Sex-based differences in odds of motor vehicle crash injury outcomes.

OBJECTIVE: Several studies have documented the relative risk or odds of injury and fatality for females versus males in motor vehicle crashes (Parenteau et al. 2013, Forman et al. 2019, Brumbelow and Jermakian, 2022; Noh et al. 2022). Though, none combined National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) and Crash Investigation Sampling System (CISS). The aim of this study was to document the relative odds of various injury outcomes for females versus males while considering a broad range of crash types, pre-crash and crash variables, and occupant characteristics. METHODS: Multivariable logistic regression was carried out to study the odds of injury for females versus males. A select imputation method (Hot Deck, Approximate Bayesian Bootstrap) was applied as part of efforts to create multivariable logistic regression models for 25 different injury outcomes associated with occupants (age 13 years and older) involved in passenger vehicle crashes published in NASS-CDS (2000 to 2015) and CISS (2017-2021). Both pre-crash (n=7) and crashworthiness (n=22) predictor variables were considered, but only significant variables at p≤0.10 level were retained in final models. Six crash-type models were produced for each injury outcome; one that included all crashes, one for each of four different planar crash types (frontal, near-side, far-side, rear), and one for crashes involving rollover. These six sets of crash-type models were expanded further to include a model version that included both pre-crash/environment and crashworthiness predictor variables and one model limited to crashworthiness predictors only. Different than other recent studies, all crash types, occupant restraint conditions, and seating positions were considered. Occupant sex was retained in all models to facilitate female versus male injury outcome odds ratio (OR) assessments. RESULTS: Female versus male injury OR estimates for 300 unique models are presented. Females had significantly higher odds of injury than males in 36 models (OR>1.0, p-value ≤0.05). This contrasts with 43 models where females had significantly lower odds (OR<1.0, p≤0.05). For the remaining 221 models, there was a near even split in how often the odds of injury were non-significantly higher (n=103) and non-significantly lower (n=114) for females as compared to males (p>0.05). In four cases, the OR estimate was 1.00. Amongst the results, there was a trend for females to have higher odds of AIS 2+ injuries (MAIS 2+ OR=1.75 and 1.69 for Full and Crashworthiness models, respectively for the All Crashes dataset). These increases included higher estimates for lower extremity injuries in frontal crashes, consistent with earlier studies (e.g., Forman et al. 2019). However, for certain AIS 2+ (neck, thorax) and AIS 3+ injuries (head, neck, thorax), females had significantly lower odds of injury (p≤0.05). The trends for reduced odds of injury for females were most prevalent in non-frontal crash models.

Female crash fatality risk relative to males for similar physical impacts.

OBJECTIVE: This paper estimates the latest trends regarding the effect of sex on driver-side or right-front passenger-side occupant fatalities in fatal crashes. The focus is on how recent model year (MY) light vehicles with advanced occupant protection technologies compare to older vehicles without these protections in terms of female fatality risk relative to males. METHODS: Data from the Fatality Analysis Reporting System (FARS) from 1975 to 2019 is used to calculate estimates of female fatality risk relative to males using logistic regression models and the double-pair comparison method. These estimates are calculated in various groups of MY vehicles and occupant protection systems. Occupant protection systems observed are the use of seat belts, and the availability of dual air bags, pretensioners and load limiters in the vehicles. All vehicles used include occupants age 16 to 96. Occupants studied include front-row occupants (drivers and right-front (RF) passengers). The average between drivers and RF passengers is also calculated. RESULTS: Incremental female fatality risk estimates versus males are reduced in newer MY vehicles. Incremental relative risks for female front-row occupants (average of drivers and right-front passengers) are found to be 19.9% (± 1.3) in fatal crashes in MY 1960-1999 vehicles, and 9.4% (± 2.2) percent in MY 2000-2020 vehicles. The difference in fatality risk between females and males is further reduced when looking at MY 2010-2020 vehicles (6.3 ± 5.4%) compared to MY 1960-2009 vehicles (18.3 ± 1.2%). Incremental fatality risk estimates also decrease in vehicles with newer generations of occupant protection systems regardless of MY. When occupants are belted in vehicles with the latest generation of modern occupant protection systems (dual air bags, seat belt pretensioners and load limiters), the estimated female fatality risk relative to males (average of drivers and right-front passengers) becomes 5.8% (± 3.8), which is lower than for belted occupants in vehicles without those occupant protections. CONCLUSIONS: The disparity in fatality risk between males and females for the same physical impacts is reduced for later MY vehicles, as well as vehicles with more advanced occupant protection systems.

Single-Stage Arthroscopic Autologous Matrix-Enhanced Chondral Transplantation (AMECT) in the Hip.

Chondral defects of the acetabulum in patients with femoroacetabular impingement syndrome are an increasingly recognized cause of worse outcomes after treatment. Multiple procedures have been described for the treatment of hip cartilage lesions including microfracture, autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, and autograft and allograft transplantation. However, many of these techniques have poor long-term outcomes, require multiple surgical procedures, or rely on planned preoperative identification of the chondral lesion. This Technical Note describes our technique of autologous matrix-enhanced chondral transplantation, a single-stage treatment for acetabular cartilage lesions that harvests chondral tissue from the femoral cam deformity and combines it with chondral extracellular matrix, growth factors, and autologous peripheral blood.

Return to Basketball After Hip Arthroscopy: Minimum 2-Year Follow-up.

PURPOSE: To present minimum 2-year patient-reported outcomes (PROs) and return to sport (RTS) data for a population of basketball players after hip arthroscopy. METHODS: Data were prospectively collected and retrospectively reviewed for all patients who underwent hip arthroscopy between February 2009 and May 2014. Patients with preoperative and minimum 2-year postoperative PROs, visual analog scale score for pain, and satisfaction, who regularly played basketball within 1 year before surgery, and who attempted to RTS met the inclusion criteria. Exclusion criteria were previous ipsilateral hip surgery or conditions such as fracture, dysplasia, or femoral avascular necrosis. Patients were matched 1:1 to a control group composed of those who did not play any sports before surgery, based on the following matching criteria: age ±5 years, sex, and body mass index ±5. Statistical analysis was performed to determine significant differences in PROs. Conversion to total hip arthroplasty (THA) was considered an endpoint. RESULTS: Thirty-one patients (81.6%) met inclusion criteria with follow-up of 46.8 ± 20.6 months. The mean age was 30.0 ± 12.3, and the mean body mass index was 26.3 ± 6.5. Male patients (64.5%) outnumbered female patients (35.5%). A majority of the players (54.8%) identified themselves as recreational athletes; the remainder competed at the high school, collegiate, amateur, or professional level. There was significant (P < .001) improvement in all PRO measures and visual-analog scale scores from baseline to a minimum 2-year follow-up. At the most recent follow-up, mean patient satisfaction was 8.1 ± 2.1. Twenty-two (78.6%), and 23 patients (82.1%) achieved the patient acceptable symptom state on the modified Harris Hip Score and the Hip Outcomes Score-Sports Specific Subscale. Twenty-one (75.0%) and 17 (60.7%) patients had a minimal clinically important difference on the modified Harris Hip Score and the Hip Outcomes Score-Sports Specific Subscale, respectively. Three patients (9.7%) with an average age of 47.5 (P = .023) converted to THA at a mean of 35.9 ± 7.2 (range 29.66-43.75) months after arthroscopy. At the most recent follow-up, the RTS rate was 83.9%. Subjective ability level was the same or higher in 23 patients (74.2%). CONCLUSION: Hip arthroscopy in basketball athletes demonstrates a significant increase in PROs, a high RTS rate, and a low risk of complications. Hip arthroscopy may be considered in basketball players <40 years old for whom nonoperative treatment fails and who have a significantly limited level of play. Careful patient selection and counseling should be used when considering hip arthroscopy in basketball players >40 years old because there may be a high rate of conversion to THA. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Five-Year Outcomes and Return to Sport of Runners Undergoing Hip Arthroscopy for Labral Tears With or Without Femoroacetabular Impingement.

BACKGROUND: Recent evidence has demonstrated a high rate of return to running after hip arthroscopy for femoroacetabular impingement at short-term follow-up. The midterm outcomes and rates of continued running of these patients are unknown. PURPOSE: To evaluate midterm rates of return to running and outcomes after hip arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Data were prospectively collected for patients who underwent hip preservation surgery between July 2008 and November 2011. Patients were excluded for preoperative Tönnis osteoarthritis grade ≥2, previous ipsilateral hip conditions or hip surgery, or workers' compensation status. All patients who participated in mid- to long-distance running before their surgery and intended on returning after their operation were considered for inclusion. Preoperative and minimum 5-year postoperative measures for the following patient-reported outcome scores (PROs) were necessary for inclusion in the final cohort: the modified Harris Hip Score, Non-arthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, and visual analog scale (VAS) for pain. All patients were counseled about the risks of continued running after hip arthroscopy. RESULTS: Sixty patients (62 hips) were eligible for inclusion, of which 50 (83.3%; 52 hips) had minimum 5-year follow-up. There were 10 male hips and 42 female hips. Mean ± SD age at surgery was 32.4 ± 12.4 years (range, 14.9-62.4), and mean body mass index was 22.9 ± 3.2 (range, 17.7-30.1). Latest follow-up was recorded at a mean 69.3 ± 8.5 months (range, 60.0-92.1 months). Level of competition included 39 recreational, 7 high school, 4 collegiate, and 2 professional athletes. There were significant improvements in all PROs and VAS scores preoperatively to latest follow-up. Mean modified Harris Hip Score improved from 67.5 to 88.2; mean Non-arthritic Hip Score, from 65.9 to 88.3; mean Hip Outcome Score-Sports Specific Subscale, from 49.5 to 81.0; and mean VAS, from 5.2 to 1.5. At latest follow-up, patient satisfaction was 8.4. Thirty-nine patients (78.0%, 41 hips) had returned to running postoperatively. When stratified by level of competition, 79% (31 of 39) of recreational, 100% (7 of 7) of high school, 50% (2 of 4) of collegiate, and 50% (1 of 2) of professional athletes returned to running. CONCLUSION: Hip arthroscopy for all levels of runners is associated with a significant increase in PROs and a low risk of complications. The rate of return to running is moderately high after hip arthroscopy at midterm follow-up. Hip arthroscopy may be considered for runners presenting with symptoms of femoroacetabular impingement that fail nonoperative treatments. Patients should be educated on the rate of return to running over time and the risks of continued running after hip arthroscopy.

Midterm Outcomes and Return to Sports Among Athletes Undergoing Hip Arthroscopy.

BACKGROUND: Hip arthroscopy is an established surgical treatment for pathologic hip conditions in athletes. There is a paucity in the literature regarding outcomes and return to sport for athletes in the midterm. PURPOSE: To report minimum 5-year outcomes, return to sport, and level of sport among athletic patients who underwent hip arthroscopy. In addition, we compared 2- and 5-year outcomes to evaluate whether there is a deterioration in functional status. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Data were prospectively collected on all patients who underwent hip arthroscopy between February 2009 and November 2011 at 1 institution. Athletes at the high school, collegiate, or professional level who underwent hip arthroscopy and had preoperative patient-reported outcome (PRO) scores were considered for inclusion. Exclusion criteria were preoperative Tönnis grade >1 or prior ipsilateral hip conditions or surgery. Data on sports participation, competition level, and ability were collected. At a minimum of 5 years postoperatively, PROs, visual analog scale (VAS), iHOT-12 (short version of International Hip Outcome Tool), satisfaction, and postoperative complication data were collected. RESULTS: Seventy-seven hips met all criteria, among which 66 (85.7%) had a minimum 5-year follow-up and were included. There were 37 high school, 20 collegiate, and 9 professional athletes. Mean ± SD improvements at a minimum of 5 years were as follows: modified Harris Hip Score, 66.8 ± 16.3 to 87.0 ± 14.8 ( P < .001); nonarthritic hip score, 66.2 ± 19.9 to 87.2 ± 15.2 ( P < .001); Hip Outcome Score-Sports Specific Subscale, 47.0 ± 22.4 to 79.1 ± 23.0 ( P < .001); and VAS, 5.4 ± 2.5 to 1.8 ± 2.1 ( P < .001). At latest follow-up, mean iHOT-12 was 78.8 ± 22.7, and satisfaction was 8.2. A total of 50 athletes (53 hips, 80.3%) reported that they returned to sports; 71.2% reported "same" or "higher" sport ability as compared with a year before surgery. Postoperative complications included 3 cases (4.5%) of numbness and 1 case (1.5%) of pulmonary embolism. Ten hips (15.2%) required secondary arthroscopies, and no hips were converted to total hip arthroplasty. There were no significant differences between 2- and 5-year PROs, VAS, or satisfaction. CONCLUSION: Midterm results of hip arthroscopy in athletes are shown to be safe and favorable. Most athletes return to sports and continue to play after 5 years with the same or higher ability.

Development of thoracic injury risk functions for the THOR ATD.

The Test Device for Human Occupant Restraint (THOR) 50th percentile male anthropomorphic test device (ATD) aims to improve the ability to predict the risk of chest injury to restrained automobile occupants by measuring dynamic chest deflection at multiple locations. This research aimed to describe the methods for developing a thoracic injury risk function (IRF) using the multi-point chest deflection metrics from the 50th percentile male THOR Metric ATD with the SD-3 shoulder and associating to post-mortem human subjects (PMHS) outcomes that were matched on identical frontal and frontal-oblique impact sled testing conditions. Several deflection metrics were assessed as potential predictor variables for AIS 3+ injury risk, including a combined metric, called PC Score, which was generated from a principal component analysis. A parametric survival analysis (specifically, accelerated failure time (AFT) with Weibull distribution) was assessed in the development of the IRF. Model fit was assessed using various modeling diagnostics, including the area under the receiver operating characteristic curve (AUC). Models based on resultant deflection consistently exhibited improved fit compared to models based on x-axis deflection or chord deflection. Risk functions for the THOR PC Score and Cmax (maximum resultant deflection) were qualitatively equivalent, producing AUCs of 0.857 and 0.861, respectively. Adjusting for the potential confounding effects of age, AFT survival models with Cmax or PC Score as the primary deflection metric resulted in the THOR injury risk models with the best combination of biomechanical appropriateness, potential utility and model fit, and may be recommended as injury predictors.

Desmopression is an effective adjunct treatment for reversing excessive hyponatremia overcorrection.

We report a case of a 50-year-old malnourished African American male with hiccups, nausea and vomiting who was brought to the Emergency Department after repeated seizures at home. Laboratory evaluations revealed sodium (Na(+)) 107 mmol/L, unmeasurably low potassium, chloride < 60 mmol/L, bicarbonate of 38 mmol/L and serum osmolality 217 mOsm/kg. Seizures were controlled with 3% saline IV. Once nausea was controlled with iv antiemetics, he developed large volume free water diuresis with 6 L of dilute urine in 8 h (urine osmolality 40-60 mOsm/kg) and serum sodium rapidly rose to 126 mmol/L in 12 h. Both intravenous desmopressin and 5% dextrose in water was given to achieve a concentrated urine and to temporarily reverse the acute rise of sodium, respectively. Serum Na(+) was gradually re-corrected in 2-3 mmol/L daily increments from 118 mmol/L until 130 mmol/L. Hypokalemia was slowly corrected with resultant auto-correction of metabolic alkalosis. The patient discharged home with no neurologic sequaele on the 11(th) hospital day. In euvolemic hyponatremic patients, controlling nausea may contribute to unpredictable free water diuresis. The addition of an antidiuretic hormone analog, such as desmopressin can limit urine output and prevent an unpredictable rise of the serum sodium.

Development of brain injury criteria (BrIC).

Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship between CSDM - BrIC and MPS - BrIC respectively. AIS 3+, 4+ and 5+ field risk of anatomic brain injuries was also estimated using the National Automotive Sampling System - Crashworthiness Data System (NASS-CDS) database for crash conditions similar to the frontal NCAP and side impact conditions that the ATDs were tested in. This was done to assess the risk curve ratios derived from HIC risk curves. The results of the study indicated that: (1) the two available human head models - SIMon and GHBMC - were found to be highly correlated when CSDMs and max principal strains were compared; (2) BrIC correlates best to both - CSDM and MPS, and rotational velocity (not rotational acceleration) is the mechanism for brain injuries; and (3) the critical values for angular velocity are directionally dependent, and are independent of the ATD used for measuring them. The newly developed brain injury criterion is a complement to the existing HIC, which is based on translational accelerations. Together, the two criteria may be able to capture most brain injuries and skull fractures occurring in automotive or any other impact environment. One of the main limitations for any brain injury criterion, including BrIC, is the lack of human injury data to validate the criteria against, although some approximation for AIS 2+ injury is given based on the angular velocities calculated at 50% probability of concussion in college football players instrumented with 5 DOF helmet system. Despite the limitations, a new kinematic rotational brain injury criterion - BrIC - may offer a way to capture brain injuries in situations when using translational accelerations based HIC alone may not be sufficient.

IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin up-regulation.

Interleukin (IL)-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumor microenvironment of cancer patients where it correlates with the grade of malignancy. The direct effect of IL-4 on cancer cells has been associated with increased cell survival; however, its role in cancer cell proliferation and related mechanisms is still unclear. Here it was shown that in a nutrient-depleted environment, IL-4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrient-depletion stress, IL-4 activates mitogen-activated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAP-signaling-specific inhibitors, it was shown that IL-4-induced proliferation is mediated by JNK activation. In fact, JNK-inhibitor-V (JNKi-V) stunted IL-4-mediated cell proliferation. Furthermore, it was found that IL-4 induces survivin up-regulation in nutrient-depleted cancer cells. Using survivin-short-hairpin-RNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of IL-4-mediated proliferation. In addition, the significance of survivin up-regulation in a stressed environment was assessed in prostate cancer mouse xenografts. It was found that survivin knockdown decreases tumor progression in correlation with cancer cell proliferation. Furthermore, under nutrient depletion stress, IL -4 could induce proliferation in cancer cells from multiple origins: MDA-MB-231 (breast), A253 (head and neck), and SKOV-3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, IL-4 triggers a simultaneous activation of the JNK-pathway and the up-regulation of survivin turning on a cancer proliferation mechanism.

The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment.

CC chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein-1) has been demonstrated to recruit monocytes to tumor sites. Monocytes are capable of being differentiated into tumor-associated macrophages (TAMs) and osteoclasts (OCs). TAMs have been shown to promote tumor growth in several cancer types. Osteoclasts have also been known to play an important role in cancer bone metastasis. To investigate the effects of CCL2 on tumorigenesis and its potential effects on bone metastasis of human prostate cancer, CCL2 was overexpressed into a luciferase-tagged human prostate cancer cell line PC-3. In vitro, the conditioned medium of CCL2 overexpressing PC-3luc cells (PC-3(lucCCL2)) was a potent chemoattractant for mouse monocytes in comparison to a conditioned medium from PC-3(lucMock). In addition, CCL2 overexpression increased the growth of transplanted xenografts and increased the accumulation of macrophages in vivo. In a tumor dissemination model, PC-3(lucCCL2) enhanced the growth of bone metastasis, which was associated with more functional OCs. Neutralizing antibodies targeting both human and mouse CCL2 inhibited the growth of PC-3(luc), which was accompanied by a decrease in macrophage recruitment to the tumor. These findings suggest that CCL2 increases tumor growth and bone metastasis through recruitment of macrophages and OCs to the tumor site.

CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization.

CCL2 and interleukin (IL)-6 are among the most prevalent cytokines in the tumor microenvironment, with expression generally correlating with tumor progression and metastasis. CCL2 and IL-6 induced expression of each other in CD11b(+) cells isolated from human peripheral blood. It was demonstrated that both cytokines induce up-regulation of the antiapoptotic proteins cFLIP(L) (cellular caspase-8 (FLICE)-like inhibitory protein), Bcl-2, and Bcl-X(L) and inhibit the cleavage of caspase-8 and subsequent activation of the caspase-cascade, thus protecting cells from apoptosis under serum deprivation stress. Furthermore, both cytokines induced hyperactivation of autophagy in these cells. Upon CCL2 or IL-6 stimulation, CD11b(+) cells demonstrated a significant increase in the mannose receptor (CD206) and the CD14(+)/CD206(+) double-positive cells, suggesting a polarization of macrophages toward the CD206(+) M2-type phenotype. Caspase-8 inhibitors mimicked the cytokine-induced up-regulation of autophagy and M2 polarization. Furthermore, E64D and leupeptin, which are able to function as inhibitors of autophagic degradation, reversed the effect of caspase-8 inhibitors in the M2-macrophage polarization, indicating a role of autophagy in this mechanism. Additionally, in patients with advanced castrate-resistant prostate cancer, metastatic lesions exhibited an increased CD14(+)/CD206(+) double-positive cell population compared with normal tissues. Altogether, these findings suggest a role for CCL2 and IL-6 in the survival of myeloid monocytes recruited to the tumor microenvironment and their differentiation toward tumor-promoting M2-type macrophages via inhibition of caspase-8 cleavage and enhanced autophagy.