ATV-Related Trauma in the Pediatric Population.

BACKGROUND: All-terrain vehicles (ATVs) are prevalent in Appalachia and cause significant morbidity and mortality in the pediatric population. This study investigated the injury types and severity in pediatric patients over a 15-year period. METHODS: A retrospective chart review was performed on pediatric ATV-related traumas presenting to our institution from 2005 to 2020. Patients were divided into 3 age groups (0-7, 8-12, and 13-17 y) to evaluate differences in accident demographics, hospitalization, Glasgow Coma Scale, Injury Severity Score, substance use, characterization of orthopaedic and nonorthopaedic injuries, and procedures performed. RESULTS: Inclusion criteria were met by 802 patients. Males represented 71.7% (n=575) and females 28.3% (n=227); the mean age was 12.4 years. The majority (88.5%, n=710) of patients admitted following their accident had a mean stay length of 3.3 days. Of admissions, intensive care unit admission was required by 23.8%, n=191 (mean stay 4.0 d). There were 7 fatalities. The vast majority of accidents occurred between May and September (79.2%, n=635). In patients with documented helmet status, 45% (n=271) were helmeted. Roughly half of all patients (n=393) sustained a fracture (excluding fractures to the head), 370 sustained an injury to the head/face, 129 sustained intra-abdominal/intra-thoracic injuries, and 29 sustained injuries to all 3 systems. The most common fractures involved the forearm (n=98), femur (n=65), and spine (n=59). The most common open fractures were the tibia (n=12), humerus (n=8), and forearm (n=8). The oldest group was more likely than the middle or younger groups to sustain spine ( P <0.0001), pelvis ( P =0.0001), hand ( P =0.0089), and foot ( P =0.0487) fractures. Ethanol testing was positive in 5.0% (n=25) of the oldest group and cannabinoids were present in 6.8% (n=34). The youngest group was significantly more likely to sustain a fracture of the humerus than the middle or older groups ( P <0.0001). Orthopaedic surgical management was required in 24.4% (n=196) of patients. CONCLUSIONS: Pediatric ATV accidents present a significant source of morbidity and mortality. Further intervention is necessary to minimize pediatric ATV injuries. LEVEL OF EVIDENCE: Level IV-Retrospective Case Series.

Higher Activity Level Following Total Knee Arthroplasty Is Not Deleterious to Mid-Term Implant Survivorship.

BACKGROUND: The impact of a patient's activity level following total knee arthroplasty (TKA) remains controversial, with some surgeons concerned about increased polyethylene wear, aseptic loosening, and revisions. The purpose of this study is to report on implant survivorship and outcomes of high activity patients compared to low activity patients after TKA. METHODS: A retrospective review identified 1611 patients (2038 knees) that underwent TKA with 5-year minimum follow-up. Patients were divided in 2 groups based on their University of California Los Angeles (UCLA) activity level: low activity (LA) (UCLA ≤5) and high activity (HA) (UCLA ≥6). Outcomes included range of motion, Knee Society scores, complications, and reoperations. Parametric survival analysis was performed to evaluate the significance of activity level on survivorship while controlling for age, gender, preoperative pain, Knee Society clinical scores, Knee Society functional scores, and body mass index (BMI). RESULTS: Mean follow-up was 11.4 years (range 5.1-15.9). The LA group had significantly more female patients, were older, had higher BMI, and had lower functional scores preoperatively (all with P < .001). The HA group had significantly higher improvements in Knee Society scores (P < .001) and pain postoperatively (P < .001). Revisions were performed in 4% of the LA group and 1.7% knees of the HA group (P = .003). After controlling for age, gender, preoperative pain, Knee Society clinical scores, Knee Society functional scores, and BMI, a higher postoperative activity level remained a significant factor for improved survivorship with an odds ratio of 2.4 (95% confidence interval 1.2-4.7, P = .011). The all-cause 12-year survivorship was 98% for the HA group and 95.3% for the LA group (P = .003). The aseptic 12-year survivorship was 98.4% for the HA group and 96.3% for the LA group (P = .02). CONCLUSION: Highly active patients had increased survivorship at 5-year minimum follow-up compared to lower activity patients after TKA. Patient activity level after TKA may not need to be limited with modern implants.

Impact of Morbid Obesity on Overnight Stay and Early Complications With Outpatient Arthroplasty.

BACKGROUND: The shift toward outpatient joint arthroplasty is rapidly growing, but concerns still remain on whether certain patients should be excluded from same-day discharge arthroplasty. The purpose of this study is to evaluate whether morbid obesity is a risk factor for perioperative complications after outpatient joint arthroplasty. METHODS: A retrospective review was performed from 2013 to 2017 of all outpatient primary total hip, total knee, partial knee, and revision hip and knee arthroplasties, yielding a cohort of 4863 patients (5988 arthroplasty procedures). Patients were separated and analyzed based on 2 groups: nonmorbidly obese (NMO) (BMI < 40 kg/m2) and morbidly obese (MO) (BMI ≥ 40 kg/m2). The NMO group consisted of 4870 arthroplasties and the MO group consisted of 1118 arthroplasties. Overnight stays, medical complications, and early perioperative complications were assessed between groups. RESULTS: Overnight stays occurred in 5.4% of NMO patients and 9.1% of MO patients (P < .001), with medical reasons for the overnight stay occurring in 3.2% of NMO and 6.4% of MO patients (P < .001). Respiratory/sleep apnea was the leading medical reason leading to overnight stay occurring in 4% of MO patients and 0.8% of NMO patients (P < .001). There was no significant difference between groups in direct facility transfers, emergency room visits/admissions, or medical complications within 90 days. Wound revisions, nonrevision surgery, or revisions within 90 days were significant between groups. CONCLUSION: MO patients did not have an increased risk of 90-day medical complications, readmission, or revisions after outpatient arthroplasty. However, MO patients did have a significantly higher incidence of overnight stay.

The effect of implant prosthesis complications on patient satisfaction.

STATEMENT OF PROBLEM: How complications regarding implant prostheses affect patient satisfaction and oral health-related quality of life (OHRQoL) is unclear. PURPOSE: The purpose of this retrospective study was to compare patient satisfaction with implant restorations in patients with or without a history of complications. These data were used to determine whether implant prosthesis complications affected self-reported OHRQoL. MATERIAL AND METHODS: Data were gathered from 176 edentulous and partially dentate patients who had received implant prostheses consisting of implant-supported crowns, implant-supported overdentures, and screw-retained fixed dental prostheses (FDPs) in predoctoral and postdoctoral clinics between January 1, 2010, and December 31, 2014. Demographics and complications were self-reported by means of a survey. Patients rated their OHRQoL using the Quality of Life with Implant-Prostheses (QoLIP-10) questionnaire. Means were compared by using a 1-way ANOVA to compare the variables of prosthesis complications, sociodemographic data, and patient satisfaction. Significantly different variables were further evaluated using a post hoc Tukey-Kramer Honestly Significant Different (HSD) test (α=.05). RESULTS: Statistically significant differences in patient satisfaction were found related to prosthesis complications, gender, and marital status. The most common complication for implant-supported crowns was screw loosening. For implant-supported overdentures and screw-retained FDPs, the most common complication was repair of the prosthesis. Those who had experienced complications reported lower OHRQoL scores than those who had not. Women and widows/widowers overall reported lower OHRQoL scores. The OHRQoL scores of women with and without prosthesis complications were not statistically different (P=.073). No significant differences were found relative to age (P=.937) or education (P=.302). Patients without complications with implant-supported crowns reported the lowest satisfaction because of oral hygiene difficulties. The lowest satisfaction in patients with complications of implant-supported overdentures and screw-retained FDPs was related to worry/concern because of problems with the implant prosthesis. CONCLUSIONS: The results of this survey suggest that patients who experience complications with an implant prosthesis report a lower OHRQoL score than those who do not. Future studies are needed to evaluate patient satisfaction by comparing prosthesis complications with and without implants to determine whether patients who have had complications with implant prostheses are more satisfied than those who have experienced complications with conventional prostheses.

Can a Multilevel STI/HIV Prevention Strategy for High Risk African American Adolescents Improve Life Satisfaction?

Addressing adolescent sexual risk behaviors in the STI/HIV prevention literature is well documented; however, impacts from interventions on life satisfaction are relatively unexplored. This study examined data (n = 1658) from a randomized, multi-site, multi-level STI/HIV prevention intervention trial (Project iMPAACS) to determine whether increased protective and reduced sexual risk-taking behaviors associated with STI/HIV would also improve self-reported life satisfaction. Taking into account the nested study design and controlling for confounders, a mixed model ANOVA was performed where Total mean life satisfaction scores were analyzed at baseline and 3, 6, 12, and 18 months post-recruitment. Significance levels of 0.05 were used to determine significance and η 2 was used to assess effect size. We hypothesized that as intervention participants engaged in the intentional activity associated with increasing protective behaviors and reducing sexual risk-taking behaviors associated with STI/HIV, life satisfaction reports would also improve over the course of the intervention. A significant main effect for sex was detected (F = 5.19, p = .02, η 2 = .03), along with three interactions: between experimental condition and media intervention (F = 7.96, p = .005, η 2= .04); experimental condition, sex, and media intervention (F = 6.51, p = .01, η 2 = .04); and experimental condition, sex, assessment point, and media intervention (F = 3.23, p = .01, η 2 = .02). With the exception of the control condition, female life satisfaction reports improved from baseline assessments to 18-months post-recruitment, whereas male reports decreased. Project iMPPACS was not designed with the intent on improving participants' life satisfaction. However, study results suggest incorporating strategies to address subjective well-being into future adolescent STI/HIV risk-reduction interventions is beneficial for females and additional research is necessary for males.

Direct Anterior Approach and Perioperative Fracture With a Single-Taper Wedge Femoral Component.

BACKGROUND: Despite growing interest in direct anterior approach total hip arthroplasty, perioperative femoral fracture and early aseptic loosening are increasingly recognized complications. Previous research has documented the role of surgeon experience in association with these femoral complications. The purpose of this study was to explore the relationship between femoral component design and early periprosthetic femoral complications. METHODS: This was an extension of previous work with an updated patient cohort of 5090 consecutive direct anterior primary total hip arthroplasties at a single institution with a single-taper, wedge femoral stem comprising 4 variants involving length and geometry: group 1, full-length, standard profile; group 2, full-length, reduced distal profile; group 3, short-length, standard profile; and group 4, short-length, reduced distal profile. Records were reviewed retrospectively for the incidence of early postoperative periprosthetic fracture or aseptic loosening and analyzed with regard to patient demographics and femoral stem type. RESULTS: There were 42 (0.83%) periprosthetic femur complications observed in the early postoperative period. Increased age (P < .001) and female gender (P = .023) were significantly associated with incidence of femoral complications in univariate analysis, while age maintained this significant relationship in multivariate analysis (P < .001). There was a trend toward increased complication rate in patients receiving a short stem with full profile taper (1.27%, P = .0539). CONCLUSION: Despite an overall low rate of femoral complications after direct anterior total hip arthroplasty, the risk is increased in elderly patients and females. Furthermore, femoral stem design may portend an elevated risk of these complications.

Surgical Approach and Hip Laterality Affect Accuracy of Acetabular Component Placement in Primary Total Hip Arthroplasty.

INTRODUCTION: Controversy remains if the anterior approach improves acetabular component alignment, and many studies have compared approaches with different surgeons over different timeframes. The purpose of this study was to assess a single surgeon's experience over a one-year timeframe and radiographically compare acetabular component positioning with the direct anterior versus direct lateral approach. Secondarily, this study compares acetabular component position differences between right and left hips for a right-hand dominant surgeon. MATERIALS AND METHODS: Postoperative radiographs of 289 primary total hip arthroplasties (THAs) performed by a single right-hand dominant surgeon in 2014 were reviewed for abduction, anteversion, and medial cup seating. Component position was compared to surgical approach with 152 direct anterior (DA) THAs (53%) and 137 direct lateral (DL) THAs (47%). The operative side was also compared to surgeon hand dominance. Surgeons target was 40° abduction, 20° anteversion ±5°, and seating to the teardrop ±5mm. Lewinnek target was also assessed. RESULTS: DA hips had a significantly lower abduction angle (p=0.04), less abduction target outliers (p<0.001), less abduction Lewinnek outliers (p<0.001), less target anteversion outliers (p<0.001), closer seating to teardrop (p<0.001), and less seating outliers (p<0.001). The combined target and Lewinnek safe zone were achieved more often in DA (p<0.001, p=0.042). Controlling for body mass index (BMI), the combined target achievement remained significantly better for DA (p=0.02), but combined Lewinnek was not significant (p=0.07). In the DA approach, right hips had a significantly lower abduction angle (p=0.03), less Lewinnek anteversion outliers (p=0.043), and less combined Lewinnek outliers (p=0.027). In the DL group, right hips had significantly higher anteversion angles (p=0.004) and Lewinnek anteversion outliers (p=0.033). CONCLUSION: The anterior approach improved target abduction, anteversion, and medialization compared to the direct lateral approach. Significant differences in component positioning were found in both approaches based on the surgeons dominant and non-dominant side.

Demand on skillfulness modulates interhemispheric inhibition of motor cortices.

The role of primary motor cortex (M1) in the control of hand movements is still unclear. Functional magnetic resonance imaging (fMRI) studies of unimanual performance reported a relationship between level of precision of a motor task and additional ipsilateral M1 (iM1) activation. In the present study, we determined whether the demand on accuracy of a movement influences the magnitude of the inhibitory effect between primary motor cortices (IHI). We used transcranial magnetic stimulation (TMS) to measure active IHI (aIHI) of the iM1 on the contralateral M1 (cM1) in the premovement period of a left-hand motor task. Ten healthy participants manipulated a joystick to point to targets of two different sizes. For aIHI, the conditioning stimulus (CS) was applied to iM1, and the test stimulus (TS) to cM1, with an interstimulus interval of 10 ms. The amount of the inhibitory effect of the CS on the motor-evoked potential (MEP) of the subsequent TS was expressed as percentage of the mean MEP amplitude evoked by the single TS. Across different time points of aIHI measurements in the premovement period, there was a significant effect for target size on aIHI. Preparing to point to small targets was associated with weaker aIHI compared with pointing to large targets. The present findings suggest that, during the premovement period, aIHI from iM1 on cM1 is modulated by the demand on accuracy of the motor task. This is consistent with task fMRI findings showing bilateral M1 activation during high-precision movements but only unilateral M1 activity during low-precision movements.

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

PURPOSE: Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. METHODS: Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). RESULTS: Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05). CONCLUSIONS: Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program.

Association between birth characteristics and coronary disease risk factors among fifth graders.

OBJECTIVE: To evaluate the associations between selected birth characteristics-prematurity and poor intrauterine growth-and risk factors for coronary artery disease detected among children enrolled in the fifth grade. STUDY DESIGN: Children (n = 3054) with matched birth and fifth grade health screening data on body mass index (BMI), systolic blood pressure, and fasting lipid profiles were analyzed using MANOVA with the following independent variables of weight gain by the fifth grade: BMI percentile, normal or overweight/obese (BMI ≥ 85 th percentile), prematurity, and intrauterine growth (ie, small for gestational age [SGA], appropriate for gestational age [AGA], or large for gestational age [LGA]). RESULTS: LGA status at birth was associated with overweight/obesity later in life. In fifth grade, overweight/obese children had elevated systolic blood pressure and abnormal levels of most fasting serum lipids compared with normal-weight children regardless of birth characteristics. Beyond the effects of BMI percentile, preterm infants had higher levels of triglycerides (TG) than term infants by the fifth grade (P < .05). SGA infants who become overweight/obese had higher levels of TGs and very low-density lipoproteins compared with AGA and LGA infants, whether overweight or normal weight (P < .05). CONCLUSION: BMI ≥ 85 th percentile in the fifth grade is associated with abnormalities in most coronary artery risk factors regardless of birth characteristics. Beyond the effects of BMI percentile in the fifth grade, preterm infants had higher TG levels than term infants. SGA infants who were overweight/obese in the fifth grade had higher TG and very low-density lipoprotein levels compared with AGA and LGA infants who were overweight/obese or of normal weight in the fifth grade.

Nanosphere pharmacodynamics improves safety of immunostimulatory cytokine therapy.

Systemic administration of interleukin (IL)-12 induces potent anti-tumor immune responses in preclinical cancer models through the systemic activation of effector immune cells and release of proinflammatory cytokines. IL-12-loaded PLGA nanospheres (IL12ns) are hypothesized to improve therapeutic efficacy and thwart unwanted side effects observed in previous human clinical trials. Through the investigation of peripheral blood and local tissue immune responses in healthy BALB/c mice, the immune-protective pharmacodynamics of IL12ns were suggested. Nanospheres increased pro-inflammatory plasma cytokines/chemokines (IFN-γ, IL-6, TNF-α, and CXCL10) without inducing maladaptive transcriptomic signatures in circulating peripheral immune cells. Gene expression profiling revealed activation of pro-inflammatory signaling pathways in systemic tissues, the likely source of these effector cytokines. These data support that nanosphere pharmacodynamics, including shielding IL-12 from circulating immune cells, depositing peripherally in systemic immune tissues, and then slowly eluting bioactive cytokine, thereafter, are essential to safe immunostimulatory therapy.

Circulating maternal perfluoroalkyl substances during pregnancy in the C8 Health Study.

Perfluoroalkyl substances are manmade chemicals used in many consumer products and have become ubiquitous in the environment. Animal studies and a limited number of human studies have demonstrated developmental effects in offspring exposed to perfluoroalkyl substances in utero, but the implications of timing of in utero exposure have not been systematically investigated. The present study investigated variation in perfluorocarbon levels of 9952 women of childbearing age who had been exposed to perfluorooctanoic acid (PFOA) in drinking water contaminated by industrial waste. An analysis of variance with contrast was performed to compare the levels of PFOA and perfluorooctanesulfonic acid (PFOS) in pregnant and nonpregnant women overall and during each trimester of pregnancy. We found that pregnant women had lower circulating PFOA and PFOS concentrations in peripheral blood than nonpregnant women and that PFOA levels were consistently lower throughout all trimesters for pregnancy, suggesting transfer to the fetus at an early stage of gestation. These results are discussed in the context of the endocrine-disrupting properties of perfluoroalkyl substances that have been characterized in animal and human studies. Our conclusion is that further, systematic study of the potential implications of intrauterine perfluorocarbon exposure during critical periods of fetal development is urgently needed.

Can antenatal ultrasounds help predict postnatal outcomes in babies born with gastrochisis? The West Virginia experience.

OBJECTIVE: Gastrochisis is a congenital condition resulting in significant morbidity and mortality. Multiple studies have been done to evaluate the value of prognostic indicators with conflicting results. The aim of this study was to evaluate the role of ultrasound in this condition at a single institution while limiting the provider variables that may affect neonatal outcome. METHODS: The antepartum charts of expectant mothers of affected fetuses as well as the neonatal hospital charts were reviewed at length. The cases were identified over a period of 4 years from April 1998 to February 2002. In addition, the archived photographs of ultrasounds performed on these fetuses were also reviewed and reread by two independent providers who were blinded to the outcome. Adverse neonatal outcome, including death and time to feeding (amongst many other variables) were assessed against the different ultrasound parameters including bowel thickness and dilation. RESULTS: 25 patients were identified in the stated time frame. Six cases had to be dropped from the final analysis due to incomplete data including the transfer of 3 babies. There were 4 neonatal deaths. The mean birth weight was 2384 grams. There was a significant association with dilation and delta dilation (defined as the difference in bowel dilation from the final ultrasound from the baseline ultrasound cutoff of 4 mm) and time to feeding, time on ventilator and hospital stay. (P< 0.005). Other ultrasound parameters were not significantly correlated with neonatal outcome. CONCLUSION: Most ultrasound parameters do not help prognosticate the neonatal outcome in babies affected with this condition except for dilation and delta dilation, which are strong predictors of morbidity in the post delivery period. This information may be helpful to providers and parents of affected fetuses.

Low Molecular Weight Heparin Is Superior for Venous Thromboembolism Prophylaxis in High-Risk Geriatric Patients.

INTRODUCTION: Venous thromboembolism (VTE) is a source of preventable morbidity and mortality in critically ill trauma patients. Age is one independent risk factor. Geriatric patients embody a population at high thromboembolic and hemorrhagic risk. Currently, there is little guidance between low molecular weight heparin (LMWH) and unfractionated heparin (UFH) for anticoagulant prophylaxis in the geriatric trauma patient. METHODS: A retrospective review was conducted at an ACS verified, Level I Trauma center from 2014 to 2018. All patients 65 years or older, with high-risk injuries and admitted to the trauma service were included. Choice of agent was at provider discretion. Patients in renal failure, or those that received no chemoprophylaxis, were excluded. The primary outcomes were the diagnosis of deep vein thrombosis or pulmonary embolism and bleeding associated complications (gastrointestinal bleed, TBI expansion, hematoma development). RESULTS: This study evaluated 375 subjects, 245 (65%) received enoxaparin and 130 (35%) received heparin. DVT developed in 6.9% of UFH patients, compared to 3.3% with LMWH (P = .1). PE was present in 3.8% of UFH group, but only .4% in the LMWH group (P = .01). Combined rate of DVT/PE was significantly lower (P = .006) with LMWH (3.7%) compared to UFH (10.8%). 10 patients had documented bleeding events, and there was no significant association between bleeding and the use of LMWH or UFH. CONCLUSIONS: VTE events are more common in geriatric patients treated with UFH compared to LMWH. There was no associated increase in bleeding complications when LMWH was utilized. LMWH should be considered the chemoprophylatic agent of choice in high risk geriatric trauma patients.

Association of Loneliness and Mindfulness in Substance Use Treatment Retention.

BACKGROUND: Elevated mental illness prevalence complicates efforts designed to address the opioid crisis in Appalachia. The recovery community acknowledges that loneliness impacts mood and engagement in care factors; however, the predictive relationship between loneliness and retention in medication-assisted outpatient treatment programs has not been explored. Our objectives were to identify associations between mental health factors and retention in treatment and elucidate treatment retention odds. Data were collected from eighty participants (n = 57 retained, n = 23 not retained) of a mindfulness-based relapse prevention (MBRP) intervention for individuals receiving medication for opioid use disorder (MOUD) in Appalachia. Loneliness, depression, and anxiety did not differ between the retained and not retained, nor did they predict not being retained; however, mindfulness was significantly lower among those not retained in treatment compared to those retained (OR = 0.956, 95% CI (0.912-1.00), and p < 0.05). Preliminary findings provide evidence for mindfulness training integration as part of effective treatment, with aims to further elucidate the effectiveness of mindfulness therapies on symptom reduction in co-occurring mental health disorders, loneliness, and MOUD treatment retention.

Melphalan exposure induces an interleukin-6 deficit in bone marrow stromal cells and osteoblasts.

Bone marrow stromal cells (BMSC) and osteoblasts are critical components of the microenvironment that support hematopoietic recovery following bone marrow transplantation. Aggressive chemotherapy not only affects tumor cells, but also influences additional structural and functional components of the microenvironment. Successful reconstitution of hematopoiesis following stem cell or bone marrow transplantation after aggressive chemotherapy is dependent upon components of the microenvironment maintaining their supportive function. This includes secretion of soluble factors and expression of cellular adhesion molecules that impact on development of hematopoietic cells. In the current study, we investigated the effects of chemotherapy treatment on BMSC and human osteoblast (HOB) expression of interleukin-6 (IL-6) as one regulatory factor. IL-6 is a pleiotropic cytokine which has diverse effects on hematopoietic cell development. In the current study we demonstrate that exposure of BMSC or HOB to melphalan leads to decreases in IL-6 protein expression. Decreased IL-6 protein is the most pronounced following melphalan exposure compared to several other chemotherapeutic agents tested. We also observed that melphalan decreased IL-6 mRNA in both BMSC and HOB. Finally, using a model of BMSC or HOB co-cultured with myeloma cells exposed to melphalan, we observed that IL-6 protein was also decreased, consistent with treatment of adherent cells alone. Collectively, these observations are of dual significance. First, suggesting that chemotherapy induced IL-6 deficits in the bone marrow occur which may result in defective hematopoietic support of early progenitor cells. In contrast, the decrease in IL-6 protein may be a beneficial mechanism by which melphalan acts as a valuable therapeutic agent for treatment of multiple myeloma, where IL-6 present in the bone marrow acts as a proliferative factor and contributes to disease progression. Taken together, these data emphasize the responsiveness of the microenvironment to diverse stress that is important to consider in therapeutic settings.

Left atrial volume by echocardiography in patients with false positive myocardial perfusion scans.

A stress-induced myocardial perfusion abnormality (MPS), in the absence of angiographically significant epicardial coronary artery disease, is considered a "false-positive" test result. We hypothesized that echocardiography would provide complementary prognostic and pathophysiologic data relevant to the management of patients with MPS and normal coronary angiograms. Accordingly, left atrial volume index (LAVi) was assessed by echocardiography in 38 patients with false positive MPS as defined by normal coronary angiograms and 26 patients with true negative MPS from a total of 1,356 patients stressed from July 2006-May 2008. Pathologically abnormal elevation of LAVi (≥ 32 mL/m(2)) was observed in 16 of 19 women (84%) and 11 of 19 men (58%) in the false positive MPS (FPMPS) group while none of the patients in the true negative MPS (TNMPS) group had elevated LAVi. In the FPMPS group mean LAVi was significantly higher in women than men (40.64 ± 11.4 mL/m(2) versus 32.6 ± 10.5 mL/m(2), P = 0.01). The mean LAVi in the FPMPS group was significantly different from the TNMPS group (36.6 ± 11.6 versus 21 ± 7 mL/m(2), P = 0.000). A stepwise logistic regression determined BSA, LAV and LAVi as useful in predicting false positive and true negative MPS. All three were significant predictors (P < 0.01) and the area under the ROC curve was 0.91. Our findings in this relatively small cohort suggest that patients with false positive MPS have a greater increased LAVi.

Infant homicide and accidental death in the United States, 1940-2005: ethics and epidemiological classification.

Potential ethical issues can arise during the process of epidemiological classification. For example, unnatural infant deaths are classified as accidental deaths or homicides. Societal sensitivity to the physical abuse and neglect of children has increased over recent decades. This enhanced sensitivity could impact reported infant homicide rates. Infant homicide and accident mortality rates in boys and girls in the USA from 1940 to 2005 were analysed. In 1940, infant accident mortality rates were over 20 times greater than infant homicide rates in both boys and girls. After about 1980, when the ratio of infant accident mortality rates to infant homicide rates decreased to less than five, and the sum of infant accident and homicide rates became relatively constant, further decreases in infant accident mortality rates were associated with increases in reported infant homicide rates. These findings suggest that the dramatic decline of accidental infant mortality and recent increased societal sensitivity to child abuse may be related to the increased infant homicide rates observed in the USA since 1980 rather than an actual increase in societal violence directed against infants. Ethical consequences of epidemiological classification, involving the principles of beneficence, non-maleficence and justice, are suggested by observed patterns in infant accidental deaths and homicides in the USA from 1940 to 2005.

Violence in the emergency department: a national survey of emergency medicine residents and attending physicians.

BACKGROUND: Violence in the Emergency Department (ED) is a well-known phenomenon. Few studies have been done to assess the incidence and nature of violence in the ED. STUDY OBJECTIVES: The purpose of this study was to assess the incidence of violence in the ED nationwide. METHODS: This study was a prospective, cross-sectional online survey of Emergency Medicine (EM) residents and attending physicians. Of the 134 accredited United States (US) EM residency programs, 65 programs were randomly selected and invited to participate. RESULTS: Overall, 272 surveys were returned, of which 263 (97%) were completed and further analyzed. At least one workplace violence act in the previous 12 months was reported by 78% (95% confidence interval 73-83%) of respondents, with 21% reporting more than one type of violent act. Workplace violence was experienced similarly between males and females (79% vs. 75%, respectively; p = 0.65), and was more common in EDs with annual volumes over 60,000 patients (82% vs. 67%; p = 0.01). The most common type of workplace violence was verbal threats (75%) followed by physical assaults (21%), confrontations outside the workplace (5%), and stalking (2%). Security was available full time in most settings (98%), but was least likely to be physically present in patient care areas. The majority of respondent EDs did not screen for weapons (40% screened) or have metal detectors (38% had metal detectors). Only 16% of programs provided violence workshops, and less than 10% offered self-defense training. CONCLUSION: Despite the high incidence of workplace violence experienced by the emergency physicians who responded to our survey, less than half of these respondents worked in EDs that screened for weapons or had metal detectors. An even smaller number of physicians worked in settings that provided violence workshops or self-defense training.