Background and purpose
Comorbidity of acute ischaemic stroke with Covid‐19 is a challenging condition, potentially influencing the decision of whether to administer intravenous thrombolysis (IVT). We ...aimed to assess the 1‐month outcome in ischaemic stroke patients with Covid‐19 infection who received IVT alone or before thrombectomy (bridging therapy).
Methods
As a collaboration initiative promoted by the Italian Stroke Organization, all Italian stroke units (n = 190) were contacted and invited to participate in data collection on stroke patients with Covid‐19 who received IVT.
Results
Seventy‐five invited centers agreed to participate. Thirty patients received IVT alone and 17 received bridging therapy between 21 February 2020 and 30 April 2020 in 20 centers (n = 18, Northern Italy; n = 2, Central Italy). At 1 month, 14 (30.4%) patients died and 20 (62.5%) survivors had a modified Rankin Scale (mRS) score of 3 to 5. At 24 to 36 hours, asymptomatic intracerebral hemorrhage (ICH) was reported in eight (17.4%) patients and symptomatic ICH (sICH) in two (4.3%) patients. Causes of death were severe ischaemic stroke (n = 8), a new ischaemic stroke (n = 2), acute respiratory failure (n = 1), acute renal failure (n = 1), acute myocardial infarction (n = 1), and endocarditis (n = 1). In survivors with a 1‐month mRS score of 3 to 5, baseline glucose level was higher, whereas endovascular procedure time in cases of bridging therapy was longer. Baseline National Institutes of Health Stroke Scale glucose and creatinine levels were higher in patients who died.
Conclusions
Intravenous thrombolysis for patients with stroke and Covid‐19 was not a rare event in the most affected areas by pandemic, and rates of 1‐month unfavorable outcomes were high compared to previous data from the pre–Covid‐19 literature. However, risk of sICH was not increased.
Seventy‐five centers agreed to participate in the study. Forty‐seven stroke patients with Covid‐19 were treated with thrombolysis alone (n = 30) or bridging therapy (n = 17) in 20 centers (n = 18, Northern Italy; n = 2, Central Italy). During the study period, 283 stroke patients were treated with thrombolysis alone (n = 266, Northern Italy; n = 17, Central Italy) and 167 stroke patients with bridging therapy (n = 156, Northern Italy; n = 11, Central Italy) in the 20 enrolled centers. Rates of 1‐month unfavorable outcomes (death: 30.4%; mRs score 3–5: 62.5%) were high compared to previous data from the pre–Covid‐19 literature. However, risk of sICH (4.3%) was not increased.
Highlights • Creatine, is a compound that is critical for energy metabolism of nervous cells. • Creatine absence by deficit of creatine transporter, causes serious diseases. • Creatine crosses the ...BBB and the neuronal membrane slowly only using its transporter. • Creatine-derived molecules could cross BBB and membrane independently of the transporter. • Creatine-derived may be a useful strategy in creatine transporter deficiency.
Atrial fibrillation (AF) is the most common cardiac arrhythmia in adult and old people and represents a risk factor for stroke. Correct AF individuation bears strong relevance in primary and ...secondary stroke prevention. Our goal was to evaluate the reliability of a low-cost, non-invasive technology in detecting AF in acute stroke patients. AFib model BP3MQ1-2D (Microlife USA, Dunedin, FL) showed good accuracy in diagnosing AF in a general cardiologic outpatient population. We carried out an observational study in patients with recent stroke. We studied 207 subjects, 103 men, 104 women, mean age (±SD) 77.7 ± 11.34 years, who underwent a test by AFib device with indication of AF or lack of it. The golden standard was a 12-lead EKG done immediately and evaluated by a certified cardiologist. We computed estimates of Sensitivity and Specificity and their 95 % confidence intervals (CI). AF was present in 38 subjects from the sample of 207 (18.4 %). AFib correctly demonstrated AF in 34 and failed diagnosing AF in 4 cases; on the other hand, AFib correctly excluded AF in 167 and caused an erroneous diagnosis of AF in 2 cases. The Sensitivity was 0.895 (95 % CI 0.7597–0.958) and the Specificity was 0.988 (95 % CI 0.958–0.997). The AFib device global accuracy was 0.971 (95 % CI 0.938–0.987). This device was able to detect AF with high specificity and a good sensitivity. This device may be considered as an accurate tool in detecting AF in stroke patients.
Previously, we have shown that the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) and singleagent carboplatin produce similar survival and progression-free survival rates in women ...with ovarian cancer. Subsequently, paclitaxel combined with platinum has become a widely accepted treatment for the disease. We aimed to compare the safety and efficacy of paclitaxel plus carboplatin with a control of either CAP or carboplatin alone.
Between February, 1995, and October, 1998, we enrolled 2074 patients from 130 centres in eight countries. Women were randomly assigned paclitaxel plus carboplatin or control, the control (CAP or single-agent carboplatin) being chosen by the patient and clinician before randomisation. The primary outcome measure was overall survival. Secondary outcomes were progression-free survival and toxicity. Analysis was by intention to treat.
With a median follow-up of 51 months, 1265 patients had died, and survival curves showed no evidence of a difference in overall survival between paclitaxel plus carboplatin and control (hazard ratio 0·98, 95% CI 0·87–1·10, p=0·74). The median overall survival was 36·1 months on paclitaxel plus carboplatin and 35·4 months on control (difference 0·7 months, 95% CI −3·6 to 4·7). 1538 patients had progressive disease or died, and again, Kaplan-Meier curves showed no evidence of a difference between the groups (hazard ratio 0·93, 95% CI 0·84–1·03, p=0·16). Median progression-free survival was 17·3 months on paclitaxel plus carboplatin and 16·1 months on control (difference 1·2 months, 95% CI −0·5 to 2·8). Paclitaxel plus carboplatin caused more alopecia, fever, and sensory neuropathy than carboplatin alone, and more sensory neuropathy than CAP. CAP was associated with more fever than paclitaxel plus carboplatin.
Single-agent carboplatin and CAP are as effective as paclitaxel plus carboplatin as first-line treatment for women requiring chemotherapy for ovarian cancer. The favourable toxicity profile of single-agent carboplatin suggests that this drug is a reasonable option as first-line chemotherapy for ovarian cancer.
Background and purpose
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability ...and whose phenotype modulators are still unknown.
Methods
In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age‐related leukoencephalopathy (ARL).
Results
We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (β = −0.418, P < 0.003) in CADASIL patients and the executive function index (β = −0.321, P = 0.028) in ARL.
Conclusions
This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.
Abstract Creatine, an ergogenic compound essential for brain function, is very hydrophilic and needs a transporter to cross lipid-rich cells' plasma membranes. Hereditary creatine transporter ...deficiency is a severe incurable neurological disease where creatine is missing from the brain. Creatine esters are more lipophylic than creatine and may not need the transporter to cross plasma membranes. Thus, they may represent a useful therapy for hereditary creatine transporter deficiency. Creatine ethyl ester (CEE) is commercially available and widely used as a nutritional supplement. It was reported that it enters the cells of patients lacking the transporter but was not useful when administered in vivo , by oral route, to affected patients. In this paper we investigated the effects of CEE in in vitro brain slices before and after biochemical block of the creatine transporter. We found that CEE is rapidly degraded in the aqueous incubation medium to creatinine, however it remains in solution long enough to cause an increase in tissue content of creatine and, more prominently, phosphocreatine. Both CEE and creatine delayed the anoxia-induced failure of synaptic transmission, and there was no difference between the two compounds. Contrary to what we expected, CEE did not increase tissue creatine content after the creatine transporter was blocked. We confirm that CEE is probably not an effective treatment for hereditary creatine transporter deficiency. Two factors seem to affect the possibility for creatine esters to be exploited in the therapy of creatine transporter deficiency. First, the size of their alcohol moiety should be increased since this would increase the lipophilicity of the compound and improve its ability to diffuse through biological membranes. Second, creatine esters should be further modified to slow their degradation to creatinine and increase their half-life in aqueous solutions. Moreover, we should not forget the possibility that they are degraded in vivo by plasma esterases.
Abstract Phosphocreatine–Mg-complex acetate (PCr-Mg-CPLX) is a creatine-derived compound that in previous in vitro research was able to increase neuronal creatine independently of the creatine ...transporter, thus providing hope to cure the hereditary syndrome of creatine transporter deficiency. In previous research we showed that it reproduces in vitro the known neuroprotective effect of creatine against anoxic damage. In the present paper we investigated if PCr-Mg-CPLX reproduces this neuroprotective effect in vivo, too. We used a mouse model of transient middle cerebral artery occlusion. Mice received PCr-Mg-CPLX or a mixture of the two separate compounds phosphocreatine (PCr) and MgSO4 , or vehicle. The injections were done 60 min and 30 min before ischemia. Forty-eight hours after ischemia neurological damage was evaluated with Clark's behavioural tests, then the infarct volume was measured. PCr-Mg-CPLX reduced the infarct volume by 48%, an effect that was not duplicated by the separate administration of PCr and MgSO4 and the neurological damage was decreased in a statistically significant way. We conclude that PCr-Mg-CPLX affords in vivo neuroprotection when administered before ischemia. These results are comparable to previous research on creatine administration in experimental stroke. PCr-Mg-CPLX maintains creatine-like neuroprotective effects in vivo as well as in vitro. Our study suggests that PCr-Mg-CPLX might have a therapeutic role in the treatment of hereditary creatine transporter deficiency and of conditions where there is a high risk of impending stroke or cerebral ischemic damage, like high-risk transient ischemic attacks, open heart surgery, and carotid surgery.
Hereditary creatine transporter deficiency causes brain damage, despite the brain having the enzymes to synthesize creatine. Such damage occurring despite an endogenous synthesis is not easily ...explained. This condition is incurable, because creatine may not be delivered to the brain without its transporter. Creatine-derived compounds that crossed the blood–brain barrier in a transporter-independent fashion would be useful in the therapy of hereditary creatine transporter deficiency, and possibly also in neuroprotection against brain anoxia or ischemia. We tested the double hypothesis that: (1) the creatine carrier is needed to make creatine cross the plasma membrane of brain cells and (2) creatine-derived molecules may cross this plasma membrane independently of the creatine carrier. In
in vitro mouse hippocampal slices, incubation with creatine increased creatine and phosphocreatine content of the tissue. Inhibition of the creatine transporter with 3-guanidinopropionic acid (GPA) dose-dependently prevented this increase. Incubation with creatine benzyl ester (CrOBzl) or phosphocreatine–Mg-complex acetate (PCr-Mg-CPLX) increased tissue creatine content, not phosphocreatine. This increase was not prevented by GPA. Thus, the creatine transporter is required for creatine uptake through the plasma membrane. Since there is a strong indication that creatine in the brain is mainly synthesized by glial cells and transferred to neurons, this might explain why hereditary transporter deficiency is attended by severe brain damage despite the possibility of an endogenous synthesis. CrOBzl and PCr-Mg-CPLX cross the plasma membrane in a transporter-independent way, and might be useful in the therapy of hereditary creatine transporter deficiency. They may also prove useful in the therapy of brain anoxia or ischemia.
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