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Scientific Reports Apr 2024Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to...
Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to maintain vascular health. In this study, we conducted pharmacological experiments to determine whether ASP4058, a sphingosine 1-phosphate receptor 1/5 (S1P1/5) agonist, is useful in abnormal vascular pathology in the eye. First, human retinal microvascular endothelial cells (HRMECs) were examined using vascular endothelial growth factor (VEGF)-induced cell proliferation and hyperpermeability. ASP4058 showed high affinity and inhibited VEGF-induced proliferation and hyperpermeability of HRMECs. Furthermore, S1P1 expression and localization changes were examined in the murine laser-induced choroidal neovascularization (CNV) model, a mouse model of exudative age-related macular degeneration, and the efficacy of ASP4058 was verified. In the CNV model mice, S1P1 tended to decrease in expression immediately after laser irradiation and colocalized with endothelial cells and Müller glial cells. Oral administration of ASP4058 also suppressed vascular hyperpermeability and CNV, and the effect was comparable to that of the intravitreal administration of aflibercept, an anti-VEGF drug. Next, efficacy was also examined in a retinal vein occlusion (RVO) model in which retinal vascular permeability was increased. ASP4058 dose-dependently suppressed the intraretinal edema. In addition, it suppressed the expansion of the perfusion area observed in the RVO model. ASP4058 also suppressed the production of VEGF in the eye. Collectively, ASP4058 can be a potential therapeutic agent that normalizes abnormal vascular pathology, such as age-related macular degeneration and RVO, through its direct action on endothelial cells.
Topics: Animals; Humans; Choroidal Neovascularization; Mice; Disease Models, Animal; Sphingosine-1-Phosphate Receptors; Endothelial Cells; Vascular Endothelial Growth Factor A; Cell Proliferation; Mice, Inbred C57BL; Receptors, Lysosphingolipid; Male
PubMed: 38678148
DOI: 10.1038/s41598-024-60540-6 -
European Heart Journal. Case Reports Apr 2024Aortic regurgitation (AR) associated with detachment of the aortic valve commissure is extremely rare. We present a case of progressively worsening severe chronic AR due...
BACKGROUND
Aortic regurgitation (AR) associated with detachment of the aortic valve commissure is extremely rare. We present a case of progressively worsening severe chronic AR due to detachment of the aortic valve commissure during hospitalization that was confirmed with multimodality imaging.
CASE SUMMARY
A 50-year-old male with Marfan syndrome visited our hospital to receive treatment for cholelithiasis. Pre-operative examination revealed severe AR and aortic root aneurysm. Because the patient was asymptomatic, it was decided that cholecystectomy should be performed first. However, the patient's heart failure worsened acutely when his blood pressure increased just before induction of anaesthesia. The patient required intubation and management of heart failure. Five days later, the patient underwent cholecystectomy. He was treated for heart failure and underwent open heart surgery on the 35th hospital day. Intraoperative transoesophageal echocardiography revealed that his AR was caused by both enlargement of the aortic root and localized dissection of the aortic valve commissure, which was supported by intraoperative findings and histopathological evaluation. Aortic regurgitation was exacerbated by a new localized dissection, resulting in acute worsening of heart failure.
DISCUSSION
Aortic valve commissure detachment can easily lead to sudden onset of severe AR, deteriorating haemodynamics, and acute pulmonary oedema. Since delayed medical treatment leads to poor clinical outcomes, prompt and accurate diagnosis and appropriately timed surgical intervention are essential. This very rare case of severe AR worsening due to spontaneous aortic valve commissure dissection was evaluated with multiple modalities during hospitalization. Understanding this clinical condition will help cardiologists provide better medical care.
PubMed: 38651082
DOI: 10.1093/ehjcr/ytae178 -
Trials Apr 2024Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe...
Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked,...
BACKGROUND
Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME.
OBJECTIVE
The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity.
METHODS
TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups.
KEY SAFETY
Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3.
DISCUSSION
The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs.
TRIAL REGISTRATION
EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.
Topics: Humans; Macular Edema; Retinal Vein Occlusion; Diabetic Retinopathy; Laser Coagulation; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; France; Visual Acuity; Treatment Outcome; Multicenter Studies as Topic; Intravitreal Injections; Time Factors; Equivalence Trials as Topic; Combined Modality Therapy
PubMed: 38649937
DOI: 10.1186/s13063-024-07994-1 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To report the long-term functional, anatomical and safety outcomes of 0.2 μg/day fluocinolone acetonide 0.19mg in patients with persistent or recurrent diabetic macular...
Real-World Evidence of the Long-Term Effectiveness of 0.2 μg/Day Fluocinolone Acetonide Implant in Persistent and Recurrent Diabetic Macular Edema - A Single Center Study.
PURPOSE
To report the long-term functional, anatomical and safety outcomes of 0.2 μg/day fluocinolone acetonide 0.19mg in patients with persistent or recurrent diabetic macular edema (DME).
METHODS
Retrospective, observational, single-center study of patients with recurrent or persistent DME. All patients received 0.2 μg/day of fluocinolone acetonide 0.19mg, and data were collected at baseline and months 1, 3, 6, 12, 24 and 36 after implantation. Outcomes measured included best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and safety outcomes.
RESULTS
A total of 28 eyes from 28 patients were included. The mean age was 66.5 years (95% CI 62.8-70.2) with a mean duration of DME of 8.8 years (95% CI 7.7-10.0). Only two eyes were phakic. Mean follow-up was 25.4 months (95% CI 21.2-29.6). Mean BCVA at baseline was 48.6 ETDRS letters (95% CI 41.3-55.8) and improved as early as month 1 of follow-up with a mean gain in BCVA of 7.8 (95% CI 4.3-11.3) ETDRS letters (p<0.001). Statistically significant improvements in BCVA were also observed at months 6, 12 and 24. At baseline, patients had a mean CMT of 530.5µm (95% CI 463.0-598.0), and a decrease in CMT was observed, starting at the first month of follow-up (mean CMT reduction of -170.5µm, 95% CI -223.8- -117.1; p<0.001). Statistically significant decreases in CMT were also observed at months 6, 12, 24, and 36, with the maximum decrease observed at month 12 (p<0.001). Mean IOP at baseline was 16.4mmHg (95% CI 15.3-17.5) and nine eyes (32.1%) had an IOP ≥21mmHg during follow-up.
CONCLUSION
Our results support the effectiveness and safety profile of fluocinolone acetonide. Although additional long-term real-world evidence is required, fluocinolone acetonide may represent a safe strategy for daily, low-dose, sustained and localized release to the posterior segment of the eye, providing both functional and anatomical benefits in DME.
PubMed: 38646183
DOI: 10.2147/OPTH.S382920 -
Journal of Cardiology Cases Apr 2024Giant cell myocarditis (GCM) is a potentially lethal subtype of myocarditis. Herein, we report a case of a 22-year-old woman with GCM who was successfully treated with...
Complete remission of giant cell myocarditis by prednisolone monotherapy: A case with mild inflammation demonstrated by mismatch between T2-high intensity areas and late gadolinium enhancement.
UNLABELLED
Giant cell myocarditis (GCM) is a potentially lethal subtype of myocarditis. Herein, we report a case of a 22-year-old woman with GCM who was successfully treated with prednisolone monotherapy. The patient had a fever and shortness of breath and was referred to our hospital. Laboratory test results revealed elevated troponin I levels. Cardiac magnetic resonance (CMR) showed high intensity in the inferoseptal segment of the left ventricle on T2-weighted short tau inversion recovery imaging without late gadolinium enhancement (LGE), suggesting predominant edema rather than necrosis. The patient was diagnosed with GCM based on an endomyocardial biopsy, which revealed lymphocyte infiltration and multinucleated giant cells in the absence of granuloma formation. Subsequently, the patient received intravenous methylprednisolone at 1000 mg/day for 3 days followed by oral prednisolone at 30 mg/day, which normalized troponin levels. Follow-up CMR revealed improved cardiac inflammation; therefore, the patient was discharged without prescribing another immunosuppressive agent. Prednisolone was tapered and terminated three years after discharge. The patient went one year without medication and had no recurrence of GCM on follow-up. This case highlights the presence of mild GCM, successfully treated by steroid monotherapy, in which the mismatch between high-intensity T2 areas and LGE suggests mild inflammation.
LEARNING OBJECTIVE
Giant cell myocarditis (GCM) is potentially lethal and usually requires multiple immunosuppressive agents. Here, we report a patient with GCM with preserved left ventricular ejection fraction. Cardiac magnetic resonance revealed focal high T2 signal intensity areas without late gadolinium enhancement, indicating myocardial edema without necrosis. The patient remained in remission with prednisolone monotherapy for 2 years. Our report indicates that "mild" GCM may be treated with prednisolone monotherapy.
PubMed: 38646085
DOI: 10.1016/j.jccase.2023.12.007 -
Acta Radiologica Open May 2024In staging early rectal cancers (ERC), submucosal tumor depth is one of the most important features determining the possibility of local excision (LE). The micro-enema...
Early rectal cancer: The diagnostic performance of MRI supplemented with a rectal micro-enema and a modified staging system to identify tumors eligible for local excision.
BACKGROUND
In staging early rectal cancers (ERC), submucosal tumor depth is one of the most important features determining the possibility of local excision (LE). The micro-enema (Bisacodyl) induces submucosal edema and may hypothetically improve the visualization of tumor depth.
PURPOSE
To test the diagnostic performance of MRI to identify ERC suitable for LE when adding a pre-procedural micro-enema and concurrent use of a modified classification system.
MATERIAL AND METHODS
In this prospective study, we consecutively included 73 patients with newly diagnosed rectal tumors. Two experienced radiologists independently interpreted the MRI examinations, and diagnostic performance was calculated for local tumors eligible for LE (Tis-T1sm2, = 43) and non-local tumors too advanced for LE (T1sm3-T3b, = 30). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were registered for each reader. Inter- and intra-reader agreements were assessed by kappa statistics. Lymph node status was derived from the clinical MRI reports.
RESULTS
Reader1/reader2 achieved sensitivities of 93%/86%, specificities of 90%/83%, PPV of 93%/88%, and NPV of 90%/81%, respectively, for identifying tumors eligible for LE. Rates of overstaging of local tumors were 7% and 14% for the two readers, and kappa values for the inter- and intra-reader agreement were 0.69 and 0.80, respectively. For tumors ≤T2, all metastatic lymph nodes were smaller than 3 mm on histopathology.
CONCLUSION
MRI after a rectal micro-enema and concurrent use of a modified staging system achieved good diagnostic performance to identify tumors suitable for LE. The rate of overstaging of local tumors was comparable to results reported in previous endorectal ultrasound (ERUS) studies.
PubMed: 38645439
DOI: 10.1177/20584601241241523 -
PloS One 2024Quantitative studies have provided valuable statistical insights into Health-Related Quality of Life (HRQoL) among patients with Heart Failure (HF), yet they often lack...
BACKGROUND
Quantitative studies have provided valuable statistical insights into Health-Related Quality of Life (HRQoL) among patients with Heart Failure (HF), yet they often lack the depth to fully capture the nuanced, subjective experiences of living with HF particularly in the specific context of Jordan. This study explores the personal narratives of HF patients to understand the full impact of HF on their daily lives, revealing HRQoL aspects that quantitative metrics often miss. This is crucial in developing regions, where the increasing prevalence of HF intersects with local healthcare practices, cultural views, and patient expectations, providing key insights for tailored interventions and better patient care.
METHODS
Utilizing a phenomenological qualitative design, this study conducted face-to-face semi-structured interviews with 25 HF patients to deeply explore their lived experiences. Thematic analysis was employed to identify major themes related to their perceptions of HF as a disease, its impact on various HRQoL domains, and their recommended strategies to enhance HRQoL.
RESULTS
The study involved 25 participants (13 males, 12 females), aged 26-88 years (mean 63), with diverse education and heart failure (HF) severities. It revealed three themes: HF perceptions, its impact on health-related quality of life (HRQoL) across physical, psychosocial, spiritual, cognitive, and economic domains, and HRQoL improvement strategies. Participants had varied HF knowledge; some lacked basic understanding. The physical impact was most significant, affecting daily life and causing symptoms like breathing difficulties, coughing, edema, and fatigue. This physical aspect influenced their psychosocial and spiritual lives, cognitive functions, and economic stability, leading to fear, frustration, worry, social isolation, spiritual and cognitive challenges, and employment problems.
CONCLUSIONS
The results underscores the need for holistic healthcare approaches, integrating medical, psychological, and social support. Key recommendations include integrated care models, comprehensive patient education, support networks, and policy interventions to enhance HF patient care.
Topics: Male; Female; Humans; Quality of Life; Jordan; Heart Failure; Social Support; Qualitative Research
PubMed: 38635600
DOI: 10.1371/journal.pone.0298893 -
Cureus Mar 2024Iatrogenic venous compression syndrome is defined by extrinsic vein compression due to medical hardware, particularly relevant after joint replacement surgeries....
Iatrogenic venous compression syndrome is defined by extrinsic vein compression due to medical hardware, particularly relevant after joint replacement surgeries. Inserting medical hardware can lead to immediate risks such as deep vein thrombosis and pulmonary embolisms due to local tissue inflammation. The long-term issues include venous insufficiency due to chronic vessel irritation, subsequently causing intimal proliferation and thickening. Despite the existing knowledge of venous compression syndromes, iatrogenic cases are severely underreported. Here, we present a unique case of bilateral common femoral vein compression in a patient with May-Thurner syndrome and prior bilateral hip arthroplasty. An 85-year-old man with a history of venous insufficiency and bilateral hip arthroplasty for osteoarthritis presented with bilateral leg edema. Unsuccessful sclerotherapy and radiofrequency ablation led to a referral to a vascular specialist for venous duplex scans, venograms, and intravascular ultrasound. May-Thurner syndrome was revealed in the left common iliac vein, prompting the deployment of an 18 mm × 16 mm stent. Subsequently, during a venogram, what initially appeared to be a vasospasm in the left common femoral vein was diagnosed as extrinsic iatrogenic venous compression due to acetabular hip screws. This was found after two IV injections of 400 mg nitrogen and one balloon angioplasty could not resolve the compression. After advancement over a 0.35" microwire and accurate positioning over the center of the left common femoral vein lesion, a 16 mm × 90 mm stent was deployed. The venogram and intravascular ultrasound also showed a similar compression in the right common femoral vein. Another 400 mg IV nitrogen did not expand the lesion, so it was concluded that there was similarly an iatrogenic venous compression of the right common femoral vein, also due to acetabular hip screws in the right femur. A follow-up was scheduled a couple of weeks later to address the issue in the right common femoral vein. The underreported issue of iatrogenic venous compression following joint replacements highlights the need for better recognition and management of vascular complications due to inflammation and intimal proliferation. This is especially the case in high-risk patients, such as those with May-Thurner syndrome.
PubMed: 38633923
DOI: 10.7759/cureus.56362 -
BMC Ophthalmology Apr 2024Kidney and eye diseases may be closely linked. Tears of the retinal pigment epithelium (RPE) have been reported to be related to kidney diseases, such as IgA nephropathy... (Review)
Review
BACKGROUND
Kidney and eye diseases may be closely linked. Tears of the retinal pigment epithelium (RPE) have been reported to be related to kidney diseases, such as IgA nephropathy and light-chain deposition disease. However, pigment epithelium tears associated with membranous nephropathy have not been reported or systematically analysed.
CASE PRESENTATION
A 68-year-old man presented with decreased right eye visual acuity. Optical coherence tomography (OCT) revealed cystic macular edema, localized serous detachment of the retina and loss of the outer retinal structure in the right eye and retinal pigment epithelium detachment (PED) combined with serous detachment of the retina in the left eye. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) revealed giant RPE tears in the right eye and exudative age-related macular degeneration in the left eye. The patient also suffered from severe membranous nephropathy-autoimmune glomerulonephritis. Renal biopsy immunofluorescence revealed a roughly granular pattern, with immunoglobulin G (IgA), immunoglobulin G (IgG), IgM, complement C3(Components 3), λ light chain and κ light chain subepithelial staining.
CONCLUSIONS
It is hypothesized that severe membranous nephropathy caused immune complex deposition on the surface of Bruch membrane, resulting in weakened adhesion between the RPE and Bruch membrane and impaired RPE pump function, combined with age-related macular degeneration, leading to giant RPE tears in the right eye. Close attention should be given to the ocular condition of patients with membranous nephropathy to facilitate timely treatment and avoid serious consequences.
Topics: Male; Humans; Aged; Retinal Pigment Epithelium; Glomerulonephritis, Membranous; Macular Degeneration; Fluorescein Angiography; Retinal Perforations; Retinal Detachment; Tomography, Optical Coherence; Epithelium; Immunoglobulin G
PubMed: 38632537
DOI: 10.1186/s12886-024-03426-5