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INTRODUCTION: Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking.METHODS: We systematically searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach.RESULTS: Seven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52-0.85; P = 0.001; I 2 = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53-1.12; P = 0.18; I 2 = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44-0.85; P = 0.004; I 2 = 59%). The GRADE certainty of evidence was high for the outcome of OS. CONCLUSIONS: Neoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer.

BACKGROUND: The aim of this study was to determine pancreatic surgery specific short- and long-term complications of pediatric, adolescent and young adult (PAYA) patients who underwent pancreatic resection, as compared to a comparator cohort of adults.METHODS: A nationwide retrospective cohort study was performed in PAYA patients who underwent pancreatic resection between 2007 and 2016. PAYA was defined as all patients RESULTS: A total of 230 patients were included in the PAYA cohort (112 distal pancreatectomies, 99 pancreatoduodenectomies), and 2526 patients in the comparator cohort. For pancreatoduodenectomy, severe morbidity (29.3% vs. 28.6%; P = 0.881), in-hospital mortality (1% vs. 4%; P = 0.179) and textbook outcome (62% vs. 58%; P = 0.572) were comparable between the PAYA and the comparator cohort. These outcomes were also similar for distal pancreatectomy. After pancreatoduodenectomy, new-onset diabetes mellitus (8% vs. 16%) and exocrine pancreatic insufficiency (27% vs. 73%) were lower in the PAYA cohort when compared to adult literature.CONCLUSION: Pancreatic surgery-specific complications were comparable with patients ≥40 years. Development of endocrine and exocrine insufficiency in PAYA patients who underwent pancreatoduodenectomy, however, was substantially lower compared to adult literature.

Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

Introduction Coronavirus disease 2019 (COVID-19) has a high burden on the healthcare system. Prediction models may assist in triaging patients. We aimed to assess the value of several prediction models in COVID-19 patients in the emergency department (ED). Methods In this retrospective study, ED patients with COVID-19 were included. Prediction models were selected based on their feasibility. Primary outcome was 30-day mortality, secondary outcomes were 14-day mortality and a composite outcome of 30-day mortality and admission to medium care unit (MCU) or intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). Results We included 403 patients. Thirty-day mortality was 23.6%, 14-day mortality was 19.1%, 66 patients (16.4%) were admitted to ICU, 48 patients (11.9%) to MCU, and 152 patients (37.7%) met the composite endpoint. Eleven prediction models were included. The RISE UP score and 4 C mortality scores showed very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84, 95% CI 0.79-0.88 for both), significantly higher than that of the other models. Conclusion The RISE UP score and 4 C mortality score can be used to recognise patients at high risk for poor outcome and may assist in guiding decision-making and allocating resources.

The prognosis of kidney transplant recipients (KTR) with vascular calcification (VC) in the aorto-iliac arteries is unclear. We performed a systematic review and meta-analysis to investigate their survival outcomes. Studies from January 1st, 2000 until March 5th, 2019 were included. Outcomes for meta-analysis were patient survival, (death-censored) graft survival and delayed graft function (DGF). Twenty-one studies were identified, eight provided data for meta-analysis. KTR with VC had a significantly increased mortality risk [1-year: risk ratio (RR) 2.19 (1.39–3.44), 5-year: RR 2.28 (1.86–2.79)]. The risk of 1-year graft loss was three times higher in recipients with VC [RR 3.15 (1.30–7.64)]. The risk of graft loss censored for death [1-year: RR 2.26 (0.58–2.73), 3-year: RR 2.19 (0.49–9.82)] and the risk of DGF (RR 1.24, 95% CI 0.98–1.58) were not statistically different. The quality of the evidence was rated as very low. To conclude, the presence of VC was associated with an increased mortality risk and risk of graft loss. In this small sample size, no statistical significant association between VC and DGF or risk of death-censored graft loss could be demonstrated. For interpretation of the outcomes, the quality and sample size of the evidence should be taken into consideration.

OBJECTIVES: The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS). METHODS: This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010-2017). In addition, a systematic literature search was performed. RESULTS: In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized. CONCLUSIONS: Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized.

TPS4171 Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials (including the Dutch PREOPANC trial) have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including gemcitabine-based chemoradiotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether total neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine (i.e. the intervention arm of the PREOPANC trial) in patients with resectable or borderline resectable pancreatic cancer. Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) added during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients, assuming an accrual period of 3 years and 1.5 years follow-up. Between June 2018 and January 2021, 375 patients were enrolled in 20 centers in the Netherlands and accrual is complete. Final analyses are expected at the end of 2022. Netherlands Trial Register: NL7094. Clinical trial information: NL7094.

Background and Aims B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study aimed to identify minimal residual autoimmunity (MRA) in the B-cell compartment of AAV patients treated with RTX. Method EuroFlow-based highly-sensitive flow cytometry (HSFC) was employed to study B-cell and plasma cell (PC) subsets in-depth in AAV patients before and after RTX treatment. Additionally, peripheral blood mononuclear cells (PBMCs) of these RTX-treated AAV patients were cultured and in vitro stimulated with CpG, IL-2, and IL-21 to induce antibody-secreting cells (ASC). (ANCA)-IgG was measured in these supernatants by ELISA. Results By employing EuroFlow-based HSFC, we detected circulating CD19+ B-cells at all timepoints after RTX treatment, in contrast to conventional low-sensitive flow cytometry. Pre-germinal center (Pre-GC) B-cells, memory B-cells and CD20+CD138− plasmablasts (PBs) were rapidly and strongly reduced, while CD20−CD138− PrePC and CD20-CD138+ mature (m)PCs were reduced slower and remained detectable. Both memory B-cells and CD20− PCs remained detectable after RTX. Serum ANCA-IgG decreased significantly upon RTX. Changes in ANCA levels strongly correlated with changes in naive, switched CD27+ and CD27− (double-negative) memory B-cells, but not with plasma cells. Lastly, we demonstrated in vitro ANCA production by AAV PBMCs, 24 and 48 weeks after RTX treatment reflecting MRA in the memory compartment of AAV patients. Conclusion We demonstrated that RTX induced strong reductions in circulating B-cells, but never resulted in complete B-cell depletion. Despite strongly reduced B-cell numbers after RTX, ANCA-specific memory B-cells were still detectable in AAV patients. Thus, MRA is identifiable in AAV and can provide a potential novel approach in personalizing RTX treatment in AAV patients.

ObjectiveTo mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed RISE UP score has very good discriminatory value with respect to short-term mortality in older patients in the emergency department (ED). It consists of six items: age, abnormal vital signs, albumin, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and bilirubin. We hypothesized that the RISE UP score could have discriminatory value with regard to 30-day mortality in ED patients with COVID-19.SettingTwo EDs of the Zuyderland Medical Centre (MC), secondary care hospital in the Netherlands.ParticipantsThe study sample consisted of 642 adult ED patients diagnosed with COVID-19 between March 3rd until May 25th 2020. Inclusion criteria were: 1) admission to the hospital with symptoms suggestive of COVID-19, and 2) positive result of the polymerase chain reaction (PCR), or (very) high suspicion of COVID-19 according to the chest computed tomography (CT) scan.OutcomePrimary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU).ResultsWithin 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value with respect to 30-day mortality (AUC 0.77, 95% CI 0.73-0.81), and to the composite outcome (AUC 0.72, 95% CI 0.68-0.76). Patients with RISE UP scores below 10% (121 patients) had favourable outcome (0% mortality and 5% ICU admissions). Patients with a RISE UP score above 30% (221 patients) were at high risk of adverse outcome (46.6% mortality and 19% ICU admissions).ConclusionThe RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome, and may help guiding decision-making and allocating healthcare resources.

IntroductionCoronavirus disease 2019 (COVID-19) has a high burden on the healthcare system and demands information on the outcome early after admission to the emergency department (ED). Previously developed prediction models may assist in triaging patients when allocating healthcare resources. We aimed to assess the value of several prediction models when applied to COVID-19 patients in the ED.MethodsAll consecutive COVID-19 patients who visited the ED of a combined secondary/tertiary care center were included. Prediction models were selected based on their feasibility. The primary outcome was 30-day mortality, secondary outcomes were 14-day mortality, and a composite outcome of 30-day mortality and admission to the medium care unit (MCU) or the intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC).ResultsA total of 403 ED patients were diagnosed with COVID-19. Within 30 days, 95 patients died (23.6%), 14-day mortality was 19.1%. Forty-eight patients (11.9%) were admitted to the MCU, 66 patients (16.4%) to the ICU and 152 patients (37.7%) met the composite endpoint. Eleven models were included: RISE UP score, 4C mortality score, CURB-65, MEWS, REMS, abbMEDS, SOFA, APACHE II, CALL score, ACP index and Host risk factor score. The RISE UP score and 4C mortality score showed a very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84 respectively, 95% CI 0.79-0.88 for both), for 14-day mortality (AUC 0.83, 95% CI: 0.79-0.88, for both) and for the composite outcome (AUC 0.79 and 0.77 respectively, 95% CI 0.75-0.84). The discriminatory performance of the RISE UP score and 4C mortality score was significantly higher compared to that of the other models.ConclusionThe RISE UP score and 4C mortality score have good discriminatory performance in predicting adverse outcome in ED patients with COVID-19. These prediction models can be used to recognize patients at high risk for short-term poor outcome and may assist in guiding clinical decision-making and allocating healthcare resources.

Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. We present a case of a 26-year-old man who presented to our hospital after intentionally ingesting 30 tablets of Triumeq. An intoxication with Triumeq can lead to several side effects. An overdose of abacavir and lamivudine can cause mitochondrial toxicity and lactic acidosis. An intoxication with dolutegravir appears to be relatively harmless. As Triumeq will be used on a regular basis as treatment for patients with HIV-1 infection, these intoxications are expected to be encountered more often.

Introduction/Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) to guide physicians in clinical management. Methodology Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3–37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth (figure 1). Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n=62) and advanced stage (n=15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n=62, figure 2), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n=45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusion Survival of patients diagnosed with early stage HL during pregnancy appears not statistically different from matched non-pregnant controls, however future prospective research is necessary to investigate the efficacy of chemotherapy during pregnancy. Awareness of complications as preterm delivery and low birth weight is important. Disclosure This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. We are grateful to the Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) for their support. FA is senior clinical investigator of the F.W.O. MJH was supported by Charles University research project Progres Q28 and Q34 and by grant MH CZ - DRO (‘Kralovske Vinohrady University Hospital - FNKV, 00064173’). The funding sources did not influence study design. There are no conflicting interests to declare.

Background. Patients with end-stage renal disease and aortoiliac stenosis are often considered ineligible for kidney transplantation, although kidney transplantation has been acknowledged as the best therapy for end-stage renal disease. The clinical outcomes of kidney transplantation in patients with aortoiliac stenosis are not well-studied. This study aimed to assess the impact of aortoiliac stenosis on graft and patient survival. Methods. This retrospective, single-center study included kidney transplant recipients transplanted between January 1, 2000, and December 31, 2016, who received contrast-enhanced imaging. Patients with aortoiliac stenosis were classified using the Trans-Atlantic Inter-Society Consensus (TASC) II classification and categorized as having TASC II A/B lesions or having TASC II C/D lesions. Patients without aortoiliac stenosis were functioning as controls. Results. A total number of 374 patients was included in this study (n = 88 with TASC II lesions, n = 286 as controls). Death-censored graft survival was similar to the controls. Patient and uncensored graft survival was decreased in patients with TASC II C/D lesions (log-rank test P < 0.001). Patients with TASC II C/D lesions had a higher risk of 90-day mortality (hazard ratio, 3.96; 95% confidence interval, 1.12-14.04). In multivariable analysis, having a TASC II C/D lesion was an independent risk factor for mortality (hazard ratio, 3.25; 95% confidence interval, 1.87-5.67; P < 0.001). Having any TASC II lesion was not a risk factor for graft loss (overall P = 0.282). Conclusions. Kidney transplantation in patients with TASC II A/B is feasible and safe without increased risk of perioperative mortality. TASC II C/D decreases patient survival. Death-censored graft survival is unaffected.

Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P

Oral presentation Eliminating Occupational Disease: Translating Research into Action, EPICOH 2017, EPICOH 2017, 28–31 August 2017, Edinburgh, UK. Objective To identify the main determinants of occupational diseases at both the individual and the population level. Methods This study used data from the Dutch National Working Conditions Survey (NWCS 2014; occupational disease confirmed by a doctor, self-reported, employees). Multivariate regression analyses were performed to assess the independent association at the individual level (OR) between each determinant and the presence of at least one occupational disease. Additionally, the Population Attributable Risk (PAR) was calculated for each determinant in order to assess the risk at the population level as well. Results The top three determinants that may be influenced and also contributed most to musculoskeletal occupational diseases, were the same at the individual and the population level: ‘Repetitive movements‘ (PAR=40.0%; OR=2.25), ‘Working in uncomfortable positions/bad posture‘ (PAR=17.7%; OR=1.62), and ‘High job demands‘ (PAR=17.6%; OR=1.57). Determinants that contributed most to psychological occupational diseases were also the same on the individual and population level: ‘Low engagement‘ (PAR=33.6%; OR=2.27), ‘Conflict with supervisor‘ (PAR=16.7%; OR=1.51), and ‘High emotional demands‘ (PAR=14.4%; OR=2.85). Conclusion These determinants may be influenced through education, measures and/or policies at the workplace or on higher levels, in order to decrease the prevalence of occupational diseases in the working population.

Introduction Female sex workers (FSW) are at risk for HPV-induced diseases but are currently not targeted by the HPV vaccination program in the Netherlands. We explored the determinants of their intention to get vaccinated against HPV in case vaccination would be offered to them in the near future. Methods In 2016, FSW aged >18 years having an STI consultation with the Prostitution and Health Centre (P and G292) in Amsterdam, either at the clinic or at their working location, were invited to complete a questionnaire assessing the socio-psychological determinants of their HPV vaccination intention (scale ranging from −3 to +3). Determinants of HPV vaccination intention were assessed with uni- and multivariable linear regression. Additionally, we explored the effect of out-of-pocket payment on intention. Results Between May and September 2016, 293 FSW participated; 98 (34%) worked in clubs/private houses/massage salons, 111 (38%) worked at ‘prostitution windows’, and 81 (28%) worked as escorts or from home. The median age was 29 years (IQR 25–37). HPV vaccination intention was relatively high (mean 2.0; 95% CI:1.8–2.2). In multivariable analysis attitude (β=0.6; 95% CI:0.5–0.7), descriptive norm (β=0.3; 95% CI:0.2–0.4), self-efficacy (β=0.2; 95% CI:0.1–0.3), beliefs (β=0.1; 95% CI:0.0–0.2) and anticipated regret (β=0.1; 95% CI:0.0–0.2) were the strongest predictors of HPV vaccination intention. Demographic variables did not improve the multivariable regression model. The explained variance in the model (R2) was 0.54. HPV vaccination intention decreased significantly when vaccination would require out-of-pocket payment (€50 mean: 1.2 (95%CI: 0.8–1.7); €100 mean: 1.6 (95%CI: 1.1–2.0); € 200 mean: 1.0 (95%CI: 0.5–1.5); € 350 mean: 0.2 (95%CI: −0.2–0.7). Conclusion HPV vaccination intention among FSW in Amsterdam appears to be very high. The included socio-psychological factors explained most of the variance in HPV vaccination intention among FSW. Out-of-pocket payment had a significant negative effect on HPV vaccination intention.

Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) registered by the International Network on Cancer, Infertility and Pregnancy (INCIP) to guide physicians in clinical management. Methods Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the INCIP registry. For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3 – 37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth. Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n = 62) and advanced stage (n = 15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n = 62), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n = 45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusions Although further prospective research on the efficacy of chemotherapy during pregnancy is necessary, survival of patients diagnosed with early stage HL during pregnancy appears not to be statistically different from matched non-pregnant controls, Awareness of complications as preterm delivery and low birth weight is important in this population. Clinical trial identification NTC00330447. Legal entity responsible for the study The authors. Funding European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 647047 Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) Charles University Research Project Progres Q28 and Q34 and by grant MH CZ - DRO ("Kralovske Vinohrady University Hospital - FNKV, 00064173"). Disclosure All authors have declared no conflicts of interest.

Introduction Uptake is an important determinant of the effectiveness of population-based screening. Uptake of colorectal cancer (CRC) screening generally remains sub-optimal. Aim To determine factors influencing the decision whether to participate or not among individuals invited for faecal occult blood test (FOBT) or flexible sigmoidoscopy (FS) screening. Methods A questionnaire was sent to a stratified random sample of individuals aged 50–74, previously invited for a randomised CRC screening trial offering FOBT or FS, and a reference group from the same population not previously invited (screening naive group). The questionnaire assessed reasons for (non)-participation, individuals’ characteristics associated with participation, knowledge, attitudes and level of informed choice. Results The response rate was 75% ( n = 341/452) for CRC screening participants, 21% ( n = 676/3212) for non-participants and 38% ( n = 192/500) for screening-naive individuals. The main reasons for FOBT and FS participation were acquiring certainty about CRC presence and possible early CRC detection. Anticipated regret and positive attitudes towards CRC screening were strong predictors of actual participation and intention to participate in a next round. The main reason for non-participation in FOBT screening was lack of abdominal complaints. Non-participation in FS screening was additionally influenced by worries about burden. Eighty-one percent of participants and 12% of non-participants made an informed choice on participation. Conclusion Only 12% of non-participants made an informed choice not to participate. These results imply that governments and/or organizations offering screening should focus on adequately informing and educating target populations about the harms and benefits of CRC screening. This may impact uptake of CRC screening.

Time limitations and unwanted health effects may act as barriers to participation in colorectal cancer (CRC) screening. The aim of the study was to measure the time requirements and health effects of colonoscopy and computed tomography colonography (CTC) screening. This was a prospective diary study in a consecutive sample within a randomized controlled CRC screening trial, comparing primary colonoscopy and CTC screening for average-risk individuals aged 50 - 74 years. The diary ended when all screening-related complaints had passed. The diary was returned by 75 % (241/322) of colonoscopy and 75 % (127/170) of CTC screenees. The median interval between leaving home and returning from the examination was longer for colonoscopy (4 hours and 18 minutes [4:18], interquartile range [IQR] 3:30 - 5:00) than for CTC (2:30 hours, IQR 2:06 - 3:00; P < 0.001). Similarly, the time to return to routine activities was longer after colonoscopy (3:54 hours, IQR 1:48 - 15:00) than after CTC (1:36 hours, IQR 0:54 - 4:42). The duration of screening-related symptoms after the examination was shorter for colonoscopy (11:00 hours, IQR 2:54 - 20:00) than for CTC (22:00 hours; IQR 5:30 - 47:00; P < 0.001). Abdominal complaints were reported more frequently after CTC. Anxiety, pain, and quality of life worsened during the screening process, with no differences between the two examinations. Compared with colonoscopy, CTC screening required less time and allowed screenees to return to their daily activities more quickly. In contrast, CTC was associated with a twofold longer duration of screening-related symptoms. Feelings of anxiety, pain, and quality of life scores were similar during colonoscopy and CTC screening. These results should be incorporated into cost-effectiveness analyses of CRC screening techniques

BACKGROUND: Little is known about the effect of participating in a colorectal cancer (CRC) screening programme on quality of life (QOL), neither for participants with a negative nor for those with a positive test result. These findings, however, are important to evaluate the impact of CRC screening. METHODS: Participants from CRC screening trials were sent a questionnaire, which included validated measures on generic health-related QOL, generic anxiety and screen-specific anxiety. Both faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) participants, either with negative or positive test results, were addressed. RESULTS: The response rate was 73% (1289 out of 1772) for FIT and 78% (536 out of 689) for FS participants, with mean ages varying from 63-66 years. Positive FIT participants had worse physical (PCS-12, 47.1 vs 48.3, P = 0.02), but equal mental QOL scores (MCS-12, 51.1 vs 51.6, P = 0.26). Positive and negative FS participants had similar QOL scores. Both FIT and FS participants with a positive test result reported more screen-specific anxiety than negative FIT and FS participants. Positive and n CONCLUSION: Our findings indicate that the burden of participating in CRC screening may be limited. Conducting a prospective study to confirm these results is recommended. British Journal of Cancer (2012) 107, 1295-1301. doi:10.1038/bjc.2012.386 www.bjcancer.com Published online 6 September 2012 (C) 2012 Cancer Research UK

An 86-year-old man presented with severe pain in the upper abdomen along with fever. On physical examination, we found an arterial blood pressure of 84/43 mm Hg, a heart rate of 80 bpm and a temperature of 38.3°C. The abdomen was painful and peristalsis was absent. Empiric antibiotic therapy for sepsis was started with amoxicillin/clavulanate and gentamicin. CT scan of the abdomen revealed an emphysematous cholecystitis. Percutaneous ultrasound-guided cholecystostomy was applied. Bile cultures revealed Clostridium perfringens. Emphysematous cholecystitis is a life-threatening form of acute cholecystitis that occurs as a consequence of ischaemic injury to the gallbladder, followed by translocation of gas-forming bacteria (ie, C. perfringens, Escherichia coli, Klebsiella and Streptococci). The mortality associated with emphysematous cholecystitis is higher than in non-emphysematous cholecystitis (15% vs 4%). Therefore, early diagnosis with radiological imaging is of vital importance.2016 BMJ Publishing Group Ltd.

This final report for the SERDP project MM-1414 covers research results accomplished since the projects inception in 2005. The basic premise of the project is the theoretical understanding achieved through SERDP SEED project UX-1285, which predicted that spatially variable frequency-dependent susceptibility in soils hosting UXO can produce strong background response in both electromagnetic and magnetic data. Such responses can mask UXO signatures or produce false alarms. Improving UXO detection and discrimination in such strongly magnetic environments requires the characterization and removal of these responses. The overall objective has therefore been to understand and characterize the spatial variation and frequency dependence of soil magnetic susceptibility so effective means can be developed for characterizing and removing soil responses. We have modified and implemented two filtering approaches for UXO magnetic data in order to separate the response of strong magnetic geology from UXO anomalies. The two methods are an iterative Wiener filter approach, and a wavelet filter approach. Finally, we have modified an approach, originally developed under a separate project, for automatic detection of UXO anomalies in total-field magnetic data. The method is based on the concept of structural index (SI). We further developed the method by implementing it in combination with pre-processed data using the iterative Wiener and wavelet filters for removing strong geologic responses in the magnetic data. The goal of this component has been to better understand and develop practical procedures, appropriate to a geologic setting, for integrating new filtering technologies with recently developed methodologies for detecting UXO in magnetic environments. In parallel to development and implementation of filters for UXO magnetic data sets, MM-1414 utilized data inversion simulations to quantify the effectiveness of different processing techniques.

BACKGROUND: Guidelines underline the role of individual preferences in the selection of a screening test, as insufficient evidence is available to recommend one screening test over another. We conducted a study to determine the preferences of individuals and to predict uptake for colorectal cancer (CRC) screening programmes using various screening tests. METHODS: A discrete choice experiment (DCE) questionnaire was distributed among naive subjects, yet to be screened, and previously screened subjects, aged 50-75 years. Subjects were asked to choose between scenarios on the basis of faecal occult blood test (FOBT), flexible sigmoidoscopy (FS), total colonoscopy (TC) with various test-specific screening intervals and mortality reductions, and no screening (opt-out). RESULTS: In total, 489 out of 1498 (33%) screening-naive subjects (52% male; mean age +/- s.d. 61 +/- 7 years) and 545 out of 769 (71%) previously screened subjects (52% male; mean age +/- s.d. 61 +/- 6 years) returned the questionnaire. The type of screening test, screening interval, and risk reduction of CRC-related mortality influenced subjects' preferences (all P

Introduction: In many countries uptake of colorectal cancer (CRC) screening remains low. Aim: To assess how procedural characteristics of CRC screening programmes determine preferences for participation and how individuals weigh these against the perceived benefits from participation in CRC screening. Methods: A discrete choice experiment was conducted among subjects in the age group of 50-75 years, including both screening-naive subjects and participants of a CRC screening programme. Subjects were asked on their preferences for aspects of CRC screening programmes using scenarios based on pain, risk of complications, screening location, preparation, duration of procedure, screening interval and risk reduction of CRC-related death. Results: The response was 31% (156/500) for screening-naive and 57% (124/210) for CRC screening participants. All aspects proved to significantly influence the respondents' preferences. For both groups combined, respondents required an additional relative risk reduction of CRC-related death by a screening programme of 1% for every additional 10 min of duration, 5% in order to expose themselves to a small risk of complications, 10% to accept mild pain, 10% to undergo preparation with an enema, 12% to use 0.751 of oral preparation combined with 12 h fasting and 32% to use an extensive bowel preparation. Screening intervals shorter than 10 years were significantly preferred to a 10-year screening interval. Conclusion: This study shows that especially type of bowel preparation, risk reduction of CRC related death and length of screening interval influence CRC screening preferences. Furthermore, improving awareness on CRC mortality reduction by CRC screening may increase uptake. (C) 2009 Elsevier Ltd. All rights reserved.

Magnetic properties of soils have been highlighted as a primary detrimental environmental effect on the performance of geophysical systems for detection of unexploded ordnance (UXO) and mine targets. A recent workshop at Cranfield University, U.K., aimed to identify knowledge gaps related to soil magnetism. Eight invited speakers from multidisciplinary areas provided briefings on state‐of‐the‐art research linked to soil magnetism and geophysical sensing. Contributions from other participants provided additional insights from a range of disciplines through case studies and applications. The workshop included break‐out sessions to identify current gaps in knowledge and to determine priority areas for investment in research to further developments in UXO and mine detection in magnetic soil environments. Key recommendations for future research investments have been grouped in categories including soils, theory and modeling, instrumentation, and communication.

Recent studies have demonstrated the potentially serious impact of magnetic soils on the detection of buried objects such as land mines and unexploded ordnance (UXO) using magnetometers and electromagnetic inductions sensors, two methods that are routinely used in clearance operations. Magnetic soils can cause both equipment malfunctions and an increase in false alarms due to the presence of anomalies that have a geologic or pedogenic origin. To improve the discrimination performance of land mine and UXO detection sensors, there is a need for a better understanding of the natural variability in magnetic characteristics of soils. This research addressed this need by develop a conceptual model for the prediction of magnetic characteristics of soils developed on a wide range of geological parent materials, of different ages, and in diverse climatological environments. The research provides the Army with a new approach to the non-intrusive geophysical characterization of subsurface materials and their spatial distribution; the prediction of location, frequency, and scale of subsurface heterogeneity. The conceptual model that we have developed will allow for a better prediction of sensor capabilities in many iron-oxide containing field soils.

Electromagnetic sensors such as ground penetrating radar and electromagnetic induction sensors are among the most widely used methods for the detection of buried land mines and unexploded ordnance. However, the performance of these sensors depends on the dielectric properties of the soil, which in turn are related to soil properties such as texture, bulk density, and water content. To predict the performance of electromagnetic sensors it is common to estimate the soil dielectric properties using models. However, the wide variety of available models, each with its own characteristics, makes it difficult to select the appropriate one for each occasion. In this paper we present an overview of the available methods, ranging from phenomenological Cole-Cole and Debye models to volume-based dielectric mixing models, and (semi-) empirical pedotransfer functions.