Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Listeriosis outbreak caused by acid curd cheese Quargel , Austria and Germany 2009.

We report an outbreak of listeriosis in Austria and Germany due to the consumption of Quargel cheese produced by an Austrian manufacturer. At the time of writing this report, the outbreak was known to account for 14 outbreak cases in 2009, including four cases with lethal outcome. On 23 January 2010, the cheese product was voluntarily withdrawn from the market.

Update: Multinational listeriosis outbreak due to 'Quargel', a sour milk curd cheese, caused by two different L. monocytogenes serotype 1/2a strains, 2009-2010.

We previously reported an outbreak of listeriosis in Austria and Germany due to consumption of Quargel cheese. It comprised 14 cases (including five fatalities) infected by a serotype 1/2a Listeria monocytogenes (clone 1), with onset of illness from June 2009 to January 2010. A second strain of L. monocytogenes serotype 1/2a (clone 2) spread by this product could be linked to further 13 cases in Austria (two fatal), six in Germany (one fatal) and one case in the Czech Republic, with onset of disease from December 2009 to end of February 2010.

Re-irradiation of recurrent glioblastoma as part of a sequential multimodality treatment concept.

PURPOSE: The aim of this retrospective study was to evaluate survival outcomes in well-performing, mainly, young patients receiving a sequence of all available therapeutic options for relapsed glioblastoma, including re-irradiation. METHODS: We performed a retrospective analysis of 27 patients irradiated twice for glioblastoma between 2008 and 2016. In the first line, all had surgical treatment of the tumor followed by radiotherapy with a total dose of 60 Gy and temozolomide. All re-irradiated patients were treated with a total dose of 36 Gy in 12 fractions. The endpoints were death from glioblastoma or any cause, and toxicity after re-irradiation. RESULTS: The median follow-up of survivors was 35.6 months. At the time of analysis, 25 patients had died. The median time between first and second radiotherapy was 18.9 months (6.1-58.4). Re-irradiation was performed at different time points of first, second and third progression. The median overall survival after first diagnosis was 39.2 months. Five years after first surgery, nearly 20% of the patients were alive. CONCLUSION: Carefully planned re-irradiation of the brain is a safe therapy for recurrent glioblastoma. Younger and well-performing patients benefit from all available therapy options. Every patient should be discussed in a multidisciplinary setting at each time point of tumor progression. Further prospective studies are needed to define the optimal time, dose and volume of re-irradiation.

Outbreak of acute gastroenteritis in an Austrian boarding school, September 2006.

An outbreak of acute gastroenteritis occurred in September 2006 in a boarding school in eastern Austria. Of 113 cases, 101 were hospitalised. In order to identify the outbreak source, a retrospective cohort study on the group at risk was performed, including 222 pupils and 30 staff members. Food exposure in the canteen of the school was identified as the most relevant common link among the cases in the case series investigation. Although the preliminary microbiological investigation made Norovirus infections possible, an in-depth descriptive epidemiological investigation later pointed to food intoxication rather than a viral infection as the cause of the outbreak. The analytical epidemiological investigation implicated boiled rice and chicken wings served in the canteen as the most likely source of the outbreak. Staphylococcus aureus was identified as the causative agent. Further molecular characterisation revealed that the predominant S. aureus type in this outbreak was a new spa type, t2046. The same spa type was isolated from stool specimens of the majority of the cases investigated, from samples of the incriminated boiled rice, and also from a swab of a palmar skin lesion of one of the healthy kitchen workers, who is therefore the most likely source of contamination. This outbreak underlines again the importance of compliance with the basic guidelines for kitchen hygiene.

Cytotoxic T-lymphocyte responses in cattle infected with bovine viral diarrhea virus.

A system for a reproducible in vitro restimulation of bovine viral diarrhea virus (BVDV)-specific cytotoxic T-cells (CTL) was developed. Lymphocyte cultures of BVDV-immunised cattle were stimulated with infectious BVDV isolate PT810 and recombinant bovine interleukin-2 for 12 to 25 days. A specific lysis of Concanavalin A-stimulated BVDV-infected autologous target cells was observed, whereas allogeneic BVDV-infected target cells were only marginally lysed as detected by flow cytometry. BVDV-specific lymphocyte transformation was further characterised by the expression of bovine lymphocyte activation antigens and bovine MHC class-II molecules. Secondary stimulation of CTL was influenced by in vitro production of BVDV-specific neutralising antibodies, which were secreted exclusively in BVDV-inoculated lymphocyte cultures of immunised cattle. These results demonstrate the presence of CTL in peripheral blood mononuclear cells (PBMC) of immunised cattle which can kill autologous BVDV-infected antigen-presenting cells after in vitro restimulation.

Lingual flap retraction and prevention of lingual nerve damage associated with third molar surgery: a systematic review of the literature.

OBJECTIVE: Lingual nerve damage sometimes occurs after the removal of third molars. The use of a lingual retractor has been advocated to protect the lingual nerve. A systematic review of the literature was undertaken to evaluate the incidence of lingual nerve damage after third molar surgery and the effect of a lingual retractor on nerve damage. STUDY DESIGN: An exhaustive computerized search of several databases and references cited in the various studies was performed. Predetermined inclusion and exclusion criteria were used to identify the 8 published studies acceptable for detailed analysis. The incidence and spontaneous recovery of lingual nerve injury for the following 3 surgical techniques were evaluated: the buccal approach with lingual flap retraction (BA+), or the buccal approach without lingual flap retraction (BA-), and the lingual split technique with lingual flap retraction (LS). RESULTS: In the 8 selected articles, lingual nerve injury occurred in 9.6%, 6.4%, and 0.6% of the pooled LS, BA+, and BA- procedures, respectively. On the basis of risk ratios comparing combined incidence rates, lingual nerve injury is 8.8 times more likely to occur in BA+ than in BA- procedures (CI = 4.3-17.8), 13.3 times more likely to occur in LS than in BA- procedures (CI = 6.6-26.9), and 1.5 times more likely to occur in LS than in BA+ procedures (CI = 1.2-1.8). Permanent lingual nerve injury occurred in 0.1%, 0.6%, and 0.2% of the combined LS, BA+, and BA- procedures, respectively. The combined permanent incidence risk ratios were not calculated because of the low permanent incidence rates. CONCLUSIONS: The use of a lingual nerve retractor during third molar surgery was associated with an increased incidence of temporary nerve damage and was neither protective nor detrimental with respect to the incidence of permanent nerve damage.

Comparison of liver function with two new/mixed intravenous lipid emulsions in children with intestinal failure.

BACKGROUND/OBJECTIVE: The high incidence of liver disease associated with intravenous soybean lipid has led to development and use of alternative intravenous lipid emulsions (ILEs). The aim of this study was to compare two new/mixed ILEs: a medium-chain triglyceride (MCT) combined with soybean (i.e., Lipofundin) and a combination of both these lipids with additional olive and fish oils (SMOF). SUBJECTS/METHODS: Neonates/premature infants newly starting parenteral nutrition (PN) treatment and children with abnormal liver function tests, alanine transferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT) 1.5x upper limit of normal and/or total bilirubin >50 µmol/l for >2 weeks on treatment with PN containing pure soybean ILE (Intralipid 20%; Fresenius Kabi), were started on/changed to either SMOF or Lipofundin. RESULTS of biochemistry and clinical outcome were compared on commencing and discontinuing treatment according to the new ILE used. RESULTS: One hundred and twenty-seven children aged 0-16 (median 0.6) years were included. Fifity-six were given Lipofundin and 71 SMOF. Fifty-three of 127 started PN for the first time and 74 had had previous treatment with Intralipid. During treatment, ALT and ALP levels fell significantly (P<0.008 on SMOF; P<0.05 on Lipofundin), with additional significant reduction in γ-GT with SMOF. Hyperbilirubinaemia incidence decreased from 34% on starting to 24% on discontinuing treatment (P⩽0.05). Infection rate/1000 catheter days, full blood count, serum triglyceride and cholesterol levels were similar with both ILEs. CONCLUSION: Addition of MCT to soybean ILE was associated with improved liver function. There was an even greater improvement when olive and fish oils were also added with higher incidence of resolution of abnormal liver function tests and reduced inflammation.

Prevalence of undernutrition during hospitalisation in a children's hospital: what happens during admission?

BACKGROUND/OBJECTIVE: The aim of the study was to compare the prevalence of undernutrition in children on presentation to hospital and on discharge. METHODS: On a screening week, 141 children aged from birth to 17 years who were hospitalised for ⩾72 h were reviewed on presentation and discharge or after 3 months (if still in hospital) by auditing hospital records. Weight for age standard deviation (s.d.<-2) was used to define undernutrition on admission and discharge. The number of children referred for dietetic advice was recorded. RESULTS: The prevalence of undernutrition on admission was 27% (14% moderate (s.d.: -2 to -3) and 13% severe (s.d.: ⩾-3)) according to weight s.d. and increased to 32% by discharge (11% moderate; 21% severe). The most nutritionally vulnerable children, with a prevalence of undernutrition from 33 to 53% on admission, were aged less than 2 years, inpatients for >1 month and those with multiple medical problems. In all, 74% (n=104) of cases were referred to Dietetics, including 73% (n=79) of those without evidence of undernutrition. CONCLUSIONS: Undernutrition is a major problem in children during hospitalisation. The risk of nutritional depletion needs to be identified at the time of admission, especially for children under 2 years and those with multiple medical problems, in order to initiate appropriate nutritional intervention.

Review of the diagnoses predisposing infants to intestinal failure on hospitalized parenteral nutrition.

During the last 3 decades the use of parenteral nutrition (PN) and the aggressive introduction of enteral feeding in daily practice have transformed the outcome for even the sickest of these infants. More than 90% of infants and children now survive after extensive small bowel resection in the neonatal period. During the last 3 decades the use of parenteral nutrition (PN) and the aggressive introduction of enteral feeding in daily practice have transformed the outcome for even the sickest of these children. The aim of this study was to review the diagnoses (other than infants purely premature) that predispose infants to intestinal failure (IF) and dependency on PN as well as their outcomes. A total of 63 children less than 1 year old received PN for more than 28 days including 35 (56%) boys; 29% of cases were preterm infants with a median gestational age of 26.5 weeks (range, 24-33 weeks). The median age at the start of PN was 0.25 years or 3 months. Median duration of PN treatment was 62 days and median duration of hospitalization was 128 days. Twenty-three (36.5%) children had a primary nondigestive disorder (PNDD) and 40 (63.5%), a primary digestive disorder (PDD). Forty (63.5%) children with severe intestinal failure were successfully weaned off PN; whereas 8 (13%) infants with severe gastrointestinal diseases remained dependent on IV nutrition. Fourteen (22%) patients died. Infants less than 1 year of age with severe intestinal failure have up to a 75% survival rate, with a 65% chance of achieving intestinal autonomy. For children presenting with PDD in infancy, there is a high risk of needing long-term PN.

Sepsis and its etiology among hospitalized children less than 1 year of age with intestinal failure on parenteral nutrition.

Infections accompany intestinal failure (IF) more commonly in children than in adults, with reported incidences of 2% to 29%. Appropriate care of the central venous catheter is the most important factor preventing infections; but in addition, bacteria translocate from the dysmotile gut as a possible source of septicemia. The aim of this retrospective analysis was to investigate the rate and the epidemiologic profile of septicemia in the patient group at greatest risk, namely, children less than 1 year of age with IF on parenteral nutrition (PN). Among 63 children less than 1 year of age who were included over a 2-year period, 55% were boys. The overall median age at the start of PN was 0.3 years, with a mean duration of 80 days. Some 68% of patients had at least one episode of septicemia, experiencing a mean of 1.5 episodes (range, 1-12). Also, 19% of children displayed polymicrobial bloodstream infections. The most common Gram-positive pathogens were Staphylococcus spp and Enterococcus spp; the Gram-negative pathogens were Klebsiella spp followed by Enterobacter spp and E. coli. Infants less than 1 year of age with IF >28 days experienced a high (68%) rate of sepsis. There was no difference in the incidence of catheter-related blood stream infection according to the primary underlying diagnosis. The most common pathogens were Staphylococcus spp and Enterococcus spp, similar to etiologies of sepsis among children in intensive care units.

Glomerular filtration rate estimates decrease during high altitude expedition but increase with Lake Louise acute mountain sickness scores.

AIM: Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited. METHODS: Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests. RESULTS: eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01). CONCLUSIONS: Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.

FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities.

Fibroblast growth factor 5 (FGF5) is widely expressed in embryonic but scarcely in adult tissues. Here we report simultaneous overexpression of FGF5 and its predominant high-affinity receptor (FGFR1 IIIc) in astrocytic brain tumour specimens (N=49) and cell cultures (N=49). The levels of both ligand and receptor increased with enhanced malignancy in vivo and in vitro. Furthermore, secreted FGF5 protein was generally present in the supernatants of glioblastoma (GBM) cells. siRNA-mediated FGF5 downmodulation reduced moderately but significantly GBM cell proliferation while recombinant FGF5 (rFGF5) increased this parameter preferentially in cell lines with low endogenous expression levels. Apoptosis induction by prolonged serum starvation was significantly prevented by rFGF5. Moreover, tumour cell migration was distinctly stimulated by rFGF5 but attenuated by FGF5 siRNA. Blockade of FGFR1-mediated signals by pharmacological FGFR inhibitors or a dominant-negative FGFR1 IIIc protein inhibited GBM cell proliferation and/or induced apoptotic cell death. Moreover, rFGF5 and supernatants of highly FGF5-positive GBM cell lines specifically stimulated proliferation, migration and tube formation of human umbilical vein endothelial cells. In summary, we demonstrate for the first time that FGF5 contributes to the malignant progression of human astrocytic brain tumours by both autocrine and paracrine effects.

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma.

Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re-operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O6-methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence.

Most of diaplacentally transferred allergen is retained in the placenta.

BACKGROUND: Transplacental transfer of nutritive and inhalant allergens has been described being potentially responsible for a series of events leading to antigen-specific immune responses in the fetus. As such, cord blood T cell responses appear ubiquitously. However, studies failed to reveal a consistent dose-response relationship between antenatal allergen exposure and allergen-specific cellular reactivity in cord blood. OBJECTIVE: To examine the transfer process of allergens (ovalbumin (OVA), beta-lactoglobulin (BLG), birch pollen allergen Bet v1) in placental tissue (BeWo cell line, ex vivo placenta model). METHODS: The choriocarcinoma cell line BeWo was used to study the allergen uptake and transfer experiments in vitro. In the ex vivo placenta model the contribution of different placental compartments was evaluated. For this, immuno-histochemistry, immuno-electronmicroscopy and ELISA techniques were applied using monoclonal antibodies to Bet v1, OVA and -BLG. RESULTS: In vitro transfer studies on a BeWo cell-layer revealed an intracellular allergen uptake and a trans-trophoblastic allergen transfer, which was temperature- and concentration dependent, pH sensitive and asymmetric. Allergen-specific staining of placental tissue after allergen perfusion (BLG) demonstrated bulk of the allergen in the syncytio-trophoblastic cell layer and minor staining in the villous stroma and in the endothelium of fetal vessels. Immunogold staining revealed an accumulation of the perfused allergen in the trophoblastic basement membrane. CONCLUSION: In vitro/ex vivo trans-trophoblastic and trans-placental allergen transfer is shown with an accumulation of most of the allergen in placental tissues, potentially explaining the missing direct dose-response relationship between prenatal (maternal) allergen exposure and allergen-specific cellular reactivity in cord blood.

Persistence of orientation toward a temporarily invisible landmark in Drosophila melanogaster.

In arena experiments with the walking fruit fly, we found a remarkable persistence of orientation toward a landmark that disappeared during the fly's approach. The directional stability achieved by 'after-fixation' allows a fly to continue pursuit under natural conditions, where a selected target is frequently concealed by surrounding structures. The persistence of after-fixation was investigated in Buridan's paradigm, where a fly walks persistently back and forth between two inaccessible landmarks. Upon disappearance of a selected target, the flies maintained their intended course for more than 15 body lengths of approximately 2.5 mm in about 50% of the trials. About 13% even exceeded 75 body lengths. About 88% of the approaches clustered in equal portions around peaks at 2.4 s and 8.6 s. About 12% of the approaches persisted even longer. In contrast, a single peak at about 2.2 s is sufficient to describe the persistence of orientation in a random walk. The ability to pursue an invisible landmark is disturbed neither by a transient angular deviation from the course toward this landmark, when this target disappeared, nor by a distracting second landmark. Accordingly, after-fixation seems to require an internal representation of the direction toward the concealed target, and idiothetical course control to maintain this direction.

Direct evidence for transplacental allergen transfer.

Allergies are increasing, and despite deeper insights into the immunologic basis of these diseases, preventive measures are not yet efficient. As the induction of allergic diseases is often triggered in early childhood, perinatal or prenatal preventive strategies would be beneficial. We investigated the transfer of inhalant and nutritive allergens across the human placenta. For this purpose, the maternal side of a placental cotyledon was perfused in vitro with an allergen-containing medium, and a specific ELISA was used to detect the allergens on the fetal side. Both allergens evaluated, birch pollen major allergen Bet v1 and the milk allergen beta-lactoglobulin, could be shown to cross the placenta. The nutritive allergen beta-lactoglobulin was not only transferred across the placenta in all eight experiments, but was also detectable within the first minutes of perfusion. The peak allergen concentration on the fetal side could be increased by addition of human immunoglobulin. For the inhalant allergen Bet v1, transfer was observed in two of 10 placental experiments, and only if human immunoglobulin was added. A pulsatility wave with a frequency of 30-35 min suggested an active transfer mechanism. We conclude that allergens are actively and selectively transferred across the placenta. Therefore, controlled maternal allergen exposure might offer new ways to induce tolerance to specific allergens in the fetus.

[Early diagnosis of bronchial carcinoma. Technical endoscopic progress--a step toward new screening concepts?]. / Frühdiagnostik des Bronchialkarzinoms. Technisch-endoskopische Neuentwicklungen--ein Anstoss für neue Screening-Konzepte?

Lung cancer is the most common neoplasm of our days. Its mortality has remained invariably high over the last decades and the search for effective preventive and therapeutic strategies is as imperative as ever. Carcinogenesis is a process requiring years until invasive malignancy has developed and hence offers a sufficient period for early detection of (pre-)malignant lesions. Now, tools seem available to achieve this goal: technical refinements advocate a reappraisal of screening methods for lung cancer. Also, apart from conventional diagnostic procedures, which are reviewed in this article, photodynamic and autofluorescence bronchoscopy deserve particular attention. Recent data, showing sensitivity for detection of premalignant lesions increased by factor 1.9 to 2.7 as compared to white light bronchoscopy, suggest markedly improved diagnostic options. With these new instruments, especially when combined with screening programs of high-risk groups, earliest possible diagnosis and successful therapeutic intervention seem a promising concept of reduction of lung cancer mortality.