Impact of Intensive Blood Pressure Lowering After Multiple-Attempt Endovascular Thrombectomy : a secondary analysis of the OPTIMAL-BP trial.

BACKGROUND: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain. AIMS: This study aimed to investigate whether conventional and intensive BP management differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups. METHODS: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target <140 mm Hg) and conventional (systolic BP target 140-180 mm Hg) BP managements during the 24 hours after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality within 3 months. RESULTS: Of the 305 patients (median 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs. conventional, 54.9%, adjusted OR 0.33, 95% CI 0.12-0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs. conventional, 54.2%, adjusted OR 0.73, 95% CI 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups. CONCLUSIONS: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 hours resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Combined use of anticoagulant and antiplatelet on outcome after stroke in patients with nonvalvular atrial fibrillation and systemic atherosclerosis.

This study aimed to investigate whether there was a difference in one-year outcome after stroke between patients treated with antiplatelet and anticoagulation (OAC + antiplatelet) and those with anticoagulation only (OAC), when comorbid atherosclerotic disease was present with non-valvular atrial fibrillation (NVAF). This was a retrospective study using a prospective cohort of consecutive patients with ischemic stroke. Patients with NVAF and comorbid atherosclerotic disease were assigned to the OAC + antiplatelet or OAC group based on discharge medication. All-cause mortality, recurrent ischemic stroke, hemorrhagic stroke, myocardial infarction, and bleeding events within 1 year after the index stroke were compared. Of the 445 patients included in this study, 149 (33.5%) were treated with OAC + antiplatelet. There were no significant differences in all outcomes between groups. After inverse probability of treatment weighting, OAC + antiplatelet was associated with a lower risk of all-cause mortality (hazard ratio 0.48; 95% confidence interval 0.23-0.98; P = 0.045) and myocardial infarction (0% vs. 3.0%, P < 0.001). The risk of hemorrhagic stroke was not significantly different (P = 0.123). OAC + antiplatelet was associated with a decreased risk of all-cause mortality and myocardial infarction but an increased risk of ischemic stroke among patients with NVAF and systemic atherosclerotic diseases.

Initial stroke severity and discharge outcome in patients with muscle mass deficit.

This study aimed to investigate the association between muscle mass deficit and the initial severity of ischemic stroke. The impact of muscle mass deficit on the discharge outcome was also evaluated. This retrospective study included 660 patients with acute ischemic stroke who underwent bioelectrical impedance analyses. We compared the National Institute of Health Stroke Scale (NIHSS) score, occurrence of moderate stroke (NIHSSS ≥ 5) at admission, and unfavorable functional outcome (modified Rankin Scale score ≥ 2) at discharge between patients with and without muscle mass deficit using Poisson and logistic regression analyses. The mean age of the study patients was 65.6 ± 13.0, and 63.3% were males. Muscle mass deficit was present in 24.4% of patients. Muscle mass deficit was significantly and independently associated with NIHSS score or moderate stroke (all p < 0.05). This association was noted regardless of patient characteristics. Among the respective NIHSS items, muscle mass deficit was significantly associated with facial palsy, motor function of the arm or leg, limb ataxia, and dysarthria. Muscle mass deficit also led to unfavorable functional outcome, which was mediated by the initial NIHSS score. In conclusion, muscle mass deficit is associated with higher NIHSS score and unfavorable functional outcome in patients with acute ischemic stroke.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Association of clot ultrastructure with clot perviousness in stroke patients.

Clot perviousness on computerized tomography (CT) is predictive of response to reperfusion therapy. This study aimed to determine the association of clot perviousness with ultrastructural features of clot in stroke patients undergoing endovascular thrombectomy. We quantitatively analyzed the ultrastructural components identified using scanning electron microscopy. The clot components were determined in the inner portions of the clots. Clot perviousness was assessed as thrombus attenuation increase (TAI) using noncontrast CT and CT angiography. We compared the association between the identified ultrastructural components and clot perviousness. The proportion of pores consisted of 3.5% on scanning electron microscopy images. The proportion of porosity in the inner portion was 2.5%. Among the ultrastructural components, polyhedrocytes were most commonly observed. The mean TAI was 9.3 ± 10.0 (median 5.6, interquartile range 1.1-14.3) Hounsfield units. TAI correlated positively with inner porosity (r = 0.422, p = 0.020). Among the ultrastructural clot components, TAI was independently associated with polyhedrocytes (B = - 0.134, SE = 0.051, p = 0.008). Clot perviousness is associated with porosity and the proportion of polyhdrocytes of clots.

Efficacy and safety of Kumpe access catheter for pre-percutaneous nephrolithotomy renal access in modified supine percutaneous nephrolithotomy.

INTRODUCTION: Traditionally, a pigtail catheter (PCN) is placed for preoperative renal access before performing percutaneous nephrolithotomy (PCNL). However, PCN can hamper the passage of the guidewire to the ureter, due to which, access tract can be lost. Therefore, Kumpe Access Catheter (KMP) has been proposed for preoperative renal access before PCNL. In this study, we analyzed the efficacy and safety of KMP for surgical outcomes in modified supine PCNL compared to those in PCN. MATERIALS AND METHODS: From July 2017 to December 2020, 232 patients underwent modified supine PCNL at a single tertiary center, of which 151 patients were enrolled in this study after excluding patients who underwent bilateral surgery, multiple punctures, or combined operations. Enrolled patients were divided into two groups according to the type of pre-PCNL nephrostomy catheter used: PCN versus KMP. A pre-PCNL nephrostomy catheter was selected based on the radiologist's preference. A single surgeon performed all PCNL procedures. Patient characteristics and surgical outcomes, including stone-free rate, operation time, radiation exposure time (RET), and complications, were compared between the two groups. RESULTS: Of the 151 patients, 53 underwent PCN placement, and 98 underwent KMP placement for pre-PCNL nephrostomy. Patient baseline characteristics were comparable between the two groups, except for the renal stone type and multiplicity. The operation time, stone-free rate, and complication rate were not significantly different between the two groups; however, RET was significantly shorter in the KMP group. CONCLUSION: The surgical outcomes of KMP placement were comparable to those of PCN and showed shorter RET during modified supine PCNL. Based on our results, we recommend KMP placement for pre-PCNL nephrostomy, particularly for reducing RET during supine PCNL.

Prognostic value of central blood pressure on the outcomes of embolic stroke of undetermined source.

We investigated the prognostic impact of central blood pressure (BP) on outcomes in patients with embolic stroke of undetermined source (ESUS). The prognostic value of central BP according to ESUS subtype was also evaluated. We recruited patients with ESUS and data on their central BP parameters (central systolic BP [SBP], central diastolic BP [DBP], central pulse pressure [PP], augmentation pressure [AP], and augmentation index [AIx]) during admission. ESUS subtype classification was arteriogenic embolism, minor cardioembolism, two or more causes, and no cause. Major adverse cardiovascular event (MACE) was defined as recurrent stroke, acute coronary syndrome, hospitalization for heart failure, or death. Over a median of 45.8 months, 746 patients with ESUS were enrolled and followed up. Patients had a mean age of 62.8 years, and 62.2% were male. Multivariable Cox regression analysis showed that central SBP and PP were associated with MACE. All-cause mortality was independently associated with AIx. In patients with no cause ESUS, central SBP and PP, AP, and AIx were independently associated with MACE. AP and AIx were independently associated with all-cause mortality (all p < 0.05). We demonstrated that central BP can predict poor long-term prognosis in patients with ESUS, especially those with the no cause ESUS subtype.

Development of bisphenol A-removing recombinant Escherichia coli by monomeric and dimeric surface display of bisphenol A-binding peptide.

Peptide-displaying Escherichia coli cells were investigated for use in adsorptive removal of bisphenol A (BPA) both in Luria-Bertani medium including BPA or ATM thermal paper eluted wastewater. Two recombinant strains were constructed with monomeric and dimeric repeats of the 7-mer BPA-binding peptide (KSLENSY), respectively. Greater than threefold increased adsorption of BPA [230.4 µmol BPA per g dry cell weight (DCW)] was found in dimeric peptide-displaying cells compared to monomeric strains (63.4 µmol per g DCW) in 15 ppm BPA solution. The selective removal of BPA from a mixture of BPA analogs (bisphenol F and bisphenol S) was verified in both monomeric and dimeric peptide-displaying cells. The binding chemistry of BPA with the peptide was assumed, based on molecular docking analysis, to be the interaction of BPA with serine and asparagine residues within the 7-mer peptide sequence. The peptide-displaying cells also functioned efficiently in thermal paper eluted wastewater containing 14.5 ppm BPA.

Kinetic evidence for the interactive inhibition of laccase from Trametes versicolor by pH and chloride.

The interactive inhibitory effects of pH and chloride on the catalysis of laccase from Trametes versicolor were investigated by studying the alteration of inhibition characteristics of sodium chloride at different pHs for the oxidation of 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid). At pH 3.0, the addition of sodium chloride (50 mM) brought about a 40-fold increase in Km(app) and a 4-fold decrease in Vmax(app). As the pH increased to 7.0, the inhibitory effects of sodium chloride became significantly weakened. The mixed-inhibition mechanism was successfully used to quantitatively estimate the competitive and uncompetitive inhibition strengths by chloride at two different pHs (pH 3.0 and 6.0). At pH 3.0, the competitive inhibition constant, Ki, was 0.35 mM, whereas the uncompetitive inhibition constant, Ki', was 18.1 mM, indicating that the major cause of the laccase inhibition by chloride is due to the competitive inhibition step. At a higher pH of 6.0, where the inhibition of the laccase by hydroxide ions takes effect, the inhibition of the laccase by chloride diminished to a great extent, showing increased values of both the competitive inhibition constant (Ki= 23.7 mM) and uncompetitive inhibition constant (Ki' = 324 mM). These kinetic results evidenced that the hydroxide anion and chloride share a common mechanism to inhibit the laccase activity.

Induction and relaxation dynamics of the regulatory network controlling the type III secretion system encoded within Salmonella pathogenicity island 1.

Bacterial pathogenesis requires the precise spatial and temporal control of gene expression, the dynamics of which are controlled by regulatory networks. A network encoded within Salmonella Pathogenicity Island 1 controls the expression of a type III protein secretion system involved in the invasion of host cells. The dynamics of this network are measured in single cells using promoter-green fluorescent protein (gfp) reporters and flow cytometry. During induction, there is a temporal order of gene expression, with transcriptional inputs turning on first, followed by structural and effector genes. The promoters show varying stochastic properties, where graded inputs are converted into all-or-none and hybrid responses. The relaxation dynamics are measured by shifting cells from inducing to noninducing conditions and by measuring fluorescence decay. The gfp expressed from promoters controlling the transcriptional inputs (hilC and hilD) and structural genes (prgH) decay exponentially, with a characteristic time of 50-55 min. In contrast, the gfp expressed from a promoter controlling the expression of effectors (sicA) persists for 110+/-9 min. This promoter is controlled by a genetic circuit, formed by a transcription factor (InvF), a chaperone (SicA), and a secreted protein (SipC), that regulates effector expression in response to the secretion capacity of the cell. A mathematical model of this circuit demonstrates that the delay is due to a split positive feedback loop. This model is tested in a DeltasicA knockout strain, where sicA is complemented with and without the feedback loop. The delay is eliminated when the feedback loop is deleted. Furthermore, a robustness analysis of the model predicts that the delay time can be tuned by changing the affinity of SicA:InvF multimers for an operator in the sicA promoter. This prediction is used to construct a targeted library, which contains mutants with both longer and shorter delays. This combination of theory and experiments provides a platform for predicting how genetic perturbations lead to changes in the global dynamics of a regulatory network.