MYD88 mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis

The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of MYC/BCL2/BCL6 as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in MYD88/CD79B. We investigated whether MYD88/CD79B mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, MYD88/CD79B mutations were identified by allele-specific polymerase chain reaction or next-generationsequencing, MYC/BCL2/BCL6 rearrangements were analyzed by fluorescence in situ hybridization, and EBV was studied by EBV-encoded RNA in situ hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. MYD88 and CD79B mutations were identified in 29.6% and 12.3%, MYC, BCL2, and BCL6 rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and MYD88/CD79B mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. MYD88-mutated DLBCL had a significantly inferior 5-year overall survival than wild-type MYD88 DLBCL (log-rank; P=0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying .1 aberrancy (log-rank; P=0.010). MYD88 mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining MYD88-mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of MYD88 in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies

De ontwikkeling van het Leeksterveld - IVO3 op- en afrit A7 Leeksterveld : een bureauonderzoek en inventariserend veldonderzoek in de vorm van boringen

Lit.opg

Glycosylation changes as important factors for the susceptibility to urinary tract infection

FimH is the type 1 fimbrial tip adhesin and invasin of Escherichia coli. Its ligands are the glycans on specific proteins enriched in membrane microdomains. FimH binding shows high-affinity recognition of paucimannosidic glycans, which are shortened high-mannose glycans such as oligomannose-3 and -5. FimH can recognize equally the (single) high-mannose glycan on uroplakin la, on the urinary defence protein uromodulin or Tamm-Horsfall glycoprotein and on the intestinal GP2 glycoprotein present in Peyer's patches. E. coil bacteria may attach to epithelial cells via hundreds of fimbriae in a multivalent fashion. This binding is considered to provoke conformational changes in the glycoprotein receptor that translate into signalling in the cytoplasm of the infected epithelial cell. Bladder cell invasion by the uropathogenic bacterium is the prelude to recurrent and persistent urinary tract infections in humans. Patients suffering from diabetes mellitus are more prone to contract urinary tract infections. in a study of women, despite longer treatments with a more potent antibiotic, these patients also have more often recurrences of urinary tract infections compared with women without diabetes. Type 1 fimbriae are the most important virulence factors used not only for adhesion of E. coli in the urinary tract, but also for the colonization by E. coli in patients with Crohn's disease or ulcerative colitis. It appears that the increased prevalence of urinary tract infections in diabetic women is not the result of a difference in the bacteria, but is due to changes in the uroepithelial cells leading to an increased adherence of E. coil expressing type 1 fimbriae. Hypothetically, these changes are in the glycosylation of the infected cells. The present article focuses on possible underlying mechanisms for glycosylation changes in the uroepithelial cell receptors for FimH. Like diabetes, bacterial adhesion induces apoptosis that may bring the endoplasmic reticulum membrane with immature mannosylated glycoproteins to the surface. Indicatively, clathrin-mediated vesicle trafficking of glucose transporters is disturbed in diabetics, which would interfere further with the biosynthesis and localization of complex N-linked glycans

A wearable patch based remote early warning score (REWS) in major abdominal cancer surgery patients

INTRODUCTION: The shift toward remote patient monitoring methods to detect clinical deterioration requires testing of wearable devices in real-life clinical settings. This study aimed to develop a remote early warning scoring (REWS) system based on continuous measurements using a wearable device, and compare its diagnostic performance for the detection of deterioration to the diagnostic performance of the conventional modified early warning score (MEWS). MATERIALS AND METHODS: The study population of this prospective, single center trial consisted of patients who underwent major abdominal cancer surgery and were monitored using routine in-hospital spotcheck measurements of the vital parameters. Heart and respiratory rates were measured continuously using a wireless accelerometer patch (HealthDot). The prediction by MEWS of deterioration toward a complication graded Clavien-Dindo of 2 or higher was compared to the REWS derived from continuous measurements by the wearable patch. MAIN RESULTS: A total of 103 patients and 1909 spot-check measurements were included in the analysis. Postoperative deterioration was observed in 29 patients. For both EWS systems, the sensitivity (MEWS: 0.20 95% CI: [0.13-0.29], REWS: 0.20 95% CI: [0.13-0.29]) and specificity (MEWS: 0.96 95% CI: [0.95-0.97], REWS: 0.96 95% CI: [0.95-0.97]) were assessed. CONCLUSIONS: The diagnostic value of the REWS method, based on continuous measurements of the heart and respiratory rates, is comparable to that of the MEWS in patients following major abdominal cancer surgery. The wearable patch could detect the same amount of deteriorations, without requiring manual spot check measurements

Structural Sampling of Glycan Interaction Profiles Reveals Mucosal Receptors for Fimbrial Adhesins of Enterotoxigenic Escherichia coli

biolog

The Accuracy of Wrist-Worn Photoplethysmogram-Measured Heart and Respiratory Rates in Abdominal Surgery Patients: Observational Prospective Clinical Validation Study

BACKGROUND: Postoperative deterioration is often preceded by abnormal vital parameters. Therefore, vital parameters of postoperative patients are routinely measured by nursing staff. Wrist-worn sensors could potentially provide an alternative tool for the measurement of vital parameters in low-acuity settings. These devices would allow more frequent or even continuous measurements of vital parameters without relying on time-consuming manual measurements, provided their accuracy in this clinical population is established. OBJECTIVE: This study aimed to assess the accuracy of heart rate (HR) and respiratory rate (RR) measures obtained via a wearable photoplethysmography (PPG) wristband in a cohort of postoperative patients. METHODS: The accuracy of the wrist-worn PPG sensor was assessed in 62 post-abdominal surgery patients (mean age 55, SD 15 years; median BMI 34, IQR 25-40 kg/m 2). The wearable obtained HR and RR measurements were compared to those of the reference monitor in the postanesthesia or intensive care unit. Bland-Altman and Clarke error grid analyses were performed to determine agreement and clinical accuracy. RESULTS: Data were collected for a median of 1.2 hours per patient. With a coverage of 94% for HR and 34% for RR, the device was able to provide accurate measurements for the large majority of the measurements as 98% and 93% of the measurements were within 5 bpm or 3 rpm of the reference signal. Additionally, 100% of the HR and 98% of the RR measurements were clinically acceptable on Clarke error grid analysis. CONCLUSIONS: The wrist-worn PPG device is able to provide measurements of HR and RR that can be seen as sufficiently accurate for clinical applications. Considering the coverage, the device was able to continuously monitor HR and report RR when measurements of sufficient quality were obtained. TRIAL REGISTRATION: ClinicalTrials.gov NCT03923127; https://www.clinicaltrials.gov/ct2/show/NCT03923127

Perspectieven voor interventies in de bijstand: Experimenten Participatiewet

Welke handelings- en interventiestrategieën van gemeenten dragen bij aan perspectief op werk en een verbetering van het welbevinden en vertrouwen van mensen in de bijstand? Zes gemeenten – Groningen, Utrecht, Tilburg, Wageningen, Deventer en Nijmegen – hebben de afgelopen jaren (van 1 oktober 2017 tot 31 december 2019) unieke randomised controlled trials uitgevoerd in de bijstand. De volgende (combinatie van) interventies zijn onderzocht: ontheffing van re-integratieverplichtingen, intensivering van begeleiding en vrijlating van bijverdiensten. Er is zowel gekeken naar uitstroom naar werk als naar baanzoekintensiteit, welbevinden, zelfredzaamheid en sociaal vertrouwen. De uitstroom naar werk is bij alle interventies niet lager dan de huidige aanpak, terwijl de uitstroom naar deeltijdwerk in sommige gemeenten hoger is. Vooral intensivering op maat en vrijlating kan uitstroom naar werk (minimaal in deeltijd) vergroten. Voor wat betreft de effecten op baanzoekintensiteit, zelfredzaamheid, welbevinden en vertrouwen, is het beeld diffuus. We vinden kleine en soms ook positieve effecten, vooral voor zelfredzaamheid en vertrouwen, maar het beeld is niet eenduidig. De kleine aantallen deelnemers in de experimenten maken het lastig statistisch significante effecten te vinden

Accuracy of vital parameters measured by a wearable patch following major abdominal cancer surgery

Introduction: Recent advances in wearable technology allow for the development of wirelessly connected sensors to continuously measure vital parameters in the general ward or even at home. The present study assesses the accuracy of a wearable patch (Healthdot) for continuous monitoring of heartrate (HR) and respiration rate (RR). Materials and methods: The Healthdot measures HR and RR by means of chest accelerometry. The study population consisted of patients following major abdominal oncological surgery. The analysis focused on the agreement between HR and RR measured by the Healthdot and the gold standard patient monitor in the intensive and post-anesthesia care unit. Results: For HR, a total of 112 h of measurements was collected in 26 patients. For RR, a total of 102 h of measurements was collected in 21 patients. On second to second analysis, 97% of the HR and 87% of the RR measurements were within 5 bpm and 3 rpm of the reference monitor. Assessment of 5-min averaged data resulted in 96% of the HR and 95% of the RR measurements within 5 bpm and 3 rpm of the reference monitor. A Clarke error grid analysis showed that 100% of the HR and 99.4% of the 5-min averaged data was clinically acceptable. Conclusion: The Healthdot accurately measured HR and RR in a cohort of patients recovering from major abdominal surgery, provided that good quality data was obtained. These results push the Healthdot forward as a clinically acceptable tool in low acuity settings for unobtrusive, automatic, wireless and continuous monitoring