bluuebunny/crossref_metadata_2025 huggingface dataset:
Firearm homicide mortality is influenced by structural racism in US metropolitan areas
Authors: Houghton August , Jackson-Weaver Olan , Toraih Eman , Burley Nicholas , Byrne Terence , McGrew Patrick , Duchesne Juan , Tatum Danielle , Taghavi Sharven
Published: April 2021

INTRODUCTION

Metropolitan cities in the United States suffer from higher rates of gun violence. However, the specific structural factors associated with increased gun violence are poorly defined. We hypothesized that firearm homicide in metropolitan cities would be impacted by Black-White segregation index.

METHODS

This cross-sectional analysis evaluated 51 US metropolitan statistical areas (MSAs) using data from 2013 to 2017. Several measures of structural racism were examined, including the Brooking Institute’s Black-White segregation index. Demographic data were derived from the US Census Bureau, US Department of Education, and US Department of Labor. Crime data and firearm homicide mortality rates were obtained from the Federal Bureau of Investigation and the Centers for Disease Control. Spearman ρ and linear regression were performed.

RESULTS

Firearm mortality was associated with multiple measures of structural racism and racial disparity, including White-Black segregation index, unemployment rate, poverty rate, single parent household, percent Black population, and crime rates. In regression analysis, percentage Black population exhibited the strongest association with firearm homicide mortality (β = 0.42, p < 0.001). Black-White segregation index (β = 0.41, p = 0.001) and percent children living in single-parent households (β = 0.41, p = 0.002) were also associated with higher firearm homicide mortality. Firearm legislation scores were associated with lower firearm homicide mortality (β = −0.20 p = 0.02). High school and college graduation rates were not associated with firearm homicide mortality and were not included in the final model.

CONCLUSION

Firearm homicide disproportionately impacts communities of color and is associated with measures of structural racism, such as White-Black segregation index. Public health interventions targeting gun violence must address these systemic inequities. Furthermore, given the association between firearm mortality and single-parent households, intervention programs for at-risk youth may be particularly effective.

LEVEL OF EVIDENCE

Epidemiological level II.
Making the call in the field: Validating emergency medical services identification of anatomic trauma triage criteria
Authors: Deeb Andrew-Paul , Phelos Heather M. , Peitzman Andrew B. , Billiar Timothy R. , Sperry Jason L. , Brown Joshua B.
Published: April 2021

BACKGROUND

The National Field Triage Guidelines were created to inform triage decisions by emergency medical services (EMS) providers and include eight anatomic injuries that prompt transportation to a Level I/II trauma center. It is unclear how accurately EMS providers recognize these injuries. Our objective was to compare EMS-identified anatomic triage criteria with International Classification of Diseases-10th revision (ICD-10) coding of these criteria, as well as their association with trauma center need (TCN).

METHODS

Scene patients 16 years and older in the NTDB during 2017 were included. National Field Triage Guidelines anatomic criteria were classified based on EMS documentation and ICD-10 diagnosis codes. The primary outcome was TCN, a composite of Injury Severity Score greater than 15, intensive care unit admission, urgent surgery, or emergency department death. Prevalence of anatomic criteria and their association with TCN was compared in EMS-identified versus ICD-10–coded criteria. Diagnostic performance to predict TCN was compared.

RESULTS

There were 669,795 patients analyzed. The ICD-10 coding demonstrated a greater prevalence of injury detection. Emergency medical service–identified versus ICD-10–coded anatomic criteria were less sensitive (31% vs. 59%), but more specific (91% vs. 73%) and accurate (71% vs. 68%) for predicting TCN. Emergency medical service providers demonstrated a marked reduction in false positives (9% vs. 27%) but higher rates of false negatives (69% vs. 42%) in predicting TCN from anatomic criteria. Odds of TCN were significantly greater for EMS-identified criteria (adjusted odds ratio, 4.5; 95% confidence interval, 4.46–4.58) versus ICD-10 coding (adjusted odds ratio 3.7; 95% confidence interval, 3.71–3.79). Of EMS-identified injuries, penetrating injury, flail chest, and two or more proximal long bone fractures were associated with greater TCN than ICD-10 coding.

CONCLUSION

When evaluating the anatomic criteria, EMS demonstrate greater specificity and accuracy in predicting TCN, as well as reduced false positives compared with ICD-10 coding. Emergency medical services identification is less sensitive for anatomic criteria; however, EMS identify the most clinically significant injuries. Further study is warranted to identify the most clinically important anatomic triage criteria to improve our triage protocols.

LEVEL OF EVIDENCE

Care management, Level IV; Prognostic, Level III.
Thromboelastography with platelet mapping: Limited predictive ability in detecting preinjury antiplatelet agent use
Authors: Barton Cassie A. , Oetken Heath J. , Roberti Gregory J. , Dewey Elizabeth N. , Goodman Andrew , Schreiber Martin
Published: April 2021

BACKGROUND

Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population.

METHODS

A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs).

RESULTS

A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely.

CONCLUSION

High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations.

LEVEL OF EVIDENCE

Diagnostic test, level II.
Can educational videos reduce opioid consumption in trauma inpatients? A cluster-randomized pilot study
Authors: Tseng Esther S. , Zolin Samuel J. , Young Brian T. , Claridge Jeffrey A. , Conrad-Schnetz Kristen J. , Curfman Eric T. , Wise Nicole L. , Lemaitre Vetrica C. , Ho Vanessa P.
Published: April 2021

BACKGROUND

Opioids are often used to treat pain after traumatic injury, but patient education on safe use of opioids is not standard. To address this gap, we created a video-based opioid education program for patients. We hypothesized that video viewing would lead to a decrease in overall opioid use and morphine equivalent doses (MEDs) on their penultimate hospital day. Our secondary aim was to study barriers to video implementation.

METHODS

We performed a prospective pragmatic cluster-randomized pilot study of video education for trauma floor patients. One of two equivalent trauma floors was selected as the intervention group; patients were equally likely to be admitted to either floor. Nursing staff were to show videos to English-speaking or Spanish-literate patients within 1 day of floor arrival, excluding patients with Glasgow Coma Scale score less than 15. Opioid use and MEDs taken on the day before discharge were compared. Intention to treat (ITT) (intervention vs. control) and per-protocol groups (video viewers vs. nonviewers) were compared (α = 0.05). Protocol compliance was also assessed.

RESULTS

In intention to treat analysis, there was no difference in percent of patients using opioids or MEDs on the day before discharge. In per-protocol analysis, there was no different in percent of patients using opioids on the day before discharge. However, video viewers still on opioids took significantly fewer MEDs than patients who did not see the video (26 vs. 38, p < 0.05). Protocol compliance was poor; only 46% of the intervention group saw the videos.

CONCLUSION

Video-based education did not reduce inpatient opioid consumption, although there may be benefits in specific subgroups. Implementation was hindered by staffing and workflow limitations, and staff bias may have limited the effect of randomization. We must continue to establish effective methods to educate patients about safe pain management and translate these into standard practices.

LEVEL OF EVIDENCE

Therapeutic, Level IV
A quasiexperimental study of targeted normoxia in critically ill trauma patients
Authors: Dylla Layne , Anderson Erin L. , Douin David J. , Jackson Conner L. , Rice John D. , Schauer Steven G. , Neumann Robert T. , Bebarta Vikhyat S. , Wright Franklin L. , Ginde Adit A.
Published: April 2021

BACKGROUND

Avoidance of hypoxia and hyperoxia may reduce morbidity and mortality in critically ill civilian and military trauma patients. The objective of this study was to determine if a multimodal quality improvement intervention increases adherence to a consensus-based, targeted normoxia strategy. We hypothesized that this intervention would safely improve compliance with targeted normoxia.

METHODS

This is a pre/postquasiexperimental pilot study to improve adherence to normoxia, defined as a pulse oximetry (SpO2) of 90% to 96% or an arterial partial pressure oxygen (PaO2) of 60 to 100 mm Hg. We used a multimodal informatics and educational intervention guiding clinicians to safely titrate supplemental oxygen to normoxia based on SpO2 monitoring in critically ill trauma patients admitted to the surgical-trauma or neurosurgical intensive care unit within 24 hours of emergency department arrival. The primary outcome was effectiveness in delivering targeted normoxia (i.e., an increase in the probability of being in the targeted normoxia range and/or a reduction in the probability of being on a higher fraction-inspired oxygen concentration [FiO2]).

RESULTS

Analysis included 371 preintervention subjects and 201 postintervention subjects. Preintervention and postintervention subjects were of similar age, race/ethnicity, and sex and had similar comorbidities and Acute Physiologic and Chronic Health Evaluation II scores. Overall, the adjusted probability of being hyperoxic while on supplemental oxygen was reduced during the postintervention period (adjusted odds ratio, 0.74; 95% confidence interval, 0.57–0.97). There was a higher probability of being on room air (FiO2, 0.21) in the postintervention period (adjusted odds ratio, 1.38; 95% confidence interval, 0.83–2.30). In addition, there was a decreased amount of patient time spent on higher levels of FiO2 (FiO2, >40%) without a concomitant increase in hypoxia.

CONCLUSION

A multimodal intervention targeting normoxia in critically ill trauma patients increased normoxia and lowered the use of supplemental oxygen. A large clinical trial is needed to validate the impact of this protocol on patient-centered clinical outcomes.

LEVEL OF EVIDENCE

Therapeutic/care management, level II.
Adhesive small bowel obstruction: Single band or matted adhesions? A predictive model based on computed tomography scan
Authors: Guerrini Jacopo , Zugna Daniela , Poretti Dario , Samà Laura , Costa Guido , Mei Simona , Ceolin Martina , Biloslavo Alan , Zago Mauro , Viganò Luca , Kurihara Hayato
Published: April 2021

BACKGROUND

Preoperative identification of the cause of adhesive small bowel obstruction (ASBO) is crucial for decision making. Some computed tomography (CT) findings can be indicative of single adhesive bands or matted adhesions. Our aim was to build a predictive model based on CT data to discriminate ASBO due to single adhesive band or matted adhesions.

METHODS

A retrospective single center study was conducted, covering all consecutive patients with a preoperative CT scan, undergoing urgent surgery for ASBO between January 1, 2005, and December 31, 2017. Preoperative CT scans were blindly reviewed, and all the CT findings indicative of single adhesive band or matted adhesions described in literature were recorded. According to intraoperative findings, ASBOs were retrospectively classified into single band and matted ASBO. All observed CT findings were compared between the two groups. A predictive model based on logistic regression was developed, and its ability was quantified by discrimination and calibration. Internal cross-validation was conducted by bootstrap resampling.

RESULTS

A total of 116 patients were analyzed (males, 53.5%; median age, 68 years; single band ASBO in 65.5% of cases). The odds of single band ASBO were increased four times in presence of complete obstruction (odds ratios, 4.19; 95% confidence interval, 1.49–12.56) and seven times in presence of fat notch sign (odds ratios, 7.37; 95% confidence interval, 1.83–40.03). The predictive model combining all CT findings had an accuracy of 86% in single band ASBO prediction. Accuracy decreased to 79% in the internal validation. Sensitivity, specificity, and positive and negative predictive values were calculated at different cut-points of the predicted risk: using a 0.70 cut-point, the specificity is 80%, the sensitivity is 68%, and the positive and negative predictive values are 87% and 57%, respectively.

CONCLUSION

The proposed predictive model based on combination of specific CT findings may elucidate whether ASBO is caused by single bands or matted adhesions and, consequently, influence the clinical pathway.

LEVEL OF EVIDENCE

Prognostic study, level IV
The effect of sexual dysfunction on health-related quality of life in men following traumatic pelvic fractures
Authors: Wang Alice Y. , Vavilala Monica S. , Rivara Frederick P. , Johnsen Niels V.
Published: April 2021

BACKGROUND

Pelvic trauma disproportionately affects a younger population and has the potential to cause long-term sexual dysfunction. We hypothesized that the presence of sexual dysfunction after traumatic pelvic fracture negatively impacts health-related quality of life (HrQOL) in men.

METHODS

A total of 228 patients with traumatic pelvic fractures treated at a level 1 trauma center between 2012 and 2017 completed a survey that evaluated postinjury HrQOL and sexual function. Inverse probability weighting was used to adjust for survey nonresponse. Pelvic fracture characteristics were classified based on the Orthopedic Trauma Association classification system. Sexual function was evaluated using the International Index of Erectile Function, and HrQOL was evaluated using the EuroQol 5 Dimensions Questionnaire (EQ-5D). Quality-adjusted life years were determined based on calculated EQ-5D utility indices. Multiple regression models were created to evaluate the association between sexual health and HrQOL.

RESULTS

After inverse probability weighting and adjustment for potential confounders, a decrease in International Index of Erectile Function was associated with a decline in overall HrQOL as measured by the EQ-5D visual analog scale (β = 0.28, p = 0.02). No association was identified between Orthopedic Trauma Association pelvic fracture configuration and risk of postinjury erectile dysfunction (ED) (p = 0.99). Furthermore, 53.3% of men reported persistent ED at a median of 42.6 months (interquartile range, 28.0–63.3 months) following injury. The presence of ED was independently associated with a decrease in HrQOL (β = 10.92, p < 0.001). This difference equates to a loss of 1.6 quality-adjusted life years per 10 years for men with ED following pelvic fracture relative to those without.

CONCLUSION

Sexual dysfunction is an independent risk factor for decreased HrQOL in pelvic trauma survivors. Further work is needed to create appropriate patient-centered survivorship care pathways that incorporate sexual health evaluation.

LEVEL OF EVIDENCE

Prognostic, level IV.
Is resuscitative endovascular balloon occlusion of the aorta for computed tomography diagnosis feasible or not? A Japanese single-center, retrospective, observational study
Authors: Otsuka Hiroyuki , Takeda Michihiro , Sai Kisei , Sakoda Naoki , Uehata Atsushi , Sato Toshiki , Sakurai Keiji , Aoki Hiromichi , Yamagiwa Takeshi , Iizuka Shinichi , Inokuchi Sadaki
Published: April 2021

BACKGROUND

Advances in medical equipment have resulted in changes in the management of severe trauma. The role of resuscitative endovascular balloon occlusion of the aorta (REBOA) in this scenario is still unclear. This study aimed to evaluate the usage of REBOA and utility of computed tomography (CT) in the setting of aortic occlusion in our current trauma management.

METHODS

This Japanese single-tertiary center, retrospective, and observational study analyzed 77 patients who experienced severe trauma and persistent hypotension between October 2014 and March 2020.

RESULTS

All patients required urgent hemostasis. Twenty patients underwent REBOA, 11 underwent open aortic cross-clamping, and 46 did not undergo aortic occlusion. Among patients who underwent aortic occlusion, 19 patients underwent prehemostasis CT, and 7 patients underwent operative exploration without prehemostasis CT for identifying active bleeding sites. The 24-hour and 28-day survival rates in patients who underwent CT were not inferior to those in patients who did not undergo CT (24-hour survival rate, 84.2% vs. 57.1%; 28-day survival rate, 47.4% vs. 28.6%). Moreover, the patients who underwent CT had less discordance between primary hemostasis site and main bleeding site compared with patients who did not undergo CT (5% vs. 71.4%, p = 0.001). In the patients who underwent prehemostasis CT, REBOA was the most common approach of aortic occlusion. Most of the bleeding control sites were located in the retroperitoneal space. There were many patients who underwent interventional radiology for hemostasis.

CONCLUSION

In a limited number of patients whose cardiac arrests were imminent and in whom no active bleeding sites could be clearly identified without CT findings, REBOA for CT diagnosis may be effective; however, further investigations are needed.

LEVEL OF EVIDENCE

Therapeutic/care management study, level V.
Antithrombotic choice in blunt cerebrovascular injuries: Experience at a tertiary trauma center, systematic review, and meta-analysis
Authors: Ku Jerry C. , Priola Stefano M. , Mathieu Francois , Taslimi Shervin , Pasarikovski Christopher R. , Zeiler Frederick A. , Machnowska Matylda , Nathens Avery , Yang Victor X.D. , da Costa Leodante
Published: April 2021

BACKGROUND

Blunt cerebrovascular injuries (BCVIs) may occur following trauma and lead to ischemic stroke if untreated. Antithrombotic therapy decreases this risk; however, the optimal agent has yet to be determined in this population. The aim of this study was to compare the risk-benefit profile of antiplatelet (AP) versus anticoagulant (AC) therapy in rates of ischemic stroke and hemorrhagic complications in BCVI patients.

METHODS

We performed a retrospective review of BCVI patients at our tertiary care Trauma hospital from 2010 to 2015, and a systematic review and meta-analysis of the literature. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to September 16, 2019. References of included publications were searched manually for other relevant articles. The search was limited to articles in humans, in patients 18 years or older, and in English. Studies that reported treatment-stratified clinical outcomes following AP or AC treatment in BCVI patients were included. Exclusion criteria included case reports, case series with n < 5, review articles, conference abstracts, animal studies, and non–peer-reviewed publications. Data were extracted from each study independently by two reviewers, including study design, country of origin, sex and age of patients, Injury Severity Score, Biffl grade, type of treatment, ischemic stroke rate, and hemorrhage rate. Pooled estimates using odds ratio (OR) were combined using a random-effects model using a Mantel-Hanzel weighting. The main outcome of interest was rate of ischemic stroke due to BCVI, and the secondary outcome was hemorrhage rate based on AC or AP treatment.

RESULTS

In total, there were 2044 BCVI patients, as reported in the 22 studies in combination with our institutional data. The stroke rate was not significantly different between the two treatment groups (OR, 1.27; 95% confidence interval, 0.40–3.99); however, the hemorrhage rate was decreased in AP versus AC treated groups (OR, 0.38; 95% confidence interval, 0.15–1.00).

CONCLUSION

Based on this meta-analysis, both AC and AP seem similarly effective in preventing ischemic stroke, but AP is better tolerated in the trauma population. This suggests that AP therapy may be preferred, but this should be further assessed with prospective randomized trials.

LEVEL OF EVIDENCE

Review article, level II.
Between the devil and the deep blue sea: A review of 25 modern naval mass casualty incidents with implications for future Distributed Maritime Operations
Authors: Tadlock Matthew D. , Gurney Jennifer , Tripp Michael S. , Cancio Leopoldo C. , Sise Michael J. , Bandle Jesse , Cubano Miguel , Lee Joseph , Vasquez Matthew , Acosta José A.
Published: April 2021

In the future, United States Navy Role 1 and Role 2 shipboard medical departments will be caring for patients during Distributed Maritime Operations in both contested and noncontested austere environments; likely for prolonged periods of time. This literature review examines 25 modern naval mass casualty incidents over a 40-year period representative of naval warfare, routine naval operations, and ship-based health service support of air and land operations. Challenges, lessons learned, and injury patterns are identified to prepare afloat medical departments for the future fight.

LEVEL OF EVIDENCE

Literature Review, level V.
Efficacy of past, present, and future fluid strategies in an improved large animal model of non-compressible intra-abdominal hemorrhage
Authors: Donaldson Ross I. , Graham Todd L. , Fisher Timothy C. , Armstrong Jonathan , Buchanan Oliver J. , Cambridge John , Ross James D.
Published: April 2021

BACKGROUND

Noncompressible hemorrhage is a leading cause of potentially survivable combat death, with the vast majority of such deaths occurring in the out-of-hospital environment. While large animal models of this process are important for device and therapeutic development, clinical practice has changed over time and past models must follow suit. Developed in conjunction with regulatory feedback, this study presents a modernized, out-of-hospital, noncompressible hemorrhage model, in conjunction with a randomized study of past, present, and future fluid options following a hypotensive resuscitation protocol consistent with current clinical practice.

METHODS

We performed a randomized controlled experiment comparing three fluid resuscitation options in Yorkshire swine. Baseline data from animals of same size from previous experiments were analyzed (n = 70), and mean systolic blood pressure was determined, with a permissive hypotension resuscitation target defined as a 25% decrease from normal (67 mm Hg). After animal preparation, a grade IV to V liver laceration was induced. Animals bled freely for a 10-minute “time-to-responder” period, after which resuscitation occurred with randomized fluid in boluses to the goal target: 6% hetastarch in lactated electrolyte injection (HEX), normal saline (NS), or fresh whole blood (FWB). Animals were monitored for a total simulated “delay to definitive care” period of 2 hours postinjury.

RESULTS

At the end of the 2-hour study period, 8.3% (1 of 12 swine) of the HEX group, 50% (6 of 12 swine) of the NS group, and 75% (9 of 12 swine) of the FWB had survived (p = 0.006), with Holm-Sidak pairwise comparisons showing a significant difference between HEX and FWB and (p = 0.005). Fresh whole blood had significantly higher systemic vascular resistance and hemoglobin levels compared with other groups (p = 0.003 and p = 0.001, respectively).

CONCLUSION

Survival data support the movement away from HEX toward NS and, preferably, FWB in clinical practice and translational animal modeling. The presented model allows for future research including basic science, as well as translational studies of novel diagnostics, therapeutics, and devices.
Do surgical emergencies stay at home? Observations from the first United States Coronavirus epicenter
Authors: Dong Caroline T. , Liveris Anna , Lewis Erin R. , Mascharak Smita , Chao Edward , Reddy Srinivas H. , Teperman Sheldon H. , McNelis John , Stone Melvin E.
Published: April 2021

BACKGROUND

During the coronavirus disease 2019 pandemic, New York instituted a statewide stay-at-home mandate to lower viral transmission. While public health guidelines advised continued provision of timely care for patients, disruption of safety-net health care and public fear have been proposed to be related to indirect deaths because of delays in presentation. We hypothesized that admissions for emergency general surgery (EGS) diagnoses would decrease during the pandemic and that mortality for these patients would increase.

METHODS

A multicenter observational study comparing EGS admissions from January to May 2020 to 2018 and 2019 across 11 NYC hospitals in the largest public health care system in the United States was performed. Emergency general surgery diagnoses were defined using International Classification Diseases, Tenth Revision, codes and grouped into seven common diagnosis categories: appendicitis, cholecystitis, small/large bowel, peptic ulcer disease, groin hernia, ventral hernia, and necrotizing soft tissue infection. Baseline demographics were compared including age, race/ethnicity, and payor status. Outcomes included coronavirus disease (COVID) status and mortality.

RESULTS

A total of 1,376 patients were admitted for EGS diagnoses from January to May 2020, a decrease compared with both 2018 (1,789) and 2019 (1,668) (p < 0.0001). This drop was most notable after the stay-at-home mandate (March 22, 2020; week 12). From March to May 2020, 3.3%, 19.2%, and 6.0% of EGS admissions were incidentally COVID positive, respectively. Mortality increased in March to May 2020 compared with 2019 (2.2% vs. 0.7%); this difference was statistically significant between April 2020 and April 2019 (4.1% vs. 0.9%, p = 0.045).

CONCLUSION

Supporting our hypothesis, the coronavirus disease 2019 pandemic and subsequent stay-at-home mandate resulted in decreased EGS admissions between March and May 2020 compared with prior years. During this time, there was also a statistically significant increase in mortality, which peaked at the height of COVID infection rates in our population.

LEVEL OF EVIDENCE

Epidemiological, level IV.
Fragmentation of care in the blunt abdominal trauma patient: Capturing our true outcomes and impact on care
Authors: Carr Matthew J. , Badiee Jayraan , Benham Derek A. , Diaz Joseph A. , Calvo Richard Y. , Sise C. Beth , Sise Michael J. , Bansal Vishal , Martin Matthew J.
Published: April 2021

BACKGROUND

Trauma care is associated with unplanned readmissions, which may occur at facilities other than the index treatment facility. This “fragmentation of care” may be associated with adverse outcomes. We evaluated a statewide database that includes readmissions to analyze the incidence and impact of FC.

METHODS

The California Office of Statewide Health Planning and Development patient discharge data set was evaluated for calendar years 2016 to 2018. Patients 15 years or older diagnosed with blunt abdominal solid organ injury during the index admission were identified. Readmissions were evaluated postdischarge at 1, 3, and 6 months. Patients readmitted within 6 months to a facility other than the index admission facility (fragmented care [FC]) were compared with those readmitted to their index admission facility (non-FC). Logistic regression modeling was used to evaluate risk of FC.

RESULTS

Of the total 1,580 patients, there were 752 FC (47.6%) and 828 (52.4%) non-FC. Readmissions representing FC at months 1, 3, and 6 were 40.3%, 49.3%, and 53.4%, respectively. At index admission, the groups were demographically and clinically similar, with similar rates of abdominal operations and complications. Non-FC patients had a higher rate of abdominal reoperation at readmission (5.8% non-FC vs. 2.9% FC, p = 0.006). In an adjusted model, multiple readmissions (odds ratio [OR] 1.11, p = 0.014), readmission >30 days after index facility discharge (OR, 1.98; p < 0.001), and discharge to a nonmedical facility (OR, 2.46; p < 0.0001) were associated with increased odds of FC. Operative intervention at index admission was associated with lower odds of FC (OR, 0.77; p = 0.039). However, FC was not independently associated with demographic or insurance characteristics.

CONCLUSION

The rate of FC among patients with blunt abdominal injury is high. The risk of FC is mitigated when patients are managed operatively during the index admission. Trauma systems should implement measures to ensure that these patients are followed postdischarge.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level III; Care management, level IV.
Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
Authors: Ikegame Satoshi , Siddiquey Mohammed N. A. , Hung Chuan-Tien , Haas Griffin , Brambilla Luca , Oguntuyo Kasopefoluwa Y. , Kowdle Shreyas , Vilardo Ariel Esteban , Edelstein Alexis , Perandones Claudia , Kamil Jeremy P. , Lee Benhur
Published: April 2021

The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.
CliP: subclonal architecture reconstruction of cancer cells in DNA sequencing data using a penalized likelihood model
Authors: Jiang Yujie , Yu Kaixian , Ji Shuangxi , Shin Seung Jun , Cao Shaolong , Montierth Matthew D , Huang Licai , Kopetz Scott , Msaouel Pavlos , Wang Jennifer Rui , Kimmel Marek , Zhu Hongtu , Wang Wenyi
Published: April 2021

Subpopulations of tumor cells characterized by mutation profiles may confer differential fitness and consequently influence prognosis of cancers. Understanding subclonal architecture has the potential to provide biological insight in tumor evolution and advance precision cancer treatment. Recent methods comprehensively integrate single nucleotide variants (SNVs) and copy number aberrations (CNAs) to reconstruct subclonal architecture using whole-genome or whole-exome sequencing (WGS, WES) data from bulk tumor samples. However, the commonly used Bayesian methods require a large amount of computational resources, a prior knowledge of the number of subclones, and extensive post-processing. Regularized likelihood modeling approach, never explored for subclonal reconstruction, can inherently address these drawbacks. We therefore propose a model-based method,Clonal structureidentification through pair-wisePenalization, or CliP, for clustering subclonal mutations without prior knowledge or post-processing. The CliP model is applicable to genomic regions with or without CNAs. CliP demonstrates high accuracy in subclonal reconstruction through extensive simulation studies. Utilizing the well-established regularized likelihood framework, CliP takes only 16 hours to process WGS data from 2,778 tumor samples in the ICGC-PCAWG study, and 38 hours to process WES data from 9,564 tumor samples in the TCGA study. In summary, a penalized likelihood framework for subclonal reconstruction will help address intrinsic drawbacks of existing methods and expand the scope of computational analysis for cancer evolution in large cancer genomic studies. The associated software tool is freely available at:https://github.com/wwylab/CliP.
Dynamic product-precursor relationships underlie cuticular lipid accumulation on maize silks
Authors: Chen Keting , Alexander Liza E. , Mahgoub Umnia , Okazaki Yozo , Higashi Yasuhiro , Takano Kouji , Loneman Derek , Dennison Tesia S. , Lopez Miriam , Claussen Reid , Peddicord Layton , Saito Kazuki , Lauter Nick , Dorman Karin S. , Nikolau Basil J. , Yandeau-Nelson Marna D.
Published: April 2021

The hydrophobic cuticle is the first line of defense between aerial portions of a plant and the external environment. On maize silks, the cuticular cutin matrix is infused with cuticular lipids, consisting of a homologous series of very-long-chain fatty acids (VLCFAs), aldehydes, and hydrocarbons that serve as precursors, intermediates, and end-products of the elongation, reduction, and decarbonylation reactions of the hydrocarbon-producing pathway. To deconvolute the potentially confounding impacts of the silk microenvironment and silk development on the hydrocarbon-producing pathway, spatio-temporal cuticular lipid profiling was conducted on the agronomically important inbreds B73 and Mo17, and their reciprocal hybrids. Statistical interrogation via multivariate analyses of the metabolite abundances of the hydrocarbon-producing pathway demonstrate that the cellular VLCFA pool is positively correlated with the cuticular lipid metabolome, and this metabolome is primarily affected by the silk microenvironment and the plant genotype. Moreover, genotype has a major effect on the pathway, with increased cuticular hydrocarbon and concomitant reduction of cuticular VLCFA accumulation on B73 silks, suggesting that conversion of VLCFAs to hydrocarbons is more effective in B73 than Mo17. Statistical modeling of the ratios between cuticular hydrocarbons and cuticular VLCFAs reveals the complexity of the product-precursor ratio relationship, demonstrating a significant role of precursor chain length. Longer-chain VLCFAs are preferentially utilized as precursors for hydrocarbon biosynthesis. Collectively, these findings demonstrate maize silks as an effective and novel system for dissection of the complex dynamics of cuticular lipid accumulation in plants.

One-sentence Summary

The product-precursor ratios in the cuticular hydrocarbon-producing pathway are impacted by fatty acid precursor chain length, plant genotype and the spatio-temporal dynamic gradients of maize silks.
Dynamic functional connectivity links with treatment response of electroconvulsive therapy in major depressive disorder
Authors: Sendi Mohammad S. E. , Dini Hossein , Sui Jing , Fu Zening , Espinoza Randall , Narr Katherine , Qi Shile , Abbott Christopher C. , van Rooij Sanne , Riva-Posse Patricio , Mayberg Helen S. , Calhoun Vince D.
Published: April 2021

Background

Electroconvulsive Therapy (ECT) is one of the most effective treatments for major depressive disorder (DEP). There is recently increasing attention to evaluate ECT’s effect on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of DEP patients with healthy participants, investigate whether dynamic functional network connectivity network (dFNC) estimated from rs-fMRI predicts the ECT outcome, and explore the effect of ECT on brain network states.

Method

Resting-state fMRI data were collected from 119 patients with depression or DEP (76 females), and 61 Healthy (HC) participants (34 females) with an age mean of 52.25 (N=180) years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale (HDRS) were 25.59±6.14 and 11.48±9.07, respectively. Twenty-four independent components from default mode (DMN) and cognitive control network (CCN) were extracted using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each participant. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each individual spends in each state, called occupancy rate or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, number of treatment, and site. Finally, we evaluated the effectiveness of ECT by comparing pre-and post-ECT OCR of DEP and HC participants.

Results

The main findings include: 1) DEP patients had significantly lower OCR values than the HC group in a state, where connectivity between CCN and DMN was relatively higher than other states (corrected p= 0.015), 2) Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, predicted the HDRS changes (R=0.23 corrected p=0.03). This means that those DEP patients who spend less time in this state showed more HDRS change, and 3) The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spend in state 2 (corrected p=0.03). Finally, we found ECT increases the total traveled distance in DEP.

Conclusion

Our finding suggests that dFNC features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identified a possible underlying mechanism associated with the ECT effect in DEP patients.
A meta-analysis of Microarray Data is Effective for Identifying Gravity-Sensitive Genes
Authors: Liang Yin , Wang Mengxue , Liu Yun , Wang Chen , Takahashi Ken , Naruse Keiji
Published: April 2021

Gravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells to simulated microgravity using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin transporter geneSLCO2A1decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level ofSLCO2A1, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.
Multiplexed 3D atlas of state transitions and immune interactions in colorectal cancer
Authors: Lin Jia-Ren , Wang Shu , Coy Shannon , Chen Yu-An , Yapp Clarence , Tyler Madison , Nariya Maulik K. , Heiser Cody N. , Lau Ken S. , Santagata Sandro , Sorger Peter K.
Published: April 2021

Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells characterized by high intratumoral variation. We use highly multiplexed tissue imaging, 3D reconstruction, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. Quantitation of these features in high-plex marker space reveals recurrent transitions from one tumor morphology to the next, some of which are coincident with long-range gradients in the expression of oncogenes and epigenetic regulators. At the tumor invasive margin, where tumor, normal, and immune cells compete, T-cell suppression involves multiple cell types and 3D imaging shows that seemingly localized 2D features such as tertiary lymphoid structures are commonly interconnected and have graded molecular properties. Thus, while cancer genetics emphasizes the importance of discrete changes in tumor state, whole-specimen imaging reveals large-scale morphological and molecular gradients analogous to those in developing tissues.
Effective Therapy Targeting Cytochromebc1PreventsBabesiaErythrocytic Development and Protects from Lethal Infection
Authors: Chiu Joy E. , Renard Isaline , Pal Anasuya C. , Singh Pallavi , Vydyam Pratap , Thekkiniath Jose , Kumar Madelyn , Gihaz Shalev , Pou Sovitj , Winter Rolf W. , Dodean Rozalia , Nilsen Aaron C. , Riscoe Michael K. , Doggett J. Stone , Mamoun Choukri Ben
Published: April 2021

Targeting conserved metabolic processes that are essential for viability of pathogens, such asPlasmodiumandBabesiathat cause blood-borne diseases, is an effective strategy to eliminate malaria and babesiosis infections with no recrudescence. One interesting target is the mitochondrial cytochromebc1complex, which could be inhibited by drugs such as endochin-like quinolones (ELQ) and atovaquone. We used the tick-transmitted and culturable blood-borne pathogenBabesia duncanito evaluate the structure-activity relationship, safety, efficacy and mode of action of ELQs. We identified a potent and highly selective ELQ prodrug (ELQ-502), which alone or in combination with atovaquone eliminatesB. microtiandB. duncaniinfectionsin vitroand in mouse models of parasitemia and lethal infection. The strong efficacy at low dose, excellent safety, bioavailability and long half-life of this experimental therapy makes it an ideal clinical candidate for the treatment of human infections caused byBabesiaand its closely related apicomplexan parasites.
Root meristem shaping via brassinosteroid-controlled cell geometry
Authors: Fridman Y. , Strauss S. , Horev G. , Ackerman-Lavert M. , Benaim A Reiner , Lane B , Smith R.S. , Savaldi-Goldstein S.
Published: April 2021

Growth extent and direction determine cell and whole-organ architecture. How they are spatiotemporally modulated to control size and shape? Here we tackled this question by studying the effect of brassinosteroid (BR) signaling on the structure of the root meristem. Quantification of the 3D geometry of thousands of individual meristematic cells across different tissue types showed that modulation of BR signaling yields distinct changes in growth rate and anisotropy, which affects the time cells spend in the meristem and has a strong impact on final root form. By contrast, the hormone effect on cell volume was minor, establishing cell volume as invariant to the effect of BR. Thus, BR has highest effect on cell shape and growth anisotropy, regulating overall radial growth of the meristem, while maintaining a coherent distribution of cell sizes. Moving from single-cell quantification to the whole organ, we developed a computational model of radial growth that demonstrates how differential growth regulation by BR between the inner and outer tissues shapes the meristem. The model explains the unintuitive outcomes of tissue-specific perturbation of BR signaling and suggests that the inner and outer tissues have independent but coordinated roles in growth regulation.
HaloTag9: an engineered protein tag to improve fluorophore performance
Authors: Frei Michelle S. , Tarnawski Miroslaw , Roberti Julia , Koch Birgit , Hiblot Julien , Johnsson Kai
Published: April 2021

HaloTag9 is an engineered variant of HaloTag7 with up to 40% higher brightness and increased fluorescence lifetime when labeled with fluorogenic rhodamines. Moreover, combining HaloTag9 with HaloTag7 and other fluorescent probes enabled live-cell multiplexing using a single fluorophore and the generation of a fluorescence lifetime-based biosensor. The increased brightness of HaloTag9 and its use in fluorescence lifetime multiplexing makes it a powerful tool for live-cell imaging.
Physical observables to determine the nature of membrane-less cellular sub-compartments
Authors: Heltberg Mathias Luidor , Miné-Hattab Judith , Taddei Angela , Walczak Aleksandra M. , Mora Thierry
Published: April 2021

The spatial organization of complex biochemical reactions is essential for the regulation of cellular processes. Membrane-less structures called foci containing high concentrations of specific proteins have been reported in a variety of contexts, but the mechanism of their formation is not fully understood. Several competing mechanisms exist that are difficult to distinguish empirically, including liquid-liquid phase separation, and the trapping of molecules by multiple binding sites. Here we propose a theoretical framework and outline observables to differentiate between these scenarios from single molecule tracking experiments. In the binding site model, we derive relations between the distribution of proteins, their diffusion properties, and their radial displacement. We predict that protein search times can be reduced for targets inside a liquid droplet, but not in an aggregate of slowly moving binding sites. These results are applicable to future experiments and suggest different biological roles for liquid droplet and binding site foci.