The National Dutch Breast Implant Registry: user-reported experiences and importance

Background: Robust (inter-)national breast implant registries are important. For some, registries are an administrative burden, for others they represent a solution for the discussions involving breast implants. The DBIR is one of the first national, opt-out, clinical registries of breast implants, providing information for clinical auditing and product recall. Four years after its introduction, it is time to address users’ comments in order to keep improving quality of registration, and patient safety. This study assesses users’ feedback focusing on importance of registration, logistics and user experience, and areas of improvement. Methods: In May 2018, a standardized online study–specific questionnaire was sent out to all members of the Netherlands Society of Plastic Surgery. Descriptive statistics were reported in absolute frequencies and/or percentages. Results: A total of 102 members responded to the questionnaire (response rate, 24.2%). Of all respondents, 97.1% were actively registering in DBIR. Respondents rated the importance of registration in DBIR as 8.1 out of 10 points. Ninety-one respondents suggested improvements for the DBIR. All comments were related to registration convenience and provision of automatically generated data. Conclusions: Respondents believe that registration is highly important and worth the administrative burden. However, we should collectively keep improving accuracy, usability and sustainability of breast

The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3 in colorectal cancer

In gastric cancer, a new epigenetic mechanism of tumour suppressor loss has been suggested where the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is responsible for loss of expression of RUNX3. This is consistent with EZH2 upregulation in multiple cancer types being associated with poor prognosis. We investigated whether EZH2 influences the expression of RUNX3 in colorectal cancer (CRC) and whether this is independent of methylation. We determined protein and messenger RNA (mRNA) levels of EZH2 and RUNX3 and assessed RUNX3 methylation with methylation-specific polymerase chain reaction using 72 human CRCs and 8 CRC cell lines. We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation. Despite higher levels of EZH2 and lower levels of RUNX3 in CRC specimens in general, no inverse correlation between EZH2 and RUNX3 in paired samples was found arguing against a major role for histone methylation in silencing RUNX3 in CRC. Conversely, downregulation of RUNX3 mRNA in the same tumours was associated with RUNX3 DNA methylation (P < 0.05). In cell lines, knockdown of EZH2 removed the repressive chromatin marks from RUNX3 but did not result in RUNX3 re-expression. However, it prevented the re-silencing of RUNX3 after the removal of demethylating agents. In conclusion, DNA methylation is primarily responsible for the transcriptional silencing of RUNX3 in CRC, but EZH2 and histone methylation are necessary for its methylation-dependent re-silencing after the removal of demethylating agents. These results would predict that inhibitors of EZH2 and histone methylation would enhance the effects of demethylating agents in cancer therapy

Crises and collective socio-economic phenomena: simple models and challenges

Financial and economic history is strewn with bubbles and crashes, booms and busts, crises and upheavals of all sorts. Understanding the origin of these events is arguably one of the most important problems in economic theory. In this paper, we review recent efforts to include heterogeneities and interactions in models of decision. We argue that the Random Field Ising model (RFIM) indeed provides a unifying framework to account for many collective socio-economic phenomena that lead to sudden ruptures and crises. We discuss different models that can capture potentially destabilising self-referential feedback loops, induced either by herding, i.e. reference to peers, or trending, i.e. reference to the past, and account for some of the phenomenology missing in the standard models. We discuss some empirically testable predictions of these models, for example robust signatures of RFIM-like herding effects, or the logarithmic decay of spatial correlations of voting patterns. One of the most striking result, inspired by statistical physics methods, is that Adam Smith's invisible hand can badly fail at solving simple coordination problems. We also insist on the issue of time-scales, that can be extremely long in some cases, and prevent socially optimal equilibria to be reached. As a theoretical challenge, the study of so-called "detailed-balance" violating decision rules is needed to decide whether conclusions based on current models (that all assume detailed-balance) are indeed robust and generic.Comment: Review paper accepted for a special issue of J Stat Phys; several minor improvements along reviewers' comment

Identifying booms and busts in house prices under heterogeneous expectations

We introduce heterogeneous expectations in a standard housing market model linking housing rental levels to fundamental buying prices. Using quarterly data we estimate the model parameters for eight different countries, US, UK, NL, JP, CH, ES, SE and BE. We find that the data support heterogeneity in expectations, with temporary endogenous switching between fundamental mean-reverting and trend-following chartists beliefs based on their relative performance. For all countries we identify temporary house price bubbles, amplified by trend extrapolation, and crashes reinforced by fundamentalists. The qualitative predictions of such non-linear models are very different from standard linear benchmarks, with important policy implications. The fundamental price becomes unstable, e.g. when the interest rate is set too low or mortgage tax deductions too high, giving rise to multiple non-fundamental equilibria and/or global instability

Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Effect of Total Breast Reconstruction with Autologous Fat Transfer Using an Expansion Device vs Implants on Quality of Life among Patients with Breast Cancer:A Randomized Clinical Trial

Importance: There is a need for a new, less invasive breast reconstruction option for patients who undergo mastectomy in their breast cancer treatment. Objective: To investigate quality of life (QoL) among patients undergoing a new breast reconstruction technique, autologous fat transfer (AFT), compared with that among patients undergoing implant-based reconstruction (IBR). Design, Setting, and Participants: The BREAST trial was a randomized clinical trial conducted between November 2, 2015, and October 31, 2021, performed in 7 hospitals across the Netherlands. Follow-up was 12 months. Referrals could be obtained from general practitioners and all departments from participating or nonparticipating hospitals. The patients with breast cancer who had undergone mastectomy and were seeking breast reconstruction were screened for eligibility (radiotherapy history and physique) by participating plastic surgeons. Patients receiving postmastectomy radiotherapy were excluded. Interventions: Breast reconstruction with AFT plus expansion or 2-phased IBR. Randomization was done in a 1:1 ratio. Main Outcomes and Measures: The statistical analysis was performed per protocol. The predefined primary outcome was QoL at 12 months after final surgery. This was measured by the BREAST-Q questionnaire, a validated breast reconstruction surgery questionnaire. Questions on the BREAST-Q questionnaire are scored from 0 to 100, with a higher score indicating greater satisfaction or better QoL (depending on the scale). Secondary outcomes were breast volume and the safety and efficacy of the techniques. Results: A total of 193 female patients (mean [SD] age, 49.2 [10.6] years) 18 years or older who desired breast reconstruction were included, of whom 91 patients in the AFT group (mean [SD] age, 49.3 [10.3] years) and 80 in the IBR group (mean age, 49.1 [11.0] years) received the allocated intervention. In total, 64 women in the AFT group and 68 women in the IBR group completed follow-up. In the IBR group, 18 patients dropped out mainly due to their aversion to implant use while in the AFT group 6 patients ended their treatment prematurely because of the burden (that is, the treatment being too heavy or tiring). The BREAST-Q scores were higher in the AFT group in all 5 domains and significantly higher in 3: satisfaction with breasts (difference, 9.9; P =.002), physical well-being: chest (difference; 7.6; P =.007), and satisfaction with outcome (difference, 7.6; P =.04). Linear mixed-effects regression analysis showed that QoL change over time was dependent on the treatment group in favor of AFT. The mean (SD) breast volume achieved differed between the groups (AFT: 300.3 [111.4] mL; IBR: 384.1 [86.6] mL). No differences in oncological serious adverse events were found. Conclusions and Relevance: This randomized clinical trial found higher QoL and an increase in QoL scores over time in the AFT group compared with the IBR group. No evidence was found that AFT was unsafe. This is encouraging news since it provides a third, less invasive reconstruction option for patients with breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02339779

Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI).

OBJECTIVE: To assess whether a combination of adalimumab and superior to adalimumab alone in the treatment of perianal fistulising disease (CD). DESIGN: Randomised, double-blind, placebo controlled trial Dutch hospitals. In total, 76 CD patients with active perianal disease were enrolled. After adalimumab induction therapy (160/80 mg patients received 40 mg every other week together with ciprofloxacin 500 placebo twice daily for 12 weeks. After 12 weeks, adalimumab was Follow-up was 24 weeks. Primary endpoint (clinical response) was defined reduction of fistulas from baseline to week 12. Secondary endpoints remission (closure of all fistulas), Perianal Crohn's Disease Activity Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Clinical response was observed in 71% of treated with adalimumab plus ciprofloxacin and in 47% treated with plus placebo (p=0.047). Likewise, remission rate at week 12 was higher (p=0.009) in the combination group (65%) compared with adalimumab placebo (33%). Combination treatment was associated with a higher mean change and mean IBDQ change at week 12 (p=0.005 and p=0.009, week 24, no difference in clinical response between the two treatment observed (p=0.22). No difference in safety issues was observed. Combination therapy of adalimumab and ciprofloxacin is more effective adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained. TRIAL REGISTRATION: Identifier: NCT00736983