Clinical and Economic Outcomes of Telemedicine Programs in the Intensive Care Unit: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the impact of telemedicine programs in intensive care unit (Tele-ICU) on ICU or hospital mortality or ICU or hospital length of stay and to summarize available data on implementation cost of Tele-ICU. METHODS: Controlled trails or observational studies assessing outcomes of interest were identified by searching 7 electronic databases from inception to July 2016 and related journals and conference literatures between 2000 and 2016. Two reviewers independently screened searched records, extracted data, and assessed the quality of included studies. Random-effect models were applied to meta-analyses and sensitivity analysis. RESULTS: Nineteen of 1035 records fulfilled the inclusion criteria. The pooled effects demonstrated that Tele-ICU programs were associated with reductions in ICU mortality (15 studies; risk ratio [RR], 0.83; 95% confidence interval [CI], 0.72 to 0.96; P = .01), hospital mortality (13 studies; RR, 0.74; 95% CIs, 0.58 to 0.96; P = .02), and ICU length of stay (9 studies; mean difference [MD], -0.63; 95% CI, -0.28 to 0.17; P = .007). However, there is no significant association between the reduction in hospital length of stay and Tele-ICU programs. Summary data concerning costs suggested approximately US$50 000 to US$100 000 per Tele-ICU bed was required to implement Tele-ICU programs for the first year. Hospital costs of US$2600 reduction to US$5600 increase per patient were estimated using Tele-ICU programs. CONCLUSIONS: This systematic review and meta-analysis provided limited evidence that Tele-ICU approaches may reduce the ICU and hospital mortality, shorten the ICU length of stay, but have no significant effect in hospital length of stay. Implementation of Tele-ICU programs substantially costs and its long-term cost-effectiveness is still unclear.

Remote Limb Preconditioning Generates a Neuroprotective Effect by Modulating the Extrinsic Apoptotic Pathway and TRAIL-Receptors Expression.

As remote limb preconditioning (RPC) ameliorates brain damage after ischemic cerebral stroke (ICS), the purpose of the present study was to explore the molecular mechanisms in the course of RPC. Results of TUNEL staining and cleaved caspase-3 expression showed that ischemia-induced neuronal apoptosis was inhibited by RPC. The expression changes in cleaved caspase-8, cFLIP, Bid itself, and its truncated form represented that RPC suppressed the activation of extrinsic apoptotic pathway during ICS. Then, the level of cytoplasmic cytochrome c was also decreased by RPC. In addition, RPC might partially suppress TNF-related apoptosis-inducing ligand (TRAIL)-induced extrinsic apoptosis through downregulation of TRAIL death receptors and upregulation of TRAIL decoy receptors. As a counterproof, immunoneutralization of TRAIL in dMCAO rats resulted in significant restraint of tissue damage and in a marked functional recovery. Our data complemented the knowledge of RPC neuroprotective mechanism and provided new evidence for its clinical application.

Carotid artery intima-media thickness associated with prognosis of intracranial branch atheromatous disease.

BACKGROUND AND PURPOSE: Small deep brain infarcts are often caused by two different vascular pathologies: branch atheromatous disease (BAD) and lipohyalinotic degeneration (LD). In this study, we compare the clinical characteristics of BAD and LD and investigate the role of C-reactive protein (CRP), homocysteine (Hcy), and carotid artery intima-media thickness (IMT) in the prognosis of patients with BAD and LD. METHODS: Of 262 adult patients with small deep infarcts, 104 were considered BAD and 158 were considered LD. Data compared included clinical information, prevalence of lacune and leukoaraiosis, Hcy, CRP, carotid artery IMT, deterioration during admission, and recurrence of ischemic stroke (IS) within 1 year. RESULTS: Patients with LD have severe leukoaraiosis and higher prevalence of lacune and intracerebral hemorrhage compared with those with BAD. Patients with BAD have higher initial National Institutes of Health Stroke Scale scores and incidence of progressive motor deficits compared with those with LD; CRP is associated with the progression in both groups. There is no statistical difference of recurring risk of IS within 1 year between the two groups; by multivariable logistic regression analysis, carotid artery IMT was an independent risk factor for recurrence of IS in 1 year in patients with BAD. CONCLUSION: BAD as an independent clinical entity has different clinical and radiological characteristics compared with LD. Carotid artery IMT is an independent risk factor for recurrence of IS in patients with BAD.

Angiogenesis contributes to the neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats.

Ischemic stroke is one of the leading causes of mortality and disability worldwide. Previous studies have indicated that hyperbaric oxygen preconditioning (HBO-PC) can induce neuroprotection against focal cerebral ischemia. However, the underlying mechanisms are still not fully understood, and the optimal regimen for preconditioning must be confirmed. In the present study, we designed eight preconditioning regimens and compared their neuroprotective effects. Hyperbaric oxygen preconditioning every other day for there sessions exhibited the best neuroprotective effect; the infarct volume was reduced by almost 50% at 48 h after middle cerebral artery occlusion. We also found that HBO-PC significantly increased the microvessel density and the CD31-positive cells in the penumbra at 72 h after stroke. These results indicate that angiogenesis is involved in the neuroprotection induced by HBO-PC. Moreover, we explored the roles of HIF-1α and angiogenic factors in the angiogenesis process induced by HBO-PC. The results from western blotting demonstrated that protein expression of Ang-2 in the HBO-PC group was significantly increased. In conclusion, HBO-PC reduced brain injury and improved neurological function after focal cerebral ischemia, as partly mediated by the increased microvessel density in the penumbra, and this effect may result from the upregulation of Ang-2.

Telerehabilitation Approaches for Stroke Patients: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Stroke remains one of the most common causes of adult disability in the world. In recent years, diverse telerehabilitation programs have been conceived and studied to improve the abilities of the activities of daily living and increased independence of stroke patients living at home. The systematic review was conducted to determine whether telerehabilitation leads to an improvement in abilities of activities of daily living for stroke patients. METHODS: Randomized controlled trials (RCTs) evaluating the effects of telerehabilitation in stroke survivors living at home were identified by searching 7 electronic databases from inception to March 2015, and by hand searching for conference literatures between 2000 and 2015. Assessments of risk bias and data extraction were conducted independently by 2 reviews. RESULTS: The search strategy identified 2587 records, of which 11 studies were thought to be eligible. Pooled results from 7 studies showed no significant differences in abilities of activities of daily living (Barthel Index scale: standardized mean difference [SMD] -.05, 95% confidence interval [CI] -.24 to .13; Berg Balance Scale: SMD -.05, 95% CI -.7 to .37) and motor function (Fugl-Meyer Extremity: SMD .05, 95% CI -.09 to 1.09) between groups. CONCLUSIONS: This review provides limited, moderate evidence that telerehabilitation of all approaches has equal effects with conventional rehabilitation in improving abilities of activities of daily living and motor function for stroke survivors. Further research of RCTs in this area (rehabilitation field of telemedicine) is ungently required to extend the evidence base.

Leukocyte indicators and variations predict worse outcomes after intravenous thrombolysis in patients with acute ischemic stroke.

Leukocytes are systematic inflammation indicators related to stroke prognosis and can exhibit large dynamic waves before and after recombinant tissue plasminogen activator (r-tPA) therapy. However, additional evidence is needed to determine the prognostic significance of various leukocytes including both static and dynamic data among patients who underwent r-tPA therapy. A total of 251 patients treated with r-tPA were included; their leukocyte data were collected at two time points, and patients were followed up for three months. Analysis revealed the following findings. (i) Patients with hemorrhagic transformation (HT) and unfavorable outcomes had a higher level of leukocytes after r-tPA therapy (leukocyte count (adjusted OR (aOR) 1.191 for HT and 1.184 for unfavorable outcomes), neutrophil count (aOR 1.215 and 1.214), neutrophil-to-lymphocyte ratio (NLR; aOR 1.084 and 1.091)) and larger dynamic leukocyte changes. (ii)Among all leukocytes, the NLR after r-tPA administration demonstrated the strongest correlation with HT and unfavorable outcomes. (iii) Patients with an NLR ≥ 3.322 had a 3.492-fold increased risk for HT, and those with an NLR ≥ 5.511 had a 3.024-fold increased risk for functional outcomes. Overall, this study shows that leukocytes, especially leukocyte count, neutrophil count and the NLR, are independently associated with HT and functional outcomes in stroke patients.

The difference in red blood cell distribution width from before to after thrombolysis as a prognostic factor in acute ischemic stroke patients: A 2-year follow-up.

Purpose: The aim of our study was to determine whether delta red blood cell distribution (ΔRDW) improves neurological outcomes in acute ischemic stroke (AIS) patients 2 years after intravenous thrombolysis (IVT) therapy. Methods: AIS patients who received IVT between January 2013 and December 2019 were retrospectively analyzed. In accordance with their mRS scores, the patients were divided into two groups. A binary logistic regression analysis was conducted to determine the influencing factors of adverse functional outcomes. It was decided to evaluate the variables' the predictive ability by using the area under the receiver operating characteristic. For the poor neurological recovery risk model, features were selected using the LASSO regression model. We also developed a predictive model based on logistic regression analysis, which combined the features selected in the minimum absolute contraction and selection operator regression models. An evaluation of the discrimination, calibration, and clinical applicability of the predictive model was conducted using the C index, calibration chart, and decision curve analysis. Internal validation was evaluated via bootstrapping. Results: Binary logistic regression analysis showed that ΔRDW was an independent influencing factor for poor neurofunctional outcomes. The most appropriate ΔRDW cut-off value for predicting the recovery of poor neurological outcomes was 18.9% (sensitivity: 89.9%, specificity: 78.6%, p < 0.001). The predictive factors included in the nomogram were age, the occurrence of CHD, stroke, AF, ΔRDW, NIHSS score at onset, interval time from onset to IVT, and whether there were indwelling urine catheters and gastric tubes. The model has not only a good discrimination ability, which was indicated by an overall C index of 0.891 (95% confidence interval: 0.829-0.953), but also a considerable calibration ability. Decision curve analysis showed that the nomogram of adverse neurological outcomes recovery was useful in the clinical practice when intervention was implemented above the threshold of 1% possibility of adverse neurological outcomes recovery. Conclusion: In patients with AIS after thrombolysis, the ΔRDW is a potential influencing factor that can be readily used to predict the likelihood of poor neurological function recovery.

AATF Competitively Interacts with Nuclear AIF and Inhibits Parthanatos of Neurons in dMCAO/R and OGD/R Models.

Ischemic stroke (IS) poses a heavy burden on the healthcare system, and revascularization is the most effective treatment. However, ischemia/reperfusion (I/R) injury, one main cause of revascularization complications, significantly hinders IS recovery. Unfortunately, none of the neuroprotectants tested to date has been successfully translated clinically for post-revascularization I/R injury therapy. In multiple pathophysiological processes, apoptosis antagonizing transcription factor (AATF) serves as a cell protector, but its role in neuronal I/R injury is unknown. Therefore, we firstly demonstrated the expression profiles of AATF in a distal middle cerebral artery occlusion/reperfusion (dMCAO/R) model and found that AATF expression was increased in cortical neuron after dMCAO/R. Over-expressing AATF reduced infarct volume, alleviated neuronal death, and promoted neurological functions. Next, we used an oxygen-glucose deprivation/reoxygenation (OGD/R) model to investigate the mechanism of AATF. Results indicated that AATF alleviated OGD/R-induced large-scale DNA fragmentation, which suggested that the protective effect of AATF may be attributed to parthanatos inhibition. After that, we examined the regulatory mechanism of AATF. We found that AATF did not affect poly (ADP-ribose) accumulation and apoptosis-inducing factor (AIF) nucleus translocation. AATF competitively interacted with nuclear AIF, which inhibited AIF from binding DNA. At last, we verified the effect and mechanism of AATF in dMCAO/R model. The present study, for the first time, demonstrates the expression, function, and mechanism of AATF in the context of neuronal I/R injury via dMCAO/R and OGD/R model, which provides new evidence in this area and may facilitate exploring new therapeutic targets.

Altered static and dynamic voxel-mirrored homotopic connectivity in subacute stroke patients: a resting-state fMRI study.

Sixty-four subacute stroke patients and 55 age-matched healthy controls (HCs) underwent a resting-state functional magnetic resonance imaging scan using an echo-planar imaging sequence and high-resolution sagittal T1-weighted images using a three-dimensional magnetization-prepared rapid gradient echo sequence. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) was computed, respectively. The relationships between the clinical measures, including National Institutes of Health Stroke Scale (NIHSS), illness duration, Fugl-Meyer assessment for upper and lower extremities (FMA-total) and size of lesion volume, and the static/ dynamic VMHC variability alterations in stroke patients were calculated. The stroke patients showed significantly increased static VMHC in the corpus callosum, middle occipital gyrus and inferior parietal gyrus, and decreased static VMHC in the inferior temporal gyrus and precentral gyrus (PreCG) compared with those of HCs. For dynamic VMHC variability, increased dynamic VMHC variability in the inferior temporal gyrus and PreCG was detected in stroke patients relative to that in HCs. Correlation analysis exhibited that significant negative correlations were shown between the FMA scores and dynamic VMHC variability in PreCG. The present study suggests that combined static and dynamic VMHC could be helpful to evaluate the motor function of stroke patients and understand the intrinsic differences of inter-hemispheric coordination after stroke.

Ischemic Preconditioning Upregulates Decoy Receptors to Protect SH-SY5Y Cells from OGD Induced Cellular Damage by Inhibiting TRAIL Pathway and Agitating PI3K/Akt Pathway.

As ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia, the purpose of the present study is to explore the molecular mechanisms of ischemic preconditioning induced cerebral protective effect. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, which induces apoptosis through binding to its death receptors (DR4 and DR5). When TRAIL binds to decoy receptors (DcR1 and DcR2), as DcRs lack intact cytoplasmic death domain, TRAIL fails to induce neuronal apoptosis. In the present study, we demonstrated that ischemic preconditioning upregulated DcR1 and DcR2, which subsequently inhibited oxygen glucose deprivation-induced cellular apoptosis. Then, we investigated the protective molecular mechanism of DcRs after ischemic preconditioning treatment. Results showed that DcR1 could competitively bind to TRAIL and partially inhibit TRAIL-induced cellular apoptosis. On the other hand, DcR2 could disturb DRs-associated death-inducing signaling complex formation (DISC), which further inhibited capase-8 activation. Besides, we also found that ischemic preconditioning activated IPC-induced Akt phosphorylation via regulating DcR2 level. Thus, ischemic preconditioning upregulated decoy receptors, which protected cells from oxygen glucose deprivation-induced cellular damage by inhibiting TRAIL-induced apoptosis and agitating PI3K/Akt pathway. Our data complemented the knowledge of neuroprotective mechanism of ischemic preconditioning and provided new evidence for supporting its clinical application.

Effects of home-based telerehabilitation in patients with stroke: A randomized controlled trial.

OBJECTIVE: To determine the effects of a 12-week home-based motor training telerehabilitation program in patients with subcortical stroke by combining motor function assessments and multimodality MRI analysis methods. METHODS: Fifty-two patients with stroke and hemiplegia were randomly assigned to either a home-based motor training telerehabilitation (TR) group or a conventional rehabilitation (CR) group for 12 weeks. The Fugl-Meyer assessment (FMA) for upper and lower extremities and the modified Barthel Index were used as primary outcomes. The secondary outcomes included resting-state functional connectivity (rsFC) between the bilateral M1 areas, gray matter volumes of the primary motor cortex (M1) areas, and white matter integrity of the corticospinal tract. Analysis of covariance was applied to examine the effects of the home-based motor training TR program on neural function recovery and brain plasticity. RESULTS: Compared with the CR group, the TR group showed significant improvement in the FMA (p = 0.011) and significantly increased M1-M1 rsFC (p = 0.031) at the end of the rehabilitation. The M1-M1 rsFC change was significantly positively correlated with the FMA change in the TR group (p = 0.018). CONCLUSION: This study showed a beneficial effect of the home-based motor training telerehabilitation program on motor function in patients with stroke, which was accompanied by enhanced interhemispheric functional connectivity of the M1 areas. We inferred that it is feasible, safe, and efficacious for patients with stroke to receive professional rehabilitation training at home. The combined use of imaging biomarkers should be encouraged in motor training clinical studies in patients with stroke. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with stroke with hemiplegia, home-based telerehabilitation compared to conventional rehabilitation significantly improves some motor function tests.

Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning.

We examined the temporal factors of postconditioning, assessed whether gradual reperfusion reduces infarcts, and compared postconditioning's protection with that of both rapid and delayed preconditioning. Focal ischemia was generated by permanent occlusion of the left distal middle cerebral artery (dMCA) combined with 30 min of occlusion of both common carotid arteries (CCA) in rats. Postconditioning was performed by repetitive brief release and occlusion of CCA after 30 min of CCA occlusion. Gradual reperfusion was generated by controlled release of the bilateral CCA. We confirmed that postconditioning disrupted the early reperfusion but improved cerebral blood flow (CBF) thereafter. Postconditioning with three cycles, but not with 10 cycles, of 30 sec CCA release and 10 sec CCA occlusion (30s/10s) reduced infarction measured at 2 days after stroke. In addition, postconditioning with 10 cycles, but not with three cycles, of 10s/10s reduced infarction but it lost protection when initiated at 3 min after reperfusion. In addition, gradual reperfusion also reduced infarction. Moreover, both rapid and delayed preconditioning conducted 60 min and 3 days before stroke reduced infarct sizes. However, no additional protection was detected when postconditioning was combined with either rapid or delayed preconditioning. In conclusion, gradual reperfusion reduced infarction; postconditioning's protection depended on the number of cycles and duration of each cycle of reperfusion and occlusion and the onset time of postconditioning; postconditioning's protection was comparable to that of rapid preconditioning but not as robust as that of delayed preconditioning.

Synthesis of a potent and selective (18)F-labeled delta-opioid receptor antagonist derived from the Dmt-Tic pharmacophore for positron emission tomography imaging.

Identification and pharmacological characterization of two new selective delta-opioid receptor antagonists, derived from the Dmt-Tic pharmacophore, of potential utility in positron emission tomography (PET) imaging are described. On the basis of its high delta selectivity, H-Dmt-Tic--Lys(Z)-OH (reference compound 1) is a useful starting point for the synthesis of (18)F-labeled compounds prepared by the coupling of N-succinimidyl 4-[ (18)F]fluorobenzoate ([(18)F]SFB) with Boc-Dmt-Tic--Lys(Z)-OH under slightly basic conditions at 37 degrees C for 15 min, deprotection with TFA, and HPLC purification. The total synthesis time was 120 min, and the decay-corrected radiochemical yield of [(18)F]- 1 was about 25-30% ( n = 5) starting from [(18)F]SFB ( n = 5) with an effective specific activity about 46 GBq/micromol. In vitro autoradiography studies showed prominent uptake of [ (18)F]- 1 in the striatum and cortex with significant blocking by 1 and UFP-501 (selective delta-opioid receptor antagonist), suggesting high specific binding of [(18)F]- 1 to delta-opioid receptors. Noninvasive microPET imaging studies revealed the absence of [(18)F]- 1 in rat brain, since it fails to cross the blood-brain barrier. This study demonstrates the suitability of [ (18)F]- 1 for imaging peripheral delta-opioid receptors.

Inhibiting caspase-3 activity blocks beta-catenin degradation after focal ischemia in rat.

Beta-catenin can be cleaved by caspase-3 or degraded by activated glycogen synthase kinase-3beta via phosphorylating beta-catenin. We tested the hypothesis that beta-catenin undergoes degradation after stroke, and its degradation is dependent on caspase activity. Stroke was generated by permanent middle cerebral artery occlusion and 1 h of transient bilateral common carotid artery occlusion in rats. Active caspase-3 was expressed in the ischemic cortex from 5 to 48 h after stroke, whereas beta-catenin markedly degraded at 24 and 48 h after stroke. The caspase 3-specific inhibitor, Z-DQMD-FMK, attenuated beta-catenin degradation, but it did not affect phosphorylation of both beta-catenin and glycogen synthase kinase-3beta. In conclusion, beta-catenin degraded after stroke, and its degradation was caspase-3 dependent.

Hypothermia blocks beta-catenin degradation after focal ischemia in rats.

Dephosphorylated and activated glycogen synthase kinase (GSK) 3beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3beta and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3beta dephosphorylation. Because hypothermia reduces infarction, these results contradict with previous studies showing that GSK 3beta dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3beta protein. Corresponding to GSK 3beta activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of beta-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia.

Downregulation of lipocalin-2 and Bim expression after remote limb preconditioning in the ischemic rat brain.

Although it has been proved that remote limb preconditioning (RPC) can exert neurological protection effects after ischemic cerebral stroke (ICS), the underlying mechanisms of RPC still need to be elucidated for its better transformation to clinical application. Lipocalin-2 (LCN2) was upregulated after cerebral ischemia and mediated reperfusion injury in the models of ischemic stroke. So here, we investigated that whether RPC could downregulate the levels of LCN2 protein and its receptor resulting from cerebral ischemia reperfusion (I/R) injury. The results showed that RPC could decrease the expression of LCN2 protein, but having no obvious effects on its receptor except the time point of 72 h after cerebral ischemia. Furthermore, we observed the downregulation of Bim after RPC in the course of ICS.

Effectiveness and neural mechanisms of home-based telerehabilitation in patients with stroke based on fMRI and DTI: A study protocol for a randomized controlled trial.

BACKGROUND: Stroke is one of leading diseases causing adult death and disability worldwide. Home-based telerehabilitation has become a novel approach for stroke patients as effective as conventional rehabilitation, and more convenient and economical than conventional rehabilitation. However, there is no study assessing the mechanism of home-based telerehabilitation in promoting motor recovery among stroke patients with hemiplegic. AIMS: This study is designed to determine the efficacy and explore the mechanism of motor recovery after home-based telerehabilitation in stroke patients with motor deficits. METHODS/DESIGN: In a single-blinded randomized controlled pilot study, patients with acute subcortical stroke (n = 40) are assigned to receive home-based telerehabilitation or conventional rehabilitation. Task-based or resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), and Fugl-Meyer assessment (FMA) score will acquired before and after rehabilitation. Activation volume of bilateral primary motor (M1), supplementary motor area (SMA), premotor cortex (PMC); lateralization index (LI) of interhemispheric M1, SMA, and PMC; functional connectivity of bilateral M1, SMA, PMC; fractional anisotropy (FA) will be measured; correlation analyses will be performed between neuroimaging biomarkers and FMA score pre- and postrehabilitation. DISCUSSION: We present a study design and rationale to explore the effectiveness and neural mechanism of home-based rehabilitation for stroke patients with motor deficits. The study limitations related to the small-amount sample. Moreover, home-based rehabilitation may provide an alternative means of recovery for stroke patients. Ultimately, results of this trial will help to understand the neural mechanism of home-based telerehabilitation among stroke patients with hand movement disorder.

Defibrinogen Therapy for Acute Ischemic Stroke: 1332 Consecutive Cases.

This study aimed to examine the effectiveness of defibrinogen therapy on functional recovery and safety among 1332 consecutive ischemic stroke patients who had not received intravenous thrombolysis with recombinant tissue plasminogen activator. Stroke patients undergoing conservative and relatively individualized multiple-day dosing regimens of defibrinogen therapy between January 1, 2008 and May 30, 2016 were enrolled. Data were analyzed according to functional success (Barthel Index of 95 or 100, mRS of 0 or 1) and safety variables (intracranial hemorrhage, mortality and stroke recurrence). At 12 months, 18.62% (203/1087) of patients were lost to follow-up. The functional success rates were 39.84% (526/1320) and 42.23% (459/1087) as assessed by BI at 3 months and 12 months, respectively. Fifteen patients had asymptomatic intracranial hemorrhage within 24 hours after the initial defibrase administration. During the 14 days after hospitalization, 12 patients were diagnosed with symptomatic intracranial hemorrhage (sICH) and a total of 12 patients died from all causes. At 3 months, 56 patients were dead and 21 patients had recurrent stroke. The percentage of death and recurrence of stroke at 12 months were 6.81% and 3.22%, respectively. Results from the historical control showed no significant differences of functional success were detected between the patients treated with rt-PA within 6 hours of stroke onset in NINDS II and the patients treated with defibrase within 6 hours after stroke in the present study. The multiple-day dosing regimen of defibrinogen therapy using defibrase applied in the present study could achieve functional improvement among acute ischemic stroke patients, with low risks of mortality when compared with other similar studies. However, the efficacy and safety of such a defibrinogenating therapy is needed to be verified by RCTs with large sample size.

Alterations of static functional connectivity and dynamic functional connectivity in motor execution regions after stroke.

The aims of this study were to examine both static functional connectivity (FC) and dynamic FC alterations in motor execution regions after stroke and to investigate whether the altered static or dynamic FC was associated with the clinical behaviors in stroke patients. Seventy-six stroke patients and 55 healthy controls (HC) were recruited. Static FC and dynamic FC maps were computed based on the seeds of six core regions in motor execution network. Correlation analyses were performed between static or dynamic FC and clinical behavioral scores in stroke patients. Compared with the HC, the stroke patients had significantly higher static FC between the seeds and the precentral or postcentral gyrus, frontal gyrus, inferior parietal lobule, thalamus and insula, and lower static FC between the seeds and the cerebellum and middle temporal gyrus. There were significant differences in dynamic FC between the seeds and precuneus, calcarine gyrus, insula, inferior parietal lobule, precentral gyrus, and middle temporal, frontal or occipital gyrus between the stroke patients and HC. Furthermore, a significant negative correlation was found between the Fugl-Meyer assessment scores and dynamic FC of the ipsilesional primary motor cortex and contralesional precentral gyrus in patients. The current study shows that the patterns of both static FC and dynamic FC changed after stroke, and correlation between motor function and temporal variability in the FC of the precentral gyrus was significant in stroke patients. Our findings indicate that dynamic FC might be a potential indicator for evaluating motor function after stroke.

Dynamic Alterations in Spontaneous Neural Activity in Multiple Brain Networks in Subacute Stroke Patients: A Resting-State fMRI Study.

Objective: To examine whether subacute stroke patients would exhibit abnormal dynamic characteristics of brain activity relative to healthy controls (HC) and to investigate whether the altered dynamic regional indexes were associated with clinical behavior in stroke patients. Methods: The dynamic amplitude of low-frequency fluctuations (dALFF) and dynamic regional homogeneity (dReHo) in 42 subacute stroke patients and 55 healthy controls were compared. Correlation analyses between dALFF and dReHo in regions showing significant intergroup differences and clinical scores (i.e., the National Institutes of Health Stroke Scale, Fugl-Meyer assessment and lesion volume size) were conducted in stroke patients. Receiver operating characteristic (ROC) curve analysis was used to determine the potential value of altered dynamic regional indexes to identify stroke patients. Results: Significantly dALFF in the bilateral cerebellum posterior lobe (CPL), ipsilesional superior parietal lobe, ipsilesional inferior temporal gyrus (ITG), the midline supplementary motor area (SMA), ipsilesional putamen and lentiform nucleus were detected in stroke patients compared to HC. Relative to the HC group, the stroke patients showed significant differences in dReHo in the contralesional rectal gyrus, contralesional ITG, contralesional pons, ipsilesional middle frontal gyrus (MFG). Significant correlations between dALFF variability in midline SMA and Fugl-Meyer assessment (FMA) scores or between dReHo variability in the ipsilesional MFG and FMA scores were detected in stroke patients. Furthermore, the ROC curve revealed that dynamic ALFF at SMA and ReHo at ipsilesional MFG might have the potential to distinguish stroke patients. Conclusion: The pattern of intrinsic brain activity variability is altered in stroke patients compared with HC, and dynamic ALFF/ReHo might be potential tools to assess stroke patients' motor function.