Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.

BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients >18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 + 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy.Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, p=0.007). Preoperative Karnofsky Performance Score (KPS) < 80 showed a reduced OS (4.2 vs. 18 months, p=0.02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, p=0.0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, p=0.4006). CONCLUSION: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.

Methylation subgroup and molecular heterogeneity is a hallmark of glioblastoma: implications for biopsy targeting, classification and therapy.

BACKGROUND: Intratumoral heterogeneity at the cellular and molecular level is a hallmark of glioblastoma (GB) that contributes to treatment resistance and poor clinical outcome. Little is known regarding epigenetic heterogeneity and intratumoral phylogeny and their implication for molecular classification and targeted therapies. PATIENTS AND METHODS: Multiple tissue biopsies (238 in total) were sampled from 56 newly-diagnosed, treatment-naive GB patients from a prospective in-house cohort and publicly available data and profiled for DNA methylation using the Illumina MethylationEPIC array. Methylation-based classification using the glioma classifier developed by Ceccarelli et al. and estimation of the MGMT promoter methylation status via the MGMT-STP27 model were carried out. In addition, copy number variations (CNVs) and phylogeny were analyzed. RESULTS: Almost half of the patients (22/56, 39%) harbored tumors composed of heterogeneous methylation subtypes. We found two predominant subtype combinations: classic-/mesenchymal-like, and mesenchymal-/pilocytic astrocytoma-like. Nine patients (16%) had tumors composed of subvolumes with and without MGMT promoter methylation, whereas 20 patients (36%) were homogeneously methylated, and 27 patients (48%) were homogeneously unmethylated. CNV analysis revealed high variations in many genes, including CDKN2A/B, EGFR, and PTEN. Phylogenetic analysis correspondingly showed a general pattern of CDKN2A/B loss and gain of EGFR, PDGFRA, and CDK4 during early stages of tumor development. CONCLUSIONS: (Epi)genetic intratumoral heterogeneity is a hallmark of GB, both at DNA methylation and CNV level. This intratumoral heterogeneity is of utmost importance for molecular classification as well as for defining therapeutic targets in this disease, as single biopsies might underestimate the true molecular diversity in a tumor.

Obesity and perioperative adverse events in patients undergoing complex revision surgery for the thoracolumbar spine.

BACKGROUND: There are no previous studies that evaluate the effect of obesity on patients undergoing complex revision thoracolumbar spine surgery. The primary objective was to determine the relationship between obesity and perioperative adverse events (AEs) with patients undergoing complex revision thoracolumbar spine surgery while controlling for psoas muscle index (PMI) as a confounding variable. The secondary objective was to determine the relationship between obesity and 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, and post-operative length of stay (LOS). METHODS: Between May 2016 and February 2020, a retrospective analysis of individuals undergoing complex revision surgery of the thoracolumbar spine was performed at a single institution. Obesity was defined as BMI ≥ 30.0 kg/m2. PMI < 500 mm2/m2 for males and < 412 mm2/m2 for females were used to define low muscle mass. A Spine Surgical Invasiveness Index (SSII) > 10 was used to define complex revision surgery. A multivariable logistic regression model was used to ascertain the effects of low muscle mass, obesity, age, and gender on the likelihood of the occurrence of any AE. RESULTS: A total of 114 consecutive patients were included in the study. Fifty-four patients were in the obese cohort and 60 patients in the non-obese cohort. There was not a significant difference in perioperative outcomes of both the obese and non-obese patients. There were 22 obese patients (40.7%) and 33 non-obese patients (55.0%) that experienced any AE (p = 0.130). Multivariable analysis demonstrated that individuals with low muscle mass had a significantly higher likelihood for an AE than individuals with normal or high muscle mass (OR: 7.53, 95% CI: 3.05-18.60). Obesity did not have a significant effect in predicting AEs. CONCLUSIONS: Obesity is not associated with perioperative AEs, 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, or post-operative length of stay (LOS) among patients undergoing complex revision thoracolumbar spine surgery. LEVEL OF EVIDENCE: III.

Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression.

PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.

Outcomes after stereotactic radiosurgery of brain metastases in patients with malignant melanoma and validation of the melanoma molGPA.

INTRODUCTION: Malignant melanoma is the third most common primary in the diagnosis of brain metastases. Stereotactic radiosurgery (SRS) is a well-established treatment option in limited brain disease. We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity. METHODS: We evaluated 173 brain metastases in 83 patients with malignant melanoma. All were treated with SRS median dose of 20 Gy prescribed to the 80 or 100% isodose line between 2002 and 2019. All patients were followed-up regularly, including contrast-enhanced brain imaging as well as clinical examination, initially 6 weeks after treatment, then in quarterly follow-up. RESULTS: The median age was 61 years (range 27-80); 36 female and 47 male patients were treated. After a median follow-up of 5.7 months, median OS (overall survival) was 9.7 months 95%-KI 4.7-14.7). LC (local control) at 6 months, 12, 24 months was 89%, 86%, and 72%, respectively (median was not reached). Median DBC (distant brain control) was 8.2 months (95%-KI 4.7-11.7). For OS, a KPS ≥ 80%, a positive BRAF mutation status, a small PTV (planning target volume), the absence of extracranial metastases, as well as a GPA and melanoma molGPA > 2 were prognostic factors. In the MVA, a small PTV and a melanoma molGPA > 2 remained significant. CONCLUSION: The present survival outcomes support the use of the disease-specific melanoma molGPA as reliable prognostic score. Favorable outcomes for SRS compared to other studies were observed. In the treatment of brain metastases of malignant melanoma patients, a multidisciplinary approach consisting of surgery, SRS, chemotherapy, and immunotherapy should be considered.

Sarcopenia predicts perioperative adverse events following complex revision surgery for the thoracolumbar spine.

BACKGROUND CONTEXT: Sarcopenia measured by psoas muscle index (PMI) has been shown to predict perioperative mortality and adverse events (AEs) after various surgical procedures. However, this relationship has not been studied in complex revision thoracolumbar spine surgery. PURPOSE: This study aimed to determine the relationship between sarcopenia and perioperative AEs among patients undergoing complex revision thoracolumbar spine surgery. STUDY DESIGN: Retrospective cohort study PATIENT SAMPLE: A retrospective analysis was performed at a single institution between May 2016 and February 2020 of patients undergoing complex revision thoracolumbar spine surgery by three board certified fellowship-trained orthopaedic spine surgeons. OUTCOME MEASURES: Perioperative adverse events including postoperative anemia requiring transfusion, cardiac complication, sepsis, wound complication, delirium, intra-operative dural tear, acute kidney injury, pneumonia, urinary tract infection, urinary retention, epidural hematoma, and deep vein thrombosis. Secondary outcome measures were 30-day readmission rates, 30-day re-operation rates, in-hospital mortality rates, discharge disposition, and postoperative length of stay (LOS). METHODS: Sarcopenia was analyzed using PMI, calculated at the L3 vertebral body measured on preoperative magnetic resonance imaging (MRI) or computed tomography (CT) normalized to height2 (mm2/m2). Receiver operating characteristic (ROC) curve analysis and Youden index were used to determine gender-specific PMI cut-off values for predicting perioperative AEs. Sarcopenia was defined as PMI below the cut-off values. Complex revision surgery was defined as Spine Surgical Invasiveness Index >10. RESULTS: A total of 114 consecutive patients were included in the study. ROC curve analysis demonstrated PMI <500 mm2/m2 for males and <412 mm2/m2 for females as predictors for perioperative AEs. 49 patients were in the sarcopenia cohort and 65 patients in the nonsarcopenia cohort. The sarcopenia group had higher overall perioperative AEs (75.5% vs 27.7%, p<.001) and individual AEs including: postoperative anemia requiring transfusion, wound complication, delirium, acute kidney injury, pneumonia, urinary tract infection, and deep vein thrombosis. The sarcopenia group had higher 30-day reoperation rate (14.3% vs 3.1%, p=.037), 30-day readmission rate (16.3% vs 3.1%, p=.018), rate of discharge to a facility (83.7% vs 50.8%, p<.001), and longer length of stay (LOS) (7.3±4.2 days vs 5.6±3.5 days, p=.023). CONCLUSIONS: Sarcopenia measured by PMI is associated with higher perioperative AEs, 30-day readmission rates, 30-day reoperation rates, rate of discharge to a facility, and longer LOS among patients undergoing complex revision thoracolumbar spine surgery.

Two-dimensional parametric parenchymal blood flow in transarterial chemoembolisation for hepatocellular carcinoma: perfusion change quantification and tumour response prediction at 3 months post-intervention.

AIM: To evaluate the feasibility and potential value of two-dimensional (2D) parametric parenchymal blood flow (2D-PPBF) for the assessment of perfusion changes during transarterial chemoembolisation with drug-eluting beads (DEB-TACE) and to analyse correlations of 2D-PPBF parameters and tumour response. MATERIALS AND METHODS: Thirty-two patients (six women, 26 men, mean age: 67±8.9 years) with unresectable hepatocellular carcinoma (HCC) who underwent their first DEB-TACE were included in this study. To quantify perfusion changes using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed. Ratios were calculated between the reference region of interest (ROI) and the wash-in rate (WIR), the arrival to peak (AP) and the area under the curve (AUC) of the generated time-density curves. Comparisons between pre- and post-embolisation data were made using the Wilcoxon signed-rank test. Tumour response was assessed at 3 months using the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and correlated to changes of 2D-PPBF parameters. RESULTS: All 2D-PPBF parameters derived from the ROI-based time-attenuation curves were significantly different pre-versus post-DEB-TACE. Although the AUC, the WIR and target lesion size measured in accordance with mRECIST decreased (p≤0.0001) significantly, AP values showed a significant increase (p = 0.0033). Tumour response after DEB-TACE correlated with changes in the AUC (p = 0.01, r = -0.45). CONCLUSION: 2D-PPBF offers an objective approach to analyse perfusion changes of embolised tumour tissue following DEB-TACE and can therefore be used to predict tumour response.

Percutaneous isolated hepatic perfusion (chemosaturation) with melphalan following right hemihepatectomy in patients with cholangiocarcinoma and metastatic uveal melanoma: peri- and post-interventional adverse events and therapy response compared to a matched group without prior liver surgery.

To evaluate feasibility, frequency and severity of peri-procedural complications and post-procedural adverse events (AEs) in patients with advanced cholangiocarcinoma or liver metastasis of uveal melanoma and prior hemihepatectomy undergoing chemosaturation percutaneous hepatic perfusion (CS-PHP) and to analyze therapy response and overall survival compared to a matched group without prior surgery. CS-PHP performed between 10/2014 and 02/2018 were retrospectively assessed. To determine peri-procedural safety and post-procedural adverse events, hospital records and hematological, hepatic and biliary function were categorized using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (1-5; mild-death). Significance was tested using Wilcoxon signed-rank and Mann-Whitney U test. Kaplan-Meier estimation and log-rank test assessed survival. Overall 21 CS-PHP in seven patients (4/7 males; 52 ± 10 years) with hemihepatectomy (grouphemihep) and 22 CS-PHP in seven patients (3/7 males; 63 ± 12 years) without prior surgery (groupnoresection) were included. No complications occurred during the CS-PHP procedures. Transient changes (CTCAE grade 1-2) of liver enzymes and blood cells followed all procedures. In comparison, grouphemihep presented slightly more AEs grade 3-4 (e.g. thrombocytopenia in 57% (12/21) vs. 41% (9/22; p = 0.37)) 5-7 days after CS-PHP. These AEs were self-limiting or responsive to treatment (insignificant difference of pre-interventional to 21-45 days post-interventional values (p > 0.05)). One patient in grouphemihep with high tumor burden died eight days following CS-PHP. No deaths occurred in groupnoresection. In comparison, overall survival after first diagnosis was insignificantly shorter in groupnoresection (44.7(32-56.1) months) than in grouphemihep (48.3(34.6-72.8) months; p = 0.48). The severity of adverse events following CS-PHP in patients after hemihepatectomy was comparable to a matched group without prior liver surgery. Thus, the performance of CS-PHP is not substantially compromised by a prior hemihepatectomy.

Novas construções em análise perante o vazio psíquico, o tédio e a apatia / New constructions in analysis in the face of psychic emptiness, boredom and apathy / Nuevas construcciones en análisis ante el vacío psíquico, o el tedio y la apatía / Nouvelles constructions en cours d'analyse face au vide psychique, à l'ennui et à l'apathie

RESUMO No texto "Construções em análise", Freud afirma que a tarefa do analista envolve uma atividade de construção, originária da complementação e da integração dos restos conservados da história do analisando. Neste artigo, sustenta-se que, além do modelo de 1937, existem outras formas de construção em análise, concebidas a partir da relação da dupla analista-analisando e decorrentes do vínculo transferencial. Essas construções repercutem na simbolização primária e na elaboração de novas narrativas sobre o vazio psíquico. Propõe-se que, nos casos de vazio psíquico, tédio e apatia, o analista há de se envolver em um trabalho de construção para revitalizar a cena analítica, propiciar uma rota de simbolização do material cindido do analisando e contribuir para que a análise funcione como um espaço potencial para esse fim. Exemplifica-se tal manejo com um caso clínico da chamada síndrome da resignação.

ABSTRACT In the text Constructions in Analysis, Freud (1937/2018) states that the task of the analyst involves a construction activity, originating from the "complementation" and "integration of surviving remains" of the analysand's history. The aim of this article is to argue that, besides this 1937 model, there are also other forms of constructions in analysis, conceived from the relationship between analyst-analysand and resulting from the transference-countertransference link - constructions that generate repercussions on primary symbolization and the elaboration of new narratives about the psychic void. It is proposed that, in cases of psychic emptiness, boredom and apathy, the analyst should engage in a constructive work to revitalize the analytic scene, providing a route of symbolization of the analysand's split material and contributing to the analysis functioning as a potential space for that purpose. Such management is exemplified with a clinical case of the so-called Resignation Syndrome.

RESUMEN En el texto "Construcciones en análisis", Freud afirma que la tarea del analista envuelve una actividad de construcción, que tiene origen en la complementación y la integración de los restos conservados de la historia del analizado. En este artículo, se sostiene que, además del modelo de 1937, existen otras formas de construcción en análisis, concebidas a partir de la relación entre el dúo analista-analizado y decurrentes del vínculo transferencial. Estas construcciones repercuten en el simbolismo primario y en la elaboración de nuevas narrativas sobre el vacío psíquico. Se propone que, en los casos de vacío psíquico, tedio y apatía, el analista se envolverá en un trabajo de construcción para revitalizar la escena analítica, propiciar una ruta de simbolismo del material escindido del analizado y contribuir para que el análisis funcione como un espacio potencial para esa finalidad. Se ejemplifica tal manejo con un caso clínico de la llamada síndrome de la resignación.

RÉSUMÉ Dans le texte Constructions en analyse, Freud (1937/2018) affirme que la tâche de l'analyste implique une activité de construction, qui découle de la «complémentation¼ et de « l'intégration de vestiges conservés ¼ de l'histoire de l'analysant. Dans cet article, on soutient que, outre ce modèle de 1937, il existe aussi d'autres formes de constructions en cours d'analyse, conçues à partir de la relation entre l'analyste et l'analysant et résultant du lien transfert / contre-transfert, constructions qui ont des répercussions sur la symbolisation primaire et l'élaboration de nouveaux récits concernant le vide psychique. Il est proposé que, dans les cas de vide psychique, d'ennui et d'apathie, l'analyste s'engage dans un travail de construction visant à revitaliser la scène analytique, à fournir une voie de symbolisation du matériel scindé de l'analysant et à contribuer au fonctionnement de l'analyse en tant qu'un espace potentiel à cet effet. Une telle gestion est illustrée par la mention d'un cas clinique du syndrome dit de résignation.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Sub-decapitation in suicidal chainsaw injury: report of a rare case and operative management.

Chainsaw accidents are severe injuries, mostly work-related and concerning upper or lower extremities. Few suicidal chainsaw injuries are reported, all of them fatal. We report the case of a 23-year-old man who attempted suicide by sub-decapitation with a chainsaw, its successful (peri-) operative management, and clinical course along with a discussion of the contemporary management and body of evidence of such lesions. Chainsaw injuries are severe traumas. Stepwise surgery with maximal functional reconstruction is safe and optimal clinical outcome can be achieved.

Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas.

PURPOSE: Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS: Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS: In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS: We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

Urinary peptidome analyses for the diagnosis of chronic kidney disease in dogs.

Chronic kidney disease (CKD) is clinically important in canine medicine. Current diagnostic tools lack sensitivity for detection of subclinical CKD. The aim of the present study was to evaluate urinary peptidome analysis for diagnosis of CKD in dogs. Capillary electrophoresis coupled to mass spectrometry analysis demonstrated presence of approximately 5400 peptides in dog urine. Comparison of urinary peptide abundance of dogs with and without CKD led to the identification of 133 differentially excreted peptides (adjusted P for each peptide <0.05). Sequence information was obtained for 35 of these peptides. This 35 peptide subset and the total group of 133 peptides were used to construct two predictive models of CKD which were subsequently validated by researchers masked to results in an independent cohort of 20 dogs. Both models diagnosed CKD with an area under the receiver operating characteristic (ROC) curve of 0.88 (95% confidence intervals [CI], 0.72-1.0). Most differentially excreted peptides represented fragments of collagen I, indicating possible association with fibrotic processes in CKD (similar to the equivalent human urinary peptide CKD model, CKD273). This first study of the urinary peptidome in dogs identified peptides that were associated with presence of CKD. Future studies are needed to validate the utility of this model for diagnosis and prediction of progression of canine CKD in a clinical setting.

[Cervical spine involvement in rheumatoid arthritis : Diagnostics and treatment of instability due to rheumatism]. / Rheumatoide Arthritis der zervikalen Wirbelsäule : Diagnostik und Therapie rheumatisch bedingter Instabilitäten.

In addition to involvement of small peripheral joints, the cervical spine is the second most affected body region in rheumatoid arthritis (RA). Due to improvement of pharmaceutical treatment in recent years, new data show that there is a decreasing prevalence of cervical involvement; however, depending on the severity of cervical lesions surgical treatment still plays an important role. The sequelae of involvement of the cervical spine are craniocervical and atlantoaxial instability, which can cause severe pain, neural deficits and even death. Multimodal conservative treatment can lead to an alleviation of pain but in cases of therapy-resistant pain or neural deficits surgical treatment alone is essential to improve patient outcome. For isolated atlantoaxial instability (AAS), atlantoaxial fusion by posterior C1-2 fixation according to Harms and Goel is the method of choice. Posterior stabilization including C0 should be avoided whenever possible due to substantial limitations in range of movement.

Evaluation of radiation-related invasion in primary patient-derived glioma cells and validation with established cell lines: impact of different radiation qualities with differing LET.

PURPOSE: Glioblastoma multiforme (GBM) is the most common primary brain tumor and has a very poor overall prognosis. Multimodal treatment is still inefficient and one main reason is the invasive nature of GBM cells, enabling the tumor cells to escape from the treatment area causing tumor progression. This experimental study describes the effect of low- and high-LET irradiation on the invasion of primary GBM cells with a validation in established cell systems. METHODS: Seven patient derived primary GBM as well as three established cell lines (LN229, LN18 and U87) were used in this study. Invasion was investigated using Matrigel® coated transwell chambers. Irradiation was performed with low- (X-ray) and high-LET (alpha particles) radiation. The colony formation assay was chosen to determine the corresponding alpha particle dose equivalent to the X-ray dose. RESULTS: 4 Gy X-ray irradiation increased the invasive potential of six patient derived GBM cells as well as two of the established lines. In contrast, alpha particle irradiation with an equivalent dose of 1.3 Gy did not show any effect on the invasive behavior. The findings were validated with established cell lines. CONCLUSION: Our results show that in contrast to low-LET irradiation high-LET irradiation does not enhance the invasion of established and primary glioblastoma cell lines. We therefore suggest that high-LET irradiation could become an alternative treatment option. To fully exploit the benefits of high-LET irradiation concerning the invasion of GBM further molecular studies should be performed.

[C5 palsy after multi-segmental cervical decompression : How can it be avoided?] / Die C5-Parese nach multisegmentaler zervikaler Dekompression : Wie kann diese vermieden werden?

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) as well as posterior instrumentation of the cervical spine are frequently performed surgeries for cervical disc prolapse or spinal stenosis. Surgery itself harbors a very low risk of adverse events. Postoperative palsy of the C5 nerve root, however, is a severe complication and its origin is still not fully understood. The risk of such a C5 palsy is reported to be between 0 and 30%; 5% on average according to the literature. OBJECTIVES: To describe underlying pathomechanisms and to recommend strategies for risk reduction. MATERIALS AND METHODS: An extensive literature research via Medline was performed. RESULTS: Potential risk factors are male gender, sagittal diameter below 5.6 mm, anterior approach, and higher age. CONCLUSIONS: Currently available data only originates from retrospective or anatomical studies. A prospective register study with the goal to put light on the pathogenesis is currently being performed.

[Intraoperative neuromonitoring in cervical deformity surgery]. / Intraoperatives Neuromonitoring in der rekonstruktiven Halswirbelsäulenchirurgie.

Correction of cervical deformity is associated with a considerable risk of neurological deterioration. The use of intraoperative neuromonitoring (IOM) can, however, significantly increase patient safety. Nonetheless, data on the effectiveness of IOM during reconstructive cervical surgery are very limited. Since the surgical maneuvers in reconstructive cervical surgery represent the same dangers to the spinal cord as in scoliosis correction, the same influence of IOM on the clinical outcome may be assumed. IOM has been shown to decrease the rate of neurological complications in scoliosis surgery. Herein, we discuss the current evidence for the efficacy of IOM during reconstructive cervical surgery as well as during scoliosis surgery.

[Operative treatment of the degenerative cervical spine]. / Operative Versorgung der degenerativen Halswirbelsäule.

BACKGROUND: Degenerative alterations of the cervical spine often entail disc herniations and stenoses of the spinal canal and/or neural foramen. Mediolateral or lateral compression of nerve roots causes cervical radiculopathy, which is an indication for surgery in cases of significant motor deficits or refractory pain. Median canal encroachment may result in compression of the spinal cord and cervical myelopathy. Its natural history is typically characterized by episodic deterioration, so that surgical decompression is indicated in cases of clear myelopathic signs. OBJECTIVE: The aim of the present article is to outline the operative options for patients with cervical radiculopathy and myelopathy. Furthermore, we describe the operative complications and the outcome in these patients. MATERIAL AND METHODS: For this manuscript a systematic PubMed search was carried out, the papers were systematically analyzed for the best evidence and this was combined with the authors' experience. RESULTS AND CONCLUSION: Depending on the cervical pathology, the most prevalent surgical options for radiculopathy include anterior cervical discectomy and fusion (ACDF), cervical arthroplasty or posterior cervical foraminotomy. Cervical myelopathy may be decompressed by ACDF, corpectomy or posterior approaches like laminectomy plus instrumented fusion or laminoplasty. The outcome depends on the cervical pathology and the type of operation. Overall, in long-term follow-up studies the results of all surgical techniques on the cervical spine are generally considered to be very good, although specific patient characteristics are more suited for a particular approach.