Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

Rhabdomyolysis in Severe COVID-19: Male Sex, High Body Mass Index, and Prone Positioning Confer High Risk.

BACKGROUND: Bedside experience and studies of critically ill patients with coronavirus disease 2019 (COVID-19) indicate COVID-19 to be a devastating multisystem disease. We aim to describe the incidence, associated variables, and outcomes of rhabdomyolysis in critically ill COVID-19 patients. MATERIALS AND METHODS: Data for all critically ill adult patients (≥18 years old) admitted to the ICU at a large academic medical center with confirmed COVID-19 between March 13, 2020 and April 18, 2020 were prospectively collected. Patients with serum creatine kinase (CK) concentrations greater than 1000 U/L were diagnosed with rhabdomyolysis. Patients were further stratified as having moderate (serum CK concentration 1000-4999 U/L) or severe (serum CK concentration ≥5000 U/L) rhabdomyolysis. Univariate and multivariate analyses were performed to identify outcomes and variables associated with the development of rhabdomyolysis. RESULTS: Of 235 critically ill COVID-19 patients, 114 (48.5%) met diagnostic criteria for rhabdomyolysis. Patients with rhabdomyolysis more often required mechanical ventilation (P < 0.001), prone positioning (P < 0.001), pharmacological paralysis (P < 0.001), renal replacement therapy (P = 0.010), and extracorporeal membrane oxygenation (ECMO) (P = 0.025). They also had longer median ICU length of stay (LOS) (P < 0.001) and hospital LOS (P < 0.001). No difference in mortality was observed. Male sex, patients with morbid obesity, SOFA score, and prone positioning were independently associated with rhabdomyolysis. CONCLUSIONS: Nearly half of critically ill COVID-19 patients in our cohort met diagnostic criteria for rhabdomyolysis. Male sex, morbid obesity, SOFA score, and prone position were independently associated with rhabdomyolysis.

General Versus Neuraxial Anesthesia for Appendectomy: A Multicenter International Study.

BACKGROUND: In resource-limited countries, open appendectomy is still performed under general anesthesia (GA) or neuraxial anesthesia (NA). We sought to compare the postoperative outcomes of appendectomy under NA versus GA. METHODS: We conducted a post hoc analysis of the International Patterns of Opioid Prescribing (iPOP) multicenter study. All patients ≥ 16 years-old who underwent an open appendectomy between October 2016 and March 2017 in one of the 14 participating hospitals were included. Patients were stratified into two groups: NA-defined as spinal or epidural-and GA. All-cause morbidity, hospital length of stay (LOS), and pain severity were assessed using univariate analysis followed by multivariable logistic regression adjusting for the following preoperative characteristics: age, gender, body mass index (BMI), smoking, history of opioid use, emergency status, and country. RESULTS: A total of 655 patients were included, 353 of which were in the NA group and 302 in the GA group. The countries operating under NA were Colombia (39%), Thailand (31%), China (23%), and Brazil (7%). Overall, NA patients were younger (mean age (SD): 34.5 (14.4) vs. 40.7 (17.9), p-value < 0.001) and had a lower BMI (mean (SD): 23.5 (3.8) vs. 24.3 (5.2), p-value = 0.040) than GA patients. On multivariable analysis, NA was independently associated with less postoperative complications (OR, 95% CI: 0.30 [0.10-0.94]) and shorter hospital LOS (LOS > 3 days, OR, 95% CI: 0.47 [0.32-0.68]) compared to GA. There was no difference in postoperative pain severity between the two techniques. CONCLUSIONS: Open appendectomy performed under NA is associated with improved outcomes compared to that performed under GA. Further randomized controlled studies should examine the safety and value of NA in lower abdominal surgery.

Using the Field Artificial Intelligence Triage (FAIT) tool to predict hospital critical care resource utilization in patients with truncal gunshot wounds.

BACKGROUND: Tiered trauma triage systems have resulted in a significant mortality reduction, but models have remained unchanged. The aim of this study was to develop and test an artificial intelligence algorithm to predict critical care resource utilization. METHODS: We queried the ACS-TQIP 2017-18 database for truncal gunshot wounds(GSW). An information-aware deep neural network (DNN-IAD) model was trained to predict ICU admission and need for mechanical ventilation (MV). Input variables included demographics, comorbidities, vital signs, and external injuries. The model's performance was assessed using the area under receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). RESULTS: For the ICU admission analysis, we included 39,916 patients. For the MV need analysis, 39,591 patients were included. Median (IQR) age was 27 (22,36). AUROC and AUPRC for predicting ICU need were 84.8 ± 0.5 and 75.4 ± 0.5, and the AUROC and AUPRC for MV need were 86.8 ± 0.5 and 72.5 ± 0.6. CONCLUSIONS: Our model predicts hospital utilization outcomes in patients with truncal GSW with high accuracy, allowing early resource mobilization and rapid triage decisions in hospitals with capacity issues and austere environments.

Whole Blood Resuscitation is Safe in Pediatric Trauma Patients: A Multicenter Study.

INTRODUCTION: Whole blood (WB) resuscitation has been associated with a mortality benefit in trauma patients. Several small series report the safe use of WB in the pediatric trauma population. We performed a subgroup analysis of the pediatric patients from a large prospective multicenter trial comparing patients receiving WB or blood component therapy (BCT) during trauma resuscitation. We hypothesized that WB resuscitation would be safe compared to BCT resuscitation in pediatric trauma patients. METHODS: This study included pediatric trauma patients (0-17 y), from ten level-I trauma centers, who received any blood transfusion during initial resuscitation. Patients were included in the WB group if they received at least one unit of WB during their resuscitation, and the BCT group was composed of patients receiving traditional blood product resuscitation. The primary outcome was in-hospital mortality with secondary outcomes being complications. Multivariate logistic regression was performed to assess for mortality and complications in those treated with WB vs BCT. RESULTS: Ninety patients, with both penetrating and blunt mechanisms of injury (MOI), were enrolled in the study (WB: 62 (69%), BCT: 28 (21%)). Whole blood patients were more likely to be male. There were no differences in age, MOI, shock index, or injury severity score between groups. On logistic regression, there was no difference in complications. Mortality was not different between the groups (P = .983). CONCLUSION: Our data suggest WB resuscitation is safe when compared to BCT resuscitation in the care of critically injured pediatric trauma patients.

Prehospital extremity tourniquet placements-performance evaluation of non-EMS placement of a lifesaving device.

BACKGROUND: The education of civilians and first responders in prehospital tourniquet (PT) utilization has spread rapidly. We aimed to describe trends in emergency medical services (EMS) and non-EMS PT utilization, and their ability to identify proper clinical indications and to appropriately apply tourniquets in the field. METHODS: A retrospective cohort study was conducted to evaluate all adult patients with PTs who presented at two Level I trauma centers between January 2015 and December 2019. Data were collected via an electronic patient query tool and cross-referenced with institutional Trauma Registries. Medically trained abstractors determined if PTs were clinically indicated (limb amputation, vascular hard signs, injury requiring hemostasis procedure, or significant documented blood loss). PTs were further designated as appropriately or inappropriately applied (based on tourniquet location, venous tourniquet, greater than 2-h ischemic time). Descriptive statistics and univariate analyses were performed. RESULTS: 146 patients met inclusion criteria. The incidence of yearly PT placements increased between 2015 and 2019, with an increase in placement by non-EMS personnel (police, firefighter, bystander, and patient). Improvised PTs were frequently utilized by bystanders and patients, whereas first responders had high rates of commercial tourniquet use. A high proportion of tourniquets were placed without indication (72/146, 49%); however, the proportion of PTs placed without a proper indication across applier groups was not statistically different (p = 0.99). Rates of inappropriately applied PTs ranged from 21 to 46% across all groups applying PTs. CONCLUSIONS: PT placement was increasingly performed by non-EMS personnel. Present data indicate that non-EMS persons applied PTs at a similar performance level of those applied by EMS. Study LevelLevel III.

Adding to the story, did penetrating trauma really increase? changes in trauma patterns during the COVID-19 pandemic: A multi-institutional, multi-region investigation.

BACKGROUND: Results from single-region studies suggest that stay at home orders (SAHOs) had unforeseen consequences on the volume and patterns of traumatic injury during the initial months of the Coronavirus disease 2019 (COVID-19). The aim of this study was to describe, using a multi-regional approach, the effects of COVID-19 SAHOs on trauma volume and patterns of traumatic injury in the US. METHODS: A retrospective cohort study was performed at four verified Level I trauma centers spanning three geographical regions across the United States (US). The study period spanned from April 1, 2020 - July 31, 2020 including a month-matched 2019 cohort. Patients were categorized into pre-COVID-19 (PCOV19) and first COVID-19 surge (FCOV19S) cohorts. Patient demographic, injury, and outcome data were collected via Trauma Registry queries. Univariate and multivariate analyses were performed. RESULTS: A total 5,616 patients presented to participating study centers during the PCOV19 (2,916) and FCOV19S (2,700) study periods.  Blunt injury volume decreased (p = 0.006) due to a significant reduction in the number of motor vehicle collisions (MVCs) (p = 0.003). Penetrating trauma experienced a significant increase, 8% (246/2916) in 2019 to 11% (285/2,700) in 2020 (p = 0.007), which was associated with study site (p = 0.002), not SAHOs. Finally, study site was significantly associated with changes in nearly all injury mechanisms, whereas SAHOs accounted for observed decreases in calculated weekly averages of blunt injuries (p < 0.02) and MVCs (p = 0.003). CONCLUSION: Results of this study suggest that COVID-19 and initial SAHOs had variable consequences on patterns of traumatic injury, and that region-specific shifts in traumatic injury ensued during initial SAHOs. These results suggest that other factors, potentially socioeconomic or cultural, confound trauma volumes and types arising from SAHOs. Future analyses must consider how regional changes may be obscured with pooled cohorts, and focus on characterizing community-level changes to aid municipal preparation for future similar events.

Planning for the Next Pandemic: Trauma Injuries Require Pre-COVID-19 Levels of High-Intensity Resources.

As hospital systems plan for health care utilization surges and stress, understanding the necessary resources of a trauma system is essential for planning capacity. We aimed to describe trends in high-intensity resource utilization (operating room [OR] usage and intensive care unit [ICU] admissions) for trauma care during the initial months of the COVID-19 pandemic. Trauma registry data (2019 pre-COVID-19 and 2020 COVID-19) were collected retrospectively from 4 level I trauma centers. Direct emergency department (ED) disposition to the OR or ICU was used as a proxy for high-intensity resource utilization. No change in the incidence of direct ED to ICU or ED to OR utilization was observed (2019: 24%, 2020 23%; P = .62 and 2019: 11%, 2020 10%; P = .71, respectively). These results suggest the need for continued access to ICU space and OR theaters for traumatic injury during national health emergencies, even when levels of trauma appear to be decreasing.

Implications of the national Stop the Bleed campaign: The swinging pendulum of prehospital tourniquet application in civilian limb trauma.

BACKGROUND: Prehospital tourniquet (PHT) utilization has increased in response to mass casualty events. We aimed to describe the incidence, therapeutic effectiveness, and morbidity associated with tourniquet placement in all patients treated with PHT application. METHODS: A retrospective observational cohort study was performed to evaluate all adults with a PHT who presented at two Level I trauma centers between January 2015 and December 2019. Medically trained abstractors determined if the PHT was clinically indicated (placed for limb amputation, vascular hard signs, injury requiring hemostasis procedure, or significant documented blood loss). Prehospital tourniquets were further designated as appropriately or inappropriately applied (based on PHT anatomic placement location, occurrence of a venous tourniquet, or ischemic time defined as >2 hours). Statistical analyses were performed to generate primary and secondary results. RESULTS: A total of 147 patients met study inclusion criteria, of which 70% met the criteria for trauma registry inclusion. Total incidence of PHT utilization increased from 2015 to 2019, with increasing proportions of PHTs placed by nonemergency medical service personnel. Improvised PHTs were frequently used. Prehospital tourniquets were clinically indicated in 51% of patients. Overall, 39 (27%) patients had a PHT that was inappropriately placed, five of which resulted in significant morbidity. CONCLUSION: In summary, prehospital tourniquet application has become widely adopted in the civilian setting, frequently performed by civilian and nonemergency medical service personnel. Of PHTs placed, nearly half had no clear indication for placement and over a quarter of PHTs were misapplied with notable associated morbidity. Results suggest that the topics of clinical indication and appropriate application of tourniquets may be important areas for continued focus in future tourniquet educational programs, as well as future quality assessment efforts. LEVEL OF EVIDENCE: Epidemiological, level III; Therapeutic, level IV.

Does the Emergency Surgery Score predict failure to discharge the patient home? A nationwide analysis.

BACKGROUND: The Emergency Surgery Score (ESS) is a point-based scoring system validated to predict mortality and morbidity in emergency general surgery (EGS). In addition to demographics and comorbidities, ESS accounts for the acuity of disease at presentation. We sought to examine whether ESS can predict the destination of discharge of EGS patients, as a proxy for quality of life at discharge. METHODS: Using the 2007 to 2017 American College of Surgeons National Surgical Quality Improvement Program database, we identified all EGS patients. EGS cases were defined as per American College of Surgeons National Surgical Quality Improvement Program as those performed by a general surgeon within a short interval from diagnosis or the onset of related symptomatology, when the patient's well-being and outcome may be threatened by unnecessary delay and patient's status could deteriorate unpredictably or rapidly. Emergency Surgery Score patients were then categorized by their discharge disposition to home versus rehabilitation or nursing facilities. All patients with missing ESS or discharge disposition and those discharged to hospice, senior communities, or separate acute care facilities were excluded. Emergency Surgery Score was calculated for each patient. C statistics were used to study the correlation between ESS and the destination of discharge. RESULTS: Of 6,485,915 patients, 84,694 were included. The mean age was 57 years, 51% were female, and 79.6% were discharged home. The mean ESS was 5. Emergency Surgery Score accurately and reliably predicted the discharge destination with a C statistic of 0.83. For example, ESS of 1, 10, and 20 were associated with 0.9%, 56.5%, and 100% rates of discharge to a rehabilitation or nursing facility instead of home. CONCLUSION: Emergency Surgery Score accurately predicts which EGS patients require discharge to rehabilitation or nursing facilities and can thus be used for preoperatively counseling patients and families and for improving early discharge preparations, when appropriate. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Development of a field artificial intelligence triage tool: Confidence in the prediction of shock, transfusion, and definitive surgical therapy in patients with truncal gunshot wounds.

BACKGROUND: In-field triage tools for trauma patients are limited by availability of information, linear risk classification, and a lack of confidence reporting. We therefore set out to develop and test a machine learning algorithm that can overcome these limitations by accurately and confidently making predictions to support in-field triage in the first hours after traumatic injury. METHODS: Using an American College of Surgeons Trauma Quality Improvement Program-derived database of truncal and junctional gunshot wound (GSW) patients (aged 16-60 years), we trained an information-aware Dirichlet deep neural network (field artificial intelligence triage). Using supervised training, field artificial intelligence triage was trained to predict shock and the need for major hemorrhage control procedures or early massive transfusion (MT) using GSW anatomical locations, vital signs, and patient information available in the field. In parallel, a confidence model was developed to predict the true-class probability (scale of 0-1), indicating the likelihood that the prediction made was correct, based on the values and interconnectivity of input variables. RESULTS: A total of 29,816 patients met all the inclusion criteria. Shock, major surgery, and early MT were identified in 13.0%, 22.4%, and 6.3% of the included patients, respectively. Field artificial intelligence triage achieved mean areas under the receiver operating characteristic curve of 0.89, 0.86, and 0.82 for prediction of shock, early MT, and major surgery, respectively, for 80/20 train-test splits over 1,000 epochs. Mean predicted true-class probability for errors/correct predictions was 0.25/0.87 for shock, 0.30/0.81 for MT, and 0.24/0.69 for major surgery. CONCLUSION: Field artificial intelligence triage accurately identifies potential shock in truncal GSW patients and predicts their need for MT and major surgery, with a high degree of certainty. The presented model is an important proof of concept. Future iterations will use an expansion of databases to refine and validate the model, further adding to its potential to improve triage in the field, both in civilian and military settings. LEVEL OF EVIDENCE: Prognostic, Level III.

Multisystem outcomes and predictors of mortality in critically ill patients with COVID-19: Demographics and disease acuity matter more than comorbidities or treatment modalities.

BACKGROUND: We sought to describe characteristics, multisystem outcomes, and predictors of mortality of the critically ill COVID-19 patients in the largest hospital in Massachusetts. METHODS: This is a prospective cohort study. All patients admitted to the intensive care unit (ICU) with reverse-transcriptase-polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 14, 2020, and April 28, 2020, were included; hospital and multisystem outcomes were evaluated. Data were collected from electronic records. Acute respiratory distress syndrome (ARDS) was defined as PaO2/FiO2 ratio of ≤300 during admission and bilateral radiographic pulmonary opacities. Multivariable logistic regression analyses adjusting for available confounders were performed to identify predictors of mortality. RESULTS: A total of 235 patients were included. The median (interquartile range [IQR]) Sequential Organ Failure Assessment score was 5 (3-8), and the median (IQR) PaO2/FiO2 was 208 (146-300) with 86.4% of patients meeting criteria for ARDS. The median (IQR) follow-up was 92 (86-99) days, and the median ICU length of stay was 16 (8-25) days; 62.1% of patients were proned, 49.8% required neuromuscular blockade, and 3.4% required extracorporeal membrane oxygenation. The most common complications were shock (88.9%), acute kidney injury (AKI) (69.8%), secondary bacterial pneumonia (70.6%), and pressure ulcers (51.1%). As of July 8, 2020, 175 patients (74.5%) were discharged alive (61.7% to skilled nursing or rehabilitation facility), 58 (24.7%) died in the hospital, and only 2 patients were still hospitalized, but out of the ICU. Age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12), higher median Sequential Organ Failure Assessment score at ICU admission (OR, 1.24; 95% CI, 1.06-1.43), elevated creatine kinase of ≥1,000 U/L at hospital admission (OR, 6.64; 95% CI, 1.51-29.17), and severe ARDS (OR, 5.24; 95% CI, 1.18-23.29) independently predicted hospital mortality.Comorbidities, steroids, and hydroxychloroquine treatment did not predict mortality. CONCLUSION: We present here the outcomes of critically ill patients with COVID-19. Age, acuity of disease, and severe ARDS predicted mortality rather than comorbidities. LEVEL OF EVIDENCE: Prognostic, level III.

Pain or No Pain, We Will Give You Opioids: Relationship Between Number of Opioid Pills Prescribed and Severity of Pain after Operation in US vs Non-US Patients.

BACKGROUND: Patients in the US receive disproportionally higher amounts of opioids after operations compared with their non-US counterparts. We aimed to assess the relationship between perceived pain severity after operation and the amount of opioid medications prescribed at discharge in US vs non-US patients. METHODS: We conducted a post-hoc analysis of the International Patterns of Opioid Prescribing multicenter study. Patients 16 years and older who underwent appendectomy, cholecystectomy, or inguinal herniorrhaphy in 1 of 14 participating hospitals across 8 countries between October 2016 and March 2017 were included. In hospitals where pain severity was assessed using a 0 to 10 visual analog scale before hospital discharge, patients were stratified into the following groups, depending on the pain severity: none, mild (1 to 3), moderate (4 to 6), and severe (7 to 10). The number of opioid prescriptions, total number of pills, and oral morphine equivalents prescribed were calculated for each group and US and non-US patients were compared. RESULTS: A total of 2,024 patients were included. Eighty-three percent of US patients without pain were prescribed opioids compared with 8.7% of non-US patients without pain (p < 0.001). The number of opioid prescriptions, number of pills, and oral morphine equivalents prescribed were similar across the 4 pain severity groups in US patients (p > 0.05). In contrast, the number of opioid prescriptions, number of opioid pills, and oral morphine equivalents prescribed among non-US patients were incrementally higher as the pain severity progressed from no pain to severe pain (all, p < 0.05). CONCLUSIONS: US patients are prescribed opioids at high rates and doses regardless of pain severity. Additional efforts should be directed toward tailoring opioid prescriptions to patients' needs.

Comparison of outcomes in non-head injured trauma patients using pre-injury warfarin or direct oral anticoagulant therapy.

BACKGROUND: Patients on prehospital anticoagulation with warfarin or direct oral anticoagulants (DOACs) represent a vulnerable subset of the trauma population. While protocolized warfarin reversal is widely available and easily implemented, prehospital anticoagulation with DOAC is cost prohibitive with only a few reversal options. This study aims to compare hospital outcomes of non-head injured trauma patients taking pre-injury DOAC versus warfarin. METHODS: A retrospective cohort study at a level 1 trauma center was performed. All adult trauma patients with pre-injury anticoagulation admitted between January 2015 and December 2018, were stratified into DOAC-using and warfarin-using groups. Patients were excluded if they had traumatic brain injury (TBI). Univariate and multivariable analyses were performed. Outcomes measures included in-hospital mortality, blood transfusion requirements, ICU length of stay (LOS), hospital LOS and discharge disposition. RESULTS: 374 non-TBI trauma patients on anticoagulation were identified, of which 134 were on DOACs and 240 on warfarin. Patients on DOACs had a higher ISS (9 [IQR, 9-10] vs. 9 [IQR, 5-9]; p<0.001), and lower admission INR values (1.2 [IQR, 1.1-1.3] vs 2.4 [IQR, 1.8-2.7]; p<0.001) than warfarin users. Use of reversal agents was higher in warfarin users (p<0.001). Relative to warfarin, DOAC users did not differ significantly with respect to hospital mortality (OR 0.47, 95% CI [0.13-1.73]). Multivariable analysis (not possible for mortality) did not show significant difference for RBC transfusion requirements (OR 0.92 [0.51-1.67]), ICU LOS (OR 1.08 [0.53-2.19]), hospital LOS (OR 1.10 [0.70-1.74]) or discharge disposition (OR 0.56 [0.29-1.11]) between the groups. CONCLUSION: Despite lower reversal rates and higher ISS, non-TBI trauma patients with pre-injury DOAC use had similar outcomes as patients on pre-injury warfarin. There may be equipoise to have larger, prospective studies evaluating the comparative safety of DOACs and warfarin in the population prone to low energy fall type injuries.

A low dose heparinized saline protocol is associated with improved duration of arterial line patency in critically ill COVID-19 patients.

PURPOSE: Critically ill patients with Coronavirus Disease 2019 (COVID-19) have high rates of line thrombosis. Our objective was to examine the safety and efficacy of a low dose heparinized saline (LDHS) arterial line (a-line) patency protocol in this population. MATERIALS AND METHODS: In this observational cohort study, patients ≥18 years with COVID-19 admitted to an ICU at one institution from March 20-May 25, 2020 were divided into two cohorts. Pre-LDHS patients had an episode of a-line thrombosis between March 20-April 19. Post-LDHS patients had an episode of a-line thrombosis between April 20-May 25 and received an LDHS solution (10 units/h) through their a-line pressure bag. RESULTS: Forty-one patients (pre-LDHS) and 30 patients (post-LDHS) were identified. Baseline characteristics were similar between groups, including age (61 versus 54 years; p = 0.24), median Sequential Organ Failure Assessment score (6 versus 7; p = 0.67) and systemic anticoagulation (47% versus 32%; p = 0.32). Median duration of a-line patency was significantly longer in post-LDHS versus pre-LDHS patients (8.5 versus 2.9 days; p < 0.001). The incidence of bleeding complications was similar between cohorts (13% vs. 10%; p = 0.71). CONCLUSIONS: A LDHS protocol was associated with a clinically significant improvement in a-line patency duration in COVID-19 patients, without increased bleeding risk.

Complementary Genetic Targeting and Monosynaptic Input Mapping Reveal Recruitment and Refinement of Distributed Corticostriatal Ensembles by Cocaine.

Drugs of abuse elicit powerful experiences that engage populations of neurons broadly distributed throughout the brain. To determine how synaptic connectivity is organized to enable robust communication between populations of drug-activated neurons, we developed a complementary targeting system for monosynaptic rabies virus (RV) tracing that identifies direct inputs to activated versus nonactivated neuronal populations. Analysis of over 100,000 synaptic input neurons demonstrated that cocaine-activated neurons comprise selectively connected but broadly distributed corticostriatal networks. Electrophysiological assays using optogenetics to stimulate activated versus nonactivated inputs revealed stronger synapses between coactivated cortical pyramidal neurons and neurons in the dorsal striatum (DS). Repeated cocaine exposure further enhanced the connectivity specifically between drug-activated neurons in the orbitofrontal cortex (OFC) and coactive DS neurons. Selective chemogenetic silencing of cocaine-activated OFC neurons or their terminals in the DS disrupted behavioral sensitization, demonstrating the utility of this methodology for identifying novel circuit elements that contribute to behavioral plasticity.