Trends in Demographic and Geographic Disparities in Stroke Mortality Among Older Adults in the United States.

BACKGROUND: Stroke is a leading cause of morbidity and mortality in the United States among older adults. However, the impact of demographic and geographic risk factors remains ambiguous. A clear understanding of these associations and updated trends in stroke mortality can influence health policies and interventions. METHODS: This study characterizes stroke mortality among older adults (age ≥55) in the US from January 1999 to December 2020, sourcing data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. Segmented regression was used to analyze trends in crude mortality rate and age-adjusted mortality rate (AAMR) per 100,000 individuals stratified by stroke subcategory, sex, ethnicity, urbanization, and state. RESULTS: A total of 3,691,305 stroke deaths occurred in older adults in the US between 1999 and 2020 (AAMR = 233.3), with an overall decrease in AAMR during these years. The highest mortality rates were seen in nonspecified stroke (AAMR = 173.5), those 85 or older (crude mortality rate1276.7), men (AAMR = 239.2), non-Hispanic African American adults (AAMR = 319.0), and noncore populations (AAMR = 276.1). Stroke mortality decreased in all states from 1999 to 2019 with the greatest and least decreases seen in California (-61.9%) and Mississippi (-35.0%), respectively. The coronavirus pandemic pandemic saw increased stroke deaths in most groups. CONCLUSIONS: While there's a decline in stroke-related deaths among US older adults, outcome disparities remain across demographic and geographic sectors. The surge in stroke deaths during coronavirus pandemic reaffirms the need for policies that address these disparities.

Health Care Costs Following Anterior Cervical Discectomy and Fusion or Cervical Disc Arthroplasty.

STUDY DESIGN: Observational cohort study. OBJECTIVE: To describe the postoperative costs associated with both anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) in the two-year period following surgery. SUMMARY OF BACKGROUND DATA: CDA has become an increasingly common alternative to ACDF for the treatment of cervical disc disorders. Although a number of studies have compared clinical outcomes between both procedures, much less is known about the postoperative economic burden of each procedure. MATERIALS AND METHODS: By analyzing a commercial insurance claims database (Marketscan, Merative), patients who underwent one-level or two-level ACDF and CDA procedures between January 1, 2017 and December 31, 2017 were identified and included in the study. The primary outcome was the cost of payments for postoperative management in the two-year period following ACDF or CDA. Identified postoperative interventions included in the study were: (i) physical therapy, (ii) pain medication, (iii) injections, (iv) psychological treatment, and (iv) subsequent spine surgeries. RESULTS: Totally, 2304 patients (age: 49.0±9.4 yr; male, 50.1%) were included in the study. In all, 1723 (74.8%) patients underwent ACDF, while 581 (25.2%) underwent CDA. The cost of surgery was similar between both groups (ACDF: $26,819±23,449; CDA: $25,954±20,620; P =0.429). Thirty-day, 90-day, and two-year global costs were all lower for patients who underwent CDA compared with ACDF ($31,024 vs. $34,411, $33,064 vs. $37,517, and $55,723 vs. $68,113, respectively). CONCLUSION: Lower two-year health care costs were found for patients undergoing CDA compared with ACDF. Further work is necessary to determine the drivers of these findings and the associated longer-term outcomes.

Intraoperative Closed Reduction of Traumatic Lateraloptosis: Operative Nuances.

BACKGROUND AND IMPORTANCE: Traumatic lateral spondyloptosis, or lateraloptosis, is the complete lateral dislocation of the spine. Reduction in these dislocations presents unique challenges, especially in cases of preserved neurological function. Open techniques carry significant risks of cerebrospinal fluid leak and neurological injury. For traditional spondyloptosis, off-table closed techniques have been described but may result in loss of the reduction when the patient is transferred to the operative table. An on-table closed reduction technique has potential advantages over previously described open reduction or off-table techniques for the treatment of lateraloptosis. CLINICAL PRESENTATION: The authors describe an on-table closed reduction technique for lateraloptosis, presenting an illustrative case in which the technique was applied. This technique is compared with alternative open and off-table reduction techniques described in the literature. The patient had good mechanical and neurological outcomes. At 14 months postoperatively, she is neurologically intact, back to work involving heavy lifting, and has only moderate back pain. CONCLUSION: On-table closed reduction before open fixation should be considered in cases of lateraloptosis, particularly when there is preserved neurological function.

Anterior Cervical Discectomy and Fusion With Structural Allograft is Associated With Lower Postoperative Health Care Utilization and Reoperations Compared With Cage Implants.

BACKGROUND AND OBJECTIVES: Implants represent a large component of surgical cost, with several available options for anterior cervical discectomy and fusion (ACDF). Rising ACDF volume highlights the need for accurate cost characterization among implant configurations to inform efficient utilization. METHODS: A cohort study of patients who underwent 1-level or 2-level ACDF in 2017 was conducted using the MarketScan national insurance databases, which contain deidentified clinical and financial data. Implant configurations included plate with cage, standalone cage, and plate with structural allograft. Patients who switched insurance providers within 2 years after surgery or underwent concurrent posterior cervical surgery, cervical disk arthroplasty, or cervical corpectomy were excluded. A combined plate/cage and standalone cage group was compared with the allograft group followed by the comparison of the plate/cage and standalone cage groups. In total, 30-day, 90-day, and 2-year aggregate costs; component costs of physical therapy, injections, medications, psychological treatment, and subsequent spine surgery; and reoperation rates were evaluated. RESULTS: Of 1723 patients identified, 360 (20.9%) underwent surgery with plate/cage, 184 (10.7%) with standalone cage, and 1179 (68.4%) with allograft. Aggregate costs were lower in the allograft group compared with the combined cage group at 90 days ($36 428 vs $39 875, P = .04) and 2 years ($64 951 vs $74 965, P = .005) postoperatively. There were no significant differences in aggregate costs between the plate/cage and standalone cage groups. The 2-year reoperation rate was higher in the combined cage compared with the allograft group (23.9% vs 10.9%, P < .001) and was also higher in the standalone cage compared with the plate/cage group (32.0% vs 19.7%, P = .002). CONCLUSION: Compared with alternative ACDF constructs, allograft is associated with lower postoperative costs and reoperation rates. Although costs are similar, reoperation rates are lower with plate/cage constructs compared with those of standalone cages. Surgeons should consider these financial and clinical differences when selecting implant configurations.

Public health insurance, frailty, and lack of home support predict rehab discharge following elective anterior cervical discectomy and fusion.

BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is a commonly-performed and generally well-tolerated procedure used to treat cervical disc herniation. Rarely, patients require discharge to inpatient rehab, leading to inconvenience for the patient and increased healthcare expenditure for the medical system. PURPOSE: The objective of this study was to create an accurate and practical predictive model for, as well as delineate associated factors with, rehab discharge following elective ACDF. STUDY DESIGN: This was a retrospective, single-center, cohort study. PATIENT SAMPLE: Patients who underwent ACDF between 2012 and 2022 were included. Those with confounding diagnoses or who underwent concurrent, staged, or nonelective procedures were excluded. OUTCOME MEASURES: Primary outcomes for this study included measurements of accuracy for predicting rehab discharge. Secondary outcomes included associations of variables with rehab discharge. METHODS: Current Procedural Terminology codes identified patients. Charts were reviewed to obtain additional demographic and clinical characteristics on which an initial univariate analysis was performed. Two logistic regression and two machine learning models were trained and evaluated on the data using cross-validation. A multimodel logistic regression was implemented to analyze independent variable associations with rehab discharge. RESULTS: A total of 466 patients were included in the study. The logistic regression model with minimum corrected Akaike information criterion score performed best overall, with the highest values for area under the receiver operating characteristic curve (0.83), Youden's J statistic (0.71), balanced accuracy (85.7%), sensitivity (90.3%), and positive predictive value (38.5%). Rehab discharge was associated with a modified frailty index of 2 (p=.007), lack of home support (p=.002), and having Medicare or Medicaid insurance (p=.007) after correction for multiple hypotheses. CONCLUSIONS: Nonmedical social determinants of health, such as having public insurance or a lack of support at home, may play a role in rehab discharge following elective ACDF. In combination with the modified frailty index and other variables, these factors can be used to predict rehab discharge with high accuracy, improving the patient experience and reducing healthcare costs.

Moderate-Affinity Affibodies Modulate the Delivery and Bioactivity of Bone Morphogenetic Protein-2.

Uncontrolled bone morphogenetic protein-2 (BMP-2) release can lead to off-target bone growth and other adverse events. To tackle this challenge, yeast surface display is used to identify unique BMP-2-specific protein binders known as affibodies that bind to BMP-2 with different affinities. Biolayer interferometry reveals an equilibrium dissociation constant of 10.7 nm for the interaction between BMP-2 and high-affinity affibody and 34.8 nm for the interaction between BMP-2 and the low-affinity affibody. The low-affinity affibody-BMP-2 interaction also exhibits an off-rate constant that is an order of magnitude higher. Computational modeling of affibody-BMP-2 binding predicts that the high- and low-affinity affibodies bind to two distinct sites on BMP-2 that function as different cell-receptor binding sites. BMP-2 binding to affibodies reduces expression of the osteogenic marker alkaline phosphatase (ALP) in C2C12 myoblasts. Affibody-conjugated polyethylene glycol-maleimide hydrogels increase uptake of BMP-2 compared to affibody-free hydrogels, and high-affinity hydrogels exhibit lower BMP-2 release into serum compared to low-affinity hydrogels and affibody-free hydrogels over four weeks. Loading BMP-2 into affibody-conjugated hydrogels prolongs ALP activity of C2C12 myoblasts compared to soluble BMP-2. This work demonstrates that affibodies with different affinities can modulate BMP-2 delivery and activity, creating a promising approach for controlling BMP-2 delivery in clinical applications.

Challenges of Integrating APOL1 Genetic Test Results into the Electronic Health Record.

OBJECTIVES: Integrating genetic test results into the electronic health record (EHR) is essential for integrating genetic testing into clinical practice. This article describes the organizational challenges of integrating discrete apolipoprotein L1 (APOL1) genetic test results into the EHR for a research study on culturally sensitive genetic counseling for living kidney donors. METHODS: We convened a multidisciplinary team across three institutions (Northwestern University, Northwestern Memorial HealthCare [NMHC], and OHSU Knight Diagnostic Laboratories [KDL]), including researchers, physicians, clinical information technology, and project management. Through a series of meetings over a year between the team and the genetic testing laboratory, we explored and adjusted our EHR integration plan based on regulatory and budgetary constraints. RESULTS: Our original proposal was to transmit results from KDL to NMHC as structured data sent via Health Level Seven (HL7) v2 message. This was ultimately deemed infeasible given the time and resources required to establish the interface, and the low number of samples to be processed for the study (n = 316). We next explored the use of Epic's Care Everywhere interoperability platform, but learned it was not possible as a laboratory test ordered for a research study; even though our intent was to study the APOL1 genetic test result's clinical use and impact, test results were still considered "research results." Faced with two remaining options-downloading a PDF from the KDL laboratory portal or scanning a faxed result from KDL-only a PDF of the APOL1 test result could be integrated into the EHR, reinforcing the status quo. CONCLUSION: Even with early and ongoing stakeholder engagement, dedicated project management, and funding, unanticipated implementation challenges-especially for research projects-can result in drastic design tradeoffs.

Functional identification of hot-spot mutations in cardiac calcium channel genes associated with the J wave syndromes.

J wave syndrome (JWS) is an inherited cardiac channelopathy associated with malignant ventricular arrhythmias and sudden cardiac death (SCD), which comprises early repolarization syndrome and Brugada syndrome. Here, we explore the association between variants in the L-type calcium channel gene subunits, α1C (CACNA1C) and ß2b (CACNB2b), and the JWS phenotype. Using next-generation genetic sequencing of 402 JWS probands and their family members, we identified a CACNA1C-G37R (p.Gly37Arg) mutation in five individuals in four families, two of which had a family history of SCD as well as a CACNB2b-S143F (p.Ser143Phe) mutation in seven individuals in three families, two of which had a family history of SCD. The variants were located in exon 2 in CACNA1C and exon 5 in CACNB2b; both were in highly conserved amino acid residues. Whole-cell patch-clamp results showed that compared with the wild-type group, calcium current density of CACNB2b-S143F and CACNA1C-G37R were significantly lower displaying a dominant-negative effect. Our findings provide further support for the hypothesis that variants in CACNA1C and CACNB2b are associated with JWS. The results suggest that mutations in these two genes lead to loss-of-function of the cardiac calcium channel current warranting their inclusion in genetic screening protocols. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Complications Related to Deep Brain Stimulation Lead Implantation: A Single-Surgeon Case Series.

BACKGROUND: Deep brain stimulation (DBS) is the mainstay of surgical treatment for movement disorders, yet previous studies have shown widely varying complication rates. Given the elective nature of DBS surgery, minimizing surgical complications is imperative. OBJECTIVE: To evaluate short-term and long-term complications related to DBS lead implantation surgeries performed by an experienced surgeon and provide an updated benchmark comparison for other DBS centers and alternative therapies. METHODS: A retrospective chart review of patients who underwent DBS lead implantation surgery by a single surgeon at our institution between 2012 and 2020 was conducted. Demographic and clinical data including surgical complications were collected. A Kaplan-Meier survival analysis was used to evaluate the cumulative risk of lead revision or removal over time. Associations between patient characteristics and various complications were evaluated. RESULTS: Four hundred fifty-one DBS leads were placed in 255 patients. Thirteen leads and 11 patients required revision. In total, 3.6% (95% CI [1.3%-5.9%]) of patients required revision at 1 year and 4.8% (95% CI [1.9%-7.6%]) at 5 years, with per-lead revision rates of 2.3% (95% CI [0.9%-3.6%]) and 3.3% (95% CI [1.5%-5.1%]), respectively. Less common diagnoses such as Tourette syndrome, post-traumatic tremor, and cluster headache trended toward association with lead revision or removal. CONCLUSION: DBS performed by an experienced surgeon is associated with extremely low complication rates.

OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy.

Mitochondrial stress triggers a response in the cell's mitochondria and nucleus, but how these stress responses are coordinated in vivo is poorly understood. Here, we characterize a family with myopathy caused by a dominant p.G58R mutation in the mitochondrial protein CHCHD10. To understand the disease etiology, we developed a knockin (KI) mouse model and found that mutant CHCHD10 aggregated in affected tissues, applying a toxic protein stress to the inner mitochondrial membrane. Unexpectedly, the survival of CHCHD10-KI mice depended on a protective stress response mediated by the mitochondrial metalloendopeptidase OMA1. The OMA1 stress response acted both locally within mitochondria, causing mitochondrial fragmentation, and signaled outside the mitochondria, activating the integrated stress response through cleavage of DAP3-binding cell death enhancer 1 (DELE1). We additionally identified an isoform switch in the terminal complex of the electron transport chain as a component of this response. Our results demonstrate that OMA1 was critical for neonatal survival conditionally in the setting of inner mitochondrial membrane stress, coordinating local and global stress responses to reshape the mitochondrial network and proteome.

Prevention and regression of megamitochondria and steatosis by blocking mitochondrial fusion in the liver.

Non-alcoholic steatohepatitis (NASH) is a most common chronic liver disease that is manifested by steatosis, inflammation, fibrosis, and tissue damage. Hepatocytes produce giant mitochondria termed megamitochondria in patients with NASH. It has been shown that gene knockout of OPA1, a mitochondrial dynamin-related GTPase that mediates mitochondrial fusion, prevents megamitochondria formation and liver damage in a NASH mouse model induced by a methionine-choline-deficient (MCD) diet. However, it is unknown whether blocking mitochondrial fusion mitigates NASH pathologies. Here, we acutely depleted OPA1 using antisense oligonucleotides in the NASH mouse model before or after megamitochondria formation. When OPA1 ASOs were applied at the disease onset, they effectively prevented megamitochondria formation and liver pathologies in the MCD model. Notably, even when applied after mice robustly developed NASH pathologies, OPA1 targeting effectively regressed megamitochondria and the disease phenotypes. Thus, our data show the efficacy of mitochondrial dynamics as a unique therapy for megamitochondria-associated liver disease.

Antisense Oligonucleotide-Mediated Silencing of Mitochondrial Fusion and Fission Factors Modulates Mitochondrial Dynamics and Rescues Mitochondrial Dysfunction.

Mitochondria are highly dynamic organelles that produce ATP and maintain metabolic, catabolic, and redox homeostasis. Mitochondria owe this dynamic nature to their constant fission and fusion-processes that are regulated, in part, by fusion factors (MFN1 and MFN2) and fission factors (DRP1, FIS1, MFF, MIEF1, MIEF2) located on the outer mitochondrial membrane. While mitochondrial fusion and fission are known to influence mitochondrial morphology and function, a key question is whether rebalancing mitochondrial morphology can ameliorate mitochondrial dysfunction in the context of mitochondrial pathology. In this study, we used antisense oligonucleotides (ASOs) to systematically evaluate the effects of fusion and fission factors in vitro. Free uptake by cells of fusion or fission factor ASOs caused robust decreases in target gene expression and altered a variety of mitochondrial parameters, including mitochondrial size and respiration, which were dose dependent. In Mfn1 knockout mouse embryonic fibroblasts (MEFs) and MFN2-R94Q (Charcot-Marie-Tooth Type 2 Disease-associated mutation) MEFs, two cellular models of mitochondrial dysfunction, we found that ASO-mediated silencing of only Drp1 restored mitochondrial morphology and enhanced mitochondrial respiration. Together, these data demonstrate in vitro proof-of-concept for rebalancing mitochondrial morphology to rescue function using ASOs and suggest that ASO-mediated modulation of mitochondrial dynamics may be a viable therapeutic approach to restore mitochondrial homeostasis in diseases driven by mitochondrial dysfunction.

The Impact of Anticoagulation on Trauma Outcomes : An National Trauma Data Bank Study.

BACKGROUND: Increased prevalence of patients on anticoagulants and the advent of new therapies raise concern over how these patients fare if they sustain a traumatic injury. We investigated the role of prehospitalization anticoagulation therapy in trauma-related mortality and postacute disposition. METHODS: A retrospective analysis was performed on patients who sustained traumatic injury identified in the 2017 National Trauma Data Bank (NTDB). Patients with and without anticoagulation therapy were analyzed to identify differences in demographics, injury type, Injury Severity Score (ISS), and trauma outcomes including hospital length of stay, ER, final hospital disposition, and mortality. Logistic regression was used to correlate anticoagulation to mortality and facility discharge. RESULTS: Of the 1 000 596 patients included, 73 602 (7%) patients were on anticoagulants at the time of their trauma. Increased age was the strongest predictor for anticoagulation therapy (odds ratio 5.54, 95% CI 5.44-5.63), but being female and white were also independent predictors of anticoagulation (P < .001). Patients on anticoagulants had a significantly longer length of stay (5.11 days; 95% CI 5.06-5.15) than those who were not (4.37 days, 95% CI 4.36-4.39), were 2.20 times more likely to die (95% CI 2.12-2.28, P < .001), and were 2.77 times more likely to be discharged to a facility (95% CI 2.73-2.81, P < .001). Anticoagulation remained a significant predictor of worse trauma outcomes even when accounting for age and ISS in multivariate analysis. DISCUSSION: Anticoagulation preceding trauma-related admission is associated with higher mortality and an increased likelihood of the need for a posthospital care facility.

A novel and translational role for autophagy in antisense oligonucleotide trafficking and activity.

Endocytosis is a mechanism by which cells sense their environment and internalize various nutrients, growth factors and signaling molecules. This process initiates at the plasma membrane, converges with autophagy, and terminates at the lysosome. It is well-established that cellular uptake of antisense oligonucleotides (ASOs) proceeds through the endocytic pathway; however, only a small fraction escapes endosomal trafficking while the majority are rendered inactive in the lysosome. Since these pathways converge and share common molecular machinery, it is unclear if autophagy-related trafficking participates in ASO uptake or whether modulation of autophagy affects ASO activity and localization. To address these questions, we investigated the effects of autophagy modulation on ASO activity in cells and mice. We found that enhancing autophagy through small-molecule mTOR inhibition, serum-starvation/fasting, and ketogenic diet, increased ASO-mediated target reduction in vitro and in vivo. Additionally, autophagy activation enhanced the localization of ASOs into autophagosomes without altering intracellular concentrations or trafficking to other compartments. These results support a novel role for autophagy and the autophagosome as a previously unidentified compartment that participates in and contributes to enhanced ASO activity. Further, we demonstrate non-chemical methods to enhance autophagy and subsequent ASO activity using translatable approaches such as fasting or ketogenic diet.

Predicting mortality in traumatic intracranial hemorrhage.

OBJECTIVE: Traumatic intracranial hemorrhage (tICH) is a significant source of morbidity and mortality in trauma patients. While prognostic models for tICH outcomes may assist in alerting clinicians to high-risk patients, previously developed models face limitations, including low accuracy, poor generalizability, and the use of more prognostic variables than is practical. This study aimed to construct a simpler and more accurate method of risk stratification for all tICH patients. METHODS: The authors retrospectively identified a consecutive series of 4110 patients admitted to their institution's level 1 trauma center between 2003 and 2013. For each admission, they collected the patient's sex, age, systolic blood pressure, blood alcohol concentration, antiplatelet/anticoagulant use, Glasgow Coma Scale (GCS) score, Injury Severity Score, presence of epidural hemorrhage, presence of subdural hemorrhage, presence of subarachnoid hemorrhage, and presence of intraparenchymal hemorrhage. The final study population comprised 3564 patients following exclusion of records with missing data. The dependent variable under study was patient death. A k-fold cross-validation was carried out with the best models selected via the Akaike Information Criterion. These models risk stratified the study partitions into grade I (< 1% predicted mortality), grade II (1%-10% predicted mortality), grade III (10%-40% predicted mortality), or grade IV (> 40% predicted mortality) tICH. Predicted mortalities were compared with actual mortalities within grades to assess calibration. Concordance was also evaluated. A final model was constructed using the entire data set. Subgroup analysis was conducted for each hemorrhage type. RESULTS: Cross-validation demonstrated good calibration (p < 0.001 for all grades) with a mean concordance of 0.881 (95% CI 0.865-0.898). In the authors' final model, older age, lower blood alcohol concentration, antiplatelet/anticoagulant use, lower GCS score, and higher Injury Severity Score were all associated with greater mortality. Subgroup analysis showed successful stratification for subarachnoid, intraparenchymal, grade II-IV subdural, and grade I epidural hemorrhages. CONCLUSIONS: The authors developed a risk stratification model for tICH of any GCS score with concordance comparable to prior models and excellent calibration. These findings are applicable to multiple hemorrhage subtypes and can assist in identifying low-risk patients for more efficient resource allocation, facilitate family conversations regarding goals of care, and stratify patients for research purposes. Future work will include testing of more variables, validation of this model across institutions, as well as creation of a simplified model whose outputs can be calculated mentally.

Mouse genome-wide association studies and systems genetics uncover the genetic architecture associated with hepatic pharmacokinetic and pharmacodynamic properties of a constrained ethyl antisense oligonucleotide targeting Malat1.

Antisense oligonucleotides (ASOs) have demonstrated variation of efficacy in patient populations. This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics (PK) and pharmacodynamics (PD). Genome wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the uptake and efficacy of a single dose of a Malat1 constrained ethyl (cEt) modified ASO. The GWA of the HMDP identified two significant associations on chromosomes 4 and 10 with hepatic Malat1 ASO concentrations. Stabilin 2 (Stab2) and vesicle associated membrane protein 3 (Vamp3) were identified by cis-eQTL analysis. HMDP strains with lower Stab2 expression and Stab2 KO mice displayed significantly lower PK than strains with higher Stab2 expression and the wild type (WT) animals respectively, confirming the role of Stab2 in regulating hepatic Malat1 ASO uptake. GWA examining ASO efficacy uncovered three loci associated with Malat1 potency: Small Subunit Processome Component (Utp11l) on chromosome 4, Rho associated coiled-coil containing protein kinase 2 (Rock2) and Aci-reductone dioxygenase (Adi1) on chromosome 12. Our results demonstrate the utility of mouse GWAS using the HMDP in detecting genes capable of impacting the uptake of ASOs, and identifies genes critical for the activity of ASOs in vivo.

Factors associated with the progression of conservatively managed acute traumatic subdural hemorrhage.

PURPOSE: Traumatic subdural hemorrhage (SDH) is associated with high mortality, yet many patients are not managed surgically. We sought to understand what factors might be associated with SDH enlargement to contribute to the triage of these conservatively managed patients. MATERIALS AND METHODS: A consecutive series of 117 patients admitted to our institution's level 1 trauma center for SDH between January 1, 2010 and December 31, 2010 were evaluated. Volumetric measurement of SDHs was performed on initial and follow-up head computed tomography (CT) scans with recording of initial midline shift and classification by location. Multimodel analysis quantified associations with change in SDH volume. RESULTS: Systolic blood pressure, presence of subarachnoid hemorrhage, and initial SDH volume demonstrated positive associations with change in SDH volume, while initial midline shift and transfusion of platelets demonstrated negative associations. Initial convexity SDH volume demonstrated positive association with change in convexity SDH volume, while initial midline shift and transfusion of platelets demonstrated negative associations. Anticoagulant/antiplatelet use demonstrated positive association with change in tentorial SDH volume, while time between CT scans demonstrated negative association. CONCLUSIONS: Platelet transfusion, anticoagulation, and hypertension have significant associations with expansion in non-surgical cases of SDH. Monitoring these factors may assist triaging these patients.

Bubbles in the Brain: A Rare Complication Following Transthoracic Echocardiography.

With nearly 700,000 cases every year, ischemic stroke represents the third leading cause of death in the United States.1,2 Nearly thirty percent of all ischemic strokes are due to embolism.3 A standard component of every stroke work-up at most institutions, echocardiography is vital not only for diagnosis but also for prevention and treatment of cardiac sources of embolism. Visualization of right-to-left shunting is often contrast-enhanced with micro bubbles created by mixing saline with air, a so-called "bubble study." We present a case of an 89-year-old woman who suffered cerebral air embolism and massive infarction following a routine bubble Transthoracic Echocardiogram.

Blossoming contusions: identifying factors contributing to the expansion of traumatic intracerebral hemorrhage.

Here, the authors examined the factors involved in the volumetric progression of traumatic brain contusions. The variables significant in this progression are identified, and the expansion rate of a brain bleed can now effectively be predicted given the presenting characteristics of the patient.

Increased postsynaptic Ca2+ reduces mini frequency at the Drosophila larval NMJ.

Repetitive stimulation of the Drosophila larval NMJ can produce a reduction in the frequency of miniature excitatory postsynaptic currents. By buffering postsynaptic Ca2+ , it was shown that the decrease in "mini" frequency was due to an increase in postsynaptic Ca2+ .