NLRP3 Inflammasome in Autoinflammatory Diseases and Periodontitis Advance in the Management.

Inflammatory chemicals are released by the immune system in response to any perceived danger, including irritants and pathogenic organisms. The caspase activation and the response of inflammation are governed by inflammasomes, which are sensors and transmitters of the innate immune system. They have always been linked to swelling and pain. Research has mainly concentrated on the NOD-like protein transmitter 3 (NLRP3) inflammasome. Interleukin (IL)-1 and IL-18 are pro-inflammatory cytokines that are activated by the NOD-like antibody protein receptor 3 (NLRP3), which controls innate immune responses. The NLRP3 inflammasome has been associated with gum disease and other autoimmune inflammatory diseases in several studies. Scientists' discovery of IL-1's central role in the pathophysiology of numerous autoimmune disorders has increased public awareness of these conditions. The first disease to be connected with aberrant inflammasome activation was the autoinflammatory cryopyrin-associated periodic syndrome (CAPS). Targeted therapeutics against IL-1 have been delayed in development because their underlying reasons are poorly understood. The NLRP3 inflammasome has recently been related to higher production and activation in periodontitis. Multiple periodontal cell types are controlled by the NLRP3 inflammasome. To promote osteoclast genesis, the NLRP3 inflammasome either increases receptor-activator of nuclear factor kappa beta ligand (RANKL) synthesis or decreases osteoclast-promoting gene (OPG) levels. By boosting cytokines that promote inflammation in the periodontal ligament fibroblasts and triggering apoptosis in osteoblasts, the NLRP3 inflammasome regulates immune cell activity. These findings support further investigation into the NLRP3 inflammasome as a therapeutic target for the medical treatment of periodontitis. This article provides a short overview of the NLRP3 inflammatory proteins and discusses their role in the onset of autoinflammatory disorders (AIDs) and periodontitis.

Computational Screening of Some Phytochemicals to Identify Best Modulators for Ligand Binding Domain of Estrogen Receptor Alpha.

OBJECTIVE: The peculiar aim of this study is to discover and identify the most effective and potential inhibitors against the most influential target ERα receptor by in silico studies of 45 phytochemicals from six diverse ayurvedic medicinal plants. METHODS: The molecular docking investigation was carried out by the genetic algorithm program of AutoDock Vina. The molecular dynamic (MD) simulation investigations were conducted using the Desmond tool of Schrödinger molecular modelling. This study identified the top ten highest binding energy phytochemicals that were taken for drug-likeness test and ADMET profile prediction with the help of the web-based server QikpropADME. RESULTS: Molecular docking study revealed that ellagic acid (-9.3 kcal/mol), emodin (-9.1 kcal/mol), rhein (-9.1 kcal/mol), andquercetin (-9.0 kcal/mol) phytochemicals showed similar binding affinity as standard tamoxifen towards the target protein ERα. MD studies showed that all four compounds possess comparatively stable ligand-protein complexes with ERα target compared to the tamoxifen-ERα complex. Among the four compounds, phytochemical rhein formed a more stable complex than standard tamoxifen. ADMET studies for the top ten highest binding energy phytochemicals showed a better safety profile. CONCLUSION: Additionally, these compounds are being reported for the first time in this study as possible inhibitors of ERα for treating breast cancer, according to the notion of drug repurposing. Hence, these phytochemicals can be further studied and used as a parent core molecule to develop innovative lead molecules for breast cancer therapy.

The Relationship Between Manifestation of Diabetes Insipidus and Estimated Glomerular Filtration Rate in Brain Death.

OBJECTIVES: Systematic reviews have revealed that up to 50% of patients with brain death have residual hypothalamic/pituitary activity based on the absence of central diabetes insipidus (DI). We hypothesized that different degrees of renal dysfunction may impact the presence of DI in patients with brain death. DESIGN: Single-center prospective data collection. SETTING: ICUs in a tertiary academic hospital. PATIENTS: All adult patients declared brain dead over 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: DI was diagnosed by polyuria, low urine specific gravity, and increasing serum sodium, measured in close proximity. Renal function was assessed by the estimated glomerular filtration rate (eGFR), calculated using the simplified modification of diet in renal disease equation. Analysis was completed in 192 of 234 patients with brain death after excluding those with missing data, those younger than 18 years and those on vasopressin infusions. One hundred twenty-two patients (63.5%) developed DI and 70 patients (36.5%) did not. The proportion of DI decreased significantly with decreasing eGFR: for eGFR greater than 60 mL/min, DI was present in 77.2%; for eGFR 15-60 mL/min, DI was present in 54.5%; for eGFR 14.9-9.8 mL/min, DI was present in 32%; none of the 14 patients with eGFR less than or equal to 9.7 mL/min ever experienced DI ( p < 0.001). Using logistic regression, for every 10 mL/min decrease in eGFR, the odds of DI decreased 0.83 times (95% CI, 0.76-0.90, p < 0.001). CONCLUSIONS: Renal dysfunction significantly impacts DI's clinical manifestation in brain death. We report that patients who experience brain death with severe renal dysfunction may not develop clinical signs of DI.

In-vitro antiviral activity and in-silico targeted study of quinoline-3-carboxylate derivatives against SARS-Cov-2 isolate.

In recent years, the viral outbreak named COVID-19 showed that infectious diseases have a huge impact on both global health and the financial and economic sectors. The lack of efficacious antiviral drugs worsened the health problem. Based on our previous experience, we investigated in vitro and in silico a series of quinoline-3-carboxylate derivatives against a SARS-CoV-2 isolate. In the present study, the in-vitro antiviral activity of a series of quinoline-3-carboxylate compounds and the in silico target-based molecular dynamics (MD) and metabolic studies are reported. The compounds' activity against SARS-CoV-2 was evaluated using plaque assay and RT-qPCR. Moreover, from the docking scores, it appears that the most active compounds (1j and 1o) exhibit stronger binding affinity to the primary viral protease (NSP5) and the exoribonuclease domain of non structural protein 14 (NSP14). Additionally, the in-silico metabolic analysis of 1j and 1o defines CYP2C9 and CYP3A4 as the major P450 enzymes involved in their metabolism.

Targeting lipid-sensing nuclear receptors PPAR (α, γ, ß/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists.

The global prevalence of obesity-related systemic disorders, including non-alcoholic fatty liver disease (NAFLD), and cancers are rapidly rising. Several of these disorders involve peroxisome proliferator-activated receptors (PPARs) as one of the key cell signaling pathways. PPARs are nuclear receptors that play a central role in lipid metabolism and glucose homeostasis. They can activate or suppress the genes responsible for inflammation, adipogenesis, and energy balance, making them promising therapeutic targets for treating metabolic disorders. In this study, an attempt has been made to screen novel PPAR pan-agonists from the ZINC database targeting the three PPAR family of receptors (α, γ, ß/δ), using molecular docking and molecular dynamics (MD) simulations. The top scoring five ligands with strong binding affinity against all the three PPAR isoforms were eprosartan, canagliflozin, pralatrexate, sacubitril, olaparib. The ADMET analysis was performed to assess the pharmacokinetic profile of the top 5 molecules. On the basis of ADMET analysis, the top ligand was subjected to MD simulations, and compared with lanifibranor (reference PPAR pan-agonist). Comparatively, the top-scoring ligand showed better protein-ligand complex (PLC) stability with all the PPARs (α, γ, ß/δ). When experimentally tested in in vitro cell culture model of NAFLD, eprosartan showed dose dependent decrease in lipid accumulation and oxidative damage. These outcomes suggest potential PPAR pan-agonist molecules for further experimental validation and pharmacological development, towards treatment of PPAR-mediated metabolic disorders.

Urinary Ammonium in Clinical Medicine: Direct Measurement and the Urine Anion Gap as a Surrogate Marker During Metabolic Acidosis.

Ammonium is the most important component of urinary acid excretion, normally accounting for about two-third of net acid excretion. In this article, we discuss urine ammonium not only in the evaluation of metabolic acidosis but also in other clinical conditions such as chronic kidney disease. Different methods to measure urine NH4+ that have been employed over the years are discussed. The enzymatic method used by clinical laboratories in the United States to measure plasma ammonia via the glutamate dehydrogenase can be used for urine ammonium. The urine anion gap calculation can be used as a rough marker of urine ammonium in the initial bedside evaluation of metabolic acidosis such as in distal renal tubular acidosis. Urine ammonium measurements, however, should be made more available in clinical medicine for a precise evaluation of this important component of urinary acid excretion.

Retrospective Review of Chromane Analogues as Anti-protozoal Leads: A Decade's Worth of Evolution.

Tropical, vector-borne, and neglected diseases with a limited number of medication therapies include Leishmaniasis, Malaria, Chagas and Human African Trypanosomiasis (HAT). Chromones are a large class of heterocyclic compounds with significant applications. This heterocycle has long aroused the interest of scientists and the general public from biosynthetic and synthetic points of view owing to its interesting pharmacological activities. Chromones and their hybrids and isomeric forms proved to be an exciting scaffold to investigate these diseases. The in vitro activities of Chromone, Chromane, and a panel of other related benzopyran class compounds against Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, Trypanosoma cruzi, and numerous Leishmanial and Malarial species were investigated in our previous studies. The current article briefly describes the neglected diseases and the current treatment. This review aims to attempt to find better alternatives by scrutinizing natural and synthetic derivatives for which chromones and their analogues were discovered to be a new and highly effective scaffold for the treatment of neglected diseases, including compounds with dual activity or activity against multiple parasites. Additionally, the efficacy of other new scaffolds was also thoroughly examined. This article also discusses prospects for identifying more unique targets for the disease, focusing on flavonoids as drug molecules that are less cytotoxic and high antiprotozoal potential. It also emphasizes the changes that can be made while searching for potential therapies-comparing existing treatments against protozoal diseases and the advantages of the newer chromone analogues over them. Finally, the structure- activity relationship at each atom of the chromone has also been highlighted.

Urinary Angiotensinogen in Patients With Type 1 Diabetes With Microalbuminuria: Gender Differences and Effect of Intensive Insulin Therapy.

Introduction: Angiotensinogen (AOG) is the precursor of peptides of the renin angiotensin system (RAS). Because insulin up-regulates transcriptional factors that normally repress kidney AOG synthesis, we evaluated urinary AOG (uAOG) in patients with type 1 diabetes (T1D) and microalbuminuria who are receiving either intensive or conventional insulin therapy. Methods: Urine samples from participants of the Diabetes Control and Complications Trial (DCCT) were used for the following: (i) uAOG/creatinine measurements in 103 patients with microalbuminuria and 103 patients with normoalbuminuria, matched for age, gender, disease duration, and allocation to insulin therapy; and (ii) uAOG/creatinine measurements from patients with microalbuminuria allocated to intensive insulin therapy (n = 58) or conventional insulin therapy (n = 41) after 3 years on each modality. Results: uAOG was higher in patients who started with microalbuminuria than in those with normoalbuminuria (6.65 vs. 4.0 ng/mg creatinine, P < 0.01). uAOG was higher in females than in males with microalbuminuria (11.7 vs. 5.4 ng/mg creatinine, P = 0.015). uAOG was lower in patients with microalbuminuria allocated to intensive insulin therapy than in conventional insulin therapy (3.98 vs. 7.42 ng/mg creatinine, P < 0.01). These differences in uAOG were observed though albumin excretion rate (AER) was not significantly different. Conclusion: In patients with T1D and microalbuminuria, uAOG is increased and varies with gender and the type of insulin therapy independently of AER. This suggests that AOG production is increased in females and it is decreased by intensive insulin therapy. The reduction in uAOG with intensive insulin therapy, by kidney RAS downregulation, may contribute to the known renoprotective action associated with intensive insulin and improved glycemic control.

The effect of different finishing polishing protocols on stain absorption and color stability of resin composite restorations.

PURPOSE: To evaluate the degree of stain absorption of resin composite following different finishing and polishing protocols and to evaluate the efficacy of prophylaxis paste with or without addition of carbamide peroxide to remove composite surface stain. METHODS: 50 resin composite blocks were prepared using nano-hybrid composite (Filtek Z250XT) and giomer (Beautifil II LS). Specimens were either polished with a disk or coated with 5th/7th generation bonding or glycerin gel. The color parameters (lightness, chroma and hue) of the specimens were measured prior to staining, and after 1 and 2 weeks of staining using a color chromometer. The composite surface stain removal capability of prophylaxis pastes with or without the addition of carbamide peroxide was evaluated before and after polishing. RESULTS: The repeated measures ANOVA showed that composite polished with a polishing disk or coated with glycerin gel have better color stability compared to composite without any polishing or coated with 5th or 7th generation bonding materials. The prophylaxis paste was able to remove composite surface stain; however, the addition of carbamide peroxide did not show any additional benefit. The results suggested that polishing with polishing disks or coating with glycerin gel is useful for the color stability of resin composite. CLINICAL SIGNIFICANCE: Selection of finishing and polishing protocols varies among individual practitioners. Each of these protocols has some pros and cons concerning the esthetic and color stability of composite. The present results suggested that the use of polishing disk or glycerin gel during polymerization would be a useful protocol to achieve and maintain esthetically stable composite restorations.

An Efficient Machine Learning-Based Feature Optimization Model for the Detection of Dyslexia.

Dyslexia is among the most common neurological disorders in children. Detection of dyslexia therefore remains an important pursuit for the research works across various domains which is illustrated by the plethora of work presented in diverse scientific articles. The work presented herein attempted to utilize the potential of a unified gaming test of subjects (dyslexia/controls) in tandem with principal components derived from data to detect dyslexia. The work aims to build a machine learning model for dyslexia detection using comprehensive gaming test data. We have attempted to explore the potential of various kernel functions of the Support Vector Machine (SVM) on different number of principal components to reduce the computational complexity. A detection accuracy of 92% is obtained from the radial basis function with 5 components, and the highest detection accuracy obtained from the radial basis function with 3 components is 93%. On the contrary, the Artificial Neural Network(ANN) shows an added advantage with minimal number of hyperparameters with 3 components for obtaining an accuracy of 95%. The comparison of the proposed method with some of the existing works shows efficacy of this method for dyslexia detection.

Pipeline Embolization Stent for the Treatment of Giant Supraclinoid Aneurysms: A Case Series.

Cerebrovascular aneurysms of the supraclinoid region are a technical challenge and can be particularly difficult to treat when greater than 25 mm in diameter. Such giant aneurysms can be approached with various skull-based and endovascular surgical techniques, and the advent of the Pipeline embolization stent presents a new treatment modality. Previously used for the treatment of small aneurysms, the Pipeline embolization device (PED) is a flow diverter device that has more recently been investigated in its use for the treatment of giant aneurysms with few studies to date published about its procedural outcomes. Here, we highlight the case of three patients (two elderly and one middle-aged) presenting symptomatically with giant supraclinoid aneurysms of the cavernous internal carotid artery (ICA) and posterior communicating artery treated with the Pipeline stent and monitored on follow-up visits. We further review the most current case reports and the two clinical trials to date investigating the utility of the Pipeline stent in the treatment of large and giant cerebral aneurysms, highlighting the emerging evidence of its efficacy and long-term patient outcomes. We report successful resolution of symptoms and radiographic evidence of aneurysm size reduction on all patient follow-ups and suggest the Pipeline embolization device as a novel technique that can be utilized for the treatment of giant cerebrovascular aneurysms with emerging evidence of immediate and long-term success.

Comparison of 1 vs 2 Brain Death Examinations on Time to Death Pronouncement and Organ Donation: A 12-Year Single Center Experience.

OBJECTIVE: To fill the evidence gap on the value of a single brain death (SBD) or dual brain death (DBD) examination by providing data on irreversibility of brain function, organ donation consent, and transplantation. METHODS: Twelve-year tertiary hospital and organ procurement organization data on brain death (BD) were combined and outcomes, including consent rate for organ donation and organs recovered and transplanted after SBD and DBD, were compared after multiple adjustments for covariates. RESULTS: A total of 266 patients were declared BD, 122 after SBD and 144 after DBD. Time from event to BD declaration was longer by an average of 20.9 hours after DBD (p = 0.003). Seventy-five (73%) families of patients with SBD and 86 (72%) with DBD consented for organ donation (p = 0.79). The number of BD examinations was not a predictor for consent. No patient regained brain function during the periods following BD. Patients with SBD were more likely to have at least 1 lung transplanted (p = 0.031). The number of organs transplanted was associated with the number of examinations (ß coefficient [95% confidence interval] -0.5 [-0.97 to -0.02]; p = 0.044), along with age (for 5-year increase, -0.36 [-0.43 to -0.29]; p < 0.001) and PaO2 level (for 10 mm Hg increase, 0.026 [0.008-0.044]; p = 0.005) and decreased as the elapsed time to BD declaration increased (p = 0.019). CONCLUSIONS: A single neurologic examination to determine BD is sufficient in patients with nonanoxic catastrophic brain injuries. A second examination is without additional yield in this group and its delay reduces the number of organs transplanted.

Factors that affect consent rate for organ donation after brain death: A 12-year registry.

OBJECTIVE: To account for factors affecting family approach and consent for organ donation after brain death (BD). MATERIAL AND METHODS: A prospective cohort study in a large, tertiary, urban hospital, where we reviewed the database of all brain-dead patients between January 2006 and December 2017 cross-matched with local organ procurement organization (OPO) records. RESULTS: Two-hundred sixty-six brain-dead patients were included (55% African Americans (AAs)). Two-hundred twenty-two were approached for donation. The reason for not approaching families was medical exclusion due to cancer or multi-organ failure. Patient demographics or religion were not associated with approaching families. Lower creatinine level was the only independent factor associated with higher approach. Consent rate for organ donation was 72.5%. Consent was significantly higher in Caucasians (89% vs 62% for AAs), younger patients (46.7 vs 52.5 years old), in patients with lower creatinine at time of death (1.7 vs 2.4 mg/dL), patients for whom apnea testing was completed (92% vs 80%) and patients with diabetes insipidus (DI) (72% vs 54%). There was no significant relationship between consent and patient gender, admission diagnosis, number of examinations or completion of a confirmatory test. In a logistic regression model, only AA race independently predicted consent for donation (odds, 95% CI, 0.27, 0.12-0.57 p < .001). In a different model, apnea test completion was an additional independent predictor (3.66, 1.28-10.5 p = .015). CONCLUSIONS: Approaching families for organ donation consent was associated with medical suitability only and not with demographic or religious characteristics. AAs were 3.7 times less likely to consent for organ donation than non-AAs. Completion of apnea testing was associated with higher consent rates, an observation that needs to be explored in future studies documenting the effect on bedside family presence during this test.

Primary Posterior Fossa Lesions and Preserved Supratentorial Cerebral Blood Flow: Implications for Brain Death Determination.

BACKGROUND: Patients with primary posterior fossa catastrophic lesions may clinically meet brain death criteria, but may retain supratentorial brain function or blood flow. These patients could be declared brain-dead in the United Kingdom (UK), but not in the United States of America (USA). We report the outcome of adult patients with primary posterior fossa lesions without concurrent major supratentorial injury. METHODS: Henry Ford Hospital database was reviewed over a period of 88 months in order to identify all adult patients with isolated brainstem or posterior fossa lesions. We excluded patients with concurrent significant supratentorial pathology potentially confounding the clinical brain death examination. One more patient from a different hospital meeting these criteria was also included. RESULTS: Three patients out of 161 met inclusion criteria (1.9% of all brain deaths during this period). With the addition of a fourth patient from another hospital, 4 patients were analyzed. All four patients had catastrophic brainstem and cerebellar injuries meeting the clinical criteria of brain death with positive apnea test in the UK. All had preserved supratentorial blood flow, which after a period of 2 h to 6 days disappeared on repeat testing, allowing declaration of brain death by US criteria in all four. One patient became an organ donor. CONCLUSIONS: Patients with primary posterior fossa catastrophic lesions, who clinically seem to be brain-dead, evolve from retaining to losing supratentorial blood flow. If absent cerebral blood flow is used as an additional criterion for the declaration of death by neurological criteria, these patients are not different than those who become brain death due to supratentorial lesions.

Hemodynamic and neuro-monitoring for neurocritically ill patients: An international survey of intensivists.

PURPOSE: To investigate multimodality systemic and neuro-monitoring practices in acute brain injury (ABI) and to analyze differences among "neurointensivists" (NI; clinical practice comprised >1/3 by neurocritical care), and other intensivists (OI). METHODS: Anonymous 22-question Web-based survey among physician members of SCCM and ESICM. RESULTS: Six hundred fifty-five responded (66% completion rate); 422 (65%) were OI, and 226 (35%) were NI. More NI follow hemodynamic protocols for TBI (44.5% vs 33%, P=.007) and SAH (38% vs 21%, P<.001). For CPP optimization, NI use more arterial-waveform-analysis (AWA) (45% vs 35%, P=.019), and ultrasound (37.5% vs 28%, P=.023); NI use more PbtO2 (28% vs 10%, P<.001). In the case scenario of raised ICP/low PbtO2, most employ analgesia and/or sedation (47%) and osmotherapy (38%). More NI use pressure reactivity (vasopressor use OI 23% vs NI 34.5%, P=.014). For DCI, more NI target cardiac index (CI) (35% vs 21%, P<.001), and fluid responsiveness (62.5% vs 53%, P=.03). Also, NI use more angiography (57% vs 43.5%, P=.004), TCD (56.5% vs 38%, P<.001), CTP (32% vs16%, P<.001), and PbtO2 (18% vs 7.5%, P=.001). CONCLUSIONS: Intensivists with exposure to ABI patients employ more neuro- and hemodynamic monitoring. We found large heterogeneity and low overall use of advanced brain-physiology parameters.

The first 100 infant thoracoscopic lobectomies: Observations through the learning curve and comparison to open lobectomy.

OBJECTIVE: The objective of the study is to describe our initial 100 attempted infant thoracoscopic lobectomies for asymptomatic, prenatally diagnosed lung lesions, and compare the results to contemporaneous age-matched patients undergoing open lobectomy. BACKGROUND: Infant thoracoscopic lobectomy is a technically challenging procedure, which has only gained acceptance worldwide in recent years. METHODS: This is a retrospective review of all patients undergoing thoracoscopic or open lung lobectomy between March 2005 and January 2014. Included were all asymptomatic infants younger than 4months. Excluded were patients undergoing emergent lobectomy and patients with isolated extralobar bronchopulmonary sequestrations. RESULTS: A total of 100 attempted thoracoscopic lobectomies were compared with 188 open lobectomies. In the thoracoscopic group, mean age and weight at surgery were 7.3weeks and 4.8kg, mean operative time was 185minutes, and mean hospital stay was 3days. Twelve cases were converted to open (12%). Ten conversions occurred within the first third of the series and none in the last third. There were no mortalities. There were no differences between the thoracoscopic and open groups in perioperative complications or hospital stay. There was a significant difference in the operative time: 111minutes vs. 185minutes (open vs. thoracoscopic; p<0.001). There was a higher mean end-tidal carbon dioxide (ETCO2) and lower mean peripheral capillary oxygen saturation (SpO2) in the thoracoscopic group versus the open group (51.7 versus 38.6mmHg and 97.5 versus 99.1%, respectively). CONCLUSION: In high volume centers, the learning curve of thoracoscopic lobectomy can be overcome and the procedure can be performed with equivalent outcomes and, in our opinion, superior cosmetic results to open lobectomy.

Clevidipine for acute hypertension in patients with subarachnoid hemorrhage: a pilot study.

PURPOSE: Clevidipine is a novel, ultra-short acting dihydropyridine. We hypothesized that clevidipine would rapidly control elevated blood pressure (BP) in patients with aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: This prospective open-label pilot study evaluated the efficacy and safety of clevidipine in reducing blood pressure (BP) to a pre-specified range and within 30 min before or after clipping or coiling of the aneurysm. RESULTS: We enrolled five patients who received eight clevidipine infusions, including 1587 systolic or diastolic BP data points. The mean SBP upper and lower goals were set at 154 and 122 mmHg. The primary end point of achieving SBP control within <30 min was reached in all patients within 14.2 ± 6.4 min at an infusion rate of 10.8 ± 9.1 mg/h. The mean pre-infusion, during infusion and post-infusion SBP measurements were 165.5 ± 2.55, 146.4 ± 2.48 and 159.3 ± 11.5 mmHg ( p < 0.05 for pre- vs infusion comparison), respectively. After reaching the primary end point and during the clevidipine infusion, 17.5% and 11.8% of SBP readings were above the upper and below the lower goals, respectively. No patients re-bled. In one patient, the infusion had to be stopped temporarily three times due to SBP decrease below the lower goal. CONCLUSION: Clevidipine controlled SBP in all patients with aneurysmal SAH in <22 min and kept it within the elective range 70% of the time without major complications.