Reductions in body weight and insulin resistance are not associated with changes in grey matter volume or cortical thickness during the PREVIEW study.

INTRODUCTION: The effect of changes in body weight or insulin resistance on grey matter volume and cortical thickness change are unclear. The present observational study assessed effects of an 8-week weight loss period (≥8% of body weight), and a subsequent 22-month weight maintenance period on grey matter volume and cortical thickness. METHODS: A total of 24 participants (12f/12 m; age 52.8 ±â€¯10.6 years) with overweight/obesity and pre-diabetes were recruited. T1-weighted magnetic resonance imaging was used to determine grey matter volume and cortical thickness at baseline, after the weight loss period and after a medium to high dietary protein weight maintenance period. RESULTS: At baseline, global grey matter volume was inversely associated with HOMA-IR, adjusted for sex and age (r = -0.42; p = .049). During the weight loss period participants decreased their BMI (32.1 ±â€¯3.3 to 28.1 ±â€¯2.8 kg/m2, p < .01), body-fat (41.6 ±â€¯6.4 to 35.0 ±â€¯8.0%, p < .01) and insulin resistance (HOMA-IR: 4.0 ±â€¯2.0 to 1.8 ±â€¯0.9, p < .01). During the 22-month weight maintenance period, these parameters gradually increased again (BMI: 29.3 ±â€¯3.8 kg/m2; body-fat: 37.8 ±â€¯9.3%; HOMA-IR: 2.9 ±â€¯1.4, p < .01). Global grey matter volume and cortical thickness did not change significantly during the weight loss or weight maintenance period. Changes in body weight, body-fat percentage or insulin sensitivity were not associated with changes in global grey matter volume. CONCLUSION: In conclusion, we confirmed that global grey brain matter volume was inversely associated with insulin resistance at baseline, yet an intervention yielding a decrease in insulin resistance did not lead to changes in global grey brain matter volume or cortical thickness. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT01777893.

Functional Connectivity in Virally Suppressed Patients with HIV-Associated Neurocognitive Disorder: A Resting-State Analysis.

BACKGROUND AND PURPOSE: HIV-associated neurocognitive disorder still occurs despite virally suppressive combination antiretroviral therapy. In the pre-combination antiretroviral era and in patients without HIV suppression, HIV-associated neurocognitive disorder was caused by synaptodendritic injury resulting in impairment of neural networks, characterized by decreased attention, psychomotor slowing, and working memory deficits. Whether similar pathogenesis is true for HIV-associated neurocognitive disorder in the context of viral suppression is not clear. Resting-state fMRI has been shown to be efficient in detecting impaired neural networks in various neurologic illnesses. This pilot study aimed to assess resting-state functional connectivity of the brain in patients with active HIV-associated neurocognitive disorder in the context of HIV viral suppression in both blood and CSF. MATERIALS AND METHODS: Eighteen patients with active HIV-associated neurocognitive disorder (recent diagnosis with progressing symptoms) on combination antiretroviral therapy with viral suppression in both blood and CSF and 9 demographically matched control subjects underwent resting-state functional MR imaging. The connectivity in the 6 known neural networks was assessed. To localize significant ROIs within the HIV and control group, we performed a seed-based correlation for each known resting-state network. RESULTS: There were significant group differences between the control and HIV-associated neurocognitive disorder groups in the salience (0.26 versus 0.14, t = 2.6978, df = 25, P = .0123) and executive networks (0.52 versus 0.32, t = 2.2372, df = 25, P = .034). The covariate analysis with neuropsychological scores yielded statistically significant correlations in all 6 studied functional networks, with the most conspicuous correlation in salience networks. CONCLUSIONS: Active HIV-associated neurocognitive disorder in virally suppressed patients is associated with significantly decreased connectivity in the salience and executive networks, thereby making it potentially useful as a biomarker.

Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia.

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ⩾60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ⩾5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.

Novel score for prediction of malignant bile duct obstruction based on biochemical and clinical markers.

BACKGROUND: Early differentiation of malignant from benign bile duct obstruction is of utmost importance. AIM: To identify biochemical and clinical predictors for malignancy in patients with bile duct obstruction, and establish a predictive model by combining pre-treatment patient characteristics. A web-based application was developed for easy assessment of malignant bile duct probability (www.pmal-score.org). METHODS: One thousand hundred and thirty-five patients [median age 66 (52-75) years, 53% male] with bile duct obstruction of various aetiologies were retrospectively evaluated at our tertiary referral centre. Multivariate logistic regression analysis identified factors as independently significant for malignant bile duct obstruction. A predictive risk score was established using ROC analysis and applied to an external validation cohort of 101 patients. RESULTS: Three hundred and ninety-four patients had malignant bile duct obstruction proven by surgery, while in 741 patients benign obstruction was observed. Multivariate analysis identified various clinical factors to be predictive for malignancy. On the basis of eight predictors, a risk score for malignancy was developed [X = 0.025 * [age] + 1.239 * [1 if weight loss, otherwise 0] - 0.235 * [1 if pain, otherwise 0] + 0.649 * [1 if diabetes, otherwise 0] + 0.896 * [1 if jaundice, otherwise 0] + 0.109 * [bilirubin] + 0.0007 * [γ-GT] + 0.0003 * [AP] - 4.374]: A significant correlation between the predicted malignancy and the actual malignancy was found by ROC (AUC: 0.862; 95% CI 0.838-0.886, P < 0.0001). CONCLUSIONS: This predictive risk score estimates the risk of malignancy in patients with bile duct obstruction, and it seems to be very accurate. A better prediction enables both earlier diagnosis of malignant obstructive disease and improved management of patients with bile duct obstruction, which may result in reduced morbidity and mortality.

The ELPA library: scalable parallel eigenvalue solutions for electronic structure theory and computational science.

Obtaining the eigenvalues and eigenvectors of large matrices is a key problem in electronic structure theory and many other areas of computational science. The computational effort formally scales as O(N(3)) with the size of the investigated problem, N (e.g. the electron count in electronic structure theory), and thus often defines the system size limit that practical calculations cannot overcome. In many cases, more than just a small fraction of the possible eigenvalue/eigenvector pairs is needed, so that iterative solution strategies that focus only on a few eigenvalues become ineffective. Likewise, it is not always desirable or practical to circumvent the eigenvalue solution entirely. We here review some current developments regarding dense eigenvalue solvers and then focus on the Eigenvalue soLvers for Petascale Applications (ELPA) library, which facilitates the efficient algebraic solution of symmetric and Hermitian eigenvalue problems for dense matrices that have real-valued and complex-valued matrix entries, respectively, on parallel computer platforms. ELPA addresses standard as well as generalized eigenvalue problems, relying on the well documented matrix layout of the Scalable Linear Algebra PACKage (ScaLAPACK) library but replacing all actual parallel solution steps with subroutines of its own. For these steps, ELPA significantly outperforms the corresponding ScaLAPACK routines and proprietary libraries that implement the ScaLAPACK interface (e.g. Intel's MKL). The most time-critical step is the reduction of the matrix to tridiagonal form and the corresponding backtransformation of the eigenvectors. ELPA offers both a one-step tridiagonalization (successive Householder transformations) and a two-step transformation that is more efficient especially towards larger matrices and larger numbers of CPU cores. ELPA is based on the MPI standard, with an early hybrid MPI-OpenMPI implementation available as well. Scalability beyond 10,000 CPU cores for problem sizes arising in the field of electronic structure theory is demonstrated for current high-performance computer architectures such as Cray or Intel/Infiniband. For a matrix of dimension 260,000, scalability up to 295,000 CPU cores has been shown on BlueGene/P.

Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG.

Chemomodulation of cytarabine by fludarabine has been attributed with a higher antileukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients (n=326, of which 281 were evaluable) were randomly assigned to SHAI (cytarabine, 1 g/m(2) bid, days 1-2 and 8-9 (3 g/m(2) for patients ≤ 60 years with refractory AML or ≥ 2nd relapse); idarubicin 10 mg/m(2) daily, days 3-4 and 10-11) or F-SHAI (SHAI with fludarabine, 15 mg/m(2), 4 h before cytarabine). Although complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time to treatment failure from 2.04 to 3.38 months (median, P<0.05). Twenty-seven percent of patients proceeded to allogeneic stem cell transplantation, with a significantly higher number of patients in CR or incomplete remission in the F-SHAI group (22 vs 10%, P<0.01). In conclusion, fludarabine has a beneficial, although moderate, impact on the antileukemic efficacy of high-dose cytarabine-based salvage therapy for relapsed and refractory AML.

Human papillomavirus genotype distribution in cytologically screened women from northwest Germany.

INTRODUCTION: In this study, we evaluate the distribution of 24 human papillomavirus (HPV) genotypes in a cohort of 3,381 cytologically screened women from a rural area of northwest Germany, in correlation to cytological diagnoses and histological outcomes. MATERIALS AND METHODS: We present a retrospective study in which the HPV-genotyping results of women who attended the German cervical screening program were correlated to cytological diagnosis and histological outcome. RESULTS: HPV genotyping showed marked differences among cervical lesions. Although HPV-51 was common in all cervical lesions, it was rarely detected as single-type HPV infection in high-grade cervical intraepithelial neoplasia (CIN)3 (2/118 cases). HPV-16 and 18 were more common in CIN3 (57.6%) than in CIN2 (21.8%), but they were absent in 42.4% of all CIN3 lesions in our cohort. DISCUSSION: Our data show that HPV-16, HPV-31, HPV-51, HPV-53 and HPV-42 are the most prevalent HPV types in the different cervical lesions in this region of northwest Germany. HPV genotyping has been shown to be a powerful tool to triage atypical squamous cells of undetermined significance lesions. Considering the observed heterogeneity of HPV types in CIN2, it could also be useful to triage CIN2+ lesions. Our results underline the usefulness of a morphologically controlled screening program with HPV genotyping as a powerful additional tool.

A nine-gene signature predicting clinical outcome in cutaneous melanoma.

PURPOSE: Current histopathological staging of cutaneous melanoma is limited in predicting outcome, and complementary molecular markers are not available for prognostic assessment. The purpose of this study was to identify a quantitative gene expression score in primary melanoma and adjacent stroma that can be used in clinical routine to define, at the time of diagnosis, patient risk and need for therapy. METHODS: Expression of 92 candidate genes was quantified by RT-PCR in a training subset of 38 fresh-frozen melanomas. Correlation of gene expression with overall survival (OS) was evaluated using univariate regression analysis. Expression analysis of 11 prognostically significant genes in the complete training cohort of 91 melanomas yielded nine genes predicting outcome. Results were confirmed in a validation cohort of 44 melanomas. RESULTS: We identified a nine-gene signature associated with OS and distant metastasis-free survival. The signature comprised risk and protective genes and was applicable to melanoma samples across all AJCC stages in the presence of adjacent stroma. A signature-based risk score predicted OS in both the training cohort (multivariate regression analysis: p = 0.0004, hazard ratio 3.83) and the validation cohort, independently of AJCC staging. Consequently, when combining risk score and AJCC staging, patients in the AJCC intermediate-risk stages, IIA/B or IIIA, were re-classified either to low or high risk. CONCLUSIONS: Our gene score defines patient risk and need for therapy in melanoma. The score has the potential to be utilized in clinical routine, since it is quantitative, robust, simple, and independent of AJCC stage and sample purity.

Functional integration of parietal lobe activity in early Alzheimer disease.

OBJECTIVES: Parietal lobe dysfunction is an important characteristic of early Alzheimer disease (AD). Functional studies have shown conflicting parietal activation patterns indicative of either compensatory or dysfunctional mechanisms. This study aimed at examining activation differences in early AD using a visuospatial task. We focused on functional characteristics of the parietal lobe and examined compensation or disconnection mechanisms by combining a fMRI task with effective connectivity measures from Granger causality mapping (GCM). METHODS: Eighteen male patients with amnestic mild cognitive impairment (aMCI) and 18 male cognitively healthy older individuals were given a mental rotation task with different rotation angles. RESULTS: There were no behavioral group differences on the fMRI task. Separate measurements at each angle revealed widespread activation group differences. More temporal and parietal activation in the higher angle condition was observed in patients with aMCI. The parametric modulation, which identifies regions associated with increasing angle, confirmed these results. The GCM showed increased connectivity within the parietal lobe and between parietal and temporal regions in patients with aMCI. Decreased connectivity was found between the inferior parietal lobule and posterior cingulate gyrus. Connectivity patterns correlated with memory performance scores in patients with aMCI. CONCLUSIONS: Our results demonstrate increased effective temporoparietal connectivity in patients with aMCI, while maintaining intact behavioral performance. This might be a compensational mechanism to counteract a parietal-posterior cingulate gyrus disconnection. These findings highlight the importance of connectivity changes in the pathophysiology of AD. In addition, effective connectivity may be a promising method for evaluating interventions aimed at the promotion of compensatory mechanisms.

Single- vs. double-balloon enteroscopy in small-bowel diagnostics: a randomized multicenter trial.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is the first choice endoscopic technique for small-bowel visualization. However, preparation and handling of the double-balloon enteroscope is complex. Recently, a single-balloon enteroscopy (SBE) system has been introduced as being a simplified, less-complex balloon-assisted enteroscopy system. PATIENTS AND METHODS: This study was a randomized international multicenter trial comparing two balloon-assisted enteroscopy systems: DBE vs. SBE. Consecutive patients referred for balloon-assisted enteroscopy were randomized to either DBE or SBE. Patients were blinded with regard to the type of instrument used. The primary study outcome was oral insertion depth. Secondary outcomes included complete small-bowel visualization, anal insertion depth, patient discomfort, and adverse events. Patient discomfort during and after the procedure was scored using a visual analog scale. RESULTS: A total of 130 patients were included over 12 months: 65 with DBE and 65 with the SBE technique. Patient and procedure characteristics were comparable between the two groups. Mean oral intubation depth was 253 cm with DBE and 258 cm with SBE, showing noninferiority of SBE vs. DBE. Complete visualization of the small bowel was achieved in 18 % and 11 % of procedures in the DBE and SBE groups, respectively. Mean anal intubation depth was 107 cm in the DBE group and 118 cm in the SBE group. Diagnostic yield and mean pain scores during and after the procedures were similar in the two groups. No adverse events were observed during or after the examinations. CONCLUSIONS: This head-to-head comparison study shows that DBE and SBE have a comparable performance and diagnostic yield for evaluation of the small bowel.

Post-ERCP pancreatitis in 2364 ERCP procedures: is intraductal ultrasonography another risk factor?

BACKGROUND AND STUDY AIMS: Acute pancreatitis is considered a relevant major complication following endoscopic retrograde cholangiopancreatography (ERCP); according to literature data, the incidence varies between 1.5 % and 17 %. In the present study, we aimed to identify potentially new, hitherto unknown risk factors for post-ERCP pancreatitis. PATIENTS AND METHODS: A total of 2364 ERCP procedures performed in 1275 patients during the years 2004 - 2008 were included in the study. Post-ERCP pancreatitis was defined as acute abdominal pain within 48 hours following ERCP with at least 3-fold elevated levels of serum lipase and a requirement for analgesic drugs for at least 24 hours. The severity of the pancreatitis was determined using the Imrie score. RESULTS: In our cohort study a total of 54 different patients (2.3 %) developed post-ERCP pancreatitis. In 50 of these patients (92.6 %) the pancreatitis was mild; in 54 (7.4 %) it was severe. Patients with post-ERCP pancreatitis had highly significantly lower bilirubin levels than patients who did not have post-ERCP pancreatitis ( P < 0.001). Length of hospital stay, duration of analgesics, and need for analgesic drugs were significantly higher in patients suffering from severe pancreatitis ( P ≤ 0.01). In multivariate analysis, among other, already well-described risk factors we identified intraductal ultrasonography as another risk factor for post-ERCP pancreatitis, with a hazard ratio of 2.41 ( P = 0.004). CONCLUSIONS: According to our retrospective data, intraductal ultrasonography seems to be another independent risk factor for developing post-ERCP pancreatitis, which needs to be further elucidated in prospective studies.

Dental age estimation based on third molar eruption in First Nation people of Canada.

Forensic age estimation of living subjects has become an increasing focus of interest in modern society. One main criterion for dental age estimation in the relevant age group is the evaluation of third molar eruption. The importance of ethnic variation in dental development requires population specific data for dental age evaluation. In the present study, we determined the stages of third molar eruption in 347 female and 258 male First Nations people of Canada aged 11 to 29 years based on radiological evidence from 605 conventional orthopantomograms. The results presented here provide data on the age of alveolar, gingival, and complete eruption of the third molars in the occlusal plane that can be used for forensic estimation of the minimum and most probable ages of investigated individuals.

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG.

The objective of this study for newly diagnosed acute promyelocytic leukemia (APL) was to evaluate the efficacy of an intensified double induction chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA) followed by consolidation and 3 years maintenance therapy. In contrast to APL studies stratifying therapy according to pretreatment white blood cell (WBC) count < and > or =10 x 10(9)/l (low/intermediate and high risk according to the Sanz score), our patients received uniform therapy. From 1994 to 2005, 142 patients (age, 16-60 years) were enrolled. In the low/intermediate (n=105) vs high (n=37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of induction death were 4.8 vs 16.2% (P=0.05) and of molecular remission were 87.5 vs 91.3% (P=1). Long-term overall survival was 84.4 vs 73.0% (P=0.12), event free survival was 78.3 vs 67.3% (P=0.11), relapse free survival was 82.1 vs 80.0% (P=0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P=0.46). No relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy including HD ara-C followed by prolonged maintenance therapy reduced the relapse risk in high risk patients. Pretreatment WBC count > or =10 x 10(9)/l count was no relevant prognostic factor for relapse.

Reference study on the time frame for ossification of the distal radius and ulnar epiphyses on the hand radiograph.

Hand radiographs from 554 male and 288 female subjects aged 10-30 years, which had been taken due to traumatological indications, were evaluated. A classification into five ossification stages was applied to assess the epiphyseal development of distal radius and distal ulna (1: epiphysis not ossified; 2: epiphysis ossified, nonunion of the epiphysis and metaphysis; 3: partial union of the epiphysis and metaphysis; 4: complete union of the epiphysis and metaphysis, epiphyseal scar visible; 5: complete union of the epiphysis and metaphysis, epiphyseal scar nondiscernable). It was established that male subjects with an ossification stage 4 of the radius or ulna and female subjects with an ossification stage 5 of the radius were at least 14 years old. The occurrence of ossification stage 5 of the radius proves that a male individual has reached the age of 18 years.

Prognostic relevance of angiogenesis in stage III NSCLC receiving multimodality treatment.

Compelling evidence indicates that microvessel density (MVD) is a prognostic marker in early nonsmall cell lung cancer (NSCLC). However, its role in lymph node metastases in stage III NSCLC receiving multimodality treatment is unknown. Lymph nodes of 142 patients with stage III NSCLC, treated in a trial of the German Lung Cancer Cooperative group, were evaluated for MVD. Median follow-up was 7.39 yrs. MVD was correlated with demographic and tumour-related variables and survival. MVD (median 33.9) did not correlate with survival. However, in multimodality-treated stage IIIA patients receiving tumour resection with negative margins (R0), those with a high MVD had significantly prolonged overall survival with a median of 4.96 yrs compared with 1.99 yrs for those with low MVD (p = 0.041). Cox regression analysis revealed that MVD was a prognostic factor in R0-resected stage IIIA (hazard ratio 0.417). Furthermore, a significant correlation of MVD to stage was observed, with significantly lower MVD in stage IIIA than IIIB (p = 0.0062), and a significant correlation of MVD to histological subtype was observed, with adenocarcinoma revealing the highest scores (p = 0.0001). Increased angiogenesis within lymph node metastases is a prognostic indicator for better survival in NSCLC patients. Thus, measurement of MVD might be useful in selecting patients for future neoadjuvant treatment decisions.

Studies of the chronological course of wisdom tooth eruption in a Japanese population.

The importance of forensic age estimation in living subjects has grown over the last few years. In dental age estimation, tooth eruption is a parameter of developmental morphology that can be analyzed by either clinical examination or by evaluation of dental X-rays. In the present study, we determined the stage of wisdom tooth eruption in 549 male and 751 female Japanese subjects aged 14-26 years based on radiological evidence from 1300 conventional orthopantomograms. The results presented here provide useful data on the age of alveolar, gingival, and complete emergence of the third molars in the occlusal plane that can be utilized for forensic estimation of the minimum and most probable ages of investigated persons.

[What influences reconvalescence after lung resection?]. / Was beeinflusst die Rekonvaleszenz nach einer Lungenresektion?

INTRODUCTION: Reconvalescence after lung resections underlies several influences. The aim of this study was to outline the effect of patient and operative factors. METHODS: Between 1/97 and 6/98 a cross sectional prospective study was undertaken at the University of Ulm. 125 patients with lung resections for various reasons via anterolateral thoracotomy were included. Variants thought to affect postoperative recovery were statistically analysed using uni- and multivariate analysis. A "good postoperative recovery" (GPR) was seen as at least two of the following criteria were fulfilled on the second postoperative day: Spitzer Index >/=6, FEV1 >40% of preoperative measurement, pain on LASA scale

[The "Muenster classification" of high frequency hearing loss following cisplatin chemotherapy]. / Die "Münsteraner Klassifikation": Eine neue Einteilung der Hochtonschwerhörigkeit nach Cisplatingabe.

BACKGROUND: Slight high frequency hearing loss following cisplatin chemotherapy can be proof of an ototoxic effect even when hearing ability is not yet clinically affected. To answer scientific questions, such as the relationship between cisplatin ototoxicity and drug regime or individual tolerance, early detection of ototoxicity and a classification relating to intensity and the affected frequencies are required. A search for relevant literature resulted the WHO-classification (1991) describing clinically relevant hearing loss and two high frequency hearing loss classifications published by Khan et al. (1982) and Brock et al. (1991). Their application is compared to a new, proprietary classification. PATIENTS AND METHODS: 55 patients (32 boys, 23 girls) undergoing cisplatin chemotherapy at Muenster University Hospital from 1999 to 2004 underwent audiometric tests in our department. From this data we developed a grading system, that was based on the WHO classification, but paid special attention to early ototoxic effects, to intensity of hearing loss and to the frequencies affected: Grade 0 (normal hearing) includes hearing loss of not more than 10 dB in all frequencies. Grade 1 (beginning hearing loss) encompasses > 10 dB up to 20 dB in at least one frequency or tinnitus. Grade 2 (moderate impairment) describes hearing loss > or = 4 kHz and differentiates 2a (> 20 to 40 dB), 2b (> 40 to 60 dB) and 2c (> 60 dB). Hearing loss < 4 kHz > 20 dB in grade 3 (severe impairment, hearing aids needed) is further classified according to grade 2 in a, b and c. Grade 4 (loss of function) finally describes average hearing loss < 4 kHz of at least 80 dB. This classification is compared to the two high frequency hearing loss classifications (Khan et al. and Brock et al.). RESULTS: The Muenster classification, compared to Khan et al. and Brock et al., demonstrated the best results in the early detection of hearing loss: All children with hearing loss of at least 20 dB after therapy had already shown pathological audiograms during treatment, when those audiograms were assessed by our classification. All children whose audiograms were flagged as pathological by our classification finally developed hearing loss. In terms of the prediction of hearing loss, our classification evaluated processing audiograms with a sensitivity, specificity and efficiency of 1.0. Progressive hearing loss was detected in 45 patients (Khan et al. 30, Brock et al. 38). Therefore our classification showed a better suitability for monitoring hearing loss than the other classifications. CONCLUSION: The Muenster classification is a suitable new basis for scientific questions concerning cisplatin ototoxicity. It detects hearing loss earlier and maps progression of hearing loss more precisely than the existing high frequency classifications (Khan et al. and Brock et al.).

Implementation of a map in radical prostatectomy specimen allows visual estimation of tumor volume.

INTRODUCTION: Tumor volume is one of the best documented prognostic factors for prostate cancer. There are several methods to gain this important parameter but unfortunately most of the clinicians in the world do not get this information in their routine practice from the pathologist. We developed a standardized method to handle radical prostatectomy specimens including a special form of mapping in order to document relevant morphological data. The aim of this study was to investigate if our model of mapping prostate cancer, which we use in routine practice, may serve for visual estimation of tumor volume. METHODS: We estimated the tumor volume of prostate cancer by visual estimation of 350 maps of radical prostatectomy specimens and correlated these data with established prognostic parameters and clinical outcome. RESULTS: Significant correlations between tumor volumes, as obtained from our mapping, and known prognostic parameters such as preoperative serum levels of prostatic specific antigen, loss of differentiation, histological grade, lymph node metastasis, and margins were found. In a multivariate analysis, only Gleason score and tumor stage were shown to be independent prognostic parameters. DISCUSSION: We demonstrate that mapping of prostate cancer is more than a simple method of documentation but may serve as a method for visual estimation of tumor volume of prostate cancer after radical prostatectomy. This method can further be used for a visual documentation of the tumor stage independent of changes in the TNM classification. The method is inexpensive and practicable and can therefore be applied in routine surgical pathology.