Patient-derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment. We compared seven biomaterials, which included both published and custom-designed materials. The highest level of bone marrow niche was achieved with extracellular matrix gels and custom collagen fiber, both of which allowed for a simple non-surgical implantation. The biomaterial selection did not influence the following AML infiltration. Regarding xenotransplantation, standard intravenous administration produced the most robust engraftment, even for two out of four otherwise non-engrafting AML samples. In contrast, direct intra-scaffold xenotransplantation did not offer any advantage. In summary, we demonstrate that the combination of an injectable biomaterial for scaffold creation plus an intravenous route for AML xenotransplantation provide the most convenient and robust approach to produce AML PDX using a humanized niche.

• MeSH
• akutní myeloidní leukemie * patologie   MeSH
• biokompatibilní materiály * farmakologie   aplikace a dávkování   MeSH
• heterografty MeSH
• lidé MeSH
• myši SCID MeSH
• myši MeSH
• tkáňové podpůrné struktury * chemie   MeSH
• transplantace heterologní * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The influence of various levels of sedation depth on motor evoked potentials (MEP) reproducibility in youth is still unclear because of a lack of data. We tested the hypothesis that a deeper level of total intravenous anesthesia (TIVA) [bispectral index (BIS) 40 ± 5 compared to 60 ± 5] can affect surgeon-directed MEP and their interpretation in youths. METHODS: All patients received TIVA combined with propofol and remifentanil. TIVA was initially maintained at a BIS level of 60 ± 5. The sedation anesthesia was deepened to BIS level 40 ± 5 before the skin incision. MEP were recorded and interpreted at both BIS levels. The primary endpoint was to evaluate the effect of the depth of sedation on the MEP reproducibility directed and interpreted by the surgical team in each patient separately. The secondary endpoint was to compare the relativized MEP parameters (amplitude and latency) in percentage at various levels of sedation in each patient separately. We planned to enroll 150 patients. Due to the COVID-19 pandemic, we decided to analyze the results of the first 50 patients. RESULTS: The surgical team successfully recorded and interpreted MEP in all 50 enrolled patients in both levels of sedation depth without any clinical doubts. The MEP parameters at BIS level 40 ± 5, proportionally compared with the baseline, were latency 104% (97-110%) and the MEP amplitudes 84.5% (51-109%). CONCLUSION: Preliminary data predict that deeper sedation (BIS 40 ± 5) does not affect the surgical team's interpretation of MEP in youth patients. These results support that surgeon-directed MEP may be an alternative when neurophysiologists are unavailable.

• Publikační typ
• časopisecké články MeSH

Pevná kostěná fúze je základním předpokladem léčby rozsáhlé řady onemocnění páteře. Podmínkou je štep obsahující organické a anorganické prvky k docílení srůstu. Autograft zdravého jedince nese ideální poměr biofyzikálních vlastností vyjádřený schopností osteoindukce, osteokondukce a osteogeneze. Se stoupajícím věkem a komorbiditami ideální poměry mizí a samotný odběr je navíc zatížen morbiditou. Současně klesá kvantita štěpu. Veškeré allogenní a arteficiální náhrady kombinují biofyzikální poměry s potlačením osteogeneze. Světová data poukazují na potenciál buněčné terapie. Experimentální vývoj obsažený v tomto projektu kombinuje vývoj třídimenzionálního porózního nosiče s vhodnými fyzikálními vlastnostmi s aplikací lidských mesenchymálních stromálních buněk a endotelových prekurzorů, s cílem navrhnout a ověřit in vitro a následně in vivo na malém zvířeti produkci ideálního živého – bio-artificiálního – osteogenního nosiče s terapeutickým potenciálem pro efektivní navození pevné meziobratlové fůze.; Solid spine fusion is the key element in treatment of a large number of spine diseases. To achieve the fusion, a graft containing organic, as well as inorganic elements is essential. The autograft of a healthy individual has ideal ratio of biophysical features demonstrated in the ability of osteoinduction, osteoconduction, and osteogenesis. With increasing age and comorbidities such ideal ratio fades, harvesting procedure becomes more complicated, and the quality of the graft decreases. All allogenic and artificial replacements provide properties that are rather suppressive to osteogenesis. Recent findings highlight the potential of stem cell therapy. The R&D proposed here combines the development of a 3D porous scaffold of adequate physical characteristics with the application of human mesenchymal stromal cells and endothelial precursors. The aim is to design and verify, first in vitro and then in vivo in a small animal, the production of an ideal bio-artificial osteogenic scaffold with therapeutic potential for efficient induction of a solid intervertebral spinal fusion.

• Klíčová slova
• biomateriály, biomaterials, regenerative medicine, regenerativní medicína, spinální fúze, spinal fusion,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

PURPOSE OF THE STUDY: The study describes changes in gait parameters (temporal-spatial parameters, kinematic parameters represented by the global Gait Deviation Index) of individuals with Adolescent Idiopathic Scoliosis (AIS) compared to the healthy population. The hypothesis assumed a difference in the observed parameters between the two mentioned groups. MATERIAL AND METHODS: In a retrospective study, the temporal-spatial parameters and Gait Deviation Index (GDI) of a cohort of 45 AIS patients (36 girls and 9 boys with the mean age of 15.2 years, the mean Cobb angle of the thoracic curve of 47.3° and the lumbar curve of 51.8°) were compared to a typically developing population of 12 healthy individuals with no musculoskeletal pathology. The difference of followed-up parameters in patients with AIS compared to normal values was assessed by one-sample Student's T-test at the significance level of p = 0.05. RESULTS: The gait analysis shows significant deviations in the gait stereotype of patients with AIS compared to the healthy population. Statistically significant differences within temporal-spatial parameters were confirmed for cadence, walking speed, step time, stride time for left leg, step length, stride length and step width. The mean GDI of the cohort reached the value of 91.07 that indicates a slight alteration of gait, however, even this change is statistically significant. DISCUSSION: In our cohort of patients with AIS, we identified a significantly reduced walking speed (on average 15.4% compared to normal values. At the same time, a reduction in cadence (by an average of 7.5%) and an increase of the stride time (by an average of 12%) were recorded. Our mean GDI values were 91.07, which is consistent with the results reported in the literature for comparable groups of AIS patients. CONCLUSIONS: Our study demonstrated that AIS significantly affects gait stereotype. The differences compared to the group of healthy individuals within temporal-spatial parameters were confirmed for cadence, walking speed, duration and length of step and stride, and step width. The kinematic analysis of gait using the global (GDI) index in patients with AIS demonstrated its slight alteration. A better understanding of the change in movement stereotypes and gait in patients with AIS can bring wider possibilities for individualizing conservative treatment and also can help prevent secondary changes in the locomotor system. KEY WORDS: adolescent idiopathic scoliosis, AIS, gait analysis, Gait Deviation Index, GDI.

• MeSH
• analýza chůze * metody   MeSH
• biomechanika MeSH
• chůze (způsob) fyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• retrospektivní studie MeSH
• skolióza * patofyziologie   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

PURPOSE OF THE STUDY: Spine stabilization surgery is nowadays one of the most common spinal surgical procedures. Spinopelvic alignment is considered to be an important factor impacting the patients' preoperative diffi culties as well as the outcome of surgery. In our study, the outcomes of stabilization surgeries in patients with lumbar spine disorders were evaluated - especially in those with stenosis and spondylolisthesis, in whom the importance of sagittal parameters were assessed with respect to the patients' clinical outcomes and diffi culties. MATERIAL AND METHODS: The study included 50 patients with lumbar spine disorders who had undergone a spine stabilization surgery for a degenerative disease - lumbar spinal stenosis, spondylolisthesis between 2015 and 2017. Spino-pelvic radiological parameters and clinical parameters were evaluated using the nonparametric Kruskal-Wallis, Mann-Whitney, and Wilcoxon tests. RESULTS: In 38 of 50 patients, who at the end of the follow-up period did not have the PI-LL (pelvic incidence-lumbar lordosis) mismatch, i.e. PI-LL was ≤10°, a statistically signifi cant difference in pelvic tilt (p=0.049) and sagittal vertical axis (p<0.001) was reported, which was not the case in the remaining patients of the study population. Claudication and OSWESTRY (ODI) showed no statistically signifi cant difference. We have also compared the differences in the number of fused vertebrae and type of stabilization. A signifi cant change was seen in the claudication parameter at 12 and 24 months after surgery (p=0.007, p=0.005), with better outcomes achieved by 360° lumbar fusion compared to posterior lumbar fusion. The improvement of VAS and ODI scores in both the groups over time (from 6.1 to 3.6 or from 6.3 to 3.5 in VAS and from 62 to 32, or from 62 to 30 in ODI) was also statistically signifi cant (p<0.001 in both groups), while when comparing the groups against each other it was statistically insignifi cant. DISCUSSION: The authors confi rmed signifi cant improvement in the studied clinical parameters in all groups of patients (VAS, ODI, claudication), which is consistent with the results of recently published papers. The authors also established the correlation between different radiological parameters in the studied groups. The results do not confi rm the importance of the length or type of instrumentation for the clinical outcomes. This is consistent with the fi ndings of other published manuscripts. The authors failed to confi rm a signifi cant change in clinical parameters in dependence on the matching relationship between the pelvic incidence and lumbar lordosis. CONCLUSIONS: Proper spinopelvic balance in patients after spinal surgery is a very important indicator of postoperative development and condition, but our cohort showed no statistically signifi cant difference in the clinical outcomes of patients whose postoperative sagittal parameters were unsatisfactory. KEY WORDS: sagittal profi le, spine stabilization, pelvic tilt, pelvic incidence, sagittal vertical axis, SVA.

• MeSH
• chůze (způsob) MeSH
• lidé MeSH
• lordóza * MeSH
• neurochirurgické výkony MeSH
• páteř MeSH
• spondylolistéza * chirurgie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• MeSH
• anestetika intravenózní MeSH
• anestezie * MeSH
• ketogenní dieta * MeSH
• lidé MeSH
• motorické evokované potenciály fyziologie   MeSH
• skolióza * chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

PURPOSE OF THE STUDY This article presents the evidence and the rationale for the recommendations for surgical treatment of degenerative lumbar stenosis (DLS) and spondylolisthesis that were recently developed as a part of the Czech Clinical Practice Guideline (CPG) "The Surgical Treatment of the Degenerative Diseases of the Spine". MATERIAL AND METHODS The Guideline was drawn up in line with the Czech National Methodology of the CPG Development, which is based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We used an innovative GRADE-adolopment method that combines adoption and adaptation of the existing guidelines with de novo development of recommendations. In this paper, we present three adapted recommendations on DLS and a recommendation on spondylolisthesis developed de novo by the Czech team. RESULTS Open surgical decompression in DLS patients has been evaluated in three randomized controlled trials (RCTs). A recommendation in favour of decompression was made based on a statistically significant and clinically evident improvement in the Oswestry Disability Index (ODI) and leg pain. Decompression may be recommended for patients with symptoms of DLS in the event of correlation of significant physical limitation and the finding obtained via imaging. The authors of a systematic review of observational studies and one RCT conclude that fusion has a negligible role in the case of a simple DLS. Thus, spondylodesis should only be chosen as an adjunct to decompression in selected DLS patients. Two RCTs compared supervised rehabilitation with home or no exercise, showing no statistically significant difference between the procedures. The guideline group considers the post-surgery physical activity beneficial and suggests supervised rehabilitation in patients who have undergone surgery for DLS for the beneficial effects of exercise in the absence of known adverse effects. Four RCTs were found comparing simple decompression and decompression with fusion in patients with degenerative lumbar spondylolisthesis. None of the outcomes showed clinically significant improvement or deterioration in favour of either intervention. The guideline group concluded that for stable spondylolisthesis the results of both methods are comparable and, when other parameters are considered (balance of benefits and risks, or costs), point in favour of simple decompression. Due to the lack of scientific evidence, no recommendation has been formulated regarding unstable spondylolisthesis. The certainty of the evidence was rated as low for all recommendations. DISCUSSION Despite the unclear definition of stable/unstable slip, the inclusion of apparently unstable cases of DS in stable studies limits the conclusions of the studies. Based on the available literature, however, it can be summarized that in simple degenerative lumbar stenosis and static spondylolisthesis, fusion of the given segment is not justified. However, its use in the case of unstable (dynamic) vertebral slip is undisputable for the time being. CONCLUSIONS The guideline development group suggests decompression in patients with DLS in whom previous conservative treatment did not lead to improvement, spondylodesis only in selected patients, and post-surgical supervised rehabilitation. In patients with degenerative lumbar stenosis and spondylolisthesis with no signs of instability, the guideline development group suggests simple decompression (without fusion). Key words: degenerative lumbar stenosis, degenerative spondylolisthesis, spinal fusion, Clinical Practice Guideline, GRADE, adolopment.

• MeSH
• bederní obratle chirurgie   MeSH
• chirurgická dekomprese metody   MeSH
• fúze páteře * MeSH
• lidé MeSH
• spinální stenóza * chirurgie   MeSH
• spondylolistéza * komplikace   chirurgie   MeSH
• stenóza chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• systematický přehled MeSH

INTRODUCTION: Fibrinogen is one of the essential coagulation factors. Preoperative lower plasma fibrinogen level has been associated with higher blood loss. Scoliosis surgery presents a challenge for the anaesthetic team, one of the reasons being blood loss and transfusion management. Recently, the prophylactic fibrinogen administration has been a debated topic in various indications. It has been described for example, in urological or cardiovascular surgery, as well as in paediatrics. This pilot study is focused on verifying the feasibility of potential large randomised trial and verifying the safety of prophylactic fibrinogen administration in paediatric scoliosis surgery. METHODS AND ANALYSIS: A total of 32 paediatric patients indicated for scoliosis surgery will be recruited. Participants will be randomised into study groups in a 1:1 allocation ratio. Patients in the intervention group will receive prophylactic single dose of fibrinogen, in addition to standard of care. Patients in the control group will receive standard of care without study medication prior to skin incision. The primary aim is to assess the safety of prophylactic fibrinogen administration during scoliosis surgery in children, the incidence of any adverse events (AEs) and reactions will be monitored during participation in the study. The secondary objective is to investigate the additional safety information, feasibility and efficacy of a prophylactic fibrinogen administration. The incidence of AEs and reactions according to selected adverse events of special interest will be monitored. All collected data will be subjected to statistical analysis according to a separate statistical analysis plan. ETHICS AND DISSEMINATION: This trial follows the applicable legislation and requirements for good clinical practice according to the International Conference on Harmonisation E6(R2). All essential trial documents were approved by the relevant ethics committee and national regulatory authority (State Institute for Drug Control) and their potential amendments will be submitted for approval. TRIAL REGISTRATION NUMBER: NCT05391412.

• MeSH
• dítě MeSH
• fibrinogen terapeutické užití   MeSH
• hemostatika * terapeutické užití   MeSH
• krvácení prevence a kontrola   MeSH
• lidé MeSH
• pilotní projekty MeSH
• randomizované kontrolované studie jako téma MeSH
• skolióza * chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH