Masson’s Tumour - Case Report of a Malignant Masquerader with Literature Review

Masson’s tumour, an uncommon, benign vascular disorder was first described by Pierre Masson in 1923 as an intravascular papillary proliferation that emerged from an inflamed hemorrhoidal vein of a 68-year-old man and termed it as “Hemangioendotheliome vegetant intravasculaire”.1 He interpreted the lesion as a form of neoplasm, however, Henschen portrayed it as a reactive phenomenon. The current terminology intravascular papillary endothelial hyperplasia (IPEH) was put forward by Clearkin and Enzinger in 1976 considering it as a reactive change occurring secondary to trauma-related vascular stasis.2 The tumour constitutes 2-4 % of all skin and soft tissue tumours. The common locations are head, neck and extremities.3 Masson’s tumour being a benign entity with an excellent prognosis is essential to differentiate from its closer mimic, angiosarcoma which needs aggressive treatment. This case is put up here because of its rarity and its clinical implications.

Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI)

Introduction Hemophilia A and B are rare bleeding disorders characterized by ineffective clot formation due to impaired thrombin generation as a result of deficiency of FVIII or FIX, respectively. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic targeting antithrombin to restore thrombin generation and rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Here, we present the safety and efficacy of fitusiran prophylaxis for PwHI in a phase 3 study (ATLAS-INH; NCT03417102). Methods The ATLAS-INH study is a randomized, open-label Phase 3 study designed to evaluate the efficacy and safety of fitusiran in PwHI. Eligible males ≥12 years receiving on-demand treatment with bypassing agents (BPA) were randomized in a 2:1 ratio to receive once monthly 80 mg SC fitusiran prophylaxis or continue with on-demand BPA. The primary endpoint is annualized bleeding rate (ABR) in PwHI on fitusiran prophylaxis compared to those on BPA on-demand in the efficacy period. The secondary endpoints include spontaneous ABR, joint ABR, and quality of life (QoL) measured by Haem-A-QoL. Results 57 subjects were randomized into the study. Mean (range) age of the study participants at screening was 28.4 (13-63) yrs. Statistical significance was achieved for primary and all secondary endpoints with significant reduction in ABRs of treated bleeds: all, spontaneous and joint bleeds for fitusiran vs on-demand BPA arm (Table 1). A total of 25 patients in fitusiran arm (65.8%) had zero treated bleeding events. Efficacy of fitusiran prophylaxis treatment was seen in both hemophilia A and hemophilia B patients with inhibitors. Statistical significance was also achieved for improvement in physical health domain score, with a difference (95% CI) of -28.72 (-39.07 to -18.37, p-value <0.0001) as well as overall HRQoL and between fitusiran and on-demand BPA arms. Overall, 38 patients (92.7%) in the fitusiran arm and 11 patients (57.9%) in the on-demand BPA arm experienced at least 1 treatment emergent adverse event (TEAE). A total of 13 treatment emergent serious adverse events (TESAEs) were reported in 7 patients (17.1%) in the fitusiran arm and 8 TESAEs were reported in 5 patients (26.3%) in the on-demand BPA arm. All TESAEs were reported in 1 patient each; in the fitusiran prophylaxis arm these included events of device related infection, hematuria, spinal vascular disorder, subclavian vein thrombosis, thrombosis, acute cholecystitis, chronic cholecystitis and asymptomatic COVID-19. One patient (2.4%) in the fitusiran arm experienced TEAEs that resulted in study drug discontinuation (spinal vascular disorder and thrombosis). There were no fatal TEAEs reported. Conclusions This Phase 3 study demonstrated the efficacy of the 80 mg monthly subcutaneous prophylaxis dose of fitusiran in people with hemophilia A or B with inhibitors. Specifically, fitusiran significantly reduced bleeding with a median ABR of zero and significant proportion of people with zero bleeds, resulting in a meaningful improvement in health-related quality of life. Reported TESAEs were generally consistent with what is anticipated in an adult and adolescent population with severe hemophilia A or B with inhibitors, or with the previously identified risks of fitusiran. A revised fitusiran dosing regimen with reduced dose and dose frequency is currently being evaluated in ongoing clinical studies. Figure 1 Figure 1. Disclosures Young: Genentech/Roche, Grifols, and Takeda: Research Funding; Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy. Kavakli: Roche: Consultancy, Other: Clinical Trial Support; Novo Nordisk A/S: Consultancy, Other: Clinical Trial Support; Takeda: Consultancy, Other: Clinical Trial Support. Poloskey: Sanofi: Current Employment, Current equity holder in publicly-traded company. Qui: Sanofi: Current Employment, Current equity holder in publicly-traded company. Kichou: Sanofi: Current Employment, Current equity holder in publicly-traded company. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company; WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Mei: Sanofi: Current Employment, Current equity holder in publicly-traded company. Rangarajan: Sanofi: Other: Advisory Board; Pfizer: Other: Advisory Board; Reliance Life Sciences: Consultancy; Takeda: Other: Advisory Board, Conference Support, Speakers Bureau.

Behcet’s Disease: An In-depth Review About Pathogenesis, Gastrointestinal Manifestations And Management

Background: Behcet’s Disease (BD) is a complex inflammatory vascular disorder that follows a relapsing-remitting course with diverse clinical manifestations. The prevalence of the disease varies throughout the globe and targets different age groups. There are many variations of BD, however, intestinal BD is not only more common but has many signs and symptoms. Summary: BD is a relapsing-remitting inflammatory vascular disorder with multiple system involvement, affecting vessels of all types and sizes that targets young adults. The etiology of BD is unknown but many factors including genetic mechanisms, vascular changes, hypercoagulability and dysregulation of immune function are believed to be responsible. BD usually presents with signs and symptoms of ulcerative disease of the small intestine; endoscopy being consistent with the clinical manifestations. The mainstay of treatment depends upon the severity of the disease. Corticosteroids are recommended for severe forms of the disease and aminosalicylic acids are used in maintaining remission in mild to moderate forms of the disease. Key messages: In this review, we have tried to summarize in the present review the clinical manifestations, differential diagnoses and management of intestinal BD. Hopefully, this review will enable health policymakers to ponder over establishing clear endpoints for treatment, surveillance investigations and creating robust algorithms.

Varicose veins: our experience in KVG Medical College and Hospital, Karnataka

Background: The varicose veins is the most common vascular disorder of the lower extremities. It affects more than 5% of adult population but in India incidence of varicose veins seems to be far less common because patients come for complications such as pain, oedema, pigmentation and ulceration leading to tip of Iceberg phenomenon. This study will help in finding epidemiology, mode of presentation and effect of surgery on venous ulcers and recurrence. The aims and objectives of the study was to study the incidence of varicose veins according to age, sex and occupation with spectrum of clinical presentation in varicose veins. To determine effect of surgery in healing of varicose ulcers if present and study of recurrence upto 6 months.Methods: This prospective study involved 50 patients admitted in KVG Medical College and Hospital, Sullia with clinical diagnosis of varicose veins. The study period was 18 months inclusive of a 6 month follow up period.Results: Most patients was between 41 to 50 years (26 %.), males (74%), left side involvement in (70%) and farmer by occupation (40%) with pain as most common presenting symptom in (76%). Long saphenous system involvement in (94%). 6 patients out of 50 showed recurrence of varicose veins. 4 patient showed recurrence out of 21 venous ulcer patients.Conclusions: For varicose veins saphenofemoral junction ligation with stripping of vein with perforator ligation showed good outcome. Venous ulcers heal well after surgery with few recurrences.

Hydrolysis of a second Asp-Pro site at the N-terminus of NOTCH3 in inherited vascular dementia

Cerebrovascular pathology at the biochemical level has been informed by the study of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a vascular disorder caused by NOTCH3 mutations. Previous work in CADASIL described N-terminal proteolysis of NOTCH3 generated by specific non-enzymatic cleavage of the first Asp-Pro sequence of the protein. Here, we investigated whether the second Asp-Pro peptide bond (residues 121–122) of NOTCH3 is cleaved in CADASIL. Monospecific antibodies were generated that recognize the neo-epitope predicted to be generated by cleavage after Asp121. These antibodies were used to localize cleavage events at Asp121 in post-mortem CADASIL and control brain tissue and to investigate factors that regulate cleavage at Asp121. We report that cleavage at Asp121 occurs at a high level in the arterial media of CADASIL cerebral arteries. Leptomeningeal arteries demonstrated substantially more cleavage product than penetrating arteries in the white matter, and control vessels harbored only a small amount of cleaved NOTCH3. Proteolysis at Asp121 occurred in purified preparations of NOTCH3 ectodomain, was increased by acidic pH and reductive conditions, and required native protein conformation for cleavage. Increasing the concentration of NOTCH3 EGF-like domain protein elevated the level of proteolysis. On the other hand, several polyanionic chemicals potently blocked cleavage at Asp121. These studies demonstrate that the NOTCH3 protein in CADASIL is cleaved in multiple locations at labile Asp-Pro peptide bonds. As such, chronic brain vascular disease, like other neurodegenerative conditions, features proteolysis of pathological proteins at multiple sites which may generate small pathological peptides.

Polypyrrole-Coated Magnetite Vortex Nanoring for Hyperthermia-Boosted Photothermal/Magnetothermal Tumor Ablation Under Photoacoustic/Magnetic Resonance Guidance

Photothermal/magnetothermal-based hyperthermia cancer therapy techniques have been widely investigated, and associated nanotechnology-assisted treatments have shown promising clinical potentials. However, each method has some limitations, which have impeded extensive applications. For example, the penetration ability of the photothermal is not satisfactory, while the heating efficiency of the magnetothermal is very poor. In this study, a novel magnetite vortex nanoring nanoparticle-coated with polypyrrole (denoted as nanoring Fe3O4@PPy-PEG) was first synthesized and well-characterized. By combining photothermal and magnetothermal effects, the performance of the dual-enhanced hyperthermia was significantly improved, and was thoroughly examined in this study. Benefiting from the magnetite vortex nanoring and polypyrrole, Fe3O4@PPy-PEG showed excellent hyperthermia effects (SAR = 1,648 Wg–1) when simultaneously exposed to the alternating magnetic field (300 kHz, 45 A) and near-infrared (808 nm, 1 W cm–2) laser. What is more, nanoring Fe3O4@PPy-PEG showed a much faster heating rate, which can further augment the antitumor effect by incurring vascular disorder. Besides, Fe3O4@PPy-PEG exhibited a high transverse relaxation rate [60.61 mM–1 S–1 (Fe)] at a very low B0 field (0.35 T) and good photoacoustic effect. We believe that the results obtained herein can significantly promote the development of multifunctional nanoparticle-mediated magnetic and photo induced efficient hyperthermia therapy.

A RARE CASE OF OSLER-WEBER-RENDU SYNDROME IN PREGNANCY

Hereditary Haemorrhagic Telangiectasia is a genetic vascular disorder, having ve variants depending on underlying gene mutations and characterised by aneurysms and arterio-venous malformations. Larger AVMs present most commonly in the brain, lung, and liver. The diagnosis is mainly clinical based on the Curacao Criteria. Serious Neurological complications can occur in up to 10% of cases. Pregnancy associated hormonal changes affect the cardiovascular system manifesting in the second and third trimesters. Majority of the pregnancies are uneventful, but severe complications and even death can occur. HHT in pregnancy is considered high risk and needs management by a multidisciplinary team. Women with HHT planning pregnancy should be counselled regarding the rare but serious risks. Strict antenatal surveillance and prior awareness of the diagnosis of HHT is usually associated with good pregnancy outcomes.

Cystic adventitial disease of the popliteal artery and ILIAC vein

These two cases of successful treatment of a rare vascular disorder – cystic adventitial disease (CAD). Case 1: CAD of the popliteal artery with narrowing of the popliteal artery and intermittent claudication. Case 2: CAD of iliac vein with irreducible femoral hernia formation and iliac vein subocclusion. We described preoperative planning, surgical intervention and postoperative management in our cases. Surgery after careful preoperative planning is only one effective method of treatment of CAD and has good long-term results.

Digital Ischemia and Necrosis from Oxaliplatin

Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in direct cell cytotoxicity with resultant cell death. The most common side effects often noted are neurotoxicity, nausea, vomiting, diarrhea, hepatotoxicity and myelosuppression. Oxaliplatin induced digital ischemia and necrosis is a rare side effect that was observed in our patient. In general, digital ischemia is a rare vascular disorder that is often associated with autoimmune disease [1]. Here, we intend to present a patient with digital ischemia due to Oxaliplatin, which was a chemotherapy agent used in the treatment of his urachal adenocarcinoma.