REFORMS: Consensus-based Recommendations for Machine-learning-based Science.

Machine learning (ML) methods are proliferating in scientific research. However, the adoption of these methods has been accompanied by failures of validity, reproducibility, and generalizability. These failures can hinder scientific progress, lead to false consensus around invalid claims, and undermine the credibility of ML-based science. ML methods are often applied and fail in similar ways across disciplines. Motivated by this observation, our goal is to provide clear recommendations for conducting and reporting ML-based science. Drawing from an extensive review of past literature, we present the REFORMS checklist (recommendations for machine-learning-based science). It consists of 32 questions and a paired set of guidelines. REFORMS was developed on the basis of a consensus of 19 researchers across computer science, data science, mathematics, social sciences, and biomedical sciences. REFORMS can serve as a resource for researchers when designing and implementing a study, for referees when reviewing papers, and for journals when enforcing standards for transparency and reproducibility.

Sternal fixation for traumatic sternal fractures demonstrates better long-term quality of life outcomes than nonoperative management: A survey analysis.

INTRODUCTION: Sternal fractures are rare, causing significant pain, respiratory compromise, and decreased upper extremity range of motion. Sternal fixation (SF) is a viable treatment option; however, there remains a paucity of literature demonstrating long-term benefits. This study examined long-term outcomes of SF, hypothesizing they have better long-term quality of life (QoL) than patients managed nonoperatively (NOM). METHODS: This was a survey study at our level 1 academic hospital. All patients diagnosed with a sternal fracture were included from January 2016 to July 2021. Patients were grouped whether they received SF or NOM. Basic demographics were obtained. Three survey phone call attempts were conducted. The time from injury to survey was recorded. Outcomes included responses to the QoL survey, which included mobility, self-care, usual activities, chest pain/discomfort, and anxiety/depression. The survey scale is 1-5 (1 = worst condition possible; 5 = best possible condition). Patients were asked to rate their current health on a scale of 0-100 (100 being the best possible health imaginable). Chi square and t-tests were used. Significance was set at p < 0.05. RESULTS: Three hundred eighty four patients were surveyed. Sixty nine underwent SF and 315 were NOM. Thirty-eight (55.1%) SF patients and 126 (40%) NOM patients participated in the survey. Basic demographics were similar. Average days from sternal fracture to survey was 1198 (±492) for the SF group and 1454 (±567) for the NOM group. The SF cohort demonstrated statistically significant better QoL than the NOM cohort for all categories except anxiety/depression. CONCLUSION: SF provides better long-term QoL and better overall health scores compared to NOM.

Rural Trauma Team Development Course Positively Impacts its Desired Objectives.

BACKGROUND: The Rural Trauma Team Development Course (RTTDC) is designed to help rural hospitals better organize and manage trauma patients with limited resources. Although RTTDC is well-established, limited literature exists regarding improvement in the overall objectives for which the course was designed. The aim of this study was to analyze the goals of RTTDC, hypothesizing improvements in course objectives after course completion. METHODS: This was a prospective, observational study from 2015 through 2021. All hospitals completing the RTTDC led by our Level 1, academic trauma hospital were included. Our institutional database was queried for individual patient data. Cohorts were delineated before and after RTTDC was provided to the rural hospital. Basic demographics were obtained. Outcomes of interest included: Emergency Department (ED) dwell time, decision time to transfer, number of total images/computed tomography scans obtained, and mortality. Chi square and non-parametric median test were used. Significance was set at P < .05. RESULTS: Sixteen rural hospitals were included with a total of 472 patients transferred (240 before and 232 after). Patient demographics were similar before and after RTTDC. ED dwell time was significantly reduced by 64 min (P = .003) and decision to transfer time was cut by 62 min (P = .004) after RTTDC. Mean total radiographic images and CT scans were significantly reduced (P < .001 and P = .002, respectively) after RTTDC. Mortality was unaffected by RTTDC completion (P = .941). CONCLUSION: The RTTDC demonstrates decreased ED dwell time, decision time to transfer, and number of radiographic images obtained prior to transfer. More rural hospitals should be offered this course.

Better late than never-a single-center review of delayed rib fixation for symptomatic rib fractures and nonunions.

BACKGROUND: Surgical stabilization of rib fractures (SSRFs) has become an emerging therapy for treatment of patients with rib fractures. More commonly, it is used in the acute setting; however, delayed SSRF can be utilized for symptomatic rib fracture nonunions. Here, we describe our institution's experience with delayed SSRF, hypothesizing it is safe and resolves patient symptoms. METHODS: This is a retrospective review of patients presenting to our Level I trauma center to undergo delayed SSRF for symptomatic nonunions from January 2017 to September 2022. Delayed SSRF was defined as SSRF over 2 weeks in the outpatient setting. Basic demographics were obtained. Outcomes of interest included mean pain score (preoperatively and postoperatively), intensive care unit (ICU) and hospital length of stay (LOS), and resolution of preoperative symptoms, specifically chest wall instability, with return to activities of daily living (ADLs). RESULTS: Forty-four patients met inclusion criteria with a total of 156 symptomatic nonunion rib fractures that received delayed SSRF. The average age was 59.2 ± 11.9 years and median number of days from injury to SSRF was 172.5 (interquartile range, 27.5-200). The average number rib fractures plated per patient 3.5 ± 1.8. Only three patients required ICU admission postoperatively for no longer than 2 days. Median hospital LOS was 2 days (interquartile range 1-3 days). Average preoperative and postoperative pain score was 6.8 ± 1.9 and 2.02 ± 1.5, respectively ( p < 0.001). Chest wall instability and preoperative symptoms resolved in 93.2% of patients postoperatively ( p < 0.001). Two patients (4.5%) had postoperative complications that resolved after additional surgical intervention. Rib fracture healing was demonstrated on radiographic imaging during postoperative follow-up. CONCLUSION: Delayed SSRF is safe and demonstrates significant resolution of preoperative symptoms by decreasing pain, improving chest wall stability, and allowing patients to return to activities of daily living. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Surgical stabilization of rib fractures is associated with better return on investment for a health care institution than nonoperative management.

BACKGROUND: Surgical stabilization of rib fractures (SSRFs) continues to gain popularity due to patient benefits. However, little has been produced regarding the economic benefits of SSRF and its impact on hospital metrics such as Vizient. The aim of this study was to explore these benefits hypothesizing SSRF will demonstrate positive return on investment (ROI) for a health care institution. METHODS: This is a retrospective review of all rib fracture patients over 5 years at our Level I trauma center. Patients were grouped into SSRF versus nonoperative management. Basic demographics were obtained including case mix index (CMI). Outcomes included narcotic requirements in morphine milliequivalents prior to discharge, mortality, and discharge disposition. Furthermore, actual hospital length of stay (ALOS) versus Vizient expected length of stay were compared between cohorts. Contribution margin (CM) was also calculated. Independent t-test, paired t-test, and linear regression analysis were performed, and significance set at p < 0.05. RESULTS: A total of 1,639 patients were included; 230 (14%) underwent SSRF. Age, gender, and Injury Severity Score were similar. Surgical stabilization of rib fracture patients had more ribs fractured (7 vs. 4; p < 0.001) and more patients with flail chest (43.5% vs. 6.7%; p < 0.001). Surgical stabilization of rib fracture patients also had a significantly higher CMI (4.33 vs. 2.78; p = 0.001). Narcotic requirements and mortality were less in the SSRF cohort; 155 versus 246 morphine milliequivalents ( p < 0.001) and 1.7% versus 7.1% ( p = 0.003), respectively. Surgical stabilization of rib fracture patients were more likely to be discharged home (70.4% vs. 63.7%; p = 0.006). Surgical stabilization of rib fracture patients demonstrated shorter ALOS where nonoperative management patients demonstrated longer ALOS compared with Vizient expected length of stay. Contribution margins for SSRF patients were significantly higher and linear regression analysis showed a CM $1,128.14 higher per patient undergoing SSRF ( p < 0.001). CONCLUSION: Patients undergoing SSRF demonstrate a significant ROI for a health care organization. Despite SSRF patients having a higher CMI, they were able to be discharged sooner than expected by Vizient calculations resulting in better a CM. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

What do classroom teachers of varying backgrounds know about English spelling?

The ability to encode (spell) is an integral writing skill needed to communicate effectively. The ability to spell, also, enhances decoding as spelling and decoding are reciprocal skills that rely on knowledge of the same subskills. Spelling can also be particularly difficult for students with literacy and phonological-processing difficulties such as dyslexia. Because of the multiple benefits of knowing how to spell correctly, it is important for teachers to know the structure of the English language, so they can explicitly teach spelling. Through the administration of a survey, this study assessed 324 U.S. teachers' knowledge of English spelling patterns (Part 1). In addition, the inclusion of survey items intended to measure teachers' awareness of how children's spelling can be influenced by either African American English or the overlap between Spanish and English in emergent bilinguals. African American English and Spanish were chosen due to the underperformance of many African American and Hispanic/Latinx students on national and state reading assessments. Part 2 of the survey assessed teachers' self-efficacy in teaching spelling, while Part 3 assessed teachers' philosophy about spelling and teaching spelling. The Rasch analyses revealed that teachers whose primary area of teaching was reading outperformed those whose primary area of teaching was not reading. Additionally, teachers who taught Emergent Bilinguals outperformed those who did not on the constructs measuring words with possible influences of Spanish language on the spelling of English words. Several spelling patterns posed problems for all groups of teachers, while others were the least difficult for teachers. Practical and research implications are addressed.

Hardware Infection From Surgical Stabilization of Rib Fractures Is Lower Than Previously Reported.

Introduction Surgical stabilization of rib fractures (SSRF) is an emerging therapy for the treatment of patients with traumatic rib fractures. Despite the demonstrated benefits of SSRF, there remains a paucity of literature regarding the complications from SSRF, especially those related to hardware infection. Currently, literature quotes hardware infection rates as high as 4%. We hypothesize that the hardware infection rate is much lower than currently published. Methods This is an IRB-approved, four-year multicenter descriptive review of prospectively collected data from January 2016 to June 2022. All patients undergoing SSRF were included in the study. Exclusion criteria included those patients less that 18 years of age. Basic demographics were obtained: age, gender, Injury Severity Score (ISS), Abbreviate Injury Scale-chest (AIS-chest), flail chest (yes/no), delayed SSRF more than two weeks (yes/no), number of patients with a pre-SSRF chest tube, and number of ribs fixated. Primary outcome was hardware infection. Secondary outcomes included mortality rate and hospital length of stay (HLOS). Basic descriptive statistics were utilized for analysis. Results A total of 453 patients met criteria for inclusion in the study. Mean age was 63 ± 15.2 years and 71% were male. Mean ISS was 17.3 ± 8.5 with a mean AIS-chest of 3.2 ± 0.5. Flail chest (three consecutive ribs with two or more fractures on each rib) accounted for 32% of patients. Forty-two patients (9.3%) underwent delayed SSRF. The average number of ribs stabilized was 4.75 ± 0.71. When analyzing the primary outcome, only two patients (0.4%) developed a hardware infection requiring reoperation to remove the plates. Overall HLOS was 10.5 ± 6.8 days. Five patients suffered a mortality (1.1%), all five with ISS scores higher than 15 suggesting significant polytrauma. Conclusion This is the largest case series to date examining SSRF hardware infection. The incidence of SSRF hardware infection is very low (<0.5%), much less than quoted in current literature. Overall, SSRF is a safe procedure with low morbidity and mortality.

Impact of sternal fixation on patient outcomes: A case matched review.

INTRODUCTION: Sternal fractures are debilitating injuries often resulting in severe pain and respiratory compromise. Surgical fixation of sternal fractures is gaining popularity as a treatment modality for sternal fractures. Unfortunately, little literature exists on this topic. This study looks to further examine the benefits of sternal fixation (SF), hypothesizing SF results in improved pain, improved respiratory function, and decreased opioid use. METHODS: Retrospective review was performed between patients with sternal fractures who underwent nonoperative management (NOM) versus operative SF. Case matching was used to construct an artificial control group matched on age and Injury Severity Score using a 1:1 ratio of treatment to control. Exclusion criteria were age younger than 18 years. Outcomes of interest included mean pain score, total opioid requirements (in morphine milliequivalents) within 24 hours of discharge, intensive care unit and hospital length of stay (LOS), and incentive spirometry percent predicted value at discharge. Dependent variables were analyzed using t test, and Injury Severity Score was analyzed using the sign test. Statistical significance was set at p < 0.05. RESULTS: Fifty-eight patients from the SF cohort were matched with 58 patients from the NOM cohort. The average age was 59.8 years for the SF group and 62.2 years for the NOM group. Injury Severity Score was matched at 9 for both cohorts. Although pain scores were similar for both cohorts, the SF group required significantly less opioids at discharge (62.1 vs. 92.2 morphine milliequivalents; p = 0.007). In addition, the SF cohort demonstrated significantly improved respiratory function per incentive spirometry percent predicted value at discharge (75.5% vs. 59.9%; p < 0.001). Intensive care unit LOS and hospital LOS were similar between cohorts. CONCLUSION: Despite similarities in pain scores, intensive care unit LOS, and hospital LOS, SF was associated with decreased opioid requirements and improved respiratory function at discharge in this study. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Focusing in on gallbladder disease. Do current imaging modalities accurately depict the severity of final pathology?

BACKGROUND: Accuracy of imaging modalities for gallbladder disease(GBD) remains questionable. We hypothesize ultrasonography(US), computed tomography(CT), and magnetic resonance imaging(MRI) poorly correlate with final pathologic analysis. METHODS: This was a retrospective review of all patients who underwent cholecystectomy at our institution. Primary outcome was agreement between US, CT, and MRI, and final pathology report of the gallbladder. Cohen's Kappa statistic was used to describe the level of agreement (0 = agreement equivalent to chance, 0.1-0.2 = slight agreement, 0.21-0.40 = minimal/fair agreement, 0.41-0.60 = moderate agreement, 0.61-0.80 = substantial agreement, 0.81-0.99 = near perfect agreement, 1 = perfect agreement). Significance was set at p < 0.05. RESULTS: 1107 patients were enrolled. Average age was 48.6(±17.6); 64.2% were female. There was minimal agreement between the three imaging modalities and final pathology (US = 0.363; CT = 0.223; MRI = 0.351;p < 0.001). CONCLUSION: Poor agreement exists between imaging modalities and final pathology report for GBD. Urgent surgical intervention for patients presenting with symptoms of GBD should be considered, despite imaging results.

Finite element analysis for better evaluation of rib fractures: A pilot study.

INTRODUCTION: Modeling rib fracture stability is challenging. Computer-generated finite element analysis (FEA) is an option for assessment of chest wall stability (CWS). The objective is to explore FEA as a means to assess CWS, hypothesizing it is a reliable approach to better understand rib fracture pathophysiology. METHODS: Thoracic anatomy was generated from standardized skeletal models with internal/external organs, soft tissue and muscles using Digital Imaging and Communications in Medicine data. Material properties were assigned to bone, cartilage, skin and viscera. Simulation was performed using ANSYS Workbench (2020 R2, Canonsburg, PA). Meshing the model was completed identifying 1.3 and 2.1 million elements and nodes. An implicit solver was used for a linear/static FEA with all bony contacts identified and applied. All material behavior was modeled as isotropic/linear elastic. Six load cases were evaluated from a musculoskeletal AnyBody model; forward flexion, right/left lateral bending, right/left axial rotation and 5-kg weight arm lifting. Standard application points, directions of muscle forces, and joint positions were applied. Ten fracture cases (unilateral and bilateral) were defined and 66 model variations were simulated. Forty-three points were applied to each rib in the mid/anterior axillary lines to assess thoracic stability. Three assessment criteria were used to quantify thoracic motion: normalized mean absolute error, normalized root mean square error, and normalized interfragmentary motion. RESULTS: All three analyses demonstrated similar findings that rib fracture deformation and loss of CWS was highest for left/right axial rotation. Increased number of ribs fracture demonstrated more fracture deformation and more loss of CWS compared with a flail chest segment involving less ribs. A single rib fracture is associated with ~3% loss of CWS. Normalized interfragmentary motion deformation can increases by 230%. Chest wall stability can decrease by over 50% depending on fracture patterns. CONCLUSION: Finite element analysis is a promising technology for analyzing CWS. Future studies need to focus on clinical relevance and application of this technology. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level IV.

Severity of Illness Impacts Outcomes More than Admitting Service for Isolated Hip Fracture Patients.

INTRODUCTION: Isolated hip fractures (IHF) are common injuries in the elderly. Controversy exists about which hospital service is best suited to manage these patients. We hypothesize that baseline patient severity of illness (SOI) score drives patient outcomes, not the hospital service managing these patients. METHODS: Retrospective review of all IHF patients from 2014 to 2018 at our Level 1 trauma center. Basic demographics were obtained. Patients were divided into service line they were admitted; surgical vs non-surgical. Primary outcomes included hospital length of stay (HLOS), time to OR, time to VTE prophylaxis, complication rate (defined by the Trauma Quality Improvement Program), 30-day mortality, and readmissions. SOI score (which is DRG-based) was controlled to see if any differences in primary outcomes occurred between cohorts. Chi-square was used for categorical variables and regression analysis for continuous variables. Significance was p < 0.05. RESULTS: A total of 366 total patients were analyzed with the same ISS. A total of 102 were admitted to a surgical service and 264 to a non-surgical service. Average overall age was 80 year, 66.9% were female, and 86% were Caucasian. There was no statistical difference between outcomes when comparing admitting services. Controlling for SOI score, there was no difference between admitting service for outcomes as well. SOI score was a significant predictor for increased HLOS and complication occurrence (p < 0.001) via regression analysis, with a 6.06-fold increase in complication rate from mild to moderate SOI score (p = 0.001). CONCLUSION: There is no difference in outcomes based on admitting service and process measures. However, the SOI score is perhaps a better predictor of outcomes for isolated hip fracture patients.

"Peas in a Pod": Clustering minorly injured trauma patients together during their hospitalization results in decreased hospital costs and fewer inpatient complications.

BACKGROUND: Trauma patient care is complex. Clustering these patients within the hospital seems intuitive. This study's purpose was to explore the benefits of trauma patient clustering, hypothesizing these patients will have decreased costs and better outcomes. METHODS: This was an analysis of all adult (18-99 years) trauma patients admitted from 1/2017-1/2019 without an intensive care unit stay. Patients were grouped into those admitted to the trauma unit (TU) versus non-trauma units (NTU). Outcomes evaluated between groups were baseline demographics, direct costs, complication rates (using our TQIP registry), and discharge location. T-test, median test, and chi squared test were used. Linear regression was performed. Significance was set at p < 0.05. RESULTS: 1481 patients (684 TU and 797 NTU) were analyzed. TU patients were younger. Injury Severity Score, mortality, and hospital length of stay were similar between groups. Direct hospital costs were decreased for TU patients ($4941(±$4740) versus $5639(±$4897), p = 0.006). Fewer TU patients experienced inpatient complications (7.8% versus 13.5%, p < 0.001). More TU patients were discharged to home (78.9% versus 73.8%, p = 0.02). Linear regression analysis demonstrated admission to NTUs predicted a direct cost increase of $766.35 (p < 0.001). CONCLUSIONS: Clustering minorly injured trauma patients on a dedicated unit resulted in reduced costs, decreased complications, and higher likelihood for discharge to home.

Comparison of long-term outcomes from rib fractures for patients undergoing both operative and non-operative management: a survey analysis.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) has been gaining popularity for the treatment of rib fractures. Limited literature exists regarding the long-term effects of SSRF versus non-operative (NO) intervention. The goal of this study is to better understand these long-term effects, hypothesizing SSRF patients have better outcomes. METHODS: IRB approved survey study at our Level I trauma center. Patients suffering rib fractures from 1/2017 through 1/2019 were surveyed via phone call and asked five questions. Basic demographics obtained. The five survey questions asked: "Are you still experiencing pain from your rib fractures?"; "If yes, how would you rate your pain 1-10?"; "Are you back to your baseline activity level?"; "If no, is this related to your rib fractures?"; "Do you feel your rib fractures moving/clicking?" Paired t test, Chi square, and median tests were utilized. Significance was set at p < 0.05. RESULTS: 527 patients were called with 228 unsuccessfully reached. 47 refused to participate. 252 patients (47.8%) participated in the survey; 78 SSRF and 174 NO. Age and gender were similar between cohorts. Majority of patients suffered blunt trauma. No significant difference between ISS; 15 SSRF vs 14 NO. SSRF patients had worse chest trauma with median chest AIS of 3 (IQR 3-4) vs 3 (IQR 3-3) for NO (p < 0.001). Response to survey questions revealed similar incidences of pain between SSRF and NO cohorts (28.2% vs 27.6%; p = 0.939), however decreased pain scores for SSRF group (2 vs 4; p = 0.006). Return to baseline activity was better for the SSRF group (75.6% vs 56.3%; p = 0.143) and the incidence of rib fractures being the reason for patients not returning to baseline was decreased (26.3% vs 44.7%; p = 0.380). Lastly, SSRF resulted in significantly less movement of rib fractures (3.8% vs 13.8%; p = 0.031). CONCLUSION: Patients who undergo SSRF show significant long-term improvements in pain scores and better return to baseline function with less overall issues from their rib fractures compared to those managed non-operatively.

Discrepancies in rib fracture severity between radiologist and surgeon: A retrospective review.

BACKGROUND: Chest computed tomography (CT) scans are important for the management of rib fracture patients, especially when determining indications for surgical stabilization of rib fractures (SSRFs). Chest CTs describe the number, patterns, and severity of rib fracture displacement, driving patient management and SSRF indications. Literature is scarce comparing radiologist versus surgeon rib fracture description. We hypothesize there is significant discrepancy between how radiologists and surgeons describe rib fractures. METHODS: This was an institutional review board-approved, retrospective study conducted at a Level I academic center from December 2016 to December 2017. Adult patients (≥18 years of age) suffering rib fractures with a CT chest where included. Basic demographics were obtained. Outcomes included the difference between radiologist versus surgeon description of rib fractures and differences in the number of fractures identified. Rib fracture description was based on current literature: 1, nondisplaced; 2, minimally displaced (<50% rib width); 3, severely displaced (≥50% rib width); 4, bicortically displaced; 5, other. Descriptive analysis was used for demographics and paired t test for statistical analysis. Significance was set at p = 0.05. RESULTS: Four hundred and ten patients and 2,337 rib fractures were analyzed. Average age was 55.6(±20.6); 70.5% were male; median Injury Severity Score was 16 (interquartile range, 9-22) and chest Abbreviated Injury Scale score was 3 (interquartile range, 3-3). For all descriptive categories, radiologists consistently underappreciated the severity of rib fracture displacement compared with surgeon assessment and severity of displacement was not mentioned for 35% of rib fractures. The mean score provided by the radiologist was 1.58 (±0.63) versus 1.78 (±0.51) by the surgeon (p < 0.001). Radiologists missed 138 (5.9%) rib fractures on initial CT. The sensitivity of the radiologist to identify a severely displaced rib fracture was 54.9% with specificity of 79.9%. CONCLUSION: Discrepancy exists between radiologist and surgeon regarding rib fracture description on chest CT as radiologists routinely underappreciate fracture severity. Surgeons need to evaluate CT scans themselves to appropriately decide management strategies and SSRF indications. LEVEL OF EVIDENCE: Prognostic/Diagnostic Test, level III.

Surgical stabilization of rib fractures in octogenarians and beyond-what are the outcomes?

BACKGROUND: Prospective studies of surgical stabilization of rib fractures (SSRF) have excluded elderly patients, and no study has exclusively addressed the ≥80-year-old subgroup. We hypothesized that SSRF is associated with decreased mortality in trauma patients 80 years or older. METHODS: Multicenter retrospective cohort study involving eight centers. Patients who underwent SSRF from 2015 to 2020 were matched to controls by study center, age, injury severity score, and presence of intracranial hemorrhage. Patients with chest Abbreviated Injury Scale score less than 3, head Abbreviated Injury Scale score greater than 2, death within 24 hours, and desire for no escalation of care were excluded. A subgroup analysis compared early (0-2 days postinjury) to late (3-7 days postinjury) SSRF. Poisson regression accounting for clustered data by center calculated the relative risk (RR) of the primary outcome of mortality for SSRF versus nonoperative management. RESULTS: Of 360 patients, 133 (36.9%) underwent SSRF. Compared with nonoperative patients, SSRF patients were more severely injured and more likely to receive locoregional analgesia. There were 31 hospital deaths among the entire sample (8.6%). Multivariable regression demonstrated a decreased risk of mortality for the SSRF group, as compared with the nonoperative group (RR, 0.41; 95% confidence interval, 0.24-0.69; p < 0.01). However, SSRF patients were more likely to develop pneumonia, and had an increased duration of both mechanical ventilation and intensive care unit stay. There were no differences in discharge destination, although the SSRF group was less likely to be discharged on narcotics (RR, 0.66; 95% confidence interval, 0.48-0.90; p = 0.01). There was no difference in adjusted mortality between the early and late SSRF subgroups. CONCLUSION: Patients selected for SSRF were substantially more injured versus those managed nonoperatively. Despite this, SSRF was independently associated with decreased mortality. With careful patient selection, SSRF may be considered a viable treatment option in octogenarian/nonagenarians. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Development of Heterobivalent Theranostic Probes Having High Affinity/Selectivity for the GRPR/PSMA.

In this study, we describe the development of heterobivalent [DUPA-6-Ahx-([111In]In-DO3A)-8-Aoc-BBN ANT] and [DUPA-6-Ahx-([177Lu]Lu-DO3A)-8-Aoc-BBN ANT] radiotracers that display very high selectivity/specificity for gastrin-releasing peptide receptor (GRPR)-/prostate-specific membrane antigen (PSMA)-expressing cells. These studies include metallation, purification, characterization, and in vitro and in vivo evaluation of the new small-molecule-/peptide-based radiopharmaceuticals having utility for imaging and potentially therapy. Competitive displacement binding assays using PC-3 cells and LNCaP cell membranes showed high binding affinity for the GRPR or the PSMA. Biodistribution studies showed favorable excretion pharmacokinetics with high tumor uptake in PC-3 or PC-3 prostatic inhibin peptide (PIP) tumor-bearing mice. For example, tumor accumulation at the 1 h time point ranged from (4.74 ± 0.90) to (7.51 ± 2.61)%ID/g. Micro-single-photon emission computed tomography (microSPECT) molecular imaging investigations showed very high uptake in tumors with minimal accumulation of tracers in the surrounding collateral tissues in xenografted mice at 4 h postintravenous injection. In conclusion, [DUPA-6-Ahx-([111In]In-DO3A)-8-Aoc-BBN ANT] and [DUPA-6-Ahx-([177Lu]Lu-DO3A)-8-Aoc-BBN ANT] tracers displayed favorable pharmacokinetic and excretion profiles with high uptake and retention in tumors.

Teachers' knowledge about language constructs related to literacy skills and student achievement in low socio-economic status schools.

Teachers' knowledge is a critical component to students learning to read proficiently. The present research sought to determine the literacy knowledge of 150 urban, elementary school teachers from 11 low socio-economic schools in one of nation's largest cities. Teachers' ability to understand concepts relating to phonological awareness, phonemic awareness, alphabetic principle/phonics, and morphology as well as their knowledge about teaching these fundamental skills were assessed through a standardized measure. Using exploratory factor analysis to understand the latent constructs underlying the survey scores and hierarchical linear modelling on factor scores of each construct, the results revealed that teachers located in low socio-economic status schools did not have explicit knowledge needed to effectively teach struggling readers. Although the teachers possessed a high level of knowledge regarding syllable counting skills, they lacked knowledge related to morphology. Practical implications are provided to assist teachers in increasing their literacy knowledge.

Ultrasonographic inferior vena cava diameter response to trauma resuscitation after 1 hour predicts 24-hour fluid requirement.

BACKGROUND: Identification of occult hypovolemia in trauma patients is difficult. We hypothesized that in acute trauma patients, the response of ultrasound-measured minimum inferior vena cava diameter (IVCDMIN), IVC Collapsibility Index (IVCCI), minimum internal jugular diameter (IJVDMIN) or IJV Collapsibility Index (IJVCI) after up to 1 hour of fluid resuscitation would predict 24-hour resuscitation intravenous fluid requirements (24FR). METHODS: An NTI-funded, American Association for the Surgery of Trauma Multi-Institutional Trials Committee prospective, cohort trial was conducted at four Level I Trauma Centers. Major trauma patients were screened for an IVCD of 12 mm or less or IVCCI of 50% or less on initial focused assessment sonographic evaluations for trauma. A second IVCD was obtained 40 minutes to 60 minutes later, after standard-of-care fluid resuscitation. Patients whose second measured IVCD was less than 10 mm were deemed nonrepleted (NONREPLETED), those 10 mm or greater were repleted (REPLETED). Prehospital and initial resuscitation fluids and 24FR were recorded. Demographics, Injury Severity Score, arterial blood gasses, length of stay, interventions, and complications were recorded. Means were compared by ANOVA and categorical variables were compared via χ. Receiver operating characteristic curves analysis was used to compare the measures as 24FR predictors. RESULTS: There were 4,798 patients screened, 196 were identified with admission IVCD of 12 mm or IVCCI of 50% or less, 144 were enrolled. There were 86 REPLETED and 58 NONREPLETED. Demographics, initial hemodynamics, or laboratory measures were not significantly different. NONREPLETED had smaller IVCD (6.0 ± 3.7 mm vs. 14.2 ± 4.3 mm, p < 0.001) and higher IVCCI (41.7% ± 30.0% vs. 13.2% ± 12.7%, p < 0.001) but no significant difference in IJVD or IJVCCI. REPLETED had greater 24FR than NONREPLETED (2503 ± 1751 mL vs. 1,243 ± 1,130 mL, p = 0.003). Receiver operating characteristic analysis indicates IVCDMIN predicted 24FR (area under the curve [AUC], 0.74; 95% confidence interval [CI], 0.64-0.84; p < 0.001) as did IVCCI (AUC, 0.75; 95% CI, 0.65-0.85; p < 0.001) but not IJVDMIN (AUC, 0.48; 95% CI, 0.24-0.60; p = 0.747) or IJVCI (AUC, 0.54; 95% CI, 0.42-0.67; p = 0.591). CONCLUSION: Ultrasound assessed IVCDMIN and IVCCI response initial resuscitation predicts 24-hour fluid resuscitation requirements. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level II.

Design, synthesis and evaluation of 111In labeled DOTA-conjugated tetrapeptides having high affinity and selectivity for mu opioid receptors.

INTRODUCTION: Peripheral mu (µ) opioid receptors are implicated in pain, bowel dysfunction and the progression of certain cancers. In an effort to identify radioligands well suited for imaging these peripheral sites, we have prepared and evaluated four hydrophilic 111In labeled DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) conjugated µ tetrapeptides. METHODS: Peptides were prepared by solid-phase techniques, using orthogonal strategies to achieve branching to DOTA, and then characterized by HPLC, mass spectroscopy and amino acid analysis. Scaffolds included novel peptide H-Dmt-D-Ala-Phe-Orn-NH2 (DAPO), where Dmt = 2',6'-dimethyltyrosine, and known peptide H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA). Constructs had DOTA conjugation at the Orn4 or Lys4 side chains, or to the C-terminal through a hexanoic acid-lysine linker. Indium(III) complexation and 111In radiolabeling were accomplished by standard methods. Protein binding and Log D7.4 were determined. Binding and pharmacological profiles were obtained in vitro. Biodistribution and radiometabolite studies were conducted using male CD-1 mice. RESULTS: All four indium(III)-DOTA conjugates derived from DAPO and [Dmt1]DALDA showed good selectivity and subnanomolar affinity for µ opioid receptors. One radioligand, H-Dmt-D-Ala-Phe-Orn(δ-[111In]In-DOTA)-NH2, showed 25% specific binding in vivo to µ sites in mouse gut. Notably, this was the least polar of the series, and also showed low sensitivity to modulation of binding by sodium ions. All radioligands showed high kidney uptake of radiometabolites. CONCLUSIONS: Visualizing peripheral µ opioid receptors using 111In labeled DOTA-conjugated tetrapeptides appears feasible, but structural modifications to enhance specific binding and metabolic stability, as well as to reduce kidney uptake, will be required. ADVANCES IN KNOWLEDGE: This study shows in vivo labeling of peripheral µ opioid receptors by a tetrapeptide radioligand, and provides information that should prove useful in the design of peptide radioligands having optimal properties.

Allosteric modulation of sigma receptors by BH3 mimetics ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax).

ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax) are under intensive preclinical and clinical investigation as treatments for hematologic and other malignancies. These small molecules mimic pro-death B-cell lymphoma-2 (Bcl-2) Homology 3 (BH3) domain-only proteins. They also bear a structural resemblance to certain sigma (σ) receptor ligands. Moreover, the Bcl-2 and σ receptor protein families are both located primarily at the endoplasmic reticulum, mediate cell death and survival through protein-protein interactions, and physically associate. Accordingly, we examined the ability of the ABT series of BH3 mimetics to interact with σ receptors using radioligand-binding techniques. Negative allosteric modulation of [3H](+)-pentazocine, an agonist, binding to σ1 receptors in guinea pig brain membranes was observed for ABT-737, ABT-263 and ABT-199. Findings included reduction of specific binding to distinct plateaus in concentration-dependent fashion, significant slowing of radioligand dissociation kinetics, and decreases in radioligand affinity with no or modest changes in maximal receptor densities. Using a ternary complex model, dissociation constants (KX) for modulator binding to the σ1 receptor ranged from 1 to 2.5 µM, while negative cooperativity factors (α), representing the changes in affinity of ligand and modulator when bound as a ternary complex with the receptor, ranged from 0.15 to 0.42. These observations were extended and reinforced by studies using intact small cell (NCI-H69) and non-small cell (NCI-H23) lung cancer cells, and by using an antagonist σ1 receptor radioligand, E-N-1-(3'-[125I]iodoallyl)-N'-4-(3″,4″-dimethoxyphenethyl)piperazine, in mouse brain membranes. By contrast, exploratory studies indicate marked enhancement of the σ2 receptor binding of [3H]1,3-di-(o-tolyl)guanidine/(+)-pentazocine in NCI-H23 cells and guinea pig brain membranes. These findings raise intriguing questions regarding mechanism and potential functional outcomes.