Aims: Various dietary risk factors for type 2 diabetes have been identified. A short assessment of dietary patterns related to the risk for type 2 diabetes mellitus may be relevant in clinical practice given the largely preventable nature of the disease. The aim of this study was to investigate the reproducibility of a short food frequency questionnaire based on available knowledge of diabetes-related healthy diets. In addition, we aimed to investigate whether a Diabetes Dietary Quality Index based on this questionnaire was related to metabolic risk factors, including measures of beta cell function and insulin sensitivity. Methods: A short food frequency questionnaire was composed by selecting fourteen questions (representing eight dietary factors) from existing food frequency questionnaires on the basis of their reported relationship with diabetes risk. Healthy participants (N = 176) from a Dutch family study completed the questionnaire and a subgroup (N = 123) completed the questionnaire twice. Reproducible items from the short questionnaire were combined into an index. The association between the Diabetes Dietary Quality index and metabolic risk factors was investigated using multiple linear regression analysis. Measures of beta cell function and insulin sensitivity were derived from a mixed meal test and an euglycemic–hyperinsulinemic and modified hyperglycemic clamp test. Results: Our results show that this new short food frequency questionnaire is reliable (Intraclass Correlations ranged between 0.5 and 0.9). A higher Diabetes Dietary Quality index score was associated with lower 2 h post-meal glucose (β −0.02, SE 0.006, p < 0.05), HbA1c (β −0.07, SE 0.02, p < 0.05), total cholesterol, (β −0.02, SE 0.07, p < 0.05), LDL cholesterol, (β −0.19, SE 0.07, p < 0.05), fasting (β −0.4, SE 0.16, p < 0.05) and post-load insulin, (β −3.9, SE 1.40, p < 0.05) concentrations and the incremental AUC of glucose during MMT (β −1.9, SE 0.97, p < 0.05). The scores obtained for the oral glucose insulin sensitivity-derived mixed meal test were higher in subjects who scored higher on the Diabetes Dietary Quality index (β 0.89, 0.39, p < 0.05). In contrast, we found no significant associations between the Diabetes Dietary Quality index and clamp measures of beta cell function. Conclusions: We identified a questionnaire-derived Diabetes Dietary Quality index that was reproducible and inversely associated with a number of type 2 diabetes mellitus and metabolic risk factors, like 2 h post-meal glucose, Hba1c and LDL, and total cholesterol. Once relative validity has been established, the Diabetes Dietary Quality index could be used by health care professionals to identify individuals with diets adversely related to development of type 2 diabetes.

Abstract Aims The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to healthcare allocation. Yet the impact of COVID-19 on diabetes outpatients has not been extensively evaluated. This study aimed to assess the effect of the COVID-19 pandemic on all aspects of outpatient diabetes care, particularly diagnostics and intermediate outcomes. Methods This observational cohort study included 8,442 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2019 and 2021. A mixed-effects regression analysis was used to examine differences in target achievement of HbA1c, BMI, blood pressure, LDL-cholesterol, eGFR, and the difference in mean HbA1c between 2019 and 2020 among n=1,426 outpatients who visited in both years. Analyses were adjusted for age, sex, and BMI Results A 22.7% (21.6 - 23.8%, p<0,001) decline in outpatient volume was observed during the pandemic. BMI, lipid spectrum, kidney function, and HbA1c were assessed less frequently in 2020 than in 2019. In 2020, compared to 2019, the median HbA1c level increased by 2.2% (1.0 mmol/mol, p=0.035) and the percentages of patients with known HbA1C meeting targets below 10, 8, 7% (86, 64, and 53 mmol/mol) decreased by 0.5%, 1.7% and 1.4%, respectively. Target blood pressure ≤130/80 mmHg was achieved more often in 2020 (15.0% versus 18.3%, p= 0.018), while HbA1c ≤86 mmol/mol was achieved less (89.3% versus 87.1%, p=0.001), among n=1,426 diabetes outpatients seen in both 2019 and 2020. In patients visiting both years, HbA1c was 2.3% (1.9 mmol/l, 95% CI 1.2-2.5, p<0.001) lower during the pandemic than in the prepandemic. Conclusions The COVID pandemic impacted Dutch diabetes outpatient care by reducing patient volume by 22.7%. Among patients who received outpatient care both before and during the pandemic period, HbA1c control and blood pressure control enhanced during the pandemic. Re-evaluation of current diabetes outpatient care organization is warranted to ensure optimal diabetes care in future times.

Aims The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to allocation of healthcare resources. Yet the impact of COVID-19 on diabetes outpatients has not been extensively evaluated. This study aimed to assess the effect of the COVID-19 pandemic on diagnostics and intermediate outcomes of outpatient diabetes care pre- and during COVID. Methods This observational cohort study included 8,442 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2019 and 2021. A mixed-effects regression analysis was used to examine differences in target achievement of HbA1c, BMI, blood pressure, LDL-cholesterol, eGFR, and the difference in mean HbA1c between 2019 and 2020 among n = 1,426 outpatients who visited in both years. Analyses were adjusted for age, sex, and BMI. Results A 22.7% (21.6–23.8%, p < 0.001) decline in outpatient volume was observed during the pandemic (2020). BMI, lipid spectrum, kidney function, and HbA1c were assessed less frequently in 2020 than in 2019. In 2020, compared to 2019, the median HbA1c level increased by 2.2% (1.0 mmol/mol, p = 0.035) and the percentages of patients with known HbA1C meeting targets below 10, 8, 7% (86, 64, and 53 mmol/mol) decreased by 0.5%, 1.7% and 1.4%, respectively. Target blood pressure ≤ 130/80 mmHg was achieved more often in 2020 (15.0% versus 18.3%, p = 0.018), while HbA1c ≤ 86 mmol/mol was achieved less (89.3% versus 87.1%, p = 0.001), among diabetes outpatients seen in both 2019 and 2020. In patients visiting both years, HbA1c was 2.3% (1.9 mmol/l, 95% CI 1.2–2.5, p < 0.001) lower during the pandemic than in the prepandemic (2019). Conclusions The COVID pandemic was associated with a marked reduction in patient volume in diabetes outpatient care among five hospitals. Among patients who received outpatient care both before and during the pandemic period, HbA1c control and blood pressure control enhanced during the pandemic. Re-evaluation of current diabetes outpatient care organization is warranted to ensure optimal diabetes care in future times.

Diabetes mellitus is one of the largest global health concerns of recent times. Women with diabetes mellitus have a higher excess risk of all-cause mortality and more vascular events than men. Focusing on type 1 diabetes, this could be caused by gender inequalities in delivered diabetes care. This study aims to assess gender differences in type 1 diabetes outpatient care, particularly diagnostics and outcomes. This cross-sectional cohort study included all adult type 1 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics between 2016–2021. The frequency of process measurements, including physical examination and laboratory testing, was assessed among both sexes after adjustment for age and body mass index. Gender differences in eGFR ≥ 60, BMI-, and control in blood pressure and LDL-cholesterol were evaluated. Hospital variation in achieving HbA1c targets of 53 mmol/mol and median HbA1c were assessed. Cardiovascular risk scores were calculated in men and women using the Systematic Coronary Risk Evaluation (SCORE) European low-risk chart. Our study showed a 17% higher odds of reaching weight control and a 23% lower odds of achieving blood pressure targets in men than women. Gender-skewed cardiovascular mortality risk scores were found. Gender disparities in outcomes appear not to be caused by gender-biased attitudes in healthcare professionals since no gender differences were found in the performance of process measurements in type 1 diabetes care. In addition, hospitals appear to vary by extent of gender differences in achieving a target HbA1c of 53 mmol/mol. Gender equality exists in the diagnostic process of diabetes care. However, differences in weight control, blood pressure control, and cardiovascular mortality risk scores remain between both sexes, most likely due to multifactorial causes. Indications for interhospital variation in gender disparities in HbA1c control exist. Further focus on performance of process measurements between hospitals may identify areas for improvement of gender-skewed outcomes to further enhance Dutch diabetes care for both sexes.

Objective: Stepped-care has been suggested in the management of patients with problematic hypoglycemia and impaired awareness of hypoglycemia (IAH), initially with psychoeducational programs based on blood glucose awareness training, progressing to diabetes technology in those with persisting need. We examined the clinical effectiveness of stepped-care starting with HypoAware and adding continuous glucose monitoring (CGM) as needed, versus immediate CGM in type 1 diabetes patients with problematic hypoglycemia despite previous structured education in insulin adjustment.Research Design and Methods: A randomized controlled trial (N = 52, mean age 53, 56% females). The stepped-care group attended HypoAware. If a severe hypoglycemic event (SHE) had occurred or IAH was still present after 6 months, CGM was initiated. The control group started immediate CGM. Primary endpoint was the number of participants with self-reported SHE. Secondary outcomes, evaluated at 6 and 12 months, were glycated hemoglobin (HbA1c), the number of participants with IAH time below range (TBR; <54 mg/dL), and patient-reported outcomes (PROs).Results: At 6 months, the number of patients reporting SHE had decreased significantly more in the CGM group: -39% (P < 0.05). HbA1c decreased more in the CGM group (-0.47 percentage-points, P < 0.05). IAH was restored in 31% of patients in both groups. TBR (<54 mg/dL) was lower in the CGM group (-2.4 percentage-points, P < 0.05). In the stepped-care group, 93% started CGM/intermittently scanned CGM. At 12 months, the number of patients reporting SHE was still higher in the stepped-care group. No differences were found in PROs.Conclusions: Immediate start of CGM is more effective than a hypoglycemia-focused reeducation program in reducing SHE risk and attaining glycemic targets in individuals with problematic hypoglycemia and IAH despite previous education in insulin dose adjustment.

To meet surge capacity and to prevent hospitals from being overwhelmed with COVID-19 patients, a regional crisis task force was established during the first pandemic wave to coordinate the even distribution of COVID-19 patients in the Amsterdam region. Based on a preexisting regional management framework for acute care, this task force was led by physicians experienced in managing mass casualty incidents. A collaborative framework consisting of the regional task force, the national task force, and the region's hospital crisis coordinators facilitated intraregional and interregional patient transfers. After hospital admission rates declined following the first COVID-19 wave, a window of opportunity enabled the task forces to create, standardize, and optimize their patient transfer processes before a potential second wave commenced. Improvement was prioritized according to 3 crucial pillars: process standardization, implementation of new strategies, and continuous evaluation of the decision tree. Implementing the novel "fair share" model as a straightforward patient distribution directive supported the regional task force's decisionmaking. Standardization of the digital patient transfer registration process contributed to a uniform, structured system in which every patient transfer was verifiable on intraregional and interregional levels. Furthermore, the regional task force team was optimized and evaluation meetings were standardized. Lines of communication were enhanced, resulting in increased situational awareness among all stakeholders that indirectly provided a safety net and an improved integral framework for managing COVID-19 care capacities. In this article, we describe enhancements to a patient transfer framework that can serve as an exemplary system to meet surge capacity demands during current and future pandemics.

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.

OBJECTIVES:To develop predictive models for blood culture (BC) outcomes in an emergency department (ED) setting. DESIGN:Retrospective observational study. SETTING:ED of a large teaching hospital in the Netherlands between 1 September 2018 and 24 June 2020. PARTICIPANTS:Adult patients from whom BCs were collected in the ED. Data of demographic information, vital signs, administered medications in the ED and laboratory and radiology results were extracted from the electronic health record, if available at the end of the ED visits. MAIN OUTCOME MEASURES:The primary outcome was the performance of two models (logistic regression and gradient boosted trees) to predict bacteraemia in ED patients, defined as at least one true positive BC collected at the ED. RESULTS:In 4885 out of 51 399 ED visits (9.5%), BCs were collected. In 598/4885 (12.2%) visits, at least one of the BCs was true positive. Both a gradient boosted tree model and a logistic regression model showed good performance in predicting BC results with area under curve of the receiver operating characteristics of 0.77 (95% CI 0.73 to 0.82) and 0.78 (95% CI 0.73 to 0.82) in the test sets, respectively. In the gradient boosted tree model, the optimal threshold would predict 69% of BCs in the test set to be negative, with a negative predictive value of over 94%. CONCLUSIONS:Both models can accurately identify patients with low risk of bacteraemia at the ED in this single-centre setting and may be useful to reduce unnecessary BCs and associated healthcare costs. Further studies are necessary for validation and to investigate the potential clinical benefits and possible risks after implementation.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood pressure (BP). When SGLT2i and GLP-1RA are combined, synergistic effects on BP have been observed. The mechanisms underlying these BP reductions are incompletely understood. The aim of this study was to assess the mechanisms underlying the BP reduction with the SGLT2i dapagliflozin, GLP-1RA exenatide, and dapagliflozin-exenatide compared with placebo in people with obesity and type 2 diabetes. Methods Sixty-six people with type 2 diabetes were randomized to 16 weeks of dapagliflozin 10 mg/day, exenatide 10 µg twice daily, dapagliflozin-exenatide, or placebo treatment. The effect of treatments on estimates of: (1) plasma volume (calculated by Strauss formula, bioimpedance spectroscopy, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanometry), (4) systemic hemodynamic parameters including peripheral vascular resistance, cardiac output and stroke volume (all derived from non-invasively systemic hemodynamic monitoring), and (5) natriuresis (24-hour urine collection) were assessed after 10 days and 16 weeks of treatment. Results After 10 days, dapagliflozin reduced systolic BP (SBP) by − 4.7 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin reduced SBP by − 4.4 mmHg, and reduced sympathetic nervous system (SNS) activity. Exenatide had no effect on SBP, but reduced parasympathetic nervous system activity after 10 days and 16 weeks. After 10 days, dapagliflozin-exenatide reduced SBP by − 4.2 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin-exenatide reduced SBP by − 6.8 mmHg, and the reduction in plasma volume was still observed, but SNS activity was unaffected. Conclusions The dapagliflozin-induced plasma volume contraction may contribute to the initial SBP reduction, while a reduction in SNS activity may contribute to the persistent SBP reduction. Dapagliflozin-exenatide resulted in the largest decrease in SBP. The effect on plasma volume was comparable to dapagliflozin monotherapy, and SNS activity was not reduced, therefore other mechanisms are likely to contribute to the blood pressure lowering effect of this combination, which need further investigation. Trial registration Clinicaltrials.gov, NCT03361098.

The coronavirus disease (COVID-19) pandemic causes a large number of patients to simultaneously be in need of specialized care. In the Netherlands, hospitals scaled up their intensive care unit and clinical admission capacity at an early stage of the pandemic. The importance of coordinating resources during a pandemic has already been emphasized in the literature. Therefore, in order to prevent hospitals from being overwhelmed by COVID-19 admissions, national and regional task forces were established for the purpose of coordinating patient transfers. This review describes the experience of Regionaal Overleg Acute Zorg (ROAZ) region Noord-Holland Flevoland, in coordinating patient transfers in the Amsterdam region. In total, 130 patient transfers were coordinated by our region, of which 73% patients were transferred to a hospital within the region. Over a 2-month period, similarities regarding days with increased patient transfers were seen between our region and the national task force. In parallel, an increased incidence in hospital admissions in the Netherlands was observed. During a pandemic, an early upscale (an increase in surge spaces) of hospital admission capacity is imperative. Furthermore, it is preferred to establish national and regional task forces, coordinated by physicians experienced and trained in handling crisis situations, adhering full transparency regarding hospital admission capacity.

Sodium‐glucose cotransporter‐2 inhibitors induce less weight loss than expected. This may be explained by sodium‐glucose cotransporter‐2 inhibitor‐induced alterations in central reward‐ and satiety circuits, leading to increased appetite and food intake. Glucagon‐like peptide‐1 receptor agonists reduce appetite and body weight because of direct and indirect effects on the brain. We investigated the separate and combined effects of dapagliflozin and exenatide on the brain in response to the anticipation and consumption of food in people with obesity and type 2 diabetes.

OBJECTIVE:assess how many patients with low ambulatory diastolic blood pressure (DBP) are not identified when relying on office DBP alone, and thus have 'masked diastolic hypotension'.DESIGN:cross-sectional, retrospective cohort study.SETTING:academic hospital.SUBJECTS:848 patients treated for hypertension who received ambulatory blood pressure monitoring (ABPM).METHODS:cut-off value between on- and off-target systolic blood pressure (SBP): 140 mmHg. Cut-off for low office and/or ambulatory DBP: DBP ≤ 70 mmHg. 'Masked diastolic hypotension' was defined as office DBP > 70 mmHg and mean ambulatory DBP ≤ 70 mmHg.RESULTS:mean age of the sample was 60 ± 13 years, 50% was female, 37% had diabetes, 42% preexisting cardiovascular disease (CVD), mean office blood pressure (BP) was 134/79 mmHg. In all patients (n = 848), low office DBP was present in n = 84(10%), while n = 183(22%) had low ambulatory DBP. In all patients with normal-to-high office DBP (n = 764), n = 122(16%) had 'masked diastolic hypotension'. In this group, ambulatory DBP was 14-19 mmHg lower than office DBP. Patients with low ambulatory DBP were older, had more (cardiovascular) comorbidities, and used more (antihypertensive) drugs. Antihypertensive drugs were lowered or discontinued in 30% of all patients with 'masked diastolic hypotension' due to side effects.CONCLUSIONS:'masked diastolic hypotension' is common among patients treated for hypertension, particularly in older patients with CVD (e.g. coronary artery disease, diabetes), patient groups in which the European Society of Cardiology/Hypertension guideline advises to prevent low DBP. Although it remains to be examined at which BP levels the harms of low DBP outweigh the benefits of lowering SBP, our observations are aimed to increase awareness among physicians.

Background Treatment of diabetes mellitus has majorly improved over the past century, however, the disease burden is high and its prevalence still expanding. Further insight in the diabetes population is imperative to improve the quality of diabetes care by enhancement of knowledge-based diabetes management strategies. To this end, in 2017 a Dutch nationwide consortium of diabetologists, paediatric endocrinologists, and diabetes patients has founded a national outpatient diabetes care registry named Dutch Pediatric and Adult Registry of Diabetes (DPARD). We aim to describe the implementation of DPARD and to provide an overview of the characteristics of patients included during the first 2 years. Methods For the DPARD cohort with long-term follow-up of observational nature, hospital data are gathered directly from electronic health records and securely transferred and stored. DPARD provides weekly updated clinical information on the diabetes population care on a hospital-level benchmarked against the national average. Results Between November 2017 and January 2020, 20,857 patients were included from 8 (11%) Dutch hospitals with a level of care distribution representative of all diabetic outpatients in the Netherlands. Among patients with known diabetes type, 41% had type 1 diabetes, 51% type 2 diabetes, and 8% had diabetes due to other causes. Characteristics of the total patient population were similar to patients with unknown diabetes classification. HbA1c levels decreased over the years, while BMI levels showed an increase over time. Conclusions The national DPARD registry aims to facilitate investigation of prevalence and long-term outcomes of Dutch outpatients with diabetes mellitus and their treatment, thus allowing for quality improvement of diabetes care as well as allowing for comparison of diabetes care on an international level.

Aim To determine the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods In this predefined substudy within a randomized, double-blind, parallel-group, intervention trial, overweight people with T2D without renal impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%-point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (R-E; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference -0.40%; P = .004), without between-group differences in time-averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time-averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon-like peptide-1, renin or FENa. Change in glucagon was associated with change in R-E (R = 0.830; P = .003). Conclusions In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or R-E.

To clarify the mechanism underlying the described U-shaped relation of both low and high levels of IGF-1 with cardiovascular disease this study explores the effect of decreasing and increasing growth hormone dose in GH deficient adults on (micro)vascular function, body composition and insulin resistance. In this randomized clinical trial, thirty-two subjects receiving GH therapy with an IGF-1 concentration between −1 and 1 SD score (SDS) for at least one year were randomized to receive either a decrease (IGF-1 target level of −2 to −1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Microvascular endothelium (in)dependent vasodilatation and vasomotion, vascular stiffness by pulse wave analysis, and HOMA-IR were measured. At the end of the study 30 subjects (65.6% men, mean age 46.6 (SD 9.9) years) were analyzed. There was a favorable effect of increasing the IGF-1 level on waist circumference compared to decreasing the IGF-1 level (p=0.05), but a detrimental effect on insulin resistance (p=0.03). Decreasing IGF-1 level significantly lowered the endothelial domain of vasomotion (p=0.03), whereas increasing IGF-1 level increased the contribution of the neurogenic domain (p=0.05). This change was related to the favorable change in waist circumference. In conclusion, increasing IGF-1 levels was beneficial for body composition but detrimental with respect to insulin resistance. The contribution of the neurogenic vasomotion domain increased in parallel, and could be explained by the favorable change in waist circumference. Clinical Trial Registration ClinicalTrials.gov, identifier NCT01877512.

In adults with type 2 diabetes, men had higher markers of hyperfiltration, which could potentially explain the accelerated progression of diabetic kidney disease in men compared with women.

Foreign body giant cell (FBGC) reaction to silicone material in the lymph nodes of patients with silicone breast implants has been documented in the literature, with a number of case reports dating back to 1978. Many of these case reports describe histologic features of silicone lymphadenopathy in regional lymph nodes from patients with multiple sets of different types of implants, including single lumen smooth surface gel, single lumen textured surface gel, single lumen with polyethylene terephthalate patch, single lumen with polyurethane coating, and double lumen smooth surface. Only one other case report described a patient with highly-cohesive breast implants and silicone granulomas of the skin. In this article, we describe a patient with a clinical presentation of systemic sarcoidosis following highly cohesive breast implant placement. Histopathologic analysis and Confocal Laser Raman Microprobe (CLRM) examination were used to confirm the presence of silicone in the axillary lymph node and capsular tissues. This is the first report where chemical spectroscopic mapping has been used to establish and identify the coexistence of Schaumann bodies, consisting of calcium oxalate and calcium phosphate minerals, together with silicone implant material.

Introduction Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%–54%) and often severe complication. A prophylactic strategy is lacking. Methods and analysis The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium. Ethics and dissemination This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal. Trial registration numbers ClinicalTrials.gov ( NCT04073290 ) and EudraCT database (2018-004323-37).