Design and rationale for REVERXaL: A real-world study of patients with factor Xa inhibitor-associated major bleeds.

BACKGROUND: The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants, including factor Xa inhibitors (FXai), are replacing vitamin K antagonists as the most commonly prescribed treatment for reducing risk of thrombotic events. While the risk of FXai-associated spontaneous bleeds is established, less is understood about their management and the effect of treatment on clinical and patient-reported outcomes. The primary objectives of the REVERXaL study are to describe patient characteristics, health care interventions during the acute-care phase, in-hospital outcomes, and associations between timing of reversal/replacement agent administration and in-hospital outcomes. Secondary/exploratory objectives focus on clinical assessments and patient-reported outcome measures (PROMs) at 30 and 90 days. METHODS: REVERXaL is a multinational, observational study of hospitalized patients with FXai-associated major bleeds in Germany, Japan, the United Kingdom, and the United States. The study includes 2 cohorts of approximately 2000 patients each. Cohort A is a historic cohort for whom medical chart data will be collected from hospitalization to discharge for patients admitted for major bleeds during FXai use within 2 years prior to enrollment of Cohort B. Cohort B will prospectively enroll patients administered any reversal/replacement agent during hospitalization to manage FXai-associated major bleeds and will include the collection of clinical outcomes and PROMs data over 3 months. CONCLUSIONS: REVERXaL will generate insights on patient characteristics, treatment approaches, and associated outcomes in patients hospitalized with FXai-associated major bleeds. These data may inform clinical practice and streamline treatment pathways in this population. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT06147830.

Evaluation and treatment of gastrointestinal bleeding in patients taking anticoagulants presenting to the emergency department.

This manuscript is a consensus document of an expert panel on the Evaluation and Treatment of Gastrointestinal Bleeding in Patients Taking Anticoagulants Presenting to the Emergency Department, sponsored by the American College of Emergency Physicians.

An Analysis of New York Data: Fluctuations in Hospital Capacity Are Driven by Variability in Elective Admissions and Discharge Activity.

Background Hospital overcrowding compromises patient safety. The contribution of variability in admissions and discharges to overall hospital capacity needs to be quantified. This study describes the statewide day-to-day fluctuation in the volume of hospitalized patients, the variability and pattern of hospital admissions and discharges throughout the week, and the contribution of Emergency Department (ED) vs. elective (non-ED) admissions and discharges to the overall variability in the system across the week. Methodology This is a retrospective analysis of the New York State Statewide Planning and Research Cooperative System database, in which all New York healthcare facilities submit patient-level data monthly. The study period was from January 01 to December 31, 2015. Outcomes included total volumes of admissions and discharges and length of stay sorted by patient origin (ED vs. non-ED admits (elective)) and service type (medicine vs. surgery) by day of the week. Results We studied 1,692,090 hospital admissions. Admissions were highest on Mondays and Tuesdays and steadily decreased throughout the week. There was little variability in the ED admissions throughout the week. Surgical elective admissions had significant variability throughout the week, with higher admissions at the beginning of the week. There was a significant difference (p < 0.01) between admissions on weekdays vs. weekends. Discharges increased from Monday to Friday, with a dramatic drop on the weekends, for both ED and elective pathways. Systemwide, on Monday, hospitals were 21% above the mean volume, and on Fridays, hospitals were 32% below the mean volume. Conclusions Overall hospital capacity shows dramatic variability throughout the week, driven primarily by elective admissions and discharges from any source throughout the week. Because elective admissions are schedulable, hospitals can reduce variability by smoothing scheduling. Increased weekend discharges will also improve capacity.

Introduction of a high sensitivity troponin reduces ED length of stay.

BACKGROUND: High sensitivity cardiac troponins (hs-cTn) allow earlier identification and exclusion of acute myocardial infarction. We determined if transitioning from contemporary to high sensitivity troponin T (hs-cTnT) would reduce ED length of stay in chest pain (CP) patients. METHODS: We conducted a pragmatic, prospective, before and after study of implementing a hs-cTnT by reviewing the electronic health records in all adult ED patients presenting to a large, suburban academic medical center during the 3 months before and after transitioning from a 4th generation troponin to a 5th generation hs-cTnT (Elecsys® Troponin T-high sensitive, Roche Diagnostics, Indianapolis, IN). RESULTS: There were 1431 and 1437 CP patients before and after the intervention. Mean (SD) age was 51.5 (18) yrs. and 54.3% were female. The median (IQR) ED LOS for chest pain patients directly discharged to home was 6.2 (4.7-8.4) and 5.3 (4.0-7.2) hours before and after introducing hs-cTn respectively; difference 47 min (95%CI, 35-59); P < 0.001. The median (IQR) ED LOS for chest pain patients admitted to the hospital was 9.5 (6.6-13.8) and 8.1 (5.7-11.2) hours before and after introducing hs-cTn respectively; difference 77 min (95%CI, 35-121); P < 0.001. Overall admission rates (22 vs 21% both before and after) did not change during the study. The rates of computed tomography coronary angiography before and after the intervention were 21 and 20.4% respectively. The rates of invasive coronary angiography before and after the intervention were 5.8 and 5.6% respectively. CONCLUSIONS: Transitioning to a hs-cTnT is associated with a clinically relevant and statistically significant reduction in ED LOS for both discharged and admitted patients with and without CP with no increase in admission or coronary angiography rates.

Early Enzymatic Burn Debridement: Results of the DETECT Multicenter Randomized Controlled Trial.

Since 1970 surgeons have managed deep burns by surgical debridement and autografting. We tested the hypothesis that enzymatic debridement with NexoBrid would remove the eschar reducing surgery and achieve comparable long-term outcomes as standard of care (SOC). In this Phase 3 trial, we randomly assigned adults with deep burns (covering 3-30% of total body surface area [TBSA]) to NexoBrid, surgical or nonsurgical SOC, or placebo Gel Vehicle (GV) in a 3:3:1 ratio. The primary endpoint was complete eschar removal (ER) at the end of the debridement phase. Secondary outcomes were need for surgery, time to complete ER, and blood loss. Safety endpoints included wound closure and 12 and 24-months cosmesis on the Modified Vancouver Scar Scale. Patients were randomized to NexoBrid (n = 75), SOC (n = 75), and GV (n = 25). Complete ER was higher in the NexoBrid versus the GV group (93% vs 4%; P < .001). Surgical excision was lower in the NexoBrid vs the SOC group (4% vs 72%; P < .001). Median time to ER was 1.0 and 3.8 days for the NexoBrid and SOC respectively (P < .001). ER blood loss was lower in the NexoBrid than the SOC group (14 ± 512 mL vs 814 ± 1020 mL, respectively; P < .0001). MVSS scores at 12 and 24 months were noninferior in the NexoBrid versus SOC groups (3.7 ± 2.1 vs 5.0 ± 3.1 for the 12 months and 3.04 ± 2.2 vs 3.30 ± 2.76 for the 24 months). NexoBrid resulted in early complete ER in >90% of burn patients, reduced surgery and blood loss. NexoBrid was safe and well tolerated without deleterious effects on wound closure and scarring.

Radiographic cervical spine injury patterns in admitted blunt trauma patients with and without prehospital spinal motion restriction.

Objectives: Selective prehospital cervical spine motion restriction (C-SMR) following blunt trauma has increasingly been used by emergency medical service (EMS) providers. We determined rates of prehospital C-SMR and concomitant radiographic injury patterns. Methods: A retrospective trauma registry and chart review was conducted for all adult blunt trauma patients who were transported by EMS and hospitalized with radiographic cervical spine injuries from 2011 to 2019 at a level 1 trauma center. Results: Of 658 admitted blunt trauma patients with confirmed cervical spine injury by imaging, 117 (17.8%) did not receive prehospital C-SMR. Patients without prehospital C-SMR were significantly older (76 vs 54 years), more often had low fall as mechanism of injury (59.8% vs 15.9%) and had lower Injury Severity Score (10 vs 17). Patients without C-SMR (Non-SMR) experienced the full array of cervical spine injury types and locations. While the non-SMR patients most often had dens fractures,C-SMR patients most often had C7 fractures; frequencies of fractures at the remaining vertebral levels were comparable. On MRI, cervical spinal cord (8.5% vs 19.6%) and ligamentous injuries (5.1% vs 12.6%) occurred less often in non-SMR patients. Approximately 8.5% of non-SMR patients and 20% of C-SMR patients required cervical spine surgery. Conclusion: Patients without prehospital C-SMR demonstrate a broad array of cervical spine injuries. While the rates of certain cervical injuries are lower in prehospital non-SMR patients, they are not insignificant. Level of evidence: Level III.

Treatment of Factor-Xa Inhibitor-associated Bleeding with Andexanet Alfa or 4 Factor PCC: A Multicenter Feasibility Retrospective Study.

Background: There are no randomized trials comparing andexanet alfa and 4 factor prothrombin complex concentrate (4F-PCC) for the treatment of factor Xa inhibitor (FXa-I)-associated bleeds, and observational studies lack important patient characteristics. We pursued this study to demonstrate the feasibility of acquiring relevant patient characteristics from electronic health records. Secondarily, we explored outcomes in patients with life-threatening FXa-I associated bleeds after adjusting for these variables. Methods: We conducted a multicenter, chart review of 100 consecutive adult patients with FXa-I associated intracerebral hemorrhage (50) or gastrointestinal bleeding (50) treated with andexanet alfa or 4F-PCC. We collected demographic, clinical, laboratory, and imaging data including time from last factor FXa-I dose and bleed onset. Results: Mean (SD) age was 75 (12) years; 34% were female. Estimated time from last FXa-I dose to bleed onset was present in most cases (76%), and patients treated with andexanet alfa and 4F-PCC were similar in baseline characteristics. Hemostatic efficacy was excellent/good in 88% and 76% of patients treated with andexanet alfa and 4F-PCC, respectively (P = 0.29). Rates of thrombotic events within 90 days were 14% and 16% in andexanet alfa and 4F-PCC patients, respectively (P = 0.80). Survival to hospital discharge was 92% and 76% in andexanet alfa and 4F-PCC patients, respectively (P = 0.25). Inclusion of an exploratory propensity score and treatment in a logistic regression model resulted in an odds ratio in favor of andexanet alfa of 2.01 (95% confidence interval 0.67-6.06) for excellent/good hemostatic efficacy, although the difference was not statistically significant. Conclusion: Important patient characteristics are often documented supporting the feasibility of a large observational study comparing real-life outcomes in patients with FXa-I-associated bleeds treated with andexanet alfa or 4F-PCC. The small sample size in the current study precluded definitive conclusions regarding the safety and efficacy of andexanet alfa or 4F-PCC in FXa-I-associated bleeds.

The role of point-of-care testing in cardiac arrest patients.

BACKGROUND: Point-of-care testing (POCT) provides real time information to the clinical team, leading to early diagnosis and treatment. Whether POCT plays a role in improving outcomes in patients with out of hospital cardiac arrest (OHCA) remains unknown. The objective of this study was to describe use of POCT in OHCA and to explore its association with outcomes. METHODS: We conducted a retrospective chart review on patients transferred by emergency medical services (EMS) to the ED for out-of-hospital cardiac arrest (OHCA) in 2019. Data collected from patient charts included baseline information, the Utstein criteria for cardiac arrest, whether POCT was used, whether POCT was abnormal, and what treatment was given, if any, as a result of the abnormal POCT. Outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge. Outcomes in patients with and without POCT were compared using chi-square and t-tests. RESULTS: There were 119 study patients. Their mean (SD) age was 65 (18) years and 65% were male. Cardiac arrest was witnessed in 48% and initial rhythm was asystole in 66%. The rates of ROSC and survival were 22.7% (95%CI, 16.1-31.1) and 3.4% (95%CI, 1.3-8.3). POCT was used in 66 patients (55.4%; 95%CI, 46.5-64.1) all of whom had at least one abnormality. The results of POCT led to administration of a therapy in 60 patients (91.0%; 95%CI, 81.6-95.8). The rates of ROSC in patients with and without POCT were 22.6% vs 22.7% respectively. The rates of survival to discharge in patients with and without POCT were 0% vs 3.8% respectively. CONCLUSIONS: POCT is commonly used in the ED for patients with OHCA and its results often lead to changes in therapies. However, use of POCT was not associated with ROSC or survival to discharge.

The Association between Emergency Department Length of Stay and In-Hospital Mortality in Older Patients Using Machine Learning: An Observational Cohort Study.

The association between emergency department (ED) length of stay (EDLOS) with in-hospital mortality (IHM) in older patients remains unclear. This retrospective study aims to delineate the relationship between EDLOS and IHM in elderly patients. From the ED patients (n = 383,586) who visited an urban academic tertiary care medical center from January 2010 to December 2016, 78,478 older patients (age ≥60 years) were identified and stratified into three age subgroups: 60-74 (early elderly), 75-89 (late elderly), and ≥90 years (longevous elderly). We applied multiple machine learning approaches to identify the risk correlation trends between EDLOS and IHM, as well as boarding time (BT) and IHM. The incidence of IHM increased with age: 60-74 (2.7%), 75-89 (4.5%), and ≥90 years (6.3%). The best area under the receiver operating characteristic curve was obtained by Light Gradient Boosting Machine model for age groups 60-74, 75-89, and ≥90 years, which were 0.892 (95% CI, 0.870-0.916), 0.886 (95% CI, 0.861-0.911), and 0.838 (95% CI, 0.782-0.887), respectively. Our study showed that EDLOS and BT were statistically correlated with IHM (p < 0.001), and a significantly higher risk of IHM was found in low EDLOS and high BT. The flagged rate of quality assurance issues was higher in lower EDLOS ≤1 h (9.96%) vs. higher EDLOS 7 h

Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes.

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.

Patiromer utility as an adjunct treatment in patients needing urgent hyperkalaemia management (PLATINUM): design of a multicentre, randomised, double-blind, placebo-controlled, parallel-group study.

INTRODUCTION: Hyperkalaemia is common, life-threatening and often requires emergency department (ED) management; however, no standardised ED treatment protocol exists. Common treatments transiently reducing serum potassium (K+) (including albuterol, glucose and insulin) may cause hypoglycaemia. We outline the design and rationale of the Patiromer Utility as an Adjunct Treatment in Patients Needing Urgent Hyperkalaemia Management (PLATINUM) study, which will be the largest ED randomised controlled hyperkalaemia trial ever performed, enabling assessment of a standardised approach to hyperkalaemia management, as well as establishing a new evaluation parameter (net clinical benefit) for acute hyperkalaemia treatment investigations. METHODS AND ANALYSIS: PLATINUM is a Phase 4, multicentre, randomised, double-blind, placebo-controlled study in participants who present to the ED at approximately 30 US sites. Approximately 300 adult participants with hyperkalaemia (K+ ≥5.8 mEq/L) will be enrolled. Participants will be randomised 1:1 to receive glucose (25 g intravenously <15 min before insulin), insulin (5 units intravenous bolus) and aerosolised albuterol (10 mg over 30 min), followed by a single oral dose of either 25.2 g patiromer or placebo, with a second dose of patiromer (8.4 g) or placebo after 24 hours. The primary endpoint is net clinical benefit, defined as the mean change in the number of additional interventions less the mean change in serum K+, at hour 6. Secondary endpoints are net clinical benefit at hour 4, proportion of participants without additional K+-related medical interventions, number of additional K+-related interventions and proportion of participants with sustained K+ reduction (K+ ≤5.5 mEq/L). Safety endpoints are the incidence of adverse events, and severity of changes in serum K+ and magnesium. ETHICS AND DISSEMINATION: A central Institutional Review Board (IRB) and Ethics Committee provided protocol approval (#20201569), with subsequent approval by local IRBs at each site, and participants will provide written consent. Primary results will be published in peer-reviewed manuscripts promptly following study completion. TRIAL REGISTRATION NUMBER: NCT04443608.

Impact of HEART Score Decision Aid on Coronary Computed Tomography Angiography Utilization and Diagnostic Yield in the Emergency Department.

OBJECTIVE: Emergency physicians are challenged to efficiently and reliably risk stratify patients presenting with chest pain (CP) to optimize diagnostic testing and avoid unnecessary hospital admissions. The objective of our study was to evaluate the impact of a HEART score-based decision aid (HSDA) integrated in the electronic health record on coronary computed tomography angiography (CCTA) utilization and diagnostic yield in adult emergency department (ED) CP patients with suspected acute coronary syndrome. METHODS: We conducted a before and after study to determine whether implementation of a mandatory computerized HSDA would reduce CCTA utilization in ED CP patients and improve the diagnostic yield of obstructive coronary artery disease (CAD) (≥50%). We included all adult ED CP patients with suspected acute coronary syndrome during the first 6 months of 2018 (before) and 2020 (after) at a large academic center. CCTA utilization and obstructive CAD yield were compared in patients before and after implementing the HSDA using χ2 tests. Secondarily, we assessed the association of HEART scores and CCTA results. RESULTS: Of the 3095 CP patients during the before study period, 733 underwent CCTA. Of the 2692 CP patients during the after study period, 339 underwent CCTA. CCTA utilization before and after HSDA was 23.4% [95% confidence interval (95% CI), 22.2-25.2] and 12.6% (95% CI, 11.4-13.0), respectively; mean difference was 11.1% (95% CI, 0.9-13.0). Among 1072 patients undergoing CCTA, mean (SD) age and percent females before versus after HSDA were 54 (11) versus 56 (11) years and 50% versus 49%, respectively. We included 1014 patients (686 before and 328 after) for the yield analysis. Obstructive CAD was present in 15% (95% CI, 12.7-17.9) and 20.1% (95% CI, 16.1-24.7) before and after HSDA, respectively; mean difference was 4.9% (95% CI, 0.1-10.1). CONCLUSIONS: Implementation of a mandatory electronic health record HSDA aid reduced ED CCTA utilization by half and improved the diagnostic yield.

FOCUS may detect wall motion abnormalities in patients with ACS.

BACKGROUND: Chest pain is a common presentation to the Emergency Department (ED) with roughly 6 million visits a year. The primary diagnostic modality for the identification of acute coronary syndrome (ACS) is the electrocardiogram (ECG), which is used to screen for electrocardiographic findings representing acute coronary occlusion. It is known that the ischemia generated by an acutely occluded coronary vessel generates a wall motion abnormality which can be visualized by echocardiogram; however, emergency physician-performed focused cardiac ultrasound (FOCUS) currently does not have a formal role in the diagnosis of OMI within the emergency department. PURPOSE: We sought to define the characteristics of FOCUS performed by emergency physicians of variable training levels in the identification of RWMA in patients presenting to the emergency department with high suspicion for ACS before undergoing cardiac catheterization or formal echocardiography. We also explored whether RWMA was associated with OMI in these patients. METHODS: We performed a structured, retrospective review of adult patients presenting to a large, academic, tertiary care center with suspected ACS from July 1st, 2019, and October 24th, 2020. Patients were included if they underwent FOCUS in the ED during the time-period above for suspected ACS looking for RWMA and FOCUS images were stored and reviewable in our middleware software. The primary outcome was the accuracy, sensitivity, and specificity of FOCUS compared to formal echocardiography for the detection of RWMA. Secondary outcomes were sensitivity of FOCUS compared to formal echocardiography for detection of RWMA in patients with and without cardiac catheterization proven OMI and sensitivity and specificity of FOCUS operators based on training. RESULTS: FOCUS for RWMA performed by emergency physicians had a sensitivity of 94% (95% CI, 82-98), specificity 35% (95% CI, 15-61), and overall accuracy of 78% (95% CI, 66-87). Of all subjects, 82% underwent urgent or emergency coronary angiography, of which 71% had OMI at the time of coronary angiography of the procedure. FOCUS identified RWMA in 87% of patients with coronary angiography proven OMI. Residents (PGY-1 - PGY-3) (n = 31) were able to detect RWMA with a sensitivity of 86% (95% CI, 64-96), a specificity of 56% (95% CI, 23-85%), and an accuracy of 77 (95% CI, 58-90%). Emergency ultrasound fellows and attendings (n = 34) were able to detect RWMA with a sensitivity of 85% (95% CI, 64-95%), a specificity of 75% (95% CI, 36-96%), and an accuracy of 82% (95% CI, 65-93%). CONCLUSIONS: Our retrospective study concludes FOCUS performed by emergency physicians may be used to detect RWMA in patients with high concern for acute coronary syndrome. This may have its greatest utility in patients presenting without STEMI where the ECG is felt to be equivocal, but the clinician has high concern for OMI, in which the presence of RWMA might result in emergent cath lab activation, though this requires further study. The presence of RWMA in such cases may help to rule in OMI as a cause; however, the absence of RWMA should exclude OMI. Further research is necessary to confirm these findings.

Analgesic use in ED patients with long-bone fractures: A national assessment of racial and ethnic disparities.

BACKGROUND: It is vital to ensure equitable care is given to all patients and to eliminate any disparities in administration of analgesics and opioids in emergency department (ED) patients with long-bone fractures. Our objective was to determine whether sex, ethnic, or racial disparities still exist in administration and prescription of analgesics and opioids in ED patients with long-bone fractures using a current nationally representative database. METHODS: This was a retrospective, cross-sectional analysis of ED patients ages 15-55 years with long-bone fractures included in the National Hospital and Medical Care Survey (NHAMCS) database from 2016 to 2019. Our primary and secondary outcomes were administration of analgesics and opioids in the ED and our exploratory outcomes were prescription of analgesics and opioids in discharged patients. Outcomes were adjusted for age, sex, race, insurance, fracture location, number of fractures, and pain severity. RESULTS: Of the estimated 2.32 million ED patient visits analyzed, 65% received analgesics and 50% received opioids in the ED. On multivariable analyses, administration of analgesics was associated with female sex (OR 2.11; 95% CI 1.08-4.12) and Black race (OR 2.84; 95% CI 1.03-7.80), but not with Hispanic/Latino ethnicity (OR 2.09; 95% CI 0.72-6.04). No associations were found between opioid administration or analgesic or opioid prescription and female sex, Hispanic/Latino ethnicity, or Black race. CONCLUSIONS: Between 2016 and 2019 there were no significant sex, ethnic, or racial disparities in administration or prescription of analgesics or opioids in ED adult patients with long-bone fractures.

Triage of in vivo burn injuries and prediction of wound healing outcome using neural networks and modeling of the terahertz permittivity based on the double Debye dielectric parameters.

The initial assessment of the depth of a burn injury during triage forms the basis for determination of the course of the clinical treatment plan. However, severe skin burns are highly dynamic and hard to predict. This results in a low accuracy rate of about 60 - 75% in the diagnosis of partial-thickness burns in the acute post-burn period. Terahertz time-domain spectroscopy (THz-TDS) has demonstrated a significant potential for non-invasive and timely estimation of the burn severity. Here, we describe a methodology for the measurement and numerical modeling of the dielectric permittivity of the in vivo porcine skin burns. We use the double Debye dielectric relaxation theory to model the permittivity of the burned tissue. We further investigate the origins of dielectric contrast between the burns of various severity, as determined histologically based on the percentage of the burned dermis, using the empirical Debye parameters. We demonstrate that the five parameters of the double Debye model can form an artificial neural network classification algorithm capable of automatic diagnosis of the severity of the burn injuries, and predicting its ultimate wound healing outcome by forecasting its re-epithelialization status in 28 days. Our results demonstrate that the Debye dielectric parameters provide a physics-based approach for the extraction of the biomedical diagnostic markers from the broadband THz pulses. This method can significantly boost dimensionality reduction of THz training data in artificial intelligence models and streamline machine learning algorithms.

Longitudinal Chest X-ray Scores and their Relations with Clinical Variables and Outcomes in COVID-19 Patients.

Background: This study evaluated the temporal characteristics of lung chest X-ray (CXR) scores in COVID-19 patients during hospitalization and how they relate to other clinical variables and outcomes (alive or dead). Methods: This is a retrospective study of COVID-19 patients. CXR scores of disease severity were analyzed for: (i) survivors (N = 224) versus non-survivors (N = 28) in the general floor group, and (ii) survivors (N = 92) versus non-survivors (N = 56) in the invasive mechanical ventilation (IMV) group. Unpaired t-tests were used to compare survivors and non-survivors and between time points. Comparison across multiple time points used repeated measures ANOVA and corrected for multiple comparisons. Results: For general-floor patients, non-survivor CXR scores were significantly worse at admission compared to those of survivors (p < 0.05), and non-survivor CXR scores deteriorated at outcome (p < 0.05) whereas survivor CXR scores did not (p > 0.05). For IMV patients, survivor and non-survivor CXR scores were similar at intubation (p > 0.05), and both improved at outcome (p < 0.05), with survivor scores showing greater improvement (p < 0.05). Hospitalization and IMV duration were not different between groups (p > 0.05). CXR scores were significantly correlated with lactate dehydrogenase, respiratory rate, D-dimer, C-reactive protein, procalcitonin, ferritin, SpO2, and lymphocyte count (p < 0.05). Conclusions: Longitudinal CXR scores have the potential to provide prognosis, guide treatment, and monitor disease progression.

Hyponatremia and hypernatremia in the emergency department: severity and outcomes.

OBJECTIVE: Hyponatremia and hypernatremia are common electrolyte disorders. Few studies to date have focused on patients presenting to the emergency department (ED) with sodium (Na) disorders. Our objective was to determine the incidence and outcomes of hyponatremia and hypernatremia in ED patients. METHODS: This study was a retrospective, single-center review of electronic medical records at an academic suburban ED with approximately 100,000 annual visits. Subjects included consecutive adult ED patients with Na levels measured while in the ED in 2019. Demographic, clinical, and laboratory data were recorded. Outcomes data, including hospital admission, intensive care unit (ICU) admission, mortality, and length of stay (LOS), were recorded. The primary outcome was inhospital death. Secondary outcomes were hospital admission, ICU admission, ED LOS, and hospital LOS. Univariable and multivariable linear and logistic regression analyses were performed to explore the association of candidate predictor variables and outcomes. RESULTS: Na was measured in 57,427 adults (54%) among a total of 106,764 assessed ED visits in 2019. The mean±standard deviation age was 54±21 years, and 47% of participants were male. Mild, moderate, and severe hyponatremia and hypernatremia occurred in 8%, 2%, and 0.1% of patients and 1%, 0.2%, and <0.1% of patients, respectively. Hospital and ICU admission and mortality rates increased as Na levels increased or decreased further from normal. Adjusted odds ratio (95% confidence interval) values for hospital mortality were 2.39 (1.97-2.90) for mild hyponatremia, 3.93 (2.95-5.24) for moderate hyponatremia, 6.98 (2.87-16.40) for severe hyponatremia, 3.65 (2.47-5.40) for mild hypernatremia, 8.58 (4.92-14.94) for moderate hypernatremia, and 55.75 (11.37-273.30) for severe hypernatremia. Hypernatremia was associated with a greater risk of death than hyponatremia. Patients with hyponatremia and hypernatremia had increased LOS times compared to those with normal Na levels. CONCLUSION: Hyponatremia and hypernatremia were associated with greater rates of hospital admission, ICU admission, mortality, and prolonged hospital LOS times.

A Comparison of Topical Agents for Eschar Removal in a Porcine Model: Bromelain-enriched vs Traditional Collagenase Agents.

Surgical excision and grafting of deep partial-thickness (DPT) and full-thickness (FT) burns is a cornerstone of wound care. The use of commercially available topical enzymatic agents has been limited due to slower and less complete eschar removal than surgical excision. Using a porcine model of DPT and FT burns, we compared the eschar removal efficacy of a bromelain-enriched enzymatic agent derived from the stems of pineapple plants and a commercially available collagenase. We created 40 DPT and 40 FT burns on four anesthetized Yorkshire pigs. Eschar removal was initiated 24 hours later. Two pigs each were randomly assigned to collagenase or the bromelain-enriched agent. The bromelain-enriched agent was applied topically once for 4 hours followed by a 2-hour soaking. The collagenase was applied topically daily until complete removal of eschar or for up to 14 days. All bromelain-enriched treated FT burns underwent complete removal of the eschar after a single application while none of the collagenase-treated FT burns underwent complete removal of the eschar even after 14 days of treatment. All bromelain-enriched treated DPT burns had complete eschar removal after the single application. None of the collagenase-treated DPT burns experienced complete removal of eschar after 10 days; by day 14, 35% had complete eschar removal, 30% had >50% eschar removed, and 35% had <50% eschar removed. We conclude that eschar removal is quicker and more complete with the bromelain-enriched compared with collagenase debriding agent.

An open-label, proof-of-concept study assessing the effects of bromelain-based enzymatic debridement on biofilm and microbial loads in patients with venous leg ulcers and diabetic foot ulcers.

BACKGROUND: Most chronic wounds contain biofilm, and debridement remains the centerpiece of treatment. Enzymatic debridement is an effective tool in removing nonviable tissue, however, there is little evidence supporting its effect on planktonic and biofilm bacteria. OBJECTIVE: This study evaluated the effects of a novel BBD agent on removal of nonviable tissue, biofilm, and microbial loads in patients with chronic ulcers. MATERIALS AND METHODS: Twelve patients with DFU or VLU were treated with up to 8 once-daily applications of BBD and then followed for an additional 2 weeks. Punch biopsy specimens were collected and analyzed for biofilm, and fluorescence imaging was used to measure bacterial load. RESULTS: Ten patients completed treatment, and 7 achieved complete debridement within a median of 2 applications (range, 2-8). By the end of the 2-week follow-up period, the mean ± SD reduction in wound area was 35% ± 38. In all 6 patients who were positive for biofilm at baseline, the biofilm was reduced to single individual or no detected microorganisms by the end of treatment. Red fluorescence for Staphylococcus aureus decreased from a mean of 1.09 cm² ± 0.58 before treatment to 0.39 cm² ± 0.25 after treatment. BBD was safe and well tolerated. CONCLUSION: Preliminary data suggest that BBD is safe and that it can be used to effectively debride DFU and VLU, reduce biofilm and planktonic bacterial load, and promote reduction in wound size.