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1.
Article in English | MEDLINE | ID: mdl-39359172

ABSTRACT

AIMS: We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR). BACKGROUND: Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated. METHODS: Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study. RESULTS: We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints. CONCLUSIONS: This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR.

2.
Eur J Clin Pharmacol ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264445

ABSTRACT

BACKGROUND: As per current guidelines, acute coronary syndrome (ACS) patients who undergo percutaneous coronary intervention (PCI) should be started on dual antiplatelet therapy (DAPT) for a period of 12 months. OBJECTIVE: To assess the efficacy and safety of brief DAPT (up to 3 months) succeeded by ticagrelor monotherapy compared with a 12-month DAPT in ACS patients following PCI. METHODS: We systematically searched Cochrane, Embase, and PubMed to find relevant randomized clinical trials. Examined outcomes included the incidence of major adverse cerebrovascular and cardiovascular events (MACCE), bleeding events, and the composite incidence of net adverse clinical events (NACE). RESULTS: Our primary analysis included 21,927 ACS patients from six RCTs. Our pooled results indicate that following PCI in individuals with ACS, brief DAPT followed by ticagrelor did not increase the risk of MACCE (OR 0.92, 95% CI 0.79-1.07) but significantly reduced the risk of minor or major bleeding (OR 0.52, 95% CI 0.44-0.62) and NACE (OR 0.71, 95% CI 0.59-0.86) compared with a long-term DAPT within a follow-up of 12 months. CONCLUSION: Brief DAPT followed by ticagrelor monotherapy is superior to a 12-month DAPT in offering a net clinical advantage in ACS patients following PCI.

3.
Phys Med Biol ; 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39293489

ABSTRACT

OBJECTIVE: This study presents the first clinical implementation of an efficient online daily adaptive proton therapy workflow (DAPT). Approach: The DAPT workflow includes a pre-treatment phase, where a template and a fallback plan are optimized on the planning CT. In the online phase, the adapted plan is re-optimized on daily images from an in-room CT. Daily structures are rigidly propagated from the planning CT. Automated quality assurance (QA) involves geometric, sanity checks and an independent dose calculation from the machine files. Differences from the template plan are analyzed field-by-field, and clinical plan is assessed by reviewing the achieved clinical goals using a traffic light protocol. If the daily adapted plan fails any QA or clinical goals, the fallback plan is used. In the offline phase the delivered dose is recalculated from log-files onto the daily CT, and a gamma analysis is performed (3%/3mm). The DAPT workflow has been applied to selected adult patients treated in rigid anatomy for the last serie of the treatment between October 2023 and April 2024. Main Results: DAPT treatment sessions averaged around 23 minutes [range: 15-30 min] and did not exceed the typical 30-minute time slot. Treatment adaptation, including QA and clinical plan assessment, averaged just under 7 minutes [range: 3:30-16 min] per fraction. All plans passed the online QAs steps. In the offline phase a good agreement with the log-files reconstructed dose was achieved (minimum gamma pass rate of 97.5 %). The online adapted plan was delivered for > 85% of the fractions. In 92% of total fractions, adapted plans exhibited improved individual dose metrics to the targets and/or organs at risk. Significance: This study demonstrates the successful implementation of an online daily DAPT workflow. Notably, the duration of a DAPT session did not exceed the time slot typically allocated for non-DAPT treatment. As far as we are aware, this is a first clinical implementation of daily online adaptive proton therapy. .

5.
Front Neurol ; 15: 1415861, 2024.
Article in English | MEDLINE | ID: mdl-39206292

ABSTRACT

Background: MCA bifurcation aneurysms pose treatment challenges because of the complex hemodynamics at the bifurcation and the risk of rupture. FDS implantation has been controversial and there are only limited reports. Therefore, the aim of this study was to assess the efficacy and safety of this treatment strategy using p64 MW HPC and p48 MW HPC FDSs for MCA bifurcation aneurysms, compared with the p64 classic FDS. Materials and methods: We retrospectively analyzed our institutional database and identified all patients with saccular, non-ruptured MCA bifurcation aneurysms treated with p64 MW HPC, p48 MW HPC, or p64 classic FDS implantation alone. Aneurysms with implantation of additional devices in the same session, previous treatments, and acutely ruptured and fusiform aneurysms were excluded. Results: A total of 79 aneurysms met the inclusion criteria: 23 receiving a p64 MW HPC, 34 receiving a p48 MW HPC, and 22 receiving a p64 classic FDS. The occlusion rate was highest for the p48 MW HPC 2 mm FDS, at 88.9% at FU2, compared with 72.2% for the p64 MW HPC and 70.6% for the p64 classic. The time to aneurysm occlusion was shortest with the p64 MW HPC, at 178.31 days. The highest retreatment rate was observed with the p48 MW HPC 3 mm. Conclusion: Treatment of MCA bifurcation aneurysms with a p48 MW HPC 2 mm or p64 MW HPC FDS is a safe and reliable strategy achieving high aneurysm occlusion rates - attributable to their lower porosity in relation to the parent vessel diameter as compared to the p48 MW HPC 3 mm FDS-, with reasonable morbidity and mortality.

6.
Article in English | MEDLINE | ID: mdl-39165114

ABSTRACT

AIMS: Early identification of patients with increased bleeding risk increases the possibility to individualize antithrombotic treatment. We validated the PRECISE-DAPT score, originally developed to estimate bleeding risk in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), in coronary artery bypass grafting (CABG) patients. METHODS AND RESULTS: All patients who underwent first time, isolated CABG in Sweden 2009-2020 and survived until discharge were included. The four-item PRECISE-DAPT score, based on age, estimated glomerular filtration rate, preoperative haemoglobin concentration, and previous spontaneous bleeding, was calculated in patients discharged on DAPT (n = 6 838), or antiplatelet monotherapy (n = 15 406). High bleeding risk was defined as a score ≥ 25 in accordance with previous studies and major bleeding as hospitalization due to bleeding. Associations were assessed by C-statistics and Cox regression models.Major bleeding occurred during the first postoperative year in 130 patients (1.9%) in the DAPT group, and in 197 patients (1.3%) in the monotherapy group. The score identified 32.9% of the patients in the DAPT group and 38.2% in monotherapy groups as having high bleeding risk. The area under the ROC-curve for the score was 0.67 (95%CI 0.62-0.72) for DAPT and 0.71 (0.67-0.74) for monotherapy. The hazard ratio for high bleeding risk vs. very low risk was 4.14 (2.07-8.26) for DAPT patients, and 4.95 (2.61-9.39) for monotherapy patients, both p < 0.001. CONCLUSIONS: The PRECISE-DAPT identifies patients with increased risk for major bleeding after discharge following CABG with moderate accuracy. The accuracy is comparable to what previously has been reported for patients after PCI.

7.
Article in English | MEDLINE | ID: mdl-39179951

ABSTRACT

Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018-2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95% CI 1.14-2.52, P = 0.010). Among the 623 patients with nondisabling stroke, the proportion of mRS ≤ 1 in the IVT group was higher than the DAPT group (P = 0.009). In the subtypes of MIS with large vessel occlusion/stenosis and with isolated symptoms, the 90-day outcomes of the IVT group and DAPT group were not different (P > 0.05). In conclusion, compared with DAPT, IVT was associated with better 90-day clinical outcomes in patients with MIS (in particular, for those with mRS > 1), including earlier clinical improvement.IVT also benefited the early neurological improvement of patients with severe stenosis/occlusion of intracranial large vessels, nondisabling mild stroke, nondisabling mild stroke with isolated symptoms.

8.
Eur Heart J Open ; 4(4): oeae068, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39175846

ABSTRACT

Aims: Dual antiplatelet therapy (DAPT) can be shortened up to 1 month in high-bleeding risk (HBR) patients receiving a contemporary biodegradable-polymer sirolimus-eluting stent. We aimed to summarize the evidence on a similar DAPT regimen after biodegradable-polymer everolimus-eluting stent (EES) implantation in patients at HBR. Methods and results: We pooled the individual participant data from the available trials evaluating this strategy, namely, the SENIOR and the POEM trials. Inclusion criteria were ≥1 biodegradable-polymer EES implantation and ≤1-month duration of DAPT. The primary endpoint was the 1-year composite of cardiovascular death, myocardial infarction, or stroke. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3-5 bleeding. Landmark analyses were performed at 1 month, the time point for intended DAPT interruption. We included 766 participants (age 77.5 ± 8.2 years, women 31.9%), 323 from the SENIOR and 443 from the POEM trial. The primary endpoint occurred in 45 participants (6.0%; 95% confidence interval [CI], 4.3-7.7%) through 1 year of follow-up, with 21 (2.8%; 95% CI, 1.6-3.9%) events during the first month and 24 (3.4%; 95% CI, 2.0-4.7%) thereafter. The incidences of cardiovascular death, myocardial infarction, and stroke were 2.2% (95% CI, 0.36-2.50%), 3.1% (95% CI, 1.8-4.3%), and 1.2% (95% CI, 0.4-2.0%), respectively. BARC type 3-5 bleeding ocuurred in 1.1% (95% CI, 0.3-1.8%) at 1 month and 2.9% (95% CI, 1.6-4.1%) at 1 year. Conclusion: HBR patients receiving biodegradable-polymer EES had few ischemic and bleeding events when given 1 month of DAPT. One-month DAPT after biodegradable-polymer EES implantation seems safe in patients at HBR.

9.
Article in English | MEDLINE | ID: mdl-38987047

ABSTRACT

De-escalation of dual antiplatelet therapy (DAPT) is gaining traction as a strategy to reduce bleeding risks while ensuring ischemic outcomes. Undiscriminating de-escalation, notably in patients with high ischemic risk, might expose them to major adverse cardiac events. Platelet function and genetic tests are emerging tools to guide de-escalation, but both present specific drawbacks. Recent meta-analyses have aimed to consolidate the findings of individual trials to provide clearer insights. Yet, limitations remain for patients with concomitant high bleeding and ischemic risks. These high-risk patients are frequently underrepresented in clinical trials, and, therefore, currently available guidelines lack evidence-based recommendations for this subset. While DAPT de-escalation strategies hold promise, the choice of approach, whether clinically or assay-guided, remains complex and should be individualized.

10.
Eur Heart J ; 45(34): 3138-3148, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39016180

ABSTRACT

BACKGROUND AND AIMS: This study assessed the impact of incorporating cancer as a predictor on performance of the PRECISE-DAPT score. METHODS: A nationally linked cohort of ST-elevation myocardial infarction patients between 1 January 2005 and 31 March 2019 was derived from the UK Myocardial Ischaemia National Audit Project and the UK Hospital Episode Statistics Admitted Patient Care registries. The primary outcome was major bleeding at 1 year. A new modified score was generated by adding cancer as a binary variable to the PRECISE-DAPT score using a Cox regression model and compared its performance to the original PRECISE-DAPT score. RESULTS: A total of 216 709 ST-elevation myocardial infarction patients were included, of which 4569 had cancer. The original score showed moderate accuracy (C-statistic .60), and the modified score showed modestly higher discrimination (C-statistics .64; hazard ratio 1.03, 95% confidence interval 1.03-1.04) even in patients without cancer (C-statistics .63; hazard ratio 1.03, 95% confidence interval 1.03-1.04). The net reclassification index was .07. The bleeding rates of the modified score risk categories (high, moderate, low, and very low bleeding risk) were 6.3%, 3.8%, 2.9%, and 2.2%, respectively. According to the original score, 65.5% of cancer patients were classified as high bleeding risk (HBR) and 21.6% were low or very low bleeding risk. According to the modified score, 94.0% of cancer patients were HBR, 6.0% were moderate bleeding risk, and no cancer patient was classified as low or very low bleeding risk. CONCLUSIONS: Adding cancer to the PRECISE-DAPT score identifies the majority of patients with cancer as HBR and can improve its discrimination ability without undermining its performance in patients without cancer.


Subject(s)
Hemorrhage , Neoplasms , Humans , Male , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Neoplasms/complications , Aged , Risk Assessment/methods , Middle Aged , ST Elevation Myocardial Infarction/epidemiology , United Kingdom/epidemiology , Risk Factors , Registries , Platelet Aggregation Inhibitors/therapeutic use , Percutaneous Coronary Intervention
11.
Eur Heart J ; 45(34): 3124-3131, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39056269

ABSTRACT

Multivessel coronary artery disease is present in ∼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.


Subject(s)
Acute Coronary Syndrome , Coronary Artery Bypass , Percutaneous Coronary Intervention , Humans , Acute Coronary Syndrome/surgery , Acute Coronary Syndrome/therapy , Percutaneous Coronary Intervention/methods , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Patient Selection
12.
Acta Neurochir (Wien) ; 166(1): 271, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888678

ABSTRACT

This comprehensive review delves into the evolving field of neurointervention for intracranial aneurysms, exploring the critical adjunct of Dual Antiplatelet Therapy (DAPT) to endovascular coiling, stent-assisted coiling (SAC), flow-diversion stents, and flow-disruption (intrasaccular) devices. Despite growing evidence supporting the success of DAPT in reducing thromboembolic events, the lack of consensus on optimal regimens, doses, and duration is evident. Factors contributing to this variability include genetic polymorphisms affecting treatment response and ongoing debates regarding the clinical significance of hemorrhagic complications associated with DAPT. This review analyzes pre- and post-procedural antiplatelet usage across various interventions. The imperative lies in ongoing research to define optimal DAPT durations, ensuring a nuanced approach to the delicate balance between thrombosis and hemorrhage in intracranial aneurysm management.


Subject(s)
Endovascular Procedures , Intracranial Aneurysm , Platelet Aggregation Inhibitors , Humans , Intracranial Aneurysm/surgery , Intracranial Aneurysm/drug therapy , Endovascular Procedures/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Dual Anti-Platelet Therapy/methods , Consensus , Stents
13.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38931384

ABSTRACT

The heterogeneity of etiology may serve as a crucial factor in the challenges of treatment, including the low response rate and the delay in establishing therapeutic effect. In the present study, we examined whether social experience since early life is one of the etiologies, with the involvement of the 5-HT1A receptors, and explored the potentially therapeutic action of the subchronic administration of buspirone, a partial 5-HT1A agonist. Rats were isolation reared (IR) since their weaning, and the depressive profile indexed by the forced-swim test (FST) was examined in adulthood. Nonspecific locomotor activity was used for the IR validation. Buspirone administration (1 mg/kg/day) was introduced for 14 days (week 9-11). The immobility score of the FST was examined before and after the buspirone administration. Tissue levels of serotonin (5-HT) and its metabolite 5-HIAA were measured in the hippocampus, the amygdala, and the prefrontal cortex. Efflux levels of 5-HT, dopamine (DA), and norepinephrine (NE) were detected in the hippocampus by brain dialysis. Finally, the full 5-HT1A agonist 8-OH-DPAT (0.5 mg/kg) was acutely administered in both behavioral testing and the dialysis experiment. Our results showed (i) increased immobility time in the FST for the IR rats as compared to the social controls, which could not be reversed by the buspirone administration; (ii) IR-induced FST immobility in rats receiving buspirone was corrected by the 8-OH-DPAT; and (iii) IR-induced reduction in hippocampal 5-HT levels can be reversed by the buspirone administration. Our data indicated the 5-HT1A receptor-linked early life social experience as one of the mechanisms of later life depressive mood.

14.
Am J Cardiol ; 225: 25-34, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38871156

ABSTRACT

Shortening the duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was shown to be effective and safe in patients at high bleeding risk (HBR). We aimed to investigate the effect of 1 versus 3-month DAPT on outcomes after drug-eluting stent in HBR patients with or without chronic kidney disease (CKD). Data from 3 prospective single-arm studies (XIENCE Short DAPT Program) enrolling HBR patients after successful coronary implantation of cobalt-chromium everolimus-eluting stent (XIENCE, Abbott) were analyzed. Subjects were eligible for DAPT discontinuation at 1 or 3 months if free from ischemic events. The primary end point was all-cause death or any myocardial infarction. The key secondary end point was Bleeding Academic Research Consortium Type 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after PCI. CKD was defined as baseline creatinine clearance <60 ml/min. Of 3,286 patients, 1,432 (43.6%) had CKD. One-month versus 3-month DAPT was associated with a similar 12-month risk of the primary outcome irrespective of CKD status (CKD: 9.5% vs 10.9%, adjusted hazard ratio 0.86, 95% confidence interval 0.60 to 1.22; no-CKD: 6.6% vs 5.6%, adjusted hazard ratio 1.15, 95% confidence interval 0.77 to 1.73; p interaction 0.299). Bleeding Academic Research Consortium 2 to 5 bleeding rates were numerically but not significantly lower with 1-month versus 3-month DAPT in both CKD (9.9% vs 12%) and no-CKD (6.4% vs 9.0%) patients. In conclusion, in HBR patients, 1-month versus 3-month DAPT was associated with a similar risk of ischemic complications and a trend toward fewer bleeding events at 12 months after PCI, irrespective of CKD status.


Subject(s)
Drug-Eluting Stents , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Renal Insufficiency, Chronic , Humans , Male , Female , Renal Insufficiency, Chronic/complications , Percutaneous Coronary Intervention/methods , Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Middle Aged , Prospective Studies , Dual Anti-Platelet Therapy/methods , Hemorrhage/epidemiology , Hemorrhage/chemically induced , Coronary Artery Disease/surgery , Coronary Artery Disease/complications , Time Factors , Clopidogrel/therapeutic use , Clopidogrel/administration & dosage , Aspirin/administration & dosage , Aspirin/therapeutic use , Myocardial Infarction/epidemiology , Cause of Death/trends , Drug Administration Schedule , Risk Factors
15.
Curr Probl Cardiol ; 49(8): 102635, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38750991

ABSTRACT

BACKGROUND: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short DAPT. However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard DAPT in patients undergoing PCI at 12 months. METHODS: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529). RESULTS: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both allcause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments. CONCLUSIONS: In comparison to standard DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Purinergic P2Y Receptor Antagonists , Randomized Controlled Trials as Topic , Humans , Percutaneous Coronary Intervention/methods , Purinergic P2Y Receptor Antagonists/therapeutic use , Purinergic P2Y Receptor Antagonists/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Treatment Outcome , Dual Anti-Platelet Therapy/methods , Ticagrelor/therapeutic use
18.
J Stroke Cerebrovasc Dis ; 33(6): 106578, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636320

ABSTRACT

BACKGROUND: Notch1 signaling inhibiton with N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester] (DAPT) treatment could promote brain recovery and the intervention effect is different between striatum (STR) and cortex (CTX), which might be accounted for different changes of glial activities, but the in-depth mechanism is still unknown. The purpose of this study was to identify whether DAPT could modulate microglial subtype shifts and astroglial-endfeet aquaporin-4 (AQP4) mediated waste solute drainage. METHODS: Sprague-Dawley rats (n=10) were subjected to 90min of middle cerebral artery occlusion (MCAO) and were treated with DAPT (n=5) or act as control with no treatment (n=5). Two groups of rats underwent MRI scans at 24h and 4 week, and sacrificed at 4 week after stroke for immunofluorescence (IF). RESULTS: Compared with control rats, MRI data showed structural recovery in ipsilateral STR but not CTX. And IF showed decreased pro-inflammatory M1 microglia and increased anti-inflammatory M2 microglia in striatal lesion core and peri-lesions of STR, CTX. Meanwhile, IF showed decreased AQP4 polarity in ischemic brain tissue, however, AQP4 polarity in striatal peri-lesions of DAPT treated rats was higher than that in control rats but shows no difference in cortical peri-lesions between control and treated rats. CONCLUSIONS: The present study indicated that DAPT could promote protective microglia subtype shift and striatal astrocyte mediated waste solute drainage, that the later might be the major contributor of waste solute metabolism and one of the accounts for discrepant recovery of STR and CTX.


Subject(s)
Aquaporin 4 , Astrocytes , Dipeptides , Disease Models, Animal , Infarction, Middle Cerebral Artery , Microglia , Rats, Sprague-Dawley , Receptor, Notch1 , Recovery of Function , Signal Transduction , Animals , Aquaporin 4/metabolism , Receptor, Notch1/metabolism , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/physiopathology , Male , Astrocytes/metabolism , Astrocytes/drug effects , Astrocytes/pathology , Microglia/metabolism , Microglia/drug effects , Microglia/pathology , Dipeptides/pharmacology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Corpus Striatum/metabolism , Corpus Striatum/drug effects , Corpus Striatum/pathology , Time Factors , Neuroprotective Agents/pharmacology , Ischemic Stroke/metabolism , Ischemic Stroke/drug therapy , Ischemic Stroke/physiopathology , Ischemic Stroke/pathology
19.
ACG Case Rep J ; 11(4): e01324, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38560012

ABSTRACT

Acute appendicitis is one of the most common abdominal surgical emergencies. A laparoscopic or open appendectomy has traditionally been the gold standard. Antibiotic therapy has recently been found to be noninferior. The treatment of acute uncomplicated appendicitis remains a challenge, especially in the presence of an appendicolith. We present a case of a 59-year-old man with recent ST-elevation myocardial infarction who underwent successful endoscopic retrograde appendicitis therapy.

20.
J Robot Surg ; 18(1): 174, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613654

ABSTRACT

Prostate cancer patients often have other health conditions and take anticoagulants. It was believed that surgery under anticoagulants could worsen surgical results. This study aims to explore the safety of robot-assisted prostatectomy in anticoagulated patients, without any exclusion criteria. The study included 500 patients who underwent RARP by a single surgeon between April 2019 and August 2022. Patients were divided into two groups: Group 1, consisting of 376 men (75.2%), did not receive any anticoagulation, while Group 2, with 124 patients (24.8%), received different forms of anticoagulation. Then, the anticoagulation group was divided into 4 subgroups according to their definite anticoagulation: the aspirin 15.6%, new oral anticoagulants (NOAC) 5.4%, Vitamin K antagonist (VKA) 2%, and dual-antiplatelet therapy (DAPT) 1.8% subgroup. Postoperative complications and readmission rates were compared between the two study groups and subgroups. Patients in the combined group 2 were older and they also carried more comorbidities compared to men in group 1 (p = 0.03, p = 0.001).The study groups had similar oncological results, with 40.4% of patients having locally advanced cancers. Catheter days were longer in the anticoagulation group (4.5 vs 4 days, p = 0.001). No significant differences were observed between study groups for overall, minor, and major complications (p = 0.160, 0.100, and 0.915, respectively). In addition, readmissions were low (5.6%) and similar between the study groups (p = 0.635). Under cautious management, RARP under diverse anticoagulation regimes is safe and has comparable results to men with no medications. Further prospective studies must be conducted to confirm our findings.


Subject(s)
Robotic Surgical Procedures , Robotics , Surgeons , Male , Humans , Anticoagulants/adverse effects , Robotic Surgical Procedures/methods , Prostatectomy
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