Early Measles Vaccination During an Outbreak in the Netherlands: Short-Term and Long-Term Decreases in Antibody Respo

Background. The majority of infants will not be protected by maternal antibodies until their first measles vaccination, between 12 and 15 months of age. This provides incentive to reduce the age at measles vaccination, but immunological consequences are insufficiently understood, and long-term effects are largely unknown. Methods. A total of 79 infants who received early measles vaccination between 6 and 12 months age and a second dose at 14 months of age were compared to 44 children in a control group who received 1 dose at 14 months of age. Measles virus–specific neutralizing antibody concentrations and avidity were determined up to 4 years of age. Results. Infants who first received measles vaccination before 12 months of age had a long-term decrease in the concentration and avidity of measles virus–specific neutralizing antibodies, compared with infants in the control group. For 11.1% of children with a first dose before 9 months of age, antibody levels at 4 years of age had dropped below the cutoff for clinical protection. Conclusions. Early measles vaccination provides immediate protection in the majority of infants but yields a long-term decrease in neutralizing antibody responses, compared to vaccination at a later age. Additional vaccination at 14 months of age does not improve this. Over the long term, this may result in an increasing number of children susceptible to measles

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

Oesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of intense research. The aim of the present study was to study the prognostic significance of Met, the hepatic growth factor (HGF) receptor and a possible target for therapy in comparison to cyclooxygenase-2 (COX-2). Tumour sections from 145 consecutive patients undergoing intentionally curative surgery for oesophageal adenocarcinoma were immunohistochemically analysed for Met and COX-2 expression. Clinicopathological data were prospectively collected for all patients. Patients with high Met expression had significantly reduced overall and disease-specific 5-year survival rates (P⩽0.001 and P⩽0.001, respectively) and were more likely to develop distant metastases (P=0.002) and local recurrences (P=0.004) compared to patients with low Met expression. High COX-2 expression tended to be correlated with poor long-term survival but this did not reach statistical significance. Expression of Met was recognised as a significant and independent prognostic factor by stage-specific analysis and multivariate analysis (relative risk=2.3; 95% CI=1.3–4.1). These findings support the importance of Met in oesophageal adenocarcinoma and support the concept of Met tyrosine kinase inhibition as (neo-) adjuvant treatment

Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: Long-term results of a randomized controlled trial

Background: This is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.Methods: This trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.Results: There were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio [HR] 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.Conclusions: Preoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC

The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC): let’s cooperate! [Commentary]

The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken

Only Moderate Intra- and Inter-observer Agreement between Radiologists and Surgeons when Grading Blunt Paediatric Hepatic Injury on CT Scan

Introduction: The American Pediatric Surgical Association developed guidelines for the management of haemodynamically stable children with hepatic or splenic injury, based on grade of injury on CF scan. This study investigated the intra- and inter-observer agreement of radiologists, paediatric surgeons, trauma surgeons and hepatobiliary surgeons when scoring liver injury based on CT scan findings. Patients and Methods: CT scans of patients with blunt abdominal trauma were independently assessed twice by a fellow and a consultant radiologist, paediatric surgeon, trauma surgeon and one consultant hepatobiliary surgeon. Reviewers were unaware of the clinical course. All scans were multislice CTs with a slice thickness of 3 mm, and both the arterial and venous phase were assessed. Injury was scored using the American Association for the Surgery of Trauma (AAST) liver injury scale. Intra-observer agreement was tested using Cohen's kappa coefficient. Inter-observer agreement was tested using Cohen's kappa for the second reading of individual observers and Spearman's rank correlation for the mean of both readings from each observer. Results: CT scans of 27 patients (11 girls and 16 boys, median age 11.7 +/- 5.2 years) were reviewed. Mean AAST grade of liver injury was 3.3 +/- 1.1 for radiologists, 2.9 +/- 1.0 for paediatric surgeons, 3.0 +/- 0.9 for trauma surgeons and 3.2 +/- 0.8 for the hepatobiliary surgeon (p=0.30) Intra-observer agreement was moderate, with kappa below 0.7 for all observers except for one of the radiologists. Inter-observer correlation using Cohen's kappa coefficient was also moderate, with kappa below 0.5. In contrast, inter-observer correlation using Spearman's test was good, suggesting that there is agreement on the general severity of injury but not on the exact grading of injury using the AAST scoring system. Conclusion: Intra-observer agreement is only moderate when assessing liver injury using the AAST grading system. Only the most experienced radiologist demonstrated good intra-observer agreement which might indicate the necessity of the presence of a senior trauma radiologist at all times. However, this is not possible in most centres. Although there was agreement concerning the general severity of injury, inter-observer agreement is also moderate. These data cast doubt on the use of the AAST liver injury score alone as a decision-making tool when assessing haemodynamically stable children with blunt hepatic injury

Paediatric Blunt Liver Trauma in a Dutch Level 1 Trauma Center

Introduction: Paediatric blunt hepatic trauma treatment is changing from operative treatment (OT) to non-operative treatment (NOT). In 2000 the American Pediatric Surgical Association has published guidelines for NOT of these injuries. Little is known about the treatment of paediatric liver trauma in the Netherlands. Patients and methods: Data of all patients aged 18 years and younger admitted to our hospital for blunt hepatic trauma in the past 18 years were retrospectively analysed using a prospective trauma registry. The mechanism Of injury, treatment, ICU admission time, total admission time, morbidity and mortality were assessed. Subsequently the group was divided into patients treated before and after 2000. Results: Eighty patients were identified: 52M, 28F with a mean age of 12 years (range 2-18). Thirty patients sustained isolated liver injury. Concomitant injuries were fractures of long bones (28), abdominal (25), chest (24) and head injuries (18). Mean ISS score was 18 (range 4-57). Mortality was 8%. Mechanisms of injury consisted of bicycle (25%), car (20%), and motorcycle accidents (15%), pedestrian hit by vehicle (15%), fall from height (14%) and accidents associated with animals (11%). Haemodynamically stable patients underwent NOT (55). 25 patients (31%) underwent a laparotomy, which in 20 cases (80%) was related to hepatic injury. Although the groups treated before and after 2000 did not differ haemodynamically on admission to hospital, a shift to NOT is evident: 24/37 (63%) patients underwent NOT before 2000 versus 38/45 (84%) after 2000 (p=0.04). Complications following NOT were rare. Late onset bleeding did not occur. Two patients developed an infected biloma, requiring a laparotomy. Mean ICU stay before 2000 was 4.2 days (range 0-25 days) and 2.6 days (range 0-17 days) after 2000. Total hospital time did not decrease: 14 days (range 1-39 days) before 2000 and 14 days (range 1-60 days) after 2000. The overall mortality was 8%. All deaths occurred in the operative group and were spread evenly over both periods. Conclusion: In blunt paediatric liver trauma, the incidence and trauma mechanism seem age-related. A shift to NOT is found in the treatment of paediatric blunt hepatic trauma. NOT is the preferred treatment for the haemodynamically stable patient. Complications are rare and the success rate is 96%. The mean ICU stay has decreased but the total admission time could possibly be shortened