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Cancer Immunology, Immunotherapy : CII Dec 2022As immune checkpoint inhibitors (ICI) are increasingly being used due to effectiveness in various tumor entities, rare side effects occur more frequently. Pericardial...
BACKGROUND
As immune checkpoint inhibitors (ICI) are increasingly being used due to effectiveness in various tumor entities, rare side effects occur more frequently. Pericardial effusion has been reported in patients with advanced non-small cell lung cancer (NSCLC) after or under treatment with immune checkpoint inhibitors. However, knowledge about serositis and edemas induced by checkpoint inhibitors in other tumor entities is scarce.
METHODS AND RESULTS
Four cases with sudden onset of checkpoint inhibitor induced serositis (irSerositis) are presented including one patient with metastatic cervical cancer, two with metastatic melanoma and one with non-small cell lung cancer (NSCLC). In all cases treatment with steroids was successful in the beginning, but did not lead to complete recovery of the patients. All patients required multiple punctures. Three of the patients presented with additional peripheral edema; in one patient only the lower extremities were affected, whereas the entire body, even face and eyelids were involved in the other patients. In all patients serositis was accompanied by other immune-related adverse events (irAEs).
CONCLUSION
ICI-induced serositis and effusions are complex to diagnose and treat and might be underdiagnosed. For differentiation from malignant serositis pathology of the punctured fluid can be helpful (lymphocytes vs. malignant cells). Identifying irSerositis as early as possible is essential since steroids can improve symptoms.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Serositis; Immune Checkpoint Inhibitors; Edema
PubMed: 35576074
DOI: 10.1007/s00262-022-03211-7 -
Contact Lens & Anterior Eye : the... Feb 2022With active investigation underway for embedded-circuit contact lenses, safe oxygen supply of these novel lenses remains a question. Central-to-peripheral corneal edema...
PURPOSE
With active investigation underway for embedded-circuit contact lenses, safe oxygen supply of these novel lenses remains a question. Central-to-peripheral corneal edema for healthy eyes during wear of soft contact (SCL) and scleral lenses (SL) with embedding components is assessed.
METHODS
Various 2-dimensional (2D) designs of SL and SCL with embedded components are constructed on Comsol Multiphysics 5.5. Local corneal swelling associated with the designed lenses is determined by a recently developed 2D metabolic-swelling model. Settled central post-lens tear-film thicknesses (PoLTFs) are set at 400 μm and 3 μm for SL and SCL designs, respectively. Each lens design has an axisymmetric central and an axisymmetric peripheral embedment. Oxygen permeability (Dk) of the lens and the embedments ranges from 0 to 200 Barrer. Dimensions and location of the embedments are varied to assess optimal-design configurations to minimize central-to-peripheral corneal edema.
RESULTS
By adjusting oxygen Dk of the central embedment, the peripheral embedment, or the lens matrix polymer, corneal swelling is reduced by up to 2.5 %, 1.5 %, or 1.4 % of the baseline corneal thickness, respectively, while keeping all other parameters constant. A decrease in PoLTF thickness from 400 μm to 3 μm decreases corneal edema by up to 1.8 % of the baseline corneal thickness. Shifting the peripheral embedment farther out towards the periphery and towards the anterior lens surface reduces peak edema by up to 1.3 % and 0.6 % of the baseline corneal thickness, respectively.
CONCLUSIONS
To minimize central-to-peripheral corneal edema, embedments should be placed anteriorly and far into the periphery to allow maximal limbal metabolic support and oxygen transport in the polar direction (i.e., the θ-direction in spherical coordinates). High-oxygen transmissibility for all components and thinner PoLTF thickness are recommended to minimize corneal edema. Depending on design specifications, less than 1 % swelling over the entire cornea is achievable even with oxygen-impermeable embedments.
Topics: Contact Lenses; Contact Lenses, Hydrophilic; Cornea; Corneal Edema; Edema; Humans; Oxygen; Sclera
PubMed: 33846087
DOI: 10.1016/j.clae.2021.101443 -
Current Opinion in Rheumatology Jul 2017The Assessment of Spondyloarthritis International Society (ASAS) axial spondyloarthritis (axSpA) classification criteria marked a major step forward in SpA research,... (Review)
Review
PURPOSE OF REVIEW
The Assessment of Spondyloarthritis International Society (ASAS) axial spondyloarthritis (axSpA) classification criteria marked a major step forward in SpA research, distinguishing axial from peripheral disease, and allowing earlier identification through MRI. This facilitated all aspects of research including epidemiology, therapeutics and patient outcomes.
RECENT FINDINGS
The ASAS axSpA classification criteria have been applied broadly in research, and were validated in a recent meta-analysis of international studies. Concerns arose because of clinical differences between the clinical and imaging arms, which imply different risk for radiographic progression, and perform differently in validation studies. Low specificity of the MRI finding of sacroiliac joint bone marrow edema may lead to misclassification in populations with low axSpA prevalence. We suggest methodology to improve upon the criteria, including rigorous assessment of potential candidate criteria sets, discrete choice experiments to allow consideration of feature weights, and validation. Separately, assessment of structural and inflammatory MRI abnormalities should be performed to refine the MRI definition of sacroiliitis.
SUMMARY
The debate regarding the validation and modification of the ASAS axSpA classification criteria should lead to international efforts to build upon the gains made by these criteria, to further refine the axSpA population definitions for research and ultimately improve patient outcomes.
Topics: Bone Marrow; Disease Progression; Edema; Humans; Magnetic Resonance Imaging; Prevalence; Sacroiliac Joint; Sacroiliitis; Sensitivity and Specificity; Societies, Medical; Spondylarthritis; Spondylarthropathies; Spondylitis, Ankylosing
PubMed: 28376062
DOI: 10.1097/BOR.0000000000000402 -
Current Medical Research and Opinion Sep 2017MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors.
MATERIALS AND METHODS
The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau, Chi, and I analyses.
RESULTS
A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98-4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66-5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved.
CONCLUSION
This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.
Topics: Edema; Humans; Neoplasms; Odds Ratio; Protein Kinase Inhibitors; Risk
PubMed: 28665153
DOI: 10.1080/03007995.2017.1349657 -
Ophthalmic & Physiological Optics : the... Jun 2024To quantify the magnitude of central and peripheral scleral lens-induced corneal oedema for a range of fluid reservoir thicknesses, and to compare these experimental...
PURPOSE
To quantify the magnitude of central and peripheral scleral lens-induced corneal oedema for a range of fluid reservoir thicknesses, and to compare these experimental results with theoretical models of corneal oedema both with and without limbal metabolic support (i.e., the lateral transport of metabolites and the influence of the limbal vasculature).
METHODS
Ten young healthy participants wore scleral lenses (KATT™, Capricornia Contact Lenses) fitted with low (mean 141 μm), medium (482 μm) and high (718 μm) central fluid reservoir thickness values across three separate study visits. The scleral lens thickness, fluid reservoir thickness and stromal corneal oedema were measured using optical coherence tomography. Oedema was quantified across the central (0-2.5 mm from the corneal apex) and peripheral (1.25-3 mm from the scleral spur) cornea. Experimental data were compared with published theoretical models of central to peripheral corneal oedema.
RESULTS
Stromal oedema varied with fluid reservoir thickness (p < 0.001) for both central and peripheral regions. The mean (standard deviation) stromal oedema was greater for the medium (2.08 (1.21)%) and high (2.22 (1.31)%) fluid reservoir thickness conditions compared to the low condition (1.00 (1.01)%) (p ≤ 0.01). Stromal oedema gradually increased from the corneal centre to the periphery by ~0.3% on average (relative increase of 18%), but the change did not reach statistical significance. This trend of increasing, rather than decreasing, oedema towards the limbus is consistent with theoretical modelling of peripheral oedema without metabolic support from the limbus.
CONCLUSIONS
The central and peripheral cornea displayed a similar magnitude of oedema, with increasing levels observed for medium and high fluid reservoir thicknesses. The gradual increase in oedema towards the limbus is consistent with a 'without limbal metabolic support' theoretical model.
Topics: Humans; Corneal Edema; Sclera; Male; Tomography, Optical Coherence; Female; Adult; Young Adult; Contact Lenses; Healthy Volunteers
PubMed: 37622425
DOI: 10.1111/opo.13221 -
Expert Opinion on Drug Safety Feb 2018Controlling blood pressure is a global health priority; single-pill antihypertensive combinations may improve adherence, persistence, and outcomes. Areas covered: A... (Review)
Review
Controlling blood pressure is a global health priority; single-pill antihypertensive combinations may improve adherence, persistence, and outcomes. Areas covered: A novel combination of perindopril arginine and amlodipine besylate was recently approved. A systematic review of the literature revealed its most common adverse effects as: peripheral edema (depending on the dose of amlodipine, but attenuated by perindopril), cough, dizziness and hypotension. Dose-dependent hyperkalemia, impairment of renal function (especially in renovascular hypertension), angioedema, and teratogenicity were derived from experience with other ACE-inhibitors. Expert opinion: Substantial clinical trial experience with amlodipine or perindopril suggests that these two agents effectively lower blood pressure, and can reduce the risk of major adverse cardiovascular events, as in the Anglo-Scandinavian Cardiac Outcomes Trial. The incidence of adverse effects reported in clinical trials is lower than expected, likely due to exclusion of subjects previously exposed to its components; the nature of open-label, uncontrolled observational studies; and difficulty in recognizing and measuring cough and pedal edema. This new formulation of perindopril arginine protects its ethyl ester, without requiring physical separation from amlodipine in a single tablet, and is less hygroscopic than perindopril erbumine. These and other attributes may make this combination an attractive addition to the antihypertensive armamentarium.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Cough; Dose-Response Relationship, Drug; Drug Combinations; Edema; Humans; Hypertension; Perindopril
PubMed: 29065722
DOI: 10.1080/14740338.2018.1397129 -
Biomedicine & Pharmacotherapy =... May 2022Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart...
INTRODUCTION
Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac.
OBJECTIVES & METHODS
All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiological properties of rat ventricular cardiomyocytes.
RESULTS
A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57-85, range 32-95). The median time to onset were 23 days (IQR 10-54) and 17 days (IQR 3-30) for non-cardiogenic edema and acute heart failure, respectively. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5-13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Ca1.2 currents of ventricular cardiomyocytes.
CONCLUSION
Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Ca1.2 blockade under the experimental conditions tested.
Topics: Aged; Aged, 80 and over; Animal Experimentation; Animals; Edema; Female; Gabapentin; Heart Failure; Humans; Male; Middle Aged; Pharmacovigilance; Pregabalin; Rats
PubMed: 35303569
DOI: 10.1016/j.biopha.2022.112807 -
Current Pediatric Reviews 2020Acute hemorrhagic edema of infancy (AHEI), a benign and self-limited disease, can be easily mistaken to be a number of diseases with similar dermatological... (Review)
Review
BACKGROUND
Acute hemorrhagic edema of infancy (AHEI), a benign and self-limited disease, can be easily mistaken to be a number of diseases with similar dermatological manifestations but with potentially adverse outcomes.
OBJECTIVE
This review aimed to familiarize pediatricians with the natural history, clinical manifestations, diagnosis, and management of AHEI.
METHODS
A PubMed search was conducted in February 2020 in Clinical Queries using the key terms "acute hemorrhagic edema of infancy" OR "Finkelstein disease" OR "Seidlmayer disease". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.
RESULTS
AHEI, a rare cutaneous leukocytoclastic small-vessel vasculitis, typically presents with palpable purpura, peripheral acral edema, and frequently with fever, most often in children between 4 and 24 months of age. A significant number of children experience prodromal symptoms of an upper respiratory infection. Fever is typically low grade and is present in approximately 50% of cases. The cutaneous lesions are characterized by rapid onset of small erythematous macules or papules that progress to well demarcated, annular, rosette, medallion-like, or targetoid purpuric plaques or ecchymosis in 24 to 48 hours. The skin lesions are typically palpable, nonpruritic, and symmetrically distributed. Sites of predilection include the face, auricles, and extremities. Edema is typically nonpitting and asymmetrical and occurs primarily on the dorsum of the hands and feet, the face, and the auricles. In spite of the acuteness and extent of the cutaneous findings, the child looks well and nontoxic. Systemic and/or visceral involvement are rare. The differential diagnosis is broad and includes, among others, Henoch-Schönlein purpura. It is crucial to distinguish AHEI from the other diseases since the management of these diseases is quite different. The clinical features of mimickers of AHEI are reviewed and clues to differentiate AHEI from these mimickers are highlighted..AHEI is a benign, self-limited disease with complete spontaneous recovery in one to three weeks in the majority of cases.
CONCLUSION
Recognizing this rare disease is important for the pediatrician to rapidly differentiate AHEI from other potentially serious diseases that require prompt therapy and monitoring. With rapid recognition of AHEI, unnecessary investigations and inappropriate interventions can be prevented and parental anxiety can be avoided.
Topics: Acute Disease; Child; Diagnosis, Differential; Edema; Humans; IgA Vasculitis; Infant; Pediatricians; Vasculitis, Leukocytoclastic, Cutaneous
PubMed: 32718294
DOI: 10.2174/1573396316666200727145039 -
Acta Informatica Medica : AIM : Journal... Dec 2022Retinitis pigmentosa (RP) is a set of inherited rod-cone degenerative diseases that clinically presents with similar signs and symptoms. Mutations in one of more than 70... (Review)
Review
BACKGROUND
Retinitis pigmentosa (RP) is a set of inherited rod-cone degenerative diseases that clinically presents with similar signs and symptoms. Mutations in one of more than 70 genes are involved. Patients will commonly present with bone-spicule pigment formation, waxy optic nerve pallor, and attenuated blood vessels in the posterior pole.Symptoms often begin with progressive night blindness, mid-peripheral visual field defects, and eventual tunnel vision. Central vision loss will ultimately occur following loss of rod function. Complete blindness is uncommon.
OBJECTIVE
The aim of this article is to present two cases of retinitis pigmentosa (mother and daughter) trough optalmologic exams in our clinic. The next aim it to show how to menage a low vision service and to treat cystoid macular oedema as a complication of retinitis pigmentosa.
METHODS
All medical reports are shown in this article. Every diagnostic tool as well as report is a part from our archived history of the patients and has been throughly analysed. We also reviewed available literature using the key words retinitis pigmentosa, cystoid macular oedema, gene therapy.
CASE PRESENTATION
A 38 year old female patient for a low vision consultation. The patient was legally blind secondary to retinitis pigmentosa, which was diagnosed in her late 20s. She reported gradually progressive hazy central vision and decreasing peripheral vision in both eyes as well as severe night blindness. Other than the diagnosis of retinitis pigmentosa in both eyes,the patient had no other remarkable ocular conditions. Findings at that visit included unaided distance visual acuities VOD: 0,04 VOS: 0,06. Pupils were round with brisk responses. Extraocular muscle motility was full in both eyes. Confrontation methode visual fields were noted as temporal loss in the right eye and superior and temporal loss in the left eye. The perimetry test could not be performed due to the lack of correspondece of the patient even after a couple repetitions of the perimetry. She had normal ocular adnexa and quiet lids, conjunctiva, and sclera in both eyes. Corneas in both eyes were noted as clear epithelium, clear stroma, and clear endothelium. Anterior chambers had normal depth, iris with no pathological findings in both eyes; lens incipient sclerotic. Intraocular pressures were noted as 22 mmHg in both eyes with Icare, 21mmHg and 19 mmHg with aplanation tonometry; pahimetry corretional factor was +1 on both eyes. The vitreous was clear in both eyes. Both optic nerves were measured as 0.4 cup-to-disc ratios with no disc edema, disc hemorrhages, notching, or thinning noted.Waxy disc pallor and attenuated blood vessels were observed in both eyes. The macula in both eyes had retinal pigment epithelium (RPE) changes with no edema or hemorrhages. Bone spicule changes were noted 360 in the periphery of both eyes with no holes or tears(Figure 1a+1b+1c+1d).
CONCLUSION
We presented two cases of retinitis pigmentosa - the mother with diagnosed RP more than 15 years ago in need for low vision rehabilitation service and the daughter that got diagnosed after our initial examination and with complications in visual impairment through cystoid macular oedema.
PubMed: 36467319
DOI: 10.5455/aim.2022.30.329-333 -
European Journal of Pharmacology Jul 2020Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present...
Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present work were to further extend these findings, focusing onVD3action mechanisms at the molecular level and onits central and peripheral effects. For that, VD3 antinociceptive and mainly anti-inflammatory activities were evaluated by acute models of nociception (formalin test) and inflammation (carrageenan-induced paw edema), in mice pretreated orally for 7 days with VD3 (0.5 and 1.0 mg/kg). Afterwards, the edematous paws were evaluated by immunohistochemical assays for TNF-alpha. In addition, brains from mice pretreated with VD3, at the same conditions, were harvested for iNOS andCOX-2 immunohistochemical (IHC) assays. The anti-inflammatory effect of VD3 on human neutrophil degranulation was evaluated by the release of myeloperoxidase (MPO) activity, as well as by the reactive oxygen species production. VD3 significantly reduced the licking time in the formalin test, at the second phase (inflammatory pain). VD3 also reduced the edema volume and the number of polymorphonuclear (PMN) cells, as well as the TNF-alpha expression in the edematous paws, compared with the control group. Furthermore, VD3 significantly decreased iNOS and COX-2 expressions in brain areas, such as hippocampus and prefrontal cortex, and inhibited the degranulation of activated neutrophils by the reduction of ROS production and MPO release. Based in these results, VD3 presents anti-inflammatory and antioxidative effects, manifested at peripheral and central sites as showed in the present work for the first time.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Carrageenan; Cyclooxygenase 2; Edema; Formaldehyde; Humans; Male; Mice; Neutrophils; Nitric Oxide Synthase Type II; Pain; Pain Measurement; Peroxidase; Reactive Oxygen Species; Vitamin D; Vitamins
PubMed: 32360837
DOI: 10.1016/j.ejphar.2020.173099