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Journal of the American Heart... Oct 2016Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis. (Meta-Analysis)
Meta-Analysis Review
Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials.
BACKGROUND
Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis.
METHODS AND RESULTS
After systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated. Summary relative risks and 95% CIs were calculated using random- or fixed-effects models according to between-study heterogeneity. In total, 24 randomized trials including 4894 patients met the inclusion criteria. Meta-analysis showed that the incidence of abnormal liver function (7.91% versus 2.84%; risk ratio [RR] 2.38, 95% CI 1.36-4.18), peripheral edema (14.36% versus 9.68%; RR 1.44, 95% CI 1.20-1.74), and anemia (6.23% versus 2.44%; RR 2.69, 95% CI 1.78-4.07) was significantly higher in the ERA group compared with placebo. In comparisons of individual ERAs with placebo, bosentan (RR 3.78, 95% CI 2.42-5.91) but not macitentan (RR 1.17, 95% CI 0.42-3.31) significantly increased the risk of abnormal liver function, whereas ambrisentan (RR 0.06, 95% CI 0.01-0.45) significantly decreased that risk. Bosentan (RR 1.47, 95% CI 1.06-2.03) and ambrisentan (RR 2.02, 95% CI 1.40-2.91) but not macitentan (RR 1.08, 95% CI 0.81-1.46) significantly increased the risk of peripheral edema. Bosentan (RR 3.09, 95% CI 1.52-6.30) and macitentan (RR 2.63, 95% CI 1.54-4.47) but not ambrisentan (RR 1.30, 95% CI 0.20-8.48) significantly increased the risk of anemia. ERAs were not found to increase other reported adverse events compared with placebo.
CONCLUSIONS
The present meta-analysis showed that the main adverse effects of treatment with ERAs were hepatic transaminitis (bosentan), peripheral edema (bosentan and ambrisentan), and anemia (bosentan and macitentan).
Topics: Anemia; Chemical and Drug Induced Liver Injury; Double-Blind Method; Edema; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27912207
DOI: 10.1161/JAHA.116.003896 -
Frontiers in Pediatrics 2023The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the...
INTRODUCTION
The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the medication (osmolarity or vesicant), and the need for central pressure monitoring. The utilization of peripheral intravascular catheters (PIVCs) has shown a notable increase in the number of patients being treated. Extended dwell or midline catheters are another peripheral access option in addition to PIVCs. However, there are currently no established guidelines on their placement.
OBJECTIVES
The aim of this study is to estimate the duration of dwell time for PIVCs, analyze the specific parameters affecting it, and develop recommendations for switching to extended dwell and midline catheter placement as an alternative to peripheral access.
METHODS
The study enrolled patients aged 0-18 years admitted to the pediatric intensive care unit (PICU) for over 24 h and managed with peripheral access only over 2 years (2019-2021).
MEASUREMENTS AND MAIN RESULTS
A total of 484 patients met the specified criteria. Patients who had peripheral access exhibited a lower PRISM score and a shorter length of stay in the PICU, with mean values of 18 (SD: 8.5) and 9.5 (SD: 6.4) days, respectively, compared with patients who had central access with mean values of 8.9 (SD: 5.9) and 5.7 (SD: 3.6) days, respectively. The PIVC dwell time was found to be 50.1 h (SD: 65.3) and required an average of 1.6 insertion attempts. Patients with three or more insertions exhibited an increased odds ratio of 5.2 (95% CI: 3.1-8.5) for receiving an extended dwell or midline insertion. Increased dwell time was associated with female gender, 59.5 h (< 0.001), first attempt insertion, 53.5 h (< 0.001), use of 24 Ga bore, 56.3 h (= 0.04), left-sided insertions, 54.9 (= 0.07), less agitation, 54.8 h (= 0.02), and less edema, 61.6 (< 0.001). Decreased dwell time was associated with the use of vancomycin infusion at 24.2 h (< 0.001) and blood transfusions at 29.3 h (< 0.001).
CONCLUSIONS
Extended catheters last longer than PIVCs in PICU patients. Extended catheter placement requires consideration of the length of treatment, as well as the overall body edema, the level of the patient's restlessness, and the need for vancomycin infusion or blood transfusions, as these factors reduce PIVC dwell time and expose the patients to painful insertions. For such cases, an extended dwell catheter may be a better option, even if the projected treatment time is less than 6 days.
PubMed: 37876526
DOI: 10.3389/fped.2023.1259395 -
Journal of Neurology Dec 2020Classifying and diagnosing peripheral vestibular disorders based on their symptoms is challenging due to possible symptom overlap or atypical clinical presentation. To... (Review)
Review
BACKGROUND
Classifying and diagnosing peripheral vestibular disorders based on their symptoms is challenging due to possible symptom overlap or atypical clinical presentation. To improve the diagnostic trajectory, gadolinium-based contrast-enhanced magnetic resonance imaging of the inner ear is nowadays frequently used for the in vivo confirmation of endolymphatic hydrops in humans. However, hydrops is visualized in both healthy subjects and patients with vestibular disorders, which might make the clinical value of hydrops detection on MRI questionable.
OBJECTIVE
To investigate the diagnostic value of clinical and radiological features, including the in vivo visualization of endolymphatic hydrops, for the classification and diagnosis of vestibular disorders.
METHODS
A literature search was performed in February and March 2019 to estimate the prevalence of various features in healthy subjects and in common vestibular disorders to make a graphical comparison between healthy and abnormal.
RESULTS
Of the features studied, hydrops was found to be a highly prevalent feature in Menière's disease (99.4%). Though, hydrops has also a relatively high prevalence in patients with vestibular schwannoma (48.2%) and in healthy temporal bones (12.5%) as well. In patients diagnosed with (definite or probable) Menière's disease, hydrops is less frequently diagnosed by magnetic resonance imaging compared to the histological confirmation (82.3% versus 99.4%). The mean prevalence of radiologically diagnosed hydrops was 31% in healthy subjects, 28.1% in patients with vestibular migraine, and 25.9% in patients with vestibular schwannoma. An interesting finding was an absolute difference in hydrops prevalence between the two diagnostic techniques (histology and radiology) of 25.2% in patients with Menière's disease and 29% in patients with vestibular schwannoma.
CONCLUSIONS
Although the visualization of hydrops has a high diagnostic value in patients with definite Menière's disease, it is important to appreciate the relatively high prevalence of hydrops in healthy populations and other vestibular disorders. Endolymphatic hydrops is not a pathognomic phenomenon, and detecting hydrops should not directly indicate a diagnosis of Menière's disease. Both symptom-driven and hydrops-based classification systems have disadvantages. Therefore, it might be worth to explore features "beyond" hydrops. New analysis techniques, such as Radiomics, might play an essential role in (re)classifying vestibular disorders in the future.
Topics: Ear, Inner; Edema; Endolymphatic Hydrops; Gadolinium; Humans; Magnetic Resonance Imaging; Meniere Disease
PubMed: 33201310
DOI: 10.1007/s00415-020-10278-8 -
Journal of Biomedical Optics Oct 2021Peripheral pitting edema is a clinician-administered measure for grading edema. Peripheral edema is graded 0, 1 + , 2 + , 3 + , or...
SIGNIFICANCE
Peripheral pitting edema is a clinician-administered measure for grading edema. Peripheral edema is graded 0, 1 + , 2 + , 3 + , or 4 + , but subjectivity is a major limitation of this technique. A pilot clinical study for short-wave infrared (SWIR) molecular chemical imaging (MCI) effectiveness as an objective, non-contact quantitative peripheral edema measure is underway.
AIM
We explore if SWIR MCI can differentiate populations with and without peripheral edema. Further, we evaluate the technology for correctly stratifying subjects with peripheral edema.
APPROACH
SWIR MCI of shins from healthy subjects and heart failure (HF) patients was performed. Partial least squares discriminant analysis (PLS-DA) was used to discriminate the two populations. PLS regression (PLSR) was applied to assess the ability of MCI to grade edema.
RESULTS
Average spectra from edema exhibited higher water absorption than non-edema spectra. SWIR MCI differentiated healthy volunteers from a population representing all pitting edema grades with 97.1% accuracy (N = 103 shins). Additionally, SWIR MCI correctly classified shin pitting edema levels in patients with 81.6% accuracy.
CONCLUSIONS
Our study successfully achieved the two primary endpoints. Application of SWIR MCI to monitor patients while actively receiving HF treatment is necessary to validate SWIR MCI as an HF monitoring technology.
Topics: Discriminant Analysis; Edema; Heart Failure; Humans; Least-Squares Analysis; Molecular Imaging
PubMed: 34689443
DOI: 10.1117/1.JBO.26.10.105002 -
The Journal of Pharmacology and... Jan 2021Pharmacological openers of ATP-sensitive potassium (K) channels are effective antihypertensive agents, but off-target effects, including severe peripheral edema, limit...
Pharmacological openers of ATP-sensitive potassium (K) channels are effective antihypertensive agents, but off-target effects, including severe peripheral edema, limit their clinical usefulness. It is presumed that the arterial dilation induced by K channel openers (KCOs) increases capillary pressure to promote filtration edema. However, K channels also are expressed by lymphatic muscle cells (LMCs), raising the possibility that KCOs also attenuate lymph flow to increase interstitial fluid. The present study explored the effect of KCOs on lymphatic contractile function and lymph flow. In isolated rat mesenteric lymph vessels (LVs), the prototypic K channel opener cromakalim (0.01-3 µmol/l) progressively inhibited rhythmic contractions and calculated intraluminal flow. Minoxidil sulfate and diazoxide (0.01-100 µmol/l) had similar effects at clinically relevant plasma concentrations. High-speed in vivo imaging of the rat mesenteric lymphatic circulation revealed that superfusion of LVs with cromakalim and minoxidil sulfate (0.01-10 µmol/l) maximally decreased lymph flow in vivo by 38.4% and 27.4%, respectively. Real-time polymerase chain reaction and flow cytometry identified the abundant K channel subunits in LMCs as the pore-forming Kir6.1/6.2 and regulatory sulfonylurea receptor 2 subunits. Patch-clamp studies detected cromakalim-elicited unitary K currents in cell-attached patches of LMCs with a single-channel conductance of 46.4 pS, which is a property consistent with Kir6.1/6.2 tetrameric channels. Addition of minoxidil sulfate and diazoxide elicited unitary currents of similar amplitude. Collectively, our findings indicate that KCOs attenuate lymph flow at clinically relevant plasma concentrations as a potential contributing mechanism to peripheral edema. SIGNIFICANCE STATEMENT: ATP-sensitive potassium (K) channel openers (KCOs) are potent antihypertensive medications, but off-target effects, including severe peripheral edema, limit their clinical use. Here, we demonstrate that KCOs impair the rhythmic contractions of lymph vessels and attenuate lymph flow, which may promote edema formation. Our finding that the K channels in lymphatic muscle cells may be unique from their counterparts in arterial muscle implies that designing arterial-selective KCOs may avoid activation of lymphatic K channels and peripheral edema.
Topics: Action Potentials; Animals; Cells, Cultured; Cromakalim; Diazoxide; Edema; KATP Channels; Lymphatic Vessels; Male; Minoxidil; Muscle Contraction; Myocytes, Smooth Muscle; Potassium; Rats; Rats, Sprague-Dawley
PubMed: 33100270
DOI: 10.1124/jpet.120.000121 -
Quantitative Imaging in Medicine and... Mar 2021Ischemic cerebral edema (CE) is a major leading cause of death in patients with ischemic stroke. The CE progression is closely related to the local cerebral blood...
BACKGROUND
Ischemic cerebral edema (CE) is a major leading cause of death in patients with ischemic stroke. The CE progression is closely related to the local cerebral blood perfusion (LCBP) level surrounding the edema area. Quantitative studying the interaction between the CE and peripheral LCBP may provide new inspiration for control and even treatment of CE.
METHODS
Photothrombosis ischemia mouse model was established and observed for 9 hours using swept-source optical coherence tomography (SS-OCT). OCT-based angiography and OCT-based attenuation imaging techniques were used to reconstruct the angiograms reflecting the cerebral blood perfusion (CBP) level and optical attenuation coefficient (OAC) maps reflecting the edema state. The influence of edema on LCBP was analyzed by quantifying the blood perfusion in different spatial locations around the edema tissue, and the influence of LCBP on CE progression was revealed by comparing the changes of the edema area and LCBP level over time.
RESULTS
Preliminary studies show that the effect of edema tissue on LCBP is very significant, which shows a clear spatial dependence. LCBP near the edema tissue is 15-20% lower than that far away from the edema tissue. When the LCBP drops to around 60% of the initial value, the edema area increases sharply. In addition, the level of CBP in the contralateral hemisphere also decreases with time. When the contralateral CBP drops to around 60%, there is a certain probability that contralateral edema will occur.
CONCLUSIONS
CE progression is not only related to the LCBP around the edema tissue but also related to the CBP of non-edematous regions. Controlling the CBP level of non-edematous regions may play a positive role in the treatment of CE. This work provides a new method and inspiration for exploring the mechanism of ischemic CE progression.
PubMed: 33654667
DOI: 10.21037/qims-20-821 -
Thoracic Cancer Dec 2021In May 2020 and February 2021, capmatinib and tepotinib, respectively were approved by the Food and Drug Administration (FDA) for the treatment of metastatic non-small...
In May 2020 and February 2021, capmatinib and tepotinib, respectively were approved by the Food and Drug Administration (FDA) for the treatment of metastatic non-small cell lung carcinoma harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. Herein, we present a case of intolerable peripheral edema caused by tepotinib, in which MET inhibitor could be continued by switching to capmatinib. Peripheral edema has been identified as one of the most common adverse events in capmatinib and tepotinib; however, there is no unified management for this adverse event. This is the first report that two MET inhibitors have different effects on the development of peripheral edema, and that the MET inhibitors can be continued by switching these drugs.
Topics: Adenocarcinoma of Lung; Aged; Antineoplastic Agents; Benzamides; Brain Neoplasms; Edema; Extremities; Humans; Imidazoles; Lung Neoplasms; Male; Piperidines; Pyridazines; Pyrimidines; Triazines
PubMed: 34695875
DOI: 10.1111/1759-7714.14205 -
PloS One 2017To study the association between peripheral blood metabolic and inflammatory factors and presence of diabetic macular edema (DME) and its related anatomic features in... (Observational Study)
Observational Study
AIMS
To study the association between peripheral blood metabolic and inflammatory factors and presence of diabetic macular edema (DME) and its related anatomic features in type 2 diabetic mellitus (T2DM) patients.
MATERIAL AND METHODS
Observational cross-sectional study on a proof of concept basis. Seventy-six T2DM included patients were divided based on the presence (n = 58) or absence of DME (n = 18) according to optical coherence tomography (OCT). Ultra-widefield fluorescein angiography (UWFA) was performed in DME patients. Fasting peripheral blood sample testing included glycemia, glycated hemoglobin, creatinin and lipid levels among others. Serum levels of a broad panel of cytokines and inflammatory mediators were also analysed. OCT findings included central subfoveal thickness, diffuse retinal thickness (DRT), cystoid macular edema (CME), serous retinal detachment and epirretinal membrane. UWFA items included pattern of DME, presence of peripheral retinal ischemia and enlarged foveal avascular zone (FAZ).
RESULTS
Metabolic and inflammatory factors did not statistically differ between groups. However, several inflammatory mediators did associate to certain ocular items of DME cases: IL-6 was significantly higher in patients with DRT (p = 0.044), IL-10 was decreased in patients with CME (p = 0.012), and higher IL-8 (p = 0.031) and VEGF levels (p = 0.031) were observed in patients with enlarged FAZ.
CONCLUSION
Inflammatory and metabolic peripheral blood factors in T2DM may not be differentially associated to DME when compared to non-DME cases. However, some OCT and UWFA features of DME such as DRT, CME and enlarged FAZ may be associated to certain systemic inflammatory mediators.
Topics: Aged; Biomarkers; Cross-Sectional Studies; Cytokines; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Fluorescein Angiography; Humans; Inflammation Mediators; Macular Edema; Male; Middle Aged; Tomography, Optical Coherence
PubMed: 28328965
DOI: 10.1371/journal.pone.0173865 -
Pediatric Rheumatology Online Journal May 2024Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with...
BACKGROUND
Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with restrictive or selective dietary habits in children with global developmental delay, autism spectrum disorder, and physical disabilities. Symptoms include fatigue, irritability, joint and muscle pain, joint swellings, edema, swollen gums, easy bruising, and delayed wound healing. Early recognition and prompt intervention are essential to prevent the progression of symptomatic vitamin C deficiency in children.
CASE PRESENTATION
We present a case of a 13-year-old boy with developmental delay secondary to Lennox Gastaut syndrome referred for suspected recurrent, severe, and atypical IgA vasculitis. He presented with irritability, loss of appetite, petechial and ecchymotic lower limb lesions, unilateral gum swelling, severe arthritis, peripheral oedema, severe weight loss, anaemia, and raised inflammatory markers. Multiple investigations were performed before the diagnosis of scurvy was made. A surgical finding of friable gingival tissue with multiple loose teeth, a skin biopsy with follicular hyperkeratosis and extravasated perifollicular red blood cells, and a typical X-ray finding led to the diagnosis of scurvy.
CONCLUSION
Scurvy should be given careful consideration as a differential diagnosis in patients presenting with musculoskeletal issues, mucocutaneous complaints, and constitutional symptoms such as malaise, asthenia, irritability, and loss of appetite. A focused and detailed dietary history looking for a lack of good sources of vitamin C can be an easy indicator of this differential. Imaging studies revealing the typical features can also help make the diagnosis. Pathology of the skin revealing pathognomonic features can add to the certainty of the diagnosis. In the absence of all else, the rapid response to treatment with an appropriate dose of vitamin C has a diagnostic and therapeutic role.
Topics: Humans; Scurvy; Male; Adolescent; Diagnosis, Differential; Ascorbic Acid; IgA Vasculitis
PubMed: 38760753
DOI: 10.1186/s12969-024-00992-2 -
The Primary Care Companion For CNS... Oct 2022
Topics: Edema; Female; Fluoxetine; Humans; Postpartum Period; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 36206377
DOI: 10.4088/PCC.21cr03191