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Introduction: Spinal cord injury (SCI) animal models often utilize an open surgical laminectomy, which results in animal morbidity and also leads to changes in spinal canal diameter, spinal cord perfusion, cerebrospinal fluid flow dynamics, and spinal stability which may confound SCI research. Moreover, the use of open surgical laminectomy for injury creation lacks realism when considering human SCI scenarios. Methods: We developed a novel, image-guided, minimally invasive, large animal model of SCI which utilizes a kyphoplasty balloon inserted into the epidural space via an interlaminar approach without the need for open surgery. Results: The model was validated in 5 Yucatán pigs with imaging, neurofunctional, histologic, and electrophysiologic findings consistent with a mild compression injury. Discussion: Few large animal models exist that have the potential to reproduce the mechanisms of spinal cord injury (SCI) commonly seen in humans, which in turn limits the relevance and applicability of SCI translational research. SCI research relies heavily on animal models, which typically involve an open surgical, dorsal laminectomy which is inherently invasive and may have untoward consequences on animal morbidity and spinal physiology that limit translational impact. We developed a minimally invasive, large animal model of spinal cord injury which utilizes a kyphoplasty balloon inserted percutaneously into the spinal epidural space. Balloon inflation results in a targeted, compressive spinal cord injury with histological and electrophysiological features directly relevant to human spinal cord injury cases without the need for invasive surgery. Balloon inflation pressure, length of time that balloon remains inflated, and speed of inflation may be modified to achieve variations in injury severity and subtype.
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Electrokinetic convection-enhanced delivery (ECED) utilizes an external electric field to drive the delivery of molecules and bioactive substances to local regions of the brain through electroosmosis and electrophoresis, without the need for an applied pressure. We characterize the implementation of ECED to direct a neutrally charged fluorophore (3 kDa) from a doped biocompatible acrylic acid/acrylamide hydrogel placed on the cortical surface. We compare fluorophore infusion profiles using ECED (time = 30 min, current = 50 µA) and diffusion-only control trials, for ex vivo (N = 18) and in vivo (N = 12) experiments. The linear intensity profile of infusion to the brain is significantly higher in ECED compared to control trials, both for in vivo and ex vivo. The linear distance of infusion, area of infusion, and the displacement of peak fluorescence intensity along the direction of infusion in ECED trials compared to control trials are significantly larger for in vivo trials, but not for ex vivo trials. These results demonstrate the effectiveness of ECED to direct a solute from a surface hydrogel towards inside the brain parenchyma based predominantly on the electroosmotic vector.
Subject(s)
Brain , Convection , Drug Delivery Systems , Hydrogels , Hydrogels/chemistry , Brain/metabolism , Animals , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Fluorescent Dyes/chemistry , Fluorescent Dyes/administration & dosage , Male , RatsABSTRACT
OBJECTIVES: Demand for rapid coagulation testing for massive transfusion events led to development of an emergency hemorrhage panel (EHP; hemoglobin, platelet count, prothrombin time/international normalized ratio, and fibrinogen), with laboratory turnaround time (TAT) of less than 20 minutes. Ten years on, we asked if current laboratory practices were meeting that TAT goal and differences were evident in TAT between the 2 major institutions in our system. METHODS: We identified EHPs ordered at our 2 largest hospitals, February 2, 2021, to July 17, 2022, comparing order to specimen draw time, specimen draw to specimen received time, laboratory analytic time, and total TAT results from emergency department and operating room. Site 1 houses a level I trauma center; site 2 includes tertiary care, transplant, and obstetrics services. RESULTS: In total, 1137 EHPs were recorded in our study period. Laboratory TAT was significantly faster at site 1 (~14 vs ~27 minutes, P < .01). Average laboratory TAT was under 20 minutes at site 1 but only for 50% of specimens at site 2. Outlier specimens were collection delays at site 1 and specimen processing delays at site 2. CONCLUSIONS: The EHP can be performed as rapidly as described. However, compromises in laboratory location, available personnel, and processing differences can degrade performance.
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The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young's modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.
Subject(s)
Elasticity Imaging Techniques , Lagomorpha , Spinal Cord Injuries , Animals , Rabbits , Diffusion Tensor Imaging , Spinal Cord Injuries/diagnostic imagingABSTRACT
Control of carbon dioxide and water vapor exchange between a leaf's interior and the surrounding air is accomplished by variations in the turgor pressures in the small epidermal and guard cells that cover the leaf's surface. These pressures respond to changes in light intensity and wavelength, temperature, CO2 concentration, and air humidity. The dynamical equations that describe such processes are formally identical to those that define computation in a two-layer, adaptive, cellular nonlinear network. This exact identification suggests that leaf gas-exchange processes can be understood as analog computation and that exploiting the output of two-layer, adaptive, cellular nonlinear networks might provide new tools in applied plant research.
Subject(s)
Plant Leaves , Plant Stomata , Light , Pressure , Carbon DioxideABSTRACT
Spinal cord injury (SCI) research with animals aims to understand the neurophysiological responses resultant of injury and to identify effective interventions that can translate into clinical treatments in the future. Consistent and reliable assessments to properly measure outcomes are essential to achieve this aim and avoid issues with reproducibility. The objective of this study was to establish a baseline for implementing the forelimb reaching task (FRT) assessment and analysis that increased reproducibility of our studies. For this study, we implemented a weekly FRT training program for six weeks. During this time the language of the scoring rubric for movement elements that comprise a reaching task was simplified and expanded. We calculated intra- and inter-rater variability among participants of the study both before and after training to determine the effect changes made had on rigor and reproducibility of this behavioral assessment in a cervical SCI rodent model. All animals (n = 19) utilized for FRT behavioral assessments received moderate contusion injuries using the Ohio State University device and were tested for a period of 5 weeks post-SCI. Videos used for scoring were edited and shared with all participants of this study to test FRT score variability and the effect simplification of the scoring rubric had on overall inter-rater reliability. From our results we determined training for a minimum of three weeks in FRT analysis is necessary for rigor and reproducibility of our behavioral studies, as well as the need for two raters to be assigned per animal to ensure accuracy of results.
Subject(s)
Cervical Cord , Spinal Cord Injuries , Animals , Reproducibility of Results , Cervical Cord/injuries , Rodentia , Disease Models, Animal , Forelimb , Recovery of Function/physiology , Spinal CordABSTRACT
Patients with class III obesity are often excluded from surgery in ambulatory surgery centers (ASCs). We hypothesize that class III obesity is not a risk factor for serious post-operative complications following outpatient operations. ACS-NSQIP database from 2012 to 2018 was queried. Patients undergoing outpatient inguinal hernia repair (IHR) and laparoscopic cholecystectomy (LC) were grouped by BMI. Baseline characteristics and 30-day outcomes were compared using univariate and multivariate analyses. Of these, 79,916 patients underwent IHR and 107,471 patients underwent LC. Multivariable analysis in IHR showed increased odds of superficial SSIs in all classes of obesity compared to normal weight (P < .0001). In the LC group, there were higher rates of SSIs with obesity (P < .0001). For both surgeries, a higher rate of readmissions to the hospital were observed in class II and IIIa obesity (both P < .0001), although rates were relatively low (<3%). Class III obesity demonstrates a statistically significant increase in SSI following IHR and LC. Severe complications requiring readmission are not mirrored, suggesting the morbidly obese patients should be considered for routine surgical procedures in outpatient settings.
Subject(s)
Ambulatory Surgical Procedures , Obesity, Morbid , Postoperative Complications , Obesity, Morbid/complications , Obesity, Morbid/surgery , Humans , Hernia, Inguinal/surgery , Body Mass Index , CholecystectomyABSTRACT
COVID-19 readmissions are associated with increased patient mortality and healthcare system strain. This retrospective cohort study of PCR-confirmed COVID-19 positive adults (>18 years) hospitalized and readmitted within 30 days of discharge from index admission was performed at eight Atlanta hospitals from March to December 2020. The objective was to describe COVID-19 patient-level demographics and clinical characteristics, and community-level social determinants of health (SDoH) that contribute to 30-day readmissions. Demographics, comorbidities, COVID-19 treatment, and discharge disposition data were extracted from the index admission. ZIP codes were linked to a demographic/lifestyle database interpolating to community-level SDoH. Of 7155 patients with COVID-19, 463 (6.5%) had 30-day, unplanned, all-cause hospital readmissions. Statistically significant differences were not found in readmissions stratified by age, sex, race, or ethnicity. Patients with a high-risk Charlson Comorbidity Index had higher odds of readmission (OR 4.8 (95% CI: 2.1 to 11.0)). Remdesivir treatment and intensive care unit (ICU) care were associated with lower odds of readmission (OR 0.5 (95% CI: 0.4 to 0.8) and OR 0.5 (95% CI: 0.4 to 0.7), respectively). Patients residing in communities with larger average household size were less likely to be readmitted (OR 0.7 (95% CI: 0.5 to 0.9). In this cohort, patients who received remdesivir, were cared for in an ICU, and resided in ZIP codes with higher proportions of residents with increased social support had lower odds of readmission. These patient-level factors and community-level SDoH may be used to identify patients with COVID-19 who are at increased risk of readmission.
Subject(s)
COVID-19 Drug Treatment , Patient Readmission , Adult , Hospitals , Humans , Retrospective Studies , Risk Factors , Social Determinants of HealthABSTRACT
Solitary fibrous tumors are mesenchymal fibroblastic tumors that were originally described as intrathoracic lesions but have since been found to occur in many other locations. They may rarely occur as paratesticular masses. Here we present a peculiar case of a solitary fibrous tumor arising in the paratesticular region and exhibiting leiomyoma-like morphology. Confirmation of the tumor as a solitary fibrous tumor was achieved by RNA sequencing showing NAB2::STAT6 fusion. Possible explanations for the unusual tumor morphology include entrapment of normal smooth muscle elements and tumor differentiation into smooth muscle type cells.
Subject(s)
Genital Neoplasms, Male , Leiomyoma , Solitary Fibrous Tumors , Male , Humans , Biomarkers, Tumor/genetics , Solitary Fibrous Tumors/pathology , STAT6 Transcription Factor/genetics , Sequence Analysis, RNA , Leiomyoma/diagnosisABSTRACT
Astrocyte reactivity can directly modulate nervous system function and immune responses during disease and injury. However, the consequence of human astrocyte reactivity in response to specific contexts and within neural networks is obscure. Here, we devised a straightforward bioengineered neural organoid culture approach entailing transcription factor-driven direct differentiation of neurons and astrocytes from human pluripotent stem cells combined with genetically encoded tools for dual cell-selective activation. This strategy revealed that Gq-GPCR activation via chemogenetics in astrocytes promotes a rise in intracellular calcium followed by induction of immediate early genes and thrombospondin 1. However, astrocytes also undergo NF-κB nuclear translocation and secretion of inflammatory proteins, correlating with a decreased evoked firing rate of cocultured optogenetic neurons in suboptimal conditions, without overt neurotoxicity. Altogether, this study clarifies the intrinsic reactivity of human astrocytes in response to targeting GPCRs and delivers a bioengineered approach for organoid-based disease modeling and preclinical drug testing.
Subject(s)
Astrocytes/metabolism , Bioengineering , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Neurons/metabolism , Organoids/metabolism , Receptors, G-Protein-Coupled/metabolism , Adenosine Triphosphate/pharmacology , Astrocytes/pathology , Calcium/metabolism , Cell Line , Glial Fibrillary Acidic Protein/metabolism , Humans , Inflammation/pathology , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Pluripotent Stem Cells/metabolism , Reproducibility of Results , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism , Synaptophysin/metabolismABSTRACT
Electrical stimulation of the cervical spinal cord is gaining traction as a therapy following spinal cord injury; however, it is difficult to target the cervical motor region in a rodent using a non-penetrating stimulus compared with direct placement of intraspinal wire electrodes. Penetrating wire electrodes have been explored in rodent and pig models and, while they have proven beneficial in the injured spinal cord, the negative aspects of spinal parenchymal penetration (e.g., gliosis, neural tissue damage, and obdurate inflammation) are of concern when considering therapeutic potential. We therefore designed a novel approach for epidural stimulation of the rat spinal cord using a wireless stimulation system and ventral electrode array. Our approach allowed for preservation of mobility following surgery and was suitable for long term stimulation strategies in awake, freely functioning animals. Further, electrophysiology mapping of the ventral spinal cord revealed the ventral approach was suitable to target muscle groups of the rat forelimb and, at a single electrode lead position, different stimulation protocols could be applied to achieve unique activation patterns of the muscles of the forelimb.
Subject(s)
Cervical Vertebrae , Electric Stimulation Therapy/methods , Electric Stimulation/methods , Electrodes, Implanted , Spinal Cord Injuries/therapy , Wireless Technology , Animals , Electromyography , Forelimb , Muscle, Skeletal/physiology , Rats , Spinal Cord Injuries/physiopathologyABSTRACT
BACKGROUND: Neurodegeneration is a complex cellular process linked to prompt changes in myelin integrity and gradual neuron loss. Current imaging techniques offer estimations of myelin volumes in lesions/remyelinated areas but are limited to detect subtle injury. PURPOSE: To investigate whether measurements detected by a signal hierarchically isolated as a function of time-to-echo (SHIFT) MRI technique can determine changes in myelin integrity and fiber axolemma. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Surgically demyelinated spinal cord (SC) injury model in rodents (n = 6). FIELD STRENGTH/SEQUENCE: Gradient-echo spin-echo at 3T. ASSESSMENT: Multicompartment T2 relaxations were computed by SHIFT MRI in 75-microns-resolution images of the SC injury penumbra region 2 weeks post-trauma. G-ratio and axolemma delamination were assessed by transmission electron microscopy (TEM) in intact and injured samples. SC myelinated nerve fraction was computed by SHIFT MRI prospectively and assessed histologically. STATISTICAL TESTS: Relations between SHIFT-isolated T2 -components and TEM measurements were studied using linear regression and t-tests. Pearson's correlation and significance were computed to determine the SHIFT's sensitivity to detect myelinated fibers ratio in gray matter. Regularized least-squares-based ranking analysis was employed to determine SHIFT MRI's ability to discern intact and injured myelinated nerves. RESULTS: Biexponential signals isolated by SHIFT MRI for intact vs. lesion penumbra exhibited changes in T2 , shifting from intermediate components (25 ± 2 msec) to long (43 ± 11 msec) in white matter, and similarly in gray matter regions-of-interest (31 ± 2 to 46 ± 16 msec). These changes correlated highly with TEM g-ratio and axon delamination measurements (P < 0.05). Changes in short T2 components were observed but not statistically significant (8.5 ± 0.5 to 7 ± 3 msec, P = 0.445, and 4.0 ± 0.9 to 7 ± 3 msec, P = 0.075, respectively). SHIFT MRI's ability to detect myelinated fibers within gray matter was confirmed (P < 0.001). DATA CONCLUSION: Changes detected by SHIFT MRI are associated with abnormal intermembrane spaces formed upon mild injury, directly correlated with early neuro integrity loss. Level of Evidence 1 Technical Efficacy Stage 2.
Subject(s)
Myelin Sheath , Spinal Cord Injuries , Animals , Magnetic Resonance Imaging , Neuropil , Prospective Studies , Spinal Cord/diagnostic imagingABSTRACT
The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5âhours. All patients underwent a dCTA protocol acquired over 60âseconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6âmL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30-820.25], Pâ=â.17). Correlation between extravasation rate and HE was low (râ=â0.297, P=â.11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12âmL/min vs 0.04âmL/min, Pâ=â.03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.
Subject(s)
Cerebral Angiography/methods , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/epidemiology , Computed Tomography Angiography , Extravasation of Diagnostic and Therapeutic Materials/diagnostic imaging , Extravasation of Diagnostic and Therapeutic Materials/epidemiology , Hematoma/diagnostic imaging , Hematoma/epidemiology , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Sensitivity and SpecificityABSTRACT
Neural stimulation modulates the depolarization of neurons, thereby triggering activity-associated mechanisms of neuronal plasticity. Activity-associated mechanisms in turn play a major role in post-mitotic structure and function of adult neurons. Our understanding of the interactions between neuronal behavior, patterns of neural activity, and the surrounding environment is evolving at a rapid pace. Brain derived neurotrophic factor is a critical mediator of activity-associated plasticity, while multiple immediate early genes mediate plasticity of neurons following bouts of neural activity. New research has uncovered genetic mechanisms that govern the expression of DNA following changes in neural activity patterns, including RNAPII pause-release and activity-associated double stranded breaks. Discovery of novel mechanisms governing activity-associated plasticity of neurons hints at a layered and complex molecular control of neuronal response to depolarization. Importantly, patterns of depolarization in neurons are shown to be important mediators of genetic expression patterns and molecular responses. More research is needed to fully uncover the molecular response of different types of neurons-to-activity patterns; however, known responses might be leveraged to facilitate recovery after neural damage. Physical rehabilitation through passive or active exercise modulates neurotrophic factor expression in the brain and spinal cord and can initiate cortical plasticity commensurate with functional recovery. Rehabilitation likely relies on activity-associated mechanisms; however, it may be limited in its application. Electrical and magnetic stimulation direct specific activity patterns not accessible through passive or active exercise and work synergistically to improve standing, walking, and forelimb use after injury. Here, we review emerging concepts in the molecular mechanisms of activity-derived plasticity in order to highlight opportunities that could add value to therapeutic protocols for promoting recovery of function after trauma, disease, or age-related functional decline.
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We studied sources of variation between countries in per-capita mortality from COVID-19 (caused by the SARS-CoV-2 virus). Potential predictors of per-capita coronavirus-related mortality in 200 countries by May 9, 2020 were examined, including age, gender, obesity prevalence, temperature, urbanization, smoking, duration of the outbreak, lockdowns, viral testing, contact-tracing policies, and public mask-wearing norms and policies. Multivariable linear regression analysis was performed. In univariate analysis, the prevalence of smoking, per-capita gross domestic product, urbanization, and colder average country temperature were positively associated with coronavirus-related mortality. In a multivariable analysis of 196 countries, the duration of the outbreak in the country, and the proportion of the population aged 60 years or older were positively associated with per-capita mortality, whereas duration of mask-wearing by the public was negatively associated with mortality (all P < 0.001). Obesity and less stringent international travel restrictions were independently associated with mortality in a model which controlled for testing policy. Viral testing policies and levels were not associated with mortality. Internal lockdown was associated with a nonsignificant 2.4% reduction in mortality each week (P = 0.83). The association of contact-tracing policy with mortality was not statistically significant (P = 0.06). In countries with cultural norms or government policies supporting public mask-wearing, per-capita coronavirus mortality increased on average by just 16.2% each week, as compared with 61.9% each week in remaining countries. Societal norms and government policies supporting the wearing of masks by the public, as well as international travel controls, are independently associated with lower per-capita mortality from COVID-19.
Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Masks/supply & distribution , Pandemics , Quarantine/organization & administration , SARS-CoV-2/pathogenicity , Age Factors , COVID-19/diagnosis , COVID-19 Testing/methods , Cold Temperature , Comorbidity , Contact Tracing/legislation & jurisprudence , Global Health/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Linear Models , Multivariate Analysis , Obesity , Physical Distancing , Severity of Illness Index , Sex Factors , Smoking/physiopathology , Survival Analysis , UrbanizationABSTRACT
BACKGROUND: Dynamic CT angiography (dCTA) contrast extravasation, known as the "dynamic spot sign", can predict hematoma expansion (HE) in intracerebral hemorrhage (ICH). Recent reports suggest the phase of spot sign appearance is related to the magnitude of HE. We used dCTA to explore the association between the phase of spot sign appearance and HE, clinical outcome, and contrast extravasation rates. METHODS: We assessed consecutive patients who presented with primary ICH within 4.5 hours from symptom onset who underwent a standardized dCTA protocol and were spot sign positive. The independent variable was the phase of spot sign appearance. The primary outcome was significant HE (either 6 mL or 33% growth). Secondary outcomes included total absolute HE, mortality, and discharge mRS. Mann-Whitney U, Fisher's exact test, and logistic regression were used, as appropriate. RESULTS: Of the 35 patients with spot signs, 27/35 (77%) appeared in the arterial phase and 8/35 (23%) appeared in the venous phase. Thirty patients had follow-up CT scans. Significant HE was seen in 14/23 (60.87%) and 3/7 (42.86%) of arterial and venous cohorts, respectively (p = 0.67). The sensitivity and specificity in predicting significant HE were 82% and 31% for the arterial phase and 18% and 69% for the venous phase, respectively. There was a non-significant trend towards greater total HE, in-hospital mortality, and discharge mRS of 4-6 in the arterial spot sign cohort. Arterial spot signs demonstrated a higher median contrast extravasation rate (0.137 mL/min) compared to venous spot signs (0.109 mL/min). CONCLUSION: Our exploratory analyses suggest that spot sign appearance in the arterial phase may be more likely associated with HE and poorer prognosis in ICH. This may be related to higher extravasation rates of arterial phase spot signs. However, further studies with larger sample sizes are warranted to confirm the findings.
Subject(s)
Cerebral Angiography/methods , Cerebral Hemorrhage/mortality , Computed Tomography Angiography/methods , Extravasation of Diagnostic and Therapeutic Materials/diagnosis , Hematoma/diagnosis , Aged , Aged, 80 and over , Arteries/diagnostic imaging , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnosis , Cerebrum/blood supply , Cerebrum/diagnostic imaging , Extravasation of Diagnostic and Therapeutic Materials/etiology , Female , Follow-Up Studies , Hematoma/etiology , Hospital Mortality , Humans , Male , Predictive Value of Tests , Prognosis , Prospective Studies , Sensitivity and SpecificityABSTRACT
Although epidural spinal stimulation (ESS) results in promising therapeutic effects in individuals with spinal cord injury (SCI), its potential to generate functional motor recovery varies between individuals and remains largely unclear. However, both preclinical and clinical studies indicate the capacity of electrical and pharmacological interventions to synergistically increase the engagement of spinal sensorimotor networks and regain motor function after SCI. This study explored whether selective pharmacological antagonism of the adenosine A1 receptor subtype synergizes with ESS, thereby increasing motor response. We hypothesized that selective pharmacological antagonism of A1 receptors during ESS would produce facilitatory effects in spinal sensorimotor networks detected as an increased amplitude of spinally-evoked motor potentials and sustained duration of ESS induced activity. Terminal experiments were performed in adult rats using trains of stereotyped pulses at 40 Hz delivered at L5 with the local administration to the cord of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We demonstrated that ESS combined with the blockage of A1 receptors increased the magnitude of the endogenous modulation and postponed the decay of responses that occur during ESS alone. Although DPCPX significantly increased the yield of repetitive stimulation in intact spinal cords, the effects of A1 antagonism on motor evoked responses after an acute spinal transection was not detected. These studies support the future investigation of the optimal dosage, methods of delivery, and systemic effects of the synergistic application of A1 antagonists and spinal stimulation in the intact and injured spinal cord.
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The presence of KMT2A/AFF1 rearrangement in B-lymphoblastic leukemia (B-ALL) is an independent poor prognostic factor and has been associated with higher rate of treatment failure and higher risk of linage switch under therapy. Blinatumomab has shown promising therapeutic results in refractory or relapsed B-ALL; however, it has potential risk of inducing lineage switch, especially in KMT2A/AFF1 rearranged B-ALL into acute myeloid leukemia and/or myeloid sarcoma. We report a 40-year-old female with KMT2A/AFF1-rearranged B-ALL that was refractory to conventional chemotherapy. Following administration of blinatumomab, she developed a breast mass proven to be myeloid sarcoma, in addition to bone marrow involvement by AML. Approximately six weeks after cessation of blinatumomab, a repeat bone marrow examination revealed B/myeloid MPAL.
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Objective. To develop and implement a multimodal structured approach to intentional interprofessional experiential education at a non-academic community hospital, and to evaluate students' perceptions of the program. Methods. A multimodal structured approach to intentional interprofessional experiential education was designed that consisted of medical and pharmacy students participating together in daily pre-rounds, daily teaching rounds, and once or twice weekly lunch-and-learn sessions at a non-academic community hospital. Pre- and post-experience surveys were administered to assess students' perceptions of physician and pharmacist collaboration in interprofessional education (IPE). The survey instrument included the Student Perceptions of Physician-Pharmacist Interprofessional Clinical Education, Version 2 (SPICE-2) survey. Results. Thirty-nine students, including 18 fourth-year student pharmacists from Mercer University College of Pharmacy and 21 third-year medical students from three medical schools in the Caribbean, provided informed consent and were enrolled in the eight-month study. Students' perceptions of items related to the Interprofessional Education Collaborative (IPEC) competencies, including values/ethics for interprofessional practice, roles/responsibilities, and teams and teamwork, significantly improved from the pre- to the post-experience survey. Conclusion. A multimodal structured approach to intentional interprofessional experiential education had positive effects on students' perceptions of interprofessional clinical education targeting key components of the (IPEC) competencies. This approach may be a useful tool for implementing intentional IPE in the experiential setting.