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The Neurohospitalist Jul 2024Understanding various aspects associated with readmission after acute ischemic stroke (AIS) is an important priority. Our study aims to examine whether 60-day...
BACKGROUND AND PURPOSE
Understanding various aspects associated with readmission after acute ischemic stroke (AIS) is an important priority. Our study aims to examine whether 60-day readmission rates differed among patients with AIS who were treated with different acute reperfusion treatment modalities along with associated clinical factors.
METHODS
This is a retrospective analysis of a continuous cohort of patient with AIS, who received either intravenous recombinant tissue plasminogen activator (IV rtPA), endovascular treatment (EVT) or both, and were discharged alive. Patients readmitted within 60 days were identified as the readmission group. Multivariable logistic regression was used to identify all-cause readmission post-stroke between treatment groups.
RESULTS
The final cohort comprised of 358 patients with AIS receiving IV rtPA only (N = 160), EVT only (N = 106), or both (N = 92). Fifty-six patients were readmitted to the hospital within 60-day follow-up period. The adjusted logistic regression model indicated that compared to patients who received IV tPA only, patients receiving both IV rtPA and EVT had significantly lower odds (OR = .27; 95% CI = .10, .75)) of getting readmitted within 60-day post-discharge from stroke admission.
CONCLUSION
In this sample of AIS hospitalizations, treatment-type was positively associated with 60-day readmission. Future studies are necessary to understand whether treatment-related adverse events, and readmission are avoidable.
PubMed: 38895015
DOI: 10.1177/19418744241232020 -
International Journal of Molecular... May 2024Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators...
Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.
Topics: Animals; Mast Cells; Dermatitis, Atopic; Mice; Disease Models, Animal; Skin; alpha7 Nicotinic Acetylcholine Receptor; Inflammation; Peptide Hydrolases; Urokinase-Type Plasminogen Activator; Substance P; Stress, Physiological; Mice, Inbred C57BL; Nerve Growth Factor
PubMed: 38891925
DOI: 10.3390/ijms25115738 -
The New England Journal of Medicine Jun 2024Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear.
METHODS
We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset.
RESULTS
A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).
CONCLUSIONS
Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).
Topics: Humans; Tissue Plasminogen Activator; Male; Fibrinolytic Agents; Female; Aged; Middle Aged; Ischemic Stroke; Recombinant Proteins; Intracranial Hemorrhages; Aged, 80 and over
PubMed: 38884332
DOI: 10.1056/NEJMoa2400314 -
ARYA Atherosclerosis 2023Primary percutaneous coronary intervention (PPCI) is the gold standard approach to restore blood flow in ST-segment elevation myocardial infarction (STEMI); however, the...
INTRODUCTION
Primary percutaneous coronary intervention (PPCI) is the gold standard approach to restore blood flow in ST-segment elevation myocardial infarction (STEMI); however, the no-reflow phenomenon as a potential complication of PPCI can worsen the outcomes. It has been hypothesized that adjunctive prophylactic intracoronary infusion of low-dose fibrinolytic might improve the PPCI outcomes; however, this theory is a matter of debate. The current study aims to investigate the value of adjunctive prophylactic intracoronary low-dose alteplase to prevent the no-reflow phenomenon in patients with STEMI.
METHOD
This case-control study was conducted on 80 STEMI patients who underwent PPCI. The patients were assigned into the case group who were intervened by 10 mg adjunctive intracoronary alteplase immediately at the end of the balloon angioplasty (n=40) and controls (n=40) who underwent conventional PPCI only. The angioplasty-associated outcomes including final TIMI score, need for no-reflow treatment, ST-segment resolution, post-PPCI complications, and death were compared between the groups.
RESULTS
Alteplase use was accompanied by significantly improved final TIMI flow scores (P-value<0.001) and fewer requirements for no-reflow treatments (P-value<0.001); however, it did not improve the ST-segment resolution (P-value=0.491). The mortality rate and post-angioplasty complications did not differ between the groups (P-value>0.05).
CONCLUSION
Based on the findings of this study, adjunctive infusion of low-dose intracoronary alteplase during PPCI could not efficiently prevent the no-reflow phenomenon. Although the final TIMI flow and need for post-stenting no-reflow treatment improved, ST-segment resolution did not occur dramatically. Given that, this approach requires further investigations and should be considered cautiously.
PubMed: 38883855
DOI: 10.48305/arya.2023.41614.2890 -
Journal of Thoracic Disease May 2024There is no established standard 3 line treatment for patients with advanced non-small cell lung cancer (NSCLC). Although cytotoxic chemotherapeutic agents that are not...
Treatment rationale and protocol design: an investigator-initiated phase II study of combination treatment of nivolumab and TM5614, a PAI-1 inhibitor for previously treated patients with non-small cell lung cancer.
BACKGROUND
There is no established standard 3 line treatment for patients with advanced non-small cell lung cancer (NSCLC). Although cytotoxic chemotherapeutic agents that are not used as 1 or 2 line treatment are administrated as 3 line treatment, their anti-tumor efficacy is insufficient. Anti-programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) treatment is more effective and less toxic than chemotherapy in anti-PD-L1/PD-1 treatment-naïve patients with NSCLC. Therefore, anti-PD-L1/PD-1 therapy is considered an appropriate 3 line treatment. However, the anti-tumor efficacy is limited in patients previously treated with anti-PD-L1/PD-1 antibody. Today, new drugs are needed to increase the efficacy of anti-PD-L1/PD-1 antibodies.
METHODS
This open-label, single-arm, investigator-initiated phase II study is designed to evaluate combination treatment of nivolumab and TM5614, a plasminogen activator inhibitor (PAI-1) inhibitor as 3 or more line treatment in NSCLC patients who underwent standard treatment. The primary endpoint is the objective response rate and the secondary endpoints are progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. Recruitment began in September 2023 and is expected to continue for approximately three years.
DISCUSSION
Currently, there is no standard 3 line treatment for advanced NSCLC, and we hope that the findings of this study will facilitate more effective treatments in this setting. Ethics and dissemination: the study protocol conformed to the ethical principles outlined in the Declaration of Helsinki. All patients will provide written informed consent prior to enrollment. Results will be published in a peer-reviewed publication.
TRIAL REGISTRATION
This study is registered to Japan Registry of Clinical Trials with number: jRCT2061230039 (19/July/2023).
PubMed: 38883673
DOI: 10.21037/jtd-23-1858 -
Journal of Thoracic Disease May 2024Little is known about the role of complement activation in acute pulmonary embolism (PE). We investigated whether complement activation is associated with the severity...
BACKGROUND
Little is known about the role of complement activation in acute pulmonary embolism (PE). We investigated whether complement activation is associated with the severity of acute PE, along with the associated prothrombotic state, systemic inflammation and neutrophil extracellular traps (NETs) formation.
METHODS
We studied 109 normotensive, non-cancer PE patients (aged 58.1±15.0 years). On admission prior to initiation of anticoagulation, plasma soluble complement components, i.e., C3a and sC5b-9, were measured with enzyme-linked immunosorbent assay (ELISA), along with thrombin generation, fibrinolysis proteins (plasminogen, antiplasmin, plasminogen activator inhibitor-1), factor VIII (FVIII) activity, and fibrin clot properties, including clot permeability (K, a measure of clot density) and clot lysis time (CLT). Moreover, we determined inflammatory markers and citrullinated histone H3, a specific marker of NETs formation.
RESULTS
Patients in the lower tertile of C3a (≤1.45 ng/mL, n=37) had lower simplified Pulmonary Embolism Severity Index (sPESI) values and were less likely to have right ventricular (RV) dysfunction compared to the remaining subjects. The former subgroup also had 13% lower FVIII activity, but not fibrinogen, interleukin-6, fibrinolysis proteins, and thrombin generation. Plasma C3a levels correlated inversely with K and positively with CLT indicating formation of denser and poorly lysable clots in subjects with elevated C3a. Despite a positive association between C3a and sC5b-9, the latter parameter was solely associated with higher FVIII, but not with other variables.
CONCLUSIONS
We showed that in acute PE enhanced complement activation characterizes patients with poorer short-term prognosis who display prothrombotic fibrin clot properties and elevated FVIII, which supports the involvement of complement proteins in acute thromboembolism.
PubMed: 38883666
DOI: 10.21037/jtd-24-171 -
Cureus May 2024The no-reflow phenomenon is defined as the failure to restore coronary flow demonstrated by the reduced or missing flow in angiography despite the patent artery. There...
The no-reflow phenomenon is defined as the failure to restore coronary flow demonstrated by the reduced or missing flow in angiography despite the patent artery. There are pharmacological strategies proposed and studied to manage the no-reflow phenomenon. The medication groups used are purine nucleoside (adenosine), calcium channel blockers (verapamil, nicardipine), beta 2 receptor agonists (adrenaline, nitroprusside), fibrinolytic agents (streptokinase, tissue plasminogen activators), glycoprotein IIb/IIIa inhibitors (abciximab, tirofiban). We present a case of a woman hospitalized in non-ST elevation myocardial infarction (NSTEMI) conditions. The patient underwent coronary angiography, in which a single vessel coronary artery disease (CAD); left anterior descending (LAD) stenosis of 90% was found. In this condition, the patient underwent percutaneous coronary intervention (PCI) of LAD. The no-reflow phenomenon occurred with thrombolysis in myocardial infarction (TIMI) flow grade of 0 during the procedure. As a consequence, the patient presented chest pain and important hypotension (BP of 70/45). Because of the hypotensive state of the patient, we decided to administer intracoronary (IC) adrenaline directly. In our case, we used adrenaline as a first-line treatment for the no-flow phenomenon due to the hypotensive state during the PCI procedure. Generally, we initially use IC nitrate or IC adenosine to resolve the phenomenon, and when the no-reflow persists we use IC adrenaline because of its side effects mentioned above. Anyway, we believe that in specific cases of hypotension and bradycardia, the use of adrenaline as the first line of therapy should be considered.
PubMed: 38883139
DOI: 10.7759/cureus.60338 -
Exploration of Hypertension Following Traumatic Renal Hematoma Formation and Page Kidney Discussion.Cureus May 2024Page kidney is defined as a rare cause of secondary hypertension due to a subcapsular hematoma externally compressing the kidney resulting in the activation of the...
Page kidney is defined as a rare cause of secondary hypertension due to a subcapsular hematoma externally compressing the kidney resulting in the activation of the renin-angiotensin-aldosterone system (RAAS). This phenomenon consists of numerous etiologies including acute or chronic traumatic or non-traumatic events. In this case, we report on an acute unilateral hematoma following blunt renal trauma as the result of a fall from standing height treated with tissue plasminogen activator (tPA) infusion and image-guided drainage. Qualities within this case and how they are paralleled in the diagnosis of a Page kidney are explored. A brief review of current etiologies and management plans per the literature review will also be discussed.
PubMed: 38883132
DOI: 10.7759/cureus.60468 -
Matrix Biology Plus Aug 2024Cardiac fibrosis is characterized by excessive accumulation and deposition of ECM proteins. Cardiac fibrosis is commonly implicated in a variety of cardiovascular...
Cardiac fibrosis is characterized by excessive accumulation and deposition of ECM proteins. Cardiac fibrosis is commonly implicated in a variety of cardiovascular diseases, including post-myocardial infarction (MI). We have previously developed a dual-delivery nanogel therapeutic to deliver tissue plasminogen activator (tPA) and Y-27632 (a ROCK inhibitor) to address MI-associated coronary artery occlusion and downregulate cell-contractility mediated fibrotic responses. Initial studies were conducted on glass substrates. The study presented here employs the use of polyacrylamide (PA) gels and microgel thin films to mimic healthy and fibrotic cardiac tissue mechanics. Soft and stiff polyacrylamide substrates or high and low loss tangent microgel thin films were utilized to examine the influence of cell-substrate interactions on dual-loaded nanogel therapeutic efficacy. In the presence of Y-27632 containing nanogels, a reduction of fibrotic marker expression was noted on traditional PA gels mimicking healthy and fibrotic cardiac tissue mechanics. These findings differed on more physiologically relevant microgel thin films, where early treatment with the ROCK inhibitor intensified the fibrotic related responses.
PubMed: 38882395
DOI: 10.1016/j.mbplus.2024.100150 -
Indian Heart Journal Jun 2024Left-sided mechanical prosthetic heart valve thrombosis (PVT) occurs because of suboptimal anticoagulation and is common in low-resource settings. Urgent surgery and...
BACKGROUND
Left-sided mechanical prosthetic heart valve thrombosis (PVT) occurs because of suboptimal anticoagulation and is common in low-resource settings. Urgent surgery and fibrinolytic therapy (FT) are the two treatment options available for this condition. Urgent surgery is a high-risk procedure but results in successful restoration of valve function more often and is the treatment of choice in developed countries. In low-resource countries, FT is used as the default treatment strategy, though it is associated with lower success rates and a higher rate of bleeding and embolic complications. There are no randomized trials comparing the two modalities.
METHODS
We performed a single center randomized controlled trial comparing urgent surgery (valve replacement or thrombectomy) with FT (low-dose, slow infusion tissue plasminogen activator, tPA) in patients with symptomatic left-sided PVT. The primary outcome was the occurrence of a complete clinical response, defined as discharge from hospital with completely restored valve function, in the absence of stroke, major bleeding or non-CNS systemic embolism. Outcome assessment was done by investigators blinded to treatment allocation. The principal safety outcome was the occurrence of a composite of in-hospital death, non-fatal stroke, non-fatal major bleed or non-CNS systemic embolism. Outcomes will be assessed both in the intention-to-treat, and in the as-treated population. We will also report outcomes at one year of follow-up. The trial has completed recruitment.
CONCLUSION
This is the first randomized trial to compare urgent surgery with FT for the treatment of left-sided PVT. The results will provide evidence to help clinicians make treatment choices for these patients. (Clinical trial registration: CTRI/2017/10/010159).
PubMed: 38879396
DOI: 10.1016/j.ihj.2024.06.013