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Introduction: In Dutch Youth Health Care (YHC), child development is investigated with the Dutch Development Instrument (DDI; in Dutch: Van Wiechenonderzoek). Reference values from the DDI only indicate that at least 90% of children achieve a milestone at the recommended age. The YHC-professional is not aware whether this percentage is 90% or, for example, 99%. Aim of this study is to evaluate the reference values of the DDI in a Dutch population, and to investigate whether there are differences between boys and girls. Methods: Anonymized DDI results, collected in the period 2011-2013 by the YHC in The Hague, have been compared with results from previous studies. In addition, it was investigated whether there are relevant (≥5%) differences between boys and girls. Results: The percentage of children achieving a milestone at a recommended age varied from 81%-100%. About a quarter of the milestones showed a relevant difference between boys and girls. In most cases, the percentage of girls who achieved a milestone was higher than the percentage of boys. Conclusion: There is a large variation in the percentage of children achieving a milestone at a recommended age. It is recommended to make age-specific (and sometimes sex-specific) reference values available to YHC-professionals.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940–0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81–0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Background: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is Methods: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF).Results: Among 1402 included patients, 433 patients with a drain fluid amylase level of 5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p Conclusion: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative. (C) 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4+ and CD8+ T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8+ T-cell differentiation. Patients with MetS had significant lower CD4+ RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4+ T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

Background Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Background Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ-failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection.Methods This is a nationwide stepped-wedge, cluster randomized, superiority trial, designed in adherence to the CONSORT guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence- and consensus based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. postpancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow-up will be up to 90 days after pancreatic resection.Discussion It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice.

Huntington disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion in the HTT gene. Various HD animal models have been generated to mimic the motor, cognitive and neuropsychiatric disturbances that affect HD patients. Reproducing disease phenotypes within these models is essential to identify reliable readouts for therapy studies. We validated behavioral phenotypes shown earlier by other research groups in the BACHD rat model, using both previously applied and novel tests for motor, cognitive and anxiety-like behaviors. We first confirmed known BACHD rats' phenotypes in rotarod, open field (OF) and elevated plus maze (EPM) tests. We then assessed the reproducibility of key phenotypes in the model using new tests: cliff hanging, passive avoidance (PA), Morris water maze (MWM), light dark box and light spot tests. We confirmed impaired motor coordination in the rotarod test and reduced activity in the OF. In line with earlier results in BACHD rats using different tests, we showed impaired reversal learning in MWM and decreased anxiety-like behavior with the light spot test supporting the validity of BACHD rats as a model of HD. Results in the EPM, light dark box, cliff hanging and PA tests did not confirm earlier findings. This may depend on phenotype inconsistencies or rather be related to differences in environmental variables, test typology, experimental settings, animal age and chosen behavioral parameters.

Additional file 1. SPIRIT 2013 Checklist for the PACAP-1 trial.

Background After neoadjuvant chemoradiotherapy (nCRT) plus surgery for oesophageal cancer, 29 per cent of patients have a pathologically complete response in the resection specimen. Active surveillance after nCRT (instead of standard oesophagectomy) may improve health-related quality of life (HRQoL), but patients need to undergo frequent diagnostic tests and it is unknown whether survival is worse than that after standard oesophagectomy. Factors that influence patients' preferences, and trade-offs that patients are willing to make in their choice between surgery and active surveillance were investigated here. Methods A prospective discrete-choice experiment was conducted. Patients with oesophageal cancer completed questionnaires 4–6 weeks after nCRT, before surgery. Patients' preferences were quantified using scenarios based on five aspects: 5-year overall survival, short-term HRQoL, long-term HRQoL, the risk that oesophagectomy is still necessary, and the frequency of clinical examinations using endoscopy and PET–CT. Panel latent class analysis was used. Results Some 100 of 104 patients (96·2 per cent) responded. All aspects, except the frequency of clinical examinations, influenced patients' preferences. Five-year overall survival, the chance that oesophagectomy is still necessary and long-term HRQoL were the most important attributes. On average, based on calculation of the indifference point between standard surgery and active surveillance, patients were willing to trade off 16 per cent 5-year overall survival to reduce the risk that oesophagectomy is necessary from 100 per cent (standard surgery) to 35 per cent (active surveillance). Conclusion Patients are willing to trade off substantial 5-year survival to achieve a reduction in the risk that oesophagectomy is necessary.

Background Measuring anxiety in a reliable manner is essential for behavioural phenotyping of rodent models such as the rat model for Spinocerebellar ataxia type 17 (SCA17) where anxiety is reported in patients. An automated tool for assessing anxiety within the home cage can minimize human intervention, stress of handling, transportation and novelty. New method We applied the anxiety test “light spot” (LS) (white led directed at the food-hopper) to our transgenic SCA17 rat model in the PhenoTyper 4500 ® to extend the knowledge of this automated tool for behavioural phenotyping and to verify an anxiety-like phenotype at three different disease stages for use in future therapeutic studies. Results Locomotor activity was increased in SCA17 rats at 6 and 9 months during the first 15 min of the LS, potentially reflecting increased risk assessment. Both genotypes responded to the test with lower duration in the LS zone and higher time spent inside the shelter compared to baseline. Comparison with existing methods We present the first data of a rat model subjected to the LS. The LS can be considered more biologically relevant than a traditional test as it measures anxiety in a familiar situation. Conclusions The LS successfully evoked avoidance and shelter-seeking in rats. SCA17 rats showed a stronger approach-avoidance conflict reflected by increased activity in the area outside the LS. This home cage test, continuously monitoring pre- and post-effects, provides the opportunity for in-depth analysis, making it a potentially useful tool for detecting subtle or complex anxiety-related traits in rodents.

Introduction The efficacy of auditing is still a subject of debate and concerns exist whether auditing promotes risk averse behaviour of physicians. This study evaluates the achievements made in colorectal cancer surgery since the start of a national clinical audit and assesses potential signs of risk averse behaviour. Methods Data were extracted from the Dutch ColoRectal Audit (2009–2016). Trends in outcomes were evaluated by uni and multivariable analyses. Patients were stratified according to operative risks and changes in outcomes were expressed as absolute (ARR) and relative risk reduction (RRR). To assess signs of risk averse behaviour, trends in stoma construction in rectal cancer were analysed. Results Postoperative mortality decreased from 3.4% to 1.8% in colon cancer and from 2.3% to 1% in rectal cancer. Surgical and non-surgical complications increased, but with less reintervention. For colon cancer, the high-risk elderly patients had the largest ARR for complicated postoperative course (6.4%) and mortality (5.9%). The proportion of patients receiving a diverting stoma or end colostomy after a (L)AR decreased 11% and 7%, respectively. In low rectal cancer, patients increasingly received a non-diverted primary anastomosis (5.4% in 2011 and 14.4% in 2016). Conclusions No signs of risk averse behaviour was found since the start of the audit. Especially the high-risk elderly patients seem to have benefitted from improvements made in colon cancer treatment in the past 8 years. For rectal cancer, trends towards the construction of more primary anastomoses are seen. Future quality improvement measures should focus on reducing surgical and non-surgical complications.

Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia . However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms. Therefore, we assessed the ability of chronic PCP administration (3 mg/kg, 14 days) to induce short or long lasting behavioral changes in rats. Social behavior, including ultrasonic vocalizations and motivation for social contact were investigated at different time points, up to 29–36 days, after cessation of PCP treatment. During a social separation test, performed at 5 and 36 days, PCP treated rats spent less time near the divider that separates them from their familiar cage mate compared with saline (SAL) treated rats. Further, at short term, PCP was able to induce a decrease in social behavior. In contrast, at long-term, PCP treated animals spent more time in contact when exposed to an unfamiliar partner as compared to SAL treated rats. But, this difference was not observed when exposed to a familiar partner. We did not find any difference in ultrasonic vocalizations at all time points. The results of our study indicate that PCP is unable to induce overt long term deficits in social interaction behavior. Rather, it seems that PCP diminishes motivation for social contact. The long-term consequences of chronic PCP administration on social behavior in rodent models remain complex, and future studies addressing this are still needed.

Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Introduction: Locally advanced pancreatic cancer (LAPC) is found in 35% of patients with pancreatic cancer. However, these patients often have occult metastatic disease. Patients with occult metastases are unlikely to benefit from locoregional treatments. This study evaluated the yield of occult metastases during staging laparoscopy in patients with LAPC.Methods: Between January 2013 and January 2017 all patients with LAPC underwent a staging laparoscopy after a recent tri-phasic CT-scan of the chest and abdomen. Data were retrospectively reviewed from a prospectively maintained database. Univariate and multivariable logistic regression analysis was conducted to predict metastasis found at laparoscopy.Results: A total of 91 (41% male, median age 64 years) LAPC patients were included. The median time between CT-scan and staging laparoscopy was 21 days. During staging laparoscopy metastases were found in 17 patients (19%, 95% CI: 12%-28%). Seven (8%) patients had liver-only, 9 (10%) patients peritoneal-only, and 1 (1%) patient both liver and peritoneal metastases. Univariate logistic regression analysis showed that CEA (OR 1.056, 95% CI 1.007-1.107, p = 0.02) was the only preoperative predictor for occult metastases. In a multivariable logistic regression analysis of the preoperative risk factors again only CEA was an independent predictor for occult metastatic disease (p = 0.03). Patients with a CEA above 5 mu g/l. had a risk of occult metastasis of 91%. FOLFIRINOX was given to 69 (76%) of the patients with a median number of cycles of 8. Subsequent radiotherapy was given to 44 (48%) patients after the FOLFIRINOX treatment. Six (14%) patients underwent a resection after FOLFIRINOX and radiotherapy. The overall 1-year survival was 53% in patients without occult metastasis versus 29% with occult metastasis (p = 0.11). The 1-year OS for patients that completed FOLFIRINOX and radiotherapy was 84%.Conclusion: The yield of staging laparoscopy for occult intrahepatic or peritoneal metastases in patients with locally advanced pancreatic cancer was 19%. Staging laparoscopy is recomended for patients with LAPC for accurate staging to determine optimal treatment. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background An objective and automated method for assessing alterations in gait and motor coordination in different animal models is important for proper gait analysis. The CatWalk system has been used in pain research, ischemia, arthritis, spinal cord injury and some animal models for neurodegenerative diseases. New method Our goals were to obtain a comprehensive gait analysis of three different rat models and to identify which motor coordination parameters are affected and are the most suitable and sensitive to describe and detect ataxia with a secondary focus on possible training effects. Results Both static and dynamic parameters showed significant differences in all three models: enriched housed rats show higher walking and swing speed and longer stride length, ethanol-induced ataxia affects mainly the hind part of the body, and the SCA17 rats show coordination disturbances. Coordination changes were revealed only in the case of the ethanol-induced ataxia and the SCA17 rat model. Although training affected some gait parameters, it did not obscure group differences when those were present. Comparison with existing methods To our knowledge, a comparative gait assessment in rats with enriched housing conditions, ethanol-induced ataxia and SCA17 has not been presented before. Conclusions There is no gold standard for the use of CatWalk. Dependent on the specific effects expected, the protocol can be adjusted. By including all sessions in the analysis, any training effect should be detectable and the development of the performance over the sessions can provide insight in effects attributed to intervention, treatment or injury.

Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects the acute response of macrophages to biomaterials in vitro and whether this response is associated with biomarkers in blood. CD14(+) monocytes were isolated from blood from obese and age and gender matched lean persons. Monocyte subsets were determined based on CD14 and CD16 on their surface. C-reactive protein (CRP) was measured in peripheral blood. The response of monocyte-derived macrophages to polypropylene (PP), polylactic acid (PLA), polyethylene terephthalate (PET) mono filament, and PET-multifilament (mPET) in culture was based on cytokine production. More IL-6 (for PET), less CCL18 (all materials) and IL-1ra (for PLA) was produced by macrophages from obese patients than lean subjects. Body mass index, serum CRP and to a lesser extend percentages of monocyte subtypes correlated with IL-6, TNF alpha, CCL18, and IL-1ra production. Taken together, monocyte-derived macrophages of obese patients respond more pro-inflammatory and less anti-inflammatory to biomaterials than macrophages from lean subjects, depending on the material. These results are a step towards personalized medicine for the development of a model or even a blood test to decide which biomaterial might be suitable for each patient. (C) 2016 Elsevier Ltd. All rights reserved.

Introduction In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk. Methods A prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT’s plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed. Results 53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients’ characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%. Conclusions For PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated. Trial registration number: Dutch Trial Registry (NTR3142).

Introduction: The aim of this study is to provide insight in accuracy of diagnosing, current treatment and survival in patients with resectable esophageal and gastric neuroendocrine- and mixed adenoneuroendocrine carcinomas (NEC, MANEC).Methods: All patients with esophageal or gastric (MA)NEC, who underwent surgical resection between 2006 and 2016, were identified from the Dutch national registry for histo-and cytopathology (PALGA). Patients with a neuroendocrine tumor lower than grade 3 were excluded. Data on patients, treatment and outcomes were retrieved from the patient records. Diagnosis by endoscopic biopsy was compared with diagnosis by resection specimen. Kaplan Meier survival analysis was performed.Results: A total of 49 patients were identified in 25 hospitals, including 21 patients with esophageal (MA)NEC and 26 patients with gastric (MA)NEC on resection specimen. Biopsy diagnosis of (MA)NEC was correct in 23/27 patients. However, 20/47 patients with definitive diagnosis of (MA)NEC, were misdiagnosed on biopsy. Neoadjuvant therapy was administered in 13 (62%) esophageal (MA)NEC5 and 12 (46%) gastric (MA)NECs. Survival curves were similar with and without neoadjuvant therapy. One (4.8%) esophageal (MA)NEC and 4 (15%) gastric (MA)NEC5 died within 90 days postoperatively. For esophageal (MA)NEC the median overall survival (OS) after surgery was 37 months and 1-, 3- and 5-year OS were 71%, 50% and 35%, respectively. For gastric (MA)NEC, the median OS was 23 months and 1-, 3- and 5-year OS were 62%, 50% and 39%, respectively.Conclusion: Localized esophageal and gastric (MA)NEC are often misdiagnosed on endoscopic biopsies. After resection, long-term survival was achieved in respectively 35% and 39% of patients. (C) 2018 Published by Elsevier Ltd.

Background Social behavior related symptoms and sexual disturbances are frequently reported in Huntington disease (HD) patients, but scarcely studied in animal models. The BACHD rat model for HD carries the human full length mutated HTT with 97 CAG-CAA repeats and reproduces several HD-like features. Aims This study aims to characterize multiple aspects of social and sexual behavior in BACHD rats. Methods/techniques Rats were subjected to social interaction test, three chamber social test and mating test. While the social interaction test was applied longitudinally, three chamber and mating tests were administered in different age cohorts. Results/outcome BACHD rats showed a mild impairment in preference for novelty at 7 months as well as changes in different parameters of social interaction that were detectable by 2 months. Transgenic rats showed also increased sexual performance at the age of 3 months and a normalization of most sexual parameters at 7 months. Conclusions Our results indicate disturbed social and sexual phenotypes in the BACHD rat model. Relating these behavioral phenotypes to neurobiological alterations in relevant brain areas will help to clarify their nature and translatability to the human condition.

Background Tranexamic acid reduces blood loss associated with various surgical procedures. Postoperative bleeding caused by dissection or bleeding of the enteric staple lines is a well-known complication following bariatric surgery. Reoperation in order to restore hemostasis is frequently necessary (up to 2.5% in literature). The effect of conservative therapy using tranexamic acid for postoperative hemorrhage after bariatric surgery is still very much a novel technique. The aim is to present our results (reoperation rate and thrombo-embolic complication rate) of tranexamic acid therapy for postoperative bleeding after bariatric surgery in comparison to those in existing literature. Methods We retrospectively reviewed 1388 patients who underwent bariatric surgery (laparoscopic gastric bypass or laparoscopic gastric sleeve). Use of tranexamic acid, reoperation rate, transfusion rate and rate of thrombo-embolic complications were reviewed. Results Forty-five of 1388 (3.2%) total patients experienced significant hemorrhage after bariatric surgery. Tranexamic acid was administered in 44 of these patients. A failure of the treatment with tranexamic acid was observed in four patients. The incidence of reoperation was 0.4% for the entire population. No thrombo-embolic complications were registered for patients receiving tranexamic acid. Conclusion These findings suggest that the administration of tranexamic acid appears to be safe in reducing the reoperation rate for bleeding after bariatric surgery.

Rationale: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype.Objective: The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping.Methods: Wild-type (WT) and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance.Results: BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected.Conclusions: The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.

To investigate the extent to which 0-15-year-old children in The Hague are complying with Dutch Health Council vitamin D supplementation advice, and whether there are differences between ethnic groups.Cross-sectional study.From November 2014 up to and including October 2015, The Hague organisations for youth health care (YHC) have recorded intake of vitamin D supplementation during standard consultations. YHC 0-4 recorded whether vitamin D supplementation intake was sufficient. YHC 4-18 recorded whether vitamin D supplementation was recommended for the child (aged 4 and older, in case of coloured skin or insufficient time spent outdoors) and whether this child took sufficient vitamin D supplementation. Information on ethnic origin was taken from the digital YHC records.A large majority of those aged 0-3 received sufficient vitamin D supplementation. Intake was unknown for most 4-year-olds. Vitamin D supplementation was recommended for half of the children aged 5 or older, but a substantial number of them received no (50%) or insufficient (18%) supplementation. Among children for whom extra vitamin D was recommended, there was little difference in vitamin D use between ethnic groups.The Dutch Health Council recommendation on vitamin D supplementation is intended to prevent vitamin D deficiencies, but there is insufficient compliance by children in The Hague, especially those aged five and older.

Abscess formation and perforation are complications of acute appendicitis that lead to localized or generalized peritonitis. The long-term implications of complicated appendectomy remain largely unknown. In the present study, it was investigated whether patients with complicated appendicitis experienced more abdominal complaints after long-term follow-up when compared to uncomplicated cases. In addition, the influence of operation technique (open versus laparoscopic) was studied. A retrospective analysis of 1,481 appendectomies for acute appendicitis was performed in two centers from January 2000 until January 2006. Demographic data, operative reports, intraoperatively adhesions and complications, abdominal pain, and satisfaction were monitored. In total, 1,433 patients were invited to fill out a questionnaire with a median follow-up of 7.1 years. Questionnaires of 526 (37 %) patients were suitable for analysis. Perforation, abdominal abscesses, or adhesions at initial operation did not result in more abdominal complaints when compared to appendectomy for uncomplicated acute appendicitis. Additionally, no significant differences in abdominal complaints were seen between laparoscopic and open techniques. In conclusion, the results of our study show that after follow-up of 7 years, the incidence of abdominal complaints was not influenced by operative technique or whether acute appendicitis was complicated or not. This finding does not support a causative role for adhesions with regard to chronic abdominal complaints. Our data enables surgeons to inform their patients about the long-term results of appendectomy, whether it was complicated or not.

Contains fulltext : 169896.pdf (Publisher’s version ) (Closed access) Anxiety as a common feature of several neurodegenerative/polyglutamine diseases is an important aspect for the face validity of an animal model for Spinocerebellar Ataxia type 17 (SCA17). Risk assessment and anxiety-like traits were characterised in 3-6-9 months old rats of a transgenic model for SCA17 using the standard behavioural test elevated plus maze. In addition, c-Fos immunostainings in the basolateral amygdala evaluated neuronal activation in correlation to the behavioural responses. The most prominent behavioural effect was a higher level of risk assessment in the transgenic rats. In addition, an increase in anxiety-related behaviour in these rats was found. Although the EPM caused no overall effect on c-Fos expression, a negative correlation with the anxiety-like behavioural response was observed. Our results suggest that the SCA17 rat model displays an anxious phenotype already at 3 months of age resembling the generalized anxiety in early symptomatic SCA17 patients, thus confirming the validity of this rat model.

Background Treatment of perforated diverticulitis depends on disease severity classified according to Hinchey’s preoperative classification. This study assessed the accuracy of preoperative staging of perforated diverticulitis by computerized tomography (CT) scanning. Methods All patients who presented with perforated diverticulitis between 1999 and 2009 in two teaching hospitals of Rotterdam, the Netherlands, and in addition had a preoperative CT scan within 24 h before emergency surgery were included. Two radiologists reviewed all CT scans and were asked to classify the severity of the disease according to the Hinchey classification. The CT classification was compared to Hinchey’s classification at surgery. Results Seventy-five patients were included, 48 of whom (64 %) were classified Hinchey 3 or 4 perforated diverticulitis during surgery. The positive predictive value of preoperative CT scanning for different stages of perforated diverticulitis ranged from 45 to 89 %, and accuracy was between 71 and 92 %. The combination of a large amount of free intra-abdominal air and fluid was strongly associated with Hinchey 3 or 4 and therefore represented a reliable indicator for required surgical treatment. Conclusions The accuracy of predicting Hinchey’s classification by preoperative CT scanning is not very high. Nonetheless, free intra-abdominal air in combination with diffuse fluid is a reliable indication for surgery as it is strongly associated with perforated diverticulitis with generalized peritonitis. In 42 % of cases, Hinchey 3 perforated diverticulitis is falsely classified as Hinchey 1 or 2 by CT scanning.

Background Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. Objective This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Methods Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. Results In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats seemed to show a mild deficit in preference for social novelty, but no changes in social interest. Molecular analyses revealed that BACHD animals exposed to the social interaction test displayed decreased mRNA levels of the total form of BDNF in ventral striatum and unaltered striatal expression of D1 and D2 dopamine receptors. Conclusions Taken together, these results indicate deficits in several parameters representative of sociability. Altered BDNF expression in the ventral striatum may contribute to the deficits in sociability in 8 months old BACHD rats. These data support the validity of the BACHD rat model in mimicking features of certain social deficits that could be relevant to symptoms in patients.

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

Chronic smoking adversely affects peripheral vasculature. The aim of the present study was to investigate the effect of chronic cigarette smoking on rectal microvascular blood flow. Rectal mucosal blood flow (MBF) was measured in 80 subjects (44 smokers and 36 non-smokers). The MBF was measured in the four quadrants of the rectum by laser Doppler flowmetry. Rectal perfusion was found to be significantly lower in posterior midline compared to the other sites. In chronic smokers the observed MBF measured at the posterior and ventral sites was significantly lower compared to non-smokers (P = 0.04 and P = 0.03, respectively). Our results suggest that rectal mucosal blood flow is reduced in chronic smokers.

Perineal wound complications are frequently observed after abdominoperineal resection (APR) for rectal cancer, especially in preoperatively irradiated patients. This is the first study to investigate whether local application of gentamicin-impregnated collagen fleece reduces deep perineal wound infection after APR for rectal cancer following short-term radiotherapy.Between 2003 and 2007, a consecutive series of 40 patients underwent an APR for rectal cancer after short-course radiotherapy in our hospital. Of these patients, 19 received supplementary application of three reabsorbable gentamicin-impregnated collagen fleece sponges into the sacral cavity before closure of the perineum (group A), and 21 patients underwent primary closure of the perineal wound and served as a control group (group B). All patients received sacral drainage. A superficial perineal wound infection was defined as cellulitis with no evidence of deep tissue infection. A deep perineal wound infection was defined as skin and subcutaneous tissue breakdown with infection extending deep into the subcutaneous tissue or a wound abscess.The two groups were comparable regarding age, sex, tumour stage and level of the tumour. No postoperative mortality was observed in either group. Primary wound healing occurred in 16 patients (84%) in the gentamicin group and 9 patients (43%%) in the control group (p=0.01). The incidences of superficial perineal wound complications were 11% (two patients) in group A who received local application of gentamicin and 29% (six patients) in group B (p=0.15). Six patients (29%) in group B developed a deep infection or wound abscess, resulting in full dehiscence of the wound and sacral cavity. This devastating complication occurred in only one patient (5%) in group A (p=0.05). In most patients deep perineal wound infection was treated with vacuum therapy or drainage. The mean hospital stay of the gentamicin group was 15 days and of the control group 25 days (p=0.04).Based on the results of this study, we recommend local application of gentamicin in the sacral cavity in patients who undergo abdominoperineal resection after shortterm radiotherapy.