Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases.

Impact of Timing of Targeted Muscle Reinnervation on Pain and Opioid Intake Following Major Limb Amputation.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to play an important role in managing neuromas. However, the impact of the timing of TMR on pain visual analogue scale (VAS) scores or patient opioid use has not been thoroughly explored. We hypothesized that TMR performed acutely would lead to lower VAS scores and decreased opioid intake. METHODS: Prospectively collected data from an amputation registry at a single institution were utilized to identify patients who underwent TMR. Acute TMR was defined as TMR performed within 1 month of the major limb amputation. Primary outcomes included VAS pain scores and patient-reported opioid consumption. RESULTS: In all, 25 patients (26 limbs) were identified in the acute group, and 18 patients (18 limbs) were identified in the delayed group. At intermediate follow-up (between 4 and 8 months postoperatively) and at final follow-up, the average pain VAS score in the delayed TMR group was significantly higher than that in the acute group (5.2 vs. 1.9 at intermediate P = .01 and 6.2 vs. 1.9 at final P = .002). In all, 84% of the amputees overall were not consuming opioid medications at the time of final follow-up (79% acute, 88% delayed, P = .72). There were no statistically significant differences in opioid consumption between the acute and delayed group at intermediate follow-up (P = .35) or at final follow-up (P = .68). CONCLUSIONS: TMR is an effective procedure to reduce pain following major limb amputation. Patients with TMR performed acutely had significantly lower VAS pain scores at both intermediate and final follow-up than patients with TMR performed in a delayed setting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium.

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Aspirin, ibuprofen, and reduced risk of advanced colorectal adenoma incidence and recurrence and colorectal cancer in the PLCO Cancer Screening Trial.

BACKGROUND: Studying the differential impact of aspirin and other nonsteroidal anti-inflammatory drugs across the stages of colorectal neoplasia from early adenoma to cancer is critical for understanding the benefits of these widely used drugs. METHODS: With 13 years of follow-up, the authors prospectively evaluated the association between aspirin and ibuprofen use and incident distal adenoma (1221 cases), recurrent adenoma (862 cases), and incident colorectal cancer (CRC; 2826 cases) among men and women in the population-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. With multivariable-adjusted models, odds ratio (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for incident CRC were determined. RESULTS: The authors observed a significantly reduced risk of incident adenoma with ibuprofen use (≥30 vs <4 pills per month: OR, 0.76 [95% CI, 0.60-0.95]; Ptrend = .04), particularly advanced adenoma (OR, 0.48 [95% CI, 0.28-0.83]; Ptrend = .005). Among those with a previous adenoma detected through screening, aspirin use was associated with a decreased risk of advanced recurrent adenoma (≥30 vs <4 pills per month: OR, 0.56 [95% CI, 0.36-0.87]; Ptrend = 0.006). Both aspirin (HR, 0.88 [95% CI, 0.81-0.96]; Ptrend <.0001) and ibuprofen use (HR, 0.81 [95% CI, 0.70-0.93); Ptrend = 0.003) ≥30 versus <4 pills per month were significantly associated with reduced CRC risk. CONCLUSIONS: In this large prospective study with long-term follow-up, a beneficial role for not only aspirin, but also ibuprofen, in preventing advanced adenoma and curbing progression to recurrence and cancer among older adults was observed.

Targeted Muscle Reinnervation: A Paradigm Shift for Neuroma Management and Improved Prosthesis Control in Major Limb Amputees.

Targeted muscle reinnervation (TMR) is a procedure that redirects nerves severed by amputation to new muscle targets. In tandem with advances in myoelectric prosthetics, TMR surgery provides amputees with improved control of myoelectric prostheses and simultaneously prevents or treats painful neuromas. TMR also has an emerging role in the management of neuromas in a nonamputation setting, and it seems to be a powerful strategy to treat a wide variety of neuromas. Because the pattern of nerve transfers varies based on the availability of donor nerves and muscle targets, TMR is inherently nonprescriptive, and thus, an understanding of the principles of TMR is essential for its successful application. This review describes the rationale for and principles of TMR, and outlines techniques for TMR, which can be used at various amputation levels and for the management of neuromas in nonamputees.

Association between cesarean delivery types and obesity in preadolescence.

BACKGROUND/OBJECTIVES: The association between mode of delivery and childhood obesity remains inconclusive. Because few studies have separated C-section types (planned or unplanned C-section), our objective was to assess how these subtypes relate to preadolescent obesity. SUBJECTS/METHODS: The study consisted of 570 maternal-child pairs drawn from the WHEALS birth cohort based in Detroit, Michigan. Children were followed-up at 10 years of age where a variety of anthropometric measurements were collected. Obesity was defined based on BMI percentile (≥95th percentile), as well as through Gaussian finite mixture modeling on the anthropometric measurements. Risk ratios (RRs) and 95% confidence intervals (CIs) for obesity comparing planned and unplanned C-sections to vaginal deliveries were computed, which utilized inverse probability weights to account for loss to follow-up and multiple imputation for covariate missingness. Mediation models were fit to examine the mediation role of breastfeeding. RESULTS: After adjusting for marital status, maternal race, prenatal tobacco smoke exposure, maternal age, maternal BMI, any hypertensive disorders during pregnancy, gestational diabetes, prenatal antibiotic use, child sex, parity, and birthweight z-score, children born via planned C-section had 1.77 times higher risk of obesity (≥95th percentile), relative to those delivered vaginally ((95% CI) = (1.16, 2.72); p = 0.009). No association was found comparing unplanned C-section to vaginal delivery (RR (95% CI) = 0.75 (0.45, 1.23); p = 0.25). The results were similar but slightly stronger when obesity was defined by anthropometric class (RR (95% CI) = 2.78 (1.47, 5.26); p = 0.002). Breastfeeding did not mediate the association between mode of delivery and obesity. CONCLUSIONS: These findings indicate that children delivered via planned C-section-but not unplanned C-section-have a higher risk of preadolescent obesity, suggesting that partial labor or membrane rupture (typically experienced during unplanned C-section delivery) may offer protection. Additional research is needed to understand the biological mechanisms behind this effect, including whether microbiological differences fully or partially account for the association.

Expression quantitative trait locus fine mapping of the 17q12-21 asthma locus in African American children: a genetic association and gene expression study.

BACKGROUND: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12-21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12-21 locus. METHODS: We first did a genetic association study and meta-analysis using 17q12-21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12-21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12-21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). FINDINGS: 17q12-21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12-1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13-1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [ß] 1·35 [95% CI 1·25-1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (ß 1·15 [1·08-1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLß 1·24 [1·15-1·32], p<0·0001; and for ORMDL3 (ß 1·19 [1·12-1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (ß 1·29 [1·15-1·44], p<0·0001). INTERPRETATION: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12-21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus. FUNDING: National Institutes of Health, Office of the Director.

Clinical tests for assessing the presence and quality of the palmaris longus tendon: diagnostic accuracy of examination compared with ultrasound.

Various clinical tests are used to evaluate the palmaris longus tendon, but their accuracy is unknown. We assessed the accuracy of clinical tests (Schaeffer's, Thompson's, Mishra-I, Mishra-II) against ultrasound as the reference standard. We hypothesized that Schaeffer's was most accurate and that examination can reliably assess the palmaris longus tendon's length. Ninety-six wrists were examined clinically and evaluated with ultrasound by radiologists who were blinded to examination results. We calculated diagnostic accuracy and agreement between length measurements. Sensitivity values were as follows: Schaeffer's 94%, Mishra-I 100%, Mishra-II 100%, Thompson's 72%. Specificity values were as follows: Schaeffer's 94%, Mishra-I 83%, Mishra-II 89%, Thompson's 91%. Intraclass correlation coefficient between palmaris longus tendon length measurement on examination and ultrasound was 0.54. Schaeffer's test accurately detected this tendon with >90% sensitivity and specificity, but clinical examination less reliably measured palmaris longus tendon length. Ultrasound may be a useful adjunct to assess potential graft length preoperatively. Level of evidence: I.

Flexible model for patient engagement: Achieving quality outcomes and building a research agenda for head and neck cancer.

BACKGROUND: This article describes the benefits of patient-driven research in the field of head and neck oncology, reviews lessons learned from establishing partnerships with patients and caregivers, and serves as a model for further patient-driven research endeavors. METHODS: Head and neck cancer survivors underwent training including that of effective communication and the basics of research methodology. They then drove the agendas for monthly meetings that included a multidisciplinary team of providers, facilitated by a physician champion (S.S.C.). RESULTS: The advisors reported concrete areas for improvement of the clinical flow, including the formation of a dental oncology clinic and a post-treatment survivorship clinic. They also refined research topics of interest, such as treatment regret. The advisors have also driven efforts to increase public awareness and have participated in cancer symposiums and local presentations. CONCLUSION: Patient-driven research improves the relevance and implementation of head and neck oncology research and clinical processes.

Return to Play After Shoulder Replacement Surgery: What Is Realistic and What Does the Evidence Tell Us.

This article analyzes the available literature regarding return to sport following total shoulder arthroplasty (TSA), hemiarthroplasty (HA), and reverse shoulder arthroplasty (RTSA). It examines the quality of the available evidence and areas of future research. Most patients are able to return to preoperative sport activities following TSA, RTSA, and HA. The rates of return for TSA are slightly higher than those reported for HA and RTSA. Patients may be counseled that noncontact, low-demand activities have higher return rates. Most patients can expect to return to sports within 6 months postoperatively.

A matched quantitative computed tomography analysis of 3 surgical approaches for osteochondral reconstruction of the capitellum.

BACKGROUND: The location of capitellar osteochondritis dissecans (OCD) lesions in the sagittal plane guides the surgical approach used for autologous osteochondral transplantation. We sought to compare the capitellar region accessible for orthogonal graft placement through 3 approaches: (1) posterior anconeus-split approach; (2) lateral approach with lateral collateral ligament (LCL) preservation (LCL-preserving lateral approach); and (3) lateral approach with LCL release (LCL-sacrificing lateral approach). METHODS: The 3 approaches were sequentially performed on 9 cadaveric elbows: posterior anconeus-split approach, LCL-preserving lateral approach, and LCL-releasing lateral approach. The extent of perpendicular access was delineated with Kirschner wires. Each specimen underwent computed tomography. The accessible region was quantified as degrees on the capitellum and converted into time on a clock, where 0° corresponds to the 12-o'clock position. Generalized estimating equation modeling was used to investigate for significant within-specimen, between-approach differences. RESULTS: The LCL-preserving and LCL-sacrificing lateral approaches provided more anterior perpendicular access than the posterior anconeus-split approach (mean, 0° vs 83°; P < .001). The posterior anconeus-split approach provided more posterior perpendicular access (mean, 215.0°; P < .001) than the LCL-preserving (mean, 117°; P < .001) and LCL-sacrificing (mean, 145°; P < .001) lateral approaches. The LCL-sacrificing lateral approach provided more posterior exposure than the LCL-preserving lateral approach (mean, 145° vs 117°; P < .001). The mean arc of visualization was greater for the LCL-sacrificing lateral approach than for the LCL-preserving lateral approach (145° vs 117°, P < .001). CONCLUSIONS: A capitellar OCD lesion can be perpendicularly accessed from a posterior anconeus-split approach if it is posterior to 83° (2:46 clock-face position). A laterally based approach may be required for lesions anterior to this threshold. These data inform clinical decisions regarding the appropriate surgical approach for any OCD lesion.

Ultrasound determination of presence, length and diameter of the palmaris longus tendon.

Inadvertent median nerve harvest is a devastating complication of palmaris longus harvest. Accurate assessment of palmaris longus presence and dimensions preoperatively would minimize this risk and assure safe harvest. We hypothesized that ultrasound would accurately predict palmaris longus presence, length and diameter. Seventeen cadaveric forearms were studied using a LOGIQ-E9 ultrasound. Two radiologists assessed palmaris longus presence and dimensions. Each wrist was explored, and the tendon was harvested and measured. Inter-rater reliability and agreement between measurements was assessed. The palmaris longus was present in 13 of 17 forearms. Both radiologists correctly identified the tendon and its absence (sensitivity and specificity, 100%). Ultrasound assessment of palmaris longus dimensions significantly correlated with surgical measurements. Intraclass correlation coefficient between radiologists was 0.97. We conclude that ultrasound can determine palmaris longus presence and dimensions with excellent accuracy and inter-observer reliability. Ultrasound is useful for preoperative evaluation of the palmaris longus and its use will increase patient safety.

Location of Osteochondritis Dissecans Lesions of the Capitellum.

PURPOSE: The location of capitellar osteochondritis dissecans (OCD) lesions in the sagittal plane guides the surgical approach, and lesion location in the coronal plane influences surgical management. Although most lesions have been reported to occur between 4 o'clock and 4:30 (120° to 135° anterior to the humerus), some lesions are located elsewhere in the capitellum. The primary aim was to define the region of the capitellum affected by OCD lesions using a novel clock-face localization system. METHODS: We reviewed 104 magnetic resonance imaging examinations diagnosing a nontraumatic capitellar OCD lesion. In the sagittal plane, lesion margins were recorded as degrees on the capitellum and converted into a clock-face format in which 0° corresponds to 12:00 with the forearm facing to the right. The 0° axis (12-o'clock axis) was defined as a line parallel to the anterior humeral line that intersects the capitellum center. The following coronal measurements were recorded: lesion width, capitellar width, and distance between the lateral capitellum and lateral lesion. Two independent observers took measurements. RESULTS: In the sagittal plane, average lesion location was 92° to 150° (3:04-5:00, clock face) and ranged from 52.1° to 249.5° (1:44-8:19, clock face). Average lesion dimensions were 10.7 mm (mediolateral width) and 5.2 mm (anteroposterior depth). Interrater reliability was high (intraclass correlation coefficient = 0.98). CONCLUSIONS: Using a magnetic resonance imaging-based clock-face localization system, we found that capitellar OCD lesions affect a broad region of the capitellum in the sagittal plane. CLINICAL RELEVANCE: The clock-face localization system allows for precise description of capitellar OCD lesion location, which may facilitate intraoperative decision and longitudinal monitoring.

Early-life home environment and risk of asthma among inner-city children.

BACKGROUND: Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain. OBJECTIVE: We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children. METHODS: We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children. RESULTS: Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores. CONCLUSION: Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

BACKGROUND: Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. METHODS: We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. RESULTS: Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. CONCLUSIONS: High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. LEVEL OF EVIDENCE: Level-III, retrospective cohort study.

High Short-Term Failure Rate Associated With Decellularized Osteochondral Allograft for Treatment of Knee Cartilage Lesions.

PURPOSE: To report the short-term clinical and radiographic outcomes following the use of decellularized osteochondral (OC) allograft plugs in the treatment of distal femoral OC lesions. METHODS: An Institutional Review Board-approved database with prospectively collected data was used to identify patients treated with the decellularized OC allograft plugs implant. Demographic information, patient-reported outcomes, magnetic resonance imaging (MRI), and the number and type of reoperations were assessed. Failure was defined as revision surgery with removal of the implant. Patients were evaluated pre- and postoperatively using the Short Form-36, Activity of Daily Living Score, International Knee Documentation Committee Subjective Evaluation, Cincinnati Knee Rating System, and Marx Activity Scale. MRIs were evaluated using the OsteoChondral Allograft MRI Scoring System. RESULTS: Thirty-four patients were identified, with a mean age of 45 (±11.9) years; 71% were male. Fifteen (44%) patients had undergone prior ipsilateral surgical intervention. Mean defect size was 4 (±1.5) cm2, and median number of allografts per knee was 2 (range, 1-5). Mean follow-up duration was 15.5 months (range, 6-24). Ten patients (29%) required revision surgery with removal of the implant. Implant survivorship was 61% at 2 years. Female gender was independently predictive of failure, with a hazard ratio of 9.4 (95% confidence interval [CI], 2.0-58.9; P = .005). Defect size was also independently predictive of failure, with a hazard ratio of 1.9 per 1 cm2 increase (95% CI, 1.2-3.1; P = .005). MRIs obtained at 1 year postoperatively demonstrated significantly improved osseous integration (P = .0086) and opposing cartilage (P = .019) in the nonfailure group as compared with the failure group. CONCLUSIONS: Based on the high short-term failure rate observed in this study, the authors advise that a decellularized OC allograft plugs implant should be used with caution in the treatment of OC lesions of the knee, as similar outcomes have not been noted with other cartilage restoration techniques. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Breast Milk Transforming Growth Factor ß Is Associated With Neonatal Gut Microbial Composition.

BACKGROUND AND OBJECTIVES: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. METHODS: A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

Thrombotic and Infectious Morbidity Are Associated with Transfusion in Posterior Spine Fusion.

BACKGROUND: Although previous investigators have established an association between blood transfusion and adverse outcomes, the relative frequency of different morbid events and the association with transfusion dose are not well understood. QUESTIONS/PURPOSES: The purpose of the study is to characterize the relationship between blood transfusion and different types of morbidity after posterior spine fusion. METHODS: We retrospectively analyzed electronic medical records for 963 patients who underwent posterior spinal fusion surgery at a single institution, of which 603 (62.6%) received an allogeneic blood transfusion. Then, we assessed patient and surgical characteristics in a risk-adjusted fashion to identify various morbid event rates and independent predictors in these adverse outcomes. RESULTS: Compared to the non-transfused patients, transfused patients had a higher incidence of any morbid event (9.1 vs. 2.5%. P < 0.0001), thrombotic events (4.6 vs. 1.1%, P = 0.0025), and hospital-acquired infections (2.3 vs. 0.6%, P = 0.039). Renal, respiratory, and ischemic morbidity occurred less frequently and were not more common in transfused patients. Risk-adjusted analysis revealed a dose-response effect, whereby for each unit of allogeneic blood transfused, the risks of any morbid event (OR 1.183; 95% CI 1.103-1.274; P < 0.0001), thrombotic complication (OR 1.104; 95% CI 1.032-1.194; P = 0.0035), and infectious complication (OR 1.182; 95% CI 1.077-1.332; P = 0.0002) were increased. CONCLUSION: Our data demonstrate risk-adjusted and transfusion dose-related increases in perioperative morbidity, with thrombotic and infectious events being the most common.

Statin use and risk of multiple myeloma: An analysis from the cancer research network.

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.