Interleukin-6 as inflammatory marker of surgical site infection following spinal surgery.

BACKGROUND: In order to elucidate whether serum inflammatory markers identify patients with local surgical site infection(SSI) as underlying disease for recurrent or new symptomatology following spine surgery, we evaluated the diagnostic potential of interleukin-6(IL-6) as a marker of SSI. The diagnostic significance of IL-6 was compared to the standard serum inflammatory markers C-reactive protein(CRP) and white blood cell count (WBCC). METHOD: Ninety-eight consecutive patients with readmission due to recurrent or new symptomology after spinal surgery of degenerative spine disorders entered the study. Baseline patients' characteristics and the abovementioned inflammatory markers were collected, and arithmetical means with standard deviation, area under the curve (AUC), thresholds, sensitivity, specificity, positive(+)likelihood ratio (LR), and negative(-)LR with corresponding 95% confidence interval(95%CI) were calculated and correlated with presence or absence of SSI. RESULTS: Nine patients suffered from a SSI, whereas the remaining 89 patients had a recurrent/adjacent-segment degenerative disorder without evidence of infection. The most significant parameter for diagnosing a SSI was serum IL-6 (cut-off value > 15.3 pg/ml, AUC = 0.954, SE = 85.7%, SP = 97.3%), followed by CRP (cut-off value = 0.8 mg/dl, AUC = 0.916, SE = 88.9%, SP = 84.5%) CONCLUSIONS: In the case of recurrent or new symptomatology following spinal surgery, serum IL-6 has the highest diagnostic potential for diagnosing spinal SSI.

Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I.

BACKGROUND: Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. METHODS: We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients' past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. RESULTS: Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21-89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431-6.771) both on uni- and multivariate analysis. CONCLUSION: Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain-associated ventriculitis in patients with severe traumatic brain injury.

Objective: The aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis. Methods: Retrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors' intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis. Results: There were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0). Conclusions: The level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

Diffusion-weighted magnetic resonance imaging for detection of postoperative intracranial pyogenic abscesses in neurosurgery.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (MRI-DWI) is the modality of choice for detecting intracranial abscesses; however, it is unclear whether prior brain surgery has an influence on its diagnostic value. Thus, we assessed the robustness of MRI-DWI and determination of an ADC cutoff value for detecting intracranial abscesses in patients who underwent brain surgery. METHODS: We retrospectively evaluated 19 patients prior to surgery for postoperative supratentorial parenchymal abscesses by means of MRI-DWI. Forty randomly selected patients with routine postoperative MRI-DWI were used for comparative analyses. Clinical and serum biomarkers (C-reactive protein, interleukin-6, white blood cell count) as well as from results of early postoperative imaging findings (computed tomography and/or MRI scan) were recorded. Additionally, ADC values, T1±gadolinium, and T2/fluid-attenuated inversion recovery sequences were investigated. RESULTS: After initial surgery, early postoperative control imaging showed evidence of hemorrhage and/or hemostatic agents within the resection cavity in 10/19 patients of the abscess group and in 16/40 patients of the control group. No postoperative ischemia was detected. Neither hemostatic agents nor blood affected the mean ADC values in both the reference group (blood 2.96 ± 0.22 × 10-3 mm2/s vs. no blood 2.95 ± 0.26 × 10-3 mm2/s, p = 0.076) and in the abscess group (blood 0.87 ± 0.07 × 10-3 mm2/s vs. no blood 0.76 ± 0.06 × 10-3 mm2/s, p = 0.128). The mean ADC value within the resection cavity was significantly lower in the abscess group (1.5 T 0.88 ± 0.41 vs. 2.88 ± 0.20 × 10-3 mm2/s, p < .01; 3.0 T 0.75 ± 0.24 vs. 3.02 ± 0.26 × 10-3 mm2/s, p < 0.01). The optimal ADC cut-off for the differentiation of an abscess from normal postoperative findings was found at 1.87 × 10-3 mm2/s (area-under-the-curve 1.0, sensitivity = 100%, specificity = 100%). Moreover, no differences between the abscess patients and the control group were seen with respect to the analyzed serum biomarkers. CONCLUSION: MRI-DWI provides a robust tool to discriminate postoperative abscess formation from normal postoperative changes.

Concomitant and previous osteoporotic vertebral fractures.

Background and purpose - Patients with osteoporosis who present with an acute onset of back pain often have multiple fractures on plain radiographs. Differentiation of an acute osteoporotic vertebral fracture (AOVF) from previous fractures is difficult. The aim of this study was to investigate the incidence of concomitant AOVFs and previous OVFs in patients with symptomatic AOVFs, and to identify risk factors for concomitant AOVFs. Patients and methods - This was a prospective epidemiological study based on the Registry of Pathological Osteoporotic Vertebral Fractures (REPAPORA) with 1,005 patients and 2,874 osteoporotic vertebral fractures, which has been running since February 1, 2006. Concomitant fractures are defined as at least 2 acute short-tau inversion recovery (STIR-) positive vertebral fractures that happen concomitantly. A previous fracture is a STIR-negative fracture at the time of initial diagnostics. Logistic regression was used to examine the influence of various variables on the incidence of concomitant fractures. Results - More than 99% of osteoporotic vertebral fractures occurred in the thoracic and lumbar spine. The incidence of concomitant fractures at the time of first patient contact was 26% and that of previous fractures was 60%. The odds ratio (OR) for concomitant fractures decreased with a higher number of previous fractures (OR =0.86; p = 0.03) and higher dual-energy X-ray absorptiometry T-score (OR =0.72; p = 0.003). Interpretation - Concomitant and previous osteoporotic vertebral fractures are common. Risk factors for concomitant fractures are a low T-score and a low number of previous vertebral fractures in cases of osteoporotic vertebral fracture. An MRI scan of the the complete thoracic and lumbar spine with STIR sequence reduces the risk of under-diagnosis and under-treatment.

Re-irradiation strategies in combination with bevacizumab for recurrent malignant glioma.

The place of bevacizumab (BEV) in salvage re-irradiation (Re-RT) settings of malignant glioma is poorly defined. In the current study risk/benefit profiles of two BEV-based Re-RT protocols were analyzed and compared with that of salvage BEV plus irinotecan (BEV/IRI). According to interdisciplinary tumor board recommendations, patients were assigned to one of three BEV-based treatment protocols: (1) BEV/IRI, (2) Re-RT (36 Gy/18 fx) with concomitant BEV (Re-RT/BEV), and (3) Re-RT with concomitant/maintenance BEV (Re-RT/BEV→BEV). Prognostic factors were obtained from proportional hazards models. Adverse events were classified according to the NCI CTCAE, v4.0. 105 consecutive patients were enrolled from 08/2008 to 05/2014. Patients undergoing Re-RT experienced longer time intervals from initial diagnosis to BEV treatment (median: 22.0 months vs. 13.7 months, p = 0.001); those assigned to Re-RT/BEV→BEV rated better on the performance scale (median KPSREC: 90 vs. 70, p = 0.013). Post-recurrence survival after BEV-based treatment (PRS) was longest after Re-RT/BEV→BEV (median: 13.1 months vs. 8 months, p = 0.006). PRS after Re-RT/BEV and BEV/IRI was similar. Multivariately, higher KPSREC and Re-RT/BEV→BEV were associated with longer PRS. Treatment toxicity did not differ among groups. Re-RT/BEV→BEV is safe, feasible and effective and deserves further prospective evaluation.

A survey study on student preferences regarding pathology teaching in Germany: a call for curricular modernization.

BACKGROUND: Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized. METHODS: A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated. RESULTS: Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman's correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman's correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods. CONCLUSIONS: The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.

Synovial IL-6 as inflammatory marker in periprosthetic joint infections.

We analyzed serum and synovial biomarkers of 69 patients. 31 of them suffered from a periprosthetic joint infection (PJI) and 38 from aseptic arthralgia after total joint arthroplasty. We used Receiver-Operating-Characteristic-curves to calculate the Area-under-the-curve (AUC), cutoff-values, positive (+LR), negative (-LR) and interval-Likelihood-Ratios (iLR) for predicting a PJI. The most significant parameter was synovial interleukin-6 (IL-6) (cutoff-value ≥ 30,750 pg/ml, AUC = 0.959, SE = 90.0%, SP = 94.7%, +LR = 17.27), followed by synovial lactate (cutoff-value ≥ 8.3 mmol/l, AUC = 0.844, SE = 71.4%, SP=88.0%, +LR = 5.95), and synovial glucose (cutoff-value ≤ 44 mg/dl, AUC = 0.829, SE = 79.2%, SP = 78.6%, +LR = 3.69). IL-6 ≥ 30,750 pg/ml and lactate ≥ 10 mmol/l make a PJI very likely, IL-6 <10,000pg/ml or lactate <4.3 mmol/l makes a PJI very unlikely. If none of these thresholds are met, physicians should use the iLR of IL-6, glucose and lactate to estimate the likelihood of PJI.

The significance of interleukin-6 and lactate in the synovial fluid for diagnosing native septic arthritis.

Aim of this study was to evaluate the role of synovial interleukin-6 and synovial lactate for predicting native septic arthritis. We analyzed retrospectively synovial fluid parameters (interleukin-6, total-protein, glucose, lactate, synovial-fluid-white-blood-cell-count) of 62 patients with culture-verified native septic arthritis and compared them to 57 patients with acute aseptic arthritis. Receiver-Operating-Characteristic-curves were calculated to determine the 'Area-under-the-curves' (AUC), the best thresholds and the corresponding likelihood-ratios. The best parameter for diagnosing septic arthritis was synovial lactate (AUC = 0.864, sensitivity = 74.5%, specificity = 87.2%), followed by synovial interleukin-6 (AUC = 0.803, sensitivity = 92.5%, specificity = 64.1%) and the synovial-fluid-white-blood-cell-count (AUC = 0.782, sensitivity = 71.2%, specificity = 84.9%). Synovial lactate levels above 10 mmol/l almost proofed septic arthritis (interval-Likelihood-Ratio = 20.4), synovial interleukin-6 levels lower than 7000 pg/ml almost ruled out infection (interval-Likelihood-Ratio = 0.12). If none of these thresholds are met, physicians should estimate disease probability by the simultaneous use of the interval-Likelihood-Ratios of synovial lactate, synovial interleukin-6 and synovial-fluid-white-blood-cell-count.

Intraoperative ventricular volume restoration by intraventricular Ringer solution injection in a normal-pressure hydrocephalus patient with traumatic bilateral acute subdural hematoma and ventricular system collapse caused by cerebrospinal fluid shunt overdrainage: illustrative case.

BACKGROUND: The authors report a case of a patient with normal-pressure hydrocephalus treated with a ventriculoperitoneal shunt who developed a traumatic hemispheric bilateral acute subdural hematoma caused by quick cerebrospinal fluid (CSF) overdrainage. The authors present active ventricular CSF volume restoration as a novel treatment option. CSF overdrainage in patients with shunts may facilitate acute subdural hematoma formation even in cases of minor head trauma. Therapeutic options include CSF shunt function restriction or ligation, hematoma evacuation, or a combination of both. OBSERVATIONS: In this case, the authors performed emergency surgery with hematoma evacuation through a bilateral craniotomy and actively restored the volume of the ventricular system with a slow intraventricular injection of 37°C warmed Ringer solution through a shunt burr hole reservoir. LESSONS: In addition to hematoma evacuation and restriction of shunt function, the intraoperative restoration of ventricular volume could be a treatment option to prevent postoperative rebleeding or a space-occupying air collection in the subdural space. The risk of possible complications, such as ventricular or parenchymal bleeding, shunt dysfunction, or infections, requires further investigation. Restoration of the ventricular CSF volume by intraventricular injection of Ringer solution was in this case an efficient treatment method to prevent subdural rebleeding and a space-occupying air collection after subdural hematoma evacuation.

Giant internal carotid aneurysm: endovascular parent artery occlusion after failed treatment using a flow diverter-case report.

Treatment of giant aneurysms is challenging. While parent vessel reconstruction is the primary therapeutical target, the parent artery occlusion (PAO) is considered the next treatment option. We report a case of a 56-year-old woman with a right-sided non-ruptured giant aneurysm of the cavernous internal carotid artery. After failed aneurysm treatment by vessel remodeling through a flow diverter stent, we decided upon aneurysm coiling and PAO. Prior to the procedure, a successful balloon occlusion test (BOT) was performed, and in the second stage, just before occluding the parent artery, the BOT with induced hypotension was repeated. We achieved a good angiographic result and successful outcome without neurological deficit. In the case of failed treatment of giant aneurysm by vessel reconstruction, PAO is a therapeutical option. Prior to the vessel occlusion, a BOT with induced arterial hypotension challenge should be performed.

Efficacy of Mechanical Thrombectomy using Penumbra ACETM Aspiration Catheter Compared to Stent Retriever SolitaireTM FR in Patients with Acute Ischemic Stroke.

BACKGROUND: Mechanical thrombectomy is the standard therapy in patients with acute ischemic stroke (AIS). The primary aim of our study was to compare the procedural efficacy of the direct aspiration technique, using Penumbra ACETM aspiration catheter, and the stent retriever technique, with a SolitaireTM FR stent. Secondarily, we investigated treatment-dependent and treatment-independent factors that predict a good clinical outcome. METHODS: We analyzed our series of mechanical thrombectomies using a SolitaireTM FR stent and a Penumbra ACETM catheter. The clinical and radiographic data of 76 patients were retrospectively reviewed. Using binary logistic regression, we looked for the predictors of a good clinical outcome. RESULTS: In the Penumbra ACETM group we achieved significantly higher rates of complete vessel recanalization with lower device passage counts, shorter recanalization times, shorter procedure times and shorter fluoroscopy times (p < 0.001) compared to the SolitaireTM FR group. We observed no significant difference in good clinical outcomes (52.4% vs. 56.4%, p = 0.756). Predictors of a good clinical outcome were lower initial NIHSS scores, pial arterial collateralization on admission head CT angiography scan, shorter recanalization times and device passage counts. CONCLUSIONS: The aspiration technique using Penumbra ACETM catheter is comparable to the stent retriever technique with SolitaireTM FR regarding clinical outcomes.

Stereotactic Internal Shunt Placement in Congenital Intracranial Cysts.

INTRODUCTION: Treatment of symptomatic intracranial cysts remains a controversial issue. We present a risk/benefit profile of a minimally invasive, not yet described, stereotactic internal shunt implantation technique. The provided data might serve as a reference against which other treatment modalities could be compared. METHODS: From our prospective database, we identified a consecutive series of patients with symptomatic, untreated cysts who had undergone internal shunting from 2009 to 2017. We estimated the rates of clinical symptom improvement (RCSI), cyst reduction, total complications, and long-term complications. A minimal follow-up of 6 months was required. The prognostic factors were obtained from logistic regression models. Cyst recurrence-free survival was calculated using the Kaplan-Meier method. The outcomes data were compared with those from reported alternative treatment strategies using χ2 statistics. RESULTS: We included 38 patients. The cyst locations differed greatly and included the cerebellum (n = 2), brainstem (n = 5), and pineal area (n = 4). Cyst-associated hydrocephalus (n = 6) resolved after treatment. The 2-year cyst recurrence-free survival rate was 97%. The RCSI and rate of cyst reduction, total complications, and long-term complications was 91%, 97%, 11%, and 2.6%, respectively. We did not find any risk factors associated with the rate of total complications. The RCSI and rate of total and long-term complications compared favorably (P < 0.01) with the corresponding estimates of alternative treatments (P < 0.01). CONCLUSIONS: The described stereotactic internal shunt implantation technique is safe and can be successfully applied for treatment of cystic formations in any location in the brain.

Improving the Pharmacology Curriculum at a German Medical School: A Structured Plan Based on a Student-Guided Large-Scale Study.

With rapid progress in medicine, a thorough understanding of pharmacology remains crucial. Currently, lecturers are implementing competency-based learning objectives in medical curricula around the world. Advancing teaching modalities need to be integrated into pharmacology courses in a reasonable way. At Ludwig-Maximilians-Universität (LMU) Munich Medical Faculty, a systematic evidence-based approach was used to modernize pharmacology classes. The needs assessment was conducted by final-year students. It included focus groups and a large-scale online survey, which was distributed among all medical students at LMU, with 1018 students participating (response rate 20%). Survey results showed that most of the students (92%) aimed to become pharmacology-adept doctors. Also, a majority (88%) stated that their goal was to understand the material most critical to application of pharmacology concepts as well as prescribing practice. Only 38% of the students reported satisfaction with the current curriculum, and 93% supported modernization. Thus far, pharmacology teaching at LMU Munich had mainly consisted of lectures attended by 200 students. Now, students advocated for a stronger integration of clinical pharmacology teaching into clinical subjects in the last 2 years of medical school. Specifically, they called for classes with smaller groups of students including problem-based learning as well as video podcasts. These results provided the foundation for change in curriculum at the LMU medical school. In conclusion, a structured approach for curriculum development that considers students' views is feasible and can reveal their actual goals and demands. The approach has proven successful at LMU Munich and is transferrable to other universities.

Inflammatory Markers in Serum and Cerebrospinal Fluid for Early Detection of External Ventricular Drain-associated Ventriculitis in Patients With Subarachnoid Hemorrhage.

BACKGROUND: External ventricular drain (EVD)-associated ventriculitis is a serious complication. Early diagnosis can be difficult particularly in critically ill patients with aneurysmal subarachnoid hemorrhage (aSAH). We examined the diagnostic potential of standard serum and cerebrospinal fluid (CSF) biomarkers to differentiate between EVD-associated infections and aseptic courses in patients with aSAH. MATERIALS AND METHODS: We retrospectively evaluated the levels of inflammatory markers in serum (white blood cell count, percentage of neutrophils [sN%], and procalcitonin) and CSF (total leukocyte count [CSFTLC], CSFglucose, CSF/serumglucose ratio, CSF total protein [CSFTP]) of 63 consecutive patients with aSAH. Receiver operating characteristic curves and the area-under-the-curve (AUC) were calculated to detect the diagnostic potential, optimized threshold, sensitivity (SE), specificity (SP), + likelihood ratio (LR), and -LR of each biomarker. RESULTS: Of all patients, 17 (27%) developed an EVD-associated ventriculitis within a mean of 7.8±2.3 days after implantation. sN% had a very good diagnostic potential (AUC=0.900, SE=70.0%, SP=100%), followed by the CSFTLC with good diagnostic potential (AUC=0.841, SE=75.0%, SP=88.5%), and the CSFTP with moderate diagnostic potential (AUC=0.772, SE=73.3%, SP=76.0%). sN% higher than 70% and a CSFTLC higher than 635/µL were highly associated with the diagnosis of ventriculitis (+LR=∞ and 6.5), sN%<70% or a CSFTLC<635 made a diagnosis of ventriculitis unlikely (-LR=0.3 and 0.28). CONCLUSIONS: Routine determination of N% and CSFTLC are useful to distinguish ventriculitis from aseptic courses in the acute phase after aSAH and regardless of the bacteriological test result.

Dual-room CT with a sliding gantry for intraoperative imaging: feasibility and workflow analysis of an interdisciplinary concept.

PURPOSE: Currently, intraoperative computed tomography (iCT) is a scarcely used technique in neurosurgery. It remains unclear whether this phenomenon is explained by unfavorable iCT-related workflows and/or a limited number of indications. We here analyzed workflows of an installed dual-room iCT (DR-iCT) as compared to surgical procedures lacking iCT. We compared infection rates, utilizations rates, and the spectrum of indications of DR-iCT with that of a previously used single-room iCT. METHODS: The study refers to a consecutive series of patients undergoing either single-room iCT (January 2014-August 2014) or DR-iCT (September 2014-July 2016). A further group undergoing surgery without iCT in the interconnected operating rooms represents the reference group. Workflow measurements and infection rates were calculated. Indications for iCT and utilization rates were compared for each of the devices. CT image quality was rated. RESULTS: Application of DR-iCT led to a broader use of this technique as compared to the single-room device, which concerned in particular stereotactic neurosurgery. Accordingly, iCT utilization rates significantly increased (up to 50.8 ± 4.6 surgeries per month, p < 0.001). Workflow was slightly prolonged in case of DR-iCT imaging; the difference, however, was not statistically significant. Infections rates were low (range 0.0-0.17 infections per month) and not influenced by the utilization rate. Image quality of the DR-iCT was classified as very good in 34/43 evaluated microsurgical patients. CONCLUSIONS: The use of DR-iCT enhances utilization rates with a broader field of indications for intraoperative imaging. Workflow measurements are not significantly prolonged. The technology is safe, and the imaging quality of modern devices can be expected to be good.

Role of Cerebrospinal Fluid Markers for Predicting Shunt-Dependent Hydrocephalus in Patients with Subarachnoid Hemorrhage and External Ventricular Drain Placement.

OBJECTIVE: We sought to identify potential risk factors for the development of shunt-dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH) and external ventricular drain (EVD) insertion. In particular, the role of inflammatory markers within the cerebrospinal fluid (CSF) was assessed. METHODS: For this single-center analysis, data were generated from consecutive patients with SAH and the need for EVD implantation treated on our neurosurgical intensive care unit between 2013 and 2015. Parameters were patient characteristics (age, sex, comorbidity), severity of SAH (according to the World Federation of Neurological Society score), imaging findings (intraventricular hemorrhage, diameter of the third ventricle, location of the ruptured aneurysm), and acute course of disease (cerebral infarction, vasospasm). Moreover, the impact of EVD drainage volume and CSF markers (total protein [CSFTP], red blood cell count [CSFRBC], interleukin-6 [CSFIL-6], and glucose [CSFGlc]) was assessed. Statistics including receiver-operating-curve with corresponding area-under-the-curve (AUC) analysis were calculated using SPSS. RESULTS: Overall, 63 patients (21 males, mean age 55.2 years) were included. Twenty-one patients (30%) developed a shunt-dependent hydrocephalus. Significant risk factors for shunt dependency were the World Federation of Neurological Society score, cerebral infarction, and diameter of the third ventricle (P < 0.05). Moreover, CSF markers associated with shunt-dependent hydrocephalus included increased levels of CSFTP on days 5 (AUC = 0.72)/11 (AUC = 0.97)/14 (AUC = 0.98), CSFIL-6 on day 14 (AUC = 0.81), and CSFRBC on day 15 (AUC = 0.83). The EVD drainage volume was not prognostic. CONCLUSIONS: The time course of selected inflammatory markers in CSF may support management considerations in the early phase after SAH and critical impairment of CSF circulation.

Contrast enhancement is a prognostic factor in IDH1/2 mutant, but not in wild-type WHO grade II/III glioma as confirmed by machine learning.

BACKGROUND: Mutation of the isocitrate dehydrogenase (IDH) gene and co-deletion on chromosome 1p/19q is becoming increasingly relevant for the evaluation of clinical outcome in glioma. Among the imaging parameters, contrast enhancement (CE) in WHO II/III glioma has been reported to indicate poor outcome in the past. We aimed at reassessing the prognostic value of CE in these tumours within the framework of molecular markers using a machine learning approach (random survival forests [RSF]) as well as conventional Cox regression modelling. METHODS: 301 patients with WHO grade II (n = 181) or grade III glioma (n = 120) were stratified according to their molecular profile. Pre-operative magnetic resonance imaging (MRI) was reviewed and volumetric analyses of CE and T2 volumes were performed followed by conventional univariate and multivariate Cox analyses. Furthermore, the dataset was split into discovery and validation datasets, and RSFs were trained on the discovery dataset to predict the individual risk of each patient. Concordance indices for Cox and RSF models were determined and the variable importance of explanatory variables was assessed using the minimal-depth concept. RESULTS: In IDH mut tumours only, both conventional Cox regression modelling and RSF analyses showed that CE on initial MRI is a prognostic factor for survival with dependence on volume (p < 0.05). In contrast, presence of CE on initial MRI was not associated with outcome in IDH wt tumours. CONCLUSIONS: In patients with diffuse IDH wt gliomas WHO grade II/III, CE is not associated with survival, whereas in tumours with an IDH mutation, presence of CE on initial MRI is linked to inferior survival.

Interleukin 6 in the Cerebrospinal Fluid as a Biomarker for Onset of Vasospasm and Ventriculitis After Severe Subarachnoid Hemorrhage.

OBJECTIVE: The aim of the study was to investigate the diagnostic potential of interleukin 6 (IL-6) and other soluble biomarkers in serum and cerebrospinal fluid (CSF) for early diagnosis of cerebral vasospasm (cVSSAH) and external ventricular drain-associated ventriculitis (VCSAH) and to separate these conditions from aneurysmal subarachnoid hemorrhage (aSAH) without further complication (SAHw/o/c). METHODS: The concentrations of serum biomarkers and markers in the CSF were collected in 63 consecutive patients with aSAH and external ventricular drainage. Arithmetical means and standard deviations, area under the curve (AUC), cutoff values (C-OFF), sensitivity (SE), and specificity (SP) were calculated for markers and their correlation with SAHw/o/c, cVSSAH, and VCSAH. RESULTS: Clinical courses included 27 patients with cVSSAH, 17 with VCSAH, and 19 with SAHw/o/c. Mean ± standard deviationCSFIL-6 values were 7588 ± 4580 pg/mL at onset of VCSAH and 4102 ± 4970 pg/mL for cVSSAH and higher than 234 ± 239 pg/mL in SAHw/o/c (P < 0.001). CSFIL-6 showed excellent diagnostic potential for differing between VCSAH and SAHw/o/c (AUC, 1.00; C-OFF, 707; SE, 100%; SP, 100%), and a moderate diagnostic potential for differing VCSAH from cVSSAH (AUC, 0.757; C-OFF, 3100 pg/Ml; SE, 86.7%; SP, 70.6%). The concentration of CSFIL-6 within the cVSSAH group was significantly increased compared with SAHw/o/c (AUC, 0.937; C-OFF, 530 pg/mL; SE, 87.5%; SP, 91.7%). CONCLUSIONS: CSFIL-6 is increased after aSAH in patients with cVSSAH or VCSAH. Patients with a CSFIL-6 level higher than a C-OFF of 3100 pg/mL have an increased likelihood for VCSAH; patients with CSFIL-6 levels between 530 and 3100 pg/mL have an increased posttest probability for cVSSAH.

Diagnostic potential of inflammatory markers in septic arthritis and periprosthetic joint infections: a clinical study with 719 patients.

BACKGROUND: The aim of this study was to investigate which markers in serum and in the synovial fluid have the highest diagnostic potential for predicting septic arthritis and periprosthetic joint infections (PJIs). The likelihood ratio assesses the diagnostic utility of a diagnostic test and the likelihood that a patient has a disease. METHODS: The levels of inflammatory markers in serum [white blood cells, C-reactive protein (CRPS)] and synovial fluid [synovial fluid white blood cell count (SFWBC), percentage of polymorphonuclear cells (%PMN), lactic acid, lactate dehydrogenase (LDH), glucose, total protein] of patients suffering from septic arthritis (n = 114), PJI (n = 67), non-infectious joint diseases (n = 495) and arthralgia after total joint arthroplasty (n = 43) were determined. The arithmetical means, cut-off values, sensitivities, specificities, positive and negative likelihood ratios (+ LR, -LR), interval likelihood ratios and receiver operating characteristic curves with corresponding area under the curve (AUC) of inflammatory markers were calculated. RESULTS: The parameters with the highest diagnostic potential for differing between septic arthritis and non-infectious arthritis were the SFWBC (AUC = 0.850, cut-off value = 6.7 × 10(3)/µl, sensitivity = 81.8%, specificity = 76.5%,+ LR = 3.41, -LR = 0.24), CRPS (AUC = 0.797), %PMN (AUC = 0.766) and synovial lactate (AUC = 0.760). The highest diagnostic potential for predicting a PJI was shown by LDH (AUC = 0.833) and the SFWBC (AUC = 0.828). CONCLUSIONS: The SFWBC, CRPS, %PMN and synovial lactate were the best inflammatory markers in predicting septic arthritis. Synovial lactate levels > 10 mmol/l or an SFWBC > 50 × 10(3)/µl substantially increased disease probability, while SFWBC < 1.0 × 10(3)/µl or CRPS < 0.5 mg/dl diminished the post-test probability of septic arthritis considerably. An SFWBC < 1.1 × 10(3)/µl or a %PMN < 70% made a PJI unlikely, while SFWBC > 20 × 10(3)/µl or %PMN > 86% increased the post-test probability of a PJI. The use of the corresponding interval likelihood ratios could help physicians to estimate the probability of septic arthritis and PJI more accurately.