Delays in thrombolysis during COVID-19 are associated with worse neurological outcomes: the Society of Vascular and Interventional Neurology Multicenter Collaboration

Introduction

We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration.

Methods

We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019–02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020–7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term.

Results

Of the 676 thrombolysed patients, the median age was 70 (IQR 58–81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4–16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01–1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07–1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (p_interaction = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89–0.97, p < 0.001).

Conclusion

Treatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes.

     

High C-reactive protein levels are associated with oral hormonal menopausal therapy but not with intrauterine levonorgestrel and transdermal estradiol

OBJECTIVE: Oral hormone replacement therapy (HRT) has been linked to increased cardiovascular (CVD) morbidity. HRT causes a sustained increase in C-reactive protein (CRP), an excellent marker of subclinical inflammation and CVD. The aim of the study was to support our hypothesis that CRP, which is synthesized in the liver, is not increased in association with transdermal/intrauterine HRT. MATERIAL AND METHODS: A case-control study was performed in which CRP measurements in women receiving levonorgestrel intrauterine system combined with transdermal estradiol (LNG/TDE, n=27) were followed for 9 months or longer. CRP concentrations in these women were compared with those of either oral HRT users (n=20) or controls (n=19). RESULTS: No significant differences were found in CRP concentrations between the LGN/TDE and control groups (1.8+/-1.2 and 1.8+/-1.8 mg/L, respectively). However, CRP was significantly increased in the oral HRT group (5.5+/-2.9 mg/L, p<0.001). CONCLUSIONS: CRP is significantly increased by oral HRT but not by the LNG/TDE combination after 9 months of treatment. This trend may explain the preponderance of some menopausal women on HRT being at increased risk for the development of CVD. Therefore, the use of LNG/TDE is acceptable for relief of severe climacteric symptoms possibly not imposing an increased CVD risk documented upon oral HRT.     

Variability of Holter electrocardiographic findings in patients fulfilling the noninvasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial

In the MADIT study, a selected group of postinfarction patients with asymptomatic nonsustained ventricular tachycardia (NSVT) has been shown to benefit from prophylactic ICD treatment. The present study analyzed the variability of NSVT in a patient population fulfilling the non-invasive MADIT criteria. Three consecutive Holter ECGs were performed in weekly intervals in 68 postinfarction patients with an LVEF < or = 0.35. Patients with NSVT underwent programmed ventricular stimulation (PVS); patients were implanted with an ICD if sustained VT or VF was inducible. If NSVT was found in at least two recordings, the arrhythmia was defined as reproducible. In 28 (41%) of the 68 patients, NSVT was found in at least one recording. Seventeen patients revealed NSVT in the first, the remaining 11 in the second registration; no patient had NSVT only in the third Holter. Of the patients with NSVT, 50% had only one, 39% had two, and 11% had three positive recordings. Thus, reproducible NSVT was found in only 50% of the patients with NSVT. Predictors for reproducibility were LVEF > 0.27, NYHA Class I, absence of digitalis therapy, and > 2 NSVT per 24-hour period. Reproducible NSVT was not associated with risk factors such as elevated mean heart rate, reduced heart rate variability, late potentials, or inducibility of sustained VT during PVS. During 17 +/- 9 months of follow-up, seven (10%) patients experienced arrhythmic events: two without and five with previously documented NSVT. In the latter patients, first occurrence of NSVT was consistently in the first Holter; only two of them had reproducible NSVT. In postinfarction patients, the risk factor NSVT exhibits marked spontaneous variability, especially in those with a low number of NSVT per 24-hour period, LVEF < 0.27 or NYHA III, which limits its clinical value as a selection criterion for PVS. Reproducibility of NSVT itself does not seem to be an independent risk factor.     

Pattern of expression of engrailed in relation to gamma-aminobutyric acid immunoreactivity in the central nervous system of the adult grasshopper.

Engrailed (En) protein expression in neurons of the mesothoracic and metathoracic ganglia of the adult grasshopper, Schistocerca americana, was examined by immunohistochemistry. Each neuromere had a dorsally located cluster of En-positive neurons within the dorsal unpaired median (DUM) group, comprising one cluster in the mesothoracic ganglion (T2) and four clusters in the metathoracic ganglion, one for each component neuromere (T3, A1, A2, A3). Ventrally, En-positive neurons occurred in the posterior one-third of each neuromere. In T2 and T3, three ventral groups of neurons were labeled bilaterally. In the abdominal neuromeres, many fewer ventral neurons were En-positive. These also were bilaterally symmetrical, but did not occur in patterns that allowed assignment of homology with the T2 and T3 groups. Altogether, En-positive neurons comprised roughly 10% of the ganglionic populations. In the bilateral groups, as in the DUM groups, En expression was restricted to interneurons, consistent with the suggestion that En expression contributes to some aspect of interneuronal phenotype. En-positive neurons in the DUM groups also expressed gamma-aminobutyric acid (GABA) immunoreactivity. Further study showed that all neurons in one En-positive bilateral group and some neurons in another bilateral group were GABA immunoreactive, but that neurons in a third bilateral group were En-positive only. Additionally, several discrete clusters of neurons were GABA-immunoreactive but En-negative. A provisional morphological scheme is presented, which relates the several neuronal clusters to their likely neuroblasts of origin, as a basis for further research into the composition of neuronal lineages.     

Variables affecting the accuracy of MDCT in prediction of the proper prosthesis deployment projection for transcatheter aortic valve implantation

Objective

We evaluated multidetector computed tomography (MDCT) accuracy for the prediction of the optimal prosthetic aortic valve deployment angle in trans-catheter aortic valve implantation (TAVI) with the different variables.

Biological and mechanical characteristics of the interface between a new swelling anchor and bone.

We recently evaluated the peak pullout loads for anchors made from our new copolymeric swelling-type material compared with anchors made of a nonswelling material. In vitro and in vivo peak pullout loads of these anchors were evaluated after different intervals of implantation in the lateral femoral condyles of New Zealand White rabbits. Scanning electron microscopy and energy dispersive x-ray analyses were additionally performed on selected retrieved samples after pullout to examine the characteristics of bone attachment to the implant. The mean peak pullout load was greater for the swelling anchors than for the nonswelling anchors after 48 hours in vitro (46.0 +/- 15.8 compared with 10.8 +/- 9.1 N, p = 0.0541). After 2 weeks in vivo, it was significantly greater for the swelling anchors than for the nonswelling controls (177.7 +/- 41.3 compared with 53.7 +/- 17.5 N, p = 0.0024). The peak pullout load was also greater for the swelling anchors after 8 weeks in vivo; however, this difference was less pronounced than at 2 weeks (101.8 +/- 35.0 compared with 58.9 +/- 9.7 N, p = 0.0508). Furthermore, the swelling implants tended to induce bone deposition at the bone-implant interface. Results from this investigation reveal that the new family of dynamic implants has potential for applications requiring fixation to cancellous or osteoporotic bone.     

Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin‐induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO‐1 signalling pathway modulation

The aim of the present study was to assess the neuroprotective effects of xanthotoxin and umbelliferone in streptozotocin (STZ)‐induced cognitive dysfunction in rats. Animals were injected intracerebroventricularly (ICV) with STZ (3 mg/kg) once to induce a sporadic Alzheimer's disease (SAD)‐like condition. Xanthotoxin or umbelliferone (15 mg/kg, i.p.) were administered 5 hr after ICV‐STZ and daily for 20 consecutive days. Xanthotoxin or umbelliferone prevented cognitive deficits in the Morris water maze and object recognition tests. In parallel, xanthotoxin or umbelliferone reduced hippocampal acetylcholinestrase activity and malondialdehyde level. Moreover, xanthotoxin or umbelliferone increased glutathione content. These coumarins also modulated neuronal cell death by reducing the level of proinflammatory cytokines (tumour necrosis factor‐alpha and interleukin‐6), inhibiting the overexpression of inflammatory markers (nuclear factor κB [NF‐κB] and cyclooxygenase II), and upregulating the expression of NF‐κB inhibitor (IκB‐α). Interestingly, xanthotoxin diminished phosphorylated JAK2 and phosphorylated STAT3 protein expression, while umbelliferone markedly replenished nuclear factor erythroid‐derived 2‐like 2 (Nrf2) and haem oxygenase‐1 (HO‐1) levels. The current study provides evidence for the protective effect of xanthotoxin and umbelliferone in STZ‐induced cognitive dysfunction in rats. This effect may be attributed, at least in part, to inhibiting acetylcholinestrase and attenuating oxidative stress, neuroinflammation and neuronal loss.     

How do different delivery schedules of tailored web-based physical activity advice for breast cancer survivors influence intervention use and efficacy?

Purpose

The purpose of the study is to investigate the impact of differing delivery schedules of computer-tailored physical activity modules on engagement and physical activity behaviour change in a web-based intervention targeting breast cancer survivors.

Methods

Insufficiently active breast cancer survivors (n = 492) were randomly assigned to receive one of the following intervention schedules over 12 weeks: a three-module intervention delivered monthly, a three-module intervention delivered weekly or a single module intervention. Engagement with the website (number of logins, time on site, modules viewed, action plans completed) was measured using tracking software. Other outcomes (website acceptability, physical activity behaviour) were assessed using online surveys. Physical activity outcomes were analysed using regression models for both study completers and when applying intention-to-treat (using multiple imputation).

Results

Completers allocated to the monthly module group rated the intervention higher (b = 2.2 95 % CI = 0.02–4.53) on acceptability and had higher levels of resistance-training (IRR = 1.88, 95 % CI = 1.16–3.04) than those in the single module group. When accounting for missing data, these differences were no longer significant. The completion of at least two action plans was higher among those allocated to the monthly module group compared to those in the weekly module group (53 vs 40 %, p = 0.02); though the completion of at least two modules was higher in the weekly module group compared to the monthly module group (60 vs 46 %; p = 0.01). There were no other significant between group differences observed.

Conclusion

This study provides preliminary evidence that web-based computer-tailored interventions can be used to increase physical activity among breast cancer survivors. Further, there were some outcome differences based on how the tailored modules were delivered, with the most favourable outcomes observed in the monthly delivery group.

Implications for Cancer Survivors

This study will be useful for informing the design of future web-based interventions targeting breast cancer survivors.