Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in ...patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19.
Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality.
early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage.
We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years interquartile range, 59-79; 63 men 67.7%). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients 95% CI, 71.3-87.8). Thirty-day mortality was 29% (27 patients 95% CI, 20-39.4). Early neurological improvement was 19.5% (17 patients 95% CI, 11.8-29.5), and symptomatic intracranial hemorrhage was 5.4% (5 patients 95% CI, 1.7-12.1). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 95% CI, 1.21-5.98 per SD-log decrease in lymphocyte count, 2.66 95% CI, 1.22-5.77 per SD-log increase in aspartate, and 4.30 95% CI, 1.43-12.91 per SD-log increase in LDH).
The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.
•2nd-century roman stucco fragments studied with Raman – EDX – XRF.•The synergic use of these techniques allowed to identify all materials and pigments.•The politeness of materials and pictorial ...remains witness the richness of the Domus.
2nd-century stucco fragments from the roman Domus Valeriorum were analyzed by Raman spectroscopy (Raman), imaging X-ray fluorescence (XRF) and energy dispersive X-ray microanalysis (EDX) in order to identify the pigments and materials thereon. Cinnabar, malachite, hematite, goethite and Egyptian blue were detected by the synergistic use of these techniques whereas calcite, with some traces of gypsum, was detected as materials for the bas-relief figures and the pictorial background. This non-destructive characterization is the first carried out on the Domus Valeriorum finds. The multi-analytical approach highlighted the complementarity and versatility of these techniques, suitable for both laboratory and in-situ analysis, on macroscopic or microscopic fragments without preliminary manipulation.
Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown.
To assess the role of vaccines ...in modifying the risk of myocardial injury in COVID-19.
We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit).
1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury.
In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.
Antibiotic prophylaxis (AP) is useful to prevent antimicrobial overuse, misuse and abuse, as well against the occurrence of surgical site infections (SSIs). This study aimed to describe the ...implementation of a quality improvement intervention on AP for elective surgery, as informal interviews showed a lower than expected compliance with internal recommendations, and to evaluate intervention's effect in terms of main drug consumption.
A quality improvement intervention on all elective cases within 14 main surgical departments was performed. SQUIRE 2.0 guidelines were used in designing and reporting.
The intervention was implemented in an Italian Teaching Hospital 2 years after the adoption of internal evidence-based AP recommendations.
Professionals involved in elective surgery.
The intervention was structured into two phases: a survey was conducted during two non-consecutive weeks period (April-May 2013) to assess the adherence to the international guidelines in AP; survey's results were presented and discussed with all the surgical teams (December 2013-April 2014).
Impact on cefazolin consumption (in defined daily doses per 100 procedures).
Data of AP for 653 surgical procedures in terms of type, timing, duration, excess and defect were analyzed. An optimal AP rate resulted in 48.1% cases. Reduction in cefazolin use (-21.5%) and cost (-22.9%) was registered.
Though results cannot be generalized to all hospital populations, the implemented intervention is likely to improve AP consequently improving quality of care and reducing costs. Further studies are needed to evaluate specific outcomes such as rate of SSIs and antibiotic resistance.
No data are available regarding long-term survival of out-of-hospital cardiac arrest (OHCA) patients based on different Utstein subgroups, which are expected to significantly differ in terms of ...survival. We aimed to provide the first long-term survival analysis of OHCA patients divided according to Utstein categories.
We analyzed all the 4,924 OHCA cases prospectively enrolled in the Lombardia Cardiac Arrest Registry (Lombardia CARe) from 2015 to 2019. Pre-hospital data, survival, and cerebral performance category score (CPC) at 1, 6, and 12 months and then every year up to 5 years after the event were analyzed for each patient.
A decrease in survival was observed during the follow-up in all the Utstein categories. The risk of death of the "all-EMS treated" group exceeded the general population for all the years of follow-up with standardized mortality ratios (SMRs) of 23 (95%CI, 16.8-30.2), 6.8 (95%CI, 3.8-10.7), 3.8 (95%CI, 1.7-6.7), 4.05 (95%CI, 1.9-6.9), and 2.6 (95%CI, 1.03-4.8) from the first to the fifth year of follow-up. The risk of death was higher also for the Utstein categories "shockable bystander witnessed" and "shockable bystander CPR": SMRs of 19.4 (95%CI, 11.3-29.8) and 19.4 (95%CI, 10.8-30.6) for the first year and of 6.8 (95%CI, 6.6-13) and 8.1 (95%CI, 3.1-15.3) for the second one, respectively. Similar results were observed considering the patients discharged with a CPC of 1-2.
The mortality of OHCA patients discharged alive from the hospital is higher than the Italian standard population, also considering those with the most favorable OHCA characteristics and those discharged with good neurological outcome. Long-term follow-up should be included in the next Utstein-style revision.
Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in ...severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% 95% CI 81–94 in arm A vs 85% 74–93, HR 1.07 0.8–1.5 in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% 77–96 vs 79% 63–91, HR 1.55 0.9–2.6; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% 79–96) vs (73% 55–89, HR 1.53 0.9–2.7; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI “Lazzaro Spallanzani” Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health.
While fetal liver is a major hematopoietic organ, normal adult liver provides a suitable microenvironment for a variety of immune cells and, in several pathological conditions, may become a site of ...extramedullary hematopoiesis. The direct influence of hepatocytes on hematopoietic cell differentiation is poorly understood. We have previously reported that the Met murine hepatocyte (MMH) untransformed hepatocytic lines retain several morphological and functional features of hepatocytes in vivo and are able to support the survival, self‐renewal, and differentiation of hematopoietic precursors in a cell‐cell contact system. Here we report the effects of soluble factors released by MMH lines on bone marrow–derived cells. Lymphohematopoietic cells were cultured in two different cell contact‐free systems: transwell inserts on MMH feeder layers, and MMH conditioned medium (MMH‐CM). Both culture systems were able to promote a substantial expansion of bone marrow‐derived cells and their differentiation to natural killer (NK) cells that express the NK1.1 and U5A2‐13 markers. Purified hematopoietic stem cells (Sca‐1+Lin‐), either plated as a bulk population or as single cells, were also able to differentiate into NK cells, when cultured in MMH‐CM; thus, soluble factors secreted by MMH lines promote the expansion and differentiation of NK precursor cells. MMH‐CM‐derived NK cells are functionally active; stimulation by interleukin (IL)‐12 together with IL‐18 was required to induce interferon‐gamma (IFNγ) expression and to enhance their cytotoxic activity. In conclusion, our findings may imply a direct role of hepatocytes in NK cell development, and the system we have used may provide a tool for studying the molecular mechanisms of NK cell differentiation. (HEPATOLOGY 2004;39:1508–1516.)
Previous studies in the endometrium of ruminants showed that type I interferon (IFN) prevents oxytocin receptor (OTR) formation. We studied the effect of IFN-alpha on human myometrial cells in ...culture expressing a high density of biologically active OTR. We found that IFN-alpha induced a 35-50% decrease in OTR mRNA and protein and that this inhibition was time and dose dependent. Maximal inhibition of OTR mRNA was obtained after 2-3 days, whereas 1-(beta-mercapto-beta, beta-cyclopentamethyl-enepropionic acid,2-O-Me-Tyr,Thr4,Orn8,Tyr9-amide)-125Ivasotocin (125IOTA) binding reached a nadir after 3-4 days, with half-maximal inhibitory concentration (IC50) = 1,100 U/ml. Mathematical analysis of multiple homologous competition curves for 125IOTA indicated that IFN-alpha treatment (5,000 U/ml x 3 days) reduced just the binding capacity (Bmax) without changing the binding affinity. Accordingly, the same treatment with IFN-alpha did not affect the half-maximally effective concentration (EC50) for the oxytocin-induced increase in intracellular calcium but significantly decreased maximal responsiveness (Emax) of myometrial cells to OT stimulation. In conclusion, our data demonstrate, for the first time, a negative regulation by IFN-alpha of the steady-state expression of OTR mRNA in cultured human myometrial cells obtained from nonpregnant uteri. This inhibition was followed by a parallel decrease in both the Bmax for 125IOTA and Emax for oxytocin, suggesting a decreased OTR protein availability.
According to the guidelines of the "Third international workshop conference on GDM", we have examined 2000 pregnant women. The glucose challenge test (GCT) was positive in 408 cases (20.4%) and ...negative in 1592 (79.6%). The OGTT (Carpenter and Coustan's criteria) was performed in 647 pregnant women. GDM and IGGT prevalence was of 6.25% and 5.5% respectively and normal glucose tolerance (NGT) 88.25%. The GCT effectiveness for GDM and IGGT diagnosis is: sensibility 75.1%, specificity 44%, positive predictive value 46.4% and negative predictive value 74%. GDM and IGGT compared with NGT women were significantly older (p < 0.05) and prepregnancy BMI was higher (p < 0.01); the prevalence of previous macrosomia (p < 0.01), previous gestational diabetes (p < 0.01) and family history for diabetes mellitus (p < 0.05) was greater in GDM and IGCT. The prevalence of preterm delivery was higher in both GDM and IGCT (GDM 12.5% and IGGT 15.4% vs NGT 6%; p < 0.01), as well as the prevalence of cesarean sections (GDM 31.6% vs IGGT 23.5% and NGT 20.3%; p < 0.02), and the occurrence of macrosomia (GDM 27.6%, IGGT 16.6% and NGT 16.2%). In addition a higher prevalence (p < 0.01) of hyperbilirubinaemia, hypoglycemia and hypertrophy cardiomyopathy was observed in newborns from GDM women. Our data show that: GCT has a good specificity for GDM diagnosis, prevalence of GDM in our population is about 6%, GDM is still correlated to an elevated maternal and neonatal morbility.
We have studied the expression of the c-myc and c-abl oncogenes in two human leukemic K562 cell lines which do express hemoglobin genes retaining a differential rate of cell proliferation. Our data ...indicate that in hemin-induced K562(S) cells the expression of c-abl oncogene decreases and appears to be related to a decrease in the proliferation capacity rather than to the activation of differentiated functions. The K562(hC) cell line, which produces large amounts of Hb Gower 1 retaining an efficient rate of cell proliferation, expresses indeed the c-abl oncogene at high level.
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