Objective
To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke.
...Methods
This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019.
Results
The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min,
p
= 0.001), a significant reduction of the total number of thrombolysis (7 vs 13,
p
= 0.033), a non-significant increase of thrombectomy (15 vs 9,
p
= 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min,
p
= 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted.
Conclusions
Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances.
Sporadic inclusion body myositis (s-IBM) represents a unique disease within idiopathic inflammatory myopathies with a dual myodegenerative-autoimmune physiopathology and a lack of an efficacious ...treatment. Circulating miRNA expression could expand our knowledge of s-IBM patho-mechanisms and provide new potential disease biomarkers. To evaluate the expression of selected pre-amplified miRNAs in the serum of s-IBM patients compared to those of a sex- and age-matched healthy control group, we enrolled 14 consecutive s-IBM patients and 8 sex- and age-matched healthy controls. By using two different normalization approaches, we found one downregulated and three upregulated miRNAs. hsa-miR-192-5p was significantly downregulated, while hsa-miR-372-3p was found to be upregulated more in the s-IBM patients compared to the level of the controls. The other two miRNAs had a very low expression levels (raw Ct data > 29). hsa-miR-192-5p and hsa-miR-372-3p were found to be significantly dysregulated in the serum of s-IBM patients. These miRNAs are involved in differentiation and regeneration processes, thus possibly reflecting pathological mechanisms in s-IBM muscles and potentially representing disease biomarkers.
Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead ...express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP(+) cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient-X-linked, mouse muscular dystrophy (scid-mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.
Introduction
The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following ...lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers.
Methods
This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020–4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year.
Results
A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed.
Discussion
Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers.
The basis for molecular and cellular heterogeneity in ependymomas of the central nervous system is not understood. This study suggests a basis for this phenomenon in the selection for ...mitogen-independent (MI) stem-like cells with impaired proliferation but increased intracranial tumorigenicity. MI ependymoma cell lines created by selection for EGF/FGF2-independent proliferation exhibited constitutive activation of EGFR, AKT, and STAT3 and sensitization to the antiproliferative effects of EGFR tyrosine kinase inhibitors (TKI). One highly tumorigenic MI line harbored membrane-bound, constitutively active, truncated EGFR. Two EGFR mutants (ΔN566 and ΔN599) were identified as products of intrachromosomal rearrangements fusing the 3' coding portion of the
gene to the 5'-UTR of the
, yielding products lacking the entire extracellular ligand-binding domain of the receptor while retaining the transmembrane and tyrosine kinase domains. EGFR TKI efficiently targeted ΔN566/ΔN599-mutant-mediated signaling and prolonged the survival of mice bearing intracranial xenografts of MI cells harboring these mutations. RT-PCR sequencing of 16 childhood ependymoma samples identified
chimeric mRNAs in one infratentorial ependymoma WHO III, arguing that this fusion occurs in a small proportion of these tumors. Our findings demonstrate how
culture selections applied to genetically heterogeneous tumors can help identify focal mutations that are potentially pharmaceutically actionable in rare cancers.
.
Background and Purpose
The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and baseline mild neurological symptoms remains ...unclear. The purpose of this study was to evaluate the effectiveness of MT in this subgroup of patients.
Methods
The databases of 9 high-volume Italian stroke centers were retrospectively screened for patients with LVO in the anterior circulation and a baseline National Institute of Health Stroke Scale (NIHSS) score ≤ 5 that received either immediate MT or best medical management (BMM) with the possibility of rescue MT upon neurological worsening. Primary outcome measure was a modified Rankin Scale score of 0–1 at 90 days. Propensity score matching (PSM) analysis was used to estimate the treatment effect of immediate MT compared to BMM/rescue MT.
Results
Two hundred and seventy-two patients received immediate MT (MT group). The BMM/rescue MT group included 41 patients. The primary outcome was achieved in 78.6% (
n
= 246) of overall patients, with a higher proportion in the MT group (80.5% vs. 65.9%,
p
= 0.03) in unadjusted analysis. After PSM, patients in the MT group had a 19.5% higher chance of excellent outcome at 90 days compared to the BMM/Rescue MT group with a similar risk of death from any cause.
Conclusions
Our experience is in favor of a potential benefit of MT also in patients with LVO and a NIHSS score ≤ 5 at the time of groin puncture. Nonetheless, this issue waits for a clear-cut recommendation in a dedicated clinical trial.
Background Approximately 10%-14% of ischemic strokes occur in young adults. Aims To investigate risk factors and etiologies of strokes of young adults admitted to the “stroke unit” of Policlinico ...“Gemelli” of Rome from December 2005 to January 2013. Methods In all, 150 consecutive patients younger than 50 years diagnosed with ischemic stroke were enrolled. Clinical evaluation consisted of a complete neurologic examination and the National Institutes of Health Stroke Scale. Diagnostic workup consisted of anamnesis, extensive laboratory, radiologic, and cardiologic examination. Stroke etiologies were classified according to the Trial of Org 10172 in Acute Stroke Treatment. Results Patients' mean age was 41 ± 8.0 years. The most common risk factors were dyslipidemia (52.7%), smoking (47.3%), hypertension (39.3%), and patent foramen ovale (PFO, 32.8%). Large-artery atherosclerosis was diagnosed as the cause of stroke in 17 patients (11.3%). Cardioembolism was presumed in 36 patients (24%), most of them presented a PFO at transesophageal echocardiography. Small-vessel occlusion was diagnosed in 12 patients (8%); all of them were hypertensive and most of them presented additional risk factors. Forty-one patients (27.3%) presented a stroke of other determined etiology and 44 (29.3%) presented a stroke of undetermined etiology. The 3-year survival was 96.8% and recurrent strokes occurred in only 3 cases. Conclusions Traditional vascular risk factors are also very common in young adults with ischemic stroke, but such factors increase the susceptibility to stroke dependent to other causes as atherosclerosis and small-artery occlusion represent less than 20% of cases. Prognosis quoadvitam is good, being characterized by low mortality and recurrence rate.
We sought to verify the benefit of mechanical thrombectomy in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation and low National Institute of Health stroke ...scale score at presentation. The prospective database of our stroke center was screened for patients with acute ischemic stroke due to large vessel occlusion and a baseline National Institute of Health stroke scale score ≤5 that had undergone mechanical thrombectomy. Outcome measures were the modified Rankin Scale (mRS) score at 90 days, brain bleeding events and death at 90 days. Out of 459 patients, 17 (12 females, mean age 70 ± 14 years) with occlusion of M1 or M2 segment of middle cerebral artery and baseline National Institute of Health stroke scale score ≤5 underwent mechanical thrombectomy. Eight patients (47%) were treated within 6 hours from the onset, 5 (29%) were treated beyond 6 hours, and 4 (24%) were wake-up strokes. Effective mechanical thrombectomy was achieved in 16 patients (94%) and associated with excellent functional outcomes at 3 months (mRS 0-1) in 13 (76%). The asymptomatic brain-bleeding event was observed in one patient 4 days after effective mechanical thrombectomy concerning safety issues. One patient died 1 month after mechanical thrombectomy of a cause unrelated to stroke. Our findings favor a potential benefit of mechanical thrombectomy in patients with stroke due to large vessel occlusion and low National Institute of Health stroke scale score at presentation. These patients may also benefit from a prolonged time window for treatment.
Background: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of ...edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. Methods: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. Results: Sixty-three subjects (median age 81.0 (73.5–88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2–5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment.
Hereditary inclusion‐body myopathy (h‐IBM), or distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with onset in early adult life and a progressive course leading to ...severe disability. h‐IBM/DMRV is due to mutations of a gene (GNE) that codes for a rate‐limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been unambiguously clarified how GNE gene mutations impair muscle metabolism. Although numerous studies have indicated a key role of hyposialylation of glycoproteins in h‐IBM/DMRV pathogenesis, others have demonstrated new and unpredicted functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h‐IBM/DMRV and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of this disorder. Muscle Nerve, 2009
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