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.

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.

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.

Using Catchment Population to Estimate Sporadic Creutzfeldt-Jakob Disease Incidence.

INTRODUCTION: Catchment populations have several uses. A method using catchment population to estimate the incidence of sporadic Creutzfeldt-Jakob disease (sCJD) is described. MATERIALS AND METHODS: A cohort of nine consecutive patients diagnosed with sCJD, symptom onset spanning 26 months, were observed at a rural tertiary university medical center that has approximately 40,000 hospital discharges annually. An effective catchment population was determined using surrounding county utilization frequency that captured all nine sCJD patients and accounted for over 87% of discharges. RESULTS: The effective sCJD hospital catchment population was 1.266 million, implying an annual sCJD incidence rate of 3.39 per million (95% CIs, 1.55-6.43), assuming a Poisson distribution for sCJD occurrence. CONCLUSIONS: This annual incidence rate suggests that many sCJD patients are unrecognized and unreported. An advantage of this catchment population method is independence from death certificate accuracy, important in rare diseases that are both rapidly and invariably fatal. The relative absence of significant healthcare systems competition in this rural population enhances the reliability of this finding. The most likely explanation for the high sCJD incidence rate suggested by this study is enhanced clinical suspicion and improved diagnostic accuracy.

Does Activity Level After Primary Total Hip Arthroplasty Affect Aseptic Survival?

BACKGROUND: The purpose of this study is to evaluate survivorship and outcomes of high-activity patients compared to low-activity patients after total hip arthroplasty. METHODS: A retrospective review identified 2002 patients (2532 hip) that underwent a primary total hip arthroplasty with vitamin E-infused highly crosslinked polyethylene liner. Patients were divided into 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 Harris Hip Score, UCLA activity score, and reoperations. A multivariate nominal regression analysis was performed to evaluate the significance of postoperative activity level on survivorship. RESULTS: The mean follow-up duration was 4.5 years (range, 0.3 to 9.9 years). HA group had significantly higher improvements in Harris Hip Score (HHS) (P < .001) and UCLA activity score (P < .001). Aseptic revisions were performed in 2.1% of the LA group and in 0.4% hips of the HA group (P < .001). After controlling for age, gender, preoperative pain, HHS, and body mass index, a higher postoperative activity level remained a significant factor for improved aseptic survivorship with an odds ratio of 4.9 (95% confidence interval, 1.1 to 21.2, P = .03). The all-cause 5-year survivorship was 99% for the HA group and 96% to for the LA group (P < .001). The aseptic 5-year survivorship was 99.6% for the HA group and 98% for the LA group (P < .001). CONCLUSIONS: This study found that a higher activity level after primary THA was not deleterious to survivorship at short to midterm follow-up with modern implants.

Corticosterone and chlorpyrifos oxon exposure elicits spatiotemporal MAPK phosphoprotein signaling in a mouse brain.

Chlorpyrifos (CPF) is one of the most widely-used pesticides globally for agricultural purposes. Certain occupations (e.g., farmers, military) are at an increased risk for high-dose exposure to CPF, which can lead to seizures and irreversible brain injury. Workers with the highest risk of exposure typically experience increased circulating cortisol levels, which is related to physiological stress. To better represent this exposure scenario, a mouse model utilized exogenous administration of corticosterone (CORT; high physiologic stress mimic) in combination with chlorpyrifos oxon (CPO; oxon metabolite of CPF); this combination increases neuroinflammation post-exposure. In the present study adult male C57BL/6J mice were given CORT (200 µg/mL) in drinking water for seven days followed by a single intraperitoneal injection of CPO (8.0 mg/kg) on day eight, and euthanized 0.5, 2, and 24 h post-injection. Ten post-translationally modified proteins were measured in the frontal cortex and striatum to evaluate brain region-specific effects. The spatiotemporal response to CORT + CPO sequentially activated phosphoproteins (p-ERK1/2, p-MEK1/2, p-JNK) involved in mitogen-activated protein kinase (MAPK) signaling. Observed p-ZAP70 responses further integrated MAPK signaling and provided a spatiotemporal connection between protein phosphorylation and neuroinflammation. This study provides insight into the spatiotemporal cellular signaling cascade following CORT + CPO exposure that represent these vulnerable populations.

Differential phosphoprotein signaling in the cortex in mouse models of Gulf War Illness using corticosterone and acetylcholinesterase inhibitors.

AIMS: Veterans from the 1990-91 Gulf War were exposed to acetylcholinesterase inhibitors (AChEIs), and, following service, an estimated one-third began suffering from a medically unexplained, multi-symptom illness termed Gulf War Illness (GWI). Previous research has developed validated rodent models that include exposure to exogenous corticosterone (CORT) and AChEIs to simulate high stress and chemical exposures encountered in theater. This combination of exposures in mice resulted in a marked increase in neuroinflammation, which is a common symptom of veterans suffering from GWI. To further elucidate the mechanisms associated with these mouse models of GWI, an investigation into intracellular responses in the cortex were performed to characterize the early cellular signaling changes associated with this exposure-initiated neuroinflammation. MAIN METHODS: Adult male C57BL/6J mice were exposed to CORT in the drinking water (200 µg/mL) for 7 days followed by a single intraperitoneal injection of diisopropyl fluorophosphate (DFP; 4.0 mg/kg) or chlorpyrifos oxon (CPO; 8.0 mg/kg), on day 8 and euthanized 0.5, 2, and 24 h post-injection. Eleven post-translationally modified protein targets were measured using a multiplexed ELISA. KEY FINDINGS: Phosphoprotein responses were found to be exposure specific following AChEI insult, with and without CORT. Specifically, CORT + CPO exposure was found to sequentially activate several phosphoproteins involved in mitogen activated protein kinase signaling (p-MEK1/2, p-ERK1/2, and p-JNK). DFP alone similarly increased proteins in this pathway (p-RPS6, and p-JNK), but the addition of CORT ameliorated these affects. SIGNIFICANCE: The results of this study provide insight into differentially activated pathways depending on AChEI in these GWI models.

Semi-automated cerebral aneurysm segmentation and geometric analysis for WEB sizing utilizing a cloud-based computational platform.

BACKGROUND: Accurate aneurysm measurements are important for selecting the WEB device. The objective was to validate a cloud-based platform, SurgicalPreview (SP) against manual measurements for aneurysm analysis. METHODS: Two sets of measurements each for SP and manual methods were obtained for 40 aneurysms. Reliability and agreement were assessed with intra-class correlation coefficient (ICC) and Bland-Altman plots respectively. Kappa coefficient was used to assess agreement for predicting WEB size. RESULTS: There was good reliability for repeat SP measurements: aneurysm diameter (ICC-1, 95%CI 0.98-1), height (ICC-1, 95%CI 0.99-1) and neck diameter (ICC-0.96, 95%CI 0.93-0.98). There was good reliability for the two manual diameter (ICC-0.97, 95%CI 0.9-0.97) and height (ICC-0.93, 95%CI 0.87-0.96) measurements and moderate for neck diameter (ICC-0.76, 95%CI 0.54-0.87). There was greater agreement for SP versus manual repeat measurements on Bland-Altman plots. Reliability between the SP and manual methods was good for aneurysm diameter (ICC-0.98, 95%CI 0.95-1) and height (ICC-0.96, 95%CI-0.93-0.98) and moderate for neck. (ICC-0.6, 95%CI -0.22-0.87). The Bland-Altman plots confirmed better agreement between the two methods for the aneurysm diameter and height than the neck. There was strong agreement between the methods for predicting the WEB diameter (Kappa-0.84, 95%CI 0.71-0.97) and moderate for predicting WEB height (Kappa-0.66, 95%CI 0.43-0.89). There was moderate agreement for predicted versus deployed WEB diameter: SP (Kappa-0.56, 95%CI 0.38-0.74), Manual (Kappa-0.53, 95%CI 0.34-0.71). CONCLUSION: The SurgicalPreview® had greater agreement for repeat measurements. There was good reliability between the two methods for predicting WEB diameter and height and moderate agreement between predicted versus deployed WEB diameter.

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.

Reservation-Urban Comparison of Suicidal Ideation/Planning and Attempts in American Indian Youth.

BACKGROUND: Our aim was to identify sex- and location-specific risk factors for suicide ideation/planning and attempts among American Indian youth. METHODS: Biennial data for 6417 American Indian high school students attending reservation and urban schools were extracted from the Montana volunteer sample Youth Risk Behavior Survey data for pooled years 2003 to 2011. Logistic regression was used to identify sex- and school location-specific risk behaviors and psychosocial factors for past 12-month ideation/planning and past 12-month attempts. RESULTS: Contrary to our hypothesis, the prevalence of ideation/planning and attempts did not significantly differ between reservation/urban location; however, risk factors associated with suicidality did. Sadness/hopelessness was associated with both outcomes for all groups. However, violent victimization was associated with both outcomes only among girls. Lack of school safety was associated with attempts but not ideation/planning among all students. There were distinct differences in risk factors associated with both outcomes among boys. CONCLUSIONS: The results indicate differences and similarities in risk behaviors and psychosocial factors associated with suicidality by sex and reservation/urban setting. Implications include screening potentially at-risk students for depression, violent victimization, substance use, and school safety and use of the findings by tribal and school programs in designing prevention and intervention programs.

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.

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.

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.

Does Initiating Vaginal Sexual Intercourse During a Safer Sex Media Campaign Influence Life Satisfaction Among African American Adolescents?

PURPOSE: Addressing adolescent sexual risk behaviors in the STI/HIV prevention literature is well documented; however, intervention impacts on life satisfaction are relatively unexplored. This study is a secondary analysis of data (N = 1,658) from a randomized, multisite, multilevel safer sex media campaign (Project iMPPACS) analyzing life satisfaction across baseline and follow-up data collected from 2006 to 2008 among participants (mean age 15.08 years) who reported never having had vaginal sex at baseline (n = 787). METHODS: Participants were separated into groups based on whether they reported having vaginal sex (yes/no) at baseline. Then taking into account the nested study design and controlling for confounders, a mixed model repeated measures analysis of variance assessed whether differences in mean total life satisfaction (LS) were associated across time in the media and nonmedia study conditions separately by gender. RESULTS: A significant interaction between time and media condition was detected (p = .039) where mean total LS increased +.065 units from baseline (M = 5.364) to last contact in media cities and decreased -.084 units from baseline (M = 5.557) to last contact in nonmedia cities when controlling for the effect of initiating vaginal sex. No significant differences in LS at baseline were observed between media and nonmedia intervention cities. Results by gender suggest most positive change in LS was observed for females with mixed findings for males. CONCLUSIONS: Although Project iMPPACS was not designed with the intent on improving participants' life satisfaction, results advance the LS literature by demonstrating a temporal sequence for sexual risk taking and LS over time.

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.

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.

Rubella immunity and serum perfluoroalkyl substances: Sex and analytic strategy.

BACKGROUND: Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to childhood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations. OBJECTIVE: To examine whether serum PFASs were associated with reduced immunity to rubella immunization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage. METHODS: We analyzed a nationally representative sample of individuals ≥ 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999-2000 and 2003-2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances. RESULTS: After exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size analyses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex. CONCLUSIONS: These results support our earlier studies showing sex specific responses to PFASs and indicate the importance of thinking carefully about analytic strategies in population based toxicology research.

Excessive Postoperative Fluid Administration in Infants with Gastroschisis.

Careful fluid management is a cornerstone of neonatology because the cardiovascular, respiratory, and gastrointestinal systems in the newborn are sensitive to overhydration. Fluid management in gastroschisis is complicated by insensible fluid loss and postoperative third-space fluid shifts. Study of perioperative fluid management in gastroschisis is limited and has not undergone careful scrutiny. We reviewed perioperative fluid administration and urine output in all infants with gastroschisis over a 5-year period. Data included whether the patient underwent primary closure or staged repair, weight, and events during hospitalization (length of hospitalization and duration of gastric decompression, parenteral nutrition, and ventilator support). Paired t test gave statistical comparisons with significance at P < 0.05. From 2010 to 2014, 24 patients underwent abdominal closure, 17 had primary and 7 had staged closures. Fluid administration exceeded 100 mL/kg/d after primary closure, and was significantly higher (>150 mL/kg/d; P < 0.05) after staged closure on postoperative days 0 to 5. Postoperative urinary output exceeded 75 mL/kg/d for all patients, with higher volumes reaching 100 mL/kg/d after staged closure on postoperative days 4 to 6 (P < 0.05). Two patients died of sepsis. All survivors were discharged with intestinal continuity and gaining weight on oral feeding. Patients with gastroschisis received large volumes of fluid after operation despite similarly high urine output and positive daily fluid balances. The amounts of fluid administered after both primary and staged closure may be excessive and potentially deleterious.

Undersized Rigid Nonplanar Annuloplasty: The Key to Effective and Durable Repair of Functional Tricuspid Regurgitation.

BACKGROUND: Previous clinical experiences have demonstrated high early and late recurrence rates after repair of functional tricuspid regurgitation (TR). We investigated the results of functional TR repair with undersized rigid nonplanar annuloplasty rings. METHODS: From January 2007 to December 2013, 216 consecutive patients with moderate or greater functional TR were treated with undersized (size 26 mm or 28 mm) rigid nonplanar annuloplasty rings. RESULTS: The mean age was 69 ± 13 years. There was a previous history of cardiac operation in 25% (54 of 216 patients). Tricuspid regurgitation was graded as severe in 47% (102 of 216) and moderate in 53% (114 of 216). Concomitant operations included mitral valve procedures in 92% (198 of 216), coronary artery bypass grafting in 21% (45 of 216), aortic valve procedures in 9% (20 of 216), and cryomaze procedures in 35% (76 of 216). Size 26 mm rings were used in 38% of patients (81 of 216), and size 28 mm in 62% (135 of 216). The perioperative mortality rate was 6% (14 of 216). On predischarge echocardiography, TR grade was none or mild in 94% (176 of 187 patients), moderate in 4% (7 of 187), and severe in 2% (4 of 187). At a mean follow-up of 33.0 ± 24.0 months, TR grade was none or mild in 81% of patients (130 of 160), moderate in 16% (26 of 160), and severe in 2% (4 of 160). There were no reoperations for recurrent TR, and no patients have had tricuspid stenosis or annuloplasty ring dehiscence. CONCLUSIONS: Treatment of functional TR with undersized (26 mm or 28 mm) nonplanar rigid annuloplasty rings is safe and highly effective, with a near absence of recurrent severe TR at midterm follow-up.