Selective extraction of apixaban from plasma by dispersive solid-phase microextraction using magnetic metal organic framework combined with molecularly imprinted polymer nanocomposite.

This research aims to synthesize a specific and efficient sorbent to use in the extraction of apixaban from human plasma samples and its determination by high-performance liquid chromatography-tandem mass spectrometry. High specific surface area of metal-organic framework, magnetic property of iron oxide nanoparticles, selectively of molecular imprinted polymer toward the analyte, and the combination of dispersive solid-phase extraction method with a sensitive analysis system provided an efficient analytical method. In this study, first, a molecularly imprinted polymer combined with magnetic metal organic framework nanocomposite was prepared and then characterized using different techniques. Then the sorbent particles were used for selective extraction of the analyte from plasma samples. The efficiency of the method was improved by optimizing effective parameters. According to the validation results, wide linear range (1.02-200 ng mL-1 ), acceptable coefficient of determination (0.9938), low limit of detection (0.32 ng mL-1 ) and limit of quantification (1.02 ng mL-1 ), high extraction recovery (78%), and good precision (relative standard deviations ≤ 2.9% for intra- (n = 6) and interday (n = 6) precisions) were obtainable using the proposed method. These outcomes showed the high potential of the proposed method for screening apixaban in the human plasma samples.

Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage: The Swiss Study on Subarachnoid Hemorrhage (Swiss SOS).

BACKGROUND AND PURPOSE: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. METHODS: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. RESULTS: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0-2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3-5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. CONCLUSIONS: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03245866.

From the environment to the cells: An overview on pivotal factors which affect spreading and infection in COVID-19 pandemic.

Several factors ranging from environmental risks to the genetics of the virus and that of the hosts, affect the spread of COVID-19. The impact of physicochemical variables on virus vitality and spread should be taken into account in experimental and clinical studies. Another avenue to explore is the effect of diet and its interaction with the immune system on SARS-CoV-2 infection and mortality rate. Past year have witnessed extensive studies on virus and pathophysiology of the COVID-19 disease and the cellular mechanisms of virus spreading. However, our knowledge has not reached a level where we plan an efficient therapeutic approach to prevent the virus entry to the cells or decreasing the spreading and morbidity in severe cases of disease. The risk of infection directly correlates with the control of virus spreading via droplets and aerosol transmission, as well as patient immune system response. A key goal in virus restriction and transmission rate is to understand the physicochemical structure of aerosol and droplet formation, and the parameters that affect the droplet-borne and airborne in different environmental conditions. The lifetime of droplets on different surfaces is described based on the contact angle. Hereby, we recommend regular use of high-quality face masks in high temperature and low humidity conditions. However, in humid and cold weather conditions, wearing gloves and frequently hand washing, gain a higher priority. Additionally, social distancing rules should be respected in all aforementioned conditions. We will also discuss different routes of SARS-CoV-2 entry into the cells and how multiple genetic factors play a role in the spread of the virus. Given the role of environmental and nutritional factors, we discuss and recommend some strategies to prevent the disease and protect the population against COVID-19. Since an effective vaccine can prevent the transmission of communicable diseases and abolish pandemics, we added a brief review of candidate SARS-CoV-2 vaccines.

Association between biomarkers of bone health and osteosarcopenia among Iranian older people: The Bushehr Elderly Health (BEH) program.

BACKGROUND: Osteosarcopenia is referred to as co-incidence of osteoporosis/osteopenia and sarcopenia which is defined as a geriatric syndrome with a significant prevalence that increases morbidity and mortality. There are some relevant factors that can show an increased risk of incidence of osteosarcopenia. AIM: We aimed to consider the association of bone turnover markers such as Osteocalcin (OC), C-terminal cross-linked telopeptide (CTX), Tartrate Resistant acid Phosphatase (TRAP), Bone Alkaline Phosphatase (BALP) and also other factors like vitamin D, calcium, phosphorous, and ALP with osteosarcopenia in elderly. METHODS: We carried out a cross-sectional study on a random sample including 400 elder participants of Bushehr Elderly Health (BEH) study, in Iran. Osteopenia/ osteoporosis was defined as a T-score ≤ -1.0 standard deviation below the mean values of a young healthy adult. We defined sarcopenia as low muscle strength (handgrip strength<26 kg for men and <18 kg for women) with reduced skeletal muscle mass [Skeletal muscle index (SMI) < 7.0 kg/m2 for male and <5.4 kg/m2 for female]. Osteosarcopenia was considered as the presence of both osteopenia/osteoporosis and sarcopenia. We estimated the age-standardized prevalence of osteosarcopenia for men and women, separately. We used multivariable logistic regression to address the factors associated with osteosarcopenia. RESULTS: The results showed that there was a statistically significant difference in OC), CTX, TRAP were between the osteosarcopenia (-) and osteosarcopenia (+) groups. No statistically significant difference was observed in BALP, vitamin D, calcium, phosphorous, and ALP between the compared groups. In the multivariable logistic regression model, OC and CTX were associated with increased likelihood of osteosarcopenia [adjusted OR= 1.023(1.002-1.045 for OC, 4.363(1.389-15.474 for CTX)]. Furthermore, TRAP increases the odds of osteosarcopenia in crude model [OR= 1.333 (1.070- 1.660)]. CONCLUSIONS: We observed the association between bone turnover markers particularly OC, CTX and osteosarcopenia. Given the rapid growth of the aging population, we should focus on geriatric diseases such as musculoskeletal disorders. Bone turnover markers maybe improve the early diagnosis, screening and assess the response to therapies in people with osteosarcopenia.

Discovery of Novel Cell Surface Markers for Purification of Embryonic Dopamine Progenitors for Transplantation in Parkinson's Disease Animal Models.

Despite the progress in safety and efficacy of cell replacement therapy with pluripotent stem cells (PSCs), the presence of residual undifferentiated stem cells or proliferating neural progenitor cells with rostral identity remains a major challenge. Here we report the generation of a LIM homeobox transcription factor 1 alpha (LMX1A) knock-in GFP reporter human embryonic stem cell (hESC) line that marks the early dopaminergic progenitors during neural differentiation to find reliable membrane protein markers for isolation of midbrain dopaminergic neurons. Purified GFP positive cells in vitro exhibited expression of mRNA and proteins that characterized and matched the midbrain dopaminergic identity. Further quantitative proteomics analysis of enriched LMX1A+ cells identified several membrane-associated proteins including a polysialylated embryonic form of neural cell adhesion molecule (PSA-NCAM) and contactin 2 (CNTN2), enabling prospective isolation of LMX1A+ progenitor cells. Transplantation of human-PSC-derived purified CNTN2+ progenitors enhanced dopamine release from transplanted cells in the host brain and alleviated Parkinson's disease-related phenotypes in animal models. This study establishes an efficient approach for purification of large numbers of human-PSC-derived dopaminergic progenitors for therapeutic applications.

Injectable porcine bone demineralized and digested extracellular matrix-PEGDA hydrogel blend for bone regeneration.

Extracellular matrix (ECM) has a major role in the structural support and cellular processes of organs and tissues. Proteins extracted from the ECM have been used to fabricate different scaffolds for tissue engineering applications. The aims of the present study were to extract, characterize and fabricate a new class of hydrogel with proteins isolated from pig bone ECM and combine them with a synthetic polymer so it could be used to promote bone regeneration. Porcine bone demineralized and digested extracellular matrix (pddECM) containing collagen type I was produced, optimized and sterilized with high pressurized CO2 method. The pddECM was further blended with 20% w/v polyethylene glycol diacrylate (PEGDA) to create an injectable semi interpenetrating polymer network (SIPN) scaffold with enhanced physicochemical properties. The blend tackled the shortfall of natural polymers, such as lack of structural stability and fast degradation, preserving its structure in more than 90% after 30 days of incubation; thus, increasing the material endurance in a simulated physiological environment. The manufactured injectable hydrogel showed high cytocompatibility with hOb and SaOs-2 cells, promoting osteogenic proliferation within 21 days of culture. The hydrogel had a high compression modulus of 520 kPa, low swelling (5.3 mg/mg) and millimetric volume expansion (19.5%), all of which are favorable characteristics for bone regeneration applications.

A comparative histomorphological and micro computed tomography study of the primary stability and the osseointegration of The Sydney Mini Screw; a qualitative pilot animal study in New Zealand rabbits.

OBJECTIVE: The aim of this study was to assess the potential of improving orthodontic miniscrews' (MSs) primary stability in vivo by evaluating the dispersion capacity of an injectable bone graft substitute (iBGS) through a newly designed hollow MS [The Sydney Mini Screw (SMS)] and its integration with the cortical and trabecular bone by using the femur and tibia in a New Zealand rabbit animal model. METHODS: In total, 24 MSs were randomly placed in each proximal tibia and femur of 6 New Zealand rabbits with an open surgery process. Aarhus MSs were used as controls and the effect of injection of iBGS was studied by implanting SMSs with and without iBGS injection. The dispersion of iBGS and the integration of the SMS were studied by using micro Computed Tomography (µCT) and histochemical analysis at two time points, 0 day and 8 weeks post-implantation. RESULTS: iBGS was successfully injected through the SMS and hardened in situ. After 8 weeks, µCT results revealed that the iBGS particles were resorbed and bone tissue was formed around the SMS and within its lateral exit holes. CONCLUSIONS: This pilot animal study showed the high potential of the combined use of iBGS and SMS as a newly developed technique to promote the primary stability of MSs.

Seismic stability analyses of reinforced tapered landfill cover systems considering seepage forces.

One of the most common and economical methods for waste disposal is landfilling. The landfill cover system is one of the main components of landfills which prevents waste exposure to the environment by creating a barrier between the waste and the surrounding environment. The stability and integrity of the landfill cover system is a fundamental part of the design, construction, and maintenance of landfills. A reinforced tapered landfill cover system can be considered as a practical method for improving its stability; however, the simultaneous effects of seismic and seepage forces in the reinforced tapered landfill cover system have not been studied. The current paper provides a solution based on the limit equilibrium method in order to evaluate the stability of a reinforced tapered landfill cover system under seismic and seepage (both horizontal and parallel seepage force patterns) loading conditions. The proposed analytical approach is applied to different design cases through parametric study and the obtained results are compared to those derived from literature. Parametric study is performed to illustrate the sensitivity of the safety factor (FS) to the different design parameters. The obtained results reveal that parameters which describe the geometry have limited effects on the stability of the landfill cover system in comparison to the rest of the studied design parameters. Moreover, the comparisons between the derived results and available methods demonstrate good agreement between obtained findings with those reported in the literature.

Fabrication of a Biodegradable Implant with Tunable Characteristics for Bone Implant Applications.

Biodegradable polymers are appealing material for the manufacturing of surgical implants as such implants break down in vivo, negating the need for a subsequent operation for removal. Many biocompatible polymers produce acidic breakdown products that can lead to localized inflammation and osteolysis. This study assesses the feasibility of fabricating implants out of poly(propylene carbonate) (PPC)-starch that degrades into CO2 and water. The basic compression modulus of PPC-starch (1:1 w/w) is 34 MPa; however, the addition of glycerol (1% w/w) and water as plasticizers doubles this value and enhances the surface wettability. The bioactivity and stiffness of PPC-starch blends is increased by the addition of bioglass microparticles (10% w/w) as shown by in vitro osteoblast differentiation assay and mechanical testing. MicroCT analysis confirms that the bioglass microparticles are evenly distributed throughout biomaterial. PPC-starch-bioglass was tested in vivo in two animal models. A murine subcutaneous pellet degradation assay demonstrates that the PPC-starch-bioglass blend's volume fraction loss is 46% after 6 months postsurgery, while it is 27% for poly(lactic acid). In a rat knee implantation model, PPC-starch-bioglass screws inserted into the distal femur show osseointegration with no localized adverse effects after 3 and 12 weeks. These data support the further development of PPC-starch-bioglass as a medical biomaterial.

Validation and accuracy of intraoperative CT scan using the Philips AlluraXper FD20 angiography suite for assessment of spinal instrumentation.

BACKGROUND: With the concept of the hybrid operating room gaining popularity, the authors adapted a hybrid angiographic suite with intraoperative computed tomography (iCT) to evaluate accuracy of pedicle screw placement in spinal fusion. This retrospective review examines how well iCT detected extrapedicular screw violation, to then allow repositioning and potentially avoid revision surgery. METHODS: A total of 36 consecutive patients underwent pedicle screw placement in posterior cervical, thoracic, and lumbosacral spinal fusions. All patients underwent iCT in the Philips AlluraXper FD20 angiography suite in the lumbar spine XperCT mode and postoperative conventional computed tomography (CT) scanning. Primary endpoints included the sensitivity and specificity of iCT in detecting pedicular violation characterized as minor, moderate, or severe when compared with postoperative CT. Secondary endpoint included the incidence of replaced screws during surgery and number of revision surgeries. RESULTS: Of 241 screws placed in 16 males and 20 females, iCT detected severe pedicle violation in 25 screws (10.4%); 16 screws were then repositioned during surgery. Sensitivity and specificity of iCT to detect severe screw malposition were 92.3% and 99.1%, respectively. No revision surgeries were performed in this series. CONCLUSIONS: In our series, iCT had high sensitivity and specificity in detecting severe screw malposition. As a valuable adjunct for intraoperative assessment of pedicle screw position, immediate intraoperative correction of misplaced screws then eliminated any revision surgery for our patients.

Non-instrumented extradural lumbar spine surgery under low-dose acetylsalicylic acid: a comparative risk analysis study.

PURPOSE: Coronary artery disease (CAD) affects over one-third of adults and is the leading cause of overall mortality and morbidity. Acetylsalicylic acid (ASA) is widely used in the prevention of CAD. As the population continues to mature, the number of patients presenting for spinal surgery that are under ASA treatment is rising. Studies investigating the outcome of lumbar spine surgeries without discontinuation of ASA therapy are lacking. The purpose of this study is to evaluate the peri- and postoperative bleeding and cardiovascular complication rates of patients undergoing non-instrumented, extradural, lumbar spine surgery with or without discontinuation of low-dose ASA. METHODS: We retrospectively compared the intra- and postoperative blood loss, morbidity, mortality, blood transfusion requirements and hematologic findings in the ASA group (40 patients) and the control group (62 patients). The diagnosis in all patients was either lumbar disc herniation or spinal canal stenosis. RESULTS: Intraoperative blood loss was 221 ml in the ASA group and 140.16 ml in the control group, showing no statistical difference (p = 0.08). Postoperative blood loss was 146.58 and 167.97 ml in the ASA and control groups, respectively, also without statistical difference (p = 0.76). In the ASA group one patient developed a postoperative epidural hematoma needing revision surgery, while in the control group no postoperative epidural hematomas were seen (p = 0.40). In addition, blood transfusion requirements, hematologic findings, morbidity and mortality showed no significant difference. CONCLUSION: The continuation of ASA treatment in patients undergoing non-instrumented extradural lumbar spinal surgery seems to be safe and its perioperative continuation might therefore be recommended. Further studies confirming these results are needed.

The Extended Subfrontal and Fronto-Orbito-Zygomatic Approach in Skull Base Meningioma Surgery: Clinical, Radiologic, and Cosmetic Outcome.

OBJECTIVE: To review the outcome and cosmetic results of patients undergoing extended subfrontal and fronto-orbito-zygomatic craniotomy for resection of skull base meningiomas. METHODS: All surgeries were performed in cooperation with an oral and maxillofacial surgeon between 2006 and 2012. Clinical presentation, surgical techniques and complications, cosmetic, clinical, and radiologic outcomes are presented. RESULTS: This study included 25 consecutive patients with 26 operations. Total and subtotal tumor removal was obtained in 19 (73.1%) and 7 (26.9%) patients, respectively. Permanent postoperative complications were seen in 5 (19.2%) patients. Eight of 10 patients with preoperative visual impairment showed recovery at 6 months follow-up. Anosmia was improved in 50% and no worsening was seen in any case of hyposmia. All patients showed improved or complete correction of exophthalmos, cognitive deficits, and epilepsy. One patient (3.8%) developed a postoperative ptosis. No mortality was documented. All patients reported a favorable cosmetic satisfactory score over 6 (8.67 ±â€Š1.6). Tumor recurrence rate was 7.7% (n = 2). CONCLUSIONS: The extended subfrontal and fronto-orbito-zygomatic approach, used for resection of meningiomas located in the orbita and the skull base can provide better visibility of the tumor. In addition, these approaches lead to highly satisfying cosmetic and clinical results.

Parasagittal Dural Arteriovenous Fistula Treated With Embozene Microspheres.

PURPOSE: To describe the use of Embozene microspheres as an alternative treatment for intracranial dural arteriovenous fistulas (DAVF). CASE REPORT: The DAVF was located close to the vertex and mainly fed by the left medial meningeal artery (MMA). Embolization was performed using Embozene microspheres due to stenosis in the posterior branch of the left MMA and a conglomerate of tortuous courses in the anterior branch. Complete occlusion was achieved without complication. Neurological symptoms improved, and the patient remained asymptomatic during 1-year follow-up. Angiography at 1 year did not reveal any revascularization. CONCLUSION: Use of microspheres may be a safe and effective alternative treatment, particularly in patients with impeded access to the DAVF.

Blood clot placement model of subarachnoid hemorrhage in non-human primates.

Despite ongoing extensive and promising research to prevent and treat cerebrovascular vasospasm and delayed ischemic neurological deficits (DIND) after aneurysmal subarachnoid hemorrhage (aSAH), clinical outcomes remain unsatisfying. Neuroprotective strategies developed in basic science research laboratories need to be translated from bench-to-bedside using appropriate animal models. While a primate model is widely accepted as the best animal model mimicking development of delayed cerebral vasospasm after aSAH, its worldwide usage has dramatically decreased because of ethical and financial limitations. However, the use of primate models of subarachnoid hemorrhage (SAH) remains a recommended bridge for translation of early preclinical studies in rodents to human clinical trials. This paper discusses the technical aspects as well as advantages and disadvantages of a blood clot placement model of subarachnoid hemorrhage in non-human primates.

Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells.

INTRODUCTION: 17ß-estradiol (E2) has been found to induce vasodilation in the cardiovascular system and at physiological levels, resulting in prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) in animal models. The goal of this study was to analyze the cellular mechanism of nitric oxide (NO) production and its relation to E2, in vitro in brain and peripheral endothelial cells. METHODS: Human umbilical endothelial cells (HUVEC) and brain endothelial cells (bEnd.3) were treated with estradiol (E2, 0.1, 10, 100, and 1,000 nM), and supernatant was collected at 0, 5, 15, 30, 60, and 120 min for nitric oxide metabolome (nitrite, NO2) measurements. Cells were also treated with E2 in the presence of 1400W, a potent eNOS inhibitor, and ICI, an antagonist of estradiol receptors (ERs). Effects of E2 on eNOS protein expression were assessed with Western blot analysis. RESULTS: E2 significantly increased NO2 levels irrespective of its concentration in both cell lines by 35 % and 42 % (p < 0.05). The addition of an E2 antagonist, ICI (10 µM), prevented the E2-induced increases in NO2 levels (11 % p > 0.05). The combination of E2 (10 nM) and a NOS inhibitor (1400W, 5 µM) inhibited NO2 increases in addition (4 %, p > 0.05). E2 induced increases in eNOS protein levels and phosphorylated eNOS (eNOS(p)). CONCLUSIONS: This study indicates that E2 induces NO level increases in cerebral and peripheral endothelial cells in vitro via eNOS activation and through E2 receptor-mediated mechanisms. Further in vivo studies are warranted to evaluate the therapeutic value of estrogen for the treatment of SAH-induced vasospasm.

Proximal arterial diameters on CT angiography and digital subtraction angiography correlate both at admission and in the vasospasm period after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Comparison of artery diameters between CT angiography (CTA) and subtraction arteriography (DSA) has the limitation that measurements on DSA are provided as relative units, making a quantitative comparison difficult. On CTA, artery diameters may depend on windowing settings and may lead to false measurements. This study assesses the correlation between CTA and DSA based on measurements in a basic imaging viewer using normalized DSA values, and assesses whether the validity is time dependent. METHODS: Patients with aneurysmal subarachnoid hemorrhage (aSAH) were included if they underwent both CTA and DSA within 24 h. The analysis was performed using the basic imaging application Centricity Enterprise PACS viewer (GE Healthcare). A total of 15 arterial locations were assessed on CTA and DSA and a specific measurement protocol with normalization of all artery diameters to the cavernous segment of the internal carotid artery was used. Pearson correlation analysis was calculated to access the correlation of normalized arterial diameters measured with both methods at admission and at clinical onset of CVS. RESULTS: A total of 627 arteries in 38 patients were analyzed in both CTA and DSA. There was a significant correlation coefficient (R = 0.706) of artery diameters between CTA and DSA measures (p < 0.0001). This correlation remained high when comparing CTA and DSA at admission (correlation coefficient: 0.641; p < 0.0001) vs. in the vasospasm period (0.835; p < 0.0001). The correlation was good in all proximal artery segments and lost significance only when distal vessel segments were considered. CONCLUSION: Using basic imaging viewers, mostly accessible for clinicians, CTA is a noninvasive and reliable method to assess proximal arterial diameters of the brain in the management of cerebral vasospasm in the acute phase after aSAH. Significance is reached, independent of whether CTA is obtained in the acute phase or during the period of vasospasm, by normalization of basal cerebral artery diameters to a non-variable anatomic landmark, i.e., the petrous or cavernous internal carotid artery diameter.

Acute angiographic vasospasm and the incidence of delayed cerebral vasospasm: preliminary results.

BACKGROUND: More than half of subarachnoid hemorrhage (SAH) patients develop angiographically detectable delayed cerebral vasospasm (dCVS). It mostly occurs between days 4 and 15 after ictus and can be associated with neurological deficits that contribute to increased morbidity and mortality after SAH. Although dCVS is well studied, there are only a handful of reports on the acute phase of vasospasm (APV) occurring after treatment of intracranial aneurysms, whether ruptured or not. The aim of the current study is to elucidate the association of intraoperative cerebral vasospasm (iCVS) with the incidence of dCVS. METHOD: We retrospectively reviewed consecutive patients who were treated for aneurysmal SAH or incidental aneurysms during the study period. Angiograms of patients undergoing aneurysm treatment were reviewed. Spasm severity was classified with respect to reduction in the transverse diameter. Mild vasospasm was defined as a reduction in vessel diameter of 10-30 %; moderate, 30-50 %; and severe vasospasm, >50 %. Statistical significance was tested using the Χ² test with p < 0.05. Correlations between iCVS and other factors were investigated. RESULTS: Of 109 patients, 77 patients (33 men and 44 women) presented with acute SAH and 32 patients (9 men and 23 women) were treated for incidental aneurysms. Seventeen (22 %) of 77 patients presenting with acute SAH had evidence of acute (within 72 h after SAH ictus) CVS. In 16 of 17 (94.1 %) patients, this vasospasm was observed immediately after treatment and was therefore termed iCVS. Eleven (30 %) of 36 patients undergoing clipping and 5 (14 %) of 36 patients with endovascular aneurysm occlusion had iCVS (p = 0.07). Patients presenting with acute SAH had a higher incidence of iCVS than patients undergoing elective aneurysm treatment (p = 0.02). Only one patient (3 %) had iCVS in the elective treatment group whereas 16 (20 %) had iCVS after SAH. The incidence of dCVS, delayed ischemic neurological deficits (DNDs), and poor outcome in patients presenting with iCVS during surgical treatment of ruptured aneurysms was 56 % (p = 0.001), 63 % (p = 0.02), and 38 % (p = 0.14), respectively. CONCLUSION: APV exists and is a common finding in patients with SAH. Further studies are warranted to correlate the presence of APV with postoperative ischemia, dCVS, and outcome.

Craniotomy without flap replacement for ruptured intracranial aneurysms to reduce ischemic brain injury: a preliminary safety and feasibility analysis.

BACKGROUND: Cortical and subcortical brain ischemia following aneurysmal subarachnoid hemorrhage (aSAH) remains a central challenge in improving patient outcome. Generally the bone flap is replaced after surgical clipping and no decompression is practiced in endovascularly treated patients. The aim of this preliminary safety and feasibility study is to clarify whether a first-line decompression would improve brain perfusion and salvage more tissue at risk in patients who developed delayed vasospasm. In addition, we assessed whether the risks involved with a second surgery to replace the bone flap would affect patient outcome. METHODS: We retrospectively analyzed patients with aSAH who underwent surgical clipping and developed cerebral vasospasm from 2009 to 2012 at our institution. We selected cases where the bone flap was not replaced at initial surgery and needed a second procedure for bone flap replacement. Primary end points were new delayed ischemic neurological deficits (DINDs), the extent of brain infarctions, and patient functional outcome. Secondary end points were hazards of the second procedure for bone replacement. RESULTS: We identified six patients in whom the surgeon chose not to replace the bone flap. In four patients, this was a pterional bone flap (standard), and in two patients it was a larger frontotemporoparietal flap. Despite the limited extent of the craniotomy, only one patient (16 %) required additional decompression. Two patients (33%) developed DINDs and five patients (83 %) showed delayed cerebral infarctions on computed tomography. Of those, three patients showed good outcome (Glasgow Outcome Scale score >4 and modified Rankin Scale score <3). No complications or new neurological deficits occurred during the second surgery for bone replacement. CONCLUSIONS: To date, no standardized criteria exist to decide whether the bone flap should be removed or replaced at initial surgery. Our single-center experience in a limited number of patients reveals a pattern with respect to initial clinical parameters and imaging findings that might be a first step in developing standardized decision parameters. This may prevent secondary surgery for decompression in deleterious conditions during the vasospasm phase. Based on these findings, we have developed a protocol for a prospective study that will further investigate the benefits of this management.

The rabbit blood shunt subarachnoid haemorrhage model.

The recently introduced rabbit blood shunt subarachnoid haemorrhage model is based on the two standard procedures of subclavian artery cannulation and transcutaneous cisterna magna puncture. An extracorporeal shunt placed in between the arterial system and the subarachnoid space allows examiner-independent SAH in a closed cranium. Despite its straightforwardness, it is worth examining some specific features and characteristics of the model. We outline technical considerations to successfully perform the model with minimal mortality and morbidity. In addition, we discuss outcome measures, advantages and limitations, and the applicability of the model for the study of early brain injury and delayed cerebral vasospasm after SAH.

Effect of crystallinity on electrostatic charging in dry powder inhaler formulations.

PURPOSE: This study aimed to characterize inherent charge generated by micron-sized drug-only formulations of amorphous and crystalline salbutamol sulfate (SS). METHODS: Amorphous SS was produced by spray-drying whilst crystalline SS was produced by conditioning spray-dried SS with supercritical CO2 and menthol. Electrostatic charge of the powders was characterized in two ways. Firstly, the charge profile of the aerosols dispersed from an Aerolizer® was measured using a modified Electrostatic Low Pressure Impactor (ELPI™). Secondly, the net charge of the bulk powders generated from tumbling in containers composed of different materials (polyethylene, polyvinyl chloride, Teflon, nylon and stainless steel) was measured by a Faraday pail. RESULTS: Following aerosolization, crystalline SS appeared to show more consistent charging and mass deposition than amorphous SS. In the tumbling experiment crystalline SS had a significant correlation between net charge and work function, which was absent in amorphous SS. This may be due to the long-range crystal packing which was reflected as more predictable charging. In addition, the polarity of charging was attributed to the arrangement of SS molecules in the crystal lattice. CONCLUSIONS: The effect of crystallinity on the electrostatic charge behavior of inhalable micron-sized spherical drug particles with well-defined particle size distribution was investigated for the first time. The knowledge gained may assist in the development of optimized inhaled pharmaceutical products.