Worldwide Distribution and Extracutaneous Manifestations of Henoch-Schönlein Purpura in Adults: Narrative Review.

BACKGROUND: Henoch-Schönlein purpura (HSP), a leukocytoclastic small vessel vasculitis, exhibits both cutaneous and systemic manifestations. While predominantly observed in childhood, it may manifest in adults with more pronounced systemic involvement. Furthermore, HSP is a global phenomenon showcasing epidemiological and systemic variances. OBJECTIVE: This study aims to scrutinize extracutaneous manifestations in adults with HSP, discerning distinctions according to geographical regions on a worldwide scale. METHODS: A comprehensive search encompassing PubMed, Embase, Cochrane Library, and Web of Science was executed, covering papers published from January 1, 1970, to December 1, 2019. Keywords used included "Henoch-Schönlein purpura," "henoch schonlein purpura+adult," "IgA vasculitis+adult," "HSP+adult," and "IgAV." A total of 995 publications were identified, from which 42 studies encompassing 4064 patients were selected, with a predominant focus on cases reported in Asia, Europe, and the Americas. RESULTS: Among adults afflicted with HSP, European patients exhibited a higher propensity for male predominance (P<.001), gastrointestinal involvement (P<.001), and musculoskeletal complications (P<.001). Conversely, patients from the Americas were least likely to experience genitourinary involvement (P<.001). CONCLUSIONS: HSP demonstrates a variance in distribution and extracutaneous manifestations within distinct geographical boundaries. In the adult population, European patients exhibited a higher prevalence of male gender and gastrointestinal and musculoskeletal involvement. Asian patients were more predisposed to genitourinary involvement when compared to their American counterparts. The establishment of prospective studies using standardized reporting measures is imperative to validate the relationships unveiled in this investigation.

Non-muscle MYH10/myosin IIB recruits ESCRT-III to participate in autophagosome closure to maintain neuronal homeostasis.

Dysfunction of the endosomal sorting complex required for transport (ESCRT) has been linked to frontotemporal dementia (FTD) due in part to the accumulation of unsealed autophagosomes. However, the mechanisms of ESCRT-mediated membrane closure events on phagophores remain largely unknown. In this study, we found that partial knockdown of non-muscle MYH10/myosin IIB/zip rescues neurodegeneration in both Drosophila and human iPSC-derived cortical neurons expressing FTD-associated mutant CHMP2B, a subunit of ESCRT-III. We also found that MYH10 binds and recruits several autophagy receptor proteins during autophagosome formation induced by mutant CHMP2B or nutrient starvation. Moreover, MYH10 interacted with ESCRT-III to regulate phagophore closure by recruiting ESCRT-III to damaged mitochondria during PRKN/parkin-mediated mitophagy. Evidently, MYH10 is involved in the initiation of induced but not basal autophagy and also links ESCRT-III to mitophagosome sealing, revealing novel roles of MYH10 in the autophagy pathway and in ESCRT-related FTD pathogenesis.Abbreviations: ALS: amyotrophic lateral sclerosis; AP: autophagosome; Atg: autophagy-related; ESCRT: endosomal sorting complex required for transport; FTD: frontotemporal dementia.

Increasing Advocacy Awareness in Early Career Rheumatologists: A Web-Based Educational Tool.

OBJECTIVE: To evaluate the utility of a web-based advocacy training tool in increasing advocacy awareness. METHODS: Early career rheumatologists who attended 2019 American College of Rheumatology Advocacy 101 were invited to participate. A web-based tool consisting of 9 cases covering various aspects of advocacy was developed and included the opportunity for continuing medical education credit. A preparticipation questionnaire surveyed prior involvement, knowledge, and willingness to participate in an advocacy program. Participants rated cases based on educational quality, relevance of content, achievement of training goals, competency, and evidence of bias. Two web-based conferences were held to address technical questions, review, and discussion of cases and responses, and to obtain feedback. RESULTS: Twenty-one early career rheumatologists from 9 academic institutions enrolled, with 15 (75%) completing all cases. Correct continuing medical education answers were scored on 85% of cases. Overall educational quality of content received a mean rating of 4.3 of 5. Seven cases achieved positive ratings for relevance of case content, achievement of training goals, objectivity, and competency. All cases were assessed free of bias. Feedback indicated that 30 minutes were dedicated to each case, and that a combination of skill set and content learning were most effective. Pre- and postquestionnaire scores indicated significant improvement in knowledge of advocacy matters (P < 0.0001). CONCLUSION: A web-based advocacy training tool was successful in significantly improving awareness and knowledge of advocacy matters among early career rheumatologists. This innovative educational tool may play a vital role in shaping the future of rheumatology for both patients and physicians.

Opana-induced thrombotic microangiopathy masquerading as thrombotic thrombocytopenic purpura.

Opana (oxymorphone) is a powerful semi-synthetic opioid agonist used for chronic pain management that is ingested orally. However, improper injection of Opana can lead to a rare and fatal blood disorder known as thrombotic microangiopathy. Opana-induced thrombotic microangiopathy can be easily mistaken for thrombotic thrombocytopenic purpura (TTP), leading to the initiation of therapeutic plasma exchange. Current literature has conflicting views on the necessity of therapeutic plasma exchange for the treatment of Opana-induced thrombotic microangiopathy. In our case report, a 47-year-old Caucasian male was admitted with a presentation suspicious for TTP then underwent therapeutic plasma exchange without clinical improvement. With supportive treatment only, the patient eventually improved and later admitted to intravenously abusing oral Opana 1-2 days prior to becoming ill.

Autophagy negatively regulates early axon growth in cortical neurons.

Neurite growth requires neurite extension and retraction, which are associated with protein degradation. Autophagy is a conserved bulk degradation pathway that regulates several cellular processes. However, little is known about autophagic regulation during early neurite growth. In this study, we investigated whether autophagy was involved in early neurite growth and how it regulated neurite growth in primary cortical neurons. Components of autophagy were expressed and autophagy was activated during early neurite growth. Interestingly, inhibition of autophagy by atg7 small interfering RNA (siRNA) caused elongation of axons, while activation of autophagy by rapamycin suppressed axon growth. Surprisingly, inhibition of autophagy reduced the protein level of RhoA. Moreover, expression of RhoA suppressed axon overelongation mediated by autophagy inhibition, whereas inhibition of the RhoA signaling pathway by Y-27632 recovered rapamycin-mediated suppression of axon growth. Interestingly, hnRNP-Q1, which negatively regulates RhoA, accumulated in autophagy-deficient neurons, while its protein level was reduced by autophagy activation. Overall, our study suggests that autophagy negatively regulates axon extension via the RhoA-ROCK pathway by regulating hnRNP-Q1 in primary cortical neurons. Therefore, autophagy might serve as a fine-tuning mechanism to regulate early axon extension.

ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons.

Tar-DNA binding protein of 43kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons.