Extracellular pH and the Na+/H+ exchanger (NHE1) modulate tumor cell migration. Yet, the pH nanoenvironment at the outer surface of the cell membrane (pHem) where cell/matrix interaction occurs and matrix metalloproteinases work was never measured. We present a method to measure this pH nanoenvironment using proton-sensitive dyes to label the outer leaflet of the plasma membrane or the glycocalyx of human melanoma cells. Polarized cells generate an extracellular proton gradient at their surface that increases from the rear end to the leading edge of the lamellipodium along the direction of movement. This gradient collapses upon NHE1 inhibition by HOE642. NHE1 stimulation by intracellular acidification increases the difference in pHem between the tips of lamellipodia and the cell body in a Na+ dependent way. Thus, cells create a pH nanoenvironment that promotes cell migration by facilitating cell adhesion at their front and the release of cell/matrix contacts at their rear part.
Background and Purpose: Intracranial hemorrhage has been observed in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19), but the clinical, imaging, and pathophysiological features of intracranial bleeding during COVID-19 infection remain poorly characterized. This study describes clinical and imaging characteristics of patients with COVID-19 infection who presented with intracranial bleeding in a European multicenter cohort. Methods: This is a multicenter retrospective, observational case series including 18 consecutive patients with COVID-19 infection and intracranial hemorrhage. Data were collected from February to May 2020 at five designated European special care centers for COVID-19. The diagnosis of COVID-19 was based on laboratory-confirmed diagnosis of SARS-CoV-2. Intracranial bleeding was diagnosed on computed tomography (CT) of the brain within one month of the date of COVID-19 diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy and outcomes in COVID-19 patients presenting with intracranial bleeding were analyzed. Results: Eighteen patients had evidence of acute intracranial bleeding within 11 days (IQR 9–29) of admission. Six patients had parenchymal hemorrhage (33.3%), 11 had subarachnoid hemorrhage (SAH) (61.1%), and one patient had subdural hemorrhage (5.6%). Three patients presented with intraventricular hemorrhage (IVH) (16.7%). Conclusion: This study represents the largest case series of patients with intracranial hemorrhage diagnosed with COVID-19 based on key European countries with geospatial hotspots of SARS-CoV-2. Isolated SAH along the convexity may be a predominant bleeding manifestation and may occur in a late temporal course of severe COVID-19.
Background Celiac axis stenosis (CAS) often is an incidental finding in terms of diagnostic for hepatobiliary surgery since most cases remain asymptomatic. It remains unclear whether CAS is a risk factor for postoperative complications after hepatobiliary surgery. Therefore, the aim of this study was to evaluate the impact of an asymptomatic CAS on the postoperative morbidity and survival of patients undergoing hepatobiliary surgery. Methods We retrospectively analyzed CT scans and clinicopathological data of 250 consecutive patients undergoing hepatobiliary surgery between 2011 and 2018 in our tertiary center. We compared the postoperative course between patients with and without an incidental CAS as well as their overall survival. Results CAS was caused by atherosclerotic stenosis in 16 (64%) patients, by ligamentous stenosis in 4 (16%) and by combined conditions in 5 cases (20%). Mean age of patients in the CAS group was significantly higher in comparison to patients of the non-CAS group (71.0 vs. 59.1 years, p < 0.001). Major hepatectomy was conducted in 40% of the CAS patients and 19.6% of non-CAS patients, respectively (p = 0.036). Interestingly, no statistically significant differences in postoperative morbidity (40 vs. 46.2%, p = 0.673) or in overall survival between the groups (41.3 vs. 51.9 months, p = 0.611) were observed. Conclusion Our analysis found no correlation between an asymptomatic celiac axis stenosis and postoperative complications or overall survival after hepatobiliary surgery. Which impact the incidental CAS may have in highly complex cases remains unclear. Further studies are needed to identify patients who benefit from CAS treatment before hepatobiliary surgery.
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