Annual report on surveillance of respiratory infectious diseases 2013, the Netherlands

Het griepseizoen (influenza) 2013/2014 was erg mild, na de uitzonderlijk langdurende epidemie in het seizoen 2012/2013. Ook was het een mild seizoen wat betreft het aantal mensen dat een longontsteking (pneumonie) opliep. In 2013 waren er geen grote uitbraken van de meldingsplichtige luchtweginfectieziekten legionellose (308 meldingen), papegaaienziekte (psittacose; 51 meldingen), Q-koorts (19 meldingen) en tuberculose (848 meldingen). Deze aantallen waren in het verslagjaar vergelijkbaar of lager dan het aantal meldingen in voorgaande jaren. Dit blijkt uit de jaarlijkse surveillance luchtweginfectieziekten 2013 van het RIVM. Griep en longontsteking leiden tot veel ziekenhuisopnames en sterfte in Nederland, waardoor het RIVM ze actief volgt. In vergelijking met griep komen de meldingsplichtige luchtweginfecties in Nederlands maar weinig voor. Ze zijn meldingsplichtig, omdat tijdige maatregelen, zoals de besmettingsbron opsporen, belangrijk kunnen zijn om uitbraken of verdere verspreiding van de ziekte te voorkomen. Het RIVM volgt ook potentieel gevaarlijke nieuwe luchtweginfecties die elders in de wereld voorkomen. In mei 2014 werden voor het eerst in Nederland twee patiënten gediagnostiseerd met het MERS coronavirus. In het seizoen 2013/2014 lag het aantal mensen dat met griepachtige klachten bij de huisarts kwam begin 2014 gedurende vier weken boven de grens waarmee een griepepidemie wordt geduid. Bij de patiënten met griepachtige klachten kwam naast influenzavirus vaak RSV (respiratoir syncytieel virus) en neusverkoudheid (rhinovirus) voor. Er kwamen minder mensen met een longontsteking bij de huisarts dan voorgaande seizoenen, maar het aantal longontstekingpatiënten in verpleeghuizen bleef gelijk.The 2013/2014 influenza season was extremely mild in the Netherlands, compared to the exceptionally long-lasting epidemic in 2012/2013. In addition, the number of pneumonia patients and overall mortality, possible complications of influenza, were low. In 2013, no major outbreaks of the notifiable respiratory infectious diseases legionellosis (308 notifications), psittacosis (51 notifications), Q-fever (19 notifications) and tuberculosis (848 notifications) occurred. These incidences are either comparable to or lower than preceding years. These are the outcomes of the annual report: 'Surveillance of respiratory infectious diseases 2013, the Netherlands', published by the Dutch National Institute for Public Health and the Environment (RIVM). Influenza and pneumonia are an important cause of hospital admissions and death in the Netherlands, a reason for the RIVM to actively monitor these diseases. In comparison to influenza, notifiable respiratory infectious diseases only rarely occur. These diseases are notifiable, as timely measures like source finding, are important for preventing outbreaks and/ or ongoing transmission of the disease. The RIVM also monitors potential threats to public health from new (worldwide) respiratory infections. In May 2014, the first two cases of MERS coronavirus were diagnosed in the Netherlands. During the 2013/2014 influenza-season, the number of patients with influenza-like illness (ILI) consulting a general practitioner, was above the threshold set for an influenza epidemic for four weeks at the beginning of 2014. In nose and throat samples of ILI-patients, RSV (respiratory syncytial virus) and rhinovirus were found in addition to the influenza virus. During the 2013/2014 influenza-season, fewer patients consulted the general practitioner for pneumonia than in previous years, however the number of pneumonia patients in nursing homes was similar.Ministerie van VW

Reduced genomic tumor heterogeneity after neoadjuvat chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

Neoadjuvant chemo(radio)therapy followed by surgery is the standard of care for patients with locally advanced resectable esophageal adenocarcinoma (EAC). There is increasing evidence that drug resistance might be related to genomic heterogeneity. We investigated whether genomic tumor heterogeneity is different after cytotoxic chemotherapy and is associated with EAC patient survival. We used arrayCGH and a quantitative assessment of the whole genome DNA copy number aberration patterns (‘DNA copy number entropy’) to establish the level of genomic tumor heterogeneity in 80 EAC treated with neoadjuvant chemotherapy followed by surgery (CS group) or surgery alone (S group). The association between DNA copy number entropy, clinicopathological variables and survival was investigated. DNA copy number entropy was reduced after chemotherapy, even if there was no morphological evidence of response to therapy (p<0.001). Low DNA copy number entropy was associated with improved survival in the CS group (p=0.011) but not in the S group (p=0.396). Our results suggest that cytotoxic chemotherapy reduces DNA copy number entropy, which might be a more sensitive tumor response marker than changes in the morphological tumor phenotype. The use of DNA copy number entropy in clinical practice will require validation of our results in a prospective study

MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression

Background:MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression.Methods:Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available.Results:From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found.Conclusion:Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression. © 2009 Cancer Research UK

Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo

The chemokine CXCL12/SDF-1 and its receptor CXCR4 have been implicated in invasion, survival and proliferation of carcinoma cells. Recently, CXCR7 was identified as a second receptor for CXCL12. We observed that CXCL12 promoted proliferation of CT26 colon and KEP1 mammary carcinoma cells, and this was blocked when CXCR7 was downregulated by ‘intrakines' or RNAi, but not by CXCR4 inhibitors. The K1R mutant of CXCL12, which acts as a CXCR4 antagonist, also promoted proliferation through CXCR7 and is therefore a selective CXCR7 agonist. The effect of CXCR7 was not due to reduced apoptosis, and CXCR7 mediated chemotaxis of the carcinoma cells towards CXCL12. These results differ from those in a previous report on other carcinoma cells. We conclude that CXCL12 can be a potent growth factor for carcinoma cells by acting on CXCR7. Nevertheless, we observed no effect of complete and stable CXCR7 suppression on the growth of s.c. tumours or lung metastases of KEP1 and CT26 cells. A CXCR7 inhibitor has been reported to reduce growth of other tumours. Our results indicate that this inhibitor may not be applicable to therapy of all carcinomas

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias

MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and the association with mRNA expression in gastric cancers and to correlate methylation status to clinicopathological data. Bisulphite-treated DNA isolated from formalin-fixed and paraffin-embedded samples of 202 gastric adenocarcinomas and 22 normal gastric mucosae was subjected to real-time methylation-specific PCR (Q-MSP). Two regions within the MAL promoter (M1 and M2) were analysed. In addition, 17 frozen gastric carcinomas and two gastric cancer cell lines were analysed both by Q-MSP and real-time RT–PCR. Methylation of M1 and M2 occurred in 71 and 80% of the gastric cancers, respectively, but not in normal gastric mucosa tissue. Hypermethylation of M2, but not M1, correlated with significantly better disease-free survival in a univariate (P=0.03) and multivariate analysis (P=0.03) and with downregulation of expression (P=0.01). These results indicate that MAL has a putative tumour-suppressor gene function in gastric cancer, and detection of promoter hypermethylation may be useful as a prognostic marker

Implants in the severely resorbed mandibles: whether or not to augment? What is the clinician’s preference?

Contains fulltext : 96000.pdf (publisher's version ) (Open Access)INTRODUCTION: The aim of this study is to inventory in the Netherlands which therapy is the clinician's first choice when restoring the edentulous mandible. MATERIAL AND METHODS: A questionnaire was sent to all Dutch Oral and Maxillofacial surgeons. As part of this, the surgeons were invited to treat five virtual edentulous patients, differing only in mandibular residual height. RESULTS: In cases of a sufficient residual height of 15 mm, all surgeons were in favour to insert solely two implants to anchor an overdenture. In case of a residual height of 12 mm, 10% of the surgeons choose for an augmentation procedure. If a patient was presented with a mandibular height of 10 mm, already 40% of the OMF surgeons executed an augmentation procedure. Most (80%) surgeons prefer the (anterior) iliac crest as donor site. The choice of 'whether or not to augment' was not influenced by the surgeon's age; however, the hospital, where he was trained, did. Surgeons trained in Groningen were more in favour of installing short implants in mandibles with reduced vertical height. DISCUSSION: As the option overdenture supported on two interforaminal implants is reimbursed by the Dutch health assurance, this treatment modality is very popular in the Netherlands. From a point of costs and to minimize bypass comorbidity, surgeons should be more reluctant in executing augmentation procedures to restore the resorbed edentulous mandible as it is dated in literature that also in mandibles with a residual height of 10 mm or less, solely placing implants, thus without an augmentation procedure in advance, is a reliable treatment option

Het Rijksvaccinatieprogramma in Nederland. Ontwikkelingen in 2006

In 2006 several changes were made in the Dutch National Immunisation Programme (NIP): Hepatitis B vaccination at birth was added for children born to mothers positive for hepatitis B surface antigen; a new vaccine for diphtheria, tetanus, pertussis (a-cellular), poliomyelitis and Haemophilus influenzae (DTaP-IPV/Hib) was introduced; vaccination against pneumococcal disease was added at two, three, four and eleven months; risk groups for hepatitis B receive a combined vaccine for DTaP-IPV/Hib and HBV at the same ages; DT-IPV and aP at the age of four years were combined in one vaccine; and new MMR vaccines were introduced. As new information became available in 2006, the desirability to introduce vaccinations in the NIP for the following diseases could be (re)considered: hepatitis B (universal vaccination), rotavirus, varicella and human papillomavirus. For respiratory syncytial virus and meningococcal serogroup B disease no candidate vaccines are available yet. Extension of the programme with available vaccines for hepatitis A, influenza and tuberculosis is not (yet) recommended. The NIP in the Netherlands is effective and safe. However, continued monitoring of the effectiveness and safety of the NIP is important as changes are made regularly. Maintaining high vaccine uptake is vital to prevent (re)emergence of diseases. Furthermore, the programme should be regularly reviewed as new vaccines become available.In 2006 traden verschillende veranderingen op in het Rijksvaccinatieprogramma (RVP) in Nederland: kinderen die geboren worden uit moeders die chronisch geinfecteerd zijn met hepatitis B krijgen vlak na de geboorte een hepatitis B vaccinatie; er is een ander vaccin geintroduceerd voor difterie, kinkhoest (a-cellulair), tetanus, poliomyelitis en Haemophilus influenzae (DaKTP/Hib); vaccinatie tegen pneumokokken is toegevoegd op de leeftijd van 2, drie, vier en elf maanden; risicogroepen voor hepatitis B krijgen op diezelfde leeftijden een combinatievaccin voor DaKTP/Hib en hepatitis B; DTP en aK zijn gecombineerd in een vaccin op vierjarige leeftijd; en er zijn nieuwe BMR vaccins geintroduceerd. Op basis van informatie die in 2006 beschikbaar is gekomen wordt geadviseerd de introductie van vaccinaties voor de volgende ziekten te overwegen: hepatitis B (universele vaccinatie), rotavirus, waterpokken en humaan papillomavirus. Voor respiratoir syncytieel virus en meningokokken B zijn nog geen kandidaatvaccins beschikbaar en uitbreiding van het RVP met beschikbare vaccins voor hepatitis A, influenza en tuberculose wordt nog niet aanbevolen. Het RVP is effectief en veilig, maar voortdurende bewaking hiervan is groot belang, omdat er regelmatig veranderingen optreden. Handhaven van de hoge vaccinatiegraad is essentieel om terugkeer van ziekten te voorkomen. Verder moet regelmatig bekeken worden of het RVP aangepast moet worden aangezien er steeds nieuwe vaccins beschikbaar komen