Merkel Cells as Putative Regulatory Cells in Skin Disorders: An In Vitro Study

Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca2+-independent, as inhibition of Ca2+ channels or culture in the absence of Ca2+ failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

5 Mechanical thrombectomy in acute ischemic stroke patients with low alberta stroke program early computed tomography scores

Background and purposeLimited data exists on the benefit of mechanical thrombectomy (MT) in acute ischemic stroke patients presenting with low ASPECTS (Alberta Stroke Program Early Computed Tomography (CT) Score). The aim of this substudy was investigate the outcome of low ASPECTS (0–5) patients undergoing mechanical thrombectomy in the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) Registry.MethodsData from the STRATIS Registry, a prospective, multicenter, non-randomized, observational study of AIS LVO patients treated with the Solitaire stent-retriever as the first choice therapy within 8 hours from symptoms onset, was used to identify patients with baseline ASPECTS 0–5. CT ASPECTS was adjudicated by a core lab blinded to clinical outcomes.ResultsA total of 57/763 (7.5%) patients had a baseline ASPECTS 0–5, of which 10 were ASPECTS 0–3 and 47 ASPECTS 4–5. Mean baseline NIHSS was 19.9±5.1. The majority of patients presented with ICA (42.1%) and M1 (47.4%) occlusions. IV-rtPA was administered in 68.4%. Mean onset to arterial puncture was 276±102.9 minutes and puncture to reperfusion time was 45.3±25.3 minutes. The majority of patients (85.5%) achieved substantial reperfusion (mTICI≥2b). Ninety-day outcome was reported in 52/57 (91.2%). The rate of good functional outcome (mRS≤2) was 28.8% (versus 59.7% in ASPECTS 6–10 group, p<0.001), which is higher than the 14.1% reported in the control arm 0–5 in the HERMES pooled analysis. Symptomatic intracranial hemorrhage and mortality rates were 7.0% and 30.8%, respectively. When further dichotomizing the group to ASPECTS 0–3 and 4–5 to determine the cut-off for MT futility, the rate of good outcome was 10% and 33.3%, respectively. In investigating the interaction between age and ASPECTS 0–5, low ASPECTS patients older than 75 had a lower rate of good clinical outcome than those 65–75 and less than 65 (0%, 18.2%, 44.8%).ConclusionIn the STRATIS Registry, low ASPECTS 0–5 is associated with lower functional outcomes in patients undergoing mechanical thrombectomy. Clinical outcome in low ASPECTS may be age dependent. Prospective studies are needed to understand the benefit of MT in this patient population.DisclosuresO. Zaidat: None. D. Liebeskind: None. A. Jadhav: None. S. Ortega-Gutierrez: None. V. Szeder: None. D. Haussen: None. D. Yavagal: None. M. Froehler: None. R. Jahan: None. T. Yao: None. N. Mueller-Kronast: None