To evaluate the efficacy and safety of secukinumab in Behçet's patients with active mucocutaneous and articular manifestations refractory to previous treatments.
We retrospectively evaluated 5 ...patients treated with the IL17-inhibitor secukinumab and diagnosed with Behçet according to ISG/ICBD criteria. All patients had active mucocutaneous and articular manifestations refractory to colchicine, conventional DMARDs and at least one anti-TNFα agent. Four patients received secukinumab in the dose of 150 mg/monthly since also fulfilling the criteria for ankylosing spondylitis, while the fifth patient received secukinumab 300 mg/monthly because she met psoriatic arthritis criteria. Achievement of response was based on the number of oral ulcers, BASDAI and ASDAS for articular involvement, and BDCAF for Behçet activity. Complete response was defined as: i) decrease ≥50% in the number of oral ulcers; ii) BASDAI index <4; iii) ASDAS index <1.4; iv) decrease of 50% or more in BDCAF index.
The patient starting secukinumab 300 mg/month successfully achieved complete response within 3 months. Complete response was maintained during all 9-months follow-up. Among the 4 subjects starting secukinumab 150 mg/month, two achieved complete response at month 6, but one relapsed. This patient and the two who not achieved complete response at month 6 were switched to secukinumab 300 mg/month. Within 3 months from the dosage increase, all three subjects successfully (re)achieved complete response.
Our study suggested for the first time that secukinumab (either 150 mg and 300 mg/month) improved active mucocutaneous manifestations refractory to previous treatments, while secukinumab 300 mg/monthly resulted superior in inducing articular and complete response in Behçet's patients.
•Secukinumab is effective for Behçet's mucocutaneous and articular manifestations.•Secukinumab 300 mg is superior to 150 mg for inducing articular and complete response.•Due to secukinumab safety concerns in IBD, attention must be paid in entero-Behçet.
•The incidence of spondylodiscitis is increasing due to the increase in susceptible population and improved ascertainment.•The diagnosis is often delayed or missed.•A fungal aetiology is rare.•There ...is a global shift toward invasive candidiasis due to C. glabrata which has a variable susceptibility to antifungal drugs.
Spondylodiscitis is an infection of the vertebral column, the incidence of which is increasing due to an increase in the susceptible population and improved ascertainment. This disease has been associated with a wide range of microorganisms. Fungal spondylodiscitis is uncommon (0.5–1.6%) and strongly associated with immunosuppression and diabetes (Gouliouris et al., 2010). A rare case of Candida glabrata spondylodiscitis in a non-neutropenic diabetic patient is reported herein, along with a review of the literature.
A case of C. glabrata spondylodiscitis of L3–L4 metameres was diagnosed. The diagnosis was obtained through open biopsy of an abscess and culture examination. The patient was treated with anidulafungin and surgical debridement of the lesion.
The diagnosis of spondylodiscitis is often delayed or missed. Physicians should consider this entity in the differential diagnosis of lumbar pain in order to initiate an appropriate therapy to prevent spinal cord lesions and disability. This is particularly relevant in the case of a fungal aetiology, as there is a recognized global shift towards invasive candidiasis due to non-albicans Candida species, in particular C. glabrata, which has variable susceptibility to antifungal drugs.
The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid ...plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS.
A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed.
CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS.
Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk-benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.
Abstract
Aims
Venous thromboembolism represents frequent complication of patients with severe COVID-19 disease. Several reports about atypical thrombosis are described, rarely it has been described a ...right venticular thrombus during the course of infection. We report a case of right endoventricular thrombosis in a patient with SARS-Cov-2 pneumonia.
Methods and results
A 58-year-old man was admitted to our ward for severe respiratory failure in interstitial pneumonia. The nasopharyngeal swab for COVID-19 resulted positive. Steroids and prophylaxis with LMWH were started, associated to CPAP to maintain good gas exchange. During hospitalization a venous ECD was performed with evidence of left popliteal thrombosis despite the therapy. d-Dimer was 4463 ng/ml. A new onset AF was documented at the telemetry, without troponin elevation. A cardiac ultrasound was performed showing a right endoventricular lesion of 1.8 cm adhering to the free wall of the right ventricle. A CT-pulmonary angiogram (CTPA) resulted negative for pulmonary embolism and confirmed suspected right ventricular thrombus. Treatment with fondaparinux 7.5 mg was started. After 10 days, cardiac ultrasound shown complete resolution of thrombosis, and CT confirmed the disappearing of the mass. Dabigatran 150 mg twice/day was started. Patient clinically improved and he was discharged after 20 days of hospitalization.
Conclusions
SARS-CoV-2 infection may cause inflammation with cytokine storm and hypercoagulability leading to venous thromboembolism. Atypical thrombus formation was reported, including right-ventricle free wall. Early caridac ultrasound was critical to make diagnosis and starting prompt treatment, therefore routine cardiac ultrasound is mandatory in severe COVID-19 patients.
Hyper IgM1 is an X‐linked combined immunodeficiency caused by CD40LG mutations, potentially treatable with CD4+ T‐cell gene editing with Cas9 and a “one‐size‐fits‐most” corrective template. Contrary ...to established gene therapies, there is limited data on the genomic alterations following long‐range gene editing, and no consensus on the relevant assays. We developed drop‐off digital PCR assays for unbiased detection of large on‐target deletions and found them at high frequency upon editing. Large deletions were also common upon editing different loci and cell types and using alternative Cas9 and template delivery methods. In CD40LG edited T cells, on‐target deletions were counter‐selected in culture and further purged by enrichment for edited cells using a selector coupled to gene correction. We then validated the sensitivity of optical genome mapping for unbiased detection of genome wide rearrangements and uncovered on‐target trapping of one or more vector copies, which do not compromise functionality, upon editing using an integrase defective lentiviral donor template. No other recurring events were detected. Edited patient cells showed faithful reconstitution of CD40LG regulated expression and function with a satisfactory safety profile. Large deletions and donor template integrations should be anticipated and accounted for when designing and testing similar gene editing strategies.
Synopsis
Long range gene editing by homology‐driven recombination with Cas9 and a donor template can faithfully reconstitute gene regulation from the native locus. The current study shows that such gene editing approaches can result in heterogeneous by‐stander genomic outcomes that are difficult to assess.
Large deletions are common, can be assessed by droplet digital PCR, and may be counter selected in culture and purged by selection of edited cells.
Optical genome mapping can detect structural rearrangements with high sensitivity.
Donor integrase‐defective lentiviral templates can be integrated on‐target in multiple copies.
Large, complex on‐target rearrangements identified following CRISPR HDR gene editing of human cells demonstrate a need for careful genomic assessment prior to use in patients.
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