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1.
Eur Spine J ; 33(1): 19-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37971536

RESUMO

PURPOSE: In spine care, frailty is associated with poor outcomes. The aim of this study was to describe changes in frailty in spine care during the coronavirus disease 2019 (COVID-19) pandemic and their relation to surgical management and outcomes. METHODS: Patients hospitalized for spine pathologies between January 1, 2019, and May 17, 2022, within a nationwide network of 76 hospitals in Germany were retrospectively included. Patient frailty, types of surgery, and in-hospital mortality rates were compared between pandemic and pre-pandemic periods. RESULTS: Of the 223,418 included patients with spine pathologies, 151,766 were admitted during the pandemic and 71,652 during corresponding pre-pandemic periods in 2019. During the pandemic, the proportion of high-frailty patients increased from a range of 5.1-6.1% to 6.5-8.8% (p < 0.01), while the proportion of low frailty patients decreased from a range of 70.5-71.4% to 65.5-70.1% (p < 0.01). In most phases of the pandemic, the Elixhauser comorbidity index (ECI) showed larger increases among high compared to low frailty patients (by 0.2-1.8 vs. 0.2-0.8 [p < 0.01]). Changes in rates of spine surgery were associated with frailty, most clearly in rates of spine fusion, showing consistent increases among low frailty patients (by 2.2-2.5%) versus decreases (by 0.3-0.8%) among high-frailty patients (p < 0.02). Changes in rates of in-hospital mortality were not associated with frailty. CONCLUSIONS: During the COVID-19 pandemic, the proportion of high-frailty patients increased among those hospitalized for spine pathologies in Germany. Low frailty was associated with a rise in rates of spine surgery and high frailty with comparably larger increases in rates of comorbidities.


Assuntos
COVID-19 , Fragilidade , Humanos , Fragilidade/epidemiologia , Fragilidade/complicações , Pandemias , Estudos Retrospectivos , Alemanha/epidemiologia
2.
Biol Chem ; 402(2): 195-206, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33544472

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects.


Assuntos
Proteínas ADAM/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/metabolismo , Osteopontina/metabolismo , Proteínas ADAM/deficiência , Proteínas ADAM/genética , Animais , Neoplasias Encefálicas/patologia , Proliferação de Células , Células Cultivadas , Glioblastoma/patologia , Humanos , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neovascularização Patológica/patologia
3.
Stereotact Funct Neurosurg ; 99(1): 79-89, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32992321

RESUMO

OBJECTIVE: The aim of this work was to compare fiducial-based and intraoperative computed tomography (iCT)-based registration for frameless stereotactic brain biopsy. METHODS: Of 50 frameless stereotactic biopsies with the VarioGuide, 30 cases were registered as iCT based and 20 as fiducial based. Statistical analysis of the target registration error (TRE), dose length product, effective radiation dose (ED), operation time, and diagnostic yield was performed. RESULTS: The mean TRE was significantly lower using iCT-based registration (mean ± SD: 0.70 ± 0.32 vs. 2.43 ± 0.73 mm, p < 0.0001). The ED was significantly lower when using iCT-based registration compared to standard navigational CT (mean ± SD: 0.10 ± 0.13 vs. 2.23 ± 0.34 mSv, p < 0.0001). Post-biopsy iCT was associated with a significant lower (p < 0.0001) ED compared to standard CT (mean ± SD: 1.04 ± 0.18 vs. 1.65 ± 0.26 mSv). The mean surgical time was shorter using iCT-based registration, although the mean total operating room (OR) time did not differ significantly. The diagnostic yield was 96.7% (iCT group) versus 95% (fiducial group). Post-biopsy imaging revealed severe bleeding in 3.3% (iCT group) versus 5% (fiducial group). CONCLUSION: iCT-based registration for frameless stereotactic biopsies increases the accuracy significantly without negative effects on the surgical time or the overall time in the OR. Appropriate scan protocols in iCT registration contribute to a significant reduction of the radiation exposure. The high accuracy of the iCT makes it the more favorable registration strategy when taking biopsies of small tumors or lesions near eloquent brain areas.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Marcadores Fiduciais , Monitorização Neurofisiológica Intraoperatória/métodos , Neuronavegação/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Encéfalo/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Medicina (Kaunas) ; 56(12)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255605

RESUMO

Background and objectives: Expandable cages are frequently used to reconstruct the anterior spinal column after a corpectomy. In this retrospective study, we evaluated the perioperative advantages and disadvantages of corpectomy reconstruction with an expandable cage. Materials and Methods: Eighty-six patients (45 male and 41 female patients, medium age of 61.3 years) were treated with an expandable titanium cage for a variety of indications from January 2012 to December 2019 and analyzed retrospectively. The mean follow-up was 30.7 months. Outcome was measured by clinical examination and visual analogue scale (VAS); myelopathy was classified according to the EMS (European Myelopathy Scale) and gait disturbances with the Nurick score. Radiographic analysis comprised measurement of fusion, subsidence and the C2-C7 angle. Results: Indications included spinal canal stenosis with myelopathy (46 or 53.5%), metastasis (24 or 27.9%), spondylodiscitis (12 or 14%), and fracture (4 or 4.6%). In 39 patients (45.3%), additional dorsal stabilization (360° fusion) was performed. In 13 patients, hardware failure occurred, and in 8 patients, adjacent segment disease occurred. Improvement of pain symptoms, myelopathy, and gait following surgery were statistically significant (p < 0.05), with a medium preoperative VAS of 8, a postoperative score of 3.2, and medium EMS scores of 11.3 preoperatively vs. 14.3 postoperatively. Radiographic analysis showed successful fusion in 74 patients (86%). As shown in previous studies, correction of the C2-C7 angle did not correlate with improvement of neurological symptoms. Conclusion: Our results show that expandable titanium cages are a safe and useful tool in anterior cervical corpectomies for providing adequate anterior column support and stability.


Assuntos
Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento
5.
Eur Spine J ; 28(7): 1697-1711, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953169

RESUMO

PURPOSE: To implement a straightforward workflow that allows to establish augmented reality (AR) support in spine surgery. METHODS: Intraoperative computed tomography (iCT) applying a 32-slice movable scanner was used for navigation registration in a series of 10 patients who underwent surgery for extra- or intradural spinal lesions. Preoperative multimodal image data were integrated by nonlinear registration with the iCT images. Automatic segmentation was used to delineate the 3-dimensional (3-D) outline of the vertebra, and in addition, the tumor extent, as well as implants, was segmented and visualized. RESULTS: Automatic patient registration without user interaction resulted in high navigation accuracy with a mean registration error of only about 1 mm. Moreover, the workflow for establishing AR was straightforward and could be easily integrated in the normal surgical procedure. Low-dose iCT protocols resulted in a radiation exposure of 0.35-0.98 mSv for cervical, 2.16-6.92 mSv for thoracic, and 3.55-4.20 mSv for lumbar surgeries, which is a reduction in the effective radiation dose by 70%. The segmented structures were intuitively visualized in the surgical field using the heads-up display of the operating microscope. In parallel, the microscope video was superimposed with the segmented 3-D structures, which were visualized in a semitransparent manner along with various display modes of the image data. CONCLUSIONS: A microscope-based AR environment was successfully implemented for spinal surgery. The application of iCT for registration imaging ensures high navigational accuracy. AR greatly supports the surgeon in understanding the 3-D anatomy thereby facilitating surgery. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Realidade Aumentada , Imageamento Tridimensional , Tomografia Computadorizada Multidetectores , Procedimentos Ortopédicos/métodos , Coluna Vertebral/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos
6.
Neurosurg Focus ; 47(6): E11, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786552

RESUMO

OBJECTIVE: Low registration errors are an important prerequisite for reliable navigation, independent of its use in cranial or spinal surgery. Regardless of whether navigation is used for trajectory alignment in biopsy or implant procedures, or for sophisticated augmented reality applications, all depend on a correct registration of patient space and image space. In contrast to fiducial, landmark, or surface matching-based registration, the application of intraoperative imaging allows user-independent automatic patient registration, which is less error prone. The authors' aim in this paper was to give an overview of their experience using intraoperative CT (iCT) scanning for automatic registration with a focus on registration accuracy and radiation exposure. METHODS: A total of 645 patients underwent iCT scanning with a 32-slice movable CT scanner in combination with navigation for trajectory alignment in biopsy and implantation procedures (n = 222) and for augmented reality (n = 437) in cranial and spine procedures (347 craniotomies and 42 transsphenoidal, 56 frameless stereotactic, 59 frame-based stereotactic, and 141 spinal procedures). The target registration error was measured using skin fiducials that were not part of the registration procedure. The effective dose was calculated by multiplying the dose length product with conversion factors. RESULTS: Among all 1281 iCT scans obtained, 1172 were used for automatic patient registration (645 initial registration scans and 527 repeat iCT scans). The overall mean target registration error was 0.86 ± 0.38 mm (± SD) (craniotomy, 0.88 ± 0.39 mm; transsphenoidal, 0.92 ± 0.39 mm; frameless, 0.74 ± 0.39 mm; frame-based, 0.84 ± 0.34 mm; and spinal, 0.80 ± 0.28 mm). Compared with standard diagnostic scans, a distinct reduction of the effective dose could be achieved using low-dose protocols for the initial registration scan with mean effective doses of 0.06 ± 0.04 mSv for cranial, 0.50 ± 0.09 mSv for cervical, 4.12 ± 2.13 mSv for thoracic, and 3.37 ± 0.93 mSv for lumbar scans without impeding registration accuracy. CONCLUSIONS: Reliable automatic patient registration can be achieved using iCT scanning. Low-dose protocols ensured a low radiation exposure for the patient. Low-dose scanning had no negative effect on navigation accuracy.


Assuntos
Encefalopatias/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Neuronavegação/métodos , Doenças da Coluna Vertebral/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/cirurgia , Criança , Pré-Escolar , Craniotomia , Feminino , Marcadores Fiduciais , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Doenças da Coluna Vertebral/cirurgia , Técnicas Estereotáxicas , Adulto Jovem
7.
Acta Neurochir (Wien) ; 161(10): 2181-2193, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31300886

RESUMO

BACKGROUND: Microscope-based augmented reality (AR) is commonly used in cranial surgery; however, until recently, this technique was not implemented for spinal surgery. We prospectively investigated, how AR can be applied for intradural spinal tumor surgery. METHODS: For ten patients with intradural spinal tumors (ependymoma, glioma, hemangioblastoma, meningioma, and metastasis), AR was provided by head-up displays (HUDs) of operating microscopes. User-independent automatic AR registration was established by low-dose intraoperative computed tomography. The objects visualized by AR were segmented in preoperative imaging data; non-linear image registration was applied to consider spine flexibility. RESULTS: In all cases, AR supported surgery by visualizing the tumor outline and other relevant surrounding structures. The overall AR registration error was 0.72 ± 0.24 mm (mean ± standard deviation), a close matching of visible tumor outline and AR visualization was observed for all cases. Registration scanning resulted in a low effective dose of 0.22 ± 0.16 mSv for cervical and 1.68 ± 0.61 mSv for thoracic lesions. The mean HUD AR usage in relation to microscope time was 51.6 ± 36.7%. The HUD was switched off and turned on again in a range of 2 to 17 times (5.7 ± 4.4 times). Independent of the status of the HUD, the AR visualization was displayed on monitors throughout surgery. CONCLUSIONS: Microscope-based AR can be reliably applied to intradural spinal tumor surgery. Automatic AR registration ensures high precision and provides an intuitive visualization of the extent of the tumor and surrounding structures. Given this setting, all advanced multi-modality options of cranial AR can also be applied to spinal surgery.


Assuntos
Realidade Aumentada , Ependimoma/cirurgia , Hemangioblastoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Meningioma/cirurgia , Microscopia , Pessoa de Meia-Idade , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos
8.
Medicina (Kaunas) ; 55(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683909

RESUMO

Background and Objectives: To identify predictors of outcome after aneurysmal subarachnoid hemorrhage (aSAH) in our interdisciplinary setting. Materials and Methods: 176 patients who had been treated for aSAH by a team of neurosurgeons and neuroradiologists between 2009 and 2017 were analyzed retrospectively. Age, gender, clinical presentation according to the Hunt and Hess (H&H) grading on admission, overall clot burden, aneurysm localization, modality of aneurysm obliteration, early deterioration (ED), occurrence of vasospasm in transcranial Doppler ultrasonography, delayed cerebral ischemia (DCI), spasmolysis, decompressive craniectomy (DC), cerebrospinal fluid (CSF) shunt placement, deep vein thrombosis (DVT), pulmonary embolism (PE), severe cardiac events (SCE), mortality on Days 14, and 30 after admission, and outcome at one year after the hemorrhage according to the Glasgow Outcome Scale (GOS) were recorded. Chi square, Fisher's exact, Welch's t, and Wilcoxon rank sum served as statistical tests. Generalized linear models were fitted, and ordered logistic regression was performed. Results: SCE (p = 0.049) were a significant predictor of mortality at 14 days after aSAH, but not later during the first year after the hemorrhage. Clipping as opposed to coiling (p = 0.049) of ruptured aneurysms was a significant predictor of survival on Day 30 after aSAH, but not later during the first year after the hemorrhage, while coiling as opposed to clipping of ruptured aneurysms was significantly related to a lower frequency of DVT during hospitalization (p = 0.024). Aneurysms of the anterior circulation were significantly more often clipped, while aneurysms of the posterior circulation were significantly more often coiled (p < 0.001). Age over 70 years (p = 0.049), H&H grade on admission (p = 0.022), overall clot burden (p = 0.035), ED (p = 0.009), DCI (p = 0.013), DC (p = 0.0005), and CSF shunt placement (p = 0.038) proved to be predictive of long-term outcome after aSAH. Conclusion: Long-term results after clipping and coiling of ruptured aneurysms appear equal in an interdisciplinary setting that takes aneurysm localization, available staff, and equipment into account.


Assuntos
Equipe de Assistência ao Paciente/normas , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/tendências , Estudos Retrospectivos , Hemorragia Subaracnóidea/epidemiologia , Tomografia Computadorizada por Raios X/métodos
9.
Int J Cancer ; 142(4): 779-791, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28986926

RESUMO

Metastatic breast cancer affects long-term survival and is a major cause of cancer death for women worldwide. The Metalloprotease-Disintegrin ADAM8 promotes breast cancer development and brain metastasis in a mouse breast cancer model. Here, abundant ADAM8 expression was detected in primary human breast tumors and associated brain metastases. To investigate the function of ADAM8 in metastasis, MB-231 breast cancer cells with ADAM8 knockdown (MB-231_shA8) and scramble control cells (MB-231_shCtrl) were analyzed for their capability to develop metastases. In vitro, formation of metastatic complexes in hanging drops is dependent on ADAM8 and blocked by ADAM8 inhibition. MB-231_shA8 in contrast to MB-231_shCtrl cells were impaired in transmigration through an endothelial and a reconstituted blood-brain barrier. Out of 23 MMP and 22 ADAM genes, only the MMP-9 gene was affected by ADAM8 knockdown in MB-231_shA8 cells. Following re-expression of wild-type ADAM8 in contrast to ADAM8 lacking the cytoplasmic domain in MB-231_shA8 cells caused increased levels of activated pERK1/2 and pCREB (S133) that were associated with elevated MMP-9 transcription. Application of ADAM8 and MMP-9 antibodies reduced transmigration of MB-231 cells suggesting that ADAM8 affects transmigration of breast cancer cells by MMP-9 regulation. ADAM8-dependent transmigration was confirmed in Hs578t cells overexpressing ADAM8. Moreover, transmigration of MB-231 and Hs578t cells was significantly reduced for cells treated with an antibody directed against P-selectin glycoprotein ligand (PSGL-1), a substrate of ADAM8. From these data we conclude that ADAM8 promotes early metastatic processes such as transendothelial migration by upregulation of MMP-9 and shedding of PSGL-1 from breast cancer cells.


Assuntos
Proteínas ADAM/biossíntese , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células Endoteliais/patologia , Metaloproteinase 9 da Matriz/biossíntese , Proteínas de Membrana/biossíntese , Proteínas ADAM/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Técnicas de Cocultura , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Metaloproteinase 9 da Matriz/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Pessoa de Meia-Idade
10.
Acta Neurochir (Wien) ; 160(9): 1681-1689, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30051160

RESUMO

BACKGROUND: Registration accuracy is a main factor influencing overall navigation accuracy. Standard fiducial- or landmark-based patient registration is user dependent and error-prone. Intraoperative imaging offers the possibility for user-independent patient registration. The aim of this paper is to evaluate our initial experience applying intraoperative computed tomography (CT) for navigation registration in cranial neurosurgery, with a special focus on registration accuracy and effective radiation dose. METHODS: A total of 200 patients (141 craniotomy, 19 transsphenoidal, and 40 stereotactic burr hole procedures) were investigated by intraoperative CT applying a 32-slice movable CT scanner, which was used for automatic navigation registration. Registration accuracy was measured by at least three skin fiducials that were not part of the registration process. RESULTS: Automatic registration resulted in high registration accuracy (mean registration error: 0.93 ± 0.41 mm). Implementation of low-dose scanning protocols did not impede registration accuracy (registration error applying the full dose head protocol: 0.87 ± 0.36 mm vs. the low dose sinus protocol 0.72 ± 0.43 mm) while a reduction of the effective radiation dose by a factor of 8 could be achieved (mean effective radiation dose head protocol: 2.73 mSv vs. sinus protocol: 0.34 mSv). CONCLUSION: Intraoperative CT allows highly reliable navigation registration with low radiation exposure.


Assuntos
Craniotomia/métodos , Imageamento Tridimensional/métodos , Monitorização Intraoperatória/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos
11.
Epilepsy Behav ; 76: 56-62, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28927715

RESUMO

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy syndrome. Neuropsychological, electrophysiological, and neuroimaging studies have led to the hypothesis that JME is related to dysfunction of frontal brain regions and mainly frontal thalamocortical networks. METHODS: We investigated possible microstructural white matter abnormalities of 20 patients with JME as compared with 20 healthy control subjects using diffusion tensor imaging (DTI). We analyzed whole-head DTI scans without an a-priori hypothesis using Tract-Based Spatial Statistics (TBSS). To analyze associated gray matter changes, we applied voxel-based morphometry (VBM) to a 3D T1 magnetization prepared rapid gradient echo (MPRAGE) sequence. Neuropsychological testing and personality trait tests were performed to bridge the gap between structure and function. RESULTS: In patients, DTI revealed microstructural white matter changes in anterior parts of the Corpus callosum, anterior parts of the cingulate gyrus, and widespread frontal white matter bilaterally as well as in anterior parts of the right thalamus, which were not accompanied by gray matter changes in VBM. Microstructural changes in the cingulum correlated with personality traits. Neuropsychological test results showed impaired attention and executive functions and reduced short-term memory in the patient group. Also, there was a tendency toward alexithymia and significantly higher scores on depression. SIGNIFICANCE: The present study results showed neuropsychological deficits including frontal lobe cognitive performance and a tendency toward alexithymia as well as accompanying microstructural neuroimaging changes in patients with JME, which all point to alterations in frontal brain regions and frontal thalamocortical networks in these patients.


Assuntos
Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Epilepsia Mioclônica Juvenil/complicações , Testes Neuropsicológicos , Substância Branca/fisiopatologia , Adulto , Encéfalo , Corpo Caloso , Epilepsia Generalizada , Função Executiva/fisiologia , Feminino , Lobo Frontal , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Neuroimagem , Adulto Jovem
12.
Int J Cancer ; 139(6): 1327-39, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27144841

RESUMO

Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy.


Assuntos
Proteína ADAM12/metabolismo , Seio Cavernoso/patologia , Metaloproteinase 14 da Matriz/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Proteína ADAM12/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Metaloproteinase 14 da Matriz/genética , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/cirurgia , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
13.
Epilepsia ; 57(12): 2056-2066, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27753082

RESUMO

OBJECTIVE: To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). METHODS: In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. RESULTS: We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). SIGNIFICANCE: Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise.


Assuntos
Hospitalização/economia , Estado Epiléptico/economia , Estado Epiléptico/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/economia , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Custos e Análise de Custo , Feminino , Alemanha , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Adv Tech Stand Neurosurg ; (43): 37-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26508405

RESUMO

The implementation of fiber tracking or tractography modules in commercial navigation systems resulted in a broad availability of visualization possibilities for major white matter tracts in the neurosurgical community. Unfortunately the implemented algorithms and tracking approaches do not represent the state of the art of tractography strategies and may lead to false tracking results. The application of advanced tractography techniques for neurosurgical procedures poses even additional challenges that relate to effects of the individual anatomy that might be altered by edema and tumor, to stereotactic inaccuracies due to image distortion, as well as to registration inaccuracies and brain shift.


Assuntos
Imagem de Tensor de Difusão/métodos , Imagem de Tensor de Difusão/normas , Neuronavegação/métodos , Neuronavegação/normas , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/normas , Imagem Multimodal/métodos , Imagem Multimodal/normas , Reprodutibilidade dos Testes
15.
Case Rep Oncol ; 17(1): 337-343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404404

RESUMO

Introduction: Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses. Case Presentation: A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with KIAA1549::BRAF fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up. Conclusion: We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.

16.
Neurooncol Pract ; 10(5): 429-436, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37720392

RESUMO

Background: Little is known about delivery of neurosurgical care, complication rate and outcome of patients with high-grade glioma (HGG) during the coronavirus disease 2019 (Covid-19) pandemic. Methods: This observational, retrospective cohort study analyzed routine administrative data of all patients admitted for neurosurgical treatment of an HGG within the Helios Hospital network in Germany. Data of the Covid-19 pandemic (March 1, 2020-May 31, 2022) were compared to the pre-pandemic period (January 1, 2016-February 29, 2020). Frequency of treatment and outcome (in-hospital mortality, length of hospital stay [LOHS], time in intensive care unit [TICU] and ventilation outside the operating room [OR]) were separately analyzed for patients with microsurgical resection (MR) or stereotactic biopsy (STBx). Results: A total of 1763 patients underwent MR of an HGG (648 patients during the Covid-19 pandemic; 1115 patients in the pre-pandemic period). 513 patients underwent STBx (182 [pandemic]; 331 patients [pre-pandemic]). No significant differences were found for treatment frequency (MR: 2.95 patients/week [Covid-19 pandemic] vs. 3.04 patients/week [pre-pandemic], IRR 0.98, 95% CI: 0.89-1.07; STBx (1.82 [Covid-19 pandemic] vs. 1.86 [pre-pandemic], IRR 0.96, 95% CI: 0.80-1.16, P > .05). Rates of in-hospital mortality, infection, postoperative hemorrhage, cerebral ischemia and ventilation outside the OR were similar in both periods. Overall LOHS was significantly shorter for patients with MR and STBx during the Covid-19 pandemic. Conclusions: The Covid-19 pandemic did not affect the frequency of neurosurgical treatment of patients with an HGG based on data of a large nationwide hospital network in Germany. LOHS was significantly shorter but quality of neurosurgical care and outcome was not altered during the Covid-19 pandemic.

17.
J Neurol Surg A Cent Eur Neurosurg ; 84(1): 58-64, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35760290

RESUMO

BACKGROUND: The full impact of the COVID-19 pandemic on surgical spine care is difficult to assess due to a lack in nationwide evidence from more recent phases of the pandemic. We aimed to describe changes in in-hospital processes associated with spinal fusion procedures in the treatment of spinal infections (SI) during different phases of the pandemic. METHODS: In this retrospective observational study, we examined the in-hospital prevalence and outcomes of spinal fusion procedures for SI (along with patient characteristics, rates of transfer to intensive care units, and mortality rates) during the first four waves of the pandemic compared with the corresponding prepandemic periods in 2019. We used administrative data from a nationwide network of 76 hospitals managing 7% of all in-hospital cases in Germany. RESULTS: We observed no significant change in the prevalence of SI fusion procedures during the pandemic, neither in total numbers (349 vs. 373) nor for each wave separately. On a patient level, we found no differences in age, sex, and the prevalence of paresis, and no relevant differences in associated comorbidities. The rate of mechanical ventilation did not change during any of the examined pandemic waves: it ranged between 9.5 and 18.6% during the pandemic and 3.1 and 16.0% during the corresponding prepandemic control periods. The rate of transfer to intensive care changed only during wave 4 (from 70.4 to 54.8%; p = 0.046) but not in any other pandemic phases. We observed no changes in in-hospital mortality rates (range: 2.9-9.7% vs. 6.2-11.3%) or in duration of hospital stay (range: 26.2-30.8 days vs. 20.8-29.2 days). CONCLUSIONS: The main finding of our study is that within this nationwide network of spine care centers in Germany, the delivery of surgical treatment of SI by means of spinal fusion procedures was maintained throughout the first four waves of the pandemic. Furthermore, there were no relevant changes in patient demographics, in-hospital processes, and mortality rates.


Assuntos
COVID-19 , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , COVID-19/epidemiologia , Pandemias , Hospitais , Estudos Retrospectivos , Vértebras Cervicais/cirurgia
18.
Artigo em Inglês | MEDLINE | ID: mdl-37595628

RESUMO

BACKGROUND: The COVID-19 pandemic has significantly affected acute ischemic stroke (AIS) care. In this study, we examined the effects of the pandemic on neurosurgical AIS care by means of decompressive surgery (DS). METHODS: In this retrospective observational study, we compared the characteristics, in-hospital processes, and in-hospital mortality rates among patients hospitalized for AIS during the first four waves of the pandemic (between January 1, 2020 and October 26, 2021) versus the corresponding periods in 2019 (prepandemic). We used administrative data from a nationwide hospital network in Germany. RESULTS: Of the 177 included AIS cases with DS, 60 were from 2019 and 117 from the first four pandemic waves. Compared with the prepandemic levels, there were no changes in weekly admissions for DS during the pandemic. The same was true for patient age (range: 51.7-60.4 years), the number of female patients (range: 33.3-57.1%), and the prevalence of comorbidity, as measured by the Elixhauser Comorbidity Index (range: 13.2-20.0 points). Also, no alterations were observed in transfer to the intensive care unit (range: 87.0-100%), duration of in-hospital stay (range: 14.6-22.7 days), and in-hospital mortality rates (range: 11.8-55.6%). CONCLUSION: In Germany, compared with the prepandemic levels, AIS patients undergoing DS during the first four waves of the pandemic showed no changes in demographics, rates of comorbidity, and in-hospital mortality rates. This is in contrast to previous evidence on patients with less critical types of AIS not requiring DS and underlines the uniqueness of the subgroup of AIS patients requiring DS. Our findings suggests that these patients, in contrast to AIS patients in general, were unable to forgo hospitalization during the COVID-19 pandemic. Maintaining the delivery of DS is an essential aspect of AIS care during a pandemic.

19.
Eur Geriatr Med ; 14(6): 1383-1391, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37955830

RESUMO

PURPOSE: Among brain tumor patients, frailty is associated with poor outcomes. The COVID-19 pandemic has led to increased frailty in the general population. To date, evidence on changes in frailty among brain tumor patients during the pandemic is lacking. We aimed to compare frailty among brain tumor patients in Germany during the COVID-19 pandemic to the pre-pandemic era and to assess potential effects on brain tumor care. METHODS: In this retrospective observational study, we compared frailty among brain tumor patients hospitalized during the COVID-19 pandemic in years 2020 through 2022 to pre-pandemic years 2016 through 2019 based on administrative data from a nationwide network of 78 hospitals in Germany. Using the Hospital Frailty Risk Score (HFRS), frailty was categorized as low, intermediate, or high. We examined changes in frailty, patient demographics, the burden of comorbidity, rates of surgery, and mortality rates for different frailty groups during the pandemic and compared them to pre-pandemic levels. RESULTS: Of the 20,005 included hospitalizations for brain tumors, 7979 were during the pandemic (mean age 60.0 years (± 18.4); females: 49.8%), and 12,026 in the pre-pandemic period (mean age: 59.0 years [± 18.4]; females: 49.2%). Average daily admissions decreased from 8.2 (± 5.1) during pre-pandemic years to 7.3 (± 4.5) during the pandemic (p < 0.01). The overall median HFRS decreased from 3.1 (IQR: 0.9-7.3) during the pre-pandemic years to 2.6 (IQR: 0.3-6.8) during the pandemic (p < 0.01). At the same time, the Elixhauser Comorbidity Index (ECI) decreased from 17.0 (± 12.4) to 16.1 (± 12.0; p < 0.01), but to a larger degree among high compared to low frailty cases (by 1.8 vs. 0.3 points; p = 0.04). In the entire cohort, the mean length of stay was significantly shorter in the pandemic period (9.5 days [± 10.7]) compared with pre-pandemic levels (10.2 days [± 11.8]; p < 0.01) with similar differences in the three frailty groups. Rates of brain tumor resection increased from 29.9% in pre-pandemic years to 36.6% during the pandemic (p < 0.001) without differences between frailty levels. Rates of in-hospital mortality did not change during the pandemic (6.1% vs. 6.7%, p = 0.07), and there was no interaction with frailty. CONCLUSION: Even though our findings are limited in that the HFRS is validated only for patients ≥ 75 years of age, our study among patients of all ages hospitalized for brain tumors in Germany suggests a marked decrease in levels of frailty and in the burden of comorbidities during the COVID-19 pandemic.


Assuntos
Neoplasias Encefálicas , COVID-19 , Fragilidade , Feminino , Humanos , COVID-19/epidemiologia , Pandemias , Fragilidade/epidemiologia , Alemanha/epidemiologia , Hospitais , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia
20.
Cancers (Basel) ; 14(9)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35565431

RESUMO

BACKGROUND: The aim of surgery for skull base meningiomas is maximal resection with minimal damage to the involved cranial nerves and cerebral vessels; thus, implementation of technologies for improved orientation in the surgical field, such as neuronavigation and augmented reality (AR), is of interest. METHODS: Included in the study were 39 consecutive patients (13 male, 26 female, mean age 64.08 ± 13.5 years) who underwent surgery for skull base meningiomas using microscope-based AR and automatic patient registration using intraoperative computed tomography (iCT). RESULTS: Most common were olfactory meningiomas (6), cavernous sinus (6) and clinoidal (6) meningiomas, meningiomas of the medial (5) and lateral (5) sphenoid wing and meningiomas of the sphenoidal plane (5), followed by suprasellar (4), falcine (1) and middle fossa (1) meningiomas. There were 26 patients (66.6%) who underwent gross total resection (GTR) of the meningioma. Automatic registration applying iCT resulted in high accuracy (target registration error, 0.82 ± 0.37 mm). The effective radiation dose of the registration iCT scans was 0.58 ± 1.05 mSv. AR facilitated orientation in the resection of skull base meningiomas with encasement of cerebral vessels and compression of the optic chiasm, as well as in reoperations, increasing surgeon comfort. No injuries to critical neurovascular structures occurred. Out of 35 patients who lived to follow-up, 33 could ambulate at their last presentation. CONCLUSION: A microscope-based AR facilitates surgical orientation for resection of skull base meningiomas. Registration accuracy is very high using automatic registration with intraoperative imaging.

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