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Elevated vasoactive intestinal peptide concentrations poorly predict VIPoma
No full textVIPoma is a rare neuroendocrine tumor (NET) that is challenging to diagnose. While VIP concentrations are elevated in VIPoma, the optimal threshold for diagnostic purposes is not well defined. We aimed to study this in a single-institution population. We obtained results from vasoactive intestinal peptide (VIP) tests from 2011 to 2023 and reviewed the medical record of patients who had concentrations greater than our established assay-specific reference limit of 75 pg/mL. We compared plasma VIP concentrations between patient cohorts with and without VIPoma and determined the optimal threshold for VIP concentrations to predict a VIPoma in this population. Seventy-six patients met the selection criteria. Of these, nine cases of VIPoma were diagnosed. All patients had chronic diarrhea, and five patients had a previous diagnosis of a pancreatic neuroendocrine tumor (PNET). VIP concentrations drawn for acute/episodic diarrhea or flushing/diaphoresis did not lead to a diagnosis of a VIPoma. Mean VIP concentration was increased in patients with a VIPoma relative to those without, but the difference was not statistically significant (508 pg/mL vs 223 pg/mL, P = 0.31). Using the threshold of 75 pg/mL, the positive predictive value for a VIPoma was 12%. The optimal VIP threshold was 442 pg/mL (OR: 11.96, 95% CI: 2.00-79.69, P = 0.01), with statistically significant odds ratios starting at 200 pg/mL. Our findings suggest that elevated VIP concentrations are not predictive for a VIPoma and most patients with elevated VIP do not have a VIPoma. We recommend that VIP only be drawn in certain clinical scenarios to avoid unnecessary medical investigations.</p
The RNA binding protein Arid5a is an activator of TNF signaling in rheumatoid arthritis
No full textRheumatoid arthritis (RA) is characterized by joint inflammation and bone erosion. Understanding cytokine pathways, particularly those targeting TNF, is crucial for understanding pathology and advancing treatment development. Arid5a is a noncanonical RNA binding protein (RBP) that augments inflammation through stabilizing proinflammatory mRNAs and enhancing protein translation. We examined published datasets for ARID5A in human RA blood, T cells, and synovial tissues. A stromal cell line, epithelial cells, and primary synovial fibroblasts were used to assess the effect of TNF on Arid5a expression, localization, and function. To determine how TNF induces Arid5a, WT or Traf2-/- stromal cells were treated with NIK or IKK inhibitors. To evaluate the necessity of Arid5a in arthritis progression, Arid5a-/- mice were subjected to collagen-induced arthritis. ARID5A was elevated in patients with RA and reduced by anti-TNF therapy. TNF upregulated Arid5a through the NF-κB1/TRAF2 pathway, causing cytoplasmic relocalization. Arid5a stabilized proinflammatory transcripts and enhanced expression of chemokines that drive RA. Arid5a-/- mice were resistant to collagen-induced arthritis correlating with reduced Th17 cells in synovial tissue. Thus, Arid5a serves as a newly recognized signaling intermediate downstream of TNF that is elevated in human RA and drives pathology in murine CIA, potentially positioning this RBP as a possible therapeutic target.</p
Sex-specific performance of electrocardiographic criteria for left ventricular hypertrophy in elite athletes
No full textBACKGROUND:In athletes, left ventricular hypertrophy (LVH) criteria based on electrocardiograms (ECGs) have been validated almost exclusively in men using echocardiography. Sex-specific cardiac magnetic resonance (CMR) validation is lacking. OBJECTIVE:To evaluate ECG-LVH criteria against contrast-enhanced CMR in male and female elite athletes. METHODS:Cross-sectional study in healthy elite athletes. Eight ECG-LVH criteria of voltages and products and QRS duration were quantified using automated ECG analysis, and compared to CMR-derived LVH indicators (indexed left ventricular mass (LVM) and maximum left ventricular wall thickness (maxLVWT). Primary metrics of interest were sex-specific correlations (r) between ECG-LVH criteria and LVM/maxLVWT. Secondary metrics included discriminative performance (AUROC) and sensitivity at a 95%-specificity level for detecting increased LVM or maxLVWT. RESULTS:Among 209 elite athletes (median age 25, 45% women), men more frequently met one or more voltage criteria than women (64% vs 45%, P 5 .010). In men, no ECG-LVH criteria showed meaningful correlations or discriminative performance for LVM or maxLVWT. Only QRS duration demonstrated discriminative performance (AUROC: LVM 0.67; maxLVWT 0.74). In women, all voltage and product criteria correlated with LVM (r 5 0.25–0.45) with acceptable discrimination (AUROC: 0.63–0.73). Peguero-Lo Presti, Cornell-, and Modified Sum of 12-Lead Product showed moderate performance (sensitivities: 24%–29%) at 95% specificity in female athletes. Overall, increased precordial QRS voltages were independently correlated with lower extracellular volume (b 5 20.3 mV per %ECV, P < .001). CONCLUSION:In elite athletes, ECG-LVH criteria, except for QRS duration, lack diagnostic value for LVH in men. Voltage criteria may have diagnostic potential in women.</p
Prevalence and Risk Factors of Chronic Venous Disease in a General Population in The Netherlands:Results from the Rotterdam Study
No full textObjective: Chronic venous disease (CVD) of the lower extremities is a common health problem, with moderate to severe symptoms such as leg pain and sensation of swelling, and potentially severe complications such as venous ulcers. However, few population based, physician performed duplex ultrasound (DUS) studies on CVD prevalence and associated risk factors exist. This study aimed to assess the prevalence of the different CEAP (Clinical, Etiological, Anatomical, Pathophysiological) clinical classes, CVD CEAP clinical class C3 – C6, and superficial venous reflux in a Dutch population, along with associated risk factors. Methods: This was a population based, cross sectional cohort study embedded in the Rotterdam Study. Participants aged ≥ 40 years from one Rotterdam district were invited. Baseline demographics, CEAP classification, and DUS outcomes for superficial venous reflux were recorded. Independent risk factors for superficial venous reflux and CVD CEAP clinical class C3 – C6 were identified with multivariable logistic regression analysis. Results: Of 2 510 participants (1 441 women, 1 069 men; median age 54 years), 83.9% of participants were classified as C0 – C1, 12.7% as C2, 2.3% as C3, and 0.7% as C4 – 6. The prevalence of CVD CEAP clinical class C3 – C6 was 3.0%. Superficial venous reflux was present in 23.7%. Independent risk factors for CVD CEAP C3 – C6 included older age, being a woman, and greater height. Risk factors for superficial venous reflux included older age, being a woman, greater height, and a high waist–hip ratio. Conclusion: This study showed a prevalence of superficial venous reflux, and of CVP CEAP clinical class C3-C6 of 23.7% and 3.0%, respectively, in a general Dutch population. The identified risk factors enable identification of people at risk and optimisation of preventive measures, which could result in reduced healthcare costs.</p
Intra-annular self-expanding or balloon-expandable TAVI in small annuli:the NAVULTRA registry
No full textBACKGROUND: Comparative data between self-expanding Navitor (NAV) and balloon-expandable SAPIEN 3 Ultra (ULTRA) transcatheter heart valves (THVs) in patients with small aortic annuli are lacking. AIMS: This study sought to evaluate outcomes of transcatheter aortic valve implantation (TAVI) using the intra-annular NAV and the ULTRA THVs in severe aortic stenosis patients with small annuli. METHODS: Patients with an aortic annulus area ≤430 mm2 undergoing TAVI with either NAV or ULTRA from the NAVULTRA registry were included. Propensity-matched analysis was performed for adjustment. Primary endpoints included 1-year mortality, a composite endpoint (all-cause mortality, disabling stroke, or heart failure hospitalisation), and 30-day device-oriented outcomes (severe prosthesis-patient mismatch, moderate or greater paravalvular leak [PVL], mean gradient ≥20 mmHg). RESULTS: Among 1,617 patients, 524 propensity score-matched pairs were analysed. At 1 year, all-cause mortality was 8.8% with NAV versus 9.0% with ULTRA (adjusted p=0.585), and the composite endpoint occurred in 11.3% versus 11.8%, respectively (adjusted p=0.149). The device-oriented endpoint favoured NAV compared to ULTRA (6.0% vs 29.3%; adjusted p<0.01), with a lower residual transvalvular gradient (7.3 mmHg vs 12.7 mmHg; adjusted p<0.01), and reduced incidence of any prosthesis-patient mismatch (odds ratio 0.27, 95% confidence interval: 0.18-0.43; adjusted p<0.01). However, NAV was associated with higher rates of mild paravalvular leak (NAV 33.5% vs ULTRA 23.2%; adjusted p<0.05) and permanent pacemaker implantation (PPI; NAV 20.1% vs 11.9% ULTRA; adjusted p<0.01). CONCLUSIONS:In patients with small aortic annuli, TAVI with both NAV and ULTRA provided comparable 1-year clinical outcomes, but NAV showed better haemodynamic performance at the cost of higher rates of mild PVL and PPI.</p
Number, depth, and location of inadvertent pancreatic guidewire cannulations, and their association with post-ERCP pancreatitis:Multicenter real-time intra-procedural data
No full textBackground:Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is common. Although multiple pancreatic duct (PD) cannulations are a known risk factor for PEP, the impact of single cannulations remains controversial. We aimed to identify whether single PD cannulation is associated with PEP. Methods: We conducted a prospective multicenter study in patients undergoing ERCP for biliary indications during 2021-2024, with third-party intra-procedural data recording and 30-day follow-up. PEP was defined using consensus definitions. Associations between PD cannulations and PEP were evaluated with multivariable logistic regression, with other patient- and procedure-related risk factors and preventative interventions used as covariates. Results were reported as odds ratios (ORs). Results:PEP occurred in 282 (3.8%) of 7430 ERCPs across nine centers. From multivariable analysis, PD cannulation was statistically significantly associated with PEP, with similar odds for single and multiple cannulations in first-time patients (OR 2.03 [95%CI 1.32-3.14] for single, OR 2.18 [95%CI 1.18-4.00] for ≥5 cannulations) and all patients (OR 1.97 [95%CI 1.33-2.93] for single, OR 2.15 [95%CI 1.21-3.82] for ≥5). PD cannulation to the head (OR 2.09 [95%CI 1.36-3.21]) and body (OR 2.43 [95%CI 1.56-3.79]) were both associated with PEP, while side-branch cannulations alone were not (OR 1.18 [95%CI 0.64-2.06]). Conclusions:Single main PD duct cannulation was independently associated with PEP and appeared to be responsible for most of the magnitude of the association with PD cannulation. These data support the use of preventative interventions such as PD stenting in cases where the PD is inadvertently cannulated.<p/
Regression-based risk scores using sociodemographic and sexual behaviour data do not predict asymptomatic sexually transmitted infections among HIV PrEP users
No full textObjectives Among users of oral HIV pre-exposure prophylaxis (PrEP), condom use is low and incidence of sexually transmitted infections (STIs) is high, hence guidelines recommend STI screening every 3–6 months. Identifying individuals with higher asymptomatic STI risk for targeted screening may offer an opportunity to reduce the burden of STI screening. Methods In the Netherlands, PrEP has been offered through the National PrEP Pilot Program since 2019, which includes screening every 3 months. We included data of all individuals who received care through the PrEP programme between July 2019 and June 2022 and attended at least one PrEP care visit. STI-related symptoms and notification of possible STI exposure by sexual partners are recorded during each visit. We assessed the predictors of any chlamydia, gonorrhoea or syphilis infection diagnosed during routine asymptomatic STI screening (ie, no reported symptoms or partner notification) using logistic regression and calculated risk scores from coefficients of the multivariable logistic regression model. We estimated the sensitivity and specificity for the optimal prediction score cut-off. Results Among the 11 035 included individuals (97% men who have sex with men), 14 926 bacterial STIs (9114 diagnosed during routine asymptomatic screening) were diagnosed during a median of 24 months (IQR 15–30) of follow-up. We found that PrEP users who engaged in sex work, had condomless anal sex, participated in group sex or chemsex (ie, use of gamma-hydroxybutyrate/gamma-butyrolactone, mephedrone or crystallised methamphetamine during sex), injected drugs or used alcohol or non-chemsex-related drugs during sex had an increased risk of STIs diagnosed during routine asymptomatic screening. PrEP users born in the Netherlands and those who attended college or university had a lower STI risk. A risk score using these covariates resulted in a sensitivity of 0.55 (95% CI 0.54 to 0.56) and specificity of 0.55 (95% CI 0.54 to 0.55). Individuals eligible for STI screening accounted for 54% of STIs diagnosed during follow-up. Conclusions Using routinely available demographic and behavioural data, it was not possible to construct a well-performing risk score to identify individuals at high risk of STIs diagnosed during routine asymptomatic screening. Other factors, methods or ways to analyse data may be needed to increase predictive capacity for STI risk scores.</p
Antipsychotic plasma concentration as predictor of movement disorders and cardiometabolic side-effects:A comparison with prescription dose
No full textThe clinical evidence for antipsychotic (AP) therapeutic drug monitoring (TDM) in evaluating AP-related movement disorders and cardiometabolic side-effects remains inconsistent. This study evaluates how AP plasma concentrations associate with movement disorders and cardiometabolic side-effects over time, and compares its predictive value to prescription dose in first-episode psychosis (FEP) patients. We included 200 remitted FEP patients from the HAMLETT trial. AP plasma concentrations were standardized using robust z-scores to accommodate different AP types. The St. Hans Rating Scale and Barnes Akathisia Rating Scale assessed movement disorders. Cardiometabolic indices included body mass index, waist circumference, blood pressure, glucose, triglycerides, and cholesterol. We evaluated longitudinal associations between plasma concentrations, movement disorders and cardiometabolic side-effects using two-part and linear mixed-effects models, and compared its predictive value to prescription dose using Bayesian Information Criterion (ΔBIC). Over a median 6-month follow-up (range = 0–48), AP plasma concentrations were positively associated with odds for parkinsonism (OR = 1.81, 95 % CI 1.27, 2.57, p = 0.001). No associations were found with tardive dyskinesia, akathisia, tardive dystonia, or cardiometabolic indices. AP plasma concentrations predicted parkinsonism better than prescription dose (ΔBIC = -2.95), but showed lower predictive value for waist circumference (ΔBIC = 3.22), total cholesterol (ΔBIC = 3.70), low-density-lipoprotein cholesterol (ΔBIC = 2.14) and non-high-density-lipoprotein cholesterol (ΔBIC = 5.46). These findings suggest that in remitted FEP patients, AP TDM may be more useful than dose in evaluating parkinsonism, likely because plasma concentrations more closely reflect free drugs at striatal dopamine receptors, but it does not appear useful for cardiometabolic side-effects.</p
Quantification of bone microarchitecture and strength with photon-counting detector CT at different radiation doses:an ex-vivo and in-vivo comparison with HR-pQCT
No full textPurpose:To compare trabecular microarchitecture measurements at the distal radius and tibia from photon-counting detector CT (PCD-CT) at varying radiation doses with high-resolution peripheral quantitative CT (HR-pQCT).Methods:Two intact wrist and two intact ankle specimens from an 88-year-old man were scanned with PCD-CT at radiation doses of 2.5, 5, 10, and 20 mGy and with HR-pQCT. Additionally, clinical in-vivo HR-pQCT and PCD-CT scans at the radius and tibia were acquired of a 40-year-old woman with osteoporosis. After bone segmentation, the segmented PCD-CT and HR-pQCT scans were three-dimensionally registered. Cubic volumes (edge length: ex-vivo 6 mm, in-vivo 5 mm) were defined at corresponding locations in the PCD-CT and HR-pQCT scans based on the three-dimensional registration. For each cube, trabecular volume fraction (Tb.BV/TV), thickness (Tb.Th), number (Tb.N), separation (Tb.Sp), and heterogeneity (Tb.1/N.SD) were quantified and compared between corresponding PCD-CT and HR-pQCT cubes. Results:Ex-vivo , linear correlation coefficients ( R2 ) between PCD-CT and HR-pQCT were 0.85–0.97 at 2.5 mGy and remained stable with increasing radiation dose for all parameters except Tb.1/N.SD. For Tb.1/N.SD, R 2 increased between 2.5 and 5 mGy and remained stable at higher doses. At each radiation dose, Tb.BV/TV, Tb.N, and Tb.Th values were higher and Tb.Sp and Tb.1/N.SD lower on PCD-CT than on HR-pQCT. In-vivo , R2 was 0.89–0.95 (radius) and 0.82–0.97 (tibia). Conclusions:PCD-CT strongly correlated with HR-pQCT in trabecular microarchitecture measurements at the distal radius and tibia at low, clinically acceptable, radiation dose. Between-modality differences in microarchitecture values are likely related to chosen image analysis settings.</p
Impact of axillary disease extent defined by baseline <sup>18</sup>F-FDG PET/CT on the accuracy of axillary surgical staging after neoadjuvant systemic therapy in clinically node-positive breast cancer
No full textBackground:In clinically node-positive patients, sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and combined SLNB/MARI (RISAS-procedure) can replace axillary lymph node dissection (ALND) after neoadjuvant systemic therapy. Surgical staging outcome can be combined with baseline axillary disease on 18F-FDG PET/CT. This study assessed whether baseline axillary disease on 18F-FDG PET/CT affects the accuracy of staging-procedures. Second, when staging-procedures detected residual disease, it was assessed whether baseline axillary disease on 18F-FDG PET/CT affected the probability of remaining positive nodes at completion ALND (cALND). Method: Included were patients with baseline 18F-FDG PET/CT within the RISAStrial (NCT02800317). Patients underwent the RISAS-procedure followed by cALND. False negative rates were stratified by limited or advanced baseline axillary disease (1-3 vs. ≥4 hypermetabolic lymph nodes). When staging-procedures detected residual disease, the probability of remaining positive nodes at cALND was stratified by baseline axillary disease. Results: Of 185 patients, 116 had limited and 69 had advanced baseline axillary disease. Staging-procedures had higher accuracy in limited than advanced baseline axillary disease. When the RISAS-procedure detected residual disease, the probability of remaining positive nodes at cALND was lower in limited than advanced baseline axillary disease (44.9% vs. 91.5%,p < .001). When SLNB or MARI detected residual disease, the probability of remaining positive nodes at cALND was >88.4%, irrespective of baseline axillary disease. Conclusion: Staging-procedures had higher accuracy in patients with limited than advanced axillary disease on baseline 18F-FDG PET/CT. When staging-procedures detected residual disease, the probability of remaining positive nodes at cALND remained high.</p