Targeted next-generation sequencing of adult gliomas for retrospective prognostic evaluation and up-front diagnostics.

AIMS: We aimed to reclassify a population-based cohort of 529 adult glioma patients to evaluate the prognostic impact of the 2016 World Health Organization (WHO) central nervous system tumour classification. Moreover, we evaluated the feasibility of gene panel next-generation sequencing (NGS) in daily diagnostics of 225 prospective glioma patients. METHODS: The retrospective cohort was reclassified according to WHO 2016 criteria by immunohistochemistry for IDH-R132H, fluorescence in situ hybridization for 1p/19q-codeletion and gene panel NGS. All tumours of the prospective cohort were subjected to NGS analysis up-front. RESULTS: The entire population-based cohort was successfully reclassified according to WHO 2016 criteria. NGS results were obtained for 98% of the prospective patients. Survival analyses in the population-based cohort confirmed three major prognostic subgroups, that is, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas, IDH-mutant astrocytomas and IDH-wildtype glioblastomas. The distinction between WHO grade II and III was prognostic in patients with IDH-mutant astrocytoma. The survival of patients with IDH-wildtype diffuse astrocytomas carrying TERT promoter mutation and/or EGFR amplification overlapped with the poor survival of IDH-wildtype glioblastoma patients. CONCLUSIONS: Gene panel NGS proved feasible in daily diagnostics. In addition, our study confirms the prognostic role of glioma classification according to WHO 2016 in a large population-based cohort. Molecular features of glioblastoma in IDH-wildtype diffuse glioma were linked to poor survival corresponding to IDH-wildtype glioblastoma patients. The distinction between WHO grade II and III retained prognostic significance in patients with IDH-mutant diffuse astrocytic gliomas.

Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool.

AIMS: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. METHODS: About 502 CNS tumour samples were analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. RESULTS: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score ≥0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as 'discrepant but noncontributory'. The remaining 33.7% of cases (169/502) had a calibrated score <0.9, including 7.8% (39/502) for which no class indication was given at all (calibrated score <0.3). CONCLUSIONS: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information.

Fluorescence or X-ray cholangiography in elective laparoscopic cholecystectomy: a randomized clinical trial.

BACKGROUND: Safe laparoscopic cholecystectomy may necessitate biliary imaging, and non-invasive fluorescence cholangiography may have advantages over contrast X-ray cholangiography. This trial compared fluorescence and X-ray cholangiography for visualization of the critical junction between the cystic, common hepatic and common bile ducts. METHODS: This non-inferiority blinded RCT included patients who had either intraoperative fluorescence cholangiography using 0·05 mg/kg indocyanine green or X-ray cholangiography during elective laparoscopic cholecystectomy. RESULTS: Between March 2015 and August 2018, a total of 120 patients were randomized (60 in each group). There were no drop-outs and 30-day follow-up data were available for all patients. In intention-to-treat analysis, there was no difference between the fluorescence and X-ray cholangiography groups in ability to visualize the critical junction (49 of 60 versus 51 of 60 respectively; P = 0·230). Fluorescence cholangiography was faster by a few minutes: median 2·0 (range 0·5-5·0) versus 4·8 (1·3-17·6) min (P < 0·001). CONCLUSION: Fluorescence cholangiography was confirmed to be non-inferior to X-ray cholangiography in visualizing the critical junction during laparoscopic cholecystectomy. Registration number: NCT02344654 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La práctica de una colecistectomía laparoscópica segura puede requerir imágenes de la vía biliar, en las cuales la colangiografía con fluorescencia no invasiva puede tener ventajas sobre la colangiografía con contraste con rayos X. Este ensayo comparó la colangiografía con fluorescencia con la colangiografía con rayos X para la visualización de la unión crítica entre el conducto cístico, el conducto hepático común y los conductos biliares comunes. MÉTODOS: Ensayo clínico aleatorizado, ciego, de no inferioridad que incluyó a 120 pacientes en los que durante la colecistectomía laparoscópica electiva se practicó una colangiografía con fluorescencia intraoperatoria utilizando 0,05 mg/kg de verde de indocianina o una colangiografía con rayos X. RESULTADOS: De marzo de 2015 a agosto de 2018, se aleatorizaron un total de 120 pacientes (6 en cada grupo), en los que no hubo abandonos y con datos de seguimiento de 30 días disponibles en todos ellos. Basado en un análisis por intención de tratamiento, la capacidad de visualizar la unión crítica fue igual entre los dos grupos (49/60 versus 51/60, P = 0,23). La colangiografía con fluorescencia fue más rápida de realizar, en unos pocos minutos (mediana 2 min (rango 0,5-5,0) versus 5 min (rango 5,2-17,6), P < 0,001). CONCLUSIÓN: Se confirmó que la colangiografía con fluorescencia no fue inferior a la colangiografía con rayos X para visualizar la unión crítica durante la colecistectomía laparoscópica.

Molecular pathology of tumors of the central nervous system.

Since the update of the 4th edition of the WHO Classification of Central Nervous System (CNS) Tumors published in 2016, particular molecular characteristics are part of the definition of a subset of these neoplasms. This combined 'histo-molecular' approach allows for a much more precise diagnosis of especially diffuse gliomas and embryonal CNS tumors. This review provides an update of the most important diagnostic and prognostic markers for state-of-the-art diagnosis of primary CNS tumors. Defining molecular markers for diffuse gliomas are IDH1/IDH2 mutations, 1p/19q codeletion and mutations in histone H3 genes. Medulloblastomas, the most frequent embryonal CNS tumors, are divided into four molecularly defined groups according to the WHO 2016 Classification: wingless/integrated (WNT) signaling pathway activated, sonic hedgehog (SHH) signaling pathway activated and tumor protein p53 gene (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH-activated. Molecular characteristics are also important for the diagnosis of several other CNS tumors, such as RELA fusion-positive subtype of ependymoma, atypical teratoid rhabdoid tumor (AT/RT), embryonal tumor with multilayered rosettes, and solitary fibrous tumor/hemangiopericytoma. Immunohistochemistry is a helpful alternative for further molecular characterization of several of these tumors. Additionally, genome-wide methylation profiling is a very promising new tool in CNS tumor diagnostics. Much progress has thus been made by translating the most relevant molecular knowledge into a more precise clinical diagnosis of CNS tumors. Hopefully, this will enable more specific and more effective therapeutic approaches for the patients suffering from these tumors.

Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype.

AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double immunofluorescence. METHODS: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium-binding adaptor molecule-1 (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like TAMs. The expression levels were quantified by software-based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno- and haematoxylin-eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA-1/CD204 levels in central tumour and tumour periphery and to characterize CD204+ cells. RESULTS: Our data revealed that the amount of especially CD204+ TAMs increases with malignancy grade. In grade III-IV, high CD204 expression was associated with shorter survival, while high IBA-1 intensity correlated with a longer survival. In grade IV, CD204 showed independent prognostic value when adjusting for clinical data and the methylation status of O6-methylguanine-DNA methyltransferase. Our findings were confirmed in two bioinformatics databases. TAMs were more abundant in central tumour tissue, mesenchymal glioblastomas and gliomas with many gemistocytic cells. CD204+ TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment.

Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis.

AIMS: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. METHODS: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)-cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. RESULTS: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. CONCLUSION: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

The risk of long-term bowel dysfunction after resection for sigmoid adenocarcinoma: a cross-sectional survey comparing complete mesocolic excision with conventional surgery.

AIM: To investigate whether complete mesocolic excision (CME) might carry a higher risk of bowel dysfunction and subsequent reduction in quality of life compared with conventional resection. METHOD: A cross-sectional questionnaire study based on data from a national survey regarding long-term bowel function and a population-based cohort study comparing CME (study group) with conventional resection (control group). A total of 622 patients undergoing elective resection for Stage I-III sigmoid adenocarcinoma at four university colorectal centres between June 2008 and December 2014 were eligible to receive the questionnaire in mid-November 2015. Primary outcomes were four or more bowel movements daily, nocturnal bowel movements, unproductive call to stool, obstructive sensation and impact of bowel function on quality of life (QOL). RESULTS: One hundred and twenty-seven (69.0%) and 289 (66.0%) patients in the study and control groups, respectively, responded to the questionnaire after medians of 4.41 [interquartile range (IQR) 2.50, 5.83] and 4.57 (IQR 3.15, 5.82) years, respectively (P = 0.048). CME was not associated with: increased risk of four or more bowel movements daily [adjusted OR 1.14 (95% CI 0.59-2.14; P = 0.68)], nocturnal bowel movements [adjusted OR 1.31 (0.66-2.53; P = 0.43)], unproductive call to stool [adjusted OR 0.99 (0.54-1.77; P = 0.97)] or obstructive sensation [adjusted OR 1.01 (0.56-1.78; P = 0.96)]. While one in five patients in both groups had moderate to severe impact of bowel function on QOL, there was no association with CME. CONCLUSION: For patients with sigmoid cancer, CME is associated with neither higher risk of bowel dysfunction nor impaired QOL.

Description and validation of a new automated surveillance system for Clostridium difficile in Denmark.

The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010-2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.

Incidence of venous thromboembolic events in enhanced recovery after surgery for colon cancer: a retrospective, population-based cohort study.

AIM: Both the Danish and the National Institute of Clinical Excellence (NICE) guidelines recommend prolonged thromboprophylaxis (PT) with low-molecular-weight heparin (LMWH) for 28 days postoperatively after elective surgery for colon cancer. The evidence relies on data from two randomized clinical trials (RCTs) that included not only colon cancers but also other abdominal cancers or benign colorectal diseases. Neither of those studies investigated the risk of venous thromboembolism (VTE) under enhanced recovery after surgery (ERAS). We aim to describe the risk of VTE and estimate the cost of preventing one case of VTE by PT under ERAS. METHOD: This was a retrospective study of 2230 patients undergoing elective surgery for colon cancer Stage I-III in the Capital Region of Denmark, 1 June 2008 to 31 December 2013. Patients who were discharged on postoperative day 28 or later, died during admission or were discharged with a vitamin K antagonist, novel oral anticoagulants or LMWH were excluded. Patients with rectal cancer only were not included. End-points were symptomatic VTE diagnosed within 60 days postoperatively. RESULTS: Three-hundred and thirty patients were excluded. For the remaining 1893, the median length of stay (LOS) was 4 [interquartile range (IQR): 3-5] days. Of these 1893 patients, four (0.20%) experienced a nonfatal symptomatic VTE. All four patients had other postoperative complications before the VTE. The cost of each symptomatic VTE prevented is estimated to be between £63 709 and £111 455 when medication and home-care nursing are included. CONCLUSION: The risk of symptomatic VTE after uncomplicated, elective surgery for colon cancer with ERAS seems negligible and the cost-effectiveness of PT to prevent one symptomatic VTE seems questionable.

Ultrasound-guidance outperforms the palpation technique for peripheral venous catheterisation in anaesthetised toddlers: a randomised study.

BACKGROUND: Traditional palpation technique for peripheral venous catheter (PVC) placement can be challenging. We aimed to compare the Dynamic Needle Tip Positioning (DNTP) ultrasound technique with the palpation technique for PVC placement in anaesthetised toddlers undergoing elective, low-risk procedures. METHODS: The study was a randomised, controlled, crossover study. Five operators applied both techniques for PVC on 50 children < 4 years. The primary endpoint was first attempt success rate. The secondary endpoints were: (1) overall success rate, (2) number of skin perforations, (3) number of needle redirections, (4) number of catheters used, (5) total time, (6) needle manipulation time, (7) distance to the nearest flexion crease, (8) anatomical region of catheterisation, (9) size of the catheters and (10) the effects of visibility, and palpability of the veins. RESULTS: The first attempt success rate and the overall success rate were significantly higher in the DNTP group (42/50 vs. 30/50, P = 0.029), (50/50 vs. 42/50, P = 0.008). Furthermore, a lower number of skin perforations (60 vs. 84, P = 0.013) and needle redirections (14 vs. 131, P < 0.001) and increased distance to the nearest flexion crease (P < 0.001) were seen in the DNTP group. There were no significant differences in number of catheters used (60 vs. 75 P = 0.050) or total time (P = 0.073), however, the needle manipulation time was longer in the DNTP group (P = 0.011). The success rate decreased with less visible and palpable veins in the palpation group (p = 0.006). CONCLUSION: Ultrasound-guidance outperforms the traditional palpation technique for peripheral venous catheterisation in anaesthetised toddlers undergoing elective, low-risk procedures.

Short-term outcomes after complete mesocolic excision compared with 'conventional' colonic cancer surgery.

BACKGROUND: Complete mesocolic excision (CME) seems to be associated with improved oncological outcomes compared with 'conventional' surgery, but there is a potential for higher morbidity. METHODS: Data for patients after elective resection at the four centres in the Capital Region of Denmark (June 2008 to December 2013) were retrieved from the Danish Colorectal Cancer Group database and medical charts. Approval from a Danish ethics committee was not required (retrospective study). RESULTS: Some 529 patients who underwent CME surgery at one centre were compared with 1701 patients undergoing 'conventional' resection at the other three hospitals. Laparoscopic CME was performed in 258 (48·8 per cent) and laparoscopic 'conventional' resection in 1172 (68·9 per cent). More extended right colectomy procedures were done in the CME group (17·4 versus 3·6 per cent). The 90-day mortality rate in the CME group was 6·2 per cent versus 4·9 per cent in the 'conventional' group (P = 0·219), with a propensity score-adjusted logistic regression odds ratio (OR) of 1·22 (95 per cent c.i. 0·79 to 1·87). Laparoscopic surgery was associated with a lower risk of mortality at 90 days (OR 0·63, 0·42 to 0·95). Intraoperative injury to other organs was more common in CME operations (9·1 per cent versus 3·6 per cent for 'conventional' resection; P < 0·001), including more splenic (3·2 versus 1·2 per cent; P = 0·004) and superior mesenteric vein (1·7 versus 0·2 per cent; P < 0·001) injuries. Rates of sepsis with vasopressor requirement (6·6 versus 3·2 per cent; P = 0·001) and postoperative respiratory failure (8·1 versus 3·4 per cent; P < 0·001) were higher in the CME group. CONCLUSION: CME is associated with more intraoperative organ injuries and severe non-surgical complications than 'conventional' resection for colonic cancer.

Girls with generalized joint hypermobility display changed muscle activity and postural sway during static balance tasks.

OBJECTIVES: To study knee muscle activity and static postural sway in girls with generalized joint hypermobility (GJH). METHOD: Sixteen girls with GJH and 11 girls with non-GJH (NGJH) aged 14 years, randomly recruited among schoolchildren, participated in this study. GJH inclusion criteria were: Beighton score minimum 6/9 and one hypermobile knee; for NGJH: Beighton score maximum 5/9 and no knees with hypermobility. The participants performed a static two-legged balance test with eyes open (2EO) and eyes closed (2EC) and a one-legged stance test with eyes open (1EO). Postural sway (centre of pressure path length, COPL) was calculated, along with rambling and trembling components. Surface electromyography (sEMG) from the quadriceps (Q), hamstrings (H), and gastrocnemius (G) muscles was recorded, expressed as a percentage of the maximum voluntary EMG (%MVE), and the co-contraction index (CCI) of Q, H, and G muscle activity was calculated. Knee function was self-reported using the Knee Injury and Osteoarthritis Outcome Score for children (KOOS-Child). RESULTS: GJH had a significantly lower lateral HQ CCI and a higher medial/lateral HQ CCI ratio in all balance tasks. Group mean EMG varied from 1.3%MVE in Q (during 2EO) to 15.7%MVE in G (during 1EO). GJH had larger postural sway length than NGJH during 2EC (COPL 1.64 vs. 1.37 m/min, p < 0.001). Rambling and trembling components did not differ between groups. CONCLUSIONS: Girls with GJH and at least one hypermobile knee performed, compared with NGJH, static balance tasks with higher medial knee muscle activity relative to the lateral activity, and larger postural sway when vision was eliminated. The short- and long-term consequences should be studied further.

Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis.

T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3) compared to FoxP3Δ2, missing exon 2. Th17 and Th10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17 or Th10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or Esherichia coli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive CD4(+) CD45RA(+) CD45R0(-) T cells from HT patients into Th17 cells. Th10 cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together, our data show that an increased Th17 : Th10 ratio was found in HT patients after stimulation with thyroid-specific self-antigens. We also observed an elevated baseline production of IL-6 and transforming growth factor (TGF)-ß1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT.

Effect of high-volume systematic local infiltration analgesia in Caesarean section: a randomised, placebo-controlled trial.

BACKGROUND: Pain after Caesarean section is often treated with opioids with a risk of side effects. Wound infiltration with local anaesthetics is effective and has few side effects, but volume vs. dose concentration has not been examined. METHODS: Ninety patients scheduled for elective Caesarean section included in a randomised, double-blinded, placebo-controlled trial receiving infiltration with 50 ml ropivacaine 0.5% or 125 ml ropivacaine 0.2% or 50 ml 0.9% saline (placebo) during surgery. Surgery was performed under lumbar spinal anaesthesia. Primary endpoint was post-operative pain. Secondary endpoints were rescue analgesic, post-operative nausea and vomiting, time spent in the postanesthesia care unit (PACU) and time to first mobilisation. RESULTS: No difference in pain response between groups, but time until maximum pain score was prolonged in the ropivacaine 0.5% group compared with the placebo group (P = 0.0493). The administration of ketobemidone at 24 h post-operatively in the ropivacaine 0.5% group was reduced compared with the placebo group (P = 0.020), and between the ropivacaine 0.2% group and the ropivacaine 0.5% group (P = 0.044). No significant differences between groups were found concerning time spent in the PACU, to first mobilisation or in number of women with nausea/vomiting (P ≥ 0.05). No complications related to ropivacaine were observed. CONCLUSIONS: Systematic infiltration with a high concentration, low volume compared with low concentration, high volume showed no significant effect on post-operative pain intensity. However, a statistically significant, but clinically limited opioid sparing effect was demonstrated compared with placebo in the high concentration, low volume group.

[Nutrition and IBD-Consensus of the Austrian Working Group of IBD (Inflammatory Bowel Diseases) of the ÖGGH]. / Ernährung und chronisch entzündliche Darmerkrankungen - ein Konsensus der Arbeitsgruppe chronisch entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (Austrian Guidelines for nutrition in IBD).

This is a consensus of the Austrian working group of IBD (inflammatory bowel diseases) of the ÖGGH on nutrition in IBD. Malnutrition should be assessed in case of IBD (in 20 - 70 % of Crohn's patients) and weight loss(> 5 % within 3 months) or nutritional deficiencies or after extensive bowel resection and afterwards also treated. Malnutrition should be treated with medical therapy of IBD and also adequate - as far as possible - with oral nutritional therapy particularly because of reduced life quality, risk of opportunistic infections, osteopenia/osteoporosis, longer hospitalisations and higher mortality. Iron homeostasis, serum levels of Vitamin B12- and folic acid, 25-hydroxyvitamin D and zinc should be checked. Therapy with enteral liquid diets is only indicated as therapy of first choice in children and adolescents, but only in rare situations in adults with IBD. There is - up to now - no proven oral diet for maintenance of remission in IBD. Probiotics as E. coli Nissle could be used as alternative to mesalazine for maintenance of remission in patients with ulcerative colitis. A specific dietary counselling is mandatory in patients with ileostoma or short bowel syndrome. Malnutrition of short bowel patients is particularly dependent on the function and length of the remaining bowel, therefore the most effective medical therapy should be administered.

Hand hygiene compliance in nursing home wards: the effect of increased accessibility of alcohol-based hand rub.

BACKGROUND: Elderly nursing home residents are vulnerable to infection from micro-organisms. Hand hygiene is considered one of the most important measures to prevent transmission. AIM: To determine the effect of increased accessibility to alcohol-based hand rub (ABHR) in nursing home wards by monitoring hand hygiene compliance (HHC) among healthcare workers (HCWs). METHODS: An 11-month intervention study was conducted in a Danish six-ward nursing home. Data were collected using an automatic hand hygiene monitoring system (AHHMS). After a baseline period, one extra ABHR dispenser was placed in each of the 150 apartments. Baseline HHC was compared with the HHC during an immediate intervention period and a long-term intervention period. FINDINGS: A total of 159 HCWs were included. The AHHMS registered 341,078 hand hygiene opportunities. Overall baseline HHC was 31% (95% confidence interval: 30-32). A significant +18% absolute immediate effect (first five months) (95% CI: 17-19; P < 0.0001) and +13 percentage points (95% CI: 11-14; P < 0.0001) long-term effect (another four months) were recorded. HCWs working day shifts and short-term employees had a higher baseline HHC than HCWs working evening/night shifts. However, HCWs working night shifts achieved the greatest long-term effect with a mean +27 percentage point difference (P < 0.0001). CONCLUSION: Placing an additional ABHR dispenser strategically within staff workflow significantly increased HHC among HCWs, demonstrating a noteworthy effect. The study is the first to report the effect on nursing home dispenser accessibility as a single intervention and to show a significant unmet potential.

Non-allergic, mastocytosis-associated rhinitis.

BACKGROUND: Systemic mastocytosis (SM) is a clonal proliferative disorder of mast cells (MC) that causes pathological accumulation of mast cells in various tissues, which results in clinical symptoms (e.g. diarrhoea, urticaria) due to MC mediator release. Previous studies have shown that up to fifty percent of rhinitis symptoms in SM patients are non-allergic and it has been assumed that these nasal complaints in SM patients are due an increased nasal mast cell burden. Nevertheless, to date there are no data supporting this hypothesis. OBJECTIVE: The study aims to investigate if the presence of allergy-suggesting nasal complaints in non-allergic SM patients is correlated with objective measure of nasal mast cell burden. PATIENTS AND METHODS: Eleven adult patients with systemic mastocytosis underwent a comprehensive rhinologic work-up. All patients fulfilled the clinical ARIA criteria for rhinitis. The allergologic work-up included serological allergy testing, determination of tryptase levels (serum and nasal secretion), skin prick testing, and nasal provocation testing. RESULTS: Ten out of eleven SM patients with clinical persistent allergic rhinitis were found to be non-allergic. In these patients, the most predominant symptoms were rhinorrhea, sneezing, and itching. All three symptoms were strongly correlated with the nasal tryptase level but not to the level of serum tryptase. CONCLUSION AND CLINICAL RELEVANCE: Non-allergic persistent nasal complaints in systemic mastocytosis were significantly correlated with elevated nasal tryptase level as a measure of local MC burden. Furthermore, elevated nasal tryptase correlated with persistent rhinorrhea, sneezing, and itching as predominant symptoms, which seems to characterize a non-allergic mastocytosis-associated rhinitis (NAMAR) in systemic mastocytosis.

Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA). METHODS: Forty-eight patients undergoing unilateral THA under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length of stay were also registered. Discharge criteria were assessed twice daily (at 09:00 and 14:00 h) until discharge. Other outcomes were assessed at 2, 4, 6, 8, and 24 h after operation, and also in a questionnaire from postoperative day (POD) 1-4. RESULTS: Time to meet discharge criteria was [median (IQR) (95% CI), MP vs placebo]: 23.5 (23.3-23.7) (17.8-43.8) vs 23.5 (23.0-23.8) (20.0-46.8) h, the mean difference (95% CI) being -1.3 (-4.7 to 2.2) h, P=0.65. Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group (P<0.01), as was CRP at 24 h (P<0.0001). No other between-group differences were observed. No drug-related complications were observed at follow-up on POD30. CONCLUSIONS: MP 125 mg i.v. before surgery added to a multimodal oral analgesic regime did not reduce time to meet functional discharge criteria after THA, but improved analgesia for the first 24 h.

Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response.

BACKGROUND: Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied. OBJECTIVE: The aim was to investigate whether infection with the nematode parasite Trichuris suis alters systemic cytokine levels, cellular cytokine responses to parasite antigens and pollen allergens and/or the cytokine profile of allergic individuals. METHODS: In a randomized double-blinded placebo-controlled clinical trial (UMIN trial registry, Registration no. R000001298, Trial ID UMIN000001070, URL: http://www.umin.ac.jp/map/english), adults with grass pollen-induced allergic rhinitis received three weekly doses of 2500 Trichuris suis ova (n = 45) or placebo (n = 44) over 6 months. IFN-γ, TNF-α, IL-4, IL-5, IL-10 and IL-13 were quantified via cytometric bead array in plasma. Cytokines, including active TGF-ß, were also quantified in supernatants from peripheral blood mononuclear cells cultured with parasite antigens or pollen allergens before, during and after the grass pollen season for a sub-cohort of randomized participants (T. suis ova-treated, n = 12, Placebo-treated, n = 10). RESULTS: Helminth infection induced a Th2-polarized cytokine response comprising elevated plasma IL-5 and parasite-specific IL-4, IL-5 and IL-13, and a global shift in the profile of systemic cytokine responses. Infection also elicited high levels of the regulatory cytokine IL-10 in response to T. suis antigens. Despite increased production of T. suis-specific cytokines in T. suis ova-treated participants, allergen-specific cytokine responses during the grass pollen season and the global profile of PBMC cytokine responses were not affected by T. suis ova treatment. CONCLUSIONS AND CLINICAL RELEVANCE: This study suggests that cytokines induced by Trichuris suis ova treatment do not alter allergic reactivity to pollen during the peak of allergic rhinitis symptoms.

Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients.

OBJECTIVES: The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study. METHODS: Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered. RESULTS: Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Post-investigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed. CONCLUSION: Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.