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Objectives:\ud We aimed to review how ‘Risk of Bias In Non-randomized Studies–of Interventions’ (ROBINS-I), a Cochrane risk of bias assessment tool, has been used in recent systematic reviews.\ud \ud Study Design and Setting:\ud Database and citation searches were conducted in March 2020 to identify recently published reviews using ROBINS-I. Reported ROBINS-I assessments and data on how ROBINS-I was used were extracted from each review. Methodological quality of reviews was assessed using AMSTAR 2 (‘A MeaSurement Tool to Assess systematic Reviews’).\ud \ud Results:\ud Of 181 hits, 124 reviews were included. Risk of bias was serious/critical in 54% of assessments on average, most commonly due to confounding. Quality of reviews was mostly low, and modifications and incorrect use of ROBINS-I were common, with 20% reviews modifying the rating scale, 20% understating overall risk of bias, and 19% including critical-risk of bias studies in evidence synthesis. Poorly conducted reviews were more likely to report low/moderate risk of bias (predicted probability 57% [95% CI: 47–67] in critically low-quality reviews, 31% [19–46] in high/moderate-quality reviews).\ud \ud Conclusion:\ud Low-quality reviews frequently apply ROBINS-I incorrectly, and may thus inappropriately include or give too much weight to uncertain evidence. Readers should be aware that such problems can lead to incorrect conclusions in reviews.

Many interventions that may have large impacts on health and health inequalities, such as social and public health policies and health system reforms, are not amenable to evaluation using randomised controlled trials. The United Kingdom Medical Research Council's guidance on the evaluation of natural experiments draws attention to the need for ingenuity to identify interventions which can be robustly studied as they occur, and without experimental manipulation. Studies of intervention withdrawal may usefully widen the range of interventions that can be evaluated, allowing some interventions and policies, such as those that have developed piecemeal over a long period, to be evaluated for the first time. In particular, sudden removal may allow a more robust assessment of an intervention's long-term impact by minimising ‘learning effects’. Interpreting changes that follow withdrawal as evidence of the impact of an intervention assumes that the effect is reversible and this assumption must be carefully justified. Otherwise, withdrawal-based studies suffer similar threats to validity as intervention studies. These threats should be addressed using recognised approaches, including appropriate choice of comparators, detailed understanding of the change processes at work, careful specification of research questions, and the use of falsification tests and other methods for strengthening causal attribution.\ud \ud Evaluating intervention withdrawal provides opportunities to answer important questions about effectiveness of population health interventions, and to study the social determinants of health. Researchers, policymakers and practitioners should be alert to the opportunities provided by the withdrawal of interventions, but also aware of the pitfalls.

Background Liver resections (LRs) are performed with increasing frequency for metastatic disease. To minimize the risk of postoperative complications, a period of 6 weeks between the last dose of chemotherapy and LR is typically recommended. The current study examines postoperative morbidity and mortality following LR in patients who received chemotherapy within 30 days prior to LR. Methods The merged 2005–2007 National Surgical Quality Improvement Program (NSQIP) Participant Use File was queried for perioperative risk factors, laboratory values and postoperative occurrences or complications in patients who underwent LR. Patients were grouped according to their receipt or non-receipt of chemotherapy within 30 days prior to LR and major postoperative complications. Results A total of 2331 patients underwent LR; 2147 did not receive chemotherapy within 30 days of resection (No Chemo group) and 184 received chemotherapy within 30 days prior to resection (Chemo group). The groups were similar with regard to preoperative co-morbidities and operative factors. The median NSQIP statistically computed morbidity probability was similar between the groups (No Chemo 0.32, Chemo 0.34; P = 0.07), whereas the median mortality probability was higher in the Chemo group (0.02) than the No Chemo group (0.014; P = 0.001). Thirty-day survival was similar between the two groups (No Chemo 97%, Chemo 98%; P = 0.44). Major complication rates did not differ between the groups (No Chemo 20%, Chemo 18%; P = 0.51). Factors associated with major complications in the Chemo group included: extent of resection; intraoperative transfusion; preoperative ascites, and preoperative haematocrit. Discussion Major morbidity was not increased in Chemo patients. The strongest predictors of major postoperative complications in the Chemo group were extent of resection and intraoperative red cell transfusion. Although the NSQIP dataset does not include data about tumour type or chemotherapy regimen, these data suggest that LR may be safely performed within 30 days of chemotherapy, thereby minimizing the length of time during which patients do not receive systemic treatment.

s / Pancreatology 13 (2013) S2–S98 S64 the test cohorts and lack of a standard reference method, more studies are needed to conclude that the trypsinmethod is superior. We are developing a reference method using confocal microscopy. PII-36 Abstract id: 17. Effect of osteocalcin on human beta cell proliferation and function and its role on insulin secretion Anita Kaw, Daniel Fraga, Craig Fischer. The Methodist Hospital Research Institute, Houston, Texas, United States Introduction: Osteocalcin, a hormone produced by bone cells, has been found to increase insulin production, enhance insulin sensitivity, and promote b-cell proliferation in mouse models, however most mouse studies do not reliably affect humans in the same manner. Aims: This study sought to confirm the effect of osteocalcin on human b-cell proliferation and function and its role, if any, on insulin secretion. Materials & methods: Three variants of osteocalcin extracted and purified from bovine tibial cortical bone were investigated: osteocalcin (OC), decarboxylated osteocalcin (D-OC), and osteocalcin hexapeptide (HOC) were utilized in conjunction with a well-established islet model. Protocol included human pancreatic islet isolation from brain dead donors, islet cell culture in Memphis serum free mediumwith heparin, assessment of islet viability with flow cytometry, insulin secretion and content in vitro with western blot analysis and analysis of cellular composition by immunofluorescence. Results: Our results indicate that after 7 days in culture all three types of osteocalcin improved insulin-content and b-cell proliferation of glucose-stimulated islets, with D-OC showing the most significant and dose-dependent effect. The greatest effect on insulin enhancement was noted at the earliest time point (7 days), and this effect progressively deteriorated at later time points, reflecting perhaps senescence in our culture while apoptosis was not impacted by either osteocalcin or time in culture. Conclusion: Our findings indicate that osteocalcin or one of its variants may be utilized in patients whose disease conditions show a progressive loss of b-cell mass and function namely type 2 and, in some cases type 1 diabetes. PII-37 Abstract id: 226. Impact of pancreatic enzymes on blood glucose and insulin release in a porcine model Liudmyla Lozinska, Olena Prykhod’ko, Katarzyna Szwiec, Bj€ orn Westr€ om, Stefan Pierzynowski. Lund University, Dept Biology, Sweden Introduction: Exocrine pancreatic insufficiency (EPI) induced in young pigs by pancreatic duct ligation (PDL) results in growth arrest and a decreased ability to retain/assimilate nutrients. Aims: The aim of the study was to explore the effects of pancreatic enzyme replacement therapy (PERT) on glucose utilization and insulin secretion in this model. Materials & methods: Five EPI pigs and six control pigs were studied andmeal (MGTT), oral (OGTT), and i.v. glucose tolerance tests (IVGTT) were performed, either with or without PERT (Creon 10,000). Blood glucose was measured with a glucose-meter and plasma insulin using an ELISA kit. Results: The MGTT resulted in increased plasma glucose levels similar to that in the controls, but only a negligible increase in insulin levels. The MGTT following PERT, resulted in a prolonged increase in blood glucose (above those in controls) and insulin (below that in controls) levels. The OGTT, both with and without PERT, caused a prolonged increase in blood glucose levels compared to controls. A parallel increase in insulin levels were observed, however the increase was smaller in comparison to the controls. PERT before IVGTT, accelerated the elimination of glucose and at the same time lowered the insulin levels, with a shift in the curve peak towards that observed in the controls. Conclusion: In conclusion, the data indicates that pancreatic enzymes not only affect the availability of glucose from the food, but also affect the post-prandial insulin response in line with the incretin concept and thus suggests a factor released in response to PERT which affects glucose utilization. PII-38 Abstract id: 177. Pancreatic and pancreatic-like enzymes decrease insulin secretion together with an enhanced insulin efficiency or provoke insulin-independent glucose utilisation Olena Prykhodko, Liudmyla Lozinska, Katarzyna Szwiec, Adam Lada, Olexandr Fedkiv, Bj€ orn Westr€ om, Stefan Pierzynowski. Dept of Biology, Lund University, Sweden Introduction: The role of the exocrine pancreas in food digestion is well-studied but its’ possible (para-digestive) effects on insulin release and glucose tolerance has received less attention. Aims: We aimed to study the effects of pancreatic enzyme supplementation on blood glucose and plasma insulin in normal pigs. Materials & methods: Twelve pigs, 2.5 months old, were fasted overnight and then administered either porcine enzymes (Creon 10 000) or a mixture of pancreatic-like enzymes of microbial origin (PLEM), or empty capsules as a placebo. After 1h an intravenous glucose tolerance test (IVGTT) was performed (by infusion of 1g glucose/kg, using 50% solution). Repeated blood samples were taken and blood glucose was measured with a glucose-meter and plasma insulin levels with an ELISA-kit. Results: Blood glucose decreased 1h after enzyme administration (12.8% for Creon, 15.5% for PLEM, p