COVID-19 infection- and vaccination-related exacerbation of Darier's disease in a single patient.

Darier's disease (DD) is a rare autosomal dominantly inherited disorder. DD patients usually present with widespread keratotic eruptions with itching in the seborrheic regions that are exacerbated by various factors, including heat, sweat, and physical trauma. The SARS-CoV-2 (COVID-19) pandemic has stirred confusion among the medical community, including dermatologists, as this infection has been implicated in various skin conditions. Only a handful of reports have documented DD associated with COVID-19. Here, we report a 30-year-old male with Darier's disease whose symptoms were exacerbated following both COVID-19 vaccination and COVID-19 infection. The patient had noticed slight eruptions 7 years prior, but was not particularly concerned. After COVID-19 vaccination and infection, he had erythematous maculopapular lesions in large areas of the trunk and extremities. The previously reported pathogenic variant c.2255_2257del (p.(Ile752_Tyr753delinsAsn)) in ATP2A2 was detected in the present patient. Oral etretinate greatly improved his DD manifestations. As far as we know, the present patient is the first genetically confirmed DD case who showed both COVID-19 infection- and vaccination-related DD exacerbations independently. We think that the further accumulation of DD cases exacerbated by COVID-19 infection/vaccination is needed to clarify the mechanisms of DD aggravation.

Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck.

Angiosarcoma of the head and neck (ASHN) is one of the most aggressive malignancies of the skin, but the prognostic factors are not well known because of its rarity. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. In the present retrospective study, we suggest that low plasma fibrinogen levels predict poor prognosis for ASHN.

Future stroke risk in the chronic phase of post-percutaneous coronary intervention.

A percutaneous coronary intervention (PCI) is widely performed for acute coronary syndromes or chronic coronary syndromes. Periprocedural stroke is a clinically significant complication during PCI. The incidence of cerebrovascular events (CVEs) after PCI in the chronic phase is obscure. This study aimed to investigate the prevalence of CVEs after PCI in the chronic phase and evaluate the usefulness of a simple coronary artery calcification (CAC) evaluation method. This prospective observational study included 179 patients who underwent PCI between January 2016 and December 2018. The incidence of cerebral infarction was examined from one month after PCI to December 2019. In total, 171 individuals (134 men; mean age, 69.8 ± 9.8 years) were recruited. During a median follow-up period of 33 months, the onset of cerebral infarction was observed in 20 individuals (11.7%). More CAC sites (p = 0.009) and post-PCI for the chronic coronary syndrome (p = 0.049) showed a significant association with future CVEs. There was no significant cervical internal carotid artery stenosis for patients who occurred CVEs. The cutoff value for the number of CAC sites for predicting future CVEs was 4.5. The new and easy method accurately reflected future CVEs risk and may be clinically applicable.

Predominant localization of phosphatidylserine at the cytoplasmic leaflet of the ER, and its TMEM16K-dependent redistribution.

TMEM16K, a membrane protein carrying 10 transmembrane regions, has phospholipid scramblase activity. TMEM16K is localized to intracellular membranes, but whether it actually scrambles phospholipids inside cells has not been demonstrated, due to technical difficulties in studying intracellular lipid distributions. Here, we developed a freeze-fracture electron microscopy method that enabled us to determine the phosphatidylserine (PtdSer) distribution in the individual leaflets of cellular membranes. Using this method, we found that the endoplasmic reticulum (ER) of mammalian cells harbored abundant PtdSer in its cytoplasmic leaflet and much less in the luminal leaflet, whereas the outer and inner nuclear membranes (NMs) had equivalent amounts of PtdSer in both leaflets. The ER and NMs of budding yeast also harbored PtdSer in their cytoplasmic leaflet, but asymmetrical distribution in the ER was not observed. Treating mouse embryonic fibroblasts with the Ca2+ ionophore A23187 compromised the cytoplasmic leaflet-dominant PtdSer asymmetry in the ER and increased PtdSer in the NMs, especially in the nucleoplasmic leaflet of the inner NM. This Ca2+-induced PtdSer redistribution was not observed in TMEM16K-null fibroblasts, but was recovered in these cells by reexpressing TMEM16K. These results indicate that, similar to the plasma membrane, PtdSer in the ER of mammalian cells is predominantly localized to the cytoplasmic leaflet, and that TMEM16K directly or indirectly mediates Ca2+-dependent phospholipid scrambling in the ER.