Embolic Agent Choice in Middle Meningeal Artery Embolization as Primary or Adjunct Treatment for Chronic Subdural Hematoma: A Systematic Review and Meta-analysis.

BACKGROUND: Middle meningeal artery embolization is an emerging treatment option for chronic subdural hematomas. PURPOSE: Our aim was to assess outcomes following middle meningeal artery embolization by different techniques, including in comparison with traditional surgical methods. DATA SOURCES: We searched the literature databases from inception to March 2022. DATA SELECTION: We selected studies reporting outcomes after middle meningeal artery embolization as a primary or adjunctive treatment for chronic subdural hematoma. DATA ANALYSIS: We analyzed the risk of recurrence of chronic subdural hematoma, reoperation for recurrence or residual hematoma, complications, and radiologic and clinical outcomes using random effects modeling. Additional analyses were performed on the basis of whether middle meningeal artery embolization was used as the primary or adjunct treatment and by embolic agent type. DATA SYNTHESIS: Twenty-two studies were included with 382 patients with middle meningeal artery embolization and 1373 surgical patients. The rate of subdural hematoma recurrence was 4.1%. Fifty (4.2%) patients underwent a reoperation for a recurrent or residual subdural hematoma. Thirty-six (2.6%) experienced postoperative complications. The rates of good radiologic and clinical outcomes were 83.1% and 73.3%, respectively. Middle meningeal artery embolization was significantly associated with decreased odds of subdural hematoma reoperation (OR = 0.48; 95% CI, 23.4-99.1; P = .047) compared with surgery. The lowest rates of subdural hematoma radiologic recurrence, reoperation, and complications were observed among patients receiving embolization with Onyx, whereas good overall clinical outcome occurred most commonly with combined polyvinyl alcohol and coils. LIMITATIONS: A limitation was the retrospective design of studies included. CONCLUSIONS: Middle meningeal artery embolization is safe and effective, either as a primary or adjunctive treatment. Treatment using Onyx seems to yield lower rates of recurrence, rescue operation, and complications whereas particles and coils produce good overall clinical outcomes.

Thrombectomy Using the EmboTrap Clot-Retrieving Device for the Treatment of Acute Ischemic Stroke: A Glimpse of Clinical Evidence.

BACKGROUND: The EmboTrap Recanalization Device is a novel stent retriever for thrombectomy in the setting of acute ischemic stroke due to large-vessel occlusion. PURPOSE: Our aim was to summarize the safety and efficacy of the EmboTrap Recanalization Device in acute ischemic stroke-large-vessel occlusion through a systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE, the Cochrane Library, Web of Science, and Google Scholar were searched up to April 2022. STUDY SELECTION: Nine observational studies using the EmboTrap Recanalization Device were selected. DATA ANALYSIS: We adapted effect size with 95% CIs for dichotomous data. P value <.05 was statistically significant. DATA SYNTHESIS: The estimated rate of successful recanalization (modified TICI 2b-3) was 90% (95% CI, 86%-95%; I 2 = 82.4%); 90-day favorable outcome (mRS 0-2), 53% (95% CI, 42%-63%; I 2 = 88.6%); modified first-pass effect, 43% (95% CI, 35%-51%; I 2 = 63.7%); and first-pass effect, 36% (95% CI, 29%-46%; I 2 = 10.7%). The rate of any intracerebral hemorrhage was 19% (95% CI, 16%-22%; I 2 = 0.0%); symptomatic intracerebral hemorrhage, 5% (95% CI, 1%-8%; I 2 = 84.6%); and 90-day mortality, 14% (95% CI, 9%-19%; I 2 = 79.3%). Subgroup analysis showed higher rates of complete recanalization for EmboTrap II than for the EmboTrap System. LIMITATIONS: The included studies are single-arm without direct comparison with other stent retrievers. Some of the studies recruited had a small sample size and were limited by the retrospective study design. In addition, the uncertain heterogeneity among studies was high. CONCLUSIONS: The EmboTrap Recanalization Device is safe and efficient in treating acute ischemic stroke due to large-vessel occlusion.

Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort.

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.

The LDL receptor binding domain of apolipoprotein E directs the relative orientation of its C-terminal segment in reconstituted nascent HDL.

Apolipoprotein E (apoE) (299 residues) is a highly helical protein that plays a critical role in cholesterol homeostasis. It comprises a four-helix bundle N-terminal (NT) and a C-terminal (CT) domain that can exist in lipid-free and lipid-associated states. In humans, there are two major apoE isoforms, apoE3 and apoE4, which differ in a single residue in the NT domain, with apoE4 strongly increasing risk of Alzheimer's disease (AD) and cardiovascular diseases (CVD). It has been proposed that the CT domain initiates rapid lipid binding, followed by a slower NT domain helix bundle opening and lipid binding to yield discoidal reconstituted high density lipoprotein (rHDL). However, the contribution of the NT domain on the CT domain organization in HDL remains poorly understood. To understand this, we employed Cys-specific cross-linking and spatially-sensitive fluorophores in the NT and CT domains of apoE3 and apoE4, and in isolated CT domain. We noted that the helices in isolated CT domain are oriented parallel to those in the neighboring molecule in rHDL, whereas full length apoE3 and apoE4 adopt either an anti-parallel or hairpin-like organization. It appears that the bulky NT domain determines the spatial organization of its CT domain in rHDL, a finding that has significance for apoE4, which is more susceptible to proteolytic cleavage in AD brains, showing increased accumulation of neurotoxic NT and CT fragments. We envisage that the structural organization of HDL apoE would have profound functional consequences in its ability to regulate cholesterol homeostasis in AD and CVD.

IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies.

BACKGROUND: Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents. PATIENTS AND METHODS: Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0. RESULTS: A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab. CONCLUSIONS: IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies.

CTA Protocols in a Telestroke Network Improve Efficiency for Both Spoke and Hub Hospitals.

BACKGROUND AND PURPOSE: Telestroke networks support screening for patients with emergent large-vessel occlusions who are eligible for endovascular thrombectomy. Ideal triage processes within telestroke networks remain uncertain. We characterize the impact of implementing a routine spoke hospital CTA protocol in our integrated telestroke network on transfer and thrombectomy patterns. MATERIALS AND METHODS: A protocol-driven CTA process was introduced at 22 spoke hospitals in November 2017. We retrospectively identified prospectively collected patients who presented to a spoke hospital with National Institutes of Health Stroke Scale scores ≥6 between March 1, 2016 and March 1, 2017 (pre-CTA), and March 1, 2018 and March 1, 2019 (post-CTA). We describe the demographics, CTA utilization, spoke hospital retention rates, emergent large-vessel occlusion identification, and rates of endovascular thrombectomy. RESULTS: There were 167 patients pre-CTA and 207 post-CTA. The rate of CTA at spoke hospitals increased from 15% to 70% (P < .001). Despite increased endovascular thrombectomy screening in the extended window, the overall rates of transfer out of spoke hospitals remained similar (56% versus 54%; P = .83). There was a nonsignificant increase in transfers to our hub hospital for endovascular thrombectomy (26% versus 35%; P = .12), but patients transferred >4.5 hours from last known well increased nearly 5-fold (7% versus 34%; P < .001). The rate of endovascular thrombectomy performed on patients transferred for possible endovascular thrombectomy more than doubled (22% versus 47%; P = .011). CONCLUSIONS: Implementation of CTA at spoke hospitals in our telestroke network was feasible and improved the efficiency of stroke triage. Rates of patients retained at spoke hospitals remained stable despite higher numbers of patients screened. Emergent large-vessel occlusion confirmation at the spoke hospital lead to a more than 2-fold increase in thrombectomy rates among transferred patients at the hub.

Quality characteristics of fortified silver carp surimi with soluble dietary fiber: Effect of apple pectin and konjac glucomannan.

The study focused on assessing quality parameters of the surimi incorporated with soluble dietary fibers apple pectin and konjac glucomannan at different levels. The results showed that apple pectin at 0.025% and konjac glucomannan at a 2% level exhibited improved gel-forming ability significantly (p < 0.05). SDS- PAGE revealed high molecular weight protein crosslinks in apple pectin treated surimi gels and disappearance of myosin bands in konjac glucomannan treated surimi gels. The water holding capacity of surimi was the highest when 0.075 g/100 g of apple pectin was added. Konjac glucomannan treated gels exhibited superior whiteness values. The analysis of soluble protein revealed that hydrophobic bonds increased in both the treatments. The hardness values of pectin gels enhanced as the level increased. Other TPA parameters are shown an inconsistent trend. It can be demonstrated that the incorporation of apple pectin and konjac glucomannan at a level of 0.025 and 2.0% may be a novel strategy to improve the gel strength of the surimi.

Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers.

Although 23% of world population is infected with Mycobacterium tuberculosis (M. tb), only 5-10% manifest the disease. Individuals surely exposed to M. tb that remain asymptomatic are considered potential latent TB (LTB) cases. Such asymptomatic M. tb.-exposed individuals represent a reservoir for active TB cases. Although accurate discrimination and early treatment of patients with active TB and asymptomatic M. tb.-exposed individuals are necessary to control TB, identifying those individuals at risk of developing active TB still remains a tremendous clinical challenge. This study aimed to characterize the differences in the serum metabolic profile specifically associated to active TB infected individuals or to asymptomatic M. tb.-exposed population. Interestingly, significant changes in a specific set of metabolites were shared when comparing either asymptomatic house-hold contacts of active TB patients (HHC-TB) or active TB patients (A-TB) to clinically healthy controls (HC). Furthermore, this analysis revealed statistically significant lower serum levels of aminoacids such as alanine, lysine, glutamate and glutamine, and citrate and choline in patients with A-TB, when compared to HHC-TB. The predictive ability of these metabolic changes was also evaluated. Although further validation in independent cohorts and comparison with other pulmonary infectious diseases will be necessary to assess the clinical potential, this analysis enabled the discrimination between HHC-TB and A-TB patients with an AUC value of 0.904 (confidence interval 0.81-1.00, p-value < 0.0001). Overall, the strategy described in this work could provide a sensitive, specific, and minimally invasive method that could eventually be translated into a clinical tool for TB control.

Preserving Access: A Review of Stroke Thrombectomy during the COVID-19 Pandemic.

Thrombectomy for large-vessel-occlusion stroke is a highly impactful treatment. The spread of coronavirus 19 (COVID-19) across the United States and the globe impacts access to this crucial intervention through widespread societal and institutional changes. In this document, we review the implications of COVID-19 on the emergency care of large-vessel occlusion stroke, reviewing specific infection-control recommendations, available literature, existing resources, and expert consensus. As a population, patients with large-vessel occlusion stroke face unique challenges during pandemics. These are broad in scope. Responses to these challenges through adaptation of stroke systems of care and with imaging, thrombectomy, and postprocedural care are detailed. Preservation of access to thrombectomy must be prioritized for its public health impact. While the extent of required changes will vary by region, tiered planning for both escalation and de-escalation of measures must be a part of each practice. In addition, preparations described serve as templates in the event of future pandemics.

Association between obesity in 4- to 7-year-old children and eight types of crime: a hierarchical linear modelling approach.

OBJECTIVE: Evidence of the association between childhood obesity and neighbourhood crime is inconclusive. Most previous studies have included children of all ages, and few have examined different types of crime. The objective of this study was to investigate the association between obesity and eight different types of crime (i.e. commercial robbery, street robbery, assault, other violence, commercial break and enter, residential break and enter, theft of vehicle and theft from vehicle) among 4- to 7-year-old children in a large western Canadian city. METHODS: Cross-sectional, epidemiological study (N = 10,069) using spatial analysis and hierarchical generalized linear modelling. The outcome variable was normal weight or obesity. The exposure variable was the distance between the child's residential postal code and the closest occurrence of each type of crime. RESULTS: Controlling for distance to the closest park, frequency of each type of crime in the child's neighbourhood and neighbourhood factors (proportion of visible minorities, education and median family income), there was no association between any of the crime types and childhood obesity. CONCLUSIONS: Crime did not contribute to obesity in this sample of 4- to 7-year-old children. Replication of this study in other jurisdictions would increase confidence in these results.

Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage.

OBJECTIVE: To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). METHODS: Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). RESULTS: Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. CONCLUSIONS: IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. SIGNIFICANCE: These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development.

Telestroke-the promise and the challenge. Part one: growth and current practice.

Acute ischemic stroke remains a major public health concern, with low national treatment rates for the condition, demonstrating a disconnection between the evidence of treatment benefit and delivery of this treatment. Intravenous thrombolysis and endovascular thrombectomy are both strongly evidence supported and exquisitely time sensitive therapies. The mismatch between the distribution and incidence of stroke presentations and the availability of specialist care significantly affects access to care. Telestroke, the use of telemedicine for stroke, aims to surmount this hurdle by distributing stroke expertise more effectively, through video consultation with and examination of patients in locations removed from specialist care. This is the first of a detailed two part review, and explores the growth and current practice of telestroke, including the specific role it plays in the assessment and management of patients after emergent large vessel occlusion.

Telestroke-the promise and the challenge. Part two-expansion and horizons.

Acute ischemic stroke remains a major public health concern, with low national treatment rates for the condition, demonstrating a disconnection between the evidence of treatment benefit and delivery of this treatment. Intravenous thrombolysis and endovascular thrombectomy are both strongly evidence supported and exquisitely time sensitive therapies. The mismatch between the distribution and incidence of stroke presentations and the availability of specialist care significantly affects access to care. Telestroke, the use of telemedicine for stroke, aims to surmount this hurdle by distributing stroke expertise more effectively, through video consultation with and examination of patients in locations removed from specialist care. This is the second of a two part review, and is focused on the challenges telestroke faces for wider adoption. It further details the anticipated evolution of this novel therapeutic platform, and the potential roles it holds in stroke prevention, ambulance based care, rehabilitation, and research.

Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders.

Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the blood-brain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1ß), IL-6, 1 L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGFß induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

Low-depth shotgun sequencing resolves complete mitochondrial genome sequence of Labeo rohita.

Labeo rohita, popularly known as rohu, is a widely cultured species in whole Indian subcontinent. In the present study, we used in-silico approach to resolve complete mitochondrial genome of rohu. Low-depth shotgun sequencing using Roche 454 GS FLX (Branford, Connecticut, USA) followed by de novo assembly in CLC Genomics Workbench version 7.0.4 (Aarhus, Denmark) revealed the complete mitogenome of L. rohita to be 16 606 bp long (accession No. KR185963). It comprised of 13 protein-coding genes, 22 tRNAs, 2 rRNAs and 1 putative control region. The gene order and organization are similar to most vertebrates. The mitogenome in the present investigation has 99% similarity with that of previously reported mitogenomes of rohu and this is also evident from the phylogenetic study using maximum-likelihood (ML) tree method. This study was done to determine the feasibility, accuracy and reliability of low-depth sequence data obtained from NGS platform as compared to the Sanger sequencing. Thus, NGS technology has proven to be competent and a rapid in-silico alternative to resolve the complete mitochondrial genome sequence, thereby reducing labors and time.

Assembly and variation analyses of Clarias batrachus mitogenome retrieved from WGS data and its phylogenetic relationship with other catfishes.

Whole genome sequencing (WGS) using next generation sequencing technologies paves the way to sequence the mitochondrial genomes with greater ease and lesser time. Here, we used the WGS data of Clarias batrachus, generated from Roche 454 and Ion Torrent sequencing platforms, to assemble the complete mitogenome using both de novo and reference based approaches. Both the methods yielded almost similar results and the best assembled mitogenome was of 16,510 bp size (GenBank Acc. No. KM259918). The mitogenome annotation resulted in 13 coding genes, 22 tRNA genes, 2 rRNA genes and one control region, and the gene order was found to be identical with other catfishes. Variation analyses between assembled and the reference (GenBank Acc. No. NC_023923) mitogenome revealed 51 variations. The phylogenetic analysis of coding DNA sequences and tRNA supports the monophyly of catfishes. Two SSRs were identified in C. batrachus mitogenome, out of which one was unique to this species. Based on the relative rate of gene evolution, protein coding mitochondrial genes were found to evolve at a much faster pace than the d-loop, which in turn are followed by the rRNAs; the tRNAs showed wide variability in the rate of sequence evolution, and on average evolve the slowest. Among the coding genes, ND2 evolves most rapidly. The variations present in the coding regions of the mitogenome and their comparative analyses with other catfish species may be useful in species conservation and management programs.