Does preoperative multidisciplinary team assessment of high-risk patients improve the safety and outcomes of patients undergoing surgery?

BACKGROUND: International guidelines recommend preoperative multidisciplinary team (MDT) assessment for high-risk surgical patients. Preoperative MDT meetings can help to improve surgical care, but there is little evidence on whether they improve patient outcomes. METHODS: This paper aims to share our experience of MDT meetings for high-risk surgical patients to underline their added value to the current standard of care. An observational study of a retrospective cohort of preoperative high-risk MDT meetings of a tertiary referral hospital between January 2015 and December 2020. For 249 patients the outcomes preoperative data, MDT decisions, and patient outcomes were collected from electronic health records. MAIN RESULTS: A total of 249 patients were discussed at high-risk MDT meetings. Most of the patients (97%) were assessed as having an American Society of Anesthesiology score ≥ 3, and 219 (88%) had a European Society of Cardiology and European Society of Anaesthesiology risk score of intermediate or high. After MDT assessment, 154 (62%) were directly approved for surgery, and 39 (16%) were considered ineligible for surgery. The remaining 56 (23%) patients underwent additional assessments before reconsideration at a high-risk MDT meeting. The main reason for patients being discussed at the high-risk MDT meeting was to assess the risk-benefit ratio of surgery. Ultimately, 184 (74%) patients underwent surgery. Of the operated patients, 122 (66%) did not have a major complication in the postoperative period, and 149 patients (81%) were alive after one year. CONCLUSIONS: This cohort study shows the vulnerability and complexity of high-risk patients but also shows that the use of an MDT assessment contributes too improved peri- and postoperative treatment strategies in high-risk patients. Most patients underwent surgery after careful risk assessment and, if deemed necessary, preoperative and perioperative treatment optimization to reduce their risk.

Predicting response to neoadjuvant chemotherapy with liquid biopsies and multiparametric MRI in patients with breast cancer.

Accurate prediction of response to neoadjuvant chemotherapy (NAC) can help tailor treatment to individual patients' needs. Little is known about the combination of liquid biopsies and computer extracted features from multiparametric magnetic resonance imaging (MRI) for the prediction of NAC response in breast cancer. Here, we report on a prospective study with the aim to explore the predictive potential of this combination in adjunct to standard clinical and pathological information before, during and after NAC. The study was performed in four Dutch hospitals. Patients without metastases treated with NAC underwent 3 T multiparametric MRI scans before, during and after NAC. Liquid biopsies were obtained before every chemotherapy cycle and before surgery. Prediction models were developed using penalized linear regression to forecast residual cancer burden after NAC and evaluated for pathologic complete response (pCR) using leave-one-out-cross-validation (LOOCV). Sixty-one patients were included. Twenty-three patients (38%) achieved pCR. Most prediction models yielded the highest estimated LOOCV area under the curve (AUC) at the post-treatment timepoint. A clinical-only model including tumor grade, nodal status and receptor subtype yielded an estimated LOOCV AUC for pCR of 0.76, which increased to 0.82 by incorporating post-treatment radiological MRI assessment (i.e., the "clinical-radiological" model). The estimated LOOCV AUC was 0.84 after incorporation of computer-extracted MRI features, and 0.85 when liquid biopsy information was added instead of the radiological MRI assessment. Adding liquid biopsy information to the clinical-radiological resulted in an estimated LOOCV AUC of 0.86. In conclusion, inclusion of liquid biopsy-derived markers in clinical-radiological prediction models may have potential to improve prediction of pCR after NAC in breast cancer.

Abdominal pain in patients with inflammatory bowel disease in remission: A prospective study on contributing factors.

BACKGROUND: Abdominal pain is highly prevalent in patients with inflammatory bowel disease (IBD) in remission, but the aetiology is incompletely understood. AIM: To investigate the association of clinical, lifestyle and psychosocial factors with abdominal pain in patients with IBD in remission. METHODS: We performed a prospective multicentre study enrolling consecutive patients with IBD. Data were collected between 1 January 2020 and 1 July 2021, using myIBDcoach, an established remote monitoring platform for IBD. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as abdominal pain score ≥3 (0-10 NRS) on ≥1/3 of all assessments, combined with faecal calprotectin <150 µg/g in 90 days around periodic assessments. Disease activity, lifestyle and psychosocial factors were assessed every 1-3 months during 18 months. Using linear mixed models, the association of these factors with abdominal pain over time was analysed. RESULTS: We included 559 patients, of whom 429 (76.7%) remained in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterised by female sex, younger age, higher BMI, and shorter disease duration. They reported more often or higher levels of stress, fatigue, depressive and anxiety symptoms, and life events (all p < 0.001). In the multivariable analysis, sex, disease entity, fatigue, depressive symptoms and life events were associated with abdominal pain over time (all p < 0.05). CONCLUSION: In this cohort of patients with IBD in remission, abdominal pain was common and associated with psychosocial factors. A more holistic treatment approach for patients with IBD suffering from abdominal pain may improve quality of care and subjective wellbeing.

Good manufacturing practice production of CD34+ progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia.

Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34+ hematopoietic stem and progenitor cells (HSPC). This manufacturing process combines amongst others IL15 and IL12 and the aryl hydrocarbon receptor antagonist StemRegenin-1 (SR1) to generate a consistent and active NK cell product that fits the requirements for NK cell immunotherapy well. The cell culture protocol was first optimized to generate NK cells with required expansion and differentiation capacity in GMP-compliant closed system cell culture bags. In addition, phenotype, antitumor potency, proliferative and metabolic capacity were evaluated to characterize the HSPC-NK product. Subsequently, seven batches were manufactured for qualification of the process. All seven runs demonstrated consistent results for proliferation, differentiation and antitumor potency, and preliminary specifications for the investigational medicinal product for early clinical phase trials were set. This GMP-compliant manufacturing process for HSPC-NK cells (named RNK001 cells) is used to produce NK cell batches applied in the clinical trial 'Infusion of ex vivo-generated allogeneic natural killer cells in combination with subcutaneous IL2 in patients with acute myeloid leukemia' approved by the Dutch Ethics Committee (EudraCT 2019-001929-27).

Methods for think-aloud interviews in health-related resource-use research: the PECUNIA RUM instrument.

BACKGROUND: The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent's perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap. METHODS: Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A 'before the interview' (including translation, recruitment, training), Part B 'during the interview' (including setting, opening, completing the instrument, open-ended questions, closing), and part C 'after the interview' (including transcription and data analysis, trustworthiness). CONCLUSIONS: This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.

How to collaborate for health throughout the project timeline - a longitudinal study reflecting on implemented strategies in three projects for a healthy living environment.

BACKGROUND: When improving the health of local and regional populations, cross-sector collaboration between different policy domains, non-governmental organisations and citizens themselves is needed. Previously, enabling factors and strategies have been identified to improve cross-sector collaboration for health. However, few longitudinal studies have been conducted to understand how the implementation of strategies for cross-sector collaboration changes throughout the collaboration process. The aim of this study is therefore to learn more about the different strategies that were implemented throughout three cross-sector collaboration projects for a healthy living environment. METHODS: The realist evaluation approach was used to understand how the implemented strategies worked, in which context, why and with what outcomes. Project partners were asked to reflect on their implemented strategies at two different moments in the project timelines, and quarterly updates with project leaders were held. In addition two reference panels were organised for data triangulation. RESULTS: Three key insights for successful cross-sector collaboration throughout projects for a healthy living environment were identified, namely 1. Investing in trust among the partners and faith in the project has a positive influence on continuing the collaboration throughout the project; 2. Making stakeholders actively participate throughout the project requires additional strategies after the onset of the project, and 3. Defining roles, tasks, and other prerequisites at the start of the project helps in pursuing the project over time, but needs re-examination throughout the project. These key insights were based on multiple examples of implemented strategies, linked to context, mechanisms and outcomes. CONCLUSIONS: This study shows the different strategies that can be employed as the collaboration in projects for a healthy living environment progresses. We found that 'trust' does not merely include the relationships built between the partners, but at the onset of projects can also be based on faith in the project itself. In addition, as it can be difficult to foresee the right investments and strategies at the onset of the project, frequent reflection moments to choose fitting strategies might benefit regional partners in their cross-sector collaboration for health.

The role of a simple questionnaire predicting treatment success in children with ACNES.

BACKGROUND: Some children with chronic abdominal wall pain or groin pain do not have an inguinal hernia but suffer from anterior cutaneous nerve entrapment syndrome (ACNES). Diagnosing ACNES is challenging, especially in children as a diagnostic gold standard is lacking. A paediatric questionnaire containing 17 simple items was earlier found to discriminate between abdominal pain due or ACNES or IBS. Scores range from 0 points (ACNES very unlikely) to 17 points (ACNES very likely). The present study investigates whether this 17-item questionnaire predicted treatment success in children receiving therapy for ACNES. METHODS: Children < 18 years who presented in a single institute between February 2016 and October 2021 with symptoms and signs suggestive of ACNES completed the questionnaire before intake and treatment. Treatment success after 6-8 weeks was defined as self-reported 'pain-free' (group 1), ' > 50% less pain' (group 2) and ' < 50% less pain' (group 3). Group differences regarding sex, age, BMI, symptoms duration and questionnaire scores were analysed. RESULTS: Data of 145 children (female 78%, mean age 14.7 ± 2.3 years, mean BMI 21.1 ± 3.9) were analysed. All children received a diagnostic trigger point injection using an anaesthetic agent, and 75.5% underwent subsequent surgery for untractable pain. The three groups were comparable regarding sex distribution, age, BMI and symptoms duration. In addition, questionnaire scores were not different (group 1: n = 89, mean score 13.4 ± 2.7, group 2: n = 24, 13.4 ± 2.3 and group 3: n = 32, 13.0 ± 2.7, p > 0.05). CONCLUSIONS: Treatment success was attained in 78% of children undergoing surgery for ACNES. A simple questionnaire scoring items associated with abdominal pain did not predict treatment success.

International comparability of reference unit costs of education services: when harmonizing methodology is not enough (PECUNIA project).

BACKGROUND: Health problems can lead to costs in the education sector. However, these costs are rarely incorporated in health economic evaluations due to the lack of reference unit costs (RUCs), cost per unit of service, of education services and of validated methods to obtain them. In this study, a standardized unit cost calculation tool developed in the PECUNIA project, the PECUNIA RUC Template for services, was applied to calculate the RUCs of selected education services in five European countries. METHODS: The RUCs of special education services and of educational therapy were calculated using the information collected via an exploratory gray literature search and contact with service providers. RESULTS: The RUCs of special education services ranged from €55 to €189 per school day. The RUCs of educational therapy ranged from €6 to €25 per contact and from €5 to €35 per day. Variation was observed in the type of input data and measurement unit, among other. DISCUSSION: The tool helped reduce variability in the RUCs related to costing methodology and gain insights into other aspects that contribute to the variability (e.g. data availability). Further research and efforts to generate high quality input data are required to reduce the variability of the RUCs.

Role Of Ovarian Metastases In Colorectal Cancer (ROMIC): a Dutch study protocol to evaluate the effect of prophylactic salpingo-oophorectomy in postmenopausal women.

BACKGROUND: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients. METHODS: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy. DISCUSSION: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC. TRIAL REGISTRATION: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 . PROTOCOL VERSION: 1.0, date 2021 June 8.

MRI to assess response after neoadjuvant chemotherapy in breast cancer subtypes: a systematic review and meta-analysis.

This meta-analysis aimed to estimate and compare sensitivity, specificity, positive- (PPV) and negative predictive value (NPV) of magnetic resonance imaging (MRI) for predicting pathological complete remission (pCR) after neoadjuvant chemotherapy (NAC) in patients with early-stage breast cancer. We stratified for molecular subtype by immunohistochemistry (IHC) and explored the impact of other factors. Two researchers systematically searched PUBMED and EMBASE to select relevant studies and extract data. For meta-analysis of sensitivity and specificity, we used bivariate random-effects models. Twenty-six included studies contained 4497 patients. There was a significant impact of IHC subtype on post-NAC MRI accuracy (p = 0.0082) for pCR. The pooled sensitivity was 0.67 [95% CI 0.58-0.74] for the HR-/HER2-, 0.65 [95% CI 0.56-0.73] for the HR-/HER2+, 0.55 [95% CI 0.45-0.64] for the HR+/HER2- and 0.60 [95% CI 0.50-0.70] for the HR+/HER2+ subtype. The pooled specificity was 0.85 [95% CI 0.81-0.88] for the HR-/HER2-, 0.81 [95% CI 0.74-0.86] for the HR-/HER2+, 0.88[95% CI 0.84-0.91] for the HR+/HER2- and 0.74 [95% CI 0.63-0.83] for the HR+/HER2+ subtype. The PPV was highest in the HR-/HER2- subtype and lowest in the HR+/HER2- subtype. MRI field strength of 3.0 T was associated with a higher sensitivity compared to 1.5 T (p = 0.00063). The accuracy of MRI for predicting pCR depends on molecular subtype, which should be taken into account in clinical practice. Higher MRI field strength positively impacts accuracy. When intervention trials based on MRI response evaluation are designed, the impact of IHC subtype and field strength on MR accuracy should be considered.

Breast cancer patient-reported outcome of factors influencing cosmetic satisfaction after breast-conserving therapy.

BACKGROUND: The aim of this study was to investigate which factors patients considered to be important for determining the degree of cosmetic satisfaction with regards to perceived body image after previous breast-conserving therapy (BCT). METHODS: Outcomes considered relevant by the patients were first identified using interviews. A questionnaire based on this group input was then devised and added to the physician-based Sneeuw questionnaire. Next, a quantitative study using this questionnaire was conducted in Dutch patients treated at least 6 months earlier for (non-) invasive breast cancer by BCT. Exclusion criteria were: previous mastectomy or BCT of the contralateral breast, BCT with nipple resection, metastatic disease, local recurrence or (previous) plastic breast surgery. Descriptive statistics were used throughout. RESULTS: A total of 149 patients (aged 36-87 years) completed the questionnaire. From this focus group input, the top three factors in overall importance (important or very important) for satisfaction were: 'wearability of bra' (67%), 'breast sensitivity' (59%) and 'asymmetry' (51%). Younger patients (< 55 years) considered 'breast size' to be most important, whereas 'wearability of bra' was most frequently reported by older patients (> 55 years). Time since BCT did not significantly influence the rating of relevant factors. CONCLUSION: Patients consider 'wearability of bra', 'breast sensitivity' and 'asymmetry' as the most important factors when assessing their satisfaction with regards to cosmetic outcome and body image. These factors should be addressed in routine clinical practice during (pre) counseling.

Factors related to patient-reported cosmetic outcome after breast-conserving therapy for breast cancer.

BACKGROUND: Multiple factors can affect cosmetic outcome after breast-conserving therapy. We investigated which combination of factors could optimally predict patient reported cosmetic outcome. METHODS AND MATERIALS: Dutch patients treated with BCT between 2008 and 2013 were retrospectively analysed. Demographics, tumour characteristics, and treatment-related factors were obtained from available digital medical records. Patients were asked to indicate their degree of cosmetic satisfaction using the Harvard scale. Both univariable and multivariable logistic regression analyses were performed to create a prediction model. RESULTS: The present study based on 220 patients shows that univariable analysis radiotherapy boost (OR 4.01 [1.85-8.70], p ≤ 0.001) and adjuvant chemotherapy (OR 2.67 [1.45-4.92], p = 0.002) were significantly associated with unsatisfactory cosmetic outcome. In multivariable analyses, only a radiotherapy boost remained significantly associated (OR 4.08 [1.76-9.49], p = 0.001) with poor cosmetic outcome, while adjuvant chemotherapy was no longer associated with it (OR 1.61 [0.81-3.24), p = 0.18). These two factors, together with tumour histology and lymph node staging, showed the highest predictive values, although the predictive property of the overall model was limited (AUC = 0.69). CONCLUSION: In the present study, a variety of factors is explored. However, a radiotherapy boost was the only factor that was independently associated with a poor cosmetic outcome after BCT. This finding can be used for counselling in daily clinical practice. Creation of a prediction model will require further investigation.

Metabolic syndrome; associations with adverse outcome after colorectal surgery. A systematic review and meta-analysis.

BACKGROUND: Increasing evidence shows that patients with Metabolic Syndrome (MetS) are at risk for adverse outcome after abdominal surgery. The aim of this study was to investigate the impact of MetS and preoperative hyperglycemia, as an individual component of MetS, on adverse outcome after colorectal surgery. METHODS: A literature review was systematically performed according to the PRISMA guidelines. Inclusion criteria were observational studies that evaluated the relationship between MetS or preoperative hyperglycemia and outcomes after colorectal surgery (i.e. any complication, severe complication defined as Clavien-Dindo grade ≥ III, anastomotic leakage, surgical site infection, mortality and length of stay). RESULTS: Six studies (246.383 patients) evaluated MetS and eight studies (9.534 patients) reported on hyperglycemia. Incidence rates of MetS varied widely from 7% to 68% across studies. Meta-analysis showed that patients with MetS are more likely to develop severe complications than those without MetS (RR 1.62, 95% CI 1.01-2.59). Moreover, a non-significant trend toward increased risks for any complication (RR 1.35, 95% CI 0.91-2.00), anastomotic leakage (RR 1.67, 95% CI 0.47-5.93) and mortality (RR 1.19, 95% CI 1.00-1.43) was found. Furthermore, preoperative hyperglycemia was associated with an increased risk of surgical site infection (RR 1.35, 95% CI 1.01-1.81). CONCLUSION: MetS seem to have a negative impact on adverse outcome after colorectal surgery. As a result of few studies meeting inclusion criteria and substantial heterogeneity, evidence is not conclusive. Future prospective observational studies should improve the amount and quality in order to verify current results.

An economical and highly adaptable optogenetics system for individual and population-level manipulation of Caenorhabditis elegans.

BACKGROUND: Optogenetics allows the experimental manipulation of excitable cells by a light stimulus without the need for technically challenging and invasive procedures. The high degree of spatial, temporal, and intensity control that can be achieved with a light stimulus, combined with cell type-specific expression of light-sensitive ion channels, enables highly specific and precise stimulation of excitable cells. Optogenetic tools have therefore revolutionized the study of neuronal circuits in a number of models, including Caenorhabditis elegans. Despite the existence of several optogenetic systems that allow spatial and temporal photoactivation of light-sensitive actuators in C. elegans, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, modular, and adjustable optogenetics device for use on different microscopes and worm trackers, which we called the OptoArm. RESULTS: The OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles, and light color. We demonstrate OptoArm's power in a population-based multi-parameter study on the contributions of motor circuit cells to age-related motility decline. We found that individual components of the neuromuscular system display different rates of age-dependent deterioration. The functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit ageing. CONCLUSION: We have assembled an economical, reliable, and highly adaptable optogenetics system which can be deployed to address diverse biological questions. We provide a detailed description of the construction as well as technical and biological validation of our set-up. Importantly, use of the OptoArm is not limited to C. elegans and may benefit studies in multiple model organisms, making optogenetics more accessible to the broader research community.

Glassy dynamics of a binary Voronoi fluid: a mode-coupling analysis.

The binary Voronoi mixture is a fluid model whose interactions are derived from the Voronoi-Laguerre tessellation of the configurations of the system. The resulting interactions are local and many-body. Here we perform molecular-dynamics (MD) simulations of an equimolar mixture that is weakly polydisperse and additive. For the first time we study the structural relaxation of this mixture in the supercooled-liquid regime. From the simulations we determine the time- and temperature-dependent coherent and incoherent scattering functions for a large range of wave vectors, as well as the mean-square displacements of both particle species. We perform a detailed analysis of the dynamics by comparing the MD results with the first-principles-based idealized mode-coupling theory (MCT). To this end, we employ two approaches: fits to the asymptotic predictions of the theory, and fit-parameter-free binary MCT calculations based on static-structure-factor input from the simulations. We find that many-body interactions of the Voronoi mixture do not lead to strong qualitative differences relative to similar analyses carried out for simple liquids with pair-wise interactions. For instance, the fits give an exponent parameter λ ≈ 0.746 comparable to typical values found for simple liquids, the wavevector dependence of the Kohlrausch relaxation time is in good qualitative agreement with literature results for polydisperse hard spheres, and the MCT calculations based on static input overestimate the critical temperature, albeit only by a factor of about 1.2. This overestimation appears to be weak relative to other well-studied supercooled-liquid models such as the binary Kob-Andersen Lennard-Jones mixture. Overall, the agreement between MCT and simulation suggests that it is possible to predict several microscopic dynamic properties with qualitative, and in some cases near-quantitative, accuracy based solely on static two-point structural correlations, even though the system itself is inherently governed by many-body interactions.

[Weight gain after bariatric surgery]. / Gewichtstoename na bariatrische chirurgie.

Despite the frequent success of bariatric surgery, 20-30% of patients do not respond well. These patients may experience insufficient weight loss, defined as primary non-response, or may regain an excessive amount of weight after sufficient weight loss, defined as secondary non-response. The aetiology and subsequent treatment of these two types of non-response may differ. This is illustrated by three cases: a patient with primary non-response after gastric bypass (total weight loss 18%) treated conservatively; a patient with secondary non-response after gastric bypass (total weight loss 27%) treated conservatively and lost 7kg as a result of this therapy; a patient with secondary non-response after gastric bypass (total weight loss 27%) treated surgically though experienced malabsorptive complaints as result of distalisation. These cases can be used to demonstrate the challenges that are faced by professionals in the current treatment of post-bariatric surgery patients.

Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes.

Tracing the motion of macromolecules, viruses, and nanoparticles adsorbed onto cell membranes is currently the most direct way of probing the complex dynamic interactions behind vital biological processes, including cell signalling, trafficking, and viral infection. The resulting trajectories are usually consistent with some type of anomalous diffusion, but the molecular origins behind the observed anomalous behaviour are usually not obvious. Here we use coarse-grained molecular dynamics simulations to help identify the physical mechanisms that can give rise to experimentally observed trajectories of nanoscopic objects moving on biological membranes. We find that diffusion on membranes of high fluidities typically results in normal diffusion of the adsorbed nanoparticle, irrespective of the concentration of receptors, receptor clustering, or multivalent interactions between the particle and membrane receptors. Gel-like membranes on the other hand result in anomalous diffusion of the particle, which becomes more pronounced at higher receptor concentrations. This anomalous diffusion is characterised by local particle trapping in the regions of high receptor concentrations and fast hopping between such regions. The normal diffusion is recovered in the limit where the gel membrane is saturated with receptors. We conclude that hindered receptor diffusivity can be a common reason behind the observed anomalous diffusion of viruses, vesicles, and nanoparticles adsorbed on cell and model membranes. Our results enable direct comparison with experiments and offer a new route for interpreting motility experiments on cell membranes.

Introduction of less invasive surfactant administration (LISA), impact on diagnostic and therapeutic procedures in early life: a historical cohort study.

BACKGROUND: In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life. METHODS: Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 - December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 - May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association. RESULTS: All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity. CONCLUSION: The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA.

Banded Roux-en-Y gastric bypass in patients with super morbid obesity (BRandY-study): protocol of a cohort study with 10 year follow-up.

BACKGROUND: Weight loss outcomes after bariatric surgery are less favorable in super morbidly obese patients (BMI ≥50 kg/m2). Non-response, either defined as insufficient weight loss or weight regain after initial successful weight loss, is a matter of serious concern in these patients. The primary banded Roux-en-Y gastric bypass has shown promising results regarding weight loss in the bariatric population. However, up to now, long-term comparative data about the banded and non-banded bypass in superobese patients is lacking. The aim of this study is to assess the added value of the banded Roux-en-Y gastric bypass in superobese patients on long-term weight loss outcomes. METHODS: This single center study will evaluate superobese patients who receive a non-banded Roux-en-Y gastric bypass (NB-RYGB) and a banded Roux-en-Y gastric bypass (B-RYGB). Data from the NB-RYGB group will be collected in retrospect, while data from the B-RYGB group will be collected prospectively. When performing a B-RYGB, a 7.0-8.0 cm silastic ring (MiniMizer®) will be placed proximal to the gastrojejunostomy. The main outcomes of this study are weight loss and non-response during a 10 year follow-up period. Secondary outcomes are reduction of obesity related comorbidities and medication, (ring-related) morbidity and mortality, complications, re-operations, patient satisfaction and health-related quality of life. A total of 142 patients will be included in this study. DISCUSSION: This study will help establish the clinical utility of the B-RYGB in superobese patients. TRIAL REGISTER: NL8093. Registered 15 October 2019 - Retrospectively registered on the Dutch Registry of Clinical trials, www.trialregister.nl.