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1.
Cell ; 142(4): 613-24, 2010 Aug 20.
Article in English | MEDLINE | ID: mdl-20723761

ABSTRACT

Interferon (IFN)-induced immunoproteasomes (i-proteasomes) have been associated with improved processing of major histocompatibility complex (MHC) class I antigens. Here, we show that i-proteasomes function to protect cell viability under conditions of IFN-induced oxidative stress. IFNs trigger the production of reactive oxygen species, which induce protein oxidation and the formation of nascent, oxidant-damaged proteins. We find that the ubiquitylation machinery is concomitantly upregulated in response to IFNs, functioning to target defective ribosomal products (DRiPs) for degradation by i-proteasomes. i-proteasome-deficiency in cells and in murine inflammation models results in the formation of aggresome-like induced structures and increased sensitivity to apoptosis. Efficient clearance of these aggregates by the enhanced proteolytic activity of the i-proteasome is important for the preservation of cell viability upon IFN-induced oxidative stress. Our findings suggest that rather than having a specific role in the production of class I antigens, i-proteasomes increase the peptide supply for antigen presentation as part of a more general role in the maintenance of protein homeostasis.


Subject(s)
Histocompatibility Antigens Class I/metabolism , Interferons/immunology , Proteasome Endopeptidase Complex/immunology , Proteasome Endopeptidase Complex/metabolism , Proteins/metabolism , Animals , Antigen Presentation , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Histocompatibility Antigens Class I/immunology , Homeostasis , Humans , Inflammation/metabolism , Mice , Mice, Inbred C57BL , Ubiquitination
3.
Neurosurg Rev ; 44(4): 2239-2244, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33037537

ABSTRACT

The aim of this case series was to provide a modern cohort of patients with cerebral aspergillosis and show the effectiveness of modern treatment concepts. In a 10-year period from January 2009 to January 2019, we identified 10 patients (6 male, 4 female) who received surgery or frameless stereotactic drainage of a cerebral aspergilloma at our center. Patients' and disease characteristics were recorded. The median age was 65 (range 45 to 83). We conducted 133 cranial surgeries in 100 patients due to cerebral brain abscess (BA) during that time, which leads to a percentage of 10% of aspergilloma within BAs in our patient sample. We performed 3.1 surgeries per patient followed by antifungal treatment for 6 months (= median) according to the microbiological findings. Regarding comorbidities, the mean Charlson comorbidity index (CCI) at the time of admission was 5, representing an estimated 10-year survival of 21%. Six (60%) of 10 patients showed conditions of immunosuppression, one suffered endocarditis after replacement of aortic valves. Four patients showed associated frontobasal bone destruction, mycotic aneurysms, or thromboses. The mean duration of hospital stay was 37 days. Mortality was much lower than in literature. Sixty percent of the patients died during the follow-up period. The outcome of the two immunocompetent patients was more favorable. Cerebral aspergillosis is a rare, but still life-threatening, condition, which predominantly occurs in immunosuppressive conditions. Due to radical surgical and antifungal therapy for several months, mortality can be reduced dramatically.


Subject(s)
Brain , Mycoses , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged
4.
Neurosurg Focus ; 50(5): E7, 2021 05.
Article in English | MEDLINE | ID: mdl-33932937

ABSTRACT

OBJECTIVE: Surgical management of spinal metastases at the cervicothoracic junction (CTJ) is highly complex and relies on case-based decision-making. The aim of this multicentric study was to describe surgical procedures for metastases at the CTJ and provide guidance for clinical and surgical management. METHODS: Patients eligible for this study were those with metastases at the CTJ (C7-T2) who had been consecutively treated in 2005-2019 at 7 academic institutions across Europe. The Spine Instability Neoplastic Score, neurological function, clinical status, medical history, and surgical data for each patient were retrospectively assessed. Patients were divided into four surgical groups: 1) posterior decompression only, 2) posterior decompression and fusion, 3) anterior corpectomy and fusion, and 4) anterior corpectomy and 360° fusion. Endpoints were complications, surgical revision rate, and survival. RESULTS: Among the 238 patients eligible for inclusion this study, 37 were included in group 1 (15%), 127 in group 2 (53%), 18 in group 3 (8%), and 56 in group 4 (24%). Mechanical pain was the predominant symptom (79%, 189 patients). Surgical complications occurred in 16% (group 1), 20% (group 2), 11% (group 3), and 18% (group 4). Of these, hardware failure (HwF) occurred in 18% and led to surgical revision in 7 of 8 cases. The overall complication rate was 34%. In-hospital mortality was 5%. CONCLUSIONS: Posterior fusion and decompression was the most frequently used technique. Care should be taken to choose instrumentation techniques that offer the highest possible biomechanical load-bearing capacity to avoid HwF. Since the overall complication rate is high, the prevention of in-hospital complications seems crucial to reduce in-hospital mortality.


Subject(s)
Spinal Fusion , Spinal Neoplasms , Cervical Vertebrae/surgery , Decompression, Surgical , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/surgery , Thoracic Vertebrae/surgery , Treatment Outcome
5.
J Neurooncol ; 146(2): 347-355, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31900826

ABSTRACT

BACKGROUND: Atypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas. METHODS: The medical records of all patients who underwent surgery (2007-2017 in 4 neurosurgical departments) for a histologically diagnosed primary atypical meningioma were reviewed to assess progression-free survival (PFS) and prognostic factors. RESULTS: This analysis included 258 patients with a median age of 60 years (54.7% female). The predominant tumor locations were convexity and falx (60.9%) followed by the skull base (37.2%). Simpson grade I-II resection was achieved in 194 (75.2%) patients, Simpson grade III-IV in 53 patients (20.5%). Tumor progressed in 54 cases (20.9%). Postoperative RT was performed in 46 cases (17.8%). RT was more often applied after incomplete resection (37.7% vs. 13.4% Simpson III-IV vs. I-II). A multivariate analysis showed a significantly shorter PFS associated with Simpson III-IV [HR 1.19, (95% CI) 1.09-1.29, p < 0.001] and age > 65 years [HR 2.89, (95% CI) 1.56-5.33, p = 0.001]. A subgroup analysis with a minimal follow-up of 36 months revealed that Simpson III-IV [HR 3.01, 95% CI 1.31-6.931.03-1.24, p = 0.009] and age > 65 years [HR 2.48, 95% CI 1.20-5.13, p = 0.014] reduced PFS. The impact of postoperative RT on PFS remained statistically insignificant, even in a propensity-score matched survival analysis [n = 46; p = 0.438; OR 0.710 (0.299-1.687)]. CONCLUSIONS: In the present study, postoperative RT did not improve PFS. The most important prognostic factors remain the extent of resection and age.


Subject(s)
Meningeal Neoplasms/mortality , Meningioma/mortality , Neoplasm Recurrence, Local/mortality , Neurosurgical Procedures/mortality , Postoperative Care , Radiotherapy, Adjuvant/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Follow-Up Studies , Humans , Male , Meningeal Neoplasms/pathology , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Meningioma/pathology , Meningioma/radiotherapy , Meningioma/surgery , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies , Survival Rate , Young Adult
6.
Neurosurg Rev ; 43(4): 1101-1107, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31197623

ABSTRACT

Clinical data following head or spine trauma in patients over 90 years is rare. The aim of this study was to analyze this patient cohort, assessing clinical characteristics, outcomes, and survival rates and to identify variables that may predict early mortality. A retrospective analysis of all patients over the age of 90 that were treated between January 2006 and December 2016 at our department was performed. Patient characteristics, type of injury, and comorbidities were analyzed with regard to the 30-day mortality rate as the primary outcome. One hundred seventy-nine patients were identified. Mean age was 93 (range 90-102); 105 (59%) patients were female. One hundred thirty-two (74%) and 34 (19%) of patients presented with head and spinal trauma, respectively. Fourteen patients (8%) had a combined head and spine injury. One hundred (56%) patients were treated operatively. Mean Charlson comorbidity index was 4.1 (range 0-18), mean diagnosis count was 6.2 (range 0-12), mean geriatric index of comorbidity (GIC) was 3.3 (range 1-4), and mean Barthel index was 28 (range 0-100). The 30-day mortality rate was 31%. Multivariate cox regression analysis showed that head trauma had a 1.66 hazard ratio (p = 0.036) of dying within 30 days of admission, whereas a higher Glasgow coma score and surgical treatment had a hazard ratio of 0.88 (p = 0.0001) and 0.72 (p = 0.05) to reach the primary outcome. None of the standard geriatric scores reached any significant correlation with the primary outcome. Standard geriatric prognostic scores seem less reliable to predict mortality for patients above the age of 90. Higher Glasgow coma score and surgical treatment were associated with a higher survival probability.


Subject(s)
Aged, 80 and over , Cervical Vertebrae/injuries , Craniocerebral Trauma/mortality , Craniocerebral Trauma/surgery , Skull/injuries , Spinal Injuries/mortality , Spinal Injuries/surgery , Cohort Studies , Comorbidity , Female , Geriatric Assessment , Glasgow Coma Scale , Humans , Male , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
7.
Neurosurg Rev ; 43(1): 217-222, 2020 Feb.
Article in English | MEDLINE | ID: mdl-30293162

ABSTRACT

Cranioplasty following decompressive craniectomy is of low surgical complexity, so much so that it has become the "beginners" cranial case. However, these "simple" procedures may have high complication rates. Identification of specific risk factors would allow targeted intervention to lower the complication rates. The aim of this study was to assess the rate of complications and to evaluate potential risk factors. We conducted a review of all patients who underwent cranioplasty in our center following decompressive craniectomy for stroke or brain trauma between 2009 and 2016. One hundred fifty-two patients were identified. Fifty-three percent were male. Mean age was 48 (range 11-78). Median time from craniectomy until cranioplasty was 102 days (range 14-378). The overall rate of complications, such as postoperative bleeding, seizures, postoperative infection, and hydrocephalus, was 30%. The mortality rate was 1%. None of the following potential risk factors was associated with significantly increased risk of periprocedural complications: gender (p = 0.34), age (p = 0.39), cause of initial surgery (p = 0.08), duration of surgery (p = 0.59), time of surgery (0.24), surgical experience (p = 0.17), and time from craniectomy until cranioplasty (p = 0.27). The 30-day complication rate following cranioplasty is high, but serious permanent deficits from these complications were rare. We found no clear predictor for these 30-day complications, which renders its prevention difficult.


Subject(s)
Brain Injuries, Traumatic/surgery , Decompressive Craniectomy/adverse effects , Plastic Surgery Procedures/adverse effects , Postoperative Complications/epidemiology , Stroke/surgery , Adolescent , Adult , Aged , Child , Female , Humans , Hydrocephalus/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Seizures/epidemiology , Young Adult
8.
Neurosurg Rev ; 43(2): 807-812, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31154545

ABSTRACT

Demographic trends make it incumbent on spine surgeons to recognize the special challenges involved in caring for older patients. The aim of this study was to identify variables that may predict early mortality in geriatric patients over the age of 90 following elective hospitalization for various spinal pathologies. Retrospective analyses of all patients over the age of 90 years, which were electively treated between 2006 and 2016 at out department for various spinal conditions, were performed. Patient characteristics, type of treatment, and comorbidities were analyzed with regard to the 30-day mortality rate. Twenty-six patients were identified. Mean age was 93 years (range 91-97), 19 (73%) were female. Eighteen (69%) patients were treated operatively. Mean hospital stay was 13 days (range 2-51). Seventeen (65%) patients were on anticoagulation therapy. Mean Charlson Comorbidity Index (CCI) was 5.3 (range 1-11); mean diagnosis count (DC) was 8.3 (range 2-17); mean Geriatric Index of Comorbidity (GIC) was 2.8 (range 1-4); and mean comorbidity-polypharmacy score (GPS) was 13.3 (range 5-23). The 30-day mortality rate was 16.7% in the surgically treated group compared with 12.5% in the conservatively treated group (p = 0.9), anticoagulation therapy (p = 0.91), gender (p = 0.49), length of hospital stay (p = 0.33), GIC (p = 0.54), CCI (p = 0.74), GPS (p = 0.82), and DC (p = 0.65) did not correlate with the 30-day mortality rate. Cause of death was pulmonary embolism in two cases and unknown in one case. Thirty-day mortality rate in patients over 90 years old with degenerative spinal diseases is relatively high regardless of the treatment modality. Standard geriatric prognostic scores seem less reliable for these patients.


Subject(s)
Spinal Diseases/mortality , Spinal Diseases/therapy , Age Factors , Aged, 80 and over , Comorbidity , Female , Geriatric Assessment , Germany , Hospitalization , Humans , Male , Reproducibility of Results , Retrospective Studies , Spinal Diseases/complications , Survival Rate
9.
Acta Neurochir (Wien) ; 162(1): 89-99, 2020 01.
Article in English | MEDLINE | ID: mdl-31758260

ABSTRACT

BACKGROUND: Some recent studies indicate correlations between cervical alignment and clinical outcome after anterior cervical discectomy and fusion (ACDF) surgery. However, there still are no established criteria for the interpretation of alignment, fusion and subsidence in relation to clinical outcome. METHODS: A retrospective analysis of 208 radiographs of patients following ACDF with stand-alone PEEK cage implantation was performed. The measurements were obtained on plain radiographs in lateral and anteroposterior projections as well as flexion/extension radiographs. Cervical alignment was measured using the Gore, Laing and Cobb methods; fusion was evaluated by an assortment of radiographic hallmarks: the presence of bridging bone, the Cobb angle and the distances between the tips and bases of the spinous processes of the operated segments, respectively. For assessment of subsidence, we used the Mochida method in addition to ventral and dorsal segmental height reduction. Correlation analysis between the different radiological characteristics and clinical outcome at a minimum follow-up of 12 months was conducted. RESULTS: Two hundred and eight patients were evaluated for alignment, fusion and subsidence. Cervical alignment using the Gore and Cobb methods correlated among each other, but failed to exhibit significant correlation with clinical outcome. Interpretation of fusion rates varied greatly (43.9 to 89.4%) depending on the criteria used. Pearson coefficients between radiographic presence of pseudarthrosis and the measurements of the spinous process distances (0.595; p < 0.001), the Cobb angles (0.187; p = 0.007) and the presence of bridging bone (0.224; p < 0.001) each exhibited statistical significance. None of the methods employed significantly correlated with clinical outcome. Regarding subsidence, we found rates of 62%, 48% and 27% using the Mochida, ventral and dorsal segmental height reduction assessment methods, respectively. Pearson correlations between pairs of Mochida/ventral (r = 0.39; p = 0.66) and Mochida/dorsal (r = 0.007; p = 0.921) height reduction assessment methods were weak and no significant correlation between subsidence rates and clinical outcome was shown. CONCLUSION: All measured parameters varied depending in the measurement method used. This was most pronounced for fusion. There was a moderate positive correlation between neck pain and subsidence as measured by the Mochida method.


Subject(s)
Cervical Vertebrae/diagnostic imaging , Diskectomy/methods , Postoperative Complications/diagnostic imaging , Radiography/methods , Spinal Fusion/methods , Adult , Aged , Cervical Vertebrae/surgery , Diskectomy/adverse effects , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Radiography/standards , Spinal Fusion/adverse effects , Treatment Outcome
10.
Acta Neurochir (Wien) ; 161(12): 2527-2537, 2019 12.
Article in English | MEDLINE | ID: mdl-31602535

ABSTRACT

OBJECTIVE: To analyze psychopathological outcome and health-related quality of life (QOL) for cohorts of patients undergoing transcranial or transnasal anterior skull base surgery. METHODS: A prospective study of patients undergoing elective surgery for various entities of the anterior skull base was performed. Evaluation for depression (ADS-K score) and anxiety (PTSS, STAI-S, STAI-T, and ASI-3 scores) was done before surgery, at 3 and 12 months after surgery. The correlation between preoperative psychological burden and postoperative quality of life as measured by the SF-36 and EuroQol questionnaires was analyzed. Incidence and influence of these psychiatric comorbidities on clinical outcome were examined and compared between transnasal and transcranial subgroups. RESULTS: We included 54 patients scheduled for surgery of a pituitary adenoma or meningioma of the anterior skull base between January 2013 and July 2017. Of these, a cohort of 40 (74.1%) completed follow-up interviews after 3 and 12 months. There were 60.0% female patients, median age was 57 years. 57.5% of patients had a meningioma and were operated transcranially, while 42.5% of patients received transnasal surgery for pituitary adenoma. The proportion of pathological anxiety scores significantly decreased from 75.0 to 45.0% (p = 0.002), without difference between transnasal and transcranial subgroups. After 3 months, mean EuroQol VAS score non-significantly increased by 0.07 (p = 0.236) across the entire cohort without significant difference between transcranial and transnasal subgroups (p = 0.478). The transnasal cohort tended to score higher in anxiety scores, whereas the transcranial cohort demonstrated higher depression scores without significant difference, respectively. The individually declared emotional burden significantly decreased from 6.7 to 4.0 on the ten-point Likert scale (p < 0.001) equally for both subgroups (transnasal, - 2.3; transcranial, - 3.0; p = 0.174). On last examination, about half of the patients in each subgroup (41.2% vs. 52.2%; p = 0.491) expressed a considerable recovery of preoperative bodily complaints such as headaches, dizziness, and unrest defined as a score of at least 8 on the Likert scaled item. CONCLUSION: Both transnasal and transcranial approaches yield favorable postoperative QOL and psychopathological outcomes. The postoperative increase in QOL is partly influenced by preoperative expression of mental distress, which tends to resolve postoperatively.


Subject(s)
Headache/epidemiology , Natural Orifice Endoscopic Surgery/adverse effects , Neurosurgical Procedures/adverse effects , Postoperative Complications/epidemiology , Psychological Distress , Quality of Life , Skull Base/surgery , Adult , Aged , Female , Humans , Male , Meningeal Neoplasms/surgery , Meningioma/surgery , Middle Aged , Natural Orifice Endoscopic Surgery/methods , Neurosurgical Procedures/methods , Pituitary Neoplasms/surgery , Surveys and Questionnaires
12.
Acta Neurochir (Wien) ; 160(1): 199-203, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29075906

ABSTRACT

We report the unusual case of a young patient with reoperation after annuloplasty using the Barricaid® (Intrinsic Therapeutics, Woburn, MA, USA) closure device. Our patient, a 32-year-old man underwent lumbar discectomy and annuloplasty of the level L5-S1. Five years later, the patient presented with a new onset of low-back pain radiating into the right leg. Imaging revealed loosening of the annulus repair device. The device was removed surgically and the patient was pain free thereafter. Annular closure devices such as the Barricaid system aim to improve outcome after lumbar discectomy by reducing the risk of recurrent disc herniation of the same level. Data on long-term follow-up are missing. Here we present, to our knowledge, the first case of symptomatic device loosening.


Subject(s)
Diskectomy/adverse effects , Intervertebral Disc Displacement/surgery , Periodontal Dressings/adverse effects , Prosthesis Failure/etiology , Prosthesis-Related Infections/diagnosis , Resins, Synthetic/adverse effects , Wound Infection/diagnosis , Adult , Diskectomy/methods , Humans , Lumbar Vertebrae/surgery , Male , Prosthesis-Related Infections/etiology
13.
Acta Neurochir (Wien) ; 160(12): 2307-2312, 2018 12.
Article in English | MEDLINE | ID: mdl-30350183

ABSTRACT

BACKGROUND: The benefit of an infection prevention bundle made up of five basic procedures to avoid surgical site infections (SSIs) following cranial surgery was evaluated. METHODS: Data from all patients with first time elective brain surgery from March 2014 till May 2016 were analyzed. In April 2015, an infection prevention bundle was implemented. The rate of SSIs after first time elective cranial surgery of patients operated 1 year before and 1 year after the implementation was compared. RESULTS: Of the 321 cases operated before the implementation of the infection prevention bundle, 13 cases (4%) developed a SSI. After the implementation, only 6 patients out of 288 were re-operated due to a SSI (2%). The most frequent etiological germ cultivated was Staphylococcus aureus. CONCLUSION: The implementation of a bundle of 5 basic infection prevention steps leads to a clinical relevant reduction of SSIs.


Subject(s)
Neurosurgical Procedures/adverse effects , Staphylococcal Infections/prevention & control , Surgical Wound Infection/prevention & control , Adult , Aged , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methods , Neurosurgical Procedures/standards , Skull/surgery
14.
Acta Neurochir (Wien) ; 160(10): 2055-2062, 2018 10.
Article in English | MEDLINE | ID: mdl-30069602

ABSTRACT

BACKGROUND: Due to improved diagnostic methods, the incidence of brain abscess is still rising. Therefore, clear and evidence-based therapy for the patients who suffer from brain abscesses is necessary. Brain abscesses are potentially life-threatening conditions that possibly lead to permanent injuries even after sufficient healing has taken place. The aims of this study were to analyze the clinical aspects of patients with brain abscesses and thereby to reveal the relevant aspects for the future treatment of the brain lesions. METHODS: We retrospectively identified 47 patients (24 male, 23 female) who had received surgery or undergone the frameless stereotactic drainage of brain abscesses in our center from March 2009 to May 2017. We analyzed the clinical characteristics of the patients, as well as comorbidities and outcomes. RESULTS: The mean age was 58 (range 7 to 86). Focus identification was successful in 28 patients (60%), with the most frequent causes of brain abscesses including the following: sinusitis (25%), dental infections (25%), and mastoiditis (21%). The mean Charlson Comorbidity Index was 1.57. Among the patients, 34% showed immunosuppressive conditions. We performed 1.5 surgeries per patient (53% via craniotomy, 28% biopsies or stereotactic drainage, 19% both procedures), followed by antibiotic treatment for 6.5 weeks (mean). In 30% of patients, no bacteria could be isolated. During the follow-up period (a median of 12 months), 23.4% of the patients died. The mortality rate during the initial hospital stay was 4.3%. CONCLUSION: One third of the patients with brain abscesses showed immunosuppressive conditions, whereas brain abscesses also often occur in patients with good medical conditions. The isolation of the focus of infection is often possible. Surgical procedures showed very good outcomes. Patients over 60 years showed significantly worse clinical outcomes.


Subject(s)
Brain Abscess/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Brain Abscess/etiology , Brain Abscess/surgery , Female , Focal Infection, Dental/complications , Humans , Male , Mastoiditis/complications , Middle Aged , Sinusitis/complications
15.
J Transl Med ; 14: 6, 2016 Jan 08.
Article in English | MEDLINE | ID: mdl-26742633

ABSTRACT

BACKGROUND: Clinical diagnostic research relies upon the collection of tissue samples, and for those samples to be representative of the in vivo situation. Tissue collection procedures, including post-operative ischemia, can impact the molecular profile of the tissue at the genetic and proteomic level. Understanding the influence of factors such as ischemia on tissue samples is imperative in order to develop both markers of tissue quality and ultimately accurate diagnostic tests. METHODS: Using NanoPro1000 technology, a rapid and highly sensitive immunoassay platform, the phosphorylation status of clinically relevant cancer-related biomarkers in response to ischemia was quantified in tissue samples from 20 patients with primary colorectal cancer. Tumor tissue and adjacent normal tissue samples were collected and subjected to cold ischemia prior to nanoproteomic analysis of AKT, ERK1/2, MEK1/2, and c-MET. Ischemia-induced relative changes in overall phosphorylation and phosphorylation of individual isoforms were calculated and statistical significance determined. Any differences in baseline levels of phosphorylation between tumor tissue and normal tissue were also analyzed. RESULTS: Changes in overall phosphorylation of the selected proteins in response to ischemia revealed minor variations in both normal and tumor tissue; however, significant changes were identified in the phosphorylation of individual isoforms. In normal tissue post-operative ischemia, phosphorylation was increased in two AKT isoforms, two ERK1/2 isoforms, and one MEK1/2 isoform and decreased in one MEK1/2 isoform and one c-MET isoform. Following ischemia in tumor tissue, one AKT isoform showed decreased phosphorylation and there was an overall increase in unphosphorylated ERK1/2, whereas an increase in the phosphorylation of two MEK1/2 isoforms was observed. There were no changes in c-MET phosphorylation in tumor tissue. CONCLUSION: This study provides insight into the influence of post-operative ischemia on tissue sample biology, which may inform the future development of markers of tissue quality and assist in the development of diagnostic tests.


Subject(s)
Colorectal Neoplasms/metabolism , Ischemia/metabolism , Nanotechnology/methods , Proteomics/methods , Signal Transduction , Biological Assay , Cell Line, Tumor , ErbB Receptors/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Luminescent Measurements , Mitogen-Activated Protein Kinase Kinases/metabolism , Phosphorylation , Protein Isoforms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-met/metabolism
17.
Cancers (Basel) ; 15(14)2023 Jul 09.
Article in English | MEDLINE | ID: mdl-37509211

ABSTRACT

BACKGROUND: In diffusely infiltrating gliomas, the maximum extent of tumor resection is an important predictor of overall survival, irrespective of histological or molecular subtype or tumor grade. For glioblastoma WHO grade 4 (GBM), it has been shown that resection-related events, such as ventricular opening and ventriculitis, increase the risk for development of communicating hydrocephalus (CH) requiring cerebrospinal fluid (CSF) diversion surgery. Risk factors for the development and the incidence of hydrocephalus following resection of other types of infiltrating gliomas are less well established. In this study, we evaluated the incidence and timing of occurrence of different types of hydrocephalus and potential risk factors for the development of CH following resection of grade 2 and 3 gliomas. METHODS: 346 patients who underwent tumor resection (WHO grade 2: 42.2%; 3: 57.8%) at our department between 2006 and 2019 were analyzed retrospectively. For each patient, age, sex, WHO grade, histological type, IDH mutation and 1p/19q codeletion status, tumor localization, number of resections, rebleeding, ventriculitis, ventricular opening during resection and postoperative CSF leak were determined. Uni- as well as multivariate analyses were performed to identify associations with CH and independent risk factors. RESULTS: 24 out of 346 (6.9%) patients needed CSF diversion surgery (implantation of a ventriculoperitoneal or ventriculoatrial shunt) following resection. Nineteen patients (5.5%) had CH, on median, 44 days after the last resection (interquartile range: 18-89 days). Two patients had obstructive hydrocephalus (OH), and three patients had other CSF circulation disorders. CH was more frequent in grade 3 compared to grade 2 gliomas (8.5 vs. 1.4%). WHO grade 3 (odds ratio (OR) 7.5, p = 0.00468), rebleeding (OR 5.0, p = 0.00984), ventriculitis (OR 4.1, p = 0.00463) and infratentorial tumor localization (OR 6.6, p = 0.00300) were identified as significant independent risk factors for the development of post-resection CH. Ventricular opening was significantly associated with CH, but it was not an independent risk factor. CONCLUSION: Physicians treating brain tumor patients should be aware that postoperative CH requiring CSF shunting occurs not only in GBM but also after resection of lower-grade gliomas, especially in grade 3 tumors. It usually occurs several weeks after resection. Rebleeding and postoperative ventriculitis are independent risk factors.

18.
J Clin Med ; 12(23)2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38068280

ABSTRACT

(1) Background: There is a marked proportion of spondylodiscitis patients who die during the early stage of the disease despite the applied therapy. This study investigates this early mortality and explores the associated risk factors. (2) Methods: We conducted a retrospective analysis of spondylodiscitis patients treated at our Level I spine center between 1 January 2018 and 31 December 2022. (3) Results: Among 430 patients, 32 (7.4%) died during their hospital stay, with a median time of 28.5 days (range: 2.0-84.0 days). Six of these patients (18.75%) did not undergo surgery due to dire clinical conditions or death prior to scheduled surgery. Identified causes of in-hospital death included multiorgan failure (n = 15), acute bone marrow failure (2), cardiac failure (4), liver failure (2), acute respiratory failure (2), acute renal failure (1), and concomitant oncological disease (1). In a simple logistic regression analysis, advanced age (p = 0.0006), diabetes mellitus (p = 0.0002), previous steroid medication (p = 0.0279), Charlson Comorbidity Index (p < 0.0001), and GFR level at admission (p = 0.0008) were significant risk factors for in-hospital death. In a multiple logistic regression analysis, advanced age (p = 0.0038), diabetes mellitus (p = 0.0002), and previous steroid medication (p = 0.0281) remained significant. (4) Conclusions: Despite immediate treatment, a subset of spondylodiscitis patients experience early mortality. Particular attention should be given to elderly patients and those with diabetes or a history of steroid medication, as they face an elevated risk of a rapidly progressing and fatal disease.

19.
Sci Rep ; 13(1): 1527, 2023 01 27.
Article in English | MEDLINE | ID: mdl-36707604

ABSTRACT

Timely treatment of aneurysmal subarachnoid haemorrhage (aSAH) is key to prevent further rupture and poor outcome. We evaluated complications and outcome adjusting for time from haemorrhage to treatment. Retrospective analysis of aSAH patients admitted between 2006 and 2020. Data was collected using standardized case report forms. We compared risk factors using multivariable logistic regression. We included 853 patients, 698 (81.8%) were treated within 24 h. Patients with higher Hunt and Hess grades were admitted and treated significantly faster than those with lower grades (overall p-value < 0.001). Fifteen patients (1.8%) rebled before intervention. In the multivariable logistic analysis adjusting for timing, Barrow Neurological Institute score and intracerebral haemorrhage were significantly associated with rebleeding (overall p-value 0.006; OR 3.12, 95%CI 1.09-8.92, p = 0.03, respectively) but timing was not. Treatment > 24 h was associated with higher mortality and cerebral infarction in only the subgroup of lower grades aSAH (OR 3.13, 1.02-9.58 95%CI, p-value = 0.05; OR 7.69, 2.44-25.00, p-value < 0.001, respectively). Therefore treatment > 24 h after rupture is associated with higher mortality and cerebral infarction rates in lower grades aSAH. Delay in treatment primarily affects lower grade aSAH patients. Patients with lower grade aSAH ought to be treated with the same urgency as higher-grade aSAH.


Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/therapy , Subarachnoid Hemorrhage/complications , Retrospective Studies , Risk Factors , Cerebral Infarction/complications , Aneurysm, Ruptured/therapy , Aneurysm, Ruptured/complications , Treatment Outcome , Intracranial Aneurysm/complications , Intracranial Aneurysm/therapy
20.
Eur Stroke J ; 8(1): 301-308, 2023 03.
Article in English | MEDLINE | ID: mdl-37021154

ABSTRACT

Introduction: Hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH) is a common complication which may lead to insertion of a ventriculoperitoneal shunt (VPS). Our aim is to evaluate a possible influence of specific clinical and biochemical factors on VPS dependency with special emphasis on hyperglycaemia on admission. Patients and methods: Retrospective analysis of a monocentric database of aSAH patients. Using univariable and multivariable logistic regression analysis we evaluated factors influencing VPS dependency, with a special focus on hyperglycaemia on blood sample within 24 h of admission, dichotomised at 126 mg/dl. Factors evaluated in the univariable analysis were age, sex, known diabetes, Hunt and Hess grade, Barrow Neurological Institute scale, treatment modality, extra-ventricular drain (EVD) insertion, complications (rebleeding, vasospasm, infarction, decompressive craniectomy, ventriculitis), outcome variables and laboratory parameters (glucose, C-reactive protein, procalcitonin). Results: We included 510 consecutive patients treated with acute aSAH requiring a VPS (mean age 58.2 years, 66% were female). An EVD was inserted in 387 (75.9%) patients. In the univariable analysis, VPS dependency was associated with hyperglycaemia on admission (OR 2.56, 95%CI 1.58-4.14, p < 0.001). In the multivariable regression analysis after stepwise backward regression, factors associated with VPS dependency were hyperglycaemia >126 mg/dl on admission (OR 1.93, 95%CI 1.13-3.30, p = 0.02), ventriculitis (OR 2.33, 95%CI 1.33-4.04, p = 0.003), Hunt and Hess grade (overall p-value 0.02) and decompressive craniectomy (OR 2.68, 95%CI 1.55-4.64, p < 0.001). Conclusion: Hyperglycaemia on admission was associated with an increased probability of VPS placement. If confirmed, this finding might facilitate treatment of these patients by accelerating insertion of a permanent draining system.


Subject(s)
Cerebral Ventriculitis , Gastritis , Hyperglycemia , Subarachnoid Hemorrhage , Female , Humans , Male , Middle Aged , Cerebral Ventriculitis/complications , Gastritis/complications , Hyperglycemia/complications , Retrospective Studies , Subarachnoid Hemorrhage/complications , Ventriculoperitoneal Shunt/adverse effects
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