Intravitreal ranibizumab or conbercept for retinal arterial macroaneurysm: a case series.

BACKGROUND: There is no consensus for the standard treatment of retinal arterial macroaneurysm (RAM). Intravitreal anti-vascular endothelium growth factor (anti-VEGF) is an alternative treatment option for RAM. The purpose of this study is to describe the clinical efficacy of intravitreal ranibizumab or intravitreal conbercept for retinal arterial macroaneurysm. CASE PRESENTATION: Three cases that presented with symptomatic RAM were treated with intravitreal anti-VEGF agents. Two eyes received two intravitreal ranibizumab injections with a time interval of one month and completed a one-year follow-up, while one eye only received one intravitreal conbercept injection and was followed up for six months. Both the retinal thickness and the visual acuity were significantly improved at the final clinic visit. The macular hemorrhage and edema were resolved. There were no ocular or systemic side effects. CONCLUSIONS: Intravitreal ranibizumab or conbercept might be used as a therapeutic option for symptomatic retinal arterial macroaneurysm patients. Anti-VEGF therapy should be further investigated in a larger series with longer follow-up for this disease profile.

Behçet's Disease: Pulmonary Aneurysm Resolution with Oral Therapy and HLA B72 Allele Association.

We report the case of a woman who was diagnosed with a pulmonary artery aneurysm that was caused by Behçet's disease. The patient was initially diagnosed with community-acquired pneumonia and then pulmonary thromboembolism and aneurysm of the right pulmonary artery segmental branch was confirmed. The initial treatment consisted of anticoagulant drugs. After analysis of the family history and a positive pathergy test, the patient was diagnosed with Behçet's disease. Oral pharmacological treatment began with corticosteroids, cyclophosphamide, and anticoagulant suspension. The HLA B72 allele was identified in the patient and her two sisters, demonstrating the familial characteristic of the disease and the presence of this allele in a female patient with Behçet's disease. After 12 months of treatment, the clinical condition completely resolved.

Surgical intervention for a pediatric isolated intramedullary spinal aneurysm.

PURPOSE: To report the case of a pediatric patient with intramedullary spinal aneurysm. METHODS: A 9-year-old boy presented with low back pain and subsequent gait disturbance. He had no history of trauma. After admission, MRI revealed an intramedullary spinal cord mass lesion surrounded by hemorrhage at the cervical-thoracic junction. Initial treatment was started with intravenous methylprednisolone and bed rest. Neurological deficit disappeared under careful observation for a few months. Surgical intervention was applied for diagnosis and resection of the mass lesion to prevent recurrent hemorrhage. RESULTS: Intraoperative ultrasound sonography helped to diagnose the lesion as a spinal cord aneurysm, prior to midline myelotomy. Monitoring of transcranial muscle evoked potentials helped to avoid spinal cord damage during surgery. There has been no evidence of spinal aneurysm on MRI for 3 years after surgery and no neurological deterioration. CONCLUSION: To our knowledge, this is a first report of an intramedullary spinal cord aneurysm at the cervical-thoracic junction in a pediatric patient. Careful observation after initial symptoms followed by surgical intervention was favorable in this case.

Long-term Outcome after Thrombolysis for Acute Lower Limb Ischaemia.

OBJECTIVES: The purpose was to study long-term outcome after thrombolysis for acute arterial lower limb ischaemia, and to evaluate the results depending on the underlying aetiology of arterial occlusion. METHODS: This was a retrospective study of patients entered into a prospective database. Patients were identified in prospective databases from two vascular centres, including a large number of variables. Case records were analysed retrospectively. Through cross linkage with the Population Registry 100% accurate survival data were obtained. Between January 2001 and December 2013, 689 procedures were included. The aetiology of ischaemia was graft/stent/stent graft occlusion in 39.8%, arterial thrombosis in 27.7%, embolus in 25.1% and popliteal aneurysm in 7.4%. RESULTS: The mean follow-up was 59.4 months (95% CI, 56.1-62.7), during which 32.9% needed further re-interventions, 16.4% underwent amputation without re-intervention, and 50.7% had no re-intervention. The need for re-intervention during follow-up was 48.0% in the graft/stent occlusions group, 34.0% of the popliteal aneurysm group, 25.4% in the thrombosis group, and 16.3% in the embolus group (p < .001). The overall primary patency rates were 69.1% and 55.9% at 1 and 5 years, respectively. Primary patency at 5 years was higher for the embolus group (83.3%, p = .002) and lower for the occluded graft/stent group (43.3%, p < .001). Secondary patency rates were 80.1% and 75.2% at 1 and 5 years, respectively, without difference between the subgroups. The amputation rate was lower in the embolic group at 1 and 5 years (8.1% and 11.1%, respectively, p = .001). Survival was higher in the group with occluded popliteal aneurysms at 5 years (83.3%, p = 0.004). Amputation free survival was 72.1% and 45.2% at 1 and 5 years; lower in the occluded graft/stent group at five years (37.9%, p = .007). CONCLUSION: Intra-arterial thrombolytic therapy achieves good medium and long-term clinical outcome, reducing the need of open surgical treatment in most patients.

Neurofibromin-deficient myeloid cells are critical mediators of aneurysm formation in vivo.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 tumor suppressor gene. Neurofibromin, the protein product of NF1, functions as a negative regulator of Ras activity in circulating hematopoietic and vascular wall cells, which are critical for maintaining vessel wall homeostasis. NF1 patients have evidence of chronic inflammation resulting in the development of premature cardiovascular disease, including arterial aneurysms, which may manifest as sudden death. However, the molecular pathogenesis of NF1 aneurysm formation is unknown. METHOD AND RESULTS: With the use of an angiotensin II-induced aneurysm model, we demonstrate that heterozygous inactivation of Nf1 (Nf1(+/-)) enhanced aneurysm formation with myeloid cell infiltration and increased oxidative stress in the vessel wall. Using lineage-restricted transgenic mice, we show that loss of a single Nf1 allele in myeloid cells is sufficient to recapitulate the Nf1(+/-) aneurysm phenotype in vivo. Finally, oral administration of simvastatin or the antioxidant apocynin reduced aneurysm formation in Nf1(+/-) mice. CONCLUSION: These data provide genetic and pharmacological evidence that Nf1(+/-) myeloid cells are the cellular triggers for aneurysm formation in a novel model of NF1 vasculopathy and provide a potential therapeutic target.

Migraine-like Visual Aura Rriggered by a Large Aneurysm in the Left Extracranial Internal Carotid Artery with Successful Prevention of Recurrence by the new Anticoagulant Dabigatran: First Case Report.

PURPOSE: We present a rare case of late-onset migraine-like visual aura triggered by a large aneurysm in the left extracranial internal carotid artery. To the best of our knowledge, this is the first case of migraine-like visual aura triggered by an extracranial internal carotid artery (ICA) aneurysm. This is also the first case of migraine-like visual aura with probable thromboembolic trigger being successfully treated with a new anticoagulant, dabigatran. CASE REPORT: A 61-year-old woman complained about stereotypical episodes of a short-lasting flickering light in the right visual field for about half a year. Magnetic resonance imaging (MRI) of the head revealed a large aneurysm arising from the mid-cervical portion of the left internal carotid artery (ICA). After anticoagulant therapy with 110 mg of dabigatran twice a day, she became free from the visual symptom. CONCLUSION: Late-onset migraine with aura, especially typical aura without headache should be diagnosed carefully since it can be a challenge to distinguish it from signaling something serious. Micro-thromboembolism, commonly cardiogenic, but rarely arising from a carotid aneurysm, can trigger cerebral ischemic injury, causing transient neuronal hyperexcitability and cortical spreading depression (CSD)-like ''spontaneous'' waves propagating through the penumbra of the injured region into normally perfused tissue. The resultant symptoms may semiologically mimic visual aura. Migraine-like visual aura in this patient was successfully treated with dabigatran. It may not only imply that the patient's migraine-like visual aura was a thromboembolic event, but may also suggest the potential efficacy of the new anticoagulant, dabigatran, as the optimal alternative of warfarin in treating a thromboembolic event arising from a carotid aneurysm.

Intravitreal anti-VEGF therapy for retinal macroaneurysm.

BACKGROUND: We evaluated the effect of intravitreal anti-vascular endothelial growth factor therapy using bevacizumab or ranibizumab for retinal macroaneurysms with macular exudation. METHODS: In a retrospective interventional case series patients with retinal macroaneurysms were treated with either 1.25 mg intravitreal bevacizumab or 0.5 mg ranibizumab as first-line therapy. Patients were imaged by fluorescein angiography and optical coherence tomography. Retreatment was performed in case of persistent intraretinal or subretinal fluid in optical coherence tomography. RESULTS: Ten patients (10 eyes) with macroaneurysm involving the macula were treated with an average of 3.0 intravitreal anti-vascular endothelial growth factor injections. Mean best corrected visual acuity of all patients improved by 17 letters from baseline to the last follow-up visit. In 7 out of 10 patients, the fovea was affected by a secondary edema. In cases with foveal involvement, central retinal thickness decreased from 366 µm at baseline to 266 µm at the last follow-up visit. In the course of treatment 8 out of 10 patients showed evidence of marked regression of macular exsudation. CONCLUSION: Intravitreal anti-vascular endothelial growth factor therapy appears to be a promising treatment alternative to laser treatment in cases of retinal macroaneurysms with macular exudation.

Subgroups of children with Kawasaki disease: a data-driven cluster analysis.

BACKGROUND: Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups. METHODS: We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex. FINDINGS: Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup. INTERPRETATION: Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation. FUNDING: US National Institutes of Health and the Irving and Francine Suknow Foundation.

Glue ablation of Rasmussen's aneurysm in a case of epituberculosis.

A woman in her 40s presented with massive haemoptysis and breathlessness for 1 day. She had been diagnosed with pulmonary tuberculosis based on sputum CBNAAT (Cartridge Based Nucleic Acid Amplification Test) and was on antitubercular treatment for previous 2 weeks. Her chest X-ray showed right middle lobe lateral segment dense consolidation with bilateral nodular infiltrates. CT pulmonary angiography (CTPA) revealed a well-defined homogenously enhancing vascular lesion of size 10×11×13 mm in the right hilar region communicating with the descending branch of right pulmonary artery, suggesting a Rasmussen's aneurysm. It was in close proximity to the segmental bronchus that was almost completely occluded, suggesting epituberculosis. Transvenous pulmonary artery glue embolisation successfully achieved complete ablation of the aneurysm with preserved arterial flow. She has later completed 6 months of antitubercular treatment and is cured with no recurrence of haemoptysis. Her lung infiltrates have resolved with some lung scarring.

A Case of Idiopathic Retinitis Vasculitis Aneurysms and Neuroretinitis (IRVAN) Treated with Adalimumab.

PURPOSE: To report a case of IRVAN in a 13-year-old girl responding well to Adalimumab and Azathioprine. RESULTS: A 13-year-old girl presented to us with central scotoma for a duration of 10 months. She was treated earlier with oral steroids with poor response. Fundus examination revealed features of IRVAN. She was treated with intravitreal dexamethasone implant in both eyes with oral Mycophenolate Mofetil (MMF) with transient response to it. So she was switched over to subcutaneous Adalimumab 40 mg once in 2 weeks and oral Azathioprine 50 mg BD. The disease activity was well controlled with the current regime. CONCLUSION: Though various treatment modalities have been described in literature for the treatment of IRVAN. This is the first case of IRVAN to be treated with Adalimumab along with Azathioprine to be reported.

Idiopathic Retinal Vasculitis, Aneurysms and Neuroretinitis: Clinical Improvement with Infliximab.

PURPOSE: Idiopathic retinal vasculitis, aneurysms and neuroretinitis is a rare vision-threatening condition. If untreated vision loss occurs due to complications of progressive retinal ischaemia including retinal neovascularisation, neovascular glaucoma and retinal exudation. Despite the proposed underlying inflammatory aetiology this condition demonstrates poor response to corticosteroid treatment. The aim was to describe two paediatric cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis treated with infliximab. METHODS: Two case reports. RESULTS: Infliximab treatment led to resolution of aneurysmal dilatations and retinal vasculitis, and reversal of some retinal capillary non-perfusion. CONCLUSION: Early infliximab treatment should be considered in cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis.

Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD CAA prevention (KD-CAAP) trial protocol.

BACKGROUND: Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe. METHODS: KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes. DISCUSSION: Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children. TRIAL REGISTRATION: ISRCTN71987471- March 31, 2020; Eudract 2019-004433-17.

A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms

Objectives: Protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.5% in the general population and 3% in subjects with a first-time deep vein thrombosis (DVT). Here we report a series of 14 PC-deficient Polish patients with comprehensive clinical and molecular characteristics, including long-term follow-up data and a deep mutational analysis of the PROC gene. Patients and Methods: Fourteen unrelated probands (mean ± SD age 43.8 ± 13.0 years) with suspicion of PC deficiency, who experienced thromboembolic events and a majority of whom received anticoagulants (92.8%), were screened for PROC mutations by sequencing the nine PROC exons and their flanking intron regions. Results: Ten probands (71.4%) had missense mutations, two patients (14.3%) carried nonsense variants, and the other two subjects (14.3%) had splice-site mutations, the latter including the c.401-1G>A variant, reported here for the very first time. The proband carrying the c.401-1A allele had a hepatic artery aneurysm with a highly positive family history of aneurysms and the absence of any mutations known to predispose to this vascular anomaly. Conclusion: A novel detrimental PROC mutation was identified in a family with aneurysms, which might suggest yet unclear links of thrombophilia to vascular anomalies, including aneurysms at atypical locations in women. The present case series also supports data indicating that novel oral anticoagulants (NOACs) are effective in PC deficient patients.

Retinal microaneurysm count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme.

OBJECTIVE: To study the association between baseline retinal microaneurysm score and progression and regression of diabetic retinopathy, and response to treatment with candesartan in people with diabetes. METHODS: This was a multicenter randomized clinical trial. The progression analysis included 893 patients with Type 1 diabetes and 526 patients with Type 2 diabetes with retinal microaneurysms only at baseline. For regression, 438 with Type 1 and 216 with Type 2 diabetes qualified. Microaneurysms were scored from yearly retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Retinopathy progression and regression was defined as two or more step change on the ETDRS scale from baseline. Patients were normoalbuminuric, and normotensive with Type 1 and Type 2 diabetes or treated hypertensive with Type 2 diabetes. They were randomized to treatment with candesartan 32 mg daily or placebo and followed for 4.6 years. RESULTS: A higher microaneurysm score at baseline predicted an increased risk of retinopathy progression (HR per microaneurysm score 1.08, P < 0.0001 in Type 1 diabetes; HR 1.07, P = 0.0174 in Type 2 diabetes) and reduced the likelihood of regression (HR 0.79, P < 0.0001 in Type 1 diabetes; HR 0.85, P = 0.0009 in Type 2 diabetes), all adjusted for baseline variables and treatment. Candesartan reduced the risk of microaneurysm score progression. CONCLUSIONS: Microaneurysm counts are important prognostic indicators for worsening of retinopathy, thus microaneurysms are not benign. Treatment with renin-angiotensin system inhibitors is effective in the early stages and may improve mild diabetic retinopathy. Microaneurysm scores may be useful surrogate endpoints in clinical trials.

Pattern and outcome of vascular involvement of Omani patients with Behcet's disease.

The objective of the study is to study the pattern, frequency and outcome of vascular events in Omani patients with Behcet's disease (BD). Forty BD patients were recruited. Clinical data parameters were recorded, including age at onset, disease duration, current disease activity, and the vascular manifestations of the disease (current and past events). Disease activity was assessed by ESR, CRP and also clinically. For venous and arterial thrombotic events, imaging studies, such as Doppler ultrasonography, angiography, MRI, CT, and echocardiography were performed. Nine patients had vascular events (23%). The mean age of these patients at diagnosis of the vascular event was 24 years (range 15-37) and the mean disease duration at onset of the vascular event was 3.8 years (range 3-5); this was significant when compared with patients without thrombosis (P=0.001, Mann-Whitney test). In these patients with vascular involvement, two patients (22%) had venous lesions, three (33%) patients had arterial lesions and four patients (44%) had mixed lesions. Two patients (22%) had pulmonary artery aneurysm (PAA) and concomitant intracardiac thrombus, and further one patient also had PAA. Immunosuppressive therapy resulted in the resolution of PAA and intracardiac thrombous. In conclusion, the frequency of vascular complications of BD in our patients is similar to those reported around the world. We found younger male patients with short disease duration are at a greater risk of developing thrombosis. Medical treatment with immunosuppressive therapy without anticoagulation seems successful in treating PAA and intracardiac thrombus.

[Acute occlusion of a popliteal aneurysm - the value of intra-arterial preoperative thrombolysis]. / Oclusão aguda de aneurisma poplíteo - valor da fibrinólise intra-arterial pré-operatória.

In this paper it is presented a clinical report on intra-arterial thrombolysis of an acute thrombosed popliteal artery aneurysm. We report the technical aspects and discuss indications, principal advantages and contraindications of this form of treatment.

Activated Platelet-Homing Nanoplatform for Targeting Magnetic Resonance Imaging of Aneurysm-Related Thrombus in Rabbits.

Thrombosis is closely related to the instability of intracranial aneurysm (IA), whose rupture is associated with high morbidity and mortality. It is difficult to detect an IA-related thrombus because traditional magnetic resonance imaging (MRI) and even contrast-enhanced MRI cannot clearly distinguish a thrombus from the surrounding tissues. Herein, a nanoplatform [(MFe2O4-ZnDPA nanoparticles (NPs)], consisting of Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 NPs for imaging and Zn(II)-bis(dipicolylamine) (ZnDPA) for thrombus targeting, is constructed to target an experimental aneurysm-related thrombus in rabbits via MRI. In vitro experiments including platelet safety evaluation primarily prove that MFe2O4-ZnDPA NPs with a high MRI transverse relaxation time (T2) have good biocompatibility. MFe2O4-ZnDPA NPs could target a thrombus via the special interaction between ZnDPA and phosphatidylserine of activated platelets in the thrombus through MRI and Fe quantification assays. Moreover, after MFe2O4-ZnDPA NPs are injected into the ear vein of common carotid artery aneurysm model rabbits, MRI shows that MFe2O4-ZnDPA NPs could accumulate in the aneurysm-related thrombus from 0 to 15 min after injection and decrease in the next 45 min. Meanwhile, MFe2O4-ZnDPA NPs could decrease the MRI T2 signal of the aneurysm-related thrombus to enhance the outline of the aneurysm. This study demonstrates that a nanoplatform can enhance the detection of an aneurysm-related thrombus as well as aneurysm itself to assist further treatment of IA.