Search

Modern quantum chemistry algorithms are increasingly able to accurately predict molecular properties that are useful for chemists in research and education. Despite this progress, performing such calculations is currently unattainable to the wider chemistry community, as they often require domain expertise, computer programming skills, and powerful computer hardware. In this review, we outline methods to eliminate these barriers using cutting-edge technologies. We discuss the ingredients needed to create accessible platforms that can compute quantum chemistry properties in real time, including graphical processing units–accelerated quantum chemistry in the cloud, artificial intelligence–driven natural molecule input methods, and extended reality visualization. We end by highlighting a series of exciting applications that assemble these components to create uniquely interactive platforms for computing and visualizing spectra, 3D structures, molecular orbitals, and many other chemical properties.

Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: 5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (−0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus −1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (−0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01178320.

Adult cervical spine deformity is associated with decreased health-related quality of life, disability, and myelopathy. A number of radiographic parameters help to characterize cervical deformity and aid in the diagnosis and treatment. There are several etiologies for cervical spine deformity, the most common being iatrogenic. Additionally, spine surgery can accelerate adjacent segment degeneration which may lead to deformity. It is therefore important for all spine surgeons to be aware of the potential to cause iatrogenic cervical deformity. The aim of this review is to highlight concepts and techniques to prevent cervical deformity after spine surgery.

Opioid utilization has been well studied for inpatient anterior cervical discectomy and fusion (ACDF). However, the amount and type of opioids prescribed following ambulatory ACDF and the associated risk of persistent use are largely unknown.To characterize opioid prescription filling following single-level ambulatory ACDF compared with inpatient procedures.Retrospective cohort study.Opioid-naive patients who underwent ambulatory (no overnight stay) or inpatient single-level ACDF from 2011 to 2019 were identified from a national insurance database.Rate, amount, and type of perioperative opioid prescription.Opioid-naive patients who underwent ambulatory (no overnight stay) or inpatient single-level ACDF from 2011 to 2019 were identified from a national insurance database. Perioperative opioids were defined as opioid prescriptions 30 days before and 14 days after the procedure. Rate, amount, and type of opioid prescription were characterized. Multivariable analyses controlling for any differences in demographics and comorbidities between the two treatment groups were utilized to determine any association between surgical setting and persistent opioid use (defined as the patient still filling new opioid prescriptions90 days postoperatively).A total of 42,521 opioid-naive patients were identified, of which 2,850 were ambulatory and 39,671 were inpatient. Ambulatory ACDF was associated with slightly increased perioperative opioid prescription filling (52.7% vs 47.3% for inpatient procedures; p.001). Among the 20,280 patients (47.7%) who filled perioperative opioid prescriptions, the average amount of opioids prescribed (in morphine milligram equivalents) was similar between ambulatory and inpatient procedures (550 vs 540, p=.413). There was no association between surgical setting and persistent opioid use in patients who filled a perioperative opioid prescription, even after controlling for comorbidities, (adjusted odds ratio, 1.15, p=.066).Ambulatory ACDF patients who filled perioperative opioid prescriptions were prescribed a similar amount of opioids as those undergoing inpatient procedures. Further, ambulatory ACDF does not appear to be a risk factor for persistent opioid use. These findings are important for patient counseling as well as support the safety profile of this new surgical pathway.

Purpose Aging is a risk factor for several debilitating conditions including those related to chronic back pain and intervertebral disc degeneration, both of which have no cure. Mouse models are useful tools for studying disc degeneration and chronic back pain in a tightly controlled and clinically relevant aging environment. Moreover, mice offer the advantage of carrying out longitudinal studies to understand the etiology and progression of disc pathology induced by genetic or surgical strategies. Previously, age-related behavioral trends of discomfort and enhanced nociception in mice were reported; however, whether these measures are mediated by structural and pathological changes in the disc is unknown. Methods The goal of the present observational study was to identify behavioral correlates of age-related degenerative changes in the disc. Towards this, we collected radiographs from 150 mice (77 females) between three and 23 months of age and measured the disc height index for each level of lumbar disc. Behavioral measures were collected on several of these mice which included rearing and distance travelled in an open field test; time spent in rearing, reaching, immobile, and self-suspended in the tail suspension test; bilateral hind paw licking in response to cold allodynia using acetone; and unilateral hind paw licking in response to heat hyperalgesia using capsaicin. Results Results show that the lower lumbar discs lose height with age and these changes are independent of body composition measures including body weight, bone mineral density, fat mass, lean weight mass, percent fat mass, and percent lean mass. Disc height positively correlates with rearing and mobility in the open field test, immobility in the tail suspension test, and thermal hyperalgesia. Disc height negatively correlates with cold allodynia and rearing in the tail suspension test. Furthermore, mediation analysis shows that the lumbosacral disc significantly mediates the effect of age on rearing in the open field test, but not cold allodynia, suggesting this behavior is a useful measure of age-related axial discomfort due to disc degeneration. Conclusion In summary, the findings from the current study show that disc height are associated with measures of axial discomfort and nociception in mice.

Accurate species delimitations are fundamental to our understanding of the genetic diversity on Earth and a vital part in evolutionary and conservation biology research. In lichenized fungi, species pairs have the same morphology and chemistry. They only differ in how they reproduce with one species using sexual reproductive structures and the other using asexual propagules. To classify these as one species or two has been a point of contention, and conclusions based on Sanger sequencing, where sequence data are limited and species boundaries are usually not observed, have been refuted after analysis with genome-scale data such as restriction site-associated DNA sequencing that tends to find fixed genetic differences between the two morphs. Pseudocyphellaria glabra and P. homoeophylla have long been considered a species pair that differ in geographical ranges but co-occur in New Zealand. We used restriction site-associated DNA sequencing data and generated thousands of genetic loci across 53 individuals. The RADseq data provided high-resolution phylogenetic and population genomic information. A maximum-likelihood phylogenetic reconstruction recovered both species as separate lineages, whereas population genetics indicated some evidence for admixture among P. glabra and P. homoeophylla from New Zealand. It is not clear whether the latter is due to ancient polymorphism or recent gene flow. Our study represents another example of the usefulness of RADseq to test species boundaries that segregate closely related species in lichenized fungi.

Background Wildland–urban interface (WUI) maps identify areas with wildfire risk, but they are often outdated owing to the lack of building data. Convolutional neural networks (CNNs) can extract building locations from remote sensing data, but their accuracy in WUI areas is unknown. Additionally, CNNs are computationally intensive and technically complex, making them challenging for end-users, such as those who use or create WUI maps, to apply. Aims We identified buildings pre- and post-wildfire and estimated building destruction for three California wildfires: Camp, Tubbs and Woolsey. Methods We evaluated a CNN-based building dataset and a CNN model from a separate commercial vendor to detect buildings from high-resolution imagery. This dataset and model represent to end-users the state of the art of what is readily available for potential WUI mapping. Key results We found moderate accuracies for the building dataset and the CNN model and a severe underestimation of buildings and their destruction rates where trees occluded buildings. The CNN model performed best post-fire with accuracies ≥73%. Conclusions Existing CNNs may be used with moderate accuracy for identifying individual buildings post-fire and mapping the extent of the WUI. The implications are, however, that CNNs are too inaccurate for post-fire damage assessments or building counts in the WUI.

How do human communities integrate within food webs? Studies characterizing the historical flow of energy among people and local environments can yield important insights into managing sustainable ecosystems. Here, we combine zooarchaeological, bulk tissue, and compound-specific stable isotope data from late Holocene Santa Rosa Island to investigate the ecological role of people within a southern California nearshore marine ecosystem. We show people foraged in diverse marine habitats, including kelp forests and pelagic waters, and consumed a wide range of species. However, zooarchaeological results reveal >50% of recovered fish remains came from presumed kelp forest carnivores of mid-trophic level (3.0–4.0) such as surfperches and rockfishes. Local fishing strategies thus did not involve the preferential removal of large-bodied, high trophic level species – a pattern known as “fishing down the food web” which has been documented in modern commercial fisheries and results in the collapse of marine ecosystems. Essential amino acid δ13C analysis revealed that the historical fish community relied on basal resources from kelps and phytoplankton. This coupling of benthic and pelagic energy sources suggests late Holocene coastal food webs in the region were in a relatively stable configuration immediately prior to first European arrival. This stability likely contributed to sustaining densely populated Chumash settlements, intensive fisheries, and high local faunal diversity. Our findings provide important pre-industrial data for marine ecosystems and document some of the mechanisms behind the intensive, yet sustainable long-term fisheries of the Island Chumash.

OBJECTIVES/BACKGROUND: Post-traumatic headache (PTH) is a common symptom after mild traumatic brain injury (mTBI). Although there have been several studies that have used clinical features of PTH to attempt to predict headache recovery, currently no accurate methods exist for predicting individuals’ improvement from acute PTH. This study investigated the utility of clinical questionnaires for predicting (i) headache improvement at 3 and 6 months, and (ii) headache trajectories over the first 3 months. METHODS: We conducted a clinic-based observational longitudinal study of patients with acute PTH who completed a battery of clinical questionnaires within 0–59 days post-mTBI. The battery included headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use. Each participant completed a web-based headache diary, which was used to determine headache improvement. RESULTS: Thirty-seven participants with acute PTH (mean age = 42.7, standard deviation [SD] = 12.0; 25 females/12 males) completed questionnaires at an average of 21.7 (SD = 13.1) days post-mTBI. The classification of headache improvement or non-improvement at 3 and 6 months achieved cross-validation area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.55 to 0.89) and 0.84 (95% CI 0.66 to 1.00). Sub-models trained using only the top five features still achieved 0.72 (95% CI 0.55 to 0.90) and 0.77 (95% CI 0.52 to 1.00) AUC. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub-domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State-Trait Anxiety Inventory score. The functional regression model achieved R = 0.64 for modeling headache trajectory over the first 3 months. CONCLUSION: Questionnaires completed following mTBI have good utility for predicting headache improvement at 3 and 6 months in the future as well as the evolving headache trajectory. Reducing the battery to only three questionnaires, which assess post-concussive symptom load and biopsychosocialecologic factors, was helpful to determine a reasonable prediction accuracy for headache improvement.

Cu is a unique metal that catalyzes carbon monoxide/carbon dioxide (CO/CO2) to form high-order hydrocarbons and oxygenates through the CO/CO2 reduction reaction (CO/CO2RR) at decent selectivity and productivity.

Angina with no obstructive coronary artery disease (ANOCA) is a common entity. There is still under-recognition of this condition, but it is unclear if the referral patterns for chest pain diagnosis have changed. We aimed to determine if the prevalence of patients diagnosed with ANOCA by means of coronary angiography has changed over time.A population-based cohort of patients who had their first coronary angiogram for a chest pain syndrome in Alberta from 1995 to 2020 was extracted retrospectively from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. A temporal trend analysis was performed to compare patients with ANOCA vs obstructive coronary artery disease (CAD), and the predictors of ANOCA were investigated.In our analysis, 121,066 patients were included (26% ANOCA, 31% female, overall mean age 62 years). The percentages of ANOCA vs obstructive CAD ranged from 24.2% to 26.7% in all patients (P0.001), from 19.4% to 21.4% in patients with acute coronary syndromes (P = 0.002), and from 30.6% to 37.5% in patients with stable angina (P0.001). Independent predictors of ANOCA were female sex (odds ratio [OR] 3.34, 95% confidence interval [CI] 3.05-3.66), younger age (OR 0.96, 95% CI 0.95-0.96), history of atrial fibrillation (OR 2.18, 95% CI 1.73-2.73), and stable angina (vs myocardial infarction: OR 0.25, 95% CI 0.23-0.28; vs unstable angina: OR 0.79, 95% CI 0.70-0.89). Traditional cardiovascular risk factors were associated with obstructive CAD.There remained a high prevalence of ANOCA detected during invasive coronary angiography, which remained stable over time. This study demonstrates an opportunity to exclude obstructive CAD with less invasive testing, particularly in women.

Ambulatory surgery centers (ASC) serve an important role for hospital systems of increasing operating capacity and offloading patient volume. When seeking to perform more complex cancer surgeries at an ASC, a systematic approach with care pathways can yield success by facilitating quick recovery for patients and reducing complication rates. End-to-end patient engagement is a key component of patient-centered care at the Josie Robertson Surgery Center and begins the moment the decision to have surgery is made and extends to the postdischarge period to track recovery. Engagement includes comprehensive education, standardization of processes, and setting clear expectations for recovery and discharge.

Background Remotely sensed burned area products are critical to support fire modelling, policy, and management but often require further processing before use. Aim We calculated fire history metrics from the Landsat Burned Area Product (1984–2020) across the conterminous U.S. (CONUS) including (1) fire frequency, (2) time since last burn (TSLB), (3) year of last burn, (4) longest fire-free interval, (5) average fire interval length, and (6) contemporary fire return interval (cFRI). Methods Metrics were summarised by ecoregion and land ownership, and related to historical and cheatgrass datasets to demonstrate further applications of the products. Key results The proportion burned ranged from 0.7% in the Northeast Mixed Woods to 74.1% in the Kansas Flint Hills. The Flint Hills and Temperate Prairies showed the highest burn frequency, while the Flint Hills and the Sierra Nevada and Klamath Mountains showed the shortest TSLB. Compared to private, public land had greater burned area (19 of 31 ecoregions) and shorter cFRI (25 of 31 ecoregions). Conclusions Contemporary fire history metrics can help characterise recent fire regimes across CONUS. Implications In regions with frequent fire, comparison of contemporary with target fire regimes or invasive species datasets enables the efficient incorporation of burned area data into decision-making.

Intertrochanteric osteotomies are used to correct a variety of congenital and acquired deformities of the proximal femur in children and adolescents. Varus, valgus, flexion, extension, or rotational osteotomies at the intertrochanteric level can be used to restore normal alignment of the proximal femur, increase congruency and stability of the hip joint, facilitate healing or remodeling of the femoral head and neck, redirect the articular surface, and improve functional limb position in the case of soft-tissue contractures. The steps necessary to assess proximal femoral deformity and plan the appropriate osteotomy are described along with indications and long-term considerations.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide, with no disease-specific treatment and up to 40% of patients progressing to kidney failure. IgA nephropathy (IgAN), characterized by IgA1-containing immunodeposits in the glomeruli, is considered to be an autoimmune disease in which the kidneys are injured as innocent bystanders. Glomerular immunodeposits are thought to originate from the circulating immune complexes that contain aberrantly O-glycosylated IgA1, the main autoantigen in IgAN, bound by IgG autoantibodies. A common clinical manifestation associated with IgAN includes synpharyngitic hematuria at disease onset or during disease activity. This observation suggests a connection of disease pathogenesis with an activated mucosal immune system of the upper-respiratory and/or gastrointestinal tract and IgA1 glycosylation. In fact, some cytokines can enhance production of aberrantly O-glycosylated IgA1. This process involves abnormal cytokine signaling in IgA1-producing cells from patients with IgAN. In this article, we present our view of pathogenesis of IgAN and review how some cytokines can contribute to the disease process by enhancing production of aberrantly glycosylated IgA1. We also review current clinical trials of IgAN based on cytokine-targeting therapeutic approaches.

Cardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01-0.1 Hz) in cerebral haemodynamics has been used in functional magnetic resonance imaging as a marker of neuronal activity. Our hypothesis was that increased LFP in cerebral blood flow (CBF) would be correlated with improvements in invasive measures of neurologic health.We adapted the use of LFP for to monitoring of CBF with diffuse correlation spectroscopy. We asked whether LFP (or other optical biomarkers) correlated with invasive microdialysis biomarkers (lactate-pyruvate ratio - LPR - and glycerol concentration) of neuronal injury in the 4 h after return of spontaneous circulation in a swine model of paediatric cardiac arrest (Sus scrofa domestica, 8-11 kg, 51% female). Associations were tested using a mixed linear effects model.We found that higher LFP was associated with higher LPR and higher glycerol concentration. No other biomarkers were associated with LPR; cerebral haemoglobin concentration, oxygen extraction fraction, and one EEG metric were associated with glycerol concentration.Contrary to expectations, higher LFP in CBF was correlated with worse invasive biomarkers. Higher LFP may represent higher neurologic activity, or disruptions in neurovascular coupling. Either effect may be harmful in the acute period after cardiac arrest. Thus, these results suggest our methodology holds promise for development of new, clinically relevant biomarkers than can guide resuscitation and post-resuscitation care. Institutional protocol number: 19-001327.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman’s body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.

Context During the COVID-19 pandemic, essential in-person electrocardiogram (ECG) recordings became unfeasible, while patients continued to suffer from cardiac conditions. To circumvent these challenges, the cardiology clinic (Long Island Heart Rhythm Center [LIHRC]) at the New York Institute of Technology College of Osteopathic Medicine (NYITCOM) transitioned to a remote real-time outpatient cardiac telemetry (ROCT) service. Objectives The goal of this study is to test the hypothesis that at-home ROCT, provided by the LIHRC, is an effective method of providing ECG monitoring to symptomatic patients during the COVID-19 pandemic. Methods Seventeen patients at the LIHRC that required ECGs between March 11 and August 1, 2020, were included in this study. The patients’ medical records were de-identified and reviewed for age, gender, ROCT indications, findings, patient comfort, and ease of use. A retrospective analysis of observational de-identified data obtained from the LIHRC was approved and permitted by the NYITCOM Institutional Review Board (BHS-1465). These FDA-cleared medical devices (DMS-300, DM Software, Stateline, NV) were shipped to the patients’ homes and were self-applied through adhesive chest patches. The devices communicated with a cloud-based system that produced reports including a continuous 6-lead ECG and many other cardiovascular parameters. Additionally, a patient-activated symptom recorder was available to correlate symptoms to ECG findings. Results Seventeen patients (15 women) from the LIHRC were included in the analysis with an average monitoring duration of 27 h (range, 24–72 h). The patients’ ages ranged from 21 to 85 years old with a mean of 37 years old and a standard deviation of 19. ROCT indications included palpitations (n=9), presyncope (n=8), chest pain (n=5), syncope (n=3), and shortness of breath (n=2). One also received ROCT due to short PR intervals observed on a prepandemic ECG. Two patients experienced palpitations while wearing the ROCT device: one had supraventricular tachycardia at 150 beats per minute; the other had unifocal premature ventricular contractions (PVCs) and eventually underwent a successful cardiac ablation. Most patients experienced no symptomatic episodes during ROCT (n=15). The 6-lead ROCT ECG for five of those patients showed arrhythmias including wandering atrial pacemaker (n=2), PVCs (n=2), sinus tachycardia (n=1), premature atrial contractions (PACs) (n=1), ectopic atrial rhythms (n=1), and sinus arrhythmia (n=1). One patient who experienced issues with our device was able to obtain a device from a separate clinic and was found to have bradycardia, PVCs, and nonsustained ventricular tachycardia. Overall, 16/17 (94.1%) patients were monitored effectively with the LIHRC ROCT system, and all (17/17, 100%) patients were monitored effectively with a ROCT system either from the LIHRC or a separate clinic. Conclusions With the unique challenges of the COVID-19 pandemic, physicians can use this innovative ROCT method to prevent infection and diagnose cardiac diseases. Most patients and staff were able to utilize the system without issues. Therefore, this system may also be utilized to deliver patient-centered care to those with limited mobility when coupled with a telemedicine visit.

OBJECTIVE Severe traumatic brain injury (TBI) is a leading cause of disability and death in the pediatric population. While intracranial pressure (ICP) monitoring is the gold standard in acute neurocritical care following pediatric severe TBI, brain tissue oxygen tension (PbtO2) monitoring may also help limit secondary brain injury and improve outcomes. The authors hypothesized that pediatric patients with severe TBI and ICP + PbtO2 monitoring and treatment would have better outcomes than those who underwent ICP-only monitoring and treatment. METHODS Patients ≤ 18 years of age with severe TBI who received ICP ± PbtO2 monitoring at a quaternary children’s hospital between 1998 and 2021 were retrospectively reviewed. The relationships between conventional measurements of TBI were evaluated, i.e., ICP, cerebral perfusion pressure (CPP), and PbtO2. Differences were analyzed between patients with ICP + PbtO2 versus ICP-only monitoring on hospital and pediatric intensive care unit (PICU) length of stay (LOS), length of intubation, Pediatric Intensity Level of Therapy scale score, and functional outcome using the Glasgow Outcome Score–Extended (GOS-E) scale at 6 months postinjury. RESULTS Forty-nine patients, including 19 with ICP + PbtO2 and 30 with ICP only, were analyzed. There was a weak negative association between ICP and PbtO2 (β = −0.04). Conversely, there was a strong positive correlation between CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm Hg (β = 0.30 and β = 0.29, p < 0.001, respectively). An increased number of events of cerebral PbtO2 < 15 mm Hg or < 20 mm Hg were associated with longer hospital (p = 0.01 and p = 0.022, respectively) and PICU (p = 0.015 and p = 0.007, respectively) LOS, increased duration of mechanical ventilation (p = 0.015 when PbtO2 < 15 mm Hg), and an unfavorable 6-month GOS-E score (p = 0.045 and p = 0.022, respectively). An increased number of intracranial hypertension episodes (ICP ≥ 20 mm Hg) were associated with longer hospital (p = 0.007) and PICU (p < 0.001) LOS and longer duration of mechanical ventilation (p < 0.001). Lower minimum hourly and average daily ICP values predicted favorable GOS-E scores (p < 0.001 for both). Patients with ICP + PbtO2 monitoring experienced longer PICU LOS (p = 0.018) compared to patients with ICP-only monitoring, with no significant GOS-E score difference between groups (p = 0.733). CONCLUSIONS An increased number of cerebral hypoxic episodes and an increased number of intracranial hypertension episodes resulted in longer hospital LOS and longer duration of mechanical ventilator support. An increased number of cerebral hypoxic episodes also correlated with less favorable functional outcomes. In contrast, lower minimum hourly and average daily ICP values, but not the number of intracranial hypertension episodes, were associated with more favorable functional outcomes. There was a weak correlation between ICP and PbtO2, supporting the importance of multimodal invasive neuromonitoring in pediatric severe TBI.

Retrospective case series.Predict cost following anterior cervical discectomy and fusion (ACDF) within the 90-day global period using machine learning models.The incidence of ACDF has been increasing with a disproportionate decrease in reimbursement. As bundled payment models become common, it is imperative to identify factors that impact the cost of care.The Nationwide Readmissions Database (NRD) was accessed in 2018 for all primary ACDFs by the International Classification of Diseases 10th Revision (ICD-10) procedure codes. Costs were calculated by utilizing the total hospital charge and each hospital's cost-to-charge ratio. Hospital characteristics, such as volume of procedures performed and wage index, were also queried. Readmissions within 90 days were identified, and cost of readmissions was added to the total admission cost to represent the 90-day healthcare cost. Machine learning algorithms were used to predict patients with 90-day admission costs1 SD from the mean.There were 42,485 procedures included in this investigation with an average age of 57.7±12.3 years with 50.6% males. The average cost of the operative admission was $24,874±25,610, the average cost of readmission was $25,371±11,476, and the average total cost was $26,977±28,947 including readmissions costs. There were 10,624 patients who were categorized as high cost. Wage index, hospital volume, age, and diagnosis-related group severity were most correlated with the total cost of care. Gradient boosting trees algorithm was most predictive of the total cost of care (area under the curve=0.86).Bundled payment models utilize wage index and diagnosis-related groups to determine reimbursement of ACDF. However, machine learning algorithms identified additional variables, such as hospital volume, readmission, and patient age, that are also important for determining the cost of care. Machine learning can improve cost-effectiveness and reduce the financial burden placed upon physicians and hospitals by implementing patient-specific reimbursement.

To establish the clinical relevance of porcine model of traumatic brain injury (TBI) using the plasma biomarkers of injury with diffusion tensor imaging (DTI) over 30 days, we performed a randomized, blinded, pre-clinical trial using Yorkshire pigs weighing 7-10 kg. Twelve pigs were subjected to Sham injury (n = 5) by skin incision or TBI (n = 7) by controlled cortical impact. Blood samples were collected before the injury, then at approximately 5-day intervals until 30 days. Both groups also had DTI at 24 h and at 30 days after injury. Plasma samples were isolated and single molecule array (Simoa) was performed for glial fibrillary acidic protein (GFAP) and neurofilament light (NFL) levels. Afterwards, brain tissue samples were stained for β-APP. DTI showed fractional anisotropy (FA) decrease in the right corona radiata (ipsilateral to injury), contralateral corona radiata, and anterior corpus callosum at 1 day. At 30 days, ipsilateral corona radiata showed decreased FA. Pigs with TBI also had increase in GFAP and NFL at 1-5 days after injury. Significant difference between Sham and TBI animals continued up to 20 days. Linear regression showed significant negative correlation between ipsilateral corona radiata FA and both NFL and GFAP levels at 1 day. To further validate the degree of axonal injury found in DTI, β-APP immunohistochemistry was performed on a perilesional tissue as well as corona radiata bilaterally. Variable degree of staining was found in ipsilateral corona radiata. Porcine model of TBI replicates the acute increase in plasma biomarkers seen in clinical TBI. Further, long term white matter injury is confirmed in the areas such as the splenium and corona radiata. However, future study stratifying severe and mild TBI, as well as comparison with other subtypes of TBI such as diffuse axonal injury, may be warranted.

IntroductionThe extent of the hemodynamic benefit from AV-synchronous pacing in patients with sinus rhythm and AV block is not completely understood. Thus, we systematically investigated the association of an array of echocardiographic and epidemiological parameters with the change in cardiac output depending on the stimulation mode (AV-synchronous or AV-asynchronous pacing).MethodsPatients in sinus rhythm after previous dual chamber pacemaker implantation underwent a thorough basic echocardiographic assessment of diastolic and systolic left ventricular function, and atrial function (26 echo parameters, including novel speckle tracking strain measurements). Then, stroke volume was measured with AV-synchronous (DDD) and AV-asynchronous (VVI) pacing. Each patient represented their own control, and the sequence of stroke volume measurements was randomized.ResultsIn this prospective single-center study (NCT04068233, registration August 22nd 2019), we recruited 40 individuals. The stroke volume was higher in all patients when applying AV-synchronous DDD pacing [median increase 12.8 ml (16.9%), P DiscussionIn our cohort of patients, each subject benefited from AV-synchronous DDD pacing. No single echo parameter could predict the amount of stroke volume increase. The beneficial effect of AV-synchronous pacing on stroke volume was attenuated after prior acute myocardial infarction.ClinicalTrials.gov identifier (NCT number): NCT04068233.