Quantitative aortic Na[18F]F positron emission tomography computed tomography as a tool to associate vascular calcification with major adverse cardiovascular events.

PURPOSE: Sodium[18F]fluoride (Na[18F]F) used in positron emission tomography (PET) binds to active calcification and correlates consistently with higher cardiovascular risk. This study aims to investigate the feasibility of aortic Na[18F]F-PET in hybrid combination with low-dose computed tomography (CT) as a risk model for major adverse cardiovascular events (MACE). METHODS: Patient data and Na[18F]F-PET/CT scans from January 2019 to February 2022 were retrospectively collected at the University Medical Center Groningen (UMCG), the Netherlands. MACE-outcome was a composite of time to first documented myocardial infarction, cerebral vascular accident (CVA), acute heart failure hospitalization, and aortic aneurysms. MACE dates were recorded from the day of the scan until follow-up in December 2023. The aorta was manually segmented in all low-dose CT scans. To minimize spill-over effects from the vertebrae, the vertebrae were automatically segmented using an open-source model, dilated with 10 mm, and subtracted from the aortic mask. The total aortic Na[18F]F corrected maximum standardized uptake value (cSUVmax) and total aortic Agatston score were automatically calculated using SEQUOIA. Kaplan-Meier and Cox regression survival analysis were performed, stratifying patients into high, medium, and low cSUVmax and Agatston categories. Cox regression models were adjusted for age. RESULTS: Out of 280 identified scans, 216 scans of unique patients were included. During a median follow-up of 3.9 years, 12 MACE occurred. Kaplan-Meier survival analysis demonstrated a significant difference in MACE-free survival among the high cSUVmax group compared to the medium and low groups (p = 0.03 and p < 0.01, respectively). Similarly, patients with high Agatston scores had a significantly lower MACE-free survival probability compared to those with medium and low scores (both p < 0.01). CONCLUSION: This study highlights the potential clinical utility of Na[18F]F-PET/CT as an imaging tool to predict the risk of MACE. Clinical validation of this novel proof-of-concept method is needed to confirm these results and expand the clinical context.

Severely increased albuminuria in patients with type 2 diabetes mellitus is associated with increased subclinical atherosclerosis in femoral arteries with Na [18F]F activity as a proxy - The DETERMINE study.

BACKGROUND AND AIMS: Sodium [18F]fluoride (Na [18F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function. METHODS: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m2 91 [81-104]), G1-2A1 with T2DM (eGFR 87 [84-93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25-0.75]), G1-2A3 with T2DM (eGFR 85 [60-103], and ACR 74 [62-122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59-304]). RESULTS: Na [18F]F femoral artery grading score differed significantly in the groups with the highest Na [18F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100-446] and G4A3 with T2DM 198 [113-578]) from the lowest groups of the G1-2A1 with T2DM (33 [0-93]) and in G1-2A1 non-diabetic controls (75 [0-200], p = 0.001). Aortic Na [18F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8-73.8] vs. 17.5 [8.8-27.5] (p = 0.006) and 291 [170-511] vs. 12.2 [1.41-44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009)). CONCLUSIONS: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications.

Effect of vitamin K supplementation on serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients: A double-blind, randomized, placebo-controlled clinical trial.

Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 µg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; Pbetween group = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; Pbetween group = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; Pbetween group < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs. TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis.

OBJECTIVES: Calcinosis cutis affects 20-40% of patients with systemic sclerosis (SSc). When calcinosis cutis becomes clinically apparent, it is irreversible in most cases. Detection of active calcification formation might allow early disease-modifying interventions. We assessed the feasibility of visualizing active calcifications using [18F]Sodium Fluoride ([18F]NaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis. METHODS: In this cross-sectional, observational pilot study patients underwent a whole body [18F]NaF PET/LDCT. All patients met the 2013 ACR/EULAR SSc criteria and had clinically detectable calcinosis cutis. (Sub)cutaneous calcifications were described by three investigators. RESULTS: Nine female patients were included (median age 59.0 years [IQR 51.5-70.5]). [18F]NaF uptake was mostly visible in the fingers (n=7) and knees (n=5). [18F]NaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of [18F]NaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on [18F]NaF PET. CONCLUSION: Imaging of active calcifications in SSc is feasible using [18F]NaF PET/LDCT. Seventy percent of calcifications on LDCT were [18F]NaF PET positive. Although these findings require replication, [18F]NaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions.

The AGE Reader: A non-invasive method to assess long-term tissue damage.

AIMS: Advanced glycation endproducts (AGEs) are sugar-modified adducts which arise during non-enzymatic glycoxidative stress. These compounds may become systemically elevated in disease states, and accumulate in tissue, especially on long-lived proteins. AGEs have been implicated in various acute, and chronic diseases, stressing the need for reliable and comprehensive measuring techniques. Measurement of AGEs in tissue such as skin requires invasive skin biopsies. The AGE Reader has been developed to assess skin autofluorescence (SAF) non-invasively using the fluorescent properties of several AGEs. RESULTS/CONCLUSION: Various studies have shown that SAF is a useful marker of disease processes associated with oxidative stress. It is prospectively associated with the development of cardiovascular events in patients with diabetes, renal or cardiovascular disease, and it predicts diabetes, cardiovascular disease, and mortality in the general population. However, when measuring SAF in individual subjects, several factors may limit the reliability of the measurement. These include endogenous factors present in the skin that absorb emission light such as melanin in dark-skinned subjects, but also factors that lead to temporal changes in SAF such as acute diseases and strenuous physical exercise associated with glycoxidative stress. Also, exogenous factors could potentially influence SAF levels inadvertently such as nutrition, and for example the application of skin care products. This review will address the AGE Reader functionality and the endogenous, and exogenous factors which potentially influence the SAF assessment in individual subjects.

[18F]FDG and [18F]NaF as PET markers of systemic atherosclerosis progression: A longitudinal descriptive imaging study in patients with type 2 diabetes mellitus.

BACKGROUND: While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). METHODS: Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. RESULTS: Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P = .022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV. CONCLUSION: This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.

[Sympathicotomy in patients with drug resistant Raynaud's phenomenon]. / Sympathicotomie bij medicatieresistent fenomeen van Raynaud.

Raynaud's phenomenon (RP) is a disorder of the microvasculature which causes poor blood flow to the digits. This disorder is common in young females and may be associated with several underlying connective tissue diseases including systemic sclerosis. Although RP may have a tremendous impact on quality of life, treatment options are limited. Conventional medical treatment mainly consists of vasodilatory drugs, which are not effective in all patients and may induce undesired side effects. The current clinical lesson describes three patients with severe RP who all underwent a novel, minimally invasive, single-port thoracoscopic sympathicotomy (SPTS). Although this procedure seems promising in patients with treatment-resistant RP, as shown with patients A and B, future research has yet to show what the long-term effects are.

Low body weight and involuntary weight loss are associated with Raynaud's phenomenon in both men and women.

Objectives: Low body weight is an easily assessable cause of Raynaud's phenomenon (RP), and is frequently overlooked by clinicians. We aim to investigate the association of low body weight (body mass index < 18.5 kg/m2), involuntary weight loss, and nutritional restrictions with the presence of RP.Method: Participants from the Lifelines Cohort completed a validated self-administered connective tissue disease questionnaire. Subjects who reported cold-sensitive fingers and biphasic or triphasic colour changes were considered to suffer from RP. Patient characteristics, anthropometric measurements, and nutritional habits were collected. Statistical analyses was stratified for gender.Results: Altogether, 93 935 participants completed the questionnaire. The prevalence of RP was 4.2% [95% confidence interval (CI) 4.1-4.4%], and was three-fold higher in women than in men (5.7% vs 2.1%, p < 0.001). Subjects with RP had a significantly lower daily caloric intake than those without RP. Multivariate analysis, correcting for creatinine level, daily caloric intake, and other known aetiological factors associated with RP, revealed that low body weight [men: odds ratio (OR) 5.55 (95% CI 2.82-10.93); women: 3.14 (2.40-4.10)] and involuntary weight loss [men: OR 1.32 (1.17-1.48); women: 1.31 (1.20-1.44)] were significantly associated with the presence of RP. Low-fat diet was also associated with RP in women [OR 1.27 (1.15-1.44)].Conclusion: Low body weight and prior involuntary weight loss are associated with an increased risk of RP in both men and women. This study emphasizes that low body weight and weight loss are easily overlooked risk factors for RP, and should be assessed and monitored in subjects with RP.

Assessing recovery after cold challenge and thumb involvement can help to rule out systemic sclerosis in patients presenting with Raynaud's phenomenon.

Objective: Our aim was to study whether recovery from a Raynaud's attack and involvement of the thumb are differentiators for systemic sclerosis (SSc) in patients with Raynaud's phenomenon (RP).Method: A stepwise cooling and recovery procedure was performed, provoking an RP attack, in patients with primary Raynaud's phenomenon (PRP, n = 68) and SSc (n = 18). During the procedure, the perfusion of all five fingers during cooling and recovery was assessed by photoelectric plethysmography.Results: In SSc patients, perfusion after 10 min in one or more fingers was more frequently not restored than in PRP patients (p = 0.001), with a negative predictive value of 98%. The thumb was more frequently involved in SSc patients (p = 0.036), with a negative predictive value of 95%. Positive predictive values were low.Conclusions: In patients with RP, when there is restoration of perfusion in all fingers after 10 min or when the thumb is spared, the presence of an underlying SSc is very unlikely. Although these results need to be validated in a clinical setting in a larger prospective study, these signs can help physicians to select additional testing for SSc in RP patients.

18F-sodium fluoride positron emission tomography assessed microcalcifications in culprit and non-culprit human carotid plaques.

BACKGROUND: 18F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18F-NaF uptake with calcification visualized on microcomputed tomography (microCT). METHODS: Carotid plaques from stroke patients undergoing surgery were incubated in 18F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. RESULTS: 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18F-NaF PET VOI showed calcification on CT. CONCLUSIONS: 18F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development.

Skin autofluorescence improves the Finnish Diabetes Risk Score in the detection of diabetes in a large population-based cohort: The LifeLines Cohort Study.

AIM: The aim of the present study was to investigate whether skin autofluorescence would improve the Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes in a large population-based cohort. METHODS: Included were participants from the Dutch LifeLines Cohort Study. Skin autofluorescence was assessed in an unselected subset of participants using the AGE Reader. After the exclusion of participants with previously diagnosed diabetes (n=1635), pregnant women (n=58) and those using corticosteroids (n=345), 79,248 subjects were eligible for analysis. Diabetes was defined as fasting plasma glucose ≥7.0mmol/L, non-fasting plasma glucose ≥11.1mmol/L or HbA1c ≥6.5% (48mmol/mol). RESULTS: Diabetes was detected in 1042 participants (aged 55±12 years; 54% male). Skin autofluorescence improved the area under the receiver operating characteristic (AUROC) curve of the FINDRISC model from 0.802 to 0.811 (P<0.001). Furthermore, the addition of skin autofluorescence to FINDRISC reclassified 8-15% of all participants into more accurate risk categories (NRI: 0.080, 95% CI: 0.052-0.110). The proportion of reclassified participants was especially high (>30%) in the intermediate (1% to <5% and 5% to<10%) risk categories. When skin autofluorescence was added to a simplified model (age+body mass index), its discriminatory performance was similar to the full model+skin autofluorescence (AUROC: 0.806, P=0.062). CONCLUSION: Skin autofluorescence is a non-invasive tool that can be used to further improve the FINDRISC for diabetes detection. The new resultant model is especially useful for reclassifying people in the intermediate-risk categories, where additional blood glucose testing is needed to confirm the presence of diabetes.

The Course of Skin and Serum Biomarkers of Advanced Glycation Endproducts and Its Association with Oxidative Stress, Inflammation, Disease Severity, and Mortality during ICU Admission in Critically Ill Patients: Results from a Prospective Pilot Study.

BACKGROUND: Advanced glycation end products (AGEs) have been implicated in multiple organ failure, predominantly via their cellular receptor (RAGE) in preclinical studies. Little is known about the time course and prognostic relevance of AGEs in critically ill human patients, including those with severe sepsis. OBJECTIVE: 1) To explore the reliability of Skin Autofluorescence (AF) as an index of tissue AGEs in ICU patients, 2) to compare its levels to healthy controls, 3) to describe the time course of AGEs and influencing factors during ICU admission, and 4) to explore their association with disease severity, outcome, and markers of oxidative stress and inflammation. METHODS: Skin AF, serum N"-(carboxyethyl)lysine (CEL), N"-(carboxymethyl)lysine (CML), and soluble RAGE (sRAGE) were serially measured for a maximum of 7 days in critically ill ICU patients with multiple organ failure and compared to age-matched healthy controls. Correlations with (changes in) clinical parameters of disease severity, LDL dienes, and CRP were studied and survival analysis for in-hospital mortality was performed. RESULTS: Forty-five ICU patients (age: 59±15 years; 60% male), and 37 healthy controls (59±14; 68%) were included. Skin AF measurements in ICU patients were reproducible (CV right-left arm: 13%, day-to-day: 10%), with confounding effects of skin reflectance and plasma bilirubin levels. Skin AF was higher in ICU patients vs healthy controls (2.7±0.7 vs 1.8±0.3 au; p<0.001). Serum CEL (23±10 vs, 16±3 nmol/gr protein; p<0.001), LDL dienes (19 (15-23) vs. 9 (8-11) µmol/mmol cholesterol; <0.001), and sRAGE (1547 (998-2496) vs. 1042 (824-1388) pg/ml; p = 0.003) were significantly higher in ICU patients compared to healthy controls, while CML was not different (27 (20-39) vs 29 (25-33) nmol/gr protein). While CRP and LDL dienes decreased significantly, Skin AF and serum AGEs and sRAGE did not change significantly during the first 7 days of ICU admission. CML and CEL were strongly correlated with SOFA scores and CML above the median at baseline was associated with increased risk for mortality (Hazard ratio 3.3 (1.3-8.3); p = 0.01). All other markers did not correlate with disease severity and did not predict mortality. CONCLUSIONS: This study demonstrates that markers for the AGE-RAGE axis are elevated in critically ill patients compared to healthy controls but remain stable for at least 7 days despite clearly fading inflammation and oxidative stress. Circulating AGEs may be associated with disease severity and outcome. Further research should be conducted to elucidate the role of the AGE-RAGE axis in the exaggerated inflammatory response leading to multiple organ failure and death, and whether or not this may be a target for treatment.

Skin autofluorescence and risk of micro- and macrovascular complications in patients with Type 2 diabetes mellitus-a multi-centre study.

AIMS: Skin autofluorescence is a non-invasive marker of advanced glycation end product accumulation. In a previous study, skin autofluorescence correlated with and predicted micro- and macrovascular complications in Type 2 diabetes in a primary care setting. The present cross-sectional study aims to confirm the association between skin autofluorescence and diabetic complications in patients with Type 2 diabetes in a multi-centre secondary care setting. METHODS: We analysed 563 subjects with Type 2 diabetes mellitus from five Dutch hospitals. RESULTS: Median age was 64 years, median duration of diabetes 13 years and median HbA(1c) 58 mmol/mol (7.5%). Sixty-one per cent of patients had microvascular complications (38% nephropathy, 36% retinopathy, 35% neuropathy) and 42% had macrovascular complications. Median UK Prospective Diabetes Study 10-year risk for coronary events was 19%. Median skin autofluorescence was elevated compared with age-matched healthy control subjects: 2.77 (interquartile range 2.39-3.28) vs. 2.46 (2.08-2.84) arbitrary units. Skin autofluorescence was particularly increased in patients with complications: no complications, median 2.56 (2.26-2.90); microvascular complications, 2.79 (2.38-3.29); macrovascular complications, 2.85 (2.41-3.41); both micro- and macrovascular complications, 2.96 (2.56-3.60) arbitrary units, P < 0.001. Logistic regression analysis showed that age, duration of diabetes, renal function, gender, atrial fibrillation and skin autofluorescence were independently associated with macrovascular complications. Multiple regression analysis identified age, smoking, renal function, macrovascular complications and the number of microvascular complications as the determinants of skin autofluorescence. CONCLUSIONS: This study confirms that skin autofluorescence is increased in patients with Type 2 diabetes in a secondary care setting. Skin autofluorescence was associated with macrovascular complications in patients with diabetes and this association was independent of classical risk factors.

Coronary artery calcification score and carotid intima­media thickness in patients with hemophilia.

BACKGROUND/OBJECTIVES: The traditional view that patients with hemophilia are protected against cardiovascular disease is under debate. The aim of the present study was to evaluate the presence and extent of atherosclerosis by coronary artery calcification score (CACS) and carotid intima media thickness (IMT) in patients with hemophilia, and to evaluate their cardiovascular risk profile. METHODS: Sixty-nine patients (51 with hemophilia A; 18 with hemophilia B) were studied [median age: 52 years (interquartile range [IQR] 43­64)]. Cardiovascular risk factors and prior major adverse cardiovascular events (MACEs) were recorded. CACS was derived from electron-beam or dual-source computed tomography, and carotid IMT was assessed by ultrasound measurements and compared with age-specific reference values. RESULTS: The median CACS in all patients was 35 (IQR 0­110) and the geometric mean IMT was 0.80 mm (95% confidence interval [CI] 0.76­0.84); neither was different from the reference values. Patients with a previous MACE (n = 9) had significantly higher CACS and IMT than patients without a previous MACE:CACS median 1013 (IQR 530­1306) vs. 0 (IQR 0­67), and IMT geometric mean 1.09 mm (95% CI 0.95­1.26) vs. 0.76 mm (95% CI 0.73­0.79), both P < 0.001. A higher calculated 10-year cardiovascular risk was related to higher IMT and CACS. CONCLUSION: Patients with hemophilia are not protected against the development of atherosclerosis as measured by CACS and IMT. The extent of atherosclerosis is related to the traditional cardiovascular risk factors. This suggests that traditional cardiovascular risk factors should be monitored and treated in patients with hemophilia.

Understanding eosinophilic esophagitis: the cellular and molecular mechanisms of an emerging disease.

Eosinophilic esophagitis (EoE) has been increasingly recognized as a unique clinicopathological entity over the past two decades. In this short time, the mechanisms of a complex disease have begun to emerge. Patient studies suggest that EoE is an immunologic disease related to atopy. At the cellular level, eosinophils, mast cells, and B and T lymphocytes are increased in the esophageal mucosa in a patchy distribution throughout the length of the esophagus. Laboratory investigations have implicated aeroallergens, food allergens, and a unique T helper type 2 cytokine profile. EoE appears to be an antigen-driven hypersensitivity reaction characterized by a mixed IgE-dependent/delayed-type reaction and a distinct cascade of cytokines and growth factors. The causative events that lead to EoE in humans remain unknown.

Skin autofluorescence is elevated in neovascular age-related macular degeneration.

BACKGROUND/AIMS Skin autofluorescence (AF) is a non-invasive marker for advanced glycation endproducts (AGE) in tissues, making use of their characteristic AF pattern. The aim of this study was to investigate whether skin AF is increased in patients with neovascular age-related macular degeneration (AMD) compared with healthy controls. METHODS Skin AF was assessed in 73 consecutive patients with active and documented neovascular AMD without evidence for diabetic or hypertensive retinopathy and in 31 healthy age-matched controls. Exclusion criteria were: known renal disease, current inflammatory or malignant disease, or skin type V or VI. Skin AF was measured on the forearm and was calculated as a ratio of mean intensities detected from the skin between 420-600 and 300-420 nm. Student t test and chi(2) test were used to compare differences between groups. RESULTS Skin AF was increased in neovascular AMD compared with controls (2.57+/-0.68 vs 2.23+/-0.63 arbitrary units x 10(-2); p=0.018). In patients without vascular risk factors or cardiovascular disease, skin AF was not significantly higher than that of the controls. Skin AF correlated with age in both patients and controls. CONCLUSION Skin AF is increased in patients with neovascular AMD, suggesting that AMD is accompanied by enhanced systemic AGE accumulation, which may indicate a role in the pathophysiology of AMD.

Multiple squamous hyperplastic-fibrous inflammatory polyps of the oesophagus: a new feature of eosinophilic oesophagitis?

This report describes the unusual case of a 12-year-old boy with multiple polyps in the oesophagus and concurrent eosinophilic oesophagitis (EoE). Polyps were of a fibrous-inflammatory composition featuring eosinophils, mast cells, hyperplastic epithelium and fibrosis, which are all features described with EoE. EoE is an increasingly recognised clinicopathological disorder characterised by large numbers of eosinophils infiltrating the oesophageal mucosa. Polyps in the oesophagus are rare, have not previously been associated with EoE, and may represent a new feature of the disease.