The benefits of ventriculoperitoneal shunting in normal pressure hydrocephalus patients-a follow-up of three years.

OBJECTIVE: The ventriculoperitoneal shunt (VPS) is an established approach in treating normal pressure hydrocephalus (NPH). This study aims to examine the long-term effects of VPS regarding clinical and radiological outcomes, to explore interdependencies with comorbidities and medication, and to determine a suitable opening pressure of the programmable valve. METHODS: 127 patients with VPS were retrospectively evaluated. The Hakim triad along with Evans index (EI) and callosal angle (CA) were examined preoperatively and postoperatively at various time points up to over thirty-six months. Preexisting comorbidities and medication were considered. Adjustments to valve settings were documented along with symptom development and complications. Wilcoxon and paired-sample t-tests were used to analyze postoperative change. Chi-square, Eta-squared, and Pearson coefficients were used in correlation analyses. RESULTS: Relief from individual symptoms was most prominent within the first 6 months (p < 0.01). EI and CA significantly decreased and increased, respectively (p < 0.05). Postoperative clinical and radiological improvement was largely maintained over the follow-up period. Diabetes mellitus and apoplexy correlated with surgical outcomes (p < 0.05). The median opening pressure as a function of overall symptom management was determined to be 120 mmH2O for women and 140 mmH2O for men. CONCLUSION: VPS is effective in treating NPH with respect to both clinical and radiological outcomes, although these two components are independent of each other. Improvement is most pronounced in short-term and maintained in the long-term. Comorbidities have significant influence on the course of NPH. The valve setting does not forecast change in radiological findings; consequently, priority should be placed on the patient's clinical condition.

The Predictive Value of Transcutaneous Electrical Nerve Stimulation for Patient Selection in Peripheral Nerve Field Stimulation for Chronic Low Back Pain: A Prospective Study.

OBJECTIVE: Peripheral nerve field stimulation (PNFS) is an effective alternative treatment for patients with chronic low back pain. Transcutaneous electrical nerve stimulation (TENS) is frequently used in pain therapy. Aim of this prospective study was to examine the predictive value of TENS for later PNFS treatment. MATERIALS AND METHODS: Between 2014 and 2019, a prospective cohort study of 41 patients with chronic lumbar pain was conducted. Pain intensity (NRS) was assessed before and after TENS use, preoperatively/postoperatively and in the follow-up after three and six months, SF12v2 questionnaires with physical (PCS) and mental component summary (MCS) scores, and Oswestry disability index (ODI) questionnaire at baseline as well as three and six months after PNFS implantation. Implantation of the PNFS-system with two percutaneous leads was performed after four to seven days of positive testing. Statistical analysis was performed using depending t-test, ANOVA, and Spearman correlation. RESULTS: The cohort consisted of 41 patients (19 females, 22 males) with a median age of 60.5 years (IQR25-75 52-67). Two patients were lost to follow-up. After positive PNFS testing a pulse generator (IPG) was implanted in 15 patients with positive TENS effect and 15 patients without TENS effect. Leads were explanted in nine patients after negative PNFS trial phase. TENS positive patients showed significant correlation to a positive effect in the PNFS trial phase in NRS reduction (p = 0.042) indicating that TENS responders will also respond to PNFS (94% patients). After three and six months follow-up median NRS and SF12v2 (PCS) improved significantly in both cohorts, SF12v2 (MCS) and ODI only in the TENS positive cohort, respectively. CONCLUSION: TENS can be predictive for patient selection in PNFS, as TENS positive patients showed significant correlation with a positive PNFS trial period. Therefore, TENS positive patients might be justifiable to be directly implanted with leads and IPG. TENS positive patients further tend to show a better improvement in the follow-up.

Preoperative Elevated Levels for Depression, Anxiety, and Subjective Mental Stress Have No Influence on Outcome Measures of Peripheral Nerve Field Stimulation for Chronic Low Back Pain-A Prospective Study.

OBJECTIVE: Peripheral nerve field stimulation (PNFS) is an effective alternative treatment for patients with chronic low back pain. The treatment of low back pain strongly depends on psychological factors like anxiety, depression, and mental stress. The aim of this study was to evaluate the impact of such factors on outcome measures after lead- and implantable pulse generator-implantation. MATERIALS AND METHODS: Between 2014 and 2019, a prospective cohort study of 39 patients with chronic lumbar pain was conducted. Hospital Anxiety and Depression Scale (HADS) score was assessed at baseline to measure symptoms of anxiety and depression. Symptom checklist-90 (SCL-90) was used to measure subjective psychopathology. Pain intensity (numeric pain rating scale [NRS]), SF12v2 with Physical Component Summary and Mental Component Summary (MCS) scores, and Oswestry Disability Index (ODI) were assessed pre- and postoperatively as well as three and six months after PNFS implantation. Outcome values were compared to baseline data. Statistical analysis was performed using depending t-test and analysis of variance (ANOVA). A p value <0.05 was considered significant. RESULTS: The cohort consisted of 39 patients (18 females, 21 males) with a median age of 61 years (IQR25-75  = 52-67 years). NRS, ODI, and SF12v2 showed significant improvement in the whole follow-up period compared to baseline values (p < 0.05). Elevated HADS scores for anxiety were seen in 64.1%, for depression in 76.9% of the patients at baseline. SCL-90 was pathologic in 71.8% of the cases. A one-way ANOVA revealed no differences between elevated HADS- and SCL-90 values and all outcome measures after PNFS implantation in the whole follow-up period (p > 0.05). CONCLUSION: Chronic low back pain is often associated with psychological distress. Our study showed highly elevated levels for anxiety and depression as well as subjective mental stress in patients with chronic low back pain without negative impact on NRS, ODI, and SF12v2 in the whole follow-up after PNFS implantation.

Programmable valve breakage in shunt systems of children with posthemorrhagic hydrocephalus after minor head trauma-a case series.

PURPOSE: We report five rare cases of programmable valve breakage (Codman Hakim-Medos valve) in shunt systems of children with posthemorrhagic hydrocephalus. Only four similar studies have been published in the current literature. METHODS: Between 2013 and 2018, five children with posthemorrhagic hydrocephalus were admitted to the pediatric department. All patients had a history of slight blows to the head in a minor trauma and follow up MRI scans. After initial clinical examination, cranial computed tomography (CT) and X-ray were conducted. RESULTS: In all cases, pumping the reservoir resulted in very slow refilling. The cranial CT in one patient showed slit ventricles confirming the suspicion of overdrainage, the other cases a slight enhancement of the hydrocephalus. In lateral X-rays of the skull in comparison to the first X-ray control of the shunt valve, the pressure control chamber could be seen dislocated in the inferior part of the reservoir in all cases. Surgery revealed that the shunt valve was broken. The pressure control chamber had dropped to the bottom of the reservoir. After implantation of a new shunt valve, the symptoms resolved completely in all five children. Overall this complication occurred in 4.3% (5 of 85 implanted Codman Hakim-Medos valve) of all children necessitating ventriculoperitoneal shunt implantation between January 2013 and December 2018. CONCLUSION: The well-accepted Codman Hakim-Medos programmable valve is part of a tube-system, which is designed to offer the possibility of a reliable and precise treatment of hydrocephalus. Various mechanical and non-mechanical complications of shunt systems have been reported. Valve breakage is a very rare condition, often missed, and must be kept in mind when trauma and prior MRI scan are reported.

A Retrospective Analysis of 25 Cases With Peripheral Nerve Field Stimulation for Chronic Low Back Pain and the Predictive Value of Transcutaneous Electrical Nerve Stimulation for Patient Selection.

OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) and peripheral nerve field stimulation (PNFS) may be proposed to patients with chronic lumbar pain refractory to conventional treatment. Aim of this study was to assess the importance of preoperatively treatment with TENS as a predictive value for later successful PNFS and impact of PNFS in follow-up of 12 months. METHODS: Between 2012 and 2016, a retrospective analysis of 25 patients with chronic lumbar pain and implantation of a PNFS-system was performed. Pain intensity (NRS), health-related quality of life (EQ-5D-5L), Oswestry disability index (ODI), actual mood state scale (ASTS), and treatment satisfaction (CSQ-8) were assessed pre/postoperatively, after 6 and 12 months. TENS use before surgery was assessed. RESULTS: The cohort consisted of 25 patients with a median age of 56 years (IQR25-75 51-63). In a subgroup analysis, 18 patients used TENS before surgery, 7 did not use TENS and were excluded. No pain relief was observed in 14 patients. Ten of these patients showed later positive effect in PNFS trial stimulation. In four patients, pain relief with TENS was seen. One patient later on had no benefit after PNFS trial, three had sufficient pain relief. In the whole cohort, five patients had no benefit after PNFS trial, in 20 patients a neurostimulator was implanted. NRS, EQ-5D-5L, and ODI measures showed significant improvement in the whole follow-up after PNFS implantation. ASTS scale showed an increase of values for positive mood and a reduction in values for sorrow, fatigue, and anger. In 55%, a sustained reduction in demand for analgesics was seen after 6 months, 50% after 12 months, respectively. CONCLUSION: In this retrospective analysis, TENS has no predictive value in the selection of patients with low back pain for the PFNS treatment. PNFS is effective and safe to relieve significantly symptoms of chronic low back pain.

Cerebrospinal fluid ferritin--unspecific and unsuitable for disease monitoring.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage is sometimes difficult to diagnose radiologically. Cerebrospinal fluid (CSF) ferritin has been proposed to be highly specific and sensitive to detect hemorrhagic central nervous system (CNS) disease. We analyzed here the specificity of CSF ferritin in a large series of various CNS diseases and the influence of serum ferritin. MATERIALS AND METHODS: CSF ferritin, lactate, protein and total cell count were analyzed in 141 samples: neoplastic meningitis (n=62), subarachnoid hemorrhage (n=20), pyogenic infection (n=10), viral infection (n=10), multiple sclerosis (n=10), borreliosis (n=5) and normal controls (n=24). Cerebrospinal fluid ferritin was measured with a microparticle immunoassay. In addition, serum and CSF ferritin were compared in 18 samples of bacterial and neoplastic meningitis. RESULTS: In CNS hemorrhage, median ferritin was 51.55µg/L (sensitivity: 90%) after the second lumbar puncture. In neoplastic meningitis, the median CSF ferritin was 16.3µg/L (sensitivity: 45%). Interestingly, ferritin was higher in solid tumors than that in hematological neoplasms. In 90% of pyogenic inflammation, ferritin was elevated with a median of 53.35µg/L, while only 50% of patients with viral infection had elevated CSF ferritin. In ventricular CSF, median ferritin was 163µg/L, but only 20.6µg/L in lumbar CSF. Ferritin was normal in multiple sclerosis and borreliosis. CONCLUSIONS: Ferritin was elevated not only in hemorrhagic disease, but also in neoplastic and infectious meningitis. Ferritin was not a reliable marker of the course of disease. The influence of serum ferritin on CSF ferritin is negligible. We conclude that elevated CSF ferritin reliably, but unspecifically indicates severe CNS disease.

ZEB1 induces N-cadherin expression in human glioblastoma and may alter patient survival.

The present study investigated the expression of epithelial-mesenchymal transition (EMT)-related factors zinc finger E-box-binding homeobox 1 (ZEB1), cadherin-1 (CDH1), cadherin-2 (CDH2) and the cell cycle modulating kinase cyclin-dependent kinase 1 (CDK1) in human glioblastoma (GBM) compared to normal brain tissue, as well as whether the levels of expression were associated with the overall and progression-free survival of the GBM patients. In 44 GBM and five normal brain tissue specimens, the expression levels of ZEB1, CDH1, CDH2 and CDK1 were evaluated by real-time PCR and immunostaining, and the results were correlated with clinical data. The expression levels of all investigated genes as detected by immunostaining were significantly higher in the GBM when compared to the normal brain tissues. There was no influence on survival. A linear correlation between ZEB1 and CDH2 and CDK1 expression was observed in GBM. Moreover, ZEB1 was involved in EMT (e.g., signaling in human GBM) and high ZEB1 levels were linked to an aberrant cell cycle processing, marked by CDK1 overexpression.

A prospective randomized study comparing retractor-endoscopic vs. open release of carpal tunnel and cubital tunnel syndromes.

OBJECTIVE: To evaluate the neurological and neurophysiological outcomes of retractor-endoscopic versus open release in carpal tunnel syndrome (rCTS and oCTS, respectively) and cubital tunnel syndrome (rCbTS and oCbTS, respectively) at 3- and 12-month follow-up. METHODS: Between 2013 and 2017, 80 patients were prospectively blindly randomized. McGowan scores were used for preoperative grading and outcomes were assessed using a modified Bishop rating system (BRS). Furthermore, incapacity to work, duration of postoperative pain, hypoesthesia, atrophy, subjective weakness, and a subjective assessment of the operative result were analyzed. The differences in the cohorts were evaluated with t-tests and ANOVAs as parametric tests and Kruskal-Wallis and Mann-Whitney U tests as nonparametric tests. RESULTS: The 80 patients underwent retractor-endoscopic or open decompression of the median or ulnar nerve. The rCTS group exhibited significant improvements in neurophysiological data (P = 0.032), shorter periods of postoperative pain (P = 0.03), and less discomfort (P = 0.005), as well as significantly better BRS results after 3 months compared with the oCTS group (P = 0.005). Between the oCbS and rCbTS groups, no significant differences were observed (P > 0.05). Regarding improvements in McGowan scores, no statistically significant differences were observed between the rCTS and oCTS groups after 3 months (P = 0.52) or 12 months (P = 0.86), nor were any observed between the rCbTS and oCbTS groups after 3 months (P = 0.88) or 12 months (P = 0.10). CONCLUSION: Significantly superior results were obtained at short-term follow-up for rCTS, whereas no superiority was found for rCbTS release. This study concluded that this endoscopic procedure is safe as well as and effective and has the potential to achieve better results in carpal tunnel syndrome compared with conventional methods.

Neurosurgical shunt treatment of pediatric hydrocephalus: epidemiology and influencing factors on revision surgeries: a single-center retrospective analysis of 131 patients.

BACKGROUND: Paediatric hydrocephalus is a result of a dysfunction of cerebrospinal fluid circulation, and it has diverse pathogeneses. This study investigates the epidemiology of paediatric hydrocephalus, as well as the influences of primary aetiology and implant type on treatment complications and the development of new therapeutic approaches and strategies. METHODS: Between 2013 and 2018, a retrospective analysis of 131 children, who were suffering from hydrocephalus, was conducted. Medical charts, operative reports and clinical follow-up visits were reviewed. Statistical analysis was performed using t-test/ANOVA and Kruskal-Wallis test/Mann-Whitney U test. RESULTS: The most common pathogeneses of hydrocephalus among our patients were meningomyelocele-associated and posthaemorrhagic. The majority of patients received a programmable differential pressure valve (PPV, 77.8%) or a fixed differential pressure valve with a gravitational unit (FPgV, 14.8%). Among 333 shunt-associated surgeries, 66% of surgeries were revision surgeries and were performed because of mechanical shunt dysfunction (61%), infection (12%), or other reasons (27%). The median rate of revisions within one year for each patient was 0.15 (IQR25-75: 0.00-0.68) and was influenced by aetiology (p = 0.045) and valve type (p = 0.029). The highest rates were seen in patients with posthaemorrhagic hydrocephalus and in those with FPgVs; the lowest rates were seen in patients with meningomyelocele-associated hydrocephalus and PPVs. The occurrence of mechanical dysfunctions was correlated with FPgV patients (p = 0.014). Furthermore, the median time interval between initial shunt surgery and onset of infection was shorter than that between initial surgery and mechanical dysfunction (p = 0.033). CONCLUSIONS: Based on this research, we can state several factors that influence revision surgeries in paediatric shunt patients. With the assessment of patients' risk profiles, physicians can classify paediatric shunt patients and thus avoid unnecessary examinations or invasive procedures. Furthermore, medical providers can prevent revision surgeries if they choose shunt material in accordance with a patient's associated shunt complications.

Mechanisms and consequences of head injuries in soccer: a study of 451 patients.

OBJECT: The goal of this study was to evaluate the incidence and mechanisms of head injury during soccer games and to describe the results after spontaneous resolution of symptoms or after treatment. METHODS: In a retrospective study from 2005, records on 451 players from the German Soccer Association who had suffered various injuries were collected. The study used a questionnaire in which the player described the accident and the playing situation as well as the clinical course after trauma. This questionnaire also included information about the physical symptoms of the players and the length of their rehabilitation. Two groups were formed: one with head injuries (case group), and the other with injuries of other body parts (control group). RESULTS: Of the injuries reported, 108 (23.9%) were related to the head, 114 (25.3%) to the knee, 58 (13%) to the ankle, 56 (12%) to the calf, and 30 (7%) to the shoulder. The areas of the head most frequently involved were the facial and occipital regions. In the head injury group, the head duel was the most common playing action to lead to trauma. In those cases, the body part that hit the injured player was the elbow, arm, or head of the opponent. The most common playing situation was combat in the penalty area. The median hospitalization time after the trauma was 2 days for the case group and 5 days for the control group. The rehabilitation time for the case group was also shorter (median 6.5 days) than for the control group (median 30 days). CONCLUSIONS: Trivial head injuries in soccer can have a long and complicated course. Nevertheless, the temporary disability is shorter in most cases than for players with injuries to other parts of the body. Modifying the rules of play would be necessary to reduce the incidence of head trauma.

Antiproliferative effect of GTS-21 in glioblastoma cells.

Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. The poor prognosis and short median overall survival of patients with GBM is associated with resistance to therapy after surgical and adjuvant treatment. The expression of various acetylcholine receptors (AChR) in GBM has been widely reported. The present study aimed to investigate the expression of cholinergic system-related genes in primary GBM and to explore the antiproliferative effect of 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21) in GBM cell lines. Therefore, the expression of 28 genes associated with the cholinergic system was detected using a customized RT2 Profiler PCR Array in 44 GBM and 5 healthy control brain tissue samples. In addition, the activity of GTS-21, an alpha 7 subunit nicotinic AChR (α7 nAChR) agonist, and that of α-bungarotoxin (α-BTX), an α7 nAChR antagonist, was determined in primary and established GBM cells. Therefore, the A172, U87 and G28 cell lines and primary GBM cells were treated with GTS-21, ACh or nicotine. Cell viability was evaluated using MTT assay at 24, 48 and 72 h following cell treatment with the corresponding compounds. The results revealed that the expression of cholinergic system-related components was notably downregulated, except that of cholinergic receptor nicotinic alpha 7 subunit (CHRNA7), in primary GBM and U87 cells. However, the dominant-negative duplicate form of CHRNA7 was also downregulated. Furthermore, A172 and G28 cells exhibited a heterogeneous gene expression pattern. Additionally, GTS-21 inhibited the proliferation of GBM cells in a dose- and time-dependent manner. Interestingly, treatment with α-BTX restored the proliferation of U87 cells, but not that of A172 and G28 cells. Collectively, the findings of the present study suggested that GTS-21 may inhibit the proliferation of GBM cells and may therefore serve as a novel therapeutic approach to the treatment of GBM, which warrants further investigation.

Spinal cord stimulation for the treatment of complex regional pain syndrome leads to improvement of quality of life, reduction of pain and psychological distress: a retrospective case series with 24 months follow up.

Background and aims Complex regional pain syndrome (CRPS) is a common pain condition which is characterized by pain, functional impairment, and trophic changes. Neurosurgical treatment is not widely offered. In this study the treatment with spinal cord stimulation (SCS) was evaluated over 24 months follow up. Methods A retrospective case analysis of six patients with severe CRPS was performed. Pain chronicity was recorded with the Mainz Pain Staging System (MPSS). Pain intensity (NRS), activity level and health-related quality of life (EQ-5D-5L), the actual mood state (ASTS), and treatment satisfaction (CSQ-8) were assessed. All patients received conventional pharmacological treatments including multimodal pain therapy through their local pain therapist or in specialized centers as well as physical therapy. A SCS electrode was implanted for trial stimulation. After successful trial a neurostimulator was implanted and connected to the electrode. Patients were retrospectively analyzed before implantation and 6, 12 and 24 months postoperatively. Statistical analysis was performed using Mann-Whitney U and Wilcoxon rank-sum test. Results Patients median age was 43 years (IQR25-75 37-43 years). The median MPSS Score was 3 of 3 indicating a high pain chronicity. Median NRS before implantation of the neurostimulator was 8.8 (IQR25-75 7.6-9.3). A reduction to 7.8 (IQR25-75 4.8-8.1; p = 0.14) after 6 months, 6.5 (IQR25-75 3.8-8.1; p = 0.08) after 1 year, and 6.8 (IQR25-75 3.8-8.5; p = 0.15) after 2 years was achieved. Median EQ-5D-5L index value before treatment was 0.27 (IQR25-75 0.25-0.41) indicating a severely lowered quality of life. A significant improvement to 0.53 (IQR25-75 0.26-0.65; p = 0.03) after 6 months, 0.58 (IQR25-75 0.26-0.84; p = 0.03) after 1 year as well as after 2 years was seen. ASTS scale showed an increase of values for positive mood, and a reduction in values for sorrow, fatigue, anger and desperation during the whole follow up period. The treatment satisfaction in the whole cohort with a median CSQ-8 value of 29.5 of 32 was very high. Conclusion The results of this small case series showed a significant improvement of the EQ-5D-5L after implantation of a neurostimulator. NRS reduction was not significant but a clear tendency towards reduced values was observed. We therefore conclude that SCS is an alternative option to relieve chronic pain and psychological distress originating from CRPS if non-invasive managements of severe CRPS failed. The preoperative selection plays a crucial role for good results. Implications CRPS is difficult to treat. SCS is an alternative option to improve the quality of life and relieve chronic pain originating from severe CRPS if conservative treatment modalities fail. Further psychological distress is reduced in long-term follow up. SCS should be kept in mind for therapy refractory cases.

Transcranial Doppler Sonography Defined Vasospasm, Ischemic Brain Lesions, and Delayed Ischemic Neurological Deficit in Younger and Elderly Patients after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Vasospasm, delayed ischemic neurologic deficit (DIND), and ischemic brain lesions after acute subarachnoid hemorrhage (SAH) are associated with increased morbidity and mortality. The purpose of this study was to analyze age cutoffs for vasospasm, DIND, and ischemic brain lesions after SAH. METHODS: This study included 292 aneurysmal SAH patients from January 2005 to December 2015. Patients' data were extracted from a prospective database with measurements of transcranial Doppler sonography. Any vasospasm was defined as a maximum mean flow velocity (MMFV) >120 cm/sec. Severe vasospasms were defined as at least 2 measurements of MMFVs >200 cm/sec or an increase of MMFV >50 cm/sec/24 hours over 2 consecutive days or a new neurologic deficit. All MMFVs >120 cm/sec in absence of severe vasospasm criteria were defined as mild vasospasm. Age-related cutoff values were calculated using receiver operating curve analysis. RESULTS: Any vasospasms occurred in 142 patients and thereof mild vasospasm in 86/142 (60.6%) patients and severe vasospasm in 56/142 patients (39.4%). Significantly higher incidences of any vasospasm (P = 0.005), severe vasospasm (P = 0.003), DIND (P = 0.031), and ischemic brain lesions (P = 0.04) were observed in patients aged <50 years. According to receiver operating curve analysis, the optimal age cutoff was 50 years for the presence of overall vasospasms, severe vasospasms, DIND, and ischemic brain lesions and 65 years for mild vasospasms. CONCLUSIONS: Higher incidences of any vasospasms, severe vasospasms, DIND, and ischemic brain lesions were observed in younger SAH patients.

Defining Prolonged Length of Acute Care Stay for Surgically and Conservatively Treated Patients with Spontaneous Intracerebral Hemorrhage: A Population-Based Analysis.

BACKGROUND: The definition of prolonged length of stay (LOS) during acute care remains unclear among surgically and conservatively treated patients with intracerebral hemorrhage (ICH). METHODS: Using a population-based quality assessment registry, we calculated change points in LOS for surgically and conservatively treated patients with ICH. The influence of comorbidities, baseline characteristics at admission, and in-hospital complications on prolonged LOS was evaluated in a multivariate model. RESULTS: Overall, 13272 patients with ICH were included in the analysis. Surgical therapy of the hematoma was documented in 1405 (10.6%) patients. Change points for LOS were 22 days (CI: 8, 22; CL 98%) for surgically treated patients and 16 days (CI: 16, 16; CL: 99%) for conservatively treated patients. Ventilation therapy was related to prolonged LOS in surgically (OR: 2.2, 95% CI: 1.5-3.1; P < 0.001) and conservatively treated patients (OR: 2.5, 95% CI: 2.2-2.9; P < 0.001). Two or more in-hospital complications in surgical patients (OR: 2.7, 95% CI: 2.1-3.5) and ≥1 in conservative patients (OR: 3.0, 95% CI: 2.7-3.3) were predictors of prolonged LOS. CONCLUSION: The definition of prolonged LOS after ICH could be useful for several aspects of quality management and research. Preventing in-hospital complications could decrease the number of patients with prolonged LOS.

NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors.

AIM: The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS). MATERIALS AND METHODS: Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls. RESULTS: On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13). CONCLUSION: Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05).

High-mobility group AT-hook protein 2 expression and its prognostic significance in MGMT methylated and unmethylated glioblastoma.

High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6-methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA 2 expression was determined by performing quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in 44 glioblastoma patients and 5 non-tumorous brain specimens as controls. Gene expression levels of MGMT methylated vs. unmethylated patients, and gene expression levels between patient groups, both for qPCR and IHC data were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free survival and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered statistically significant throughout the analyses. The mean age of patients at diagnosis was 57.4 ± 15.7 years, and the median survival was 16 months (SE 2.8; 95% CI, 10.6-21.4). HMGA 2 gene expression was significantly higher in glioblastoma compared to normal brain tissue on qPCR (mean, 0.35; SD, 0.27 vs. 0.03, SD, 0.05) and IHC levels (IRS mean, 17.21; SD, 7.43 vs. 3.20; SD, 1.68) (p=0.001). Survival analysis revealed that HMGA 2 overexpression was associated with a shorter progression-free and overall survival time in patients with methylation (n=24). The present study shows a tendency that HMGA 2 overexpression correlates with a poor prognosis of glioblastoma patients independent of MGMT methylation status. The results suggest that HMGA 2 could play an important role in the treatment of glioblastoma and could have a function in prognosis of this type of cancer.