Re-Cellularization via Electroporation Therapy of the duodenum combined with GPL-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes; 12 months results of a first-in-human study.

BACKGROUND AND AIMS: Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Re-Cellularization via Electroporation Therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in T2D patients through a single ReCET procedure combined with a GLP-1 receptor agonist (GLP-1RA). Feasibility, safety, and (dose) efficacy of ReCET were assessed. METHODS: First-in-human study including patients with T2D on basal insulin (28-75years; BMI 24-40kg/m2, HbA1c ≤64mmol/mol; C-peptide ≥0.2nmol/L). The electroporation dose was optimized during the study, starting with single 600V and ending with double 750V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (GLP-1RA) was initiated. Primary endpoints were: feasibility (procedure time [catheter in-out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c ≤58mmol/mol). RESULTS: Fourteen patients underwent endoscopic ReCET. Median procedure time was 58 (IQR 49-73) minutes. ReCET demonstrated a technical success rate of 100%. No device related SAEs or severe hypoglycemic events were observed. At 12 months follow up, 12 (86%) patients remained off exogenous insulin therapy with significant improvements in glycemic control, metabolic parameters. The 2 patients in whom insulin therapy was reintroduced both received ReCET at the lowest voltage (single 600V). CONCLUSION: These results suggest that ReCET is feasible and safe. In combination with semaglutide, ReCET may be a promising therapeutic option to replace insulin therapy in selected T2D patients, while improving glycemic control and metabolic health.

Clinical Trial: Probiotics in Metformin Intolerant Patients with Type 2 Diabetes (ProGasMet).

BACKGROUND: For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2-13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. METHODS AND ANALYSIS: This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. RESULTS: 37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). CONCLUSION: A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.

Residual ß-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes.

OBJECTIVE: Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual ß-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D. RESEARCH DESIGN AND METHODS: In this cross-sectional cohort comprising 489 individuals (64% female, age 41.0 ± 14.0 years), T1D duration was 15.0 (interquartile range [IQR] 6.0-29.0) years. Individuals had a time in range (TIR) of 66% (IQR 52-80%) and a urinary C-peptide-to-creatinine ratio (UCPCR) of 0.01 (IQR 0.00-0.41) nmol/mmol. To assess ß-cell function, we measured UCPCR (detectable >0.01 nmol/mmol), and to assess α-cell function, fasting plasma glucagon/glucose ratios were measured. CGM was used to record TIR (3.9-10 mmol/L), time below range (TBR) (<3.9 mmol/L), time above range (TAR) (>10 mmol/L), and glucose coefficient of variance (CV). For CGM, 74.7% used FreeStyle Libre 2, 13.8% Medtronic Guardian, and 11.5% Dexcom G6 as their device. RESULTS: The percentage of patients with T1D who had a detectable UCPCR was 49.4%. A higher UCPCR correlated with higher TIR (r = 0.330, P < 0.05), lower TBR (r = -0.237, P < 0.05), lower TAR (r = -0.302, P < 0.05), and lower glucose CV (r = -0.356, P < 0.05). A higher UCPCR correlated negatively with HbA1c levels (r = -0.183, P < 0.05) and total daily insulin dose (r = -0.183, P < 0.05). Glucagon/glucose ratios correlated with longer TIR (r = 0.234, P < 0.05). CONCLUSIONS: Significantly longer TIR, shorter TBR and TAR, and lower CV were observed in individuals with greater UCPCR-assessed ß-cell function. Therefore, better CGM-derived metrics in individuals with preserved ß-cell function may be a contributor to a lower risk of developing long-term complications.

Ultra-low-dose CT versus chest X-ray for patients suspected of pulmonary disease at the emergency department: a multicentre randomised clinical trial.

BACKGROUND: Chest CT displays chest pathology better than chest X-ray (CXR). We evaluated the effects on health outcomes of replacing CXR by ultra-low-dose chest-CT (ULDCT) in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. METHODS: Pragmatic, multicentre, non-inferiority randomised clinical trial in patients suspected of non-traumatic pulmonary disease at the emergency department. Between 31 January 2017 and 31 May 2018, every month, participating centres were randomly allocated to using ULDCT or CXR. Primary outcome was functional health at 28 days, measured by the Short Form (SF)-12 physical component summary scale score (PCS score), non-inferiority margin was set at 1 point. Secondary outcomes included hospital admission, hospital length of stay (LOS) and patients in follow-up because of incidental findings. RESULTS: 2418 consecutive patients (ULDCT: 1208 and CXR: 1210) were included. Mean SF-12 PCS score at 28 days was 37.0 for ULDCT and 35.9 for CXR (difference 1.1; 95% lower CI: 0.003). After ULDCT, 638/1208 (52.7%) patients were admitted (median LOS of 4.8 days; IQR 2.1-8.8) compared with 659/1210 (54.5%) patients after CXR (median LOS 4.6 days; IQR 2.1-8.8). More ULDCT patients were in follow-up because of incidental findings: 26 (2.2%) versus 4 (0.3%). CONCLUSIONS: Short-term functional health was comparable between ULDCT and CXR, as were hospital admissions and LOS, but more incidental findings were found in the ULDCT group. Our trial does not support routine use of ULDCT in the work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. TRIAL REGISTRATION NUMBER: NTR6163.

Use of the National Early Warning Score for predicting deterioration of patients with acute pulmonary embolism: a post-hoc analysis of the YEARS Study.

BACKGROUND: The Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. METHODS: In haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. RESULTS: Of 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. CONCLUSION: In comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice.

The impact of a sepsis performance improvement program in the emergency department: a before-after intervention study.

PURPOSE: The latest Surviving Sepsis Campaign guidelines advocate that all hospitals use sepsis performance improvement programs. However, there is a limited evidence about how to structure such programs and what their potential impact is on sepsis management and outcomes in the emergency department (ED). In this study, we evaluated the implementation of a sepsis performance improvement program in the ED including a dedicated sepsis response team and analyzed the management and outcomes of sepsis patients before and after. METHODS: We conducted a before-after interventional study in the ED of the Amsterdam University Medical Centers, the Netherlands. The sepsis performance improvement program included regular educational meetings, daily audits and weekly feedback, a screening tool, and a dedicated multidisciplinary sepsis response team. We studied all adult patients who presented to the ED with a suspected infection and a Modified Early Warning Score (MEWS) ≥ 3 during their stay. In the postintervention phase, these patients were seen by the sepsis team. Process-related and patient-related outcomes were measured between November 2019 and February 2020 (preintervention) and December 2021-May 2022 (postintervention). RESULTS: A total of 265 patients were included in the primary study, 132 patients preintervention and 133 patients postintervention. The postintervention phase was associated with improvements in nearly all process-related outcomes, such as a shorter time to antibiotics (66 vs. 143 min; p < 0.001), increased number of lactate measurements (72.9 vs. 46.2%; p < 0.001), and improved completeness of documented MEWS scores (85.0 vs. 62.9%; p < 0.001). Except for an improvement in the number of immediate versus delayed ICU admissions (100% immediate vs. 64.3% immediate; p = 0.012), there was no improvement in the other patient-related outcomes such as 28 days mortality (14.3 vs. 9.1%; p = 0.261), during the postintervention phase. CONCLUSION: Our program stimulated physicians to make timely decisions regarding diagnostics and treatment of sepsis in the ED. Implementing the sepsis performance improvement program was associated with significant improvements in most process-related outcomes but with minimal improvements in patient-related outcomes in our cohort.

Recreational Drug Use During the Amsterdam Dance Event: Impact on Emergency Services.

Background: Recreational drug use is common at large-scale dance events such as the Amsterdam Dance Event (ADE) and severe drug-related complications and deaths occur. Increasing concentrations of cocaine, amphetamine and MDMA have been observed in samples from dance events. Therefore, large dance events are expected to cause an increasing amount of recreational drug related complaints (RDRC) and an increased demand on emergency medical services. Aim: To evaluate the impact of recreational drug related complaints (RDRC) during ADE 2016, compared to regular weeks, and to evaluate the requirement for additional medical personnel. Methods: For this prospective, observational cohort study, patients >12 years old presenting with RDRC at first aid stations (FAS), ambulance service (AA) and ED during ADE, between October 19th and October 24th 2016 were included. From 2 EDs and AA, the RDRC 2 weeks before and after ADE were also collected. Results: An estimated 375.000 people attended ADE. The number of patients with RDRC was 459 at the FAS, 113 at AA and 81 at the ED, and increased significantly during ADE with 225% at AA and with 236% at OLVG ED. Eight patients were admitted. A higher percentage of poly-drug use among ED patients (58%) was found, compared to FAS patients (25%). Also, the proportion of tourists in ED's (51%) was higher compared to FAS (30%). Conclusions: During ADE 2016, the number of intoxicated patients increased significantly. Eight patients were admitted to the hospital, without any deaths. The absolute number of patients stayed within normal range of emergency medical services capacity.

Diagnostic stewardship for blood cultures in the emergency department: A multicenter validation and prospective evaluation of a machine learning prediction tool.

BACKGROUND: Overuse of blood cultures (BCs) in emergency departments (EDs) leads to low yields and high numbers of contaminated cultures, accompanied by increased diagnostics, antibiotic usage, prolonged hospitalization, and mortality. We aimed to simplify and validate a recently developed machine learning model to help safely withhold BC testing in low-risk patients. METHODS: We extracted data from the electronic health records (EHR) for 44.123 unique ED visits with BC sampling in the Amsterdam UMC (locations VUMC and AMC; the Netherlands), Zaans Medical Center (ZMC; the Netherlands), and Beth Israel Deaconess Medical Center (BIDMC; United States) in periods between 2011 and 2021. We trained a machine learning model on the VUMC data to predict blood culture outcomes and validated it in the AMC, ZMC, and BIDMC with subsequent real-time prospective evaluation in the VUMC. FINDINGS: The model had an Area Under the Receiver Operating Characteristics curve (AUROC) of 0.81 (95%-CI = 0.78-0.83) in the VUMC test set. The most important predictors were temperature, creatinine, and C-reactive protein. The AUROCs in the validation cohorts were 0.80 (AMC; 0.78-0.82), 0.76 (ZMC; 0.74-0.78), and 0.75 (BIDMC; 0.74-0.76). During real-time prospective evaluation in the EHR of the VUMC, it reached an AUROC of 0.76 (0.71-0.81) among 590 patients with BC draws in the ED. The prospective evaluation showed that the model can be used to safely withhold blood culture analyses in at least 30% of patients in the ED. INTERPRETATION: We developed a machine learning model to predict blood culture outcomes in the ED, which retained its performance during external validation and real-time prospective evaluation. Our model can identify patients at low risk of having a positive blood culture. Using the model in practice can significantly reduce the number of blood culture analyses and thus avoid the hidden costs of false-positive culture results. FUNDING: This research project was funded by the Amsterdam Public Health - Quality of Care program and the Dutch "Doen of Laten" project (project number: 839205002).

Comparing complaint-based triage scales and early warning scores for emergency department triage.

BACKGROUND: Emergency triage systems are used globally to prioritise care based on patients' needs. These systems are commonly based on patient complaints, while the need for timely interventions on regular hospital wards is usually assessed with early warning scores (EWS). We aim to directly compare the ability of currently used triage scales and EWS scores to recognise patients in need of urgent care in the ED. METHODS: We performed a retrospective, single-centre study on all patients who presented to the ED of a Dutch Level 1 trauma centre, between 1 September 2018 and 24 June 2020 and for whom a Netherlands Triage System (NTS) score as well as a Modified Early Warning Score (MEWS) was recorded. The performance of these scores was assessed using surrogate markers for true urgency and presented using bar charts, cross tables and a paired area under the curve (AUC). RESULTS: We identified 12 317 unique patient visits where NTS and MEWS scores were documented during triage. A paired comparison of the AUC of these scores showed that the MEWS score had a significantly better AUC than the NTS for predicting the need for hospital admission (0.65 vs 0.60; p<0.001) or 30-day all-cause mortality (0.70 vs 0.60; p<0.001). Furthermore, when non-urgent MEWS scores co-occur with urgent NTS scores, the MEWS score seems to more accurately capture the urgency level that is warranted. CONCLUSIONS: The results of this study suggest that EWSs could potentially be used to replace the current emergency triage systems.

Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study).

AIMS: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. MATERIALS AND METHODS: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5-10.0% (58-86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). RESULTS: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. CONCLUSIONS: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.

Duodenal mucosal resurfacing with a GLP-1 receptor agonist increases postprandial unconjugated bile acids in patients with insulin-dependent type 2 diabetes.

Duodenal mucosal resurfacing (DMR) is a new endoscopic ablation technique aimed at improving glycemia and metabolic control in patients with type 2 diabetes mellitus (T2DM). DMR appears to improve insulin resistance, which is the root cause of T2DM, but its mechanism of action is largely unknown. Bile acids function as intestinal signaling molecules in glucose and energy metabolism via the activation of farnesoid X receptor and secondary signaling [e.g., via fibroblast growth factor 19 (FGF19)], and are linked to metabolic health. We investigated the effect of DMR and glucagon-like peptide-1 (GLP-1) on postprandial bile acid responses in 16 patients with insulin-dependent T2DM, using mixed meal tests performed at the baseline and 6 mo after the DMR procedure. The combination treatment allowed discontinuation of insulin treatment in 11/16 (69%) of patients while improving glycemic and metabolic health. We found increased postprandial unconjugated bile acid responses (all P < 0.05), an overall increased secondary bile acid response (P = 0.036) and a higher 12α-hydroxylated:non-12α-hydroxylated ratio (P < 0.001). Total bile acid concentrations were unaffected by the intervention. Postprandial FGF19 and 7-α-hydroxy-4-cholesten-3-one (C4) concentrations decreased postintervention (both P < 0.01). Our study demonstrates that DMR with GLP-1 modulates the postprandial bile acid response. The alterations in postprandial bile acid responses may be the result of changes in the microbiome, ileal bile acid uptake and improved insulin sensitivity. Controlled studies are needed to elucidate the mechanism linking the combination treatment to metabolic health and bile acids.NEW & NOTEWORTHY Glycemic and metabolic improvements are seen in patients with type 2 diabetes after replacing their insulin therapy with DMR and GLP-1. These changes are accompanied by changes in postprandial bile acid concentrations: increased unconjugated and secondary bile acids.

A Changed Gut Microbiota Diversity Is Associated With Metabolic Improvements After Duodenal Mucosal Resurfacing With Glucagon-Like-Peptide-1 Receptor Agonist in Type 2 Diabetes in a Pilot Study.

Introduction: The gut microbiota influences and interacts with the host metabolism through effects on nutrient metabolism and digestion. Duodenal Mucosal Resurfacing (DMR) is a novel endoscopic procedure involving duodenal mucosal ablation by the use of hydrothermal energy. DMR, when combined with a glucagon-like peptide-1 receptor agonist (GLP-1RA), resulted in discontinuation of exogenous insulin treatment in 69% of patients with insulin dependent type 2 diabetes mellitus (T2DM) in the INSPIRE study. These patients also experienced improved glycaemic control and metabolic health. We thus investigated if these clinical effects were associated with a change in gut microbiota alpha and beta diversity. Methods: Faecal samples from the 16 patients were obtained for Illumina shotgun sequencing at baseline and 3 months after DMR. We assessed alpha and beta diversity of the gut microbiota in these samples and analysed its correlations with changes in HbA1c, body weight, and liver MRI proton density fat fraction (PDFF). Results: HbA1c correlated negatively with alpha diversity (p=0.011, rho: -0.62) whereas changes in PDFF correlated significantly with beta diversity (p=0.036, rho: 0.55) 3 months after initiation of the combined intervention. These correlations with metabolic parameters were observed despite finding no change in gut microbiota diversity at 3 months post DMR. Discussion: The correlation between gut microbiota richness (alpha diversity) and HbA1c as well as the change in PDFF and changed microbiota composition (beta diversity) suggests that changed gut microbiota diversity is associated with metabolic improvements after DMR in combination with glucagon-like-peptide-1 receptor agonist in type 2 diabetes. Larger controlled studies are however needed to find causal links between DMR with GLP-1RA, the gut microbiota, and improvements in metabolic health.

Patient education materials to implement choosing wisely recommendations for internal medicine at the emergency department.

BACKGROUND: Choosing Wisely aims to reduce low-value care to improve quality and lower costs. In the Netherlands, this campaign offers three recommendations for internal medicine applicable in emergency departments (EDs): (1) do not place an indwelling urinary catheter in non-critically ill patients who can void; (2) do not order plain abdominal radiographs in patients with acute abdominal pain; and (3) discuss whether treatment limitations are needed. This quality improvement project aims to increase the implementation of the recommendations by patient information leaflets. METHODS: In a prospective before-after study, we collected data every other week during baseline and intervention periods (both 7 months) in two university medical centres. The primary outcomes were the adherence rates to the recommendations. RESULTS: 805 patients visited the EDs for internal medicine, of whom 391 (48.6%) were hospitalised. Only 153 (19%) patients received the information leaflet. We found no change in implementation rates of the recommendations after the introduction of the patient information leaflet. In the baseline period, 28 patients received a urinary catheter, of whom 5 (17.9%) had no appropriate indication, compared with 4 (25.0%) of 16 patients in the intervention period (p=0.572). Unnecessary abdominal X-ray occurred once in the baseline period and not in the intervention period. Treatment limitations were not reported in 13 (6.5%) of 200 hospitalised patients in the baseline period, and in 17 (8.9%) of 191 patients in the intervention period (p=0.373). CONCLUSIONS: Patient information leaflets did not increase the implementation of Choosing Wisely recommendations, which can be due to a high baseline rate and a poor dissemination of leaflets. Our ED seems not to be a practicable setting for dissemination of leaflets, since staff engagement was not possible due to high workload and shortage of qualified nursing staff in the Netherlands.

Duodenal mucosal resurfacing combined with glucagon-like peptide-1 receptor agonism to discontinue insulin in type 2 diabetes: a feasibility study.

BACKGROUND AND AIMS: Duodenal mucosal resurfacing (DMR) is an endoscopic intervention in which the duodenal mucosa is ablated by hydrothermal energy. DMR improves glycemic control in patients with type 2 diabetes (T2D), most likely by altered duodenal signaling leading to insulin sensitization. We studied whether we could discontinue insulin use in T2D patients by combining DMR with glucagon-like peptide-1 receptor agonist (GLP-1RA) and lifestyle counseling. METHODS: In this single-arm, single-center feasibility study in 16 insulin-treated patients with T2D (hemoglobin A1c [HbA1c] ≤8.0%, basal insulin <1 U/kg/day, C-peptide ≥.5 nmol/L), patients underwent a single DMR followed by a 2-week postprocedural diet, after which GLP-1RA (liraglutide) was introduced. Lifestyle counseling was provided per American Diabetes Association guidelines. The primary endpoint was percentage of patients without insulin with an HbA1c ≤7.5% (responders) at 6 months. Secondary endpoints were changes in multiple glycemic and metabolic parameters and percentage of responders at 12 and 18 months, respectively. RESULTS: All 16 patients underwent successful DMR without procedure-related serious adverse events. At 6 months, 69% of patients were off insulin therapy with an HbA1c ≤7.5%. At 12 and 18 months 56% and 53% remained off insulin, respectively. All patients significantly improved in the glycemic and metabolic parameters of homeostatic model assessment for insulin resistance, body mass index, weight, and liver fat fraction. CONCLUSIONS: In this feasibility study, the combination of a single DMR and GLP-1RA, supported by lifestyle counseling, eliminated the need for insulin therapy in most patients with T2D through 18 months postprocedure, with adequate beta-cell capacity, while improving glucose regulation and metabolic health in all patients. A randomized-sham controlled trial is currently initiated based on these results. (Clinical trial registration number: EudraCT 2017-00349-30.).

Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial.

OBJECTIVE: Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT). DESIGN: Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition. RESULTS: Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=-0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics. CONCLUSION: FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D. TRIAL REGISTRATION NUMBER: NTR3697.

Quality of acute internal medicine: A patient-centered approach. Validation and usage of the Patient Reported Measure-acute care in the Netherlands.

BACKGROUND: Providing high quality care is important and has gained more attention since the introduction of value-based healthcare. Value should be measured by outcomes achieved, relevant for patients. Patient-centeredness is one domain for quality improvement determined by the Institute of Medicine, aiming to deliver care responsive to the patient. The development and implementation of patient reported outcome- and experience measures can be used for this goal. Recently, we developed the Patient Reported Measure (PRM)-acute care, based on five relevant domains to evaluate and improve the quality of care in the Emergency Department (ED). OBJECTIVE: To validate the PRM-acute care, in order to evaluate and improve patient-centered care in the ED. METHODS: We performed a prospective questionnaire-based study. Patients ≥18 years presenting for internal medicine in the ED were eligible. The validity of the PRM-acute care was evaluated according to the COSMIN-criteria. We performed hypotheses testing to evaluate construct validity. The perceived quality of care was evaluated by statistical analysis. RESULTS: Face- and content validity was evaluated based on previously performed research and deemed good. Construct validity was supported by demonstrated differences between subgroups; patients with severe symptoms had a higher perceived quality of care. The correlation between overall satisfaction and the total mean score of the PRM-acute care (r = 0,447, p = 0.01) was significant. Overall, patients reported a mean perceived quality of care of 4.67/6.0. CONCLUSION: The PRM-acute care is a valid instrument to measure the perceived quality of care in an acute setting for internal medicine patients. Additionally, patients reported a good perceived quality of care in the ED with scores ranging from moderate to well for each of the relevant domains. Therefore, we believe that the PRM-acute care can be implemented in daily practice to evaluate the perceived quality of care and to improve the quality of acute care.

Oral butyrate does not affect innate immunity and islet autoimmunity in individuals with longstanding type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The pathophysiology of type 1 diabetes has been linked to altered gut microbiota and more specifically to a shortage of intestinal production of the short-chain fatty acid (SCFA) butyrate, which may play key roles in maintaining intestinal epithelial integrity and in human and gut microbial metabolism. Butyrate supplementation can protect against autoimmune diabetes in mouse models. We thus set out to study the effect of oral butyrate vs placebo on glucose regulation and immune variables in human participants with longstanding type 1 diabetes. METHODS: We administered a daily oral dose of 4 g sodium butyrate or placebo for 1 month to 30 individuals with longstanding type 1 diabetes, without comorbidity or medication use, in a randomised (1:1), controlled, double-blind crossover trial, with a washout period of 1 month in between. Participants were randomly allocated to the 'oral sodium butyrate capsules first' or 'oral placebo capsules first' study arm in blocks of five. The clinical investigator received blinded medication from the clinical trial pharmacy. All participants, people doing measurements or examinations, or people assessing the outcomes were blinded to group assignment. The primary outcome was a change in the innate immune phenotype (monocyte subsets and in vitro cytokine production). Secondary outcomes were changes in blood markers of islet autoimmunity (cell counts, lymphocyte stimulation indices and CD8 quantum dot assays), glucose and lipid metabolism, beta cell function (by mixed-meal test), gut microbiota and faecal SCFA. The data was collected at the Amsterdam University Medical Centers. RESULTS: All 30 participants were analysed. Faecal butyrate and propionate levels were significantly affected by oral butyrate supplementation and butyrate treatment was safe. However, this modulation of intestinal SCFAs did not result in any significant changes in adaptive or innate immunity, or in any of the other outcome variables. In our discussion, we elaborate on this important discrepancy with previous animal work. CONCLUSIONS/INTERPRETATION: Oral butyrate supplementation does not significantly affect innate or adaptive immunity in humans with longstanding type 1 diabetes. TRIAL REGISTRATION: Netherlands Trial Register: NL4832 (www.trialregister.nl). DATA AVAILABILITY: Raw sequencing data are available in the European Nucleotide Archive repository (https://www.ebi.ac.uk/ena/browse) under study PRJEB30292. FUNDING: The study was funded by a Le Ducq consortium grant, a CVON grant, a personal ZONMW-VIDI grant and a Dutch Heart Foundation grant.

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study.

BACKGROUND: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER: NCT02413567.