Probing N-substituted 4-(5-mercapto-4-ethyl-4H-1,2,4-triazol-3-yl)-N-phenylpiperdine-1-carboxamides as potent 15-LOX inhibitors supported with ADME, DFT calculations and molecular docking studies.

In our continuous efforts to find out leads against the enzyme 15-lipoxygenase (15-LOX), the current study deals with the synthesis of a series of new N-alkyl/aralkyl/aryl derivatives of 2-(4-ethyl-5-(1-phenylcarbamoyl)piperidine-4H-1,2,4-triazol-3-ylthio)methylacetamide (7a-n) with anti-LOX activities. The synthesis was started by reacting phenylisocyanate with isonipecotate that sequentially converted into N-substituted ester (1), hydrazide (2), semicarbazide (3) and N-ethylated 5-(1-phenylcarbamoyl)piperidine-1,2,4-triazole (4). The final compounds, 7a-n, were obtained by reacting 4 with various N-alkyl/aralkyl/aryl electrophiles. Both the intermediates and target compounds were characterized by FTIR, 1H, 13C NMR spectroscopy, EI-MS and HR-EI-MS spectrometry and screened against soybean 15-LOX by chemiluminescence method. The eight compounds 7e, 7j, 7h, 7a, 7g, 7b, 7n, 7c showed potent inhibitory activities against 15-LOX with values ranging from IC50 0.36 ± 0.15 µM (7e) to IC50 6.75 ± 0.17 µM (7c) compared with the reference quercetin (IC50 4.86 ± 0.14 µM) and baicalein (IC50 2.24 ± 0.13 µM). Two analogues (7l, 7f) had significantly outstanding inhibitory potential with IC50 values 12.15 ± 0.23 µM and 15.54 ± 0.26 µM, whereas, the derivatives 7i, and 7d displayed IC50 values of 21.56 ± 0.27 µM, 23.59 ± 0.24 µM and the compounds 7k, 7m were found inactive. All analogues exhibited blood mononuclear cells (MNCs) viability >75 % at 0.25 mM concentration as determined by MTT method. Calculated pharmacokinetic properties projected good lipophilicity, bioavailability and drug-likeness properties and did not violate Lipinski's/Veber rule. Molecular docking studies revealed lower binding free energies of all the derivatives than the reference compounds. The binding free energies were -9.8 kcal/mol, -9.70 k/mol and -9.20 kcal/mol for 7j, 7h and 7e, respectively, compared with the standard quercetin (-8.47 kcal/mol) and baicalein (-8.98 kcal/mol). The docked ligands formed hydrogen bonds with the amino acid residues Gln598 (7e), Arg260, Val 126 (7h), Gln762, Gln574, Thr443, Arg580 (7j) while other hydrophobic interactions observed therein further stabilized the complexes. The results of density functional theory (DFT) revealed that analogues with more stabilized lower unoccupied molecular orbital (LUMO) had significant enzyme inhibitory activity. The data collectively supports these molecules as leads against 15-LOX and demand further investigations as anti-inflammatory agents.

Review of current treatment modalities and clinical outcome of giant saccular aneurysms of the basilar apex.

Introduction: Giant aneurysms of the basilar apex represent formidable challenges as the high rupture rate of untreated lesions must be balanced against the technical complexity and potential morbidity of intervention. Research question: Review of treatment modalities and outcomes of patients harboring giant (>2.5 cm) basilar apex saccular aneurysms, in an effort to refine treatment decision-making. Material and methods: A systematic literature review through the PubMed and Scopus databases was performed according to the PRISMA guidelines to identify cases of giant basilar apex saccular aneurysms treated either microsurgically or endovascularly. Patients' demographics, aneurysm size, preoperative and postoperative neurologic status, angiographic and clinical outcomes as well as follow-up information were obtained. Results: Data from 32 studies fulfilling the inclusion criteria, including 49 patients (32 treated surgically and 17 endovascularly) was obtained. Mean patient age at presentation was 51.69 years, with a male-to-female ratio of 1:2. Mean maximum aneurysm diameter was 30.57 mm. A favorable outcome (mRS 0-2) was reported on 70.6% of endovascular and 56.3% of open surgical cases. Complete aneurysm occlusion was achieved in 55.6% of the open and 23.5% of the endovascular cases. Death rate was 33% for endovascular and 15.6% for open cases; the higher mortality of endovascular treatment is mainly attributed to the mass effect from continued brainstem compression after treatment. Discussion and conclusion: Higher rates of complete occlusion but higher morbidity are associated with microsurgery compared to endovascular modalities. Severe, clinically apparent brainstem mass effect may require decompression associated with microsurgery, when technically feasible.

Systemic C-Reactive Protein Predicts Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. METHODS: We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic curve. RESULTS: Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission C-reactive protein (CRP) levels than those without these complications (P < 0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI, and co-occurring CVS and DCI (P < 0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). CONCLUSIONS: Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

A comprehensive review of Wolbachia-mediated mechanisms to control dengue virus transmission in Aedes aegypti through innate immune pathways.

The Dengue virus (DENV), primarily spread by Aedes aegypti and also by Aedes albopictus in some regions, poses significant global health risks. Alternative techniques are urgently needed because the current control mechanisms are insufficient to reduce the transmission of DENV. Introducing Wolbachia pipientis into Ae. aegypti inhibits DENV transmission, however, the underlying mechanisms are still poorly understood. Innate immune effector upregulation, the regulation of autophagy, and intracellular competition between Wolbachia and DENV for lipids are among the theories for the mechanism of inhibition. Furthermore, mainly three immune pathways Toll, IMD, and JAK/STAT are involved in the host for the suppression of the virus. These pathways are activated by Wolbachia and DENV in the host and are responsible for the upregulation and downregulation of many genes in mosquitoes, which ultimately reduces the titer of the DENV in the host. The functioning of these immune pathways depends upon the Wolbachia, host, and virus interaction. Here, we summarize the current understanding of DENV recognition by the Ae. aegypti's immune system, aiming to create a comprehensive picture of our knowledge. Additionally, we investigated how Wolbachia regulates the activation of multiple genes associated with immune priming for the reduction of DENV.

Enhanced accuracy with Segmentation of Colorectal Polyp using NanoNetB, and Conditional Random Field Test-Time Augmentation.

Colonoscopy is a reliable diagnostic method to detect colorectal polyps early on and prevent colorectal cancer. The current examination techniques face a significant challenge of high missed rates, resulting in numerous undetected polyps and irregularities. Automated and real-time segmentation methods can help endoscopists to segment the shape and location of polyps from colonoscopy images in order to facilitate clinician's timely diagnosis and interventions. Different parameters like shapes, small sizes of polyps, and their close resemblance to surrounding tissues make this task challenging. Furthermore, high-definition image quality and reliance on the operator make real-time and accurate endoscopic image segmentation more challenging. Deep learning models utilized for segmenting polyps, designed to capture diverse patterns, are becoming progressively complex. This complexity poses challenges for real-time medical operations. In clinical settings, utilizing automated methods requires the development of accurate, lightweight models with minimal latency, ensuring seamless integration with endoscopic hardware devices. To address these challenges, in this study a novel lightweight and more generalized Enhanced Nanonet model, an improved version of Nanonet using NanonetB for real-time and precise colonoscopy image segmentation, is proposed. The proposed model enhances the performance of Nanonet using Nanonet B on the overall prediction scheme by applying data augmentation, Conditional Random Field (CRF), and Test-Time Augmentation (TTA). Six publicly available datasets are utilized to perform thorough evaluations, assess generalizability, and validate the improvements: Kvasir-SEG, Endotect Challenge 2020, Kvasir-instrument, CVC-ClinicDB, CVC-ColonDB, and CVC-300. Through extensive experimentation, using the Kvasir-SEG dataset, our model achieves a mIoU score of 0.8188 and a Dice coefficient of 0.8060 with only 132,049 parameters and employing minimal computational resources. A thorough cross-dataset evaluation was performed to assess the generalization capability of the proposed Enhanced Nanonet model across various publicly available polyp datasets for potential real-world applications. The result of this study shows that using CRF (Conditional Random Fields) and TTA (Test-Time Augmentation) enhances performance within the same dataset and also across diverse datasets with a model size of just 132,049 parameters. Also, the proposed method indicates improved results in detecting smaller and sessile polyps (flats) that are significant contributors to the high miss rates.

In silico analysis of polyphenols modulate bovine PPARγ to increase milk fat synthesis in dairy cattle via the MAPK signalling pathways.

This study investigates the potential phytochemicals that modulate bovine peroxisome proliferator-activated receptor gamma (PPARγ) and the Mitogen-Activated Protein Kinase (MAPK) pathways to enhance milk fat production in dairy animals. Bovine PPARγ, a key member of nuclear hormone receptor superfamily, plays a vital role in regulating metabolic, cellular differentiation, apoptosis, and anti-inflammatory responses in livestock, while the MAPK pathway is contributory in cellular processes that impact milk fat synthesis. This approach involved an all-inclusive molecular docking analysis of 10,000 polyphenols to identify potential PPARγ ligands. From this extensive screening, top 10 compounds were selected that exhibited the highest binding affinities to bovine PPARγ. Particularly, Curcumin sulphate, Isoflavone and Quercetin emerged as the most promising candidates. These compounds demonstrated superior docking scores (-9.28 kcal/mol, -9.27 kcal/mol and -7.31 kcal/mol respectively) and lower RMSD values compared to the synthetic bovine PPARγ agonist, 2,4-Thiazolidinedione (-4.12 kcal/mol), indicating a strong potential for modulating the receptor. Molecular dynamics simulations (MDS) further affirmed the stability of these polyphenols-bovine PPARγ complexes, suggesting their effective and sustained interactions. These polyphenols, known as fatty acid synthase inhibitors, are suggested to influence lipid metabolism pathways crucial to milk fat production, possibly through the downregulation of the MAPK pathway. The screened compounds showed favorable pharmacokinetic profiles, including non-toxicity, carcinogenicity, and high gastrointestinal absorption, positioning them as viable candidates for enhancing dairy cattle health and milk production. These findings may open new possibilities for the use of phytochemicals as feed additives in dairy animals, suggesting a novel approach to improve milk fat synthesis through the dual modulation of bovine PPARγ and MAPK pathways.

Virtual reality guided focused Sylvian approach for clipping unruptured middle cerebral artery aneurysms.

Objective: The increasing prevalence of unruptured intracranial aneurysms, detected through advanced brain imaging, necessitates a cautious approach to surgical intervention, with a focus on minimizing associated risks. This retrospective study explores the safety and better aesthetic outcomes of a Virtual Reality (VR) guided Focused Sylvian Approach (FSA) in comparison to the standard Pterional Surgical Approach (SPA) for the clipping of unruptured small-medium-size (<10 mm) Middle Cerebral Artery (MCA) aneurysms. Methods: 23 patients with 23 unruptured MCA aneurysms underwent the VR-guided FSA from June 2020 to September 2023, while 22 patients with 23 unruptured MCA aneurysms who underwent SPA were retrospectively recruited from the medical records database from January 2017 to May 2020. The comparative analysis involved surgical duration, postoperative complications, hospital stay, and a three-month follow-up patient's sequela survey. Results: All aneurysms were effectively treated. The FSA procedure demonstrated a shorter surgical duration compared to the SPA group (164 ± 48 min vs. 196 ± 133 min, P = 0.2974). Despite a slightly higher median age in the FSA group (59 vs. 56 years), the median hospital stay was shorter in the FSA group (6 days) compared to the SPA group (7 days). The SPA group exhibited a higher incidence of complications (17/23) including cephalalgia, scar irritation, scar numbness, and temporal muscle dysfunction, compared to the FSA group (1/23), with a statistical significance of P < 0.05. Although FSA cannot demonstrate significant surgical efficiency in surgical duration and hospitalization, its superior aesthetics and preservation of temporalis muscle function compared to the SPA group. Conclusion: The VR-guided FSA offers improved aesthetics and preservation of muscle function compared to the SPA. Our retrospective study underscores the potential benefits of VR-guided, personalized, focused Sylvian approaches for managing unruptured small-medium-size MCA aneurysms.

Prognostic value of platelet levels in patients with aneurysmal Subarachnoid Hemorrhage.

Pathophysiological processes following aneurysmal subarachnoid hemorrhage (aSAH) include upregulated underlying systemic inflammation, which is reflected by changes in different peripheral blood cells and their sub-populations. As inflammation is a crucial process that contributes to post-aSAH complications and clincal outcome, blood cell numbers and ratios in systemic circulation may predict the outcome and provide rapid and easy to quantify point of care biomarkers for these critically ill patients. To identify blood-derived cellular inflammatory parameters which allow a precise prediction of patient outcome after aSAH. In this single-center retrospective study, 19 whole blood-derived cellular inflammatory markers and clinical and demographic parameters for 101 aSAH patients were recorded within 24 h after aSAH. Clinical outcome was quantified with modified Rankin scale (mRS) on discharge. Proportional odds logistic regression (POLR) was used to model the patient outcome as the function of clinical parameters and inflammatory markers. The results were validated on a separate hold-out dataset (220 patients). The on-admission platelet count, mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) were found to be significant and predictive of patient outcome on discharge. Mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) predicted clinical outcome and may serve as easy to quantify point of care biomarker. The findings are potentially relevant for the management of aSAH.

Updates on traditional methods for combating malaria and emerging Wolbachia-based interventions.

The escalating challenge of malaria control necessitates innovative approaches that extend beyond traditional control strategies. This review explores the incorporation of traditional vector control techniques with emerging Wolbachia-based interventions. Wolbachia, a naturally occurring bacteria, offers a novel approach for combatting vector-borne diseases, including malaria, by reducing the mosquitoes' ability to transmit these diseases. The study explores the rationale for this integration, presenting various case studies and pilot projects that have exhibited significant success. Employing a multi-dimensional approach that includes community mobilization, environmental modifications, and new biological methods, the paper posits that integrated efforts could mark a turning point in the struggle against malaria. Our findings indicate that incorporating Wolbachia-based strategies into existing vector management programs not only is feasible but also heightens the efficacy of malaria control initiatives in different countries especially in Pakistan. The paper concludes that continued research and international collaboration are imperative for translating these promising methods from the laboratory to the field, thereby offering a more sustainable and effective malaria control strategy.

Which SDM Model, CLIMEX vs. MaxEnt, Best Forecasts Aeolesthes sarta Distribution at a Global Scale under Climate Change Scenarios?

A precise evaluation of the risk of establishing insect pests is essential for national plant protection organizations. This accuracy is crucial in negotiating international trade agreements for forestry-related commodities, which have the potential to carry pests and lead to unintended introductions in the importing countries. In our study, we employed both mechanistic and correlative niche models to assess and map the global patterns of potential establishment for Aeolesthes sarta under current and future climates. This insect is a significant pest affecting tree species of the genus Populus, Salix, Acer, Malus, Juglans, and other hardwood trees. Notably, it is also categorized as a quarantine pest in countries where it is not currently present. The mechanistic model, CLIMEX, was calibrated using species-specific physiological tolerance thresholds, providing a detailed understanding of the environmental factors influencing the species. In contrast, the correlative model, maximum entropy (MaxEnt), utilized species occurrences and spatial climatic data, offering insights into the species' distribution based on observed data and environmental conditions. The projected potential distribution from CLIMEX and MaxEnt models aligns well with the currently known distribution of A. sarta. CLIMEX predicts a broader global distribution than MaxEnt, indicating that most central and southern hemispheres are suitable for its distribution, excluding the extreme northern hemisphere, central African countries, and the northern part of Australia. Both models accurately predict the known distribution of A. sarta in the Asian continent, and their projections suggest a slight overall increase in the global distribution range of A. sarta with future changes in climate temperature, majorly concentrating in the central and northern hemispheres. Furthermore, the models anticipate suitable conditions in Europe and North America, where A. sarta currently does not occur but where its preferred host species, Populus alba, is present. The main environmental variables associated with the distribution of A. sarta at a global level were the average annual temperature and precipitation rate. The predictive models developed in this study offer insights into the global risk of A. sarta establishment and can be valuable for monitoring potential pest introductions in different countries. Additionally, policymakers and trade negotiators can utilize these models to make science-based decisions regarding pest management and international trade agreements.

Endoscopic transsphenoidal resection of parasellar abducens nerve schwannoma: A video demonstration.

Background: The abducens nerve schwannoma (ANS) in the sellar and parasellar region are extremely rare. Only around two dozen of ANS have been described in the world literature. These cases were, however, operated through the transcranial approach. We demonstrate, with the help of an edited video, that ANS located in the sellar and parasellar region can be safely and effectively operated through a transsphenoidal approach under endoscopic visualization. Case Description: Here, we present a case of a 30-year-old male who presented with a nine-month history of diplopia, weight gain, and loss of sexual functions. On neuro-opthalmological examination, a mild abducens palsy on the left side. Other cranial nerves were intact. On endocrinological testing, mild hypopituitarism on gonadal and thyroid axes. Magnetic resonance imaging (MRI) scan showed a contrast-enhanced cystic lesion in the sellar and parasellar region extending into the left temporal fossa. The patient underwent endonasal transsphenoidal endoscopic resection. A binostril standard approach was used, the left middle concha resected, and the nasoseptal flap was raised [Video 1]. The tumor was relatively soft and avascular yet invasive and could be removed with straight and curved suctions and gentle curettage. Subcapsular dissection was the key to saving the sixth nerve. Only minimal remnant posterior to the left internal carotid artery was assumed to be left behind. No cerebrospinal fluid (CSF) leakage was noted during the surgery. The skull base defect was reconstructed with the left-sided nasoseptal flap [Video 1]. Postoperatively, no new cranial nerve deficits. Diplopia is preoperative. Endocrine functions were unchanged. No CSF leak was observed. Postoperative MRI scan showed a near total resection. There was no operation-relevant complication. Diplopia resolved completely in a follow-up period of 6 months. Conclusion: The endoscopic transsphenoidal route is safe and effective for the resection of parasellar ANS. Subcapsular dissection is key to keep the sixth nerve intact.

Establishment of a novel protocol for assessing the severity of subarachnoid hemorrhage in circle Willis perforation mouse model.

The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp SAH induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB trends in subgroups, and ROB outcomes with autopsy results on postoperative days three and seven for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among SAH subgroups (P < 0.05). Strong correlations between ROB grades and autopsy findings underscored its precision. Notably, the severe group exhibited 100% mortality within 4 days post SAH onset. Single parameters (RT, OT, BWL) were insufficient for distinguishing SAH severity levels. The ROB score represents a significant advancement, offering an objective method for precise categorization and addressing inherent bleeding variations in the cWp SAH model. This standardized protocol enhances the reliability and effectiveness of the SAH translational research, providing a valuable tool for future investigations into this critical area.

Leveraging shape screening and molecular dynamics simulations to optimize PARP1-Specific chemo/radio-potentiators for antitumor drug design.

PARP1 plays a pivotal role in DNA repair within the base excision pathway, making it a promising therapeutic target for cancers involving BRCA mutations. Current study is focused on the discovery of PARP inhibitors with enhanced selectivity for PARP1. Concurrent inhibition of PARP1 with PARP2 and PARP3 affects cellular functions, potentially causing DNA damage accumulation and disrupting immune responses. In step 1, a virtual library of 593 million compounds has been screened using a shape-based screening approach to narrow down the promising scaffolds. In step 2, hierarchical docking approach embedded in Schrödinger suite was employed to select compounds with good dock score, drug-likeness and MMGBSA score. Analysis supplemented with decomposition energy, molecular dynamics (MD) simulations and hydrogen bond frequency analysis, pinpointed that active site residues; H862, G863, R878, M890, Y896 and F897 are crucial for specific binding of ZINC001258189808 and ZINC000092332196 with PARP1 as compared to PARP2 and PARP3. The binding of ZINC000656130962, ZINC000762230673, ZINC001332491123, and ZINC000579446675 also revealed interaction involving two additional active site residues of PARP1, namely N767 and E988. Weaker or no interaction was observed for these residues with PARP2 and PARP3. This approach advances our understanding of PARP-1 specific inhibitors and their mechanisms of action, facilitating the development of targeted therapeutics.

Biallelic loss-of-function variants of ZFTRAF1 cause neurodevelopmental disorder with microcephaly and hypotonia.

PURPOSE: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive. METHODS: We studied 5 affected individuals from 3 unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We used exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing. RESULTS: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from 2 unrelated families segregated 2 homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of 2 affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process. CONCLUSION: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder.

Tobacco smoke condensate-induced senescence in endothelial cells was ameliorated by colchicine treatment via suppression of NF-κB and MAPKs P38 and ERK pathways activation.

Smoking is the major cause of cardiovascular diseases and cancer. It induces oxidative stress, leading to DNA damage and cellular senescence. Senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase, which are known to play a vital role in the initiation and progression of cardiovascular diseases and metastasis in cancer. The current study investigated the smoking induced cellular senescence and employed colchicine that blocked senescence in endothelial cells exposed to tobacco smoke condensate. Colchicine prevented oxidative stress and DNA damage in tobacco smoke-condensate-treated endothelial cells. Colchicin reduced ß-gal activity, improved Lamin B1, and attenuated cell growth arrest markers P21 and P53. Colchicine also ameliorated the expression of SASP factors and inhibited the activation of NF-kB and MAPKs P38 and ERK. In summary, colchicine inhibited tobacco smoke condensate-induced senescence in endothelial cells by blocking the activation of NF-kB and MAPKs P38 and ERK.

Surgical repair of torn base of ruptured middle cerebral artery trifurcation aneurysm.

BACKGROUND: Treating complex middle cerebral artery (MCA) trifurcation aneurysms requires a delicate balance between achieving aneurysm obliteration and preserving vascular integrity. Various cerebral revascularization techniques, including bypass, and clip reconstruction are considered individually or in combination. METHODS: This case report outlines a successful repair of a ruptured neck and base of MCA trifurcation aneurysm using a suturing-clip reconstruction technique. Temporary aneurysm trapping was implemented, with maintained elevated blood pressure to ensure collateral perfusion during repair of ruptured base and neck of MCA aneurysm. CONCLUSION: The suturing-clip reconstruction exhibited long-term radiological stability, emerging as a valuable alternative for managing challenging MCA trifurcation aneurysms.

Surgical and endovascular cerebral revascularization for cerebral vasculitis with inflammatory vessel stenosis: a case series.

Autoimmune vasculitides affect the cerebral vasculature significantly in a considerable number of cases. When immunosuppressive treatments fail to prevent stenosis in cerebral vessels, treatment options for affected patients become limited. In this case series, we present four cases of pharmacoresistant vasculitis with recurrent transient ischemic attacks (TIAs) or stroke successfully treated with either extracranial-intracranial (EC-IC) bypass surgery or endovascular stenting. Both rescue treatments were effective and safe in the selected cases. Our experience suggests that cases of pharmacoresistant cerebral vasculitis with recurrent stroke may benefit from rescue revascularization in combination with maximum medical management.

CLR (C-Reactive Protein to Lymphocyte Ratio) Served as a Promising Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage (aSAH): A Retrospective Cohort Study.

Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive value of the C-reactive protein to lymphocyte ratio (CLR) for neurological functional outcome and complications after aSAH. Methods: We retrospectively analyzed a total of 166 aSAH patients who met the inclusion criteria enrolled in our study. Multivariate logistic regression analyses were performed to evaluate the independent risk factors. The predictive value of different models was compared by calculating the areas under the receiver operating characteristic (ROC) curve. Results: On-admission levels of CLR in patients with poor outcomes (6 months mRS 3-6), CVS, DCI, and CH were significantly higher than those in patients with good outcomes (6 months mRS 0-2), non-CVS, non-DCI, and non-CH. Multivariate logistic regression analysis revealed that admission CLR was independently associated with CVS (OR [95% CI] 2.116 [1.507-2.971]; p < 0.001), and DCI (OR [95% CI] 1.594 [1.220-2.084]; p = 0.001). In ROC analysis, the area under the curve (AUC) of CLR for poor outcomes (6 months mRS 3-6), CVS, DCI, and CH prediction were (AUC [95% CI] 0.639 [0.555-0.724]; p = 0.002), (AUC [95% CI] 0.834 [0.767-0.901]; p < 0.001), (AUC [95% CI] 0.679 [0.581-0.777]; p < 0.001), and (AUC [95% CI] 0.628 [0.543-0.713]; p = 0.005) revealing that admission CLR had a favorable predictive value for CVS after aSAH. The sensitivity and specificity of admission CLR for CVS prediction were 77.1% and 75.4%. On-admission CLR of 0.757 mg × 10-6 was identified as the best cutoff threshold to discriminate between CVS and non-CVS (CVS: CLR < 0.757 mg × 10-6 11/100 [11.0%] vs. CLR ≥ 0.757 mg × 10-6 37/66 [56.1%]; p < 0.001). Conclusions: High levels of on-admission CLR serve as an independent risk factor for CVS and DCI after aSAH. Admission CLR is an easy-to-quantify laboratory parameter that efficiently predicts the CVS after aSAH, which can provide some guidance for clinicians to evaluate for possible progression and treatment strategies in patients with aSAH.