Publications by authors named "Cristina Sauerland"

59 Publications

Risk of tumor recurrence in intracranial meningiomas: comparative analyses of the predictive value of the postoperative tumor volume and the Simpson classification.

J Neurosurg 2020 Jul 17:1-8. Epub 2020 Jul 17.

1Department of Neurosurgery.

Objective: In meningiomas, the Simpson grading system is applied to estimate the risk of postoperative recurrence, but might suffer from bias and limited overview of the resection cavity. In contrast, the value of the postoperative tumor volume as an objective predictor of recurrence is largely unexplored. The objective of this study was to compare the predictive value of residual tumor volume with the intraoperatively assessed extent of resection (EOR).

Methods: The Simpson grade was determined in 939 patients after surgery for initially diagnosed intracranial meningioma. Tumor volume was measured on initial postoperative MRI within 6 months after surgery. Correlation between both variables and recurrence was compared using a tree-structured Cox regression model.

Results: Recurrence correlated with Simpson grading (p = 0.003). In 423 patients (45%) with available imaging, residual tumor volume covered a broad range (0-78.5 cm3). MRI revealed tumor remnants in 8% after gross-total resection (Simpson grade I-III, range 0.12-33.5 cm3) with a Cohen's kappa coefficient of 0.7153. Postoperative tumor volume was correlated with recurrence in univariate analysis (HR 1.05 per cm3, 95% CI 1.02-1.08 per cm3, p < 0.001). A tree-structured Cox regression model revealed any postoperative tumor volume > 0 cm3 as a critical cutoff value for the prediction of relapse. Multivariate analysis confirmed the postoperative tumor volume (HR 1.05, p < 0.001) but not the Simpson grading (p = 0.398) as a predictor for recurrence.

Conclusions: EOR according to Simpson grading was overrated in 8% of tumors compared to postoperative imaging. Because the predictive value of postoperative imaging is superior to the Simpson grade, any residual tumor should be carefully considered during postoperative care of meningioma patients.
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http://dx.doi.org/10.3171/2020.4.JNS20412DOI Listing
July 2020

Predictors of Successful First-Pass Thrombectomy with a Balloon Guide Catheter: Results of a Decision Tree Analysis.

Transl Stroke Res 2020 10 23;11(5):900-909. Epub 2020 May 23.

Department of Clinical Radiology, Institute of Clinical Radiology and Neuroradiology, University Hospital of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany.

Complete recanalization after a single retrieval maneuver is an interventional goal in acute ischemic stroke and an independent factor for good clinical outcome. Anatomical biomarkers for predicting clot removal difficulties have not been comprehensively analyzed and await unused. We retrospectively evaluated 200 consecutive patients who suffered acute stroke and occlusion of the anterior circulation and were treated with mechanical thrombectomy through a balloon guide catheter (BGC). The primary objective was to evaluate the influence of carotid tortuosity and BGC positioning on the one-pass Modified Thrombolysis in Cerebral Infarction Scale (mTICI) 3 rate, and secondarily, the influence of communicating arteries on the angiographic results. After the first-pass mTICI 3, recanalization fell from 51 to 13%. The regression models and decision tree (supervised machine learning) results concurred: carotid tortuosity was the main constraint on efficacy, reducing the likelihood of mTICI 3 after one pass to 30%. BGC positioning was relevant only in carotid arteries without elongation: BGCs located in the distal internal carotid artery (ICA) had a 70% probability of complete recanalization after one pass, dropping to 43% if located in the proximal ICA. These findings demonstrate that first-pass mTICI 3 is influenced by anatomical and interventional factors capable of being anticipated, enabling the BGC technique to be adapted to patient's anatomy to enhance effectivity.
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http://dx.doi.org/10.1007/s12975-020-00784-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496051PMC
October 2020

Accuracy of intraoral scans in the mixed dentition: a prospective non-randomized comparative clinical trial.

Head Face Med 2020 May 19;16(1):11. Epub 2020 May 19.

Department of Orthodontics, University of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.

Objective: In-vivo accuracy of intraoral scans of complete mixed dentitions of patients in active treatment have not yet been investigated. The aim was to test the hypothesis that dimensional differences between intraoral scans and conventional alginate impressions in the mixed dentition are clinically irrelevant.

Methods: Trial design: Prospective non-randomized comparative clinical trial. Based on sample size calculation 44 evaluable mixed dentition jaws of patients in active orthodontic treatment were included. Each patient received an alginate impression following an intraoral scan (TRIOS® Ortho). Plaster cast was fabricated and scanned with an external scanner (ATOS-SO®). Both STL datasets were analyzed with the 3D inspection and mesh processing software GOM Inspect®. Statistical analysis comprised sample size calculation, t-test as well as nonparametric tests.

Results: The absolute mean difference between digital plaster casts and intraoral scans is 0.022 mm ± 0.027 mm (median 0.015 mm). The obtained measurements are in the range of comparable studies on full arch permanent dentitions. Gender, the size of the jaw represented by the dentition stage and upper respectively lower jaw, as well the malocclusion have no effect on the total deviations between digital plaster casts and intraoral scans. Detectable impression errors were bubbles in fissures and marginal ridges as well as incomplete alginate flow and detachment from the tray. Detectable scanning errors were incomplete distal surface of the most distal molar.

Conclusion: Dimensional differences between intraoral scans and conventional alginate impressions in the mixed dentition are clinically irrelevant for orthodontic purposes. In all clinical situations of active treatment in the mixed dentition, the intraoral scans are more detailed and less error-prone.
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http://dx.doi.org/10.1186/s13005-020-00222-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236363PMC
May 2020

Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning.

Transl Stroke Res 2020 10 14;11(5):940-949. Epub 2020 Jan 14.

Department of Clinical Radiology, Neuroradiology, University Hospital Muenster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Muenster, Germany.

Exact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48 h after production. The mean, maximum, and minimum HU values for the axial and coronal reconstructions were recorded. Each thrombus underwent a corresponding histological analysis, together with a laboratory analysis of water and iron contents. Decision trees, a type of supervised machine learning, were used to select the primary variable altering attenuation and the best parameter for predicting histology. The decision trees selected red blood cells (RBCs) for correlation with all attenuation parameters (p < 0.001). Conversely, maximum attenuation on axial CT offered the greatest accuracy for discriminating up to four groups of clot histology (p < 0.001). Similar RBC-rich thrombi displayed variable imaging associated with different iron (p = 0.023) and white blood cell contents (p = 0.019). Water content varied among the different histologies but did not in itself account for the differences in attenuation. Independent factors determining clot attenuation were the RBCs (β = 0.33, CI = 0.219-0.441, p < 0.001) followed by the iron content (β = 0.005, CI = 0.0002-0.009, p = 0.042). Our findings suggest that it is possible to extract more and valuable information from NCCT that can be extrapolated to provide insights into clot histological and chemical composition.
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http://dx.doi.org/10.1007/s12975-019-00766-zDOI Listing
October 2020

Comparing Plasma Exchange to Escalated Methyl Prednisolone in Refractory Multiple Sclerosis Relapses.

J Clin Med 2019 Dec 22;9(1). Epub 2019 Dec 22.

Neurology Clinic and Institute for Translational Neurology, University of Muenster, 48149 Münster, Germany.

Intravenous methyl prednisolone (IVMPS) represents the standard of care for multiple sclerosis (MS) relapses, but fail to improve symptoms in one quarter of patients. In this regard, apart from extending steroid treatment to a higher dose, therapeutic plasma exchange (TPE) has been recognized as a treatment option. The aim of this retrospective, monocentric study was to investigate the efficacy of TPE versus escalated dosages of IVMPS in refractory MS relapses. An in-depth medical chart review was performed to identify patients from local databases. Relapse recovery was stratified as "good/full", "average" and "worst/no" according to function score development. In total, 145 patients were analyzed. Good/average/worst recovery at discharge was observed in 60.9%/32.6%/6.5% of TPE versus 15.2%/14.1%/70.7% of IVMPS patients, respectively. A total of 53.5% of IVMPS patients received TPE as rescue treatment and 54.8% then responded satisfactorily. The multivariable odds ratio (OR) for worst/no recovery was 39.01 (95%-CI: 10.41-146.18; ≤ 0.001), favoring administration of TPE as first escalation treatment. The effects were sustained at three-month follow-ups, as OR for further deterioration was 6.48 (95%-CI: 2.48-16.89; ≤ 0.001), favoring TPE. In conclusion, TPE was superior over IVMPS in the amelioration of relapse symptoms at discharge and follow-up. This study provides class IV evidence supporting the administration of TPE as the first escalation treatment to steroid-refractory MS relapses.
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http://dx.doi.org/10.3390/jcm9010035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027010PMC
December 2019

Children with Fetal Alcohol Syndrome (FAS): 3D-Analysis of Palatal Depth and 3D-Metric Facial Length.

Int J Environ Res Public Health 2019 12 21;17(1). Epub 2019 Dec 21.

Department of Orthodontics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.

: Drinking alcohol during pregnancy can result in severe developmental disorders in the child. Symptoms of the fetal alcohol spectrum disorder (FASD) comprise growth deficiencies, abnormal facial phenotype and damage or dysfunction of the central nervous system. Numerous diagnostic methods for facial phenotyping in FASD exist, but diagnoses are still difficult. Our aim was to find additional and objective methods for the verification of FAS(D). : Three-dimensional dental models of 60 children (30 FAS and 30 controls) were used to metrically determine maximum palatal depths at the median palatine raphe. Three-dimensional facial scans were taken, and vertical distances of the face were measured at five defined facial landmarks (FP1-FP5) for each child. : Mean palatal height, total facial length (FP1-FP5) as well as FP4-FP5 did not significantly differ between the FAS group and the control group. Comparing vertical facial subdivisions, however, resulted in significant differences for distances FP1 to FP2 ( = 0.042, FAS > controls), FP2 to FP3 ( < 0.001, FAS < controls), FP3 to FP4 ( < 0.001, FAS > controls) and FP3 to FP5 ( = 0.007, FAS > controls). : Metric vertical measurements of the face can be used as additional objective criteria for FAS diagnoses. However, no significant differences were reported for palatal depth evaluation in the specific age range tested in the present study.
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http://dx.doi.org/10.3390/ijerph17010095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982319PMC
December 2019

Tooth Malformations, DMFT Index, Speech Impairment and Oral Habits in Patients with Fetal Alcohol Syndrome.

Int J Environ Res Public Health 2019 11 11;16(22). Epub 2019 Nov 11.

Department of Orthodontics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.

Fetal alcohol spectrum disorder (FASD) is a developmental disorder with severe negative lifetime consequences. Although knowledge about the harmfulness of alcohol consumption during pregnancy has spread, the prevalence of fetal alcohol spectrum disorder is very high. Our study aims at identifying fetal alcohol syndrome (FAS)-associated dental anomalies or habits, which need early attention. Sixty children (30 FAS; 30 controls) were examined prospectively. Swallowing pattern, oral habits, breastfeeding, speech therapy, ergotherapy, physiotherapy, exfoliation of teeth, DMFT (decayed, missing, filled teeth) index, modified DDE (developmental defects of enamel) index and otitis media were recorded. Swallowing pattern, exfoliation of teeth, and otitis media were not significantly different. Significant differences could be found concerning mouthbreathing ( = 0.007), oral habits ( = 0.047), age at termination of habits ( = 0.009), speech treatment ( = 0.002), ergotherapy, physiotherapy, and breastfeeding ( ≤ 0.001). DMFT ( ≤ 0.001) and modified DDE ( = 0.001) index showed significantly higher values for children with fetal alcohol syndrome. Children with fetal alcohol syndrome have a higher need for early developmental promotion such as speech treatment, ergotherapy, and physiotherapy. Mouthbreathing, habits, and lack of breastfeeding may result in orthodontic treatment needs. High DMFT and modified DDE indexes hint at a higher treatment and prevention need in dentistry.
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http://dx.doi.org/10.3390/ijerph16224401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888578PMC
November 2019

Quality of Life of Patients With Osteosarcoma in the European American Osteosarcoma Study-1 (EURAMOS-1): Development and Implementation of a Questionnaire Substudy.

JMIR Res Protoc 2019 Sep 26;8(8):e14406. Epub 2019 Sep 26.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

Background: The quality of life (QoL) of patients with osteosarcoma (OS) may be adversely affected by the disease or its treatment. Therefore, it is important to understand the QoL of patients undergoing treatment for OS to improve the QoL. We report on the first prospective international QoL study that was embedded within a large randomized clinical trial from 4 national study groups.

Objective: This paper aimed to describe the QoL study development, methodology, accrual details, and characteristics of the QoL cohort.

Methods: A total of 2260 patients registered in the EURopean AMerican Osteosarcoma Study-1 (EURAMOS-1), of whom 97.92% (2213/2260) were eligible for the optional QoL assessment and could participate in terms of questionnaire availability. Overall, 61.86% (1369/2213) of patients and/or proxies completed the QoL evaluation at the first assessment time point (E1) after the start of preoperative treatment. The QoL measures used (self- and/or proxy reports) depending on the patient's age and national study group. Participants and nonparticipants in the ancillary QoL study were compared regarding relevant demographic and disease-related characteristics at registration in the trial.

Results: The participation rate at time point E1 did not differ with regard to age, gender, the occurrence of pathological fracture, or the presence of any metastases at diagnosis. No differences were found regarding the primary tumor site. Only the national study group affiliation had an influence on participation. Participation decreased linearly with trial progress up to 20% at the final time point of QoL assessment.

Conclusions: This study demonstrates the feasibility of international cooperation for the purpose of assessing and understanding the QoL of pediatric and adolescent/young adult patients with cancer. Future outcomes of this QoL substudy will help to adapt interventions to improve QoL.
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http://dx.doi.org/10.2196/14406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819132PMC
September 2019

Asymmetry-index and orthodontic facial analysis of children with foetal alcohol syndrome using 3D-facial scans.

Pediatr Res 2020 08 7;88(2):243-249. Epub 2019 Sep 7.

Department of Orthodontics, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Background: The foetal alcohol spectrum disorder (FASD) is a complex and heterogenic disorder, caused by gestational exposure to alcohol. Patients with foetal alcohol syndrome (FAS-most severe form) show abnormal facial features. Our study aims at finding additional reliable and objective parameters for FAS diagnosis.

Methods: Facial three-dimensional scans of 30 children with FAS and 30 controls were analysed. Orthodontic profile analysis (concerning position of upper and lower jaw) was performed. Vertical facial proportions were taken and facial asymmetry index (right to left side) was calculated.

Results: Profile type was significantly different for children with FAS (p = 0.001) with lower jaws more frequently in a retral position. Profile angle was significantly larger in the group with FAS (p = 0.009). Children with FAS had shorter middle thirds and longer lower thirds of the face (p < 0.001). Stomion (point between upper and lower lip) was located significantly more caudally in the FAS group (p < 0.001). Facial asymmetry index was not significantly different.

Conclusions: Children with FAS differ significantly from controls in vertical and sagittal facial measurements. Profile analysis and measurement of vertical proportions are easy to apply standard procedures in everyday orthodontic practice and could be time-saving and objective means for additional verification of FAS.
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http://dx.doi.org/10.1038/s41390-019-0559-5DOI Listing
August 2020

3D-Analysis of Mouth, Nose and Eye Parameters in Children with Fetal Alcohol Syndrome (FAS).

Int J Environ Res Public Health 2019 07 16;16(14). Epub 2019 Jul 16.

Department of Orthodontics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.

: Fetal alcohol spectrum disorder (FASD) is a developmental disorder with severe negative lifetime consequences for the affected person. Numerous diagnostic methods for facial assessment in FAS exist, but most of them are based on subjective evaluations. Our aim was therefore to find objective methods for the verification of FAS(D). : 58 children (28 FAS; 30 controls) were examined prospectively. 3D facial scans were performed for each child and facial parameters at the mouth, nose and eye regions were measured and compared between the groups. : Significant differences could be found for the distance between right and left sulcus nasi at the transition point to the philtrum ( < 0.001), for the inner canthal distance ( = 0.001) as well as for the right and left palpebral fissure length ( < 0.001). No significant difference between the FAS and control children could be found for the measurements of mouth breadth ( = 0.267) and breadth between the left and right alares nasi ( = 0.260). : Measurements of mouth breadth and nose breadth for the alares nasi are not suitable for FAS diagnosis. In contrast, digital contactless measurements of the distance between the right and left sulcus nasi at the transition point to the philtrum, as well as the inner canthal distance and palpebral fissure length of the left and right eyes, showed significant differences when comparing children with FAS to healthy controls. These measurements could thus be additional objective means for the verification of FAS.
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http://dx.doi.org/10.3390/ijerph16142535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678862PMC
July 2019

Variability in the decision-making process of acute ischemic stroke in difficult clinical and radiological constellations: analysis based on a cross-sectional interview-administered stroke questionnaire.

Eur Radiol 2019 Nov 10;29(11):6275-6284. Epub 2019 May 10.

Institute of Clinical Radiology and Neuroradiology, University Hospital of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Muenster, Germany.

Background And Purpose: Notwithstanding guidelines, indications for mechanical thrombectomy (MT) in acute ischemic stroke are multifactorial and can be complex. Our aim was to exploratively evaluate decision-making on the advisability of performing MT in cases presented as an interview-administered questionnaire.

Methods: Fifty international raters assessed 12 cases and decided to recommend or exclude MT. Each case contained a brief summary of clinical information and eight representative images of the initial multimodal CT. The demographic characteristics and stroke protocols were recorded for raters. For each case, the reasons for excluding MT were recorded. Uni- and multivariate logistic regression analysis were performed for the different demographic and case characteristics to identify factors that might influence decision-making.

Results: All raters performed MT (median MTs/hospital/year [IQR], 100 [50-141]) with a median of 7 years of experience as first operator (IQR, 4-12). Per case, diversity in decision-making ranged between 1 (case 6, 100% yes MT) and 0.50 (case 12, 54.2% yes MT and 45.8% no MT). The most common reasons for excluding MT were small CBV/CBF mismatch (17%, 102/600), size of infarct core on the CBV map (15.2%, 91/600), and low NIHSS score (National Institute of Health Stroke Scale, 8.3%, 50/600). All clinical and radiological characteristics significantly affected the decision regarding MT, but the general characteristics of the raters were not a factor.

Conclusions: Clinical and imaging characteristics influenced the decision regarding MT in stroke. Nevertheless, a consensus was reached in only a minority of cases, revealing the current divergence of opinion regarding therapeutic decisions in difficult cases.

Key Points: • This is the first study to explore differences in decision-making in respect of mechanical thrombectomy in ischemic stroke with complex clinical and radiological constellations. • Fifty experienced international neurointerventionalists answered this interview-administered stroke questionnaire and made decisions as to whether to recommend or disadvise thrombectomy in 12 selected cases. • Diversity in decision-making for thrombectomy ranged from 1 (100% of raters offered the same answer) to 0.5 (50% indicated mechanical thrombectomy). There was a consensus in only a minority of cases, revealing the current disparity of opinion regarding therapeutic decisions in difficult cases.
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http://dx.doi.org/10.1007/s00330-019-06199-4DOI Listing
November 2019

3D Analysis of Philtrum Depth in Children with Fetal Alcohol Syndrome.

Alcohol Alcohol 2019 Mar;54(2):152-158

Department of Orthodontics, University of Münster, Albert-Schweitzer-Campus 1, Münster, Germany.

Aims: Diagnosis of fetal alcohol spectrum disorder (FASD) is complex and difficult. The estimated number of unreported FASD is thus assumed to be substantial. In our cross-sectional study, we aimed to identify possible metric differences in philtrum depth in children with fetal alcohol syndrome (FAS) compared to healthy controls based on non-invasive 3D facial scanning in order to provide an objective, metrical tool improving FASD diagnosis.

Methods: Twenty-five children with confirmed FAS and 30 healthy school children without FAS, both in the mixed dentition, were prospectively recruited and 3D facial scans were performed after recording body length, weight and head circumference. Philtrum surface data were extracted and metric philtrum depth was determined at four geometrically defined measuring points (P1-P4) along the vertical length of the philtrum.

Results: Philtrum depths at P1 (P = 0.025), P2 (P = 0.001), P3 (P < 0.001) and P4 (P = 0.001) as well as mean philtrum depth P1-P4 (P < 0.001) differed significantly between patients with and without FAS. Compared to controls, the philtrum was shallower in patients with FAS by on average 0.4 mm at each of the respective points. Whereas no differences could be determined for body height and weight, head circumference was significantly smaller in patients with FAS (P = 0.001), particularly in girls (P = 0.008).

Conclusions: Apart from head circumference, philtrum depth is significantly reduced in children with FAS and can thus be used as diagnostic indicator to aid and confirm FAS diagnosis. In contrast to visual assessments, 3D face scan methods allow a more objective quantification and can thus provide additional evidence in FAS diagnosis.
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http://dx.doi.org/10.1093/alcalc/agy088DOI Listing
March 2019

Local Tumor Control and Clinical Symptoms After Gamma Knife Radiosurgery for Residual and Recurrent Vestibular Schwannomas.

World Neurosurg 2019 Feb 14;122:e1240-e1246. Epub 2018 Nov 14.

Department of Neurosurgery, University Hospital Münster, Münster, Germany. Electronic address:

Background: The use of Gamma Knife radiosurgery (GKRS) for recurrent or residual vestibular schwannoma (VS) after microsurgery (MS) has been investigated in several retrospective studies. The purpose of this study was to identify potential risk factors for both neurologic deterioration and tumor progression after GKRS for previously operated VSs in a prospective setting.

Methods: Patients who underwent GKRS for previously operated and histopathologically confirmed VS between 1998 and 2015 were prospectively followed-up. Risk factors for therapy side effects and predictors for tumor control were investigated in uni- and multivariate analyses.

Results: A total of 160 individuals with a median age of 55 years were included. Median tumor volume prior to GKRS was 1.40 cm (range, 0.06-35.80 cm). After a median follow-up of 36 months, hearing and facial nerve function were serviceable (modified Gardner-Robertson and House-Brackmann grades I and II) in 7 (5%) and 82 (55%) patients, respectively. Deterioration to a nonserviceable facial nerve function after GKRS was found in 3% (3/89) and tended to increase with rising tumor volume (odds ratio, 1.65 per cm; 95% confidence interval, 1.00-2.71; P = 0.051). Median tumor volume prior to GKRS was higher in patients with radiologic (P = 0.020) or clinical tumor progression (P < 0.001). Critical tumor volume prior to GKRS to predict clinical and radiologic tumor progression was 1.30 cm (P < 0.001) and 3.30 cm (P = 0.019), respectively. However, in multivariate analyses, none of the analyzed variables were found to independently predict tumor progression.

Conclusions: Intended submaximal resection followed by GKRS is a viable treatment for VS. Because tumor remnant size after MS is an important predictor for recurrence after adjuvant GKRS, both brainstem and cerebellar decompression and maximal safely achievable resection should remain major goals of microsurgery.
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http://dx.doi.org/10.1016/j.wneu.2018.11.022DOI Listing
February 2019

Malocclusion Can Give Additional Hints for Diagnosis of Fetal Alcohol Spectrum Disorder.

Alcohol Alcohol 2019 Jan;54(1):56-61

Department of Orthodontics, University Münster, Albert-Schweitzer-Campus 1, Münster, Germany.

Aims: Fetal alcohol spectrum disorder (FASD) is a developmental disorder caused by maternal alcohol intake (prevalence: 0.77%). Malocclusion has been described in case reports of patients with FASD, but reliable evidence for associations between FASD and malocclusion is not documented. Malocclusion is defined as tooth irregularity (prevalence: 14.6%) or incorrect relationship between the jaws such as lateral crossbites (prevalence: 3.1%). The purpose of this study was to investigate possible associations between malocclusion and FASD.

Short Summary: FASD prevalence is high and diagnosis is very difficult; Malocclusions can give additional hints for FASD diagnosis; Patients with FASD show growth deficits concerning the maxilla; Early and consistent orthodontic supervision and therapy can prevent facial asymmetries in FASD patients.

Methods: Thirty patients with FASD and 30 patients of a healthy control group were examined. Inclusion criteria were mixed dentition, verified FASD/absence of FASD (control group), exclusion criteria were orthodontic treatment and disorders other than FASD. The extent and type of malocclusion were quantified with the peer assessment rating (PAR) index based on an analysis of orthodontic plaster models. In addition, anthropometric data such as gestational age, body weight and height at birth as well as present body weight, height and head circumference at examination date were assessed.

Results: The PAR index showed a significant increase in malocclusions in FASD patients compared to the group that were not diagnosed with FASD (P = 0.002). FASD patients showed particular differences in the upper transversal dimension with a higher prevalence of crossbites (P = 0.018) and a lower head circumference (P < 0.001). Body weight (P < 0.001) and height (P < 0.001) were significantly lower for FASD patients at time of birth, but not at the present examination date (weight: P = 0.329; height: P = 0.496). When relating weight and height measures to age using percentile curves of physiological growth, clinically relevant discrepancies could be found for FASD patients.

Conclusions: Our results show that malocclusion can provide additional evidence for FASD diagnosis. When FASD is diagnosed in a child, early referral to an orthodontist is advisable to stimulate maxillary growth and consequently prevent further malocclusions.
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http://dx.doi.org/10.1093/alcalc/agy071DOI Listing
January 2019

Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia-a phase 3 study.

Leukemia 2018 12 1;32(12):2558-2571. Epub 2018 Oct 1.

Insitute for Biostatistics and Clinical Research, University Hospital, Münster, Germany.

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184). The primary endpoint overall response rate (ORR) consisting of complete remission (CR) and incomplete remission (CR) was not significantly different (P = 0.202) between S-HAM (77%) and double induction (72%). The median overall survival was 35 months after S-HAM and 25 months after double induction (P = 0.323). Duration of critical leukopenia was significantly reduced after S-HAM (median 29 days) versus double induction (median 44 days)-P < 0.001. This translated into a significantly shortened duration of hospitalization after S-HAM (median 37 days) as compared to standard induction (median 49 days)-P < 0.001. In conclusion, dose-dense induction therapy with the S-HAM regimen shows favorable trends but no significant differences in ORR and OS compared to standard double induction. S-HAM significantly shortens critical leukopenia and the duration of hospitalization by 2 weeks.
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http://dx.doi.org/10.1038/s41375-018-0268-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286323PMC
December 2018

Quantification of macular perfusion using optical coherence tomography angiography: repeatability and impact of an eye-tracking system.

BMC Ophthalmol 2018 May 24;18(1):123. Epub 2018 May 24.

Department of Ophthalmology, University of Muenster Medical Center, Albert-Schweitzer-Campus 1, Building D15, 48149, Muenster, Germany.

Background: The aim of the study was to evaluate the impact of integration of the eye-tracking system (ET) on the repeatability of flow density measurements using optical coherence tomography (OCT) angiography.

Methods: 20 healthy subjects were included in this study. OCT-angiography was performed using RTVue XR Avanti (Optovue Inc., Fremont, California, USA). The macula was imaged using a 3 × 3 mm scan twice with and twice without activation of the ET. Flow density data of the macular in the superficial and deep OCT angiograms were extracted and analyzed.

Results: The difference between the flow density (whole en face) in the first session and second session with and without ET was statistically non-significant (with ET: superficial retinal OCT angiogram: p = 0.50; deep retinal OCT angiogram: p = 0.89; without ET: superficial retinal OCT angiogram: p = 0.81; deep retinal OCT angiogram: p = 0.24). There was no significant difference in the coefficients of repeatability for measurements with and without ET in the superficial retinal OCT angiogram (adjusted p-value = 0.176), whereas the difference was significant for the deep retinal OCT angiogram (adjusted p-value = 0.008).

Conclusions: Integration of the ET improved the repeatability of flow density measurements in the deep OCT angiogram; this needs to be considered when evaluating the long-term changes of flow density and when comparing data of different studies and different devices.
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http://dx.doi.org/10.1186/s12886-018-0789-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968584PMC
May 2018

Sucking behaviour using feeding teats with and without an anticolic system: a randomized controlled clinical trial.

BMC Pediatr 2018 03 16;18(1):115. Epub 2018 Mar 16.

Department of Orthodontics, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

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http://dx.doi.org/10.1186/s12887-018-1092-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857083PMC
March 2018

Frontline therapy of acute promyelocytic leukemia: Randomized comparison of ATRA and intensified chemotherapy versus ATRA and anthracyclines.

Eur J Haematol 2018 Feb 4;100(2):154-162. Epub 2017 Dec 4.

Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilian-University Munich, Munich, Germany.

Objectives: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high-dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99).

Patients And Results: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (P = .76), overall survival, event-free survival, leukemia-free survival, cumulative incidence of relapse at 6 years 75% vs 78% (P = .92); 75% vs 68% (P = .29); 86% vs 81% (P = .28); and 0% vs 12% (P = .04, no relapse vs four relapses), respectively. The median time to achieve molecular remission (RT-PCR negativity of PML-RARA) was 60 days in both arms (P = .12). The AMLCG regimen was associated with a longer duration of neutropenia (P = .02) and a higher rate of WHO grade ≥3 infections.

Conclusions: The small number of patients limits the reliability of conclusions. With these restrictions, the outcomes of both approaches were similar and show the limitations of ATRA and chemotherapy. The HD ara-C-containing regimen was associated with a lower relapse rate in high-risk APL.
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http://dx.doi.org/10.1111/ejh.12994DOI Listing
February 2018

Therapy of older persons with acute myeloid leukaemia.

Leuk Res 2017 09 1;60:1-10. Epub 2017 Jun 1.

University Hospital Münster, Department of Medicine A, Albert-Schweitzer-Campus 1, Geb. A1, 48129 Münster, Germany.

Most persons age≥60 y with acute myeloid leukaemia (AML) die from their disease. When interpreting clinical trials data from these persons one must be aware of substantial selection biases. Randomized trials of post-remission treatments can be performed upfront or after achieving defined landmarks. Both strategies have important limitations. Selection of the appropriate treatment is critical. Age, performance score, co-morbidities and frailty provide useful data to treatment selection. If an intensive remission induction therapy is appropriate, therapy with cytarabine and an anthracycline is the most common regimen. Non-intensive therapies consist of the hypo-methylating drugs azacitidine and decitabine, low-dose cytarabine and supportive care. Feasibility of doing an allotransplant in older persons with AML is increasing. However, only very few qualify. Results of cytogenetic testing are risk factor in young and old persons with AML. Adverse abnormalities are more frequent in older persons. Although data about the frequency of mutations in older persons with AML is increasing their prognostic impact is less clear than in younger subjects. Neither differences in the distribution of cytogenetic risk, mutations, nor differences in clinical risk factors between younger and older persons with AML completely explain the age-dependent outcome. Many drugs are in clinical development in older persons with AML. Their potential role in the treatment of older persons with AML remains to be defined.
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http://dx.doi.org/10.1016/j.leukres.2017.05.020DOI Listing
September 2017

The Simpson grading in meningioma surgery: does the tumor location influence the prognostic value?

J Neurooncol 2017 Jul 19;133(3):641-651. Epub 2017 May 19.

Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, North Rhine-Westphalia, Germany.

In meningiomas, location-specific differences of the prognostic value of the Simpson classification are sparsely investigated but can influence strategy of surgery. We therefore compared the prognostic value of the Simpson classification in different tumor locations. Progression was compared with Simpson grade in 826 meningioma patients (median age 58 years, female:male ratio 2.4) in location-specific uni- and multivariate analyses. Simpson grade strongly correlated with tumor location (p < .001). Within a median follow-up of 50 months, recurrence was observed in 107 of 803 patients (13%). In general, increasing Simpson grade (p = .002) and subtotal resection (STR, ≥grade III) were correlated with tumor recurrence [hazard ratio (HR): 1.87; p = .004]. In 268 convexity meningiomas, frequency of tumor recurrence correlated with Simpson grade (p = .034). Risk of recurrence was similar after grade I and II resections, tended to increase after grade III (HR: 2.35; p = .087) but was higher after grade IV resections (HR: 7.35; p = .003). Risk of recurrence was higher after STR (HR: 4.21; p = .001) than after gross total resection (GTR, ≤grade II). Contrarily, increasing Simpson grade and STR were not correlated with progression in 102 falx, 38 posterior fossa and nine intraventricular meningiomas. In 325 skull base lesions, risk of recurrence was similar after GTR and STR (p = .198) and was only increased after grade IV resections (HR: 3.26; p = .017). Simpson grading and extent of resection were not equally prognostic in all locations. Lower impact of extent of resection should be considered during surgery for skull base, posterior fossa and falx meningiomas.
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http://dx.doi.org/10.1007/s11060-017-2481-1DOI Listing
July 2017

Dexmedetomidine sedation combined with caudal anesthesia for lower abdominal and extremity surgery in ex-preterm and full-term infants.

Paediatr Anaesth 2017 Jun 2;27(6):637-642. Epub 2017 Mar 2.

Department of Anesthesiology and Intensive Care Medicine, University Hospital Münster, Münster, Germany.

Background: Awake caudal anesthesia is a potentially attractive option, because the administration of general anesthesia is associated with a high rate of respiratory complications and hemodynamic disturbances and potential neurotoxic effects. To facilitate the caudal puncture and subsequent surgical intervention, additional sedatives are commonly administered.

Aim: We aimed to establish a new, safe, and effective anesthetic procedure for very young children with comorbidities.

Methods: We retrospectively analyzed 23 children who underwent lower abdominal or lower extremity surgery with dexmedetomidine sedation and caudal anesthesia from January 2015 to August 2015. Dexmedetomidine was initiated with a total bolus infusion of 0.7-1.1 μg·kg followed by a continuous infusion of 1 μg·kg ·h . Bupivacaine (2.5 mg·kg ) was supplemented with 5-10 μg·kg epinephrine to strengthen and prolong motor block. According to maturity at birth, two groups were defined: ex-preterm and full-term infants.

Results: There were 12 ex-preterm and 10 full-term infants available for analysis. The median postmenstrual age was 44 (38-52) weeks in ex-preterm and 46.5 (40-72) weeks in full-term infants. Without any additional intervention, surgery was successfully accomplished in 82% of all cases. While respiratory complications were not a problem, hemodynamic disturbances commonly occurred. Maximum decreases in heart rate (HR) of 30% were accompanied by maximum decreases in mean arterial pressure (MAP) of 38%. No infant had a heart rate below 100 bpm. MAP declined in one ex-preterm infant to a minimum value of 32 mmHg.

Conclusion: Caudal anesthesia combined with dexmedetomidine sedation is an effective anesthetic technique for lower abdominal and extremity surgery in ex-preterm and full-term infants with severe comorbidities.
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http://dx.doi.org/10.1111/pan.13110DOI Listing
June 2017

Thorax-to-head ratio and defect diameter-to-head ratio in giant omphaloceles as predictor for fetal outcome.

Arch Gynecol Obstet 2017 Feb 11;295(2):325-330. Epub 2016 Nov 11.

Department of Obstetrics and Gynecology, University Hospital of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Purpose: To investigate the relationship between the thorax diameter and defect diameter of giant omphaloceles as a predictor for fetal outcome.

Methods: In a retrospective study, 17 fetuses with isolated giant omphaloceles were included for evaluation. The anterior-posterior thorax diameter and the defect diameter were measured from ultrasound images. For analysis, the thorax-to-head ratio (T/HC), the defect diameter-to-head ratio (DD/HC), and the quotient of the defect diameter and the thorax diameter (DD/T) were calculated. The days of ventilation (t ), the duration until hospital discharge (t ), and the type of treatment were recorded as outcome parameters.

Results: No relationship was found between the calculated ratios (T/HC, DD/HC, or DD/T) and neither t (r = -0.418, p = 0.095; r = -0.153, p = 0.556; and r = -0.023, p = 0.929; respectively) nor t (r = -0.391, p = 0.121; r = 0.041, p = 0.875; and r = 0.121, p = 0.645, respectively). The type of postnatal treatment was not associated with the three calculated ratios or t (r = 0.155, p = 0.553; r = 0.019, p = 0.942; and r = 0.012, p = 0.965; r = -0.009, p = 0.973, respectively). In 53% of cases, t was delayed due to additional and independent postnatal complications.

Conclusion: Thorax diameter or defect diameter of giant omphaloceles is not predictive for fetal outcome. The perinatal care of these abdominal wall defects still remains a multidisciplinary challenge, but the outcome of giant omphaloceles is favorable at experienced centers.
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http://dx.doi.org/10.1007/s00404-016-4236-1DOI Listing
February 2017

Acute myeloid leukemia with del(9q) is characterized by frequent mutations of NPM1, DNMT3A, WT1 and low expression of TLE4.

Genes Chromosomes Cancer 2017 01 25;56(1):75-86. Epub 2016 Oct 25.

Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU) München, München, Germany.

Deletions of the long arm of chromosome 9 [del(9q)] are a rare but recurring aberration in acute myeloid leukemia (AML). Del(9q) can be found as the sole abnormality or in combination with other cytogenetic aberrations such as t(8;21) and t(15;17). TLE1 and TLE4 were identified to be critical genes contained in the 9q region. We performed whole exome sequencing of 5 patients with del(9q) as the sole abnormality followed by targeted amplicon sequencing of 137 genes of 26 patients with del(9q) as sole or combined with other aberrations. We detected frequent mutations in NPM1 (10/26; 38%), DNMT3A (8/26; 31%), and WT1 (8/26; 31%) but only few FLT3-ITDs (2/26; 8%). All mutations affecting NPM1 and DNMT3A were exclusively identified in patients with del(9q) as the sole abnormality and were significantly more frequent compared to 111 patients classified as intermediate-II according to the European LeukemiaNet (10/14, 71% vs. 22/111, 20%; P < 0.001, 8/14, 57% vs. 26/111, 23%; P = 0.02). Furthermore, we identified DNMT3B to be rarely but recurrently targeted by truncating mutations in AML. Gene expression analysis of 13 patients with del(9q) and 454 patients with normal karyotype or various cytogenetic aberrations showed significant down regulation of TLE4 in patients with del(9q) (P = 0.02). Interestingly, downregulation of TLE4 was not limited to AML with del(9q), potentially representing a common mechanism in AML pathogenesis. Our comprehensive genetic analysis of the del(9q) subgroup reveals a unique mutational profile with the frequency of DNMT3A mutations in the del(9q) only subset being the highest reported so far in AML, indicating oncogenic cooperativity. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/gcc.22418DOI Listing
January 2017

Brain Invasion in Meningiomas: Incidence and Correlations with Clinical Variables and Prognosis.

World Neurosurg 2016 Sep 22;93:346-54. Epub 2016 Jun 22.

Department of Neurosurgery, University Hospital Münster, Münster, Germany. Electronic address:

Objective: In meningioma, correlation of brain invasion with prognosis and clinical variables remains controversial.

Methods: Correlation of brain invasion with clinical and histopathologic variables was investigated in 467 patients with primary intracranial meningioma.

Results: Diffuse (n = 3; 10%), clusterlike (n = 11; 34%) or fingerlike (n = 18; 56%) invasion was detected in 32 patients (7%). Brain invasion was more common in males than in females (13% vs. 5%; odds ratio, 2.75; 95% confidence interval, 1.29-5.89; P = 0.009) and pattern of invasion differed between genders (P = 0.037). Brain invasion was absent in 401 benign meningiomas and present in 48% of 60 atypical (n = 29) and 50% of 6 anaplastic (n = 3) meningiomas (P < 0.001) but was independent of tumor location and extent of resection. Progression occurred in 11% and was more frequent (31% vs. 15%; P = 0.036) in invasive than in noninvasive tumors, but only after gross total resection and in univariate analyses, and independent of invasion pattern. In atypical meningiomas, frequency of adjuvant irradiation was similar comparing invasive and noninvasive tumors and grading solely based on brain invasion (n = 20; 33%), other World Health Organization (WHO) criteria (n = 31; 52%) or a combination of both (n = 9; 15%). Risk of recurrence was lower (hazard ratio, 0.258, 95% confidence interval, 0.09-0.734; P = 0.011) when grading exclusively based on brain invasion than when further WHO criteria were in addition present and the progression-free interval among the first was similar to benign tumors.

Conclusions: Brain invasion and its patterns are correlated to gender. In contrast to the current WHO classification, invasion was associated with recurrence only after gross total resection and not independent of further histopathologic criteria of atypia.
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http://dx.doi.org/10.1016/j.wneu.2016.06.055DOI Listing
September 2016

Surgery for meningioma in the elderly and long-term survival: comparison with an age- and sex-matched general population and with younger patients.

J Neurosurg 2017 04 3;126(4):1201-1211. Epub 2016 Jun 3.

Department of Neurosurgery and.

OBJECTIVE The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population. METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into "elderly" (age ≥ 65 years, n = 162) and "younger" (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population. RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75-8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70-1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23-144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23-50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09-6.69; p = 0.032). CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.
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http://dx.doi.org/10.3171/2016.2.JNS152611DOI Listing
April 2017

Resistance to water and abrasion of a broad-spectrum sunscreen: a prospective, open-label study.

Exp Dermatol 2016 Feb 23;25(2):151-2. Epub 2015 Nov 23.

Department of Dermatology, University of Bonn, Bonn, Germany.

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http://dx.doi.org/10.1111/exd.12869DOI Listing
February 2016

Prognostic importance of expression of the Wilms' tumor 1 gene in newly diagnosed acute promyelocytic leukemia.

Leuk Lymphoma 2015 21;56(8):2289-95. Epub 2015 Jan 21.

a Department of Hematology and Oncology , University Hospital Mannheim, University of Heidelberg , Germany.

Wilms' tumor 1 gene (WT1) is known to be highly expressed in acute promyelocytic leukemia (APL) but information on its impact on prognosis is lacking. WT1 expression was analyzed in bone marrow samples of 79 patients with APL at initial diagnosis. Patients had a differing outcome according to their level of WT1 expression. In patients who achieved a complete remission (CR), low or high WT1 expression was significantly associated with inferior overall survival (OS) compared to intermediate WT1 expression (49% for WT1high vs. 63% for WT1low vs. 93% for WT1int; p=0.008). Moreover, there were significant differences in relapse-free survival (RFS) between the three expression groups (42% for WT1high vs. 63% for WT1low vs. 83% for WT1int; p=0.047). In multivariable analysis WT1 expression showed an independent prognostic impact on OS of responders to induction therapy. In conclusion, the level of WT1 expression can add prognostic information in APL risk stratification.
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http://dx.doi.org/10.3109/10428194.2014.990011DOI Listing
April 2016

The NPM1 mutation type has no impact on survival in cytogenetically normal AML.

PLoS One 2014 9;9(10):e109759. Epub 2014 Oct 9.

Laboratory for Leukemia Diagnostics, Dept. of Internal Medicine III, University Hospital Munich Großhadern, Ludwig-Maximilian-University (LMU), Munich, Germany; Clinical Cooperative Group Pathogenesis of Acute Myeloid Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.

NPM1 mutations represent frequent genetic alterations in patients with acute myeloid leukemia (AML) associated with a favorable prognosis. Different types of NPM1 mutations have been described. The purpose of our study was to evaluate the relevance of different NPM1 mutation types with regard to clinical outcome. Our analyses were based on 349 NPM1-mutated AML patients treated in the AMLCG99 trial. Complete remission rates, overall survival and relapse-free survival were not significantly different between patients with NPM1 type A or rare type mutations. The NPM1 mutation type does not seem to play a role in risk stratification of cytogenetically normal AML.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109759PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192029PMC
December 2015

Gamma Knife radiosurgery following subtotal resection of vestibular schwannoma.

J Clin Neurosci 2014 Dec 22;21(12):2077-82. Epub 2014 Jul 22.

Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany.

During treatment of large vestibular schwannomas, incomplete resection (IR) followed by Gamma Knife surgery (GKS; Elekta AB, Stockholm, Sweden) possibly offers tumor growth control and good clinical outcome, and is being discussed as an alternative to complete tumor removal with its inherent risks, especially for facial nerve function. However, available data for this concept are limited due to the small number of published studies. To analyze the effects of combined therapy in a larger cohort, we reviewed the currently available data. Six studies comprising 159 patients with a tumor diameter of at least 2 cm were included (median volume 19.95 cm(3) in four studies, n=137). GKS was performed on average 6 months postoperatively with a mean marginal dose of 11.88 Gy (mean target volume 4.42 cm(3), mean diameter 18.45 mm). Preoperatively facial nerve function was serviceable (House and Brackmann Grades I+II) in 158 of 159 patients (99.4%) and in 125 of 151 patients (82.8%, 95% confidence interval [CI] 76-88%) postoperatively. Hearing was serviceable in 29 of 151 patients (19.2%) preoperatively and in 16 of 79 patients postoperatively (20.2%, 95%CI 12-31%). Within a mean follow-up time of 50 months (range 12-102 months), facial nerve function and hearing after IR remained serviceable in 142 of 151 (94.0%, 95%CI 89-97%) and 15 of 129 patients (11.6%, 95%CI 7-18%). Tumor growth control was achieved in 149 of 159 patients (93.8%). Six patients were subjected to repeated therapy. Minimal complications were reported for microsurgery and GKS. Combined therapy was shown to be beneficial regarding both tumor control and adverse side effects among all analyzed studies.
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http://dx.doi.org/10.1016/j.jocn.2014.03.037DOI Listing
December 2014

In vivo assessment of number of milk duct orifices in lactating women and association with parameters in the mother and the infant.

BMC Pregnancy Childbirth 2014 Apr 2;14:124. Epub 2014 Apr 2.

Department of Orthodontics, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.

Background: In vitro and in vivo analyses differ between the number of milk ducts found in the lactating breast, and there is a lack of knowledge as to whether or not external factors in the mother or the child affect the number of ductal orifices. The aim of this study was to determine the number of milk duct orifices in vivo and to investigate the possible influence of variable parameters in mother and infant.

Methods:

Study Design: Prospective clinical trial. In 98 breastfeeding women we investigated the nipple surface in order to identify the number of milk duct orifices using Marmet's manual milk expression technique. In addition mothers were interviewed on different parameters of birth and breastfeeding.

Results: Every nipple had 3.90 ± 1.48 milk duct orifices on average. There was no significant difference between left and right breasts. The use of a breast pump in addition to breastfeeding did not have any effect on the number of ductal orifices. Multiparous women exhibited more ductal orifices (8.5 ± 3.0) as compared to primipara (7.1 ± 2.7). Boys were associated with significantly more ductal orifices in their mother's right breast (4.2 ± 1.7) than girls (3.5 ± 1.4). Furthermore boys were breastfed for longer per session. A shorter birth height of males correlated with more ductal orifices in left nipples. Fluid intake of mothers was associated with a higher number of ductal orifices. Restless infant behavior could not be explained by less milk duct orifices. Pain in the breast during breastfeeding did not have an influence on ductal orifices either. Psychological criteria, such as duration of maternity leave and total intended breastfeeding period, did not affect the number of orifices in the papilla mammaria of breasts during lactation.

Conclusion: For the first time an in vivo investigation of the number of ductal orifices in lactating women was conducted non-invasively and associations with variables in the mother and the child, birth parameters in infants, and breastfeeding parameters in mothers and children were assessed. We conclude that the number of activated ductal orifices on the surface of the nipple is primarily associated with functional aspects.
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http://dx.doi.org/10.1186/1471-2393-14-124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992155PMC
April 2014