One step 4x and 12x 3D-ExM: robust super-resolution microscopy in cell biology.

Super-resolution microscopy has become an indispensable tool across diverse research fields, offering unprecedented insights into biological architectures with nanometer scale resolution. Compared to traditional nanometer-scale imaging methods such as electron microscopy, super-resolution microscopy offers several advantages, including the simultaneous labeling of multiple target biomolecules with high specificity and simpler sample preparation, making it accessible to most researchers. In this study, we introduce two optimized methods of super-resolution imaging: 4-fold and 12-fold 3D-isotropic and preserved Expansion Microscopy (4x and 12x 3D-ExM). 3D-ExM is a straightforward expansion microscopy method featuring a single-step process, providing robust and reproducible 3D isotropic expansion for both 2D and 3D cell culture models. With standard confocal microscopy, 12x 3D-ExM achieves a lateral resolution of under 30 nm, enabling the visualization of nanoscale structures, including chromosomes, kinetochores, nuclear pore complexes, and Epstein-Barr virus particles. These results demonstrate that 3D-ExM provides cost-effective and user-friendly super-resolution microscopy, making it highly suitable for a wide range of cell biology research, including studies on cellular and chromatin architectures.

National trends and outcomes of hospital presentation mode for endovascular stroke treatment in the U.S.

BACKGROUND: The optimal triage strategy for patients suspected of acute ischemic stroke due to large vessel occlusion (LVO) remains debated. We explored trends in presentation mode and their outcomes for mechanical thrombectomy (MT) hospitalizations based on the National Inpatient Sample (NIS) database. METHODS: We retrospectively explored the NIS database from 2016 to 2020 for stroke hospitalizations with MT. We compared outcomes at discharge for MT hospitalizations with direct vs. transferred presentation. Outcomes comprised favorable discharge disposition (home without assistance), in-hospital mortality, and radiographic intracranial hemorrhage (ICH). RESULTS: This study included 100,865 patients undergoing MT, of whom 32,685 patients (32.4 %) were transferred (median age 71[60-81] years, 16775(51.2 %) women). The utilization of MT in the U.S. nearly doubled during the study period, whereas the proportion of in-hospital transfers for MT remained unchanged (32.1-33.2 %). White race, higher presenting NIHSS, hospital size, status, and location were independent predictors of transferred status. Transferred status was significantly associated with a lower likelihood of achieving favorable outcome (OR:0.80,95 % CI: [0.72,0.89],P<0.001) and a higher likelihood of ICH (OR:1.18, 95 % CI:[1.07,1.31],P=0.001), whereas no association was observed between presentation mode and in-hospital mortality (OR:1.07,95 % CI:[0.93,1.23],P=0.33). CONCLUSION: Patients with direct presentation for MT after a stroke had better discharge outcomes and a lower risk of hemorrhagic transformation compared to those who were transferred from another facility. Determining the optimal triage strategy for MT following LVO stroke is an insightful area for future clinical trials.

Prevalence, incidence, mortality and healthcare resource use for generalized pustular psoriasis, palmoplantar pustulosis and plaque psoriasis in England: a population-based cohort study.

BACKGROUND: Generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) are chronic inflammatory skin conditions. Accumulating evidence shows that GPP and PPP have different characteristics to plaque psoriasis and are distinct clinical entities. OBJECTIVES: To assess the epidemiology, comorbidities, mortality and healthcare use for patients in England with GPP and PPP versus those with plaque psoriasis. METHODS: We carried out a cohort study involving analyses of longitudinal electronic health record data in the Clinical Practice Research Datalink Aurum database and linked hospital and mortality data between 2008 and 2019. The primary study outcome was the incidence and prevalence rates of GPP, PPP and plaque psoriasis in England. Secondary outcomes included survival rates and healthcare resource use (HCRU) by disease type. RESULTS: We identified 373 patients with GPP, 1828 with PPP and 224 223 with plaque psoriasis. Mean (SD) age was 55.9 (18.6) years for patients with GPP, 51.5 (16.4) years for those with PPP and 48.5 (19.1) years for those with plaque psoriasis; 62.5% and 65.9% of patients with GPP and PPP, respectively, were women, vs. 49.4% of those with plaque psoriasis. About half of patients were overweight or obese at baseline (GPP 48.6%, PPP 56.0%, plaque psoriasis 45.9%). The incidence rates for GPP, PPP and plaque psoriasis were 0.25 [95% confidence interval (CI) 0.21-0.28], 2.01 (95% CI 1.92-2.11) and 103.2 (95% CI 102.5-103.9) per 100 000 person-years, respectively. From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, from 1.1 to 18.7 for PPP and from 1771.0 to 1903.8 for plaque psoriasis. Survival rates were lower for patients with GPP, particularly those who were > 55 years of age and those with a history of one or more comorbidities in each cohort. HCRU was lower in the cohort with plaque psoriasis and highest in the cohort with GPP, particularly among those who had more than one GPP flare. CONCLUSIONS: Our results provide further evidence that, in England, GPP is a distinct disease with different epidemiology, lower survival and higher HCRU than plaque psoriasis.

There are several different forms of the inflammatory skin disease called psoriasis. Plaque psoriasis is characterized by flaky or scaly patches of skin. Generalized pustular psoriasis ('GPP') causes red skin and painful pustules. Palmoplantar pustulosis ('PPP') affects the palms and soles. In this study, we used electronic health record data from general practices that contribute to a database in England called the Clinical Practice Research Datalink (CPRD). We did this to find out how common plaque psoriasis, GPP and PPP are in England and understand how people use healthcare services. The number of patients with these conditions increased between 2008 and 2019. In 2019, the most frequent condition was plaque psoriasis, followed by PPP and GPP. Among people with GPP, 3 out of 5 were women, 7 out of 10 also had a diagnosis of plaque ­psoriasis and 7 out of 10 had other illnesses. Among people with PPP, about 2 out of 3 were women, 1 out of 3 also had a diagnosis of plaque psoriasis and 2 out of 3 had other illnesses. Overall survival was lowest for people with GPP, particularly those who were older than 55 years of age and those with other illnesses. We found that a higher proportion of patients with GPP were admitted to hospital and visited A&E than those with PPP or plaque psoriasis. These patients also had more outpatient and A&E visits every year. Our results suggest that GPP has a different epidemiology than plaque psoriasis, and patients with GPP use more healthcare services and have a higher mortality rate.

National trends in the endovascular and surgical treatment of idiopathic intracranial hypertension.

BACKGROUND: The pattern of surgical treatments for Idiopathic Intracranial Hypertension (IIH) in the United States is not well-studied, specifically the trend of utilizing endovascular venous stenting (EVS) as an emerging technique. METHODS: In this cross-sectional study, we aimed to explore the national trend of utilizing different procedures for the treatment of IIH including EVS, Optic Nerve Sheath Fenestration (ONSF), and CSF Shunting, with a focus on novel endovascular procedures. Moreover, we explored rates of 90-day readmission and length of hospital stay following different procedures, besides the effects of sociodemographic and clinical parameters on procedure choice. RESULTS: 36,437 IIH patients were identified from records between 2010 and 2018. Those in the EVS group were 29 years old on average, and 93.4 % were female. Large academic hospital setting was independently associated with higher EVS utilization, while other factors were not predictive of procedure choice. The proportion of EVS use in IIH hospitalizations increased significantly from 2010 to 2018 (P < 0.001), while there was a relative decline in the frequency of shunting procedures (P = 0.001), with ONSF utilization remaining stable (P = 0.39). The rate of 90-day readmission and length of hospital stay were considerably lower following EVS compared to other procedures (Ps < 0.001). CONCLUSION: This study presents novel population-level data on national trends in the frequency and outcome of EVS for IIH therapy. EVS was associated with shorter length of hospital stays and fewer readmission rates. In addition, a continuous increase in venous stenting compared to other procedures suggests an increasing role for endovascular therapies in IIH.

Late-Onset COL4A1 Mutation with Recurrent Ischemic and Hemorrhagic Strokes.

INTRODUCTION: Mutations in type IV collagen gene COL4A1 are identified as a cause of autosomal dominant cerebrovascular disease. We report an unusual late-onset presentation. CASE REPORT: A 64-year-old male was found to have an ischemic stroke and diffuse white matter changes. Genetic testing revealed COL4A1 gene mutation of heterozygous Alu insertion at intron 16. Alu elements are known as "jumping genes," and Alu insertion is not previously reported in COL4A1 genetic syndromes. Our case has attributes consistent with a heritable leukoencephalopathy: (1) late-onset presentation, (2) intracerebral hemorrhages and microbleeds, (3) bilateral symmetrical leukoencephalopathy, (4) recurrence over a short period of time, (5) bilateral retinopathy, and (6) family history notable for brain aneurysm, kidney diseases, and early-onset stroke. CONCLUSIONS: Although the majority of COL4A1 genetic syndromes featuring cerebral small vessel disease are in children, this case highlights a late-onset patient with key features of COL4A1 syndromes associated with a heterozygous Alu intronic insertion.

Plateauing atrial fibrillation burden in acute ischemic stroke admissions in the United States from 2010 to 2020.

BACKGROUND: Utilization of oral anticoagulants for acute ischemic stroke (AIS) prevention in patients with atrial fibrillation (AF) increased in the United States over the last decade. Whether this increase has been accompanied by any change in AF prevalence in AIS at the population level remains unknown. The aim of this study is to evaluate trends in AF prevalence in AIS hospitalizations in various age, sex, and racial subgroups over the last decade. METHODS: We used data contained in the 2010-2020 National Inpatient Sample to conduct a serial cross-sectional study. Primary AIS hospitalizations with and without comorbid AF were identified using International Classification of Diseases Codes. Joinpoint regression was used to compute annualized percentage change (APC) in prevalence and to identify points of change in prevalence over time. RESULTS: Of 5,190,148 weighted primary AIS hospitalizations over the study period, 25.1% had comorbid AF. The age- and sex-standardized prevalence of AF in AIS hospitalizations increased across the entire study period 2010-2020 (average APC: 1.3%, 95% confidence interval (CI): 0.8-1.7%). Joinpoint regression showed that prevalence increased in the period 2010-2015 (APC: 2.8%, 95% CI: 1.9-3.9%) but remained stable in the period 2015-2020 (APC: -0.3%, 95% CI: -1.0 to 1.9%). Upon stratification by age and sex, prevalence increased in all age/sex groups from 2010 to 2015 and continued to increase throughout the entire study period in hospitalizations in men 18-39 years (APC: 4.0%, 95% CI: 0.2-7.9%), men 40-59 years (APC: 3.4%, 95% CI: 1.9-4.9%) and women 40-59 years (APC: 4.4%, 95% CI: 2.0-6.8%). In contrast, prevalence declined in hospitalizations in women 60-79 (APC: -1.0%, 95% CI: -0.5 to -1.5%) and women ⩾ 80 years over the period 2015-2020 but plateaued in hospitalizations in similar-aged men over the same period. CONCLUSION: AF prevalence in AIS hospitalizations in the United States increased over the period 2010-2015, then plateaued over the period 2015-2020 due to declining prevalence in hospitalizations in women ⩾ 60 years and plateauing prevalence in hospitalizations in men ⩾ 60 years.

Remdesivir, dexamethasone and angiotensin-converting enzyme inhibitors use and mortality outcomes in COVID-19 patients with concomitant troponin elevation.

BACKGROUND: There are indications that viral myocarditis, demand ischemia, and renin-angiotensin-aldosterone system pathway activation play essential roles in troponin elevation in coronavirus disease 2019 (COVID-19) patients. Antiviral medications and steroids are used to treat viral myocarditis, but their effect in patients with elevated troponin, possibly from myocarditis, has not been studied. AIM: To evaluate the effect of dexamethasone, remdesivir, and angiotensin-converting enzyme (ACE) inhibitors (ACEI) on mortality in COVID-19 patients with elevated troponin. METHODS: Our retrospective observational study involved 1788 COVID-19 patients at seven hospitals in Southern California, United States. We did a backward selection Cox multivariate regression analysis to determine predictors of mortality in our study population. Additionally, we did a Kaplan Meier survival analysis in the subset of patients with elevated troponin, comparing survival in patients that received dexamethasone, remdesivir, and ACEI with those that did not. RESULTS: The mean age was 66 years (range 20-110), troponin elevation was noted in 11.5% of the patients, and 29.9% expired. The patients' age [hazard ratio (HR) = 1.02, P < 0.001], intensive care unit admission (HR = 5.07, P < 0.001), and ventilator use (HR = 0.68, P = 0.02) were significantly associated with mortality. In the subset of patients with elevated troponin, there was no statistically significant difference in survival in those that received remdesivir (0.07), dexamethasone (P = 0.63), or ACEI (P = 0.8) and those that did not. CONCLUSION: Although elevated troponin in COVID-19 patients has been associated with viral myocarditis and ACE II receptors, conventional viral myocarditis treatment, including antiviral and steroids, and ACEI did not show any effect on mortality in these patients.

A protocol for isolating and imaging large extracellular vesicles or midbody remnants from mammalian cell culture.

Traditionally, midbody remnants (MBRs) are isolated from cell culture medium using ultracentrifugation, which is expensive and time consuming. Here, we present a protocol for isolating MBRs or large extracellular vesicles (EVs) from mammalian cell culture using either 1.5% polyethylene glycol 6000 (PEG6000) or PEG5000-coated gold nanoparticles. We describe steps for growing cells, collecting media, and precipitating MBRs and EVs from cell culture medium. We then detail characterization of MBRs through immunofluorescent antibody staining and immunofluorescent imaging.

Comparison of Different Reconstruction Flap for Maxillofacial Region: An Original Research.

Introduction: Large chunks of the tissue are sacrificed during the surgical procedures for the treatment if oral cancers. Our goal was to assess the viability of "Buccal reconstruction using the anterolateral thigh (ALT) flaps, platysma myocutaneous (PM), and radial forearm free (RFF)". Material and Methods: Sixty subjects were included in this investigation, and they were divided into 3 groups. The follow-up as accompanied for six months. Comparisons were made for the time for the operations, reduction in the width of the mouth opening and the survival rates of the flaps. The data that was collected for the above two parameters and compared for the significance using the ANOVA, keeping P < 0.05 as significant. Results: In the subjects with the PM, the width of the mouth opening reduced comparatively greater than that of the subjects who received other two flaps. The reduction in the mouth opening in the PM was significantly greater compared to that of the ALT and RFF. Survival was greater for the groups ALT and RFF compared to PM. Time of the surgery was the greatest for the ALT and least for the PF. Conclusion: The observations point to the fact that the PF requires more time than that of the other two flaps. The survival was however better for the ALT and RFF. Further research is suggested for suggesting an appropriative flap design.

Assessment of Parental Satisfaction with Various Aesthetic Crowns Among Children of Various Age Groups: An Original Research.

Introduction: Over the past ten years, parents have become more involved in choosing the aesthetic restorations for their ward. The strip crown and the prefabricated zirconia crown are some of the common anterior aesthetic complete crowns. The purpose of this study is to examine parental satisfaction over a one-year period in children aged three to five with "Strip Crowns" versus "Preformed Primary Anterior Zirconia Crowns". Materials and Procedures: Current study included 20 children. Among them their both central incisors were restored using the two varieties of crowns. The distribution of participants was done using the permuted block randomization approach. Twenty parents who participated were called back over a year to complete the questionnaire. The data was collected and compared while the statistics are deemed significant at P < 0.05. Results: Both restoration options received positive feedback from parents. With strip crowns, there was a statistically significant correlation between overall happiness and longevity of the restoration (P = 0.003) and color (P = 0.033) in zirconium crowns. The parents who expressed less pleasure with the strip crowns' longevity and the color of zirconia crowns did so overall, though. Conclusion: In conclusion, prefabricated primary anterior zirconia crowns were more popular with parents than strip crowns. All other criteria were about equally well-liked by parents, with the exception of longevity, which was more common for zirconia crowns.

3D printed elastomeric biomaterial mitigates compaction during in vitro vasculogenesis.

A key parameter for the success of most cellular implants is the formation of a complete and comprehensive intra-implant vessel network. Pre-vascularization, the generation of vessel structures in vitro prior to transplantation, provides accelerated implant perfusion via anastomosis, but scalability and ease of integration hinder clinical translation. For fibrin-based vasculogenesis approaches, the remodeling and degradation of the fragile, hydrogel matrix during the formation of vessel-like structures results in rapid, cell-mediated construct compaction leading to dense, capillary-like structures with ineffective network coverage. To resolve these challenges, vasculogenic hydrogels were embedded within a highly porous, biostable three-dimensional (3D) polydimethylsiloxane (PDMS) scaffold. Using reverse-casting of 3D-printed molds, scaffolds exhibited highly interconnected and reproducible pore structures. Pore size was optimized via in vivo screening of intra-device angiogenesis. The inclusion of the PDMS frame with vasculogenic hydrogels significantly reduced fibrin compaction in vitro, resulting in easily manipulated constructs with predictable dimensionality and increased surface area compared to fibrin hydrogel alone. Globally, vascular morphogenesis was altered by the PDMS frame, with significantly larger and less dense network structures. Vasculogenic proteomic evaluation showed a temporal impact of the addition of the PDMS frame, indicating altered cellular proliferation and migration signaling. This work establishes a platform for improving the generation of translational pre-vascularized networks for greater flexibility to meet the needs of clinically scaled, engineered tissues. STATEMENT OF SIGNIFICANCE: Competent intra-implant vascularization is a significant issue hindering the success of engineered tissues. Pre-vascularization approaches, whereby a vascular network is formed in vitro and subsequently implanted into the host to anastomose, is a promising approach but it is limited by the compacted, dense, and poorly functional microcapillary structures typically formed using soft hydrogels. Herein, we have uniquely addressed this challenge by adding a 3D printed PDMS-based open framework structure that serves to prevent hydrogel compaction. Globally, we observed distinct differences in overall construct geometry, vascular network density, compaction, and morphogenesis, indicating that this PDMS framework lead to elevated maturity of this in vitro network while retaining its global dimensions. Overall, this novel approach elevates the translational potential of pre-vascularized constructs.

Demographic Disparities in the Incidence, Clinical Characteristics, and Outcome of Posterior Reversible Encephalopathy Syndrome in the United States.

OBJECTIVES: To estimate age-specific, sex-specific, and race-specific incidence of posterior reversible encephalopathy syndrome (PRES) in the United States. METHODS: We conducted a retrospective cohort study using the State Inpatient Database of Florida (2016-2019), Maryland (2016-2019), and New York (2016-2018). All new cases of PRES in adults (18 years or older) were combined with Census data to compute incidence. We evaluated the generalizability of incident estimates to the entire country using the 2016-2019 National Readmissions Database (NRD). RESULTS: Across the study period, there were 3,716 incident hospitalizations for PRES in the selected states. The age-standardized and sex-standardized incidence of PRES was 2.7 (95% CI 2.5-2.8) cases/100,000/y. Incidence in female patients was >2 times that of male patients (3.7 vs 1.6 cases/100,000/y, p < 0.001). Incidence increased with age in both sexes (p-trend <0.001). Similar demographic distribution of first hospitalization for PRES was also noted in the entire country using the NRD. Age-standardized and sex-standardized PRES incidence in Black patients (4.2/100,000/y) was significantly greater than in Non-Hispanic White (2.7/100,000/y) and Hispanic patients (1.2/100,000/y) (p < 0.001 for pairwise comparisons). DISCUSSION: The incidence of PRES in the United States is approximately 3/100,000/y, but incidence in female patients is >2 times that of male patients. PRES incidence is higher in Black compared with non-Hispanic White and Hispanic patients.

Aneurysmal Subarachnoid Hemorrhage and Cardiac Related Fatality: Who Dies and Why?

Medical complications are a notable source of in-hospital death following aneurysmal subarachnoid hemorrhage (aSAH). However, there is a paucity of literature examining medical complications on a national scale. This study uses a national dataset to analyze the incidence rates, case fatality rates, and risk factors for in-hospital complications and mortality following aSAH. We found that the most common complications in aSAH patients (N = 170, 869) were hydrocephalus (29.3%) and hyponatremia (17.3%). Cardiac arrest was the most common cardiac complication (3.2%) and was associated with the highest case fatality rate overall (82%). Patients with cardiac arrest also had the highest odds of in-hospital mortality [odds ratio (OR), 22.92; 95% confidence interval (CI), 19.24-27.30; P < 0.0001], followed by patients with cardiogenic shock (OR, 2.96; 95% CI, 2.146-4.07; P < 0.0001). Advanced age and National Inpatient Sample-SAH Severity Score were found to be associated with an increased risk of in-hospital mortality (OR, 1.03; 95% CI, 1.03-1.03; P < 0.0001 and OR, 1.70; 95% CI, 1.65-1.75; P < 0.0001, respectively). Renal and cardiac complications are significant factors to consider in aSAH management, with cardiac arrest being the strongest indicator of case fatality and in-hospital mortality. Further research is needed to characterize factors that have contributed to the decreasing trend in case fatality rates identified for certain complications.

Inpatient cardiovascular outcomes in patients with cancer affected by viral influenza infection.

BACKGROUND: Influenza disproportionately affects individuals with underlying comorbidities. Long-term follow-up studies have shown that patients with cancer with influenza have higher mortality. However, very little is known about the in-hospital mortality and cardiovascular outcomes of influenza infection in cancer hospitalisations. METHODS: We compared the in-hospital mortality and cardiovascular outcomes in patients with cancer with and without influenza by screening the National Inpatient Sample from 2015 to 2017. A total of 9 443 421 hospitalisations with any cancer were identified, out of which 14 634 had influenza while 9 252 007 did not. A two-level hierarchical multivariate logistic regression analysis adjusted for age, sex, race, hospital type and relevant comorbidities was performed. RESULTS: The group with cancer and influenza had higher in-hospital mortality (OR 1.08; 95% CI 1.003 to 1.16; p=0.04), acute coronary syndromes (OR 1.74; 95% CI 1.57 to 1.93; p<0.0001), atrial fibrillation (OR 1.24; 95% CI 1.18 to 1.29; p<0.0001) and acute heart failure (OR 1.41; 95% CI 1.32 to 1.51; p<0.0001). CONCLUSION: Patients with cancer affected by influenza have higher in-hospital mortality and a higher prevalence of acute coronary syndrome, atrial fibrillation and acute heart failure.

Ruptured arteriovenous malformation mortality: Incidence, risk factors, and inpatient outcome score.

BACKGROUND: Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH. OBJECTIVE: We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score. METHODS: This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. RESULTS: We identified 6496 patients with ruptured AVMs comparing them to 627,185 admitted with ICH. Mortality was lower for ruptured AVMs (11%) compared to ICH (22%) [p < 0.01]. Mortality associated factors were liver disease (OR 2.64, CI 1.81-3.85, p < .001), diabetes mellitus (OR 2.42, CI 1.38-4.22, p = 0.002), alcohol abuse (OR 1.81, CI 1.31-2.49, p = 0.001), hydrocephalus (OR 3.35 CI 2.81-4.00, p < 0.001), cerebral edema (OR 1.5, 1.25-1.85, p < 0.001), cardiac arrest (OR 15, CI 7.9-30, p < 0.001), and pneumonia (OR 1.93, CI 1.51-2.47, p < 0.001). A 0-5 ruptured AVM mortality score was developed: Cardiac arrest (=3), age >60 (=1), Black race (=1), chronic liver failure (=1) diabetes mellitus (=1), pneumonia (=1), alcohol abuse (=1) and cerebral edema (=1). Mortality increased with score. No patient with 5 or more points survived. CONCLUSION: The Ruptured AVM Mortality Score allows for risk stratification on patients with ICH due to ruptured AVM. This scale could prove useful in prognostication and patient education.

Aneurysmal subarachnoid hemorrhage in pregnancy: National trends of treatment, predictors, and outcomes.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a rare event associated with significant pregnancy-associated maternal and neonatal morbidity and mortality. The optimal treatment strategy and clinical outcome of aSAH in pregnancy remains unclear. We aimed to investigate the treatment utilizations and outcomes of aSAH in pregnant people. METHODS: Using the 2010-2018 National Inpatient Sample, we identified all birth hospitalizations of women between ages of 18 to 45 associated with subarachnoid hemorrhage and aneurysm treatment were included. Multivariate analyses were used to evaluate the effect of pregnancy state, mode of treatment of aneurysms, severity of subarachnoid hemorrhage on mortality and discharge destination of this cohort. Trends in mode of treatment utilized for aneurysmal treatment in this time interval was evaluated. RESULTS: 13,351 aSAH with treatment were identified, of which 440 were associated with pregnancy. There was no significant difference in mortality or rate of discharge to home in pregnancy related hospitalization. Worse aSAH severity, chronic hypertension, and smaller hospital size was associated with significantly higher rate of mortality from aSAH during pregnancy. Worse aSAH severity was associated with lower rate of discharge to home. Like the non-pregnant cohort, the treatment of ruptured aneurysms in pregnancy are increasingly through endovascular approaches. The mode of treatment does not change the mortality or discharge destination. CONCLUSIONS: Pregnancy does not alter mortality or the discharge destination for aSAH. Ruptured aneurysms during pregnancy are increasingly treated endovascularly. Mode of aneurysm treatment does not affect mortality or discharge destination in pregnancy.

Rigorous and rapid evidence assessment in digital health with the evidence DEFINED framework.

Dozens of frameworks have been proposed to assess evidence for digital health interventions (DHIs), but existing frameworks may not facilitate DHI evidence reviews that meet the needs of stakeholder organizations including payers, health systems, trade organizations, and others. These organizations may benefit from a DHI assessment framework that is both rigorous and rapid. Here we propose a framework to assess Evidence in Digital health for EFfectiveness of INterventions with Evaluative Depth (Evidence DEFINED). Designed for real-world use, the Evidence DEFINED Quick Start Guide may help streamline DHI assessment. A checklist is provided summarizing high-priority evidence considerations in digital health. Evidence-to-recommendation guidelines are proposed, specifying degrees of adoption that may be appropriate for a range of evidence quality levels. Evidence DEFINED differs from prior frameworks in its inclusion of unique elements designed for rigor and speed. Rigor is increased by addressing three gaps in prior frameworks. First, prior frameworks are not adapted adequately to address evidence considerations that are unique to digital health. Second, prior frameworks do not specify evidence quality criteria requiring increased vigilance for DHIs in the current regulatory context. Third, extant frameworks rarely leverage established, robust methodologies that were developed for non-digital interventions. Speed is achieved in the Evidence DEFINED Framework through screening optimization and deprioritization of steps that may have limited value. The primary goals of Evidence DEFINED are to a) facilitate standardized, rapid, rigorous DHI evidence assessment in organizations and b) guide digital health solutions providers who wish to generate evidence that drives DHI adoption.

Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X1, Span 40; X2, and sonication time; X3) on the responses (particle size, Y1, and entrapment efficiency, Y2). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (-49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (p < 0.01) between niosomal gel formulation and control. Greater flux (p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (p < 0.005), with ~3 folds higher Cmax and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.

Complication Rates Following Cerebral and Coronary Angiography: Nationwide Analysis 2008-2014.

Catheter-based angiography is an essential procedure for the diagnosis and treatment of vascular complications in patients. Since cerebral and coronary angiography are similar techniques that utilize the same access sites and general principles, the associated risks overlap and should be identified to help direct patient care. The purpose of this study was to determine complication rates in a combined cohort of cerebral and coronary angiography patients, as well as conduct a comparative analysis of coronary and cerebral angiography complications. The National Inpatient Sample was queried from 2008 to 2014 to identify patients who underwent coronary or cerebral angiography. After assessment of baseline characteristics, complication rates, and disposition in the combined cohort, propensity matching was utilized to create sub-cohorts of coronary and cerebral angiography patients based on demographics and comorbidities. Comparative analysis of procedural complications and disposition was then performed. A total of 3,763,651 hospitalizations were included in our study cohort (3,505,715 coronary angiographies and 257,936 cerebral angiographies). The median age was 62.9 years, with females being 46.42%. The most prevalent comorbidities in the overall cohort were hypertension (69.92%), coronary artery disease (69.48%), smoking (35.64%), and diabetes mellitus (35.13%). Propensity matching demonstrated that the cerebral angiography cohort had lower rates of acute and unspecified renal failure (5.4% vs 9.2%, OR 0.57, 95% CI, 0.53-0.61, P < 0.001), hemorrhage/hematoma formation (0.8% vs 1.3%, OR 0.63, 95% CI, 0.54-0.73, P < 0.001), and equivalent rates of retroperitoneum hematoma formation (0.03% vs 0.04%, OR 1.49, 95% CI, 0.76-2.90, P = 0.247) and arterial embolism/ thrombus formation (0.3% vs 0.3%, OR 1.01, 95% CI, 0.81-1.27, P = 0.900). Our study showed both cerebral and coronary angiography have generally low rates of procedural complications. Matched cohort analysis demonstrated that cerebral angiography patients are at no greater risk for complications than coronary angiography patients.