Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol.

PURPOSE: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients. METHODS: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed. RESULTS: Forty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn't statistically significant. CONCLUSION: Combined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

Electroencephalographic (EEG) density spectral array monitoring in children during sevoflurane anaesthesia: a prospective observational study.

Electroencephalographic density spectral array monitoring has been developed to facilitate the interpretation of unprocessed electroencephalogram signals. The primary aim of this prospective observational study, performed in a tertiary children's hospital, was to identify the clinical applicability and validity of density spectral array monitoring in infants and children during sevoflurane anaesthesia. We included 104 children, aged < 6 years, undergoing elective surgery during sevoflurane anaesthesia. We investigated the correlation between non-steady state end-tidal sevoflurane and the expression of the four electroencephalogram frequency bands ß, α, θ and δ, representing density spectral array. Patients were divided into three age groups (< 6 months, 6-12 months, > 12 months). There was a significant correlation between end-tidal sevoflurane and density spectral array in the age groups 6-12 months (p < 0.05) and 1-6 years (p < 0.0001). In infants < 6 months of age, the relative percentages of density spectral array did not correlate with end-tidal sevoflurane. The main finding was that different end-tidal concentrations of sevoflurane produce age-dependent changes in the density spectral array power spectrum. In infants younger than 6 months-old, α and ß coherence are absent, whereas θ and δ oscillations have already emerged. In cases where anaesthesia was too deep, this presented as burst suppression on the electroencephalogram, θ disappeared, leaving the electroencephalographic activity in the δ range. Future research should address this issue, aiming to clarify whether the emergence of θ oscillations in infants helps to prevent sevoflurane overdosing.

Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years.

We analysed the association of independent variables with non-verbal cognition at 6 years in children with complete data (3441 from a cohort of 9901), of whom 415 were anaesthetised before the age of 5 years. Using multivariable regression, cognition was reduced by a mean (95% CI) score for children: anaesthetised before the age of 5 years, 2.1 (0.7-3.5), p = 0.004; born prematurely, 9.8 (4.1-15.4), p = 0.001; whose mothers smoked while pregnant, 2.3 (0.8-3.8), p = 0.004; whose mothers had lower IQ scores, 0.3 (0.2-0.3) for each unit reduction in maternal IQ, p < 0.0001. The association of child IQ with exposure to anaesthetic drugs was sensitive to missing data.

Contenido de yodo en sal a nivel de puestos de venta provenientes de distintas localidades en tres regiones argentinas / Iodine Content of Salt Available at Retail Outlets in Different Areas from Three Regions in Argentina

Introducción: La deficiencia de yodo es la principal causa prevenible de retardo mental y daño cerebral en la población. La yodación de la sal en Argentina es obligatoria según Ley 17259/67. El objetivo fue determinar el contenido de yodo en sal obtenida de puestos de venta de distintas localidades de provincias que integran la región del noroeste (NOA), nordeste (NEA) y Cuyo. Material y métodos: Estudio descriptivo y transversal. Se analizaron 80 sales adquiridas por compra directa, mercado minorista, en 10 provincias - 44 localidades. Se determinó el yodo por titulación con Tiosulfato de Sodio considerando el valor de corte de la legislación, en referencia al establecido como indicador de proceso evaluativo a nivel de salud pública (= 15 ppm) y el rango de 20-40 ppm, que asegura los requerimientos del micronutriente con el adecuado consumo de sodio. Resultados: El promedio de yodo en sal y desvío estándar fue de 24,4 ± 13,3 ppm. El 56,25 % en rango de aceptabilidad legal. Solo el 68,75 % en rango 20-40 ppm. Según marcas, 15/30 no cumplieron con los niveles requeridos de yodo. En relación a la procedencia, la región NOA fue la más afectada con 20,3 ± 13,5 ppm y 26,8 % < 15 ppm. Las sales del NEA con 24,9 ± 12,4 ppm - 18,2 % < 15 ppm. La región cuyana presentó valores mayores de yodación, 33,7 ± 9,0 ppm, sin muestras < 15 ppm pero con 23,5 % > 40 ppm. Los niveles de promedio de yodación por regiones mostraron diferencia estadísticamente significativa. Conclusiones: El hecho de que aproximadamente la mitad de las sales analizadas no aporten el nutriente por su deficiente y/o nula yodación, destaca la necesidad de implementar un sistema de promoción y sostenibilidad del monitoreo y evaluación de la calidad de la sal a distintos niveles de la cadena productiva, con el fin de ajustarse a las políticas sanitarias del doble desafío que presenta el país, de asegurar el aporte de yodo simultáneamente con la disminución del consumo de sodio, favoreciendo la equidad en la población y contribuir a la mejora de la salud pública. Rev Argent Endocrinol Metab 51:59-65, 2014 Los autores declaran no poseer conflictos de interés.

Introduction: Iodine deficiency is the main cause of preventable mental deficiency and brain damage in the population. Salt iodization is required by law 17259/67 in Argentina. The aim of the study has been to determine the iodine content of salt available at retail outlets from different localities of provinces of the northwest (NOA), northeast (NEA), and Cuyo regions. Material and Methods: Descriptive and cross-sectional study. We analyzed 80 packets of salt purchased from retail outlets in ten provinces, 44 localities. Iodine was determined by titration with sodium thiosulfate, con sidering the cut-off value established in the legislation as indicator for public health assessments (= 15 ppm) and the range of 20-40 ppm to meet the micronutrient requirements with adequate sodium consumption. Results: the average iodine content in salt and the standard deviation was 24.4 ± 13.3 ppm; 56.25 % was within the range of legal acceptance and only 68.75 % met the target range of 20 - 40 ppm. Considering brands, 15/30 did not reach the required iodine levels. From the point of view of product origin, the NOA region was the most affected, with 20.3 ± 13.5 ppm and 26.8 % < 15 ppm. For NEA salts, iodine content was 24.9 ± 12.4 ppm; 18.2 % < 15 ppm. The Cuyan region had higher levels of iodization, 33.7 ± 9.0 ppm, with no samples < 15 ppm but with 23.5 % of samples > 40 ppm. Average iodization levels by regions showed statistically significant differences. Conclusions: the fact that half the analysed salts fail to provide the nutrient requirements because of deficient or null iodization emphasises the need to implement a promotion and sustainability system of salt quality monitoring and assessment at different levels of the supply chain, in order to enforce healthcare policies designed to meet the two-fold challenge faced by our country of ensuring an adequate iodine supply and, at the same time, reducing sodium consumption, favouring social equity and improving public health. Rev Argent Endocrinol Metab 51:59-65, 2014 No financial conflicts of interest exist.

Breast ultrasound elastography--results of 193 breast lesions in a prospective study with histopathologic correlation.

PURPOSE: To evaluate the diagnostic performance of ultrasound elastography in breast masses. MATERIAL AND METHODS: 193 lesions (129 benign, 64 malignant) were analyzed with the EUB 8500 Logos-ultrasonic-unit (Hitachi Medical, Japan) and a linear-array-transducer of 7.5-13-MHz. Standard of reference was cytology (FNAfine needle aspiration) or histology (core biopsy). The elastic-score was classified according to a 6-point colour-scale (Ueno classification; 1-3 = benign, 4-5 = malignant). Conventional B-mode ultrasound (US) findings were classified according to the BI-RADS classification. Statistical analysis included sensitivity, specificity, ROC-analysis and kappa-values for intra-/interobserver reliability. RESULTS: The mean score for elasticity was 4.1 ± 0.9 for malignant lesions, and 2.1 ± 1.0 for benign lesions (p < 0.001). With a best cut-off point between elasticity scores 3 and 4, sensitivity was 96.9%, and specificity 76%. Setting a best cut-off point for conventional US between BI-RADS 4 and 5, sensitivity was 57.8%, and specificity 96.1%. Elastography provided higher sensitivity and lower specificity than conventional US, but two lesions with elasticity score 1 were false negative, whereas no lesion scored BI-RADS 1-3 were false negative. ROC-curve was 0.884 for elastography, and 0.820 for conventional US (p < 0.001). Weighted kappa-values for intra-/interobserver reliability were 0.784/0.634 for BI-RADS classification, and 0.720/0.561 for elasticity scores. CONCLUSION: In our study setting, elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer, but may complement conventional US to improve the diagnostic performance.

Hospital treatment - Is it affordable? A structured cost analysis of vaginal deliveries and planned caesarean sections.

INTRODUCTION: The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay. METHODS: To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital's computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services. RESULTS: For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83Euro/1432Euro. About 45% of the summarized costs are calculated on a reliable database. DISCUSSION: The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.

Placenta praevia--comparison of four sonographic modalities.

AIM: The aim of this study was the evaluation of four ultrasound modalities (transabdominal, perineal, transvaginal and transrectal) to examine placenta praevia or low lying placenta. METHOD: We prospectively investigated 24 patients after 25 weeks of their pregnancy with suspected placenta praevia or low lying placenta. We analysed picture quality and compared the results of all four scanning modalities with the actual diagnosis made at delivery. RESULTS: The abdominal and perineal approach provided significantly poorer scanning quality (good or moderate in 79/38 %) as compared to the transvaginal and transrectal approach (good or moderate in 83/97 %). We can state similar results concerning accuracy of the diagnosis (abdominal/perineal 42/21 %, transvaginal/transrectal 67/86 %). DISCUSSION: Our study supports the diagnostic superiority of transvaginal ultrasound in the diagnosis of placenta praevia in comparison to the abdominal/perineal view. We also show that transrectal scanning is at least equivalent in quality and safety without the imminent risks of transvaginal manipulation and infection. CONCLUSION: The evaluation of the transrectal approach proved equivalent to the standard transvaginal approach in depiction quality and diagnostic safety. Thus, with less potential trauma to the pregnancy, it is a reasonable alternative.

[Pregnancy and immunomodulatory therapy in multiple sclerosis patients]. / "Andere Umstände": Schwangerschaft und immunmodulatorische Therapie bei Multipler Sklerose.

Pregnancy and family planning issues are prominent concerns in the medical care of multiple sclerosis patients, since the disease onset often coincides with a period of life that is decisive in this regard. Multiple sclerosis is a chronic disorder with an unpredictable course and is widely treated with long-term immunomodulatory agents, raising questions regarding the complications and effects of these therapies on pregnancy. This paper gives an overview of the relevant literature and provides a basis for individual counselling of this group of multiple sclerosis patients.

Ultrasound training: the virtual patient.

OBJECTIVE: To evaluate an ultrasound training system designed to standardize teaching and learning of gynecological sonography using a virtual model. METHODS: The 'virtual patient' was based on a three-dimensional freehand ultrasound system that allows two-dimensional sonographic offline investigations of previously recorded cases, imitating a real gynecological scan. In the first test phase designed to check the congruence of real and virtual scans, 25 doctors experienced in ultrasound examined three virtual cases. During the second test phase we assessed whether training with the virtual patient helped to establish a satisfactory practical knowledge of gynecological ultrasound. This phase was carried out with 24 medical students without ultrasound experience. RESULTS: All 25 doctors successfully investigated the three cases and generated an accurate diagnosis for the first and second cases. In the third case 14 doctors made the correct diagnosis (uterus bicornis). The measurements of endometrial thickness and the diameter of a fibroid yielded acceptable results compared with the original investigation. After a short standardized video-based instruction, all 24 medical students were able to perform a basic transvaginal scan and to inspect the uterus, ovaries and the urinary bladder. Measurements of endometrial thickness by all students deviated minimally from the actual measurement. CONCLUSIONS: Training with the virtual patient appears to be comparable to performing a live gynecological ultrasound investigation and allows standardized ultrasound teaching and learning.

Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.

Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). This frequently occurs as a new mutation, manifesting one of the highest documented rates for any transversion in the human genome. To understand the biology of this mutation, we have investigated its parental origin, and the ages of the parents, in 19 families with de novo c.749C>G mutations. All ten informative cases originated from the paternal allele (95% confidence interval 74-100% paternal); the average paternal age at birth overall was 34.7 years. An exclusive paternal origin of mutations, and increased paternal age, were previously described for a different mutation (c.1138G>A) of the FGFR3 gene causing achondroplasia, as well as for mutations of the related FGFR2 gene causing Apert, Crouzon and Pfeiffer syndromes. We conclude that similar biological processes are likely to shape the occurrence of this c.749C>G mutation as for other mutations of FGFR3 as well as FGFR2.

Deletion of the TWIST gene in a large five-generation family.

In this article, we describe a large five-generation family with characteristics of the Saethre-Chotzen syndrome as well as of the blepharophimosis ptosis epicanthus inversus syndrome. Segregating with their phenotype is a deletion of the chromosome 7p21 TWIST gene locus. The TWIST gene indeed is involved in Saethre-Chotzen syndrome, a craniosynostosis syndrome further characterized by specific facial and limb abnormalities. However, only two members of our family exhibited craniosynostosis. This report demonstrates that the genetics of craniofacial anomalies are less straightforward than they sometimes appear to be. Not only craniosynostosis, but also subtle facial deformities could be indicative of an abnormality of the TWIST gene. In conclusion, the clinical spectrum of genetic abnormalities of the TWIST gene is highly variable. We therefore recommend that genetic analysis of the TWIST gene locus, including fluorescence in situ hybridization, should be considered in familial cases of facial and eyelid abnormalities without the presence of craniosynostosis.

[Sonographically guided percutaneous needle aspiration of breast abscesses - a minimal-invasive alternative to surgical incision]. / Sonographisch gesteuerte Mammaabszesspunktion als minimal-invasive Alternative zur chirurgischen Inzision.

AIM: The current standard treatment of breast abscesses is surgical incision and drainage. This method, however, frequently yields poor cosmetic results. Sonographically guided percutaneous aspiration of breast abscesses and local antibiotic treatment need to be considered as an interesting alternative. The present study aimed to compare these treatment alternatives. METHOD: The patient population analysed comprised 24 patients with 28 breast abscesses who presented to the Department of Obstetrics and Gynaecology of Munich University Hospital Grosshadern between 12/1997 and 9/2002. 25 % of these patients (6/24) suffered from a puerperal and 75 % (18/24) from a non-puerperal breast abscess. The study group of surgically treated patients comprised 15 women (16 abscesses). Ten patients (10 abscesses) were treated with the novel, minimally invasive method. The treatment success was statistically analysed using chi (2)- and t-Tests (p < 0,05). RESULTS: The minimally invasive approach did not extend the length of intravenous antibiotic treatment or hospital stay and did not lead to an increase in the need for analgesic drugs. We encountered recurrent abscesses in 31 % (5/16) of the surgical treatment group, yet none in the group undergoing minimally invasive treatment. The aesthetic-cosmetic as well as the functional result in lactating patients was satisfactory in all cases. CONCLUSION: Sonographically guided percutaneous aspiration of breast abscesses represents a less invasive and very promising alternative to surgical incision, showing the following advantages: no general anaesthesia required, a superior cosmetic result and shorter hospitalisation. The method was highly accepted by all patients treated.

Sonographic cervical volumetry in higher order multiple gestation.

OBJECTIVE: The aim of this study of multifetal pregnancies was the comparison of three-dimensional (3D) volumetry of the cervix, conventional sonographic cervical length measurement and clinical assessment. METHODS: 10 mothers were investigated in an observational study between 5/1999 and 9/2000. A total of 34 consecutive 2D- and 3D-transabdominal ultrasound measurements were performed. RESULTS: Volumetry of the cervix was possible in all 34 exams. 2D-cervical length assessment could not be obtained in 6% because the presenting fetal part obstructed the sonographic plane. Both methods allowed equal judgement of the configuration of the cervix. A significant correlation was found between mean 2D-cervical length (28.7 mm, 7.7 SD) and mean cervical volume (30.0 cm3, 16.0 SD). Parity, subjective preterm labor or need of tocolytics showed no correlation with any biometrical parameter studied. CONCLUSION: Volumetry was superior for the assessment of cervical biometry and conformation in women when the transabdominal 2D-plane was obstructed. When cervical length was obtainable by a conventional scan, the technically more complex 3D-imaging did not provide further information.

Telemedicine in ultrasound: new solutions.

The transport of dynamic ultrasound (US) pictures as video files or streams no longer presents a problem. Despite teleconferencing, this method of transfer provides no active influence on the data sent for the receiving expert. We are evaluating a software-based 3-D US system that provides the new opportunity of an active US re-evaluation of a virtual patient. The 3-D volumes can be reanalyzed, time- and examiner-independent, wherever the device is installed. To test the clinical feasibility of this virtual US investigation, we installed the device in a peripheral hospital and in our US unit. The transfer of the volume (about 10 to 15 MB) could be done with two parallel Integrated Services Digital Network (ISDN) lines with a conduction capacity of 128 KB/s. In this basic assessment, the transmission of US volumes of patients proved to be easy in the acquisition, quick in off-line transmission and reliable in off-line re-evaluation of the data.

[Fetal obstructive uropathy--diagnosis and possible treatments]. / Fetale obstruktive Uropathie--Diagnose- und Behandlungsmöglichkeiten.

BACKGROUND: Abnormalities of the urinary tract are found in up to 5% of newborns. They account for 25% of all prenatally diagnosed congenital defects and contribute 4% to perinatal mortality. When considering the prognosis of these anomalies, association with other pathological conditions has to be taken into account. MATERIALS AND METHODS: We discuss the state of the art in detection and management of fetal urinary tract abnormalities as are standard at this tertiary center of fetal medicine. RESULTS AND DISCUSSION: Posterior urethral valve, megaureter or ureteropelvic junction obstruction represent one end of a wide spectrum of obstructive uropathies, ranging from pathophysiologically minor deviations to severe impairment of renal function. Organ development, physiology of urine production and excretion as well as their potential disorders are presented. CONCLUSION: Sonographic and invasive diagnostic options in the evaluation of the urogenital tract are discussed. Careful assessment of each individual case and prognosis determine pre- and postnatal treatment.