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BACKGROUND: Trauma systems save lives by coordinating timely and effective responses to injury. However, trauma system effectiveness varies geographically, with worse outcomes observed in rural settings. Prior data suggest that undertriage may play a role in this disparity. Our aim was to explore potential driving factors for decision making among clinicians for undertriaged trauma patients. METHODS: We performed a retrospective analysis of the National Emergency Medical Services Information System database among patients who met physiologic or anatomic national field triage guideline criteria for transport to the highest level of trauma center. Undertriage was defined as transport to a non-level I/II trauma center. Multivariable logistic regression was used to determine demographic, injury, and system characteristics associated with undertriage. Undertriaged patients were then categorized into "recognized" and "unrecognized" groups using the documented reason for transport destination to identify underlying factors associated with undertriage. RESULTS: A total of 36,094 patients were analyzed. Patients in urban areas were more likely to be transported to a destination based on protocol rather than the closest available facility. As expected, patients injured in urban regions were less likely to be undertriaged than their suburban (adjusted odds ratio [aOR], 2.69; 95% confidence interval [95% CI], 2.21-3.31), rural (aOR, 2.71; 95% CI, 2.28-3.21), and wilderness counterparts (aOR, 3.99; 95% CI, 2.93-5.45). The strongest predictor of undertriage was patient/family choice (aOR, 6.29; 5.28-7.50), followed by closest facility (aOR, 5.49; 95% CI, 4.91-6.13) as the reason for hospital selection. Nonurban settings had over twice the odds of recognizing the presence of triage criteria among undertriaged patients (p < 0.05). CONCLUSION: Patients with injuries in nonurban settings and those with less apparent causes of severe injury are more likely to experience undertriage. By analyzing how prehospital clinicians choose transport destinations, we identified patient and system factors associated with undertriage. Targeting these at-risk demographics and contributing factors may help alleviate regional disparities in undertriage. LEVEL OF EVIDENCE: Diagnostic; Level IV.
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Background: Emergency general surgery (EGS) often demands timely interventions, yet data for triage and timing are limited. This study explores the relationship between hospital arrival-to-operation time and mortality in EGS patients. Study design: We performed a retrospective cohort study using an EGS registry at four hospitals, enrolling adults who underwent operative intervention for a primary American Association for the Surgery of Trauma-defined EGS diagnosis between 2021 and 2023. We excluded patients undergoing surgery more than 72 hours after admission as non-urgent and defined our exposure of interest as the time from the initial vital sign capture to the skin incision timestamp. We assessed the association between operative timing quintiles and in-hospital mortality using a mixed-effect hierarchical multivariable model, adjusting for patient demographics, comorbidities, organ dysfunction, and clustering at the hospital level. Results: A total of 1199 patients were included. The median time to operating room (OR) was 8.2 hours (IQR 4.9-20.5 hours). Prolonged time to OR increased the relative likelihood of in-hospital mortality. Patients undergoing an operation between 6.7 and 10.7 hours after first vitals had the highest odds of in-hospital mortality compared with operative times <4.2 hours (reference quintile) (adjusted OR (aOR) 68.994; 95% CI 4.608 to 1032.980, p=0.002). A similar trend was observed among patients with operative times between 24.4 and 70.9 hours (aOR 69.682; 95% CI 2.968 to 1636.038, p=0.008). Conclusion: Our findings suggest that prompt operative intervention is associated with lower in-hospital mortality rates among EGS patients. Further work to identify the most time-sensitive populations is warranted. These results may begin to inform benchmarking for triaging interventions in the EGS population to help reduce mortality rates. Level of evidence: IV.
ABSTRACT
Apelin-13, a type of active peptide, can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the specific mechanism is unclear. Cell cycle checkpoint kinase 1 (Chk1) plays an important role in DNA damage. Here, we investigated the regulatory effect of Apelin on Chk1 in ALI. Chk1-knockout and -overexpression mice were used to explore the role of Chk1 in LPS-induced ALI mice treated with or without Apelin-13. In addition, A549 cells were also treated with LPS to establish a cell model. Chk1 knockdown inhibited the destruction of alveolar structure, the damage of lung epithelial barrier function, and DNA damage in the ALI mouse model. Conversely, Chk1 overexpression had the opposite effect. Furthermore, Apelin-13 reduced Chk1 expression and DNA damage to improve the impaired lung epithelial barrier function in the ALI model. However, the high expression of Chk1 attenuated the protective effect of Apelin-13 on ALI. Notably, Apelin-13 promoted Chk1 degradation through autophagy to regulate DNA damage in LPS-treated A549 cells. In summary, Apelin-13 regulates the expression of Chk1 by promoting autophagy, thereby inhibiting epithelial DNA damage and repairing epithelial barrier function.
Subject(s)
Acute Lung Injury , Checkpoint Kinase 1 , DNA Damage , Lipopolysaccharides , Mice, Inbred C57BL , Mice, Knockout , Animals , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Lipopolysaccharides/toxicity , Mice , DNA Damage/drug effects , DNA Damage/physiology , Checkpoint Kinase 1/metabolism , Checkpoint Kinase 1/genetics , Humans , A549 Cells , Male , Disease Models, Animal , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Respiratory Mucosa/metabolism , Respiratory Mucosa/drug effectsABSTRACT
BACKGROUND: Andexanet Alfa (AA) is the only FDA approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with 4-Factor Prothrombin Complex Concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing non-inferiority of PCC. METHODS: We performed a retrospective, non-inferiority multicenter study of adult patients admitted from July 1, 2018 to December 31, 2019 who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with ICU length of stay. MICE imputation was used to account for missing data and zero-inflated poisson regression was used to account for an excess of zero units of RBC transfused. 2 Units difference in RBC transfusion was selected as non-inferior. RESULTS: Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% CI: 0.79-1.33) compared to AA after adjusting for other covariates. The averaged amount of RBC transfusion (non-zero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% CI: 0.53-2.02) units compared to AA. CONCLUSION: PCC appears non-inferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.
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INTRODUCTION: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies. METHODS: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding. RESULTS: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS. CONCLUSION: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms.
Subject(s)
Acute Kidney Injury , Erythrocyte Transfusion , Hemorrhage , Respiratory Distress Syndrome , Humans , Acute Kidney Injury/etiology , Acute Kidney Injury/blood , Acute Kidney Injury/therapy , Child , Child, Preschool , Male , Female , Infant , Erythrocyte Transfusion/adverse effects , Hemorrhage/etiology , Hemorrhage/blood , Hemorrhage/therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/therapy , Adolescent , Prospective Studies , Platelet Transfusion/adverse effects , Risk FactorsABSTRACT
BACKGROUND: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies. STUDY DESIGN AND METHODS: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses. RESULTS: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex. CONCLUSION: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age.
Subject(s)
Blood Transfusion , Hemorrhage , Humans , Male , Female , Child , Child, Preschool , Hemorrhage/therapy , Hemorrhage/mortality , Hemorrhage/etiology , Prospective Studies , Sex Factors , Adolescent , Infant , Treatment Outcome , Age FactorsABSTRACT
BACKGROUND: Air medical transport (AMT) improves outcomes for severely injured patients. The decision to fly patients is complex and must consider multiple factors. Our objective was to evaluate the interaction between geography, patient and environmental factors, and emergency medical services (EMS) system resources on AMT after trauma. We hypothesize that significant geographic variation in AMT utilization will be associated with varying levels of patient, environmental, and EMS resources. METHODS: Patients transported by EMS in the Pennsylvania state trauma registry 2000 to 2017 were included. We used our previously developed Air Medical Prehospital Triage (AMPT; ≥2 points triage to AMT) score and Geographic Emergency Medical Services Index (GEMSI; higher indicates more system resources) as measures for patient factors and EMS resources, respectively. A mixed-effects logistic regression model determined the association of AMT utilization with patient, system, and environmental variables. RESULTS: There were 195,354 patients included. Fifty-five percent of variation in AMT utilization was attributed to geographic differences. Triage to AMT by the AMPT score was associated with nearly twice the odds of AMT utilization (adjusted odds ratio, 1.894; 95% confidence interval, 1.765-2.032; p < 0.001). Each 1-point increase in GEMSI was associated with a 6.1% reduction in odds of AMT (0.939; 0.922-0.957; p < 0.001). Younger age, rural location, and more severe injuries were also associated with increased odds of AMT ( p < 0.05). When categorized by GEMSI level, the AMPT score and patient factors were more important for predicting AMT utilization in the middle tercile (moderate EMS resources) compared with the lower (low EMS resources) and higher tercile (high EMS resources). Weather, season, time-of-day, and traffic were all associated with AMT utilization ( p < 0.05). CONCLUSION: Patient, system, and environmental factors are associated with AMT utilization, which varies geographically and by EMS/trauma system resource availability. A more comprehensive approach to AMT triage could reduce variation and allow more tailored efforts toward optimizing resource allocation and outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.
Subject(s)
Emergency Medical Services , Wounds and Injuries , Humans , Triage , Pennsylvania/epidemiology , Registries , Geography , Trauma Centers , Retrospective Studies , Wounds and Injuries/therapyABSTRACT
BACKGROUND: Low-titer group O whole blood (LTOWB) or component therapy (CT) may be used to resuscitate hemorrhaging trauma patients. LTOWB may have clinical and logistical benefits and may improve survival. OBJECTIVES: We hypothesized LTOWB would improve 24-hour survival in hemorrhaging patients and would be safe and equally efficacious in non-group O compared with group O patients. METHODS: Adult trauma patients with massive transfusion protocol activations were enrolled in this observational study. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour total blood product use. A Cox regression determined the independent associations with 24-hour mortality. RESULTS: In total, 348 patients were included (CT, n = 180; LTOWB, n = 168). Demographics were similar between cohorts. Unadjusted 24-hour mortality was reduced in LTOWB vs CT: 8% vs 19% (P = .003), but 6-hour and 28-day mortality were similar. In an adjusted analysis with multivariable Cox regression, LTOWB was independently associated with reduced 24-hour mortality (hazard ratio, 0.21; 95% CI, 0.07-0.67; P = .004). LTOWB patients received significantly less 72-hour total blood products (80.9 [41.6-139.3] mL/kg vs 48.9 [25.9-106.9] mL/kg; P < .001). In stratified 24-hour survival analyses, LTOWB was associated with improved survival for patients in shock or with coagulopathy. LTOWB use in non-group O patients was not associated with increased mortality, organ injury, or adverse events. CONCLUSION: In this hypothesis-generating study, LTOWB use was independently associated with improved 24-hour survival, predominantly in patients with shock or coagulopathy. LTOWB also resulted in a 40% reduction in blood product use which equates to a median 2.4 L reduction in transfused products.
Subject(s)
Resuscitation , Wounds and Injuries , Adult , Humans , Resuscitation/adverse effects , Resuscitation/methods , Blood Transfusion/methods , Hemorrhage/therapy , Proportional Hazards Models , ABO Blood-Group System , Wounds and Injuries/complications , Wounds and Injuries/diagnosis , Wounds and Injuries/therapyABSTRACT
BACKGROUND: The American Association for the Surgery of Trauma and the American College of Surgeons have recently introduced emergency general surgery (EGS) center verification, which could enhance patient outcomes. Distance and resource availability may affect access to these centers, which has been linked to higher mortality. Although many patients can receive adequate care at community centers, those with critical conditions may require specialized treatment at EGS-verified centers. We aimed to evaluate geospatial access to potential EGS-verified centers and identify disparities across different scenarios of EGS verification program uptake in the United States. METHODS: We used hospital capabilities and verified pilot centers to estimate potential patterns of which centers would become EGS verified under four scenarios (EGS centers, high-volume EGS centers, high-volume EGS plus level 1 trauma centers, and quaternary referral centers). We calculated the spatial accessibility index using an enhanced two-step floating catchment technique to determine geospatial access for each scenario. We also evaluated social determinants of health across geospatial access using the Area Deprivation Index (ADI). RESULTS: A total of 1,932 hospitals were categorized as EGS centers, 307 as high-volume EGS centers, 401 as high-volume EGS plus level 1trauma centers, and 146 as quaternary centers. Spatial accessibility index decreased as the stringency of EGS verification increased in each scenario (226.6 [111.7-330.7], 51.8 [0-126.1], 71.52 [3.34-164.56], 6.2 [0-62.2]; p < 0.001). Within each scenario, spatial accessibility index also declined as the ADI quartile increased ( p < 0.001). The high-volume EGS plus level 1trauma center scenario had the most significant disparity in access between the first and fourth ADI quartiles (-54.68). CONCLUSION: Access to EGS-verified centers may vary considerably based on the program's implementation. Disadvantaged communities may be disproportionately affected by limited access. Further work to study regional needs can allow a strategic implementation of the EGS verification program to optimize outcomes while minimizing disparities. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.
Subject(s)
General Surgery , Surgeons , Humans , United States , Trauma Centers , Acute Care Surgery , Hospitals , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of this study was to evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies. BACKGROUND: Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS. METHODS: A retrospective analysis of prospective cohort including 8 trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18 to 90 years old with injury severity scores ≥9 transported from the scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and early mortality. RESULTS: A total of 33,511 were included with a median EMS agency volume of 374 patients annually (interquartile range: 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (adjusted odds ratio=0.95; 95% CI: 0.92-0.99, P =0.03) and 3% decreased odds of 24-hour mortality (adjusted odds ratio=0.97; 95% CI: 0.95-0.99, P =0.04). Prespecified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% vs 4.8%, P <0.01). CONCLUSIONS: A higher volume of trauma patients transported at the EMS agency level is associated with improved early mortality. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.
Subject(s)
Emergency Medical Services , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Prospective Studies , Trauma Centers , Hospital Mortality , Injury Severity ScoreABSTRACT
Cation exchange (CE) is a burgeoning method for controlled crystal synthesis; however, its applications in bioanalysis are still in their infancy. Herein, we explored the transformation of ZnIn2S4 in properties after the CE reaction with Cu2+ ions; furthermore, the discrepancy was employed to design a dual-readout detection system of photothermal and polarity-switchable photoelectrochemical (PEC) immunoassays to realize reliable detection of carcinoembryonic antigen (CEA). In the presence of CEA, the CuO nanoparticles (CuO NPs) employed as dual-signal response probes would bond to the microplates and be acidolyzed by HCl to release Cu2+, which could replace Zn2+ and In3+ via the CE reaction. After the CE reaction is completed, the photocurrent would switch from a weak anodic photocurrent to a cathode one by using a 635 nm laser as a signal amplifier, while the photothermal signal would be enhanced with 808 nm laser illumination. On the basis of the polarity-switchable PEC strategy, CEA could be accurately detected from 0.1 to 50 ng mL-1 with a limit of detection (LOD) of 48 pg mL-1 (S/N = 3). Moreover, the photothermal assay for CEA detection possesses a linear range from 0.5 to 100 ng mL-1 with a LOD of 0.21 ng mL-1. In addition, the designed sensing platform only relies on devices with portability that are permitted for point-of-care detection.
Subject(s)
Biosensing Techniques , Carcinoembryonic Antigen , Carcinoembryonic Antigen/analysis , Electrochemical Techniques/methods , Biosensing Techniques/methods , Immunoassay/methods , Limit of Detection , CationsABSTRACT
A new photoelectrochemical immunoassay based on self-assembled p-n Ag2O@Bi2O2S nanoflower heterojunction was designed and developed for quantitative monitoring of prostate-specific antigen (PSA) in biological fluids. Primarily, self-assembled p-n Ag2O@Bi2O2S nanoflower heterojunctions were served as the photoactive materials and coated onto the surface of electrodes. Subsequently, the glucose oxidase (GOx) was bound to the detection antibody (mAb2) labeled gold nanoparticles (Au NPs) and then were employed to accomplish a sandwich-like immunoreaction to generate H2O2 on a microplate incubated with monoclonal anti-PSA antibodies. In the presence of PSA, the product (H2O2) was catalyzed by the substrate, which was used as an electron sacrificial agent to improve signal conversion and capture of photogenerated electrons. Under optimum conditions, a wide linear range of 0.01-50 ng mL-1 and a low detection limit of 5.3 pg mL-1 were accomplished with the sensor, exhibiting an excellent photocurrent response. Moreover, the proposed sensor revealed satisfactory reproducibility, high selectivity, and acceptable accuracy for the real sample testing. Importantly, our work provides a novel strategy for high sensitivity detection of disease-associated biomarkers for the early diagnosis of cancers.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Male , Humans , Gold , Hydrogen Peroxide , Reproducibility of Results , Antibodies , ImmunoassayABSTRACT
Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.
Subject(s)
Peroxidase , Peroxidases , Carbon , Catalysis , Coloring AgentsABSTRACT
INTRODUCTION: Effective trauma system organization is crucial to timely access to care and requires accurate understanding of injury and resource locations. Many systems rely on home zip codes to evaluate geographic distribution of injury; however, few studies have evaluated the reliability of home as a proxy for incident location after injury. METHODS: We analyzed data from a multicenter prospective cohort collected from 2017 to 2021. Injured patients with both home and incident zip codes were included. Outcomes included discordance and differential distance between home and incident zip code. Associations of discordance with patient characteristics were determined by logistic regression. We also assessed trauma center catchment areas based on home versus incident zip codes and variation regionally at each center. RESULTS: Fifty thousand one hundred seventy-five patients were included in the analysis. Home and incident zip codes were discordant in 21,635 patients (43.1%). Injuries related to motor vehicles (aOR: 4.76 [95% CI 4.50-5.04]) and younger adults 16-64 (aOR: 2.46 [95% CI 2.28-2.65]) were most likely to be discordant. Additionally, as injury severity score increased, discordance increased. Trauma center catchment area differed up to two-thirds of zip codes when using home versus incident location. Discordance rate, discordant distance, and catchment area overlap between home and incident zip codes all varied significantly by geographic region. CONCLUSIONS: Home location as proxy for injury location should be used with caution and may impact trauma system planning and policy, especially in certain populations. More accurate geolocation data are warranted to further optimize trauma system design.
Subject(s)
Trauma Centers , Adult , Humans , Prospective Studies , Reproducibility of Results , Geography , Injury Severity ScoreABSTRACT
Therapeutic plasma exchange (TPE) has been shown to improve organ dysfunction and survival in patients with thrombotic microangiopathy and thrombocytopenia associated with multiple organ failure. There are no known therapies for the prevention of major adverse kidney events after continuous kidney replacement therapy (CKRT). The primary objective of this study was to evaluate the effect of TPE on the rate of adverse kidney events in children and young adults with thrombocytopenia at the time of CKRT initiation. DESIGN: Retrospective cohort. SETTING: Two large quaternary care pediatric hospitals. PATIENTS: All patients less than or equal to 26 years old who received CKRT between 2014 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined thrombocytopenia as a platelet count less than or equal to 100,000 (cell/mm3) at the time of CKRT initiation. We ascertained major adverse kidney events at 90 days (MAKE90) after CKRT initiation as the composite of death, need for kidney replacement therapy, or a greater than or equal to 25% decline in estimated glomerular filtration rate from baseline. We performed multivariable logistic regression and propensity score weighting to analyze the relationship between the use of TPE and MAKE90. After excluding patients with a diagnosis of thrombotic thrombocytopenia purpura and atypical hemolytic uremic syndrome (n = 6) and with thrombocytopenia due to a chronic illness (n = 2), 284 of 413 total patients (68.8%) had thrombocytopenia at CKRT initiation (51% female). Of the patients with thrombocytopenia, the median (interquartile range) age was 69 months (13-128 mo). MAKE90 occurred in 69.0% and 41.5% received TPE. The use of TPE was independently associated with reduced MAKE90 by multivariable analysis (odds ratio [OR], 0.35; 95% CI, 0.20-0.60) and by propensity score weighting (adjusted OR, 0.31; 95% CI, 0.16-0.59). CONCLUSIONS: Thrombocytopenia is common in children and young adults at CKRT initiation and is associated with increased MAKE90. In this subset of patients, our data show benefit of TPE in reducing the rate of MAKE90.
ABSTRACT
A Fe-loaded Bi2O2S nanosheet photoanode serving as photoelectric biomonitoring platform for the detection of prostate-specific antigen (PSA) using biologically inspired prussian nanoparticle (PB)-catalyzed biocatalytic precipitation strategy was developed. Primarily, the signal probe PB-mAb2 obtained by electrostatic adsorption was immobilized on a microplate in the presence of target PSA, and 4-chloro-1-naphthol (4-CN) was oxidized to benzo-4-chloro-hexadienone (4-CD) with the assistance of exogenous hydrogen peroxide, which was generated by a large number of hydroxyl radicals catalyzed by PB. The generated 4-CD showed strongly low conductivity characteristics to burst the photocurrent of highly photoactive Fe-Bi2O2S photoanode. The split incubation reaction could be suitable for high volume and low-cost rapid detection. A dynamic response range of 0.1-100 ng mL-1 with a limit of detection of 34.2 pg mL-1 was achieved with the sensor based on a photoelectric sensing platform and a biomimetic catalytic precipitation reaction. Equally important, the sensor also showed good potential in the detection of real samples compared to commercially available ELISA kits. In conclusion, this work provides a fresh scheme for the development of sensitive biosensors through a bio-inspired catalytic strategy of versatility and a photoanode coupling with high photoelectric activity.
Subject(s)
Biosensing Techniques , Nanoparticles , Neoplasms , Male , Humans , Prostate-Specific Antigen/analysis , Immunoassay , Enzyme-Linked Immunosorbent Assay , Electrochemical Techniques , Limit of DetectionABSTRACT
BACKGROUND: Prehospital resuscitation guidelines vary widely, and blood products, although likely superior, are not available for most patients in the prehospital setting. Our objective was to determine the prehospital crystalloid volume associated with the lowest mortality among patients in hemorrhagic shock. STUDY DESIGN: This is a secondary analysis of the Prehospital Air Medical Plasma trial. Injured patients from the scene with hypotension and tachycardia or severe hypotension were included. Segmented regression and generalized additive models were used to evaluate nonlinear effects of prehospital crystalloid volume on 24-hour mortality. Logistic regression evaluated the association between risk-adjusted mortality and prehospital crystalloid volume ranges to identify optimal target volumes. Inverse propensity weighting was performed to account for patient heterogeneity. RESULTS: There were 405 patients included. Segmented regression suggested the nadir of 24-hour mortality lay within 377 to 1,419 mL prehospital crystalloid. Generalized additive models suggested the nadir of 24-hour mortality lay within 242 to 1,333 mL prehospital crystalloid. A clinically operationalized range of 250 to 1,250 mL was selected based on these findings. Odds of 24-hour mortality were higher for patients receiving less than 250 mL (adjusted odds ratio [aOR] 2.46; 95% CI 1.31 to 4.83; p = 0.007) and greater than 1,250 mL (aOR 2.57; 95% CI 1.24 to 5.45; p = 0.012) compared with 250 to 1,250 mL. Propensity-weighted regression similarly demonstrated odds of 24-hour mortality were higher for patients receiving less than 250 mL (aOR 2.62; 95% CI 1.34 to 5.12; p = 0.005) and greater than 1,250 mL (aOR 2.93; 95% CI 1.36 to 6.29; p = 0.006) compared with 250 to 1,250 mL. CONCLUSIONS: Prehospital crystalloid volumes between 250 and 1,250 mL are associated with lower mortality compared with lower or higher volumes. Further work to validate these finding may provide practical volume targets for prehospital crystalloid resuscitation.
Subject(s)
Emergency Medical Services , Hypotension , Shock, Hemorrhagic , Wounds and Injuries , Humans , Crystalloid Solutions , Injury Severity Score , Resuscitation , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/therapy , Wounds and Injuries/complications , Wounds and Injuries/therapyABSTRACT
Herein, we presented a dual-readout gasochromic immunosensing platform for accurate and sensitive detection of carcinoembryonic antigen (CEA) based on Ag-doped/Pd nanoparticles loaded MoO3 nanorods (Ag/MoO3-Pd). Initially, the presence of analyte CEA would prompt the formation of sandwich-type immunoreaction, accompanied by the introduction of Pt NPs labeled on detection antibody. Upon the addition of NH3BH3, the product hydrogen (H2) will interact with Ag/MoO3-Pd as a bridge between the sensing interface and the biological assembly platform. Both photocurrent and temperature signals can serve as readouts due to the significantly increased PEC performance and enhanced photothermal conversion capability of H-Ag/MoO3-Pd (the product of Ag/MoO3-Pd react with H2) compared to Ag/MoO3-Pd. In addition, the DFT results show that the band gap of Ag/MoO3-Pd becomes narrower after the reaction with H2, thus improving the utilization of light, which theoretically explains the internal mechanism of gas sensing reaction. Under optimal conditions, the designed immunosensing platform showed good sensitivity for CEA detection with the limit of detection (LOD) of 26 pg mL-1 (photoelectrochemical mode) and 98 pg mL-1 (photothermal mode). This work not only presents the possible reaction mechanism of Ag/MoO3-Pd and H2, but also creatively applicate it in photothermal biosensors that give a new path for devising dual-readout immunosensor.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Nanoparticles , Immunoassay , Carcinoembryonic Antigen , Electrochemical Techniques , Limit of DetectionABSTRACT
Portable and on-site detection of target biomarker is of great significance in early diagnosis of diseases. Herein, we designed a portable smartphone-based PEC immunoassay platform to detect prostate specific antigen (PSA) adopting Co-doped Bi2O2S nanosheets as photoactive materials. The fast photocurrent response under visible light and excellent electrical transport rate invest Co-doped Bi2O2S with the property of being effectively excited even under a weak light source. Therefore, with the incorporation of a carriable flashlight that act as the excitation light source, disposable screen-printed electrodes, a microelectrochemical workstation and a smartphone that served as control center, point-of-care analytical detection of low-abundance small molecule analytes was successfully realized. Specifically, a sandwich-type immunoreaction was performed using alkaline phosphatase labeled secondary antibody as signal indicator. In the presence of PSA, ascorbic acid as generated through a catalytic reaction, resulting in the enhancement of photocurrent intensity. The photocurrent intensity increased linearly with the logarithm of PSA concentrations ranging from 0.2 to 50 ng mL-1 with a detection limit of 71.2 pg mL-1 (S/N = 3). This system provided an effective method for the construction of portable and miniaturized PEC sensing platform for the application of point-of-care health monitoring.
Subject(s)
Biosensing Techniques , Prostate-Specific Antigen , Humans , Male , Smartphone , Biosensing Techniques/methods , Immunoassay/methods , Alkaline Phosphatase , Limit of Detection , Electrochemical Techniques/methodsABSTRACT
OBJECTIVE: Evaluate the association of survival with helicopter transport directly to a trauma center compared with ground transport to a non-trauma center (NTC) and subsequent transfer. SUMMARY BACKGROUND DATA: Helicopter transport improves survival after injury. One potential mechanism is direct transport to a trauma center when the patient would otherwise be transported to an NTC for subsequent transfer. METHODS: Scene patients 16 years and above with positive physiological or anatomic triage criteria within PTOS 2000-2017 were included. Patients transported directly to level I/II trauma centers by helicopter were compared with patients initially transported to an NTC by ground with a subsequent helicopter transfer to a level I/II trauma center. Propensity score matching was used to evaluate the association between direct helicopter transport and survival. Individual triage criteria were evaluated to identify patients most likely to benefit from direct helicopter transport. RESULTS: In all, 36,830 patients were included. Direct helicopter transport was associated with a nearly 2-fold increase in odds of survival compared with NTC ground transport and subsequent transfer by helicopter (aOR 2.78; 95% CI 2.24-3.44, P <0.01). Triage criteria identifying patients with a survival benefit from direct helicopter transport included GCS≤13 (1.71; 1.22-2.41, P <0.01), hypotension (2.56; 1.39-4.71, P <0.01), abnormal respiratory rate (2.30; 1.36-3.89, P <0.01), paralysis (8.01; 2.03-31.69, P <0.01), hemothorax/pneumothorax (2.34; 1.36-4.05, P <0.01), and multisystem trauma (2.29; 1.08-4.84, P =0.03). CONCLUSIONS: Direct trauma center access is a mechanism driving the survival benefit of helicopter transport. First responders should consider helicopter transport for patients meeting these criteria who would otherwise be transported to an NTC.