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AIM: Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed. PURPOSE: Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed. METHODS: A total of 518 patients' aged 75 ± 10 (41-97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness. RESULTS: Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p < 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients. CONCLUSION: Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments.
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Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Estudios Prospectivos , Pacientes Internos , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/etiología , Fracturas por Compresión/cirugía , Fracturas Osteoporóticas/cirugía , Vertebroplastia/métodos , Cifoplastia/métodos , Dolor/etiología , Resultado del Tratamiento , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesionesRESUMEN
Derivatives of the recently described potent neuroprotective 7-O-cinnamoylsilibinin ester were prepared: its hemisuccinate to improve water solubility and the dehydrosilibinin ester that was shown to form in assay media to investigate its role in overall neuroprotective effects. 7-O-Cinnamoyl-2,3-dehydrosilibinin is less neuroprotective than 7-O-cinnamoylsilibinin in a murine hippocampal cell line (HT-22) and we conclude that the dehydrosilibinin derivatives are not the actual carriers of neuroprotective properties, at least in the assay applied. Solubility of the test compounds was determined in shake-flask experiments and the ester's solubility was greatly improved by introduction of a hemisuccinate at the 23-position of silibinin. Time-stability curves in assay media were recorded. The hemisuccinate ester did not act as a prodrug to release 7-O-cinnamoylsilibinin but is the second ester bond to be cleaved. Nevertheless, it still exhibits significant neuroprotection. Therefore, its greatly increased solubility might effectively counterbalance lower in vitro neuroprotection.
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Ésteres/farmacología , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Silibina/análogos & derivados , Silibina/farmacología , Agua/química , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Ésteres/síntesis química , Ésteres/química , Hipocampo/metabolismo , Ratones , Conformación Molecular , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Especies Reactivas de Oxígeno/metabolismo , Silibina/síntesis química , Solubilidad , Relación Estructura-ActividadRESUMEN
Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields.
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The case of a 43-year-old male patient is described, who suffered several injuries due to a traffic accident, including a distraction injury to the thoracic spine. A specific feature of this case was the existing spondylodesis with material fracture and secondary loss of reduction. Due to this, the guidewires of the pedicle screws were placed in a navigation pattern in the absence of adjustable pedicles and an abnormal screw corridor. This guarantees an optimal positioning with associated patient safety.
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Escoliosis , Vértebras Torácicas , Humanos , Masculino , Adulto , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesiones , Vértebras Torácicas/diagnóstico por imagen , Escoliosis/cirugía , Resultado del Tratamiento , Cirugía Asistida por Computador/métodos , Fusión Vertebral/métodos , Accidentes de TránsitoRESUMEN
The ankle fracture - the most common fracture of the lower extremities - is usually due to pro- and supination trauma and is commonly challenging for junior doctors of orthopaedics and traumatology. To accomplish sufficient surgical results, it is necessary to have surgical experience, not only because of the surrounding fragile soft tissue, but also due to the specific anatomical structures surrounding the ankle joint and the postsurgical biomechanical stress to osteosynthesis. In the following video, the most relevant steps of surgery as well as some useful tips and tricks are mentioned. The intention of the video is to convey to junior orthopaedic surgeons the most important surgical steps for their clinical daily routine.
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BACKGROUND: According to current forecasts, our society will grow older and older, so that the proportion of 6% of the German population from 2017 who were 80 years or older will increase further. The frequency of falls in this patient population lead to a further increase of sacral insufficiency fractures. HYPOTHESIS: The aim of this study is to evaluate the multimodal interdisciplinary conservative therapy regime for sacral insufficiency fractures in geriatric patients, especially on the basis of mobility and the need for assistance. PATIENTS AND METHODS: A cohort of patients, who were treated as inpatients at the Waldkrankenhaus St. Marien in Erlangen with ICD-10 for sacral fractures S32.1 as the main diagnosis, was retrospectively examined. Only newly diagnosed sacral insufficiency fractures were taken into account. Patients were divided into groups based on the factors hospital stay, fracture location on the sacrum, and location of concomitant pelvic ring injury. The Barthel Index, the Tinetti's Mobility Test and the Timed Up&Go Test were recorded. RESULTS: 46 patients met the inclusion criteria. Using the conservative therapy, improvements were achieved in all patients in terms of need for care, mobility without aids and risk of falling, also patients with an anterior and posterior pelvic ring fracture. Regard a score improvement in the Barthel Index and Tinetti Mobility Test, patients with bilateral sacral insufficiency fracture (n=17, 37.0%) did not differ significantly from patients with unilateral sacral insufficiency fracture (n=22, 47.8%). CONCLUSION: In geriatric patients, decisions about therapy should always be made on an individual and interdisciplinary basis. The conservative therapy regimen continues to play an important role in this. The collected tests-consisting of Barthel Index, Tinetti Mobility Test and Timed Up&Go Test-are well suited for further reproducible, objective studies with a larger patient collective. LEVEL OF EVIDENCE: IV.
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Fracturas por Estrés , Huesos Pélvicos , Fracturas de la Columna Vertebral , Humanos , Anciano , Sacro/lesiones , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/terapia , Estudios Retrospectivos , Tratamiento Conservador , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/terapia , Huesos Pélvicos/lesionesRESUMEN
STUDY DESIGN: Multicenter prospective cohort study. OBJECTIVE: To analyse therapeutical strategies applied to osteoporotic thoracolumbar OF 4 injuries, to assess related complications and clinical outcome. METHODS: A multicenter prospective cohort study (EOFTT) including 518 consecutive patients who were treated for an Osteoporotic vertebral compression fracture (OVCF). For the present study, only patients with OF 4 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5L, and Barthel Index after a minimum follow-up of 6 weeks. RESULTS: A total of 152 (29%) patients presented with OF 4 fractures with a mean age of 76 years (range 41-97). The most common treatment was short-segment posterior stabilization (51%; hybrid stabilization in 36%). Mean follow up was 208 days (±131 days), mean ODI was 30 ± 21. Dorsoventral stabilized patients were younger compared to the other groups (P < .001) and had significant better TuG compared to hybrid stabilization (P = .049). The other clinical outcomes did not differ in the therapy strategies (VAS pain: P = 1.000, ODI: P > .602, Barthel: P > .252, EQ-5D 5L index value: P > .610, VAS-EQ-5D 5L: P = 1.000). The inpatient complication rate was 8% after conservative and 16% after surgical treatment. During follow-up period 14% of conservatively treated patients and 3% of surgical treated patients experienced neurological deficits. CONCLUSIONS: Conservative therapy of OF 4 injuries seems to be viable option in patients with only moderate symptoms. Hybrid stabilization was the dominant treatment strategy leading to promising clinical short-term results. Stand-alone cement augmentation seems to be a valid alternative in selected cases.
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STUDY DESIGN: Subgroup analysis of a multicenter prospective cohort study. OBJECTIVE: To analyse surgical strategies applied to osteoporotic thoracolumbar osteoporotic fracture (OF) 5 injuries with anterior or posterior tension band failure and to assess related complications and clinical outcome. METHODS: A multicenter prospective cohort study (EOFTT) was conducted at 17 spine centers including 518 consecutive patients who were treated for an osteoporotic vertebral fracture (OVF). For the present study, only patients with OF 5 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale (VAS), Oswestry Disability Questionnaire (ODI), Timed Up & Go test (TUG), EQ-5D 5L, and Barthel Index. RESULTS: In total, 19 patients (78 ± 7 years, 13 female) were analysed. Operative treatment consisted of long-segment posterior instrumentation in 9 cases and short-segment posterior instrumentation in 10 cases. Pedicle screws were augmented in 68 %, augmentation of the fractured vertebra was performed in 42%, and additional anterior reconstruction was done in 21 %. Two patients (11 %) received short-segment posterior instrumentation without either anterior reconstruction or cement-augmentation of the fractured vertebra. No surgical or major complications occurred, but general postoperative complications were observed in 45%. At a follow-up of mean 20 ± 10 weeks (range, 12 to 48 weeks), patients showed significant improvements in all functional outcome parameters. CONCLUSIONS: In this analysis of patients with type OF 5 fractures, surgical stabilization was the treatment of choice and lead to significant short-term improvement in terms of functional outcome and quality of life despite a high general complication rate.
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STUDY DESIGN: Multicenter prospective cohort study. OBJECTIVE: The study aims to validate the recently developed OF score for treatment decisions in patients with osteoporotic vertebral compression fractures (OVCF). METHODS: This is a prospective multicenter cohort study (EOFTT) in 17 spine centers. All consecutive patients with OVCF were included. The decision for conservative or surgical therapy was made by the treating physician independent of the OF score recommendation. Final decisions were compared to the recommendations given by the OF score. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5 L, and Barthel Index. RESULTS: In total, 518 patients (75.3% female, age 75 ± 10) years were included. 344 (66%) patients received surgical treatment. 71% of patients were treated following the score recommendations. For an OF score cut-off value of 6.5, the sensitivity and specificity to predict actual treatment were 60% and 68% (AUC .684, P < .001). During hospitalization overall 76 (14.7%) complications occurred. The mean follow-up rate and time were 92% and 5 ± 3.5 months, respectively. While all patients in the study cohort improved in clinical outcome parameters, the effect size was significantly less in the patients not treated in line with the OF score's recommendation. Eight (3%) patients needed revision surgery. CONCLUSIONS: Patients treated according to the OF score's recommendations showed favorable short-term clinical results. Noncompliance with the score resulted in more pain and impaired functional outcome and quality of life. The OF score is a reliable and save tool to aid treatment decision in OVCF.
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Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of Gâ protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1'-(2-tolyl)-1,4'-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M1 -selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M1 positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.
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Bencimidazoles/farmacología , Carbacol/análogos & derivados , Carbacol/farmacología , Piperidinas/farmacología , Quinolinas/farmacología , Receptor Muscarínico M1/agonistas , Bencimidazoles/agonistas , Bencimidazoles/síntesis química , Bencimidazoles/metabolismo , Carbacol/agonistas , Carbacol/metabolismo , Agonismo Parcial de Drogas , Células HEK293 , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Agonistas Muscarínicos/síntesis química , Agonistas Muscarínicos/metabolismo , Agonistas Muscarínicos/farmacología , Piperidinas/agonistas , Piperidinas/síntesis química , Piperidinas/metabolismo , Quinolinas/agonistas , Quinolinas/síntesis química , Quinolinas/metabolismo , Receptor Muscarínico M1/metabolismoRESUMEN
A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22â¯cells. Despite weak activities in the FRAP assay, esters of the α,ß-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay. Cinnamic and ferulic acid esters (5a and 6a) also showed overadditive effects regarding inhibition of microglial activation, PC12â¯cell differentiation, in vitro ischemia as well as anti-aggregating abilities against Aß42 peptide and τ protein. Remarkably, the esters of ferulic acid with silybin A and silybin B (11a and 11b) showed a moderate but significant difference in both neuroprotection and in their anti-aggregating capacities. The results demonstrate that non-toxic natural antioxidants can be regioselectively connected as esters with medium-term stability exhibiting very pronounced overadditive effects in a portfolio of biological assays.