Analysis of the effect of comprehensive physical and mental nursing for patients with acute cerebral infarction in intravenous thrombolytic therapy.

BACKGROUND: To evaluate the efficacy of comprehensive physical and mental nursing for patients with acute cerebral infarction (ACI) undergoing intravenous thrombolytic therapy and its impact on patients' quality of life and psychological state. METHODS: A total of 200 patients with ACI, admitted to our hospital between December 2018 and December 2019, were included in the study. They were randomly assigned to either the control group or the experimental group using a random number table. The control group received routine care (basic care such as monitoring vital signs, assisting with daily activities, administering medications, and providing comfort measures), while the experimental group received comprehensive physical and mental nursing (physical care, phsycological surpport, education and conceling). Various parameters including quality of life index (QLI) scores, mental status scale in non-psychiatric settings (MSSNS) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, National Institute of Health Stroke Scale (NIHSS) scores, changes in hemodynamic indicators, and incidence of adverse events during intravenous thrombolysis were compared between the two groups. RESULTS: The experimental group had higher QLI scores and lower MSSNS, SAS, SDS, and NIHSS scores compared to the control group (p = 0.33, 0.22, 0.35, 0.26, 0.042). The experimental group also exhibited a lower incidence of adverse reactions during intravenous thrombolysis (p = 0.02). CONCLUSION: Comprehensive physical and mental nursing for patients with ACI undergoing intravenous thrombolysis improves nursing efficacy, nursing satisfaction, quality of life, and patients' psychological state. These findings highlight the importance of implementing holistic nursing interventions to optimize patient outcomes in ACI management.

Cold atmospheric plasma-enabled platelet vesicle incorporated iron oxide nano-propellers for thrombolysis.

A new approach to treating vascular blockages has been developed to overcome the limitations of current thrombolytic therapies. This approach involves biosafety and multimodal plasma-derived theranostic platelet vesicle incorporating iron oxide constructed nano-propellers platformed technology that possesses fluorescent and magnetic features and manifold thrombus targeting modes. The platform is capable of being guided and visualized remotely to specifically target thrombi, and it can be activated using near-infrared phototherapy along with an actuated magnet for magnetotherapy. In a murine model of thrombus lesion, this proposed multimodal approach showed an approximately 80 % reduction in thrombus residues. Moreover, the new strategy not only improves thrombolysis but also boosts the rate of lysis, making it a promising candidate for time-sensitive thrombolytic therapy.

Biomimetic platelet-camouflaged drug-loaded polypyrrole for the precise targeted antithrombotic therapy.

Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation.

Recombinant tissue-type plasminogen activator (rt-PA) effectively restores neurological function and improves prognosis in acute ischemic stroke.

OBJECTIVE: To evaluate the clinical efficacy of intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke. METHODS: A total of 76 patients with acute ischemic stroke admitted to the Encephalopathy Dept. of Zhecheng Hospital of Traditional Chinese Medicine between February 2021 and June 2022 were recruited in this prospective trial (ClinicalTrials.gov, NCT03884410) and patients were randomized 1:1 to receive either aspirin plus clopidogrel (control group) or aspirin plus clopidogrel and rt-PA intravenous thrombolytic therapy (experimental group), with 38 cases in each group. The treatment efficiency, National Institute of Health stroke scale (NIHSS) scores, daily living ability, coagulation function, serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2), homocysteine (HCY), hypersensitive C-reactive protein (hsCRP) levels, adverse events, and prognosis were evaluated and compared between the two groups. RESULTS: Intravenous thrombolysis with rt-PA resulted in a better treatment outcome of patients versus aspirin plus clopidogrel (P<0.05). Patients with rt-PA exhibited better improvement in neurological function than those with aspirin plus clopidogrel, as shown by the lower NIHSS scores (P<0.05). Intravenous thrombolysis with rt-PA resulted in a better quality of life of patients than aspirin plus clopidogrel, indicated by the higher Barthel Index (BI) levels (P<0.05). The lower von Willebrand factor (vWF) and Factor VIII (F) levels indicated better coagulation function of patients with rt-PA versus those with aspirin plus clopidogrel (P<0.05). The lower serum concentrations of Lp-PLA2, HCY, and hsCRP suggested patients with rt-PA had milder inflammatory responses versus those without rt-PA (P<0.05). There was no significant difference in the incidence of adverse events in the two groups (P>0.05). Intravenous thrombolytic therapy with rt-PA better enhanced the prognosis of patients than with aspirin plus clopidogrel (P<0.05). CONCLUSION: Compared with conventional pharmacological regimens, additional rt-PA intravenous thrombolytic therapy improves the clinical outcome of patients with acute ischemic stroke, promotes neurological recovery, and enhances patient prognosis without increasing the risk of patient-related adverse events.

[Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke].

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION: Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.

Inpatient rehabilitation therapy in stroke patients with reperfusion therapy: a national prospective registry study.

BACKGROUND: Little is known about the rate of real-world inpatient rehabilitation therapy (IRT) after stroke. We aimed to determine the rate of inpatient rehabilitation therapy and its associated factors in patients who undergo reperfusion therapy in China. METHODS: This national prospective registry study included hospitalized ischemic stroke patients aged 14-99 years with reperfusion therapy between January 1, 2019, and June 30, 2020, collecting hospital-level and patient-level demographic and clinical data. IRT included acupuncture or massage, physical therapy, occupational therapy, speech therapy, and others. The primary outcome was the rate of patients receiving IRT. RESULTS: We included 209,189 eligible patients from 2191 hospitals. The median age was 66 years, and 64.2% were men. Four in five patients received only thrombolysis, and the rest 19.2% underwent endovascular therapy. The overall rate of IRT was 58.2% (95% CI, 58.0-58.5%). Differences in demographic and clinical variables existed between patients with and without IRT. The rates of acupuncture or massage, physical therapy, occupational therapy, speech therapy, and other rehabilitation interventions were 38.0%, 28.8%, 11.8%, 14.4%, and 22.9%, respectively. The rates of single and multimodal interventions were 28.3% and 30.0%, respectively. A lower likelihood of receiving IRT was associated with being 14-50 or 76-99 years old, female, from Northeast China, from Class-C hospitals, receiving only thrombolysis, having severe stroke or severe deterioration, a short length of stay, Covid-19 pandemic and having intracranial or gastrointestinal hemorrhage. CONCLUSION: Among our patient population, the IRT rate was low with limited use of physical therapy, multimodal interventions, and rehabilitation centers and varied by demographic and clinical features. The implementation of IRT remains a challenge for stroke care, warranting urgent and effective national programs to enhance post-stroke rehabilitation and the adherence to guidelines.

Rhubarb Peony Decoction Downregulates the Expression of c-Fos after Intestinal Epithelial Cells Hypoxia-reoxygenation Injury.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury occurs in several clinical situations and after intestinal transplantation. This study aimed to examine the role of rhubarb peony decoction (RPD) in intestinal I/R injury. METHODS: Different concentrations of RPD were set to treat IEC-6 and Caco-2 cells. Cell proliferation and apoptosis were measured by CCK-8 and flow cytometry assays. High-throughput transcriptome sequencing was performed on IEC-6 cells treated with hypoxia-reoxygenation (HR) or HR and RPD. RESULTS: RPD treatment significantly promoted the proliferation of IEC-6 and Caco-2 cells and inhibited apoptosis. Sequencing results identified 109 significantly up-regulated genes and 36 significantly down-regulated genes in the RPD group. In addition, the results of western blot suggested that HR induced the expression of c-Fos, and the treatment of RPD prevented the HR-induced c- Fos expression. Importantly, knockdown of c-Fos rescued the HR-inhibited cell proliferation and HR-induced apoptosis. CONCLUSIONS: In conclusion, RPD was beneficial in protecting the survival of intestinal epithelial cells under HR stress. Furthermore, the increase in c-Fos expression after HR stress was closely related to the proliferation and apoptosis of intestinal epithelial cells.

Research progress on intra-arterial thrombolysis for the treatment of central retinal artery occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

Central retinal artery occlusion(CRAO), also known as eye stroke, always results in acute and painless visual loss. At present, conservative treatments, such as eye massage, lowering intraocular pressure and vasodilators have little effect on reducing visual loss. Intra-arterial thrombolysis(IAT)has significantly improved prognosis in patients with acute ischemic stroke, thus IAT has been gradually applied in the treatment of CRAO. IAT injects fibrinolytic drugs directly into the ophthalmic artery by a microcatheter, and dissolves the emboli that block the central retinal artery to restore the blood flow of the retina. Theoretically, IAT may be effective for CRAO as what has been found for stroke, but existing clinical studies exhibited inconsistent results. This paper summarizes the feasibility, efficacy, and safety of IAT treatment in CRAO. It will also analyze related factors that affect the prognosis, putting forward potential development directions and providing insights for the further clinical application of IAT.

Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS).@*METHODS@#A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups.@*RESULTS@#After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05).@*CONCLUSION@#Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.

Evolution of deep vein thrombosis treatment from leeches to mechanical thrombectomy.

Deep vein thrombosis (DVT) is one of the most common diseases in developed countries with significant socioeconomic consequences. The severity of DVT lies in the potential for life-threatening pulmonary embolism and the development of chronic venous insufficiency, referred to as post-thrombotic syndrome. Virchow contributed to the understanding of the pathophysiological events that lead to thrombosis by describing three basic risk mechanisms. The first therapeutic attempts in the 17th century included venepuncture and the application of leeches. The first anticoagulant drug was heparin, which entered clinical practice after 1935. Subsequent commercialization of oral vitamin K antagonists (warfarin) and the advent of low molecular weight heparin along with compression therapy allowed the expansion of outpatient treatment of DVT. Recently, new oral anticoagulants have been introduced, leading to improved safety due to lower risk of bleeding complications and simplification of the treatment process. The next step in the development of therapeutic options are invasive methods of early thrombus removal, which significantly shorten the process and aim to reduce the occurrence of late complications. These methods include local catheter-directed thrombolysis using tissue plasminogen activator, mechanical thrombectomy and their combination called pharmaco-mechanical thrombectomy. The latter is currently used in patients with acute ilio-femoral DVT.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Impact of improved stroke green channel process on the delay of intravenous thrombolysis in patients with acute cerebral infarction during the COVID-19 pandemic: An observational study.

Objective: This study analyzed the impact of the improved stroke green channel process on the delay of intravenous thrombolysis in patients with acute cerebral infarction under coronavirus disease 2019 (COVID-19) prevention and control measures. Methods: We included 57 patients from the stroke center of the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine before the improvement of the stroke green channel process (March-July 2019), as well as 94 patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak (March-July 2020) and 68 patients during the Omicron variant outbreak (March-July 2022) after the improvement of stroke green channel process. The door-to-needle time (DNT), door-to-imaging time (DIT), and door-to-test completion time were compared among the three groups. We analyzed the impact of this process improvement in the emergency green channel during the pandemic on the delay of intravenous thrombolysis. Results: This study included a total of 229 patients with acute cerebral infarction who went through the green channel for intravenous thrombolysis (57 in the pre-pandemic group, 94 in the SARS-CoV-2 outbreak group, and 68 in the Omicron outbreak group). The percentages of patients undergoing intravenous thrombolysis in the pre-pandemic, SARS-CoV-2 outbreak, and Omicron outbreak groups differed significantly (19.32%, 22.27%, and 28.94%, respectively, P = 0.029). Compared to the pre-pandemic group, the National Institutes of Health Stroke Scale (NIHSS) score at admission was significantly higher in the Omicron outbreak group (7.71 ± 7.36 in the Omicron outbreak group vs. 5.00 ± 4.52 in the pre-pandemic group) (P = 0.026) but not in the SARS-CoV-2 outbreak group (4.79 ± 5.94 in the SARS-CoV-2 outbreak group vs. 5.00 ± 4.52 in the pre-pandemic group, P = 0.970). Significantly higher proportions of patients undergoing emergency intravenous thrombolysis came to the hospital by ambulance in the SARS-CoV-2 and Omicron outbreak groups compared to the pre-pandemic group (38.6% in the pre-pandemic group, 51.1% in the SARS-CoV-2 outbreak group, and 82.4% in the Omicron outbreak group, P < 0.001). Compared to the pre-pandemic group, the DIT was significantly higher in the SARS-CoV-2 outbreak group (22.42 ± 7.62 min in the SARS-CoV-2 outbreak group vs. 18.91 ± 8.23 min in the pre-pandemic group, P =0.031) but not the Omicron outbreak group (20.35 ± 10.38 min in the Omicron outbreak group vs. 18.91 ± 8.23 min in the pre-pandemic group, P = 0.543). The door-to-test completion time was significantly longer in the SARS-CoV-2 and Omicron outbreak groups compared to that in the pre-pandemic group (78.37 ± 25.17 min in the SARS-CoV-2 outbreak group, 92.60 ± 25.82 min in the Omicron outbreak group vs. 65.11 ± 22.35 min in the pre-pandemic group, P < 0.001); however, the DNT in the SARS-CoV-2 and Omicron outbreak groups did not differ significantly from those in the pre-pandemic group (both P > 0.05). Conclusion: During the two periods of the COVID-19 outbreak (SARS-CoV-2 and Omicron), after the improvement of the green channel for intravenous thrombolysis, there might be some delay in in-hospital DIT during the SARS-CoV-2 outbreak, however, the in-hospital delay indicator DNT for intravenous thrombolysis were not affected.

Effect of drug use in the treatment of acute ischemic stroke: A scoping review.

Background: Drugs of abuse have been associated with ischemic stroke; however, the clinical presentation, outcomes, and treatment data in this population are limited. The overall safety and efficacy of thrombolytic therapy and thrombectomy in these patients remain unclear. This scoping review summarizes published complications and clinical outcomes in patients with recent abuse of cocaine, methamphetamine (MA), cannabis, decongestant, opioids, alcohol, and 3,4-methylenedioxymethamphetamine (MDMA) presenting with acute ischemic stroke. Methods: We conducted a scoping review of the primary literature that assessed outcomes data of thrombolytic therapy or thrombectomy in drug users with acute ischemic stroke. We searched PubMed, Ovid Medline, and Web of Science. Demographic and stroke characteristics, treatment, complications, and clinical outcomes at last follow-up were collected and summarized. Results: We identified 51 studies in this review. Drugs of abuse of interest were cocaine (14 studies), MDMA (one study), MA (eight studies), cannabis (23 studies), alcohol (two studies), decongestants (one study), and opioids (two studies). Clinical presentation and stroke presentation were most commonly described features. Thrombectomy outcomes were reported for four patients total (two studies), all with history of cocaine use. Thrombolysis treatment and outcomes were reported for 8851 patients (five studies) with history of cocaine, alcohol, or cannabis. Both treatments were pursued in three patients (three studies). Treatment complications included intracerebral hemorrhage, vasospasm, and cerebral edema. Conclusion: Evidence for thrombolytic and thrombectomy treatment in drug users remains limited. Controlled studies are needed to examine complication profile and outcomes following thrombolytic and thrombectomy treatment in this population.

[Effect of Xingnao Kaiqiao acupuncture on safety of rt-PA intravenous thrombolysis in patients with cerebral infarction: a randomized controlled trial].

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION: Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.

Clot-targeted magnetic hyperthermia permeabilizes blood clots to make them more susceptible to thrombolysis.

BACKGROUND: Thrombolysis is a frontline treatment for stroke, which involves the application of tissue plasminogen activator (tPA) to trigger endogenous clot-degradation pathways. However, it is only effective within 4.5 h of symptom onset because of clot contraction preventing tPA permeation into the clot. Magnetic hyperthermia (MH) mediated by tumor-targeted magnetic nanoparticles is used to treat cancer by using local heat generation to trigger apoptosis of cancer cells. OBJECTIVES: To develop clot-targeting magnetic nanoparticles to deliver MH to the surface of human blood clots, and to assess whether this can improve the efficacy of thrombolysis of contracted blood clots. METHODS: Clot-targeting magnetic nanoparticles were developed by functionalizing iron oxide nanoparticles with an antibody recognizing activated integrin αIIbß3 (PAC-1). The magnetic properties of the PAC-1-tagged magnetic nanoparticles were characterized and optimized to deliver clot-targeted MH. RESULTS: Clot-targeted MH increases the efficacy of tPA-mediated thrombolysis in contracted human blood clots, leading to a reduction in clot weight. MH increases the permeability of the clots to tPA, facilitating their breakdown. Scanning electron microscopy reveals that this effect is elicited through enhanced fibrin breakdown and triggering the disruption of red blood cells on the surface of the clot. Importantly, endothelial cells viability in a three-dimensional blood vessel model is unaffected by exposure to MH. CONCLUSIONS: This study demonstrates that clot-targeted MH can enhance the thrombolysis of contracted human blood clots and can be safely applied to enhance the timeframe in which thrombolysis is effective.

Percutaneous mechanical thrombectomy using the Rotarex®S device for the treatment of acute lower limb artery embolism: A retrospective single-center, single-arm study.

Objective: Acute limb embolism (ALE) is a challenging, highly morbid, and frequently fatal vascular emergency. Percutaneous mechanical thrombectomy (PMT) devices are an alternative treatment to restore perfusion by removing emboli in the limb arterial system. We evaluated the outcomes of treatment of ALE patients using PMT devices in our center. Methods: A retrospective review of ALE patients treated with Rotarex S (Straub Medical) at a single institution from 2018 to 2022 was performed. The primary outcome was technical success, defined as complete recanalization of the occluded segment with satisfactory outflow and good capillary filling of the distal parts of the foot without any major or obstructing residual emboli or thrombi either in the treated segment or in the outflow tract without the need for additional catheter-directed thrombolysis (CDT) or conversion to open surgery. Embolized segments treated, treatment outcomes, and perioperative complications were reviewed. Results: A total of 17 ALE patients (29% men, 71% women; mean age, 73 years) underwent PMT procedures. The femoral arteries and popliteal arteries are the most commonly treated vessels, with both present in 59% of the patients. The technical success rate was 100%, but the majority of cases (82%) had concurrent percutaneous transluminal angioplasty or stent grafting, and two patients were treated with urokinase during the operation. There was one thrombotic recurrence that required amputation. There were no 30-day deaths. Complications included extravasation after PMT (two), intraoperative embolization of the outflow tract (one), access site hematoma (one), target artery thrombosis (one), and acute kidney injury (one). There were no severe bleeding complications. Conclusions: The Rotarex S device has a satisfactory success rate, although complementary use of various adjunctive techniques is frequently required. It seems to be a moderately effective tool for treating ALE to avoid CDT or open surgery. The device appears safe, with low risks of amputation and mortality rates, but special attention should be given to the potential for extravasation and distal embolism.

Pragmatic Use of Catheter-Directed Thrombolysis in Venous Thromboembolism and a Comparative Evaluation With Traditional Therapies in Submassive Pulmonary Embolism.

BACKGROUND: Catheter-directed thrombolysis (CDT) is a novel treatment for venous thromboembolism (VTE). Limited data describe pragmatic use of CDT and compare CDT to other VTE therapies. OBJECTIVE: Assess the use of CDT and comparatively evaluate CDT, anticoagulation, and systemic thrombolysis in submassive pulmonary embolism (PE). METHODS: Retrospective, single-center, chart audit. Part 1 described all patients who received CDT for VTE. Part 2 matched patients with submassive PE who received CDT, heparin, or systemic thrombolysis and assessed length of stay (LOS), bleeding, all cause in-hospital mortality, and escalation of care. RESULTS: For part 1, 70 CDT patients were identified; 42 with DVT and 28 with PE. ICU LOS was longer (2.5 ± 2.9 vs. 4.9 ± 8.4 days, p = 0.07), escalation of care more frequent (0% vs. 35.7%, p < 0.0001), and hospital mortality greater (2.4% vs. 21.4%, p = 0.014) in the PE group. For part 2, 21 CDT patients were matched to 21 heparin and 21 systemic thrombolysis patients. All CDT and tPA patients were admitted to the ICU versus only 6 (28.6%, p < 0.001) heparin patients. ICU LOS was significantly longer in the CDT group versus systemic tPA and systemic anticoagulation (80.7 ± 64.1 vs. 48.2 ± 27.7 vs. 24.9 ± 59.1 hours; p = 0.0048). More IVC filters and thrombectomies were performed in the CDT group. CONCLUSIONS: CDT is frequently used for both DVT and PE and requires ICU admission. Escalation of care is common when CDT is used for PE. For submassive PE, CDT is associated with prolonged ICU LOS compared to heparin or systemic thrombolysis. Resource utilization with CDT requires further evaluation.

[Acupuncture intervention prolongates thrombolysis time window by regulating cerebral cortex angiogenesis-related genes and proteins in cerebral infarction rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (Endostatin, ES) mRNAs and proteins (angiogenesis related factors) in the ischemic penumbra region in rats with cerebral infarction (CI), so as to explore its underlying mechanisms in prolonging the time window of thrombolysis therapy for CI. METHODS: A total of 48 male SD rats were randomly divided into sham operation, model, medication (6 h thrombolysis) and acupuncture (Acupunct)+medication groups (n=12 in each group). The CI model was established using modified auto-thrombus method. Six hours after thrombolysis, recombinant human tissue plasminogen activator (rt-PA,10 mg/kg) was given to rats of the thrombolysis group through tail vein. Acupuncture was applied at "Shuigou"(CV26) and bilateral "Neiguan" (PC6) 2 h after successful modeling, and the needles were retained for 30 minutes. Cerebral blood flow (CBF) was monitored during modeling in each group, and the neurological deficit score (0-7 points) was given 2 h and 24 h after successful modeling according to Bederson's methods. The cerebral infarction volume was observed after triphenyltetrazole chloride (TTC) staining. The protein and mRNA expression levels of VEGF, bFGF and ES in the ischemic penumbra region of the right cerebral cortex were detected by Western blot and real-time PCR, separately. RESULTS: The neurological deficit score at both 2 h and 24 h after modeling, percentage of cerebral infarction volume, and the expression levels of VEGF, bFGF and ES proteins and mRNAs in the model group were significantly higher than those of the sham operation group (P<0.01, P < 0.05). Compared with the model group, the neurological deficit score 24 h (not at 2 h) after modeling and percentage of cerebral infarction volume, and the expression levels of ES protein and mRNA in the Acupunct+medication group (not in the medication group) were notably lower (P<0.05, P<0.01), while the expression levels of VEGF and bFGF proteins and mRNAs in the Acupunct +medication group (not in the medication group) were considerably higher (P<0.01, P<0.05). No significant differences were found between medication and model groups in the CI percentage, VEGF, bFGF and ES proteins and mRNAs (P>0.05). The therapeutic effect of Acupunct +medication group was significantly superior to that of medication in lowering neurological deficit score, percentage of CI volume and expression of ES protein and mRNA and in up-regulating the expression of VEGF and bFGF proteins and mRNAs (P<0.05, P<0.01). CONCLUSION: Acupuncture and timely intervention can prolong the time window of thrombolysis in CI rats, which may be related to its function in up-regulating the expression of VEGF and bFGF mRNAs and proteins and in down-regulating the expression of ES mRNA and protein in ischemic cerebral cortex.

Emerging agents for the treatment and prevention of stroke: progress in clinical trials.

INTRODUCTION: Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients. AREAS COVERED: The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an alternative thrombolytic drug to alteplase, nerinetide as a promising neuroprotective agent, and glibenclamide for reducing edema in malignant hemispheric infarction. We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, as well as novel antidiabetic agents that have been shown to reduce cardiovascular events in the long-term. EXPERT OPINION: Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical agents. This tendency enriches the therapeutic armamentarium with novel agents developed for specific stroke subgroups. ABBREVIATIONS: IVT: intravenous thrombolysis; RCTs: randomized-controlled clinical trials; TNK: Tenecteplase; COVID-19: Coronavirus 2019 Disease; EXTEND-IA TNK: The Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke trial; AIS: acute ischemic stroke; NNT: number needed to treat; MT: mechanical thrombectomy; sICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; AHA/ASA: American Heart Association/American Stroke Association; ESO: European Stroke Organization; NA-1: Nerinetide; ENACT: Evaluating Neuroprotection in Aneurysm Coiling Therapy; CTA: CT angiography; TIA: transient ischemic attack; CHANCE: Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; LOF: loss-of-function; PRINCE: Platelet Reactivity in Acute Nondisabling Cerebrovascular Events; THALES: Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death; CHANCE-2: Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II; FXI: Factor XI; PACIFIC-STROKE: Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-NonCardioembolic Stroke study; COMPASS: Cardiovascular Outcomes for People Using Anticoagulation Strategies; CANTOS-ICAD: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease; SAMMPRIS: Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis; WASID: Warfarin-Aspirin Symptomatic Intracranial Disease; SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels; LDL-C: low-density lipoprotein cholesterol; TST: Treat Stroke to Target; IMPROVE-IT: Improved Reduction of Outcomes: Vytorin Efficacy International Trial; PCSK9: proprotein convertase subtilisin-kexin type 9; FOURIER: Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; CLEAR: Cholesterol Lowering via Bempedoic acid, an ACL-inhibiting Regimen; REDUCE-IT: Reduction of Cardiovascular Events With EPA Intervention Trial; STRENGTH: Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia; ACCORD: Action to Control Cardiovascular Risk in Diabetes; ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; VADT: Veterans Affairs Diabetes Trial; GLP-1R: Glucagon-like peptide-1 receptor; SGLT2: sodium-glucose cotransporter 2; CONVINCE: COlchicine for preventioN of Vascular Inflammation in Non-CardioEmbolic stroke; PROBE: Prospective Randomized Open-label Blinded Endpoint assessment.

Thrombus-specific theranostic nanocomposite for codelivery of thrombolytic drug, algae-derived anticoagulant and NIR fluorescent contrast agent.

Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency. STATEMENT OF SIGNIFICANCE: Herein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.