnais tyrėjai buvo išlaikę Felasa C kategorijos egzaminą moksliniems tyrimams su tiriamaisiais gyvūnais. Tyrimas įtrauktas į ClinicalTrials.gov (Identifikacijos numeris: NCT04498715). Rezultatai Šį tyrimą sudaro 5 skirtingos studijos, apimančios tiek ikiklinikinius, tiek klinikinius tyrimus. Mūsų pradiniai tyrimai parodė, kad CaS/HA medžiaga aplink implantą osteoporoziniame kaule gali būti biologiškai suaktyvinta sistemine ZA injekcija (7-14 dienų po operacijos). Ikikliniknio tyrimo metu panaudojant osteoporozinių kaulų modelius, parodėme, kad CaS/HA pagerina biomechaninį kaulo tvirtinimasi tarp implanto ir kaulo. Taip pat buvo įrodyta, kad bisfosfonatas ZA ieško HA dalelių ir skatina kaulų susidarymą akytajame kaule. Kitas keliamas klausimas buvo susiję su tuo, kaip ikiklinikinius tyrimus būtų galima pervesti į klinikinį tyrimą? Dėl šios priežasties buvo atliktos sekančios dvi studijos, kurių metu buvo tikslas išbandyti naują stratifikacijos indeksą (FAME). FAME indeksas reikalingas, padėti nustatyti asmenis, kurie gautų daugiausiai naudos iš augmentacijos operacijos metu. Tai yra pacientai, kurie turi didelę pakartotinių lūžių riziką, bet turi mažą mirties rizika. FAME indekso naudojimo galimybė buvo patvirtinta atlikus du atskirus tyrimus, po kurių buvo pradėtas koncepcijos įrodymo klinikinis tyrimas. Išvados, rekomendacijos Klinikinėje aplinkoje, nagrinėjant sukurtų metodų klinikinį veiksmingumą pažeidžiamų ir pagyvenusių žmonių grupėje, kuriems taikomas operacinis pertrochanterinio lūžio gydymas dinaminu klubo sraigto sistema, šis derinys gali būti pranašesnis už dabartinius augmentacijos metodus pacientams su osteoporoze, taip užkertant kelią pakartotinėms operacijoms dėl trochanterinių lūžių.

Temos aktualumas Sarkomos – reti, bet agresyvūs navikai, dažnai diagnozuojami per vėlai dėl nespecifinių simptomų ir mažo informuotumo. Ankstyvas atpažinimas yra kritiškai svarbus, nes laiku pradėtas gydymas stipriai pagerina ligos prognozę. Dėl sudėtingos diagnostikos ir būtinybės taikyti specializuotą gydymą pacientai turėtų būti kuo greičiau nukreipiami į sakomų gydymo centrus. Darbo tikslas (-ai) Apžvelgti mokslines publikacijas ir pateikti rekomendacijas, kada įtarti pirminę onkologinę ligą kauluose ir minkštuosiuose audiniuose ir kur nukreipti pacientus. Tyrimo metodai Apžvelgti mokslinėje literatūroje aprašomą sarkomų diagnostiką, diferencinę diagnostiką, gydymo metodus ir pacientų nukreipimo į specializuotus centrus principus. Rezultatai Sarkomos – tai retos, bet agresyvios piktybinės kaulų ir minkštųjų audinių navikų formos, sudarančios apie 1% visų piktybinių navikų. Pagrindiniai ženklai, kurie gali padėti įtarti kaulų ar minkštųjų audinių piktybinį naviką yra: dariniai didėjantys dinamikoje, skausmingi dariniai, ypač jei skausmas nepraeina ramybėje, judėjimo apribojimas, neurologiniai simptomai (jei navikas peraugęs nervus), spontaniniai lūžiai, anksčiau taikyta spindulinė terapija, destrukcijos zonos radiologiniuose tyrimuose. Sarkomoms diagnozuoti naudojami įvairūs radiologiniai tyrimai, tarp jų dažniausiai naudojami MRT, KT bei rentgenogramos. Vis dėl to šalia radiologini tyrimų biopsija yra auksinis standartas. Tačiau svarbu suprasti, kad netinkamai atlikta biopsija gali sukelti komplikacijų, todėl ji turėtų būti atliekama specializuotuose centruose, siekiant išvengti naviko išplitimo ar netinkamo gydymo planavimo. Dėl sarkomų sudėtingumo jų gydymui būtinas multidisciplininis požiūris, apimantis ortopedus traumatologus, onkologus, radioterapeutus, patologus ir radiologus. Tinkamas pacientų nukreipimas į specializuotus centrus gali padėti užtikrinti efektyvesnį gydymą ir geresnes išgyvenamumo prognozes. Tyrimai rodo, kad apie 30% minkštųjų audinių sarkomų iš pradžių klaidingai diagnozuojamos kaip gerybiniai dariniai. Dėl nespecifinių simptomų šeimos gydytojai arba ortopedai pirminėje grandyje dažnai nukreipia pacientus vėlyvam ištyrimui – apie 35–40% pacientų iš pradžių gydomi dėl „neaiškių skausmų“ prieš gaudami tikslinius tyrimus. Vidutinis laikas nuo pirmųjų simptomų atsiradimo iki sarkomos diagnozės patvirtinimo dažnai siekia 6– 12 mėnesių, o kai kuriais atvejais – iki 24 mėnesių, todėl apie 40–50% sarkomų diagnozuojamos jau pažengusiose stadijose. Literatūros duomenimis gydymas specializuotuose centruose pagerina pacientų penkerių metų išgyvenamumą ir sumažina recidyvų dažnį nuo 50–60% iki 70–80%, priklausomai nuo sarkomos tipo ir stadijos. Multidisciplininė priežiūra leidžia tiksliau nustatyti diagnozę, parinkti optimalų gydymo metodą ir sumažinti netinkamų chirurginių intervencijų riziką. Išvados, rekomendacijos Dėl retos, bet klastingos ligos prigimties, sudėtingos diagnostikos ir būtinybės taikyti specializuotą gydymą būtina didinti informuotumą apie sarkomas. Sarkomų gydymas visuomet turi būti multidisciplininis, todėl pacientus svarbu nukreipti į specializuotus centrus. Ankstyvas atpažinimas, tinkama diagnostika ir laiku pradėtas gydy

Introduction Soft tissue sarcomas (STS) are a group of rare tumours accounting for up to 1% of malignant tumor cases. Approximately 20% of STS cases are localised in the upper extremities, with the shoulder and upper arm region affected in half of these cases (1). The preferred surgical treatment for STS is limb-sparing surgery with wide local excision, which often requires reconstruction using flaps and augmented by radiation therapy or chemotherapy (2). Case Presentation An 85-year-old patient presented with a palpable mass in the right upper arm that was first noticed 3 months ago and has since grown in size. MRI revealed a heterogeneous tumor with the signs of necrosis measured 7 x 10.7 x 10.5 cm which has overgrown a part of deltoid and triceps muscles with no invasion to the humerus. A biopsy confirmed the diagnosis of undifferentiated pleomorphic sarcoma. CT scans of the chest, abdomen and pelvis showed no signs of distant metastasis. Incidentally, a low-frequency, possibly benign 3.5 x 1.8 x 8.5 cm sized mass was discovered in the lower right chest wall and the diagnosis of neurofibroma was confirmed with a biopsy. After multidisciplinary team discussion the treatment of choice was limb-sparing surgery with wide local excision of both tumors. The significant soft tissue defect after removal of the STS was reconstructed using pedicled latissimus dorsi flap. The patient had no post-operative complications and after wound healing, postoperative radiation therapy was administered. Further follow-up with MRI and CT scans of the chest, abdomen and pelvis after 6 months revealed local tumor recurrence with multiple subcutaneous nodes and metastasis to local lymph nodes and lung tissue. Discussion Oftentimes, rarely expected STS of the upper extremity cause no pain and grow slowly, complicating adequate early detection and treatment which becomes a major challenge for the multidisciplinary team (1). In the context of STS, the functional outcomes and possible complications of upper extremity soft tissue reconstruction with a latissimus dorsi flap have yet to be evaluated and analysed (3). Conclusions Although the surgery was performed radically, the waiting time for sufficient flap integration and proper function caused a long gap without radiation therapy, which led to disease recurrence.

Introduction Avascular necrosis (AVN) of the talus can lead to progressive bone destruction and collapse of ankle and subtalar joints (1). In advanced stages, significant bone defects develop, limiting treatment options and requiring surgical intervention, such as arthrodesis with augmental bone grafting (2). Case Presentation A 59 year old male with no history of trauma, presented with right ankle edema, deformity and pain that worsens with exertion and has been progressively increasing over the past 4 months. X - ray and MRI of the right ankle revealed fragmentation and structural abnormalities of neck and body of the talus, tibiotalar and talocalcaneal joints, consistent with avascular necrosis of the talus. The surgical treatment of choice was tibiotalocalcaneal arthrodesis using retrograde intramedullary nailing with four-part fibular cortical bone graft and additional tibial bone graft to promote bony fusion and maintain adequate limb length with long-term joint stability. Additionally, immobilisation with an orthopaedic splint and non-weight bearing was applied for 12 weeks. Three months post-operation, the patient reports painless movement. Further rehabilitation and follow-up consultations are scheduled. Discussion AVN of the talus can occur without any prior traumatic event, therefore early recognition of potential underlying risk factors, such as alcohol and corticosteroid use, as well as autoimmune, metabolic and vascular diseases, can be helpful (3,4). The first step in diagnosis involves X - ray imaging to detect structural abnormalities. MRI provides a more detailed evaluation, enables earlier interventions and expands the spectrum of potential treatment options (2). Due to the advanced stage of AVN observed in this case, a tibiotalocalcaneal arthrodesis using four piece fibular bone graft was performed as the appropriate surgical intervention to preserve proper and functional limb length. Conclusions Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing and augmental cortical fibular bone grafting as a joint-sacrificing surgical treatment can lead to significant pain relief when bone structures and joints are dysfunctional in AVN of talus.

Osteoporosis affects more than 200 million people worldwide, and by 2050, that figure is anticipated to double. A noticeable decline in BMD and an increase in trabecular bone porosity are typical symptoms of the condition. This makes it difficult to secure fracture fixation hardware in fragile cancellous bone. The aim of this work is to develop methods to improve immediate mechanical anchorage and enhance bone formation around orthopaedic hardware used for the fixation of hip fractures. Within the scope of this doctoral thesis, a calcium sulphate/hydroxyapatite (CaS/HA) biomaterial and systemic bisphosphonate zoledronic acid were used to modulate peri-implant bone formation. Our main research questions were: can a CaS/HA material implanted around a metallic implant increase the immediate mechanical bone anchorage and can a CaS/HA material be biologically activated by systemically administered bisphosphonate and consequently improve bone quality? This thesis comprises of 5 different studies involving both pre-clinical and clinical research. Our initial studies demonstrated that implants augmented with CaS/HA material in osteoporotic bone and activation of HA particles by systemically administered ZA (7–14 days after surgery) leads to new bone formation. Pre-clinical data demonstrate that biomechanical advantages can be achieved from CaS/HA augmentation of lag-screws in osteoporotic bone. It has also been demonstrated that bisphosphonate ZA seeks the HA particles and promote bone formation in cancellous bone. The following questions pertained to how the pre-clinical studies could be translated into a clinical study? For this reason, the two following studies were aimed to test the feasibility of a new stratification index (FAME), that could help to identify individuals who would benefit most from augmentation treatments and had a high risk of fracture and a low risk of death before the procedure. The feasibility of using the FAME index was validated in two separate studies following, after which a proof-of-concept clinical study was initiated. In a clinical setting, looking into the clinical efficacy of the developed methods in the fragile and elderly population undergoing treatment of pertrochanteric fracture stabilization with a dynamic hip screw system, this combination could potentially be superior to present techniques for augmenting osteoporotic trochanteric fractures thereby preventing reoperations.