Venous Sac and Feeding Artery Embolization versus Feeding Artery Embolization Alone for Treating Pulmonary Arteriovenous Malformations: Draining Vein Size Outcomes

PurposeTo investigate and compare venous sac and feeding artery embolization (VFE) with feeding artery embolization (FAE) alone for treatment of pulmonary arteriovenous malformations (PAVMs), based on difference in outcomes in decrease of the size of the draining vein.Materials and MethodsTwenty-six patients (7 male and 19 female; median age [interquartile range], 58 years [46–65 years]) with 42 simple PAVMs treated with coil embolization between August 2005 and December 2018 were retrospectively evaluated. Twenty PAVMs were treated with FAE early in the study period and compared with 22 PAVMs treated with VFE later in the study period. Follow-up computed tomography images obtained 8–20 months after embolotherapy were used for outcome analysis. Data related to patient demographics; follow-up period; baseline diameters of the feeding artery, venous sac, and draining vein; draining vein diameter after treatment; and decrease in the size of the draining vein, including the number reaching a threshold of 70% decrease, were compared between the 2 groups.ResultsThe draining vein decreased in size by a median of 46.4% in the FAE group and 66.3% in the VFE group, and the difference between the 2 groups was statistically significant (P = .009). There were no significant differences in the other parameters.ConclusionsVFE leads to a greater decrease in the size of the draining vein than FAE, suggesting that VFE results in more complete occlusion than FAE for treatment of PAVMs.     

The diverse origin of bone-forming osteoblasts

Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized matrix production. Because osteoblasts have a limited lifespan, they must be constantly replenished by preosteoblasts, their immediate precursors. Because disruption of the regulation of bone-forming osteoblasts results in a variety of bone diseases, a better understanding of the origin of these cells by defining the mechanisms of bone development, remodeling, and regeneration is central to the development of novel therapeutic approaches. In recent years, substantial new insights into the origin of osteoblasts—largely owing to rapid technological advances in murine lineage-tracing approaches and other single-cell technologies—have been obtained. Collectively, these findings indicate that osteoblasts involved in bone formation under various physiological, pathological, and therapeutic conditions can be obtained from numerous sources. The origins of osteoblasts include, but are not limited to, chondrocytes in the growth plate, stromal cells in the bone marrow, quiescent bone-lining cells on the bone surface, and specialized fibroblasts in the craniofacial structures, such as sutures and periodontal ligaments. Because osteoblasts can be generated from local cellular sources, bones can flexibly respond to regenerative and anabolic cues. However, whether osteoblasts derived from different cellular sources have distinct functions remains to be investigated. Currently, we are at the initial stage to aptly unravel the incredible diversity of the origins of bone-forming osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Phase 1 study of crisaborole in Japanese healthy volunteers and patients with atopic dermatitis

Crisaborole ointment, 2%, is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD). This parallel-cohort, phase 1 study was conducted to investigate skin irritation potential and safety of crisaborole in healthy Japanese adults (cohort 1) and the safety and pharmacokinetic profile of crisaborole and metabolites AN7602 and AN8323 in Japanese adults with mild to moderate AD (cohort 2). In cohort 1, 20 healthy volunteers received single applications of crisaborole and vehicle simultaneously on separate locations under 48-h occlusion. In cohort 2, 12 patients with mild to moderate AD received crisaborole (n = 10) or vehicle (n = 2) twice daily for 8 days. Skin irritation and safety were assessed in cohort 1. Pharmacokinetics and safety were assessed in cohort 2. Skin irritation index (scale 0–400) was 40.0 for crisaborole and 5.0 for vehicle. No treatment-emergent adverse events (TEAE) were reported in cohort 1. The most common TEAE in the crisaborole group in cohort 2 were application site irritation (n = 7) and application site pain (n = 4). Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8 that was comparable with that seen in US-based participants in previous trials. Crisaborole had higher skin irritation than vehicle under occlusion in healthy Japanese adults and had an acceptable safety profile in Japanese adults with mild to moderate AD.     

Survey of Japanese dermatological vasculitis specialists on cases of cutaneous arteritis (cutaneous polyarteritis nodosa)

We developed a questionnaire to examine the findings of cutaneous arteritis among dermatological specialists experienced in vasculitis as certified by the Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. We sent a questionnaire to 12 dermatological facilities identified through the revised Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. Retrospective data obtained from 84 patients at the 12 dermatological facilities between 2012 January 2016 December were evaluated. The 84 patients were categorized into two groups, a systemic steroid treatment group (group 1, n = 52) and a no systemic steroid treatment group (group 2, n = 32). C-reactive protein in group 1 patients was significantly higher than that in group 2 patients. Frequency of fever, arthritis, myalgia- and peripheral neuropathy in group 1 was significantly higher than that in group 2. We propose that these symptoms could serve as early markers for the transfer from cutaneous arteritis to systemic polyarteritis nodosa. We further suggest that patients who are subsequently associated with cerebral hemorrhage and infarction, who are originally diagnosed as having cutaneous arteritis, could progress to systemic polyarteritis nodosa. The study demonstrated that it is important for dermatologists to detect these findings early in order to establish an accurate diagnosis and a timely treatment.     

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.