Dynamic changes of systemic inflammation response index and systemic immune-inflammation index are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Delayed cerebral ischemia (DCI) is a factor contributing to poor outcome of aneurysmal subarachnoid hemorrhage (aSAH). Serial inflammatory response is known to affect the occurrence of DCI. The aim of this study was to evaluate associations of dynamic changes of various inflammatory markers with occurrence of DCI after aSAH. METHODS: A total of 279 patients with interventional treatment for aSAH were enrolled, and dichotomized according to the occurrence of DCI. Various inflammatory markers, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and their dynamic changes were analyzed at four different time points. Receiver operating characteristic (ROC) curve analysis with area under the curve (AUC) and univariate, multivariate Cox regression analyses with hazard ratio (HR) and 95 % confidence interval (CI) were performed to identify predictors for DCI. RESULTS: Differences of SII and SIRI values between DCI (+) and DCI (-) group were significantly higher at 5-7 days than at other time points (P < 0.001 and P < 0.001, respectively). SII and SIRI had higher predicting values for DCI occurrence than other inflammatory markers (AUC: 0.862, 95 % CI: 0.786-0.928; P < 0.001 and AUC: 0.851, 95 % CI: 0.769-0.913; P < 0.001, respectively). SII at 5-7 days (HR: 1.74, 95 % CI: 1.38-3.22, P = 0.020) and SIRI at 5-7 days (HR: 1.62, 95 % CI: 1.28-2.84, P = 0.035) were associated with occurrence of DCI. CONCLUSIONS: Dynamic changes of SII and SII might be predictors of DCI occurrence in patients with aSAH.

Elevated blood viscosity is associated with delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Delayed cerebral ischemia (DCI) is a contributing factor for poor clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). Blood viscosity can reflect flow resistance and dehydration status. Our study aimed to analyze the association between blood viscosity and DCI in patients with aSAH. METHODS: In this retrospective cohort, systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) were measured at admission in patients with aSAH. Receiver operating characteristic curve analysis was used to assess the predictive values of SBV and DBV for DCI after aSAH. Univariate and multivariate logistic regression was performed to analyze the association between blood viscosity and the development of DCI. RESULTS: A total of 470 patients with aSAH were included in this study, and 184 (39.1%) patients had DCI. Optimal cut-off values of DBV and SBV were presented as 12.05 (cP) and 3.75 (cP), respectively. In addition, DBV has higher predictable value of DCI than SBV (DBV: area under the curve [AUC] 0.793; standard error [SE] 0.026; 95% CI 0.722-0.864; P < 0.001, and SBV: AUC 0.702; SE 0.040; 95% CI 0.624-0.781; P < 0.001). In multivariate logistic regression analysis, elevated DBV was a predicting factor for development of DCI (odds ratio: 1.60; 95% confidence interval: 1.32-2.58; P = 0.037). CONCLUSIONS: Blood viscosity is associated with development of DCI in patients with aSAH. Especially, DBV has a higher predictive value for the occurrence of DCI than SBV. Elevated DBV is a potential predicting factor for the occurrence of DCI.

Comparative pharmacokinetics of Theracurmin, a highly bioavailable curcumin, in healthy adult subjects.

OBJECTIVE: Theracurmin is a submicron dispersed formulation of curcumin, which was developed to increase the bioavailability of curcumin. This study aimed to compare the pharmacokinetics of curcumin administered as two Theracurmin powder products and unformulated curcumin powder. MATERIALS AND METHODS: This randomized, three-treatment, six-sequence, and three-period crossover study enrolled 24 healthy subjects. Blood sampling was done until 12 hours after the administration of Theracurmin and curcumin powder to assess pharmacokinetics using a non-compartmental method. The plasma concentration of curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: The median time to reach the maximum concentration was 1.5 - 3 hours for Theracurmin and 8 hours for curcumin powder. The two Theracurmin products showed systemic exposure profiles that were comparable to each other. The exposure ratio of Theracurmin to curcumin powder was 18.4 - 20.5 for the maximum plasma concentration and 35.9 - 42.6 for the area under the concentration-time curve from dosing to the last measurable time. CONCLUSION: In conclusion, this study showed similar systemic exposure between the two Theracurmin products. The absorption of curcumin after the administration of Theracurmin was significantly enhanced compared with curcumin powder.

Intractable hiccups caused by syringobulbia and syringomyelia associated with intramedullary spinal hemangioblastoma.

INTRODUCTION: Hiccups caused by a neoplasm in the spinal cord are rare. MATERIALS AND METHODS: We report a case of intractable hiccups caused by syringobulbia and syringomyelia associated with cervical intramedullary spinal hemangioblastoma, which was successfully treated by surgical excision. A 60-year-old man was referred from the neurology department after presenting with hiccups for 1 year. The hiccups were aggravated 3 months ago and were sustained during eating or sleeping. Several doctors administered a muscle relaxant and an anticonvulsant, but they were ineffective. Spinal MRI revealed a huge syringomyelia from C2 to T2, associated with a highly enhancing intramedullary mass lesion at the C5 level. The hiccups were ceased after removal of the tumor through a right hemilaminectomy. The pathology of the specimen was hemangioblastoma. The size of the syringobulbia and syringomyelia decreased markedly on MRI checked 5 months after surgery. CONCLUSIONS: Intractable hiccups can be caused by syringobulbia associated with an intramedullary cord tumor in the cervical area and possible mechanisms of hiccups were reviewed.

Ocular and Plasma Pharmacokinetics of Enavogliflozin Ophthalmic Solution in Preclinical Species.

An enavogliflozin ophthalmic solution (DWRX2008) is being developed to treat diabetic retinopathy and macular edema. This study evaluated the ocular distribution and plasma pharmacokinetics (PKs) of enavogliflozin in animal species. A sample of [14C] enavogliflozin was ocularly administered to two rabbits per time point at single doses of 600 µg/eye to evaluate ocular PK, which was evaluated using autoradiography until 48 h post-dose. Plasma concentrations after ocular administration in six rabbits, three rats, and three beagle dogs with single doses of 400 µg, 25 µg, and 100 µg, respectively, were investigated for 24 h. The retinal concentration of [14C] enavogliflozin reached Cmax at 2.0 h with an elimination half-life of 32.5 h, which remained above the IC50 value of sodium-dependent glucose transporter 2 until 24 h post-dose. In the plasma of rabbits, the fastest Tmax of 0.5 h and a 3.6 h half-life were observed among animal species. The relative bioavailability in rabbits after ocular administration was 3.4 compared to oral administration. Ocular administration of enavogliflozin could be a potential therapeutic route for diabetic retinal complications, based on relative bioavailability and effective delivery to the posterior ocular segment. DWRX2008 would be applicable to humans with favorable PK profiles and minimal systemic adverse effect.

Pan-immune-inflammation value predict delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

Inflammatory reaction and immune dysregulation are known as components contributing to delayed cerebral ischemia (DCI) in patients with following aneurysmal subarachnoid hemorrhage (aSAH). The objective of this study was to investigate the role of pan-immune-inflammation value (PIV) as a novel comprehensive inflammatory marker in predicting the DCI development following aSAH. A total of 1028 participants with aSAH were enrolled. There were 296 patients with DCI and 732 patients without DCI. Various inflammatory markers were analyzed using peripheral blood sample obtained at admission. Receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff value of PIV for distinguishing DCI. Multivariate analysis was used to determine independent predictors for DCI. Mean PIV was significantly higher in the DCI (+) group than in the DCI (-) group (437.6 ± 214.7 vs 242.1 ± 154.7, P = 0.007). In ROC analysis, the optimal cutoff value of PIV was 356.7 for predicting DCI (area under the curve [AUC] 0.772, 95 % confidence interval [CI] 0.718-0.816; P < 0.001). Multivariate analysis showed that high Hunt-Hess grade (odds ratio [OR] 1.70, 95 % CI 1.38-2.22; P = 0.007), thick SAH (OR 1.82, 95 % CI 1.44-2.32; P = 0.005), and elevated PIV (≥356.7) (OR 1.42, 95 % CI 1.10-1.74; P = 0.013) were independent predictors of DCI after aSAH. PIV is a potent predictor of DCI in patients with aSAH. Elevated PIV is associated with more DCI development. Thus, PIV has predictive value for DCI development.

Predictors of Emboli in Mechanical Thrombectomy for Anterior Circulation Stroke.

OBJECTIVE: Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT. METHODS: Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli. RESULTS: Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; p = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; p = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; p = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; p = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; p = 0.029) were associated with occurrence of emboli. CONCLUSION: MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.

Comparison of 4 mm-sized and 3 mm-sized Stent Retrievers in Mechanical Thrombectomy for M2 Occlusion.

INTRODUCTION: A stent retriever (SR) is widely used in mechanical thrombectomy (MT) for M2 segment occlusion. However, the suitable size of SR in M2 occlusion remains unclear. Therefore, we aimed to compare 4 mm-sized SR with 3 mm-sized SR in M2 occlusion. METHODS: Patients who underwent MT with SR for M2 occlusion were dichotomized into 4×20 mm SR and 3×20 mm SR groups. Then, 1:1 propensity score matching was performed. The M2 segment was divided into proximal and distal segments according to the occlusion site. Subgroup analysis was then performed for each cohort. RESULTS: A total of 111 patients were enrolled, with 4×20 mm SR and 3×20 mm SR applied in 72 (64.9%) and 39 (35.1%) cases, respectively. In propensity score matching, mean number of stent passages for reperfusion was significantly lower in the 4×20 mm SR group than in the 3×20 mm SR group (1.5 ± 0.8 vs. 2.1 ± 1.1; p = 0.004). First-pass reperfusion (FPR) was more highly achieved in the 4×20 mm SR group than in the 3×20 mm SR group (52.6% vs. 42.1%; p = 0.007). In both proximal and distal occlusion cohorts, the 4 mm SR group showed lower mean number of SR passage (p = 0.004 and p = 0.003, respectively) and higher FPR rate than the 3 mm SR group (p = 0.003 and p = 0.007, respectively). CONCLUSION: In MT for M2 occlusion, 4×20 mm SR enables an effective procedure with lesser SR passage for reperfusion and a higher rate of FPR than 3×20 mm SR.

Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery.

Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed-effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two-compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80-fold during CPB and warming phases, while the central compartment volume increased 2.74-fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL-6, IL-8, and TNF-α during CPB. The simulation indicated a 30 µg loading dose and 40 µg/h maintenance infusion for target-controlled infusion. Additionally, a bolus dose of 60 µg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 administered by auto-injector or pre-filled syringe: a randomized, open­label, single-dose phase I study.

BACKGROUND: This study compared the pharmacokinetics (PK), immunogenicity, and safety of candidate tocilizumab biosimilar, CT-P47, administered via auto-injector (CT-P47 AI) or pre-filled syringe (CT-P47 PFS), in healthy Asian adults. RESEARCH DESIGN AND METHODS: In this phase I, multicenter, open-label study, participants were randomized 1:1 to receive a single 162 mg/0.9 mL dose of CT-P47 via AI or PFS. Primary endpoints were area under the concentration - time curve from time zero to infinity (AUC0-inf) and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK parameters, immunogenicity, and safety outcomes were also assessed. RESULTS: Of 314 participants randomized (155 CT-P47 AI; 159 CT-P47 PFS), 310 received the study drug (153 CT-P47 AI; 157 CT-P47 PFS). Primary and secondary PK results, immunogenicity and safety were similar between groups. Ninety percent CIs for the ratio of gLSMs were within the predefined equivalence margin for AUC0-inf (85.87-102.94) and Cmax (82.98-98.16). CONCLUSIONS: PK equivalence between CT-P47 AI and CT-P47 PFS was demonstrated in healthy Asian adults, with comparable immunogenicity and safety between the two devices. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05617183.

Tocilizumab is a biologic medicine used to treat inflammatory diseases, such as rheumatoid arthritis. A biosimilar is a drug that is an almost identical copy of an approved original ('reference') biologic medicine; it has identical efficacy and safety to the original medicine but is typically less expensive. CT­P47 is in development as a possible tocilizumab biosimilar.Some patients prefer injections using an auto-injector (AI) rather than a pre-filled syringe (PFS), for reasons including ease of use and convenience. With an AI, medicine is delivered automatically by firmly pressing the device against the skin, whereas, with a PFS, a needle is inserted into the skin and medicine delivered by depressing the plunger. The injection of CT­P47 using a PFS has shown comparable pharmacokinetics (i.e., the uptake, metabolism and excretion of the drug by the body) and safety to tocilizumab. Therefore, if the pharmacokinetics and safety of CT­P47 administered via AI and PFS were shown to be similar, this might expand the choice of administration devices available to patients.In this study, 310 healthy adults received a single injection of CT­P47 via AI or PFS. Blood samples were taken over 43 days to analyze pharmacokinetics. The uptake, metabolism and elimination of CT­P47 by the body was similar when administered by each device, suggesting that CT­P47 can be administered by either AI or PFS.

Effect of Early Balloon Inflation of Balloon Guide Catheter in Mechanical Thrombectomy for Large Vessel Occlusion.

OBJECTIVE: A balloon guide catheter (BGC) is widely used in mechanical thrombectomy (MT). However, the balloon inflation timing of BGC has not been clearly established. We evaluated whether balloon inflation timing of BGC affects the results of MT. METHODS: Patients who underwent MT with BGC for anterior circulation occlusion were enrolled. Patients were dichotomized into early and late balloon inflation groups, according to the timing of BGC inflation. Angiographic and clinical outcomes were compared between the two groups. Multivariable analyses were performed to evaluate the predictive factors for first-pass reperfusion (FPR) and successful reperfusion (SR). RESULTS: Of 436 patients, the early balloon inflation group showed a shorter procedure time (21 min (11-37) vs. 29 min (14-46), p = 0.014), a higher rate of SR with aspiration only (64.0% vs. 55.4%, p = 0.016), a lower aspiration catheter delivery failure rate (11.1% vs. 19.4%, p = 0.005), less frequent technique conversion (36.0% vs. 44.5%, p = 0.009), higher rate of FPR (58.2% vs. 50.2%, p = 0.011), and a lower rate of distal embolization (7.9% vs. 11.7%, P = 0.006), compared to the late balloon inflation group. In multivariate analysis, early balloon inflation was an independent predictor for FPR (odds ratio, OR 1.53, 95% confidence interval, CI 1.37-2.57; p = 0.011) and SR (OR 1.26, 95% CI 1.18-1.64; p = 0.018). CONCLUSION: Early balloon inflation of BGC enables an effective procedure than late balloon inflation. Early balloon inflation was associated with higher rates of FPR and SR.

Comparison of Neuroform Atlas Stent-Assisted Coiling and Coiling Alone in Ruptured Intracranial Aneurysms: A Propensity Score Matching Analysis.

BACKGROUND: Although Neuroform Atlas stent is commonly used in stent-assisted coiling (SAC) to treat ruptured intracranial aneurysms (RIA), its safety and efficacy remain controversial. OBJECTIVE: To assess the safety and efficacy of SAC using Neuroform Atlas for treating RIA compared with coiling alone by performing a propensity score matching analysis. METHODS: RIA treated with coiling alone and SAC between January 2017 and May 2021 were retrospectively reviewed. Demographics, periprocedural complication rates, angiographic outcomes, and clinical outcomes of the SAC using Neuroform Atlas group and the coiling-alone group were analyzed with 1:1 propensity score matching. RESULTS: A total of 375 aneurysms were enrolled, and 274 (63.1%) aneurysms were treated with coiling alone. In total, 101 (26.9%) aneurysms were treated with SAC, and Neuroform Atlas stent was used in 71 aneurysms. In propensity score matching, the SAC using Neuroform Atlas group showed higher incidence of complete occlusion (69.0% vs 56.3%, P = .029), lower rate of recanalization (11.3% vs 25.4%, P = .011), and lesser need for retreatment (7.0% vs 16.9%, P = .016) compared with the coiling-alone group. However, there were no significant differences in periprocedural complications such as intraprocedural thrombosis or postprocedural cerebral infarct between the 2 groups. CONCLUSION: The use of Neuroform Atlas is safe and effective for SAC in RIA with comparable procedure-related complication rates but better angiographic outcome in comparison with coiling alone.

Label-free histological analysis of retrieved thrombi in acute ischemic stroke using optical diffraction tomography and deep learning.

For patients with acute ischemic stroke, histological quantification of thrombus composition provides evidence for determining appropriate treatment. However, the traditional manual segmentation of stained thrombi is laborious and inconsistent. In this study, we propose a label-free method that combines optical diffraction tomography (ODT) and deep learning (DL) to automate the histological quantification process. The DL model classifies ODT image patches with 95% accuracy, and the collective prediction generates a whole-slide map of red blood cells and fibrin. The resulting whole-slide composition displays an average error of 1.1% and does not experience staining variability, facilitating faster analysis with reduced labor. The present approach will enable rapid and quantitative evaluation of blood clot composition, expediting the preclinical research and diagnosis of cardiovascular diseases.

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study.

BACKGROUND: CT-P47 is a candidate tocilizumab biosimilar. This study assessed the pharmacokinetic (PK) equivalence of CT-P47 and European Union-approved reference tocilizumab (EU-tocilizumab) in healthy Asian adults. RESEARCH DESIGN AND METHODS: This double-blind, multicenter, parallel-group trial randomized healthy adults (1:1) to receive a single (162 mg/0.9 mL) subcutaneous dose of CT-P47 or EU-tocilizumab. The primary endpoint (Part 2) was PK equivalence by area under the concentration - time curve (AUC) from time zero to last quantifiable concentration (AUC0-last), AUC from time zero to infinity (AUC0-inf), and maximum serum concentration (Cmax). PK equivalence was concluded if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the 80-125% equivalence margin. Additional PK endpoints, immunogenicity, and safety were evaluated. RESULTS: In Part 2, 289 participants were randomized (146 CT-P47; 143 EU-tocilizumab); 284 received study drug. AUC0-last, AUC0-inf, and Cmax were equivalent between CT-P47 and EU-tocilizumab: 90% CIs for the ratios of gLSMs were within the 80-125% equivalence margin. Secondary PK endpoints, immunogenicity, and safety were comparable between groups. CONCLUSIONS: CT-P47 demonstrated PK equivalence with EU-tocilizumab and was well tolerated, following a single dose in healthy adults. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05188378.

Tocilizumab is a biologic medicine used to treat inflammatory diseases including rheumatoid arthritis. Biosimilars are drugs that are highly similar to an already approved, 'reference' biologic medicine. This means that they do not have any differences from the reference product in factors including structure, biologic function, efficacy, and safety, that might affect how well they work in patients. Biosimilars are often available at a lower cost than reference drugs, so their use can provide patients with better access to expensive treatments. There are no approved biosimilars of tocilizumab so far: CT-P47 is currently in development as a potential tocilizumab biosimilar.In the main part of this study, 289 healthy Asian volunteers were randomly allocated to receive a single injection of either CT-P47 or the reference drug, European Union-approved tocilizumab (EU-tocilizumab). The main aim of the study was to find out whether CT-P47 and EU-tocilizumab were equivalent in terms of pharmacokinetics (drug absorption, distribution, metabolism, and excretion by the body). This is part of a standard process required by regulatory authorities to ensure that biosimilars work as well as their reference drugs. Analysis of blood samples taken over 43 days showed that the pharmacokinetic profiles of CT-P47 and EU-tocilizumab were equivalent, after the volunteers received a single dose of either drug. Safety and immunogenicity (immune responses made to the drug) were also comparable between CT-P47 and EU-tocilizumab. While only healthy Asian adults were included, further research comparing CT-P47 with reference tocilizumab will help to ensure that the findings from the study can be applied to broader populations.

Multiple-dose pharmacokinetics of fesoterodine sustained-release in healthy Korean volunteers.

OBJECTIVE: Fesoterodine is a pro-drug of the active metabolite 5-hydroxymethyl tolterodine (5-HMT), a muscarinic receptor antagonist. This study aimed to evaluate the safety profile and pharmacokinetic characteristics of multiple oral doses of sustained-release fesoterodine (fesoterodine SR) in healthy Korean males. METHODS: A randomized, double-blind, placebo-controlled, multiple-dose study with two oral doses (4 mg and 8 mg) was conducted in healthy Korean male participants. The study drug was administered once daily for 5 days. The plasma concentration of 5-HMT was measured up to 72 hours after the last drug administration. The CYP2D6 genotype was analyzed using polymerase chain reaction (PCR) methods to assess the effect of genetic polymorphisms on the pharmacokinetic parameters. RESULTS: 20 participants completed the study. The mean (SD) areas under the plasma concentration-time curves during the dosing interval (AUCτ) of the 4 mg and 8 mg dose groups were 26.1 (8.0) and 64.2 (30.5) µg·h/ml and the mean peak concentrations (Cmax) were 2.6 (0.7) and 6.0 (2.0) µg/ml, respectively, at steady-state. The mean AUCτ and Cmax of 5-HMT increased in approximately the same proportion as the dose increased. Fesoterodine SR was well tolerated without any serious adverse events or abnormal clinical laboratory findings. CONCLUSION: Systemic 5-HMT exposure showed dose-proportional characteristics in the 4 mg to 8 mg dose range in healthy Korean males. Thus, 4 mg or 8 mg doses of fesoterodine SR taken once-daily were tolerable in healthy Korean males.

Prognostic significance of platelet-to-lymphocyte and platelet-to-neutrophil ratios in patients with mechanical thrombectomy for acute ischemic stroke.

OBJECTIVE: The present study aimed to analyze the correlation between platelet-to-lymphocyte ratio (PLR) and platelet-to-neutrophil ratio (PNR) with prognosis of patients who underwent mechanical thrombectomy (MT). METHODS: A total of 432 patients was included, PLR and PNR were calculated from laboratory data on admission. Prognosis was evaluated with a modified Rankin Scale at 3 months after MT. Using receiver operating characteristic (ROC) analysis, optimal cutoff values of PLR and PNR were identified to predict the prognosis after MT. Multivariate analyses were performed to identify the relationship of PLR and PLR with prognosis of MT. RESULTS: Patients with favorable outcomes had a lower mean PLR (135.0, standard deviation [SD] 120.3) with a higher mean PNR (47.1 [SD] 24.6) compared with patients with unfavorable outcomes (167.6 [SD] 139.3 and 35.4 [SD] 22.4) (p<0.001 and <0.001, respectively). In ROC analyses, the optimal cutoff value of PLR and PNR to predict the 3 months prognosis were 145 and 41, respectively (p=<0.001 and p=0.006). In multivariate analysis, PLR less than 145 (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.06-2.06; p=0.016) and PNR greater than 41 (OR 1.22, 95% CI 1.10-1.62; p=0.022) were predictors of favorable outcome at 3 months. CONCLUSIONS: In patients with MT, PLR and PNR on admission could be predictive factors of prognosis and mortality at 3 months. Decreased PLR and increased PNR were associated with favorable clinical outcome 3 months after MT.

Factors Related to Mechanical Thrombectomy Failure in Large Vessel Occlusion: A Propensity Score Matching Analysis.

OBJECTIVE: Mechanical thrombectomy (MT) is an effective treatment for large vessel occlusion (LVO) with a high successful recanalization (SR) rate. However, MT fails in a proportion of patients, leading to poor clinical outcomes. We analyzed the factors associated with the failure of MT. METHODS: A total of 648 consecutive patients with MT were enrolled. MT failure was defined as 0,1, or 2a of modified Thrombolysis in Cerebral Infarction (mTICI) grade. Failed MTs were divided into 3 categories, reaching failure, passage failure, and recanalization failure (RF). Various factors in RF and SR groups were analyzed with 1: 1 propensity score matching. RESULTS: Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of 4 or more passages and no change of method were significantly higher in the RF group than in the SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001). CONCLUSION: The failure rate for all of the MT was approximately 15%, and RF accounted for more than 70% of the failed MT. RF was associated with residual ICAS. In cases with RF, even in repeated attempts for recanalization, an alteration of the thrombectomy method should be considered.

Clinical relevance of serum procalcitonin in patients with aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV), which is closely related to the prognosis of aneurysmal subarachnoid hemorrhage (aSAH), is known to be related to an inflammatory reaction. The aim of the present study was to investigate predictable values of procalcitonin (PCT) for systemic infection and the development of CV in patients with aSAH. Patients who underwent endovascular treatment for aSAH were retrospectively enrolled. Receiver operating characteristic curve analysis was performed to evaluate the predicable value of PCT for systemic infection and CV in patients with aSAH. To clarify the association of PCT and CV, additional subgroup analysis was performed for patients without systemic infection. Multivariate logistic regression was used to explore the associations of PCT and the development of CV. A total of 374 patients with aSAH were enrolled. Of them, 164 (43.9%) had systemic infection. Optimal cutoff value of PCT for systemic infection was 0.21 ng/ml (P<0.001). In subgroup analysis of 210 patients without infection, 0.09 ng/ml of PCT level was defined as the optimal cutoff value for predicting CV after aSAH (P<0.001). In multivariate logistic regression analysis, PCT was a significant predicting factor for CV (odds ratio, 1.82; 95% confidence interval, 1.42-2.96; P=0.015). Overall, PCT had predictable value for systemic infection and the development of CV in patients who underwent endovascular treatment for aSAH. Further studies are needed to validate our results and establish its clinical applicability.

Ocular Distribution and Pharmacokinetics of 8-Oxo-2'-Deoxyguanosine: A Novel Therapeutic Candidate of Ocular Surface Diseases.

Purpose: This study evaluated the ocular distribution and plasma pharmacokinetics (PKs) of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in rabbits and rats, respectively. Methods: A test formulation containing radiolabeled [14 C]8-oxo-dG and unlabeled 8-oxo-dG was ocularly administered to rabbits as a single dose of 1 mg per body and intravenously injected to rats as a single dose of 5 mg/kg. The ocular distribution of [14 C]8-oxo-dG was evaluated using autoradiography until 48 h postdose. Plasma radioactivity in rabbits and rats was determined until 72 and 168 h, respectively. Results: After ocular instillation, [14 C]8-oxo-dG distributed into ocular tissues, and high radioactivity concentrations were observed in the ciliary body, conjunctiva, and cornea. The maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-t) were highest in the ciliary body and conjunctiva, respectively. In the conjunctiva, cornea, and aqueous humor, time to reach Cmax (Tmax) was 0.5 h, and the half-lives were 11.2, 30.2, and 15.1 h, respectively. The radioactivity of [14 C]8-oxo-dG in plasma of rabbits displayed a double-peak phenomenon with the second peak considered as Cmax (37.9 ± 3.1 ng eq./mL) occurring 24 h postdose. After systemic exposure of [14 C]8-oxo-dG in rats, a rapid decline in the initial phase and a terminal half-life of 56.1 ± 31.3 h were observed. Conclusions: Rapid ocular distribution and high concentrations in anterior ocular tissues with minimal systemic exposure were observed after the ocular instillation of 8-oxo-dG in rabbits. These PK profiles are favorable for the treatment of ocular surface diseases.

Clinical Outcomes after Spinal Cord Stimulation According to Pain Characteristics.

OBJECTIVE: Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. However, its clinical efficacy in regard to specific types of pain has not been well studied. The primary objective of this study was to retrospectively analyze the clinical outcomes of paddle-type SCS according to the type of neuropathic pain. METHODS: Seventeen patients who underwent paddle-lead SCS at our hospital were examined. Clinical outcomes were evaluated pre- and postoperatively (3 months, 1 year, and last follow-up) using the Neuropathic Pain Symptom Inventory (NPSI). The NPSI categorizes pain as superficial, deep, paroxysmal, evoked, or dysesthesia and assess the duration of the pain (pain time score). Changes in NPSI scores were compared with change in Visual analogue scale (VAS) scores. RESULTS: After SCS, the pain time score improved by 45% (independent t-test, p=0.0002) and the deep pain score improved by 58% (independent t-test, p=0.001). Improvements in the pain time score significantly correlated with improvements in the VAS score (r=0.667, p=0.003, Spearman correlation). Additionally, the morphine milligram equivalent value was markedly lower after vs. before surgery (~49 mg, pared t-test, p=0.002). No preoperative value was associated with clinical outcome. CONCLUSION: The NPSI is a useful tool for evaluating the therapeutic effects of SCS. Chronic use of a paddle-type spinal cord stimulation improved the deep pain and the pain time scores.