Delayed cerebral ischemia (DCI) is one of the most important outcome determinants for aneurysmal subarachnoid hemorrhage (aSAH). VASOGRADE, which combines World Federation of Neurological Surgeons grade and modified Fisher grade, is a useful scale for predicting DCI after aSAH. However, no studies have investigated whether VASOGRADE influences the treatment options. We retrospectively analyzed 781 aSAH patients who were prospectively enrolled in 9 primary stroke centers from 2013 to 2021. The total cohort consisted of 76 patients (9.7%) with VASOGRADE-Green, 390 patients (49.9%) with VASOGRADE-Yellow, and 315 patients (40.3%) with VASOGRADE-Red. Worse VASOGRADE had higher incidences of DCI, which occurred in 190 patients (24.3%). As only 5 patients (6.6%) with VASOGRADE-Green developed DCI, we searched for DCI-associated factors in patients with VASOGRADEs-Yellow and -Red. Multivariate analyses revealed independent treatment factors suppressing DCI as follows: no postoperative hemorrhagic complication, combined administration of fasudil hydrochloride and cilostazol, combination of clipping and cisternal drainage, and coiling for VASOGRADE-Yellow; and clipping, and administration of fasudil hydrochloride with or without cilostazol for VASOGRADE-Red. The findings suggest that treatment strategies should be determined based on VASOGRADE to prevent DCI after aSAH.

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To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the \"Box-Behnken Design\" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur\'s inhibition may be the mechanism.
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BACKGROUND: Endovascular therapy (ET) outcomes for femoropopliteal peripheral arterial disease (FP-PAD) remain suboptimal. Cilostazol therapy may improve patency rates and decrease major adverse limb events after ET for FP-PAD. Our goal is to analyze published studies evaluating the use of cilostazol after ET for FP-PAD.
METHODS: We searched MEDLINE, EMBASE, and CENTRAL for randomized and observational studies evaluating cilostazol therapy after ET for FP-PAD. We only included observational studies adjusting for confounding variables. We analyzed observational and randomized studies separately and explored heterogeneity by estimating an I2 statistic. A fixed-effects model was chosen if the I2 statistic was low. If the two-sided probability of observing the difference between groups under a true null hypothesis was less than 5%, we considered this difference statistically significant.
RESULTS: We screened 2,171 studies and included 26 papers in our analysis (5 randomized and 21 observational studies). All randomized studies were open label. In randomized studies, the odds of restenosis were lower in patients treated with cilostazol (pooled odds ratio (pOR) = 0.28, 95% confidence interval (CI) 0.18 to 0.43, p < 0.01, I2 = 0%). The odds of target lesion revascularization (TLR) were also lower in patients treated with cilostazol (pOR = 0.35, 95% CI 0.22 to 0.65, p < 0.01, I2 = 0%). In observational studies, we also identified associations between peri-interventional treatment with cilostazol and lower rates of restenosis (pooled hazard ratio (pHR) = 0.57, 95% CI 0.51 to 0.65, p <0.01, I2 = 34%), TLR (pHR = 0.53, 95% CI 0.36 to 0.79, p <0.01, I2 = 0%), and amputation (pHR = 0.54, 95% CI 0.32 to 0.90, p = 0.02, I2 = 30%).
CONCLUSIONS: In randomized open label studies, peri-interventional treatment with cilostazol after ET for FP-PAD lowered the odds of restenosis and TLR (Level 1A). Similarly, in observational studies that adjusted for confounding, peri-interventional cilostazol therapy was associated with lower rates of restenosis, TLR, and amputation (Level 2A).

Cilostazol is a phosphodiesterase III inhibitor characterized by poor solubility. This limitation can be overcome by using a drug carrier capable of delivering the drug to the target site. Cyclodextrins are essential as drug carriers because of their outstanding complexation abilities and their capacity to improve drug bioavailability. This study comprises two stages: The first involves verifying different cyclodextrins and their complexation abilities towards cilostazol. This was accomplished using molecular docking simulations (MDS) and density functional theory (DFT). Both techniques indicate that the largest Sulfobutyl Ether-β-Cyclodextrin forms the most stable complex with cilostazol. Additionally, other important parameters of the complex are described, including binding sites, dominant interactions, and thermodynamic parameters such as complexation enthalpy, Gibbs free energy, and Gibbs free energy of solvation. The second stage involves a binding study between cilostazol and Phosphodiesterse3 (PDE3). This study was conducted using molecular docking simulations, and the most important energetic parameters are detailed. This is the first such report, and we believe that the results of our predictions will pave the way for future drug development efforts using cyclodextrin-cilostazol complexes as potential therapeutics.

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.

This letter commends the article by Luzzi et al. on alternative neuroprotection strategies for aneurysmal subarachnoid hemorrhage (SAH). It highlights the pharmacological advantages of nicardipine, cilostazol, and clazosentan over nimodipine in managing cerebral vasospasm and delayed cerebral ischemia. Emphasizing the need for personalized medicine, it advocates for integrating genetic screening and advanced monitoring techniques to tailor treatments to individual patient profiles. This approach could significantly improve clinical outcomes by optimizing drug efficacy and minimizing adverse effects.

UNASSIGNED: Cilostazol has reported effectiveness for preventing aspiration pneumonia in patients with ischemic stroke, but whether it is similarly beneficial for patients with chronic limb-threatening ischemia (CLTI) is unclear.
UNASSIGNED: This retrospective single-center study enrolled 1,368 CLTI patients treated with endovascular therapy (EVT). In the multivariate analysis, predictors for aspiration pneumonia were age (hazard ratio [HR] 1.06 [95% confidence interval (CI) 1.03-1.10]), non-ambulatory status (HR 2.54 [95% CI 1.38-4.65]), the Geriatric Nutritional Risk Index (HR 0.97 [95% CI 0.95-0.99]), and cilostazol (HR 0.37 [95% CI 0.16-0.87]).
UNASSIGNED: Cilostazol administration reduced the risk of aspiration pneumonia in patients with CLTI undergoing EVT.

Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol\'s impact on the bacterium\'s ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol\'s potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.

This critique discusses neuroprotective strategies for aneurysmal subarachnoid hemorrhage (SAH), excluding Nimodipine, emphasizing alternatives like verapamil, albumin, and cilostazol. While these options show potential, their efficacy lacks robust confirmation from randomized controlled trials (RCTs), relying mainly on observational studies and small trials. The letter underscores the need for comprehensive safety assessments and long-term outcome studies to enhance practical application. Highlighting ongoing trials and emerging therapies like clazosentan and TAK-044, it advocates for future research directions focused on large-scale RCTs and combination therapies, such as cilostazol and Nimodipine, which have demonstrated synergistic benefits in reducing delayed cerebral ischemia (DCI) and improving patient outcomes.