Effect of Radiographic Contrast Media Shortage on Stroke Evaluation in the United States.

BACKGROUND AND PURPOSE: We performed this study to identify the effect of the nationwide iodinated contrast media shortage due to reduction in GE Healthcare production, initiated on April 19, 2022, on the evaluation of patients with stroke. MATERIALS AND METHODS: We analyzed the data on 72,514 patients who underwent imaging processed with commercial software in a sample of 399 hospitals in United States from February 28, 2022, through July 10, 2022. We quantified the percentage change in the daily number of CTAs and CTPs performed before and after April 19, 2022. RESULTS: The daily counts of individual patients who underwent CTAs decreased (a 9.6% reduction, P = .002) from 1.584 studies per day per hospital to 1.433 studies per day per hospital. The daily counts of individual patients who underwent CTPs decreased (a 25.9% reduction, P = .003) from 0.484 studies per day per hospital to 0.358 studies per day per hospital. A significant reduction in CTPs using GE Healthcare contrast media (43.06%, P < .001) was seen but not in CTPs using non-GE Healthcare contrast media (increase by 2.93%, P = .29). The daily counts of individual patients with large-vessel occlusion decreased (a 7.69% reduction) from 0.124 per day per hospital to 0.114 per day per hospital. CONCLUSIONS: Our analysis reported changes in the use of CTA and CTP in patients with acute ischemic stroke during the contrast media shortage. Further research needs to identify effective strategies to reduce the reliance on contrast media-based studies such as CTA and CTP without compromising patient outcomes.

Rho-kinase inhibition ameliorates non-alcoholic fatty liver disease in type 2 diabetic rats.

Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.

The ethics of practicing defensive medicine in Jordan: a diagnostic study.

BACKGROUND: Defensive medicine (DM) practice refers to the ordering or prescription of unnecessary treatments or tests while avoiding risky procedures for critically ill patients with the aim to alleviate the physician's legal responsibility and preserve reputation. Although DM practice is recognized, its dimensions are still uncertain. The subject has been highly investigated in developed countries, but unfortunately, many developing countries are unable to investigate it properly. DM has many serious ramifications, exemplified by the increase in treatment costs for patients and health systems, patients' exposure to risks, and negative effects on the psychological health of both health providers and recipients. Ultimately, the most serious consequence is the ethical consequences. METHODS: This work is based on a review of the literature related to DM worldwide and a comparison with the available knowledge found in Jordan. It is qualitative with a descriptive nature, aiming to diagnose the current DM practice in Jordan. RESULTS: This is the first published article that discusses DM in Jordan by diagnosing its ethical and economic consequences for the health system as well as for patients. Despite the knowledge of the reasons that support its practice, little is being done to solve this issue. The absence of agreeable medical malpractice law, the dearth of unified medical protocols, the overwhelming pressure imposed by patients on medical staff, and the deteriorating patient-physician relationship are some of the causes of DM practice. Surely, the solution to these issues is to focus on fortifying the ethical and humanitarian aspects on the side of both the physician and the patient to ensure positive collaboration. The ethical aim of the physician to treat the patient faithfully and do what is possible to help combined with the appreciation of the physician's efforts and the choice to not take advantage of the physician through litigation could be the most reasonable solution in the near future. CONCLUSION: Jordan is suffering from DM due to the limited financial expenditure on the health sector and the impracticality of medical malpractice law. The authors highlight that the cardinal step in solving this dilemma is restoring the ethical dimension of the patient-physician relationship.

Early Postmarket Results with EmboTrap II Stent Retriever for Mechanical Thrombectomy: A Multicenter Experience.

BACKGROUND AND PURPOSE: EmboTrap II is a novel stent retriever with a dual-layer design and distal mesh designed for acute ischemic stroke emergent large-vessel occlusions. We present the first postmarket prospective multicenter experience with the EmboTrap II stent retriever. MATERIALS AND METHODS: A prospective registry of patients treated with EmboTrap II at 7 centers following FDA approval was maintained with baseline patient characteristics, treatment details, and clinical/radiographic follow-up. RESULTS: Seventy patients were treated with EmboTrap II (mean age, 69.9 years; 48.6% women). Intravenous thrombolysis was given in 34.3%, and emergent large-vessel occlusions were located in the ICA (n = 18), M1 (n = 38), M2 or M3 (n = 13), and basilar artery (n = 1). The 5 × 33 mm device was used in 88% of cases. TICI ≥ 2b recanalization was achieved in 95.7% (82.3% in EmboTrap II-only cases), and first-pass efficacy was achieved in 35.7%. The NIHSS score improved from a preoperative average of 16.3 to 12.1 postprocedure and to 10.5 at discharge. An average of 2.5 [SD, 1.8] passes was recorded per treatment, including non-EmboTrap attempts. Definitive treatment was performed with an alternative device (aspiration or stent retriever) in 9 cases (12.9%). Some hemorrhagic conversion was noted in 22.9% of cases, of which 4.3% were symptomatic. There were no device-related complications. CONCLUSIONS: Initial postmarket results with the EmboTrap II stent retriever are favorable and comparable with those of other commercially available stent retrievers. Compared with EmboTrap II, the first-generation EmboTrap may have a higher first-pass efficacy; however, data are limited by retrospective case analysis, incomplete clinical follow-up, and small sample size, necessitating future trials.

Intracranial-derived atherosclerosis assessment: an in vitro comparison between virtual histology by intravascular ultrasonography, 7T MRI, and histopathologic findings.

BACKGROUND AND PURPOSE: Atherosclerotic plaque composition and structure contribute to the risk of plaque rupture and embolization. Virtual histology by intravascular ultrasonography and high-resolution MR imaging are new imaging modalities that have been used to characterize plaque morphology and composition in peripheral arteries. MATERIALS AND METHODS: The objectives of this study were 1) to determine the correlation between virtual histology-intravascular ultrasonography and histopathologic analysis (reference standard) and 2) to explore the comparative results of 7T MR imaging (versus histopathologic analysis), both to be performed in vitro by use of intracranial arterial segments with atherosclerotic plaques. Thirty sets of postmortem samples of intracranial circulation were prepared for the study. These samples included the middle cerebral artery (n = 20), basilar artery (n = 8), and anterior cerebral artery (n = 2). Virtual histology-intravascular ultrasonography and 7T MR imaging were performed in 34 and 10 points of interest, respectively. The formalin-fixed arteries underwent tissue processing and hematoxylin-eosin staining. The plaques were independently categorized according to revised Stary classification after review of plaque morphology and characteristics obtained from 3 modalities. The proportion of fibrous, fibrofatty, attenuated calcium, and necrotic components in the plaques were determined in histology slides and compared with virtual histology-intravascular ultrasonography and MR imaging. RESULTS: Of 34 points of interest in the vessels, 32 had atherosclerotic plaques under direct visualization. Plaques were visualized in gray-scale intravascular ultrasonography as increased wall thickness, outer wall irregularity, and protrusion. The positive predictive value of virtual histology-intravascular ultrasonography for identifying fibroatheroma was 80%. Overall, virtual histology-intravascular ultrasonography accurately diagnosed the type of the plaque in 25 of 34 samples, and κ agreement was 0.58 (moderate agreement). The sensitivity and specificity of virtual histology-intravascular ultrasonography readings for fibroatheroma were 78.9% and 73.3%, respectively. The overall sensitivity and specificity for virtual histology-intravascular ultrasonography were 73.5% and 96.6%, respectively. Plaques were identified in 7T MR imaging as increased wall thickness, luminal stenosis, or outer wall protrusion. The positive predictive value of 7T MR imaging for detecting fibrous and attenuated calcium deposits was 88% and 93%, respectively. CONCLUSIONS: This in vitro study demonstrated that virtual histology-intravascular ultrasonography and high-resolution MR imaging are reliable imaging tools to detect atherosclerotic plaques within the intracranial arterial wall, though both imaging modalities have some limitations in accurate characterization of the plaque components. Further clinical studies are needed to determine the clinical utility of plaque morphology and composition assessment by noninvasive tests.

Off-label use of drugs and devices in the neuroendovascular suite.

SUMMARY: The off-label use of drugs and devices in neuroendovascular procedures is common. Neurointerventionalists should be well aware of the level of evidence available in support of the off-label use of drugs and devices in their practice and some of the potential adverse events associated with them. These uses are categorized as I or II if they have been evaluated as primary or ancillary interventions in prospective trials/registries of neuroendovascular procedures and III if they were evaluated in case series. Category IV use is based on evaluation as primary or ancillary interventions in prospective trials/registries of non-neuroendovascular procedures. Physicians are allowed to use off-label drugs and procedures if there is strong evidence that they are beneficial for the patient. The neurointerventional professional societies agree that off-label use of drugs and devices is an important part of the specialty, but practicing providers should base their decisions on sound evidence when using such drugs and devices.

Rate and prognosis of patients under conscious sedation requiring emergent intubation during neuroendovascular procedures.

BACKGROUND AND PURPOSE: Neuroendovascular procedures are performed with the patient under conscious sedation (local anesthesia) in varying numbers of patients in different institutions, though the risk of unplanned conversion to general anesthesia is poorly characterized. Our aim was to ascertain the rate of failure of conscious sedation in patients undergoing neuroendovascular procedures and compare the in-hospital outcomes of patients who were converted from conscious sedation to general anesthesia with those whose procedures were initiated with general anesthesia. MATERIALS AND METHODS: All patients who had an endovascular procedure initiated under general anesthesia or conscious sedation were identified through a prospective data base maintained at 2 comprehensive stroke centers. Patient clinical and procedural characteristics, in-hospital deaths, and favorable outcomes (modified Rankin Scale score, 0-2) at discharge were ascertained. RESULTS: Nine hundred seven endovascular procedures were identified, of which 387 were performed with the patient under general anesthesia, while 520 procedures were initiated with conscious sedation. Among procedures initiated with intent to be performed under conscious sedation, 9 (1.7%) procedures required emergent conversion to general anesthesia. Favorable clinical outcome and in-hospital mortality in patients requiring emergent conversion from conscious sedation to general anesthesia and in those with procedures initiated with general anesthesia were not statistically different (42% versus 50%, P = .73 and 17% versus 13%, P = 1.00, respectively). CONCLUSIONS: In our study, there was a very low rate of conscious sedation failure and associated adverse outcomes among patients undergoing neuroendovascular procedures. Proper patient selection is important if procedures are to be performed with the patient under conscious sedation. Limitations of the methodology used in our study preclude us from offering specific recommendations regarding when to use a specific anesthetic protocol.

Microcatheter to recanalization (procedure time) predicts outcomes in endovascular treatment in patients with acute ischemic stroke: when do we stop?

BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke consists of various mechanical and pharmacologic modalities used for recanalization of arterial occlusions. We performed this study to determine the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. MATERIALS AND METHODS: We analyzed data from consecutive patients with acute ischemic stroke who underwent endovascular treatment during a 6-year period. Demographic characteristics, NIHSS score before and 24 hours after the procedure, and discharge mRS score were ascertained. Procedure time was defined by the time interval between microcatheter placement and recanalization or completion of the procedure. We estimated the procedure time after which favorable clinical outcome was unlikely, even after adjustment for age, time from symptom onset, and admission NIHSS scores. RESULTS: We analyzed 209 patients undergoing endovascular treatment (mean age, 65 ± 16 years; 109 [52%] men; mean admission/preprocedural NIHSS score, 15.3 ± 6.8). Complete or partial recanalization was observed in 176 (84.2%) patients, while unfavorable outcome (mRS 3-6) was observed in 138 (66%) patients at discharge. In univariate analysis, patients with procedure time ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure time ≥30 minutes (52.3% versus 72.2%, P = .0049). In our analysis, the rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment in the Prourokinase for Acute Ischemic Stroke Trial. In logistic regression analysis, unfavorable outcome was positively associated with age (P = .0012), admission NIHSS strata (P = .0017), and longer procedure times (P = .0379). CONCLUSIONS: Procedure time in patients with acute ischemic stroke appears to be a critical determinant of outcomes following endovascular treatment. This highlights the need for procedure time guidelines for patients being considered for endovascular treatment in acute ischemic stroke.

Intravascular ultrasound: principles and cerebrovascular applications.

Intravascular sonography is a valuable tool for the morphologic assessment of coronary atherosclerosis and the effect of pharmacologic and nonpharmacologic interventions on the progression or stabilization of atherosclerosis. An analysis of the different modes, applications, and limitations is provided on the basis of review of existing data from multiple clinical case studies, trials, and mechanistic studies. Intravascular sonography has been used to assess the outcomes of different percutaneous interventions, including angioplasty and stent implantation, and to provide detailed characterization of atherosclerotic lesions, aneurysms, and dissections within the cerebrovascular circulation. Evolution of intravascular sonographic technology has led to the development of more sophisticated diagnostic tools such as color-flow, virtual histology, and integrated backscatter intravascular sonography. The technologic advancement in intravascular sonography has the potential of providing more accurate information prior, during, and after a medical or endovascular intervention. Continued assessment of this diagnostic technique in both the intracranial and extracranial circulation will lead to increased use in clinical practice with the intent to improve outcomes.

Synthesis and biological activity of 2-fluoro adenine and 6-methyl purine nucleoside analogs as prodrugs for suicide gene therapy of cancer.

A novel series of 6-methylpurine nucleoside derivatives with substitutions at 5-position have been synthesised These compounds bear a 5'-heterocycle such as triazole or a imidazole with a two carbon chain, and an ether, thio ether or amine. To extend the SAR study of 2-fluoroadenine and 6-methyl purine nucleosides, their corresponding alpha-linker nucleosides with L-xylose and L-lyxose were also synthesized. All of these compounds have been evaluated for their substrate activity with E. coli PNP.

Convenient syntheses of 6-methylpurine and related nucleosides.

Efficient methods for the synthesis of 6-methylpurine (3), 9-(2-deoxy-beta-D-erythro-pentofuranosyl)-6-methylpurine (8), and 6-methyl-9-beta-D-ribofuranosylpurine (5) are described. Methodology involving the (Ph3P)4Pd catalyzed cross-coupling reaction of CH3ZnBr with several different 6-chloropurine derivatives is described in high yield. This methodology now provides a facile and high-yielding synthesis of 8, which is needed in significant amounts for studies in cancer gene therapy.

A convenient synthesis of 2'-deoxy-2-fluoroadenosine; a potential prodrug for suicide gene therapy.

A convenient synthesis of 2'-deoxy-2-fluoro-adenosine (1) is described. Deaminative fluorination of 2-aminoadenosine (2) followed by silylation of the 3', 5'-hydroxyl groups gave the corresponding 2-fluoroadenosine derivative 4 in good yield. Thiocarbonylation of 4 to thiocarbonylimidazolyl derivative 5a followed by treatment with an excess of tris(trimethylsilyl)silane (TTMSS) and tert-butyl peroxide in toluene at 80 degrees C was found to affect an efficient deoxygenation to the corresponding 2'-deoxy derivative 6. Desilylation of 6 by Et4NF in CH3CN afforded 1 in high yield.

Modeling ground water flow and radioactive transport in a fractured aquifer.

Three-dimensional numerical modeling is used to characterize ground water flow and contaminant transport at the Shoal nuclear test site in north-central Nevada. The fractured rock aquifer at the site is modeled using an equivalent porous medium approach. Field data are used to characterize the fracture system into classes: large, medium, and no/small fracture zones. Hydraulic conductivities are assigned based on discrete interval measurements. Contaminants from the Shoal test are assumed to all be located within the cavity. Several challenging issues are addressed in this study. Radionuclides are apportioned between surface deposits and volume deposits in nuclear melt glass, based on their volatility and previous observations. Surface-deposited radionuclides are released hydraulically after equilibration of the cavity with the surrounding ground water system, and as a function of ground water flow through the higher-porosity cavity into the low-porosity surrounding aquifer. Processes that are modeled include the release functions, retardation, radioactive decay, prompt injection, and ingrowth of daughter products. Prompt injection of radionuclides away from the cavity is found to increase the arrival of mass at the control plane but is not found to significantly impact calculated concentrations due to increased spreading. Behavior of the other radionuclides is affected by the slow chemical release and retardation behavior. The transport calculations are sensitive to many flow and transport parameters. Most important are the heterogeneity of the flow field and effective porosity. The effect of porosity in radioactive decay is crucial and has not been adequately addressed in the literature. For reactive solutes, retardation and the glass dissolution rate are also critical.

Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation.

Serum insulin, growth hormone (GH), insulin-like growth factors (IGFs) I and II, cortisol, and albumin concentrations were measured in 15 children with kwashiorkor, 15 with marasmic-kwashiorkor, and 21 with marasmus, before and in the survivors, after nutritional rehabilitation, as well as in 10 underweight and eight normal Egyptian children. We also evaluated arginine-induced insulin and GH secretion. IGF-I concentrations were reduced in the three severely malnourished groups (0.07 +/- 0.03, 0.05 +/- 0.03, and 0.09 +/- 0.09 U/ml, respectively) but returned to normal after refeeding. IGF-II concentrations were low in the kwashiorkor (175 +/- 79 ng/ml), marasmic-kwashiorkor (111 +/- 57 ng/ml), and marasmic children (128 +/- 70.9 ng/ml) and returned to normal after nutritional rehabilitation. Basal GH levels were high in the three severely malnourished groups (21.9, 28.8, and 16.6 ng/ml, respectively) and returned to normal after refeeding (8.1, 6.5, and 6.0 ng/ml, respectively). GH responses to arginine were depressed in the three malnourished groups and improved significantly in marasmic-kwashiorkor and marasmic children after nutritional rehabilitation. Insulin responses to arginine were impaired in kwashiorkor, and marasmic-kwashiorkor children and improved significantly after refeeding. IGF-I levels correlated significantly with percent of expected weight (r = 0.52, p less than 0.001), percent of expected height (r = 0.42, p less than 0.001), and weight/(height)2 index (r = 0.34, p less than 0.01). IGF-I levels correlated positively with insulin levels (r = 0.421, p less than 0.001) and negatively with cortisol concentrations (r = -0.400, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)