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To develop and initially validate a comprehensive pediatric musculoskeletal ultrasound (MSUS) joint‐specific scoring system, and to determine the minimum number of joints needed to identify active disease. A semiquantitative scoring system was developed by consensus and initially validated by interrater reliability using intraclass correlation coefficients (ICCs). Subsequently, newly diagnosed juvenile idiopathic arthritis patients with an active joint count of >4 had a 42‐joint MSUS performed at baseline and 3 months using this protocol. A minimum set of joints needed to identify all patients with synovitis on MSUS was obtained through a data reduction process. Spearman's correlation (rs) was calculated to determine the association between MSUS findings and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Standardized response means (SMRs) were used to assess change over time. The final joint‐specific scoring system revealed an excellent interrater reliability (ICC 0.81–0.96) for all joints. Thirty patients were enrolled. Scanning 5 joints bilaterally (wrists, second and third metacarpophalangeal joints, knees and ankles) captured 100% of children with B‐mode synovitis and had moderate correlation with the cJADAS10 at baseline (rs= 0.45). Mean ultrasound scores at baseline and follow‐up were 28.3 and 22.3, with an SRM of 0.69 (P= 0.002) for 42 joints, and 36 and 27.7, with an SRM of 0.76 (P= 0.003) for the reduced joints, respectively. A limited MSUS examination called musculoskeletal ultrasound in childhood arthritis limited examination (MUSICAL) captures all patients with active synovitis, and our new joint‐specific scoring system is highly reliable and sensitive to change.

ObjectiveMusculoskeletal ultrasound (MSUS) is increasingly being used in the evaluation of pediatric musculoskeletal diseases. In order to provide objective assessments of arthritis, reliable MSUS scoring systems are needed. Recently, joint-specific scoring systems for arthritis of the pediatric elbow, wrist, and finger joints were proposed by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) MSUS workgroup. This study aimed to assess the reliability of these scoring systems when used by sonographers with different levels of expertise.MethodsMembers of the CARRA MSUS workgroup attended training sessions for scoring the elbow, wrist, and finger. Subsequently, scoring exercises of B mode and power Doppler (PD) mode still images for each joint were performed. Interreader reliability was determined using 2-way single-score intraclass correlation coefficients (ICCs) for synovitis and Cohen [Formula] for tenosynovitis.ResultsSeventeen pediatric rheumatologists with different levels of MSUS expertise (1-15 yrs) completed a 2-hour training session and calibration exercise for each joint. Excellent reliability (ICC > 0.75) was found after the first scoring exercise for all the finger and elbow views evaluated on B mode and PD mode, and for all of the wrist views on B mode. After a second training session and a scoring exercise, the wrist PD mode views reached excellent reliability as well.ConclusionThe preliminary CARRA MSUS scoring systems for assessing arthritis of the pediatric elbow, wrist, and finger joints demonstrate excellent reliability among pediatric MSUS sonographers with different levels of expertise. With further validation, this reliable joint-specific scoring system could serve as a clinical tool and scientific outcome measure.

IMPORTANCE: Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, is currently approved by the US Food and Drug Administration for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The potential neoadjuvant role of programmed cell death 1 inhibitors in primary surgical management of HNSCC and effects on surgical outcomes are poorly understood. OBJECTIVE: To evaluate the incidence of postoperative adverse events in treatment-naive patients with advanced oral cavity cancer receiving neoadjuvant pembrolizumab when compared with matched controls, as part of a window-of-opportunity multi-institutional clinical trial assessing neoadjuvant pembrolizumab for locally advanced HNSCC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study at a single tertiary academic institution included treatment-naive patients with local regionally advanced oral cavity squamous cell carcinoma (OCSCC) who were undergoing surgical resection. EXPOSURES: Patients with local regionally advanced resectable OCSCC who received neoadjuvant pembrolizumab were retrospectively reviewed for postoperative adverse events. Controls were matched by age, race, smoking status, and overall cancer stage based on historical data at the same institution. Matched-cohort analysis was performed using a McNemar test to assess differences between the groups. MAIN OUTCOMES AND MEASURES: Incidence of adverse events following surgical resection of advanced OCSCC within 30 days of surgery and on continued follow-up. RESULTS: A total of 64 patients (32 as part of the prospective clinical trial and 32 as controls; mean [SD] age, 59.6 [10.3] years; 28 [44%] women) were included in the analysis. Postoperative adverse events in the 32 patients receiving pembrolizumab included lymphedema (n = 20 [63%]), trismus (n = 7 [22%]), return to operating room (n = 7 [22%]), wound infection (n = 7 [22%]), fistula (n = 6 [19%]), wound dehiscence (n = 4 [13%]), flap failure (n = 3 [9%]), and hematoma (n = 2 [6%]). The matched control group demonstrated similar complication rates without considerable differences, except for trismus (n = 16 [50%]), which was greater by a difference of 28.1% (95% CI, 5.6%-50.6%) in the control group. CONCLUSIONS AND RELEVANCE: This cohort study examined surgical complications among patients with local regionally advanced OCSCC treated with neoadjuvant pembrolizumab and found that serious adverse events were similar to those in patients who underwent standard-of-care treatment. This suggests that there is no increased perioperative morbidity in the use of preoperative treatment with immunotherapy. Further prospective studies are needed to validate these findings for oral cavity cancer and other subsites of the head and neck.

Pediatric uveitis can lead to sight‐threatening complications and can impact quality of life (QoL) and functioning. We aimed to examine health‐related QoL, mental health, physical disability, vision‐related functioning (VRF), and vision‐related QoL in children with juvenile idiopathic arthritis (JIA), JIA‐associated uveitis (JIA‐U), and other noninfectious uveitis. We hypothesized that there will be differences based on the presence of eye disease. A multicenter cross‐sectional study was conducted at four sites. Patients with JIA, JIA‐U, or noninfectious uveitis were enrolled. Patients and parents completed the Pediatric Quality of Life Inventory (PedsQL; health‐related QoL), the Revised Childhood Anxiety and Depression Scale (RCADS; anxiety/depression), the Childhood Health Assessment Questionnaire (C‐HAQ; physical disability), and the Effects of Youngsters' Eyesight on Quality of Life (EYE‐Q) (VRF/vision‐related QoL). Clinical characteristics and patient‐reported outcome measures were compared by diagnosis. Of 549 patients, 332 had JIA, 124 had JIA‐U, and 93 had other uveitis diagnoses. Children with JIA‐U had worse EYE‐Q scores compared to those with JIA only. In children with uveitis, those with anterior uveitis (JIA‐U and uveitis only) had less ocular complications, better EYE‐Q scores, and worse C‐HAQ and PedsQL physical summary scores compared to those with nonanterior disease. In children with anterior uveitis, those with JIA‐U had worse PedsQL physical summary and C‐HAQ scores than anterior uveitis only. Further, EYE‐Q scores were worse in children with bilateral uveitis and more visual impairment. There were no differences in RCADS scores among groups. We provide a comprehensive outcome assessment of children with JIA, JIA‐U, and other uveitis diagnoses. Differences in QoL and function were noted based on underlying disease. Our results support the addition of a vision‐specific measure to better understand the impact of uveitis.

Background: Previous studies have shown that human milk has a role in the gastrointestinal, neural, and immune development of neonates. If present in milk, adiponectin would be a promising candidate for influencing infant development, given its metabolic functions. Objectives: Our objectives were to determine whether adiponectin is present in human milk and to characterize maternal factors associated with potential variation in milk adiponectin concentrations. Design: We quantified adiponectin concentrations in human milk samples from donors to the Cincinnati Children's Research Human Milk Bank and randomly selected participants in a cohort study in Mexico City funded by the National Institutes of Health. Using cross-sectional and longitudinal data, we examined milk adiponectin concentrations in relation to lactation duration, maternal body mass index (BMI; in kg/[m.sup.2]), and ethnicity. Results: Adiponectin was detected in human skim milk (range: 4.287.9 ng/mL). In cross-sectional and longitudinal analyses, duration of lactation was negatively associated with milk adiponectin concentrations ([beta] = -0.059 [+ or -] 0.024 and -0.059 [+ or -] 0.007, respectively; P < 0.02 for both). Maternal postpregnancy BMI was positively associated with milk adiponectin concentrations ([beta] = 0.08 [+ or -] 0.02, P < 0.0001; longitudinal analysis). Mexican mothers had lower median milk adiponectin concentrations at 1 mo than did the non-Hispanic white subjects from Cincinnati (11.5 and 19.8 ng/mL; P = 0.003). Conclusions: Adiponectin is present in human milk and its concentrations are associated with duration of lactation, maternal adiposity, and ethnicity. Given the importance of adiponectin in inflammation, insulin sensitivity, and fatty acid metabolism, future studies should examine milk adiponectin's role in infant metabolic development. KEY WORDS Adiponectin, human milk, lactation, maternal adiposity

The Effects of Youngsters’ Eyesight on Quality of Life (EYE‐Q) questionnaire measures vision‐related functioning (VRF) and vision‐related quality of life (VRQoL) in children with uveitis. Our aim was to revise the alpha version of the EYE‐Q to refine VRF and VRQoL subscales and to assess the validity of the EYE‐Q. Children with juvenile idiopathic arthritis (JIA), JIA‐associated uveitis, and other noninfectious uveitis were enrolled. Patients and parents completed the EYE‐Q, Pediatric Quality of Life Inventory (overall quality of life), and Childhood Health Assessment Questionnaire (physical functioning). The development site completed the alpha version of the EYE‐Q, and the composite sites completed the beta version. We compared item‐subscale correlations, internal consistency, and construct and discriminant validity among the different versions. Of the 644 patients enrolled, 61.6% completed the alpha version, and 38.4% the beta version of the EYE‐Q. Mean ± SD patient age was 11.1 ± 4.2 years, and 70% were female. Fewer White patients (73.5%) completed the alpha version compared to the beta version (86.2%; P< 0.001). With the exception of patient‐reported VRF, both versions had similar item‐subscale correlations. Version comparisons on scale internal consistencies indicated significant differences for parent‐ and patient‐reported VRF, but each scale had a Cronbach's α of >0.80 beta. When data were combined, the EYE‐Q showed significant differences between JIA‐only and uveitis patients on all parent and patient scores, except for patient‐reported VRF. The EYE‐Q appears to be a valid measure of VRF and VRQoL in pediatric uveitis. Our results suggest it may be used as an outcome measure in multicenter pediatric uveitis studies.

IMPORTANCE: The number of female speakers at American Head and Neck Society (AHNS) conferences should ideally be consistent with the number of women entering head and neck surgery fellowships to ensure gender equity in the field. Yet the presence of women speakers at the annual AHNS meetings, which is specific to the field of head and neck cancer, endocrine and microvascular reconstructive surgery, has yet to be studied. OBJECTIVE: To determine whether the proportion of female speakers at the AHNS has increased in a manner consistent with the numbers of women entering fellowships since 2007. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study assessed 13 final meeting programs from AHNS national/international conferences from 2007 to 2019. The number of male and female participants in different roles throughout the meeting were retrospectively tracked. Participants were male and female speakers at AHNS national/international conferences who took part in the roles of scientific session presenter, scientific session moderator, expert panelist, miscellaneous moderator, and named lecturers/keynote speaker. Gender of the speaker was determined by searching names on the internet and using available published pronouns. MAIN OUTCOMES AND MEASURES: Number of speaking opportunities for men and women in different roles from 2007 to 2019 as well as number of men and women entering AHNS fellowships since 2007 and new active AHNS members since 2012. RESULTS: In this qualitative study, from 2007 to 2019, 4059 speakers were identified. Of these speakers, 902 (22%) were women and 3157 (78%) were men. Overall, there was a strong correlation between increasing years and number of women speakers from 2007 to 2019 (ρ = 0.75; 95% CI, 0.72-0.78). There were 2096 invited speaking roles that excluded research presentations, of which 400 were offered to female participants (19.1%) across the study period. There were 131 different women that made up all 400 of the opportunities that were offered to women in the years surveyed. There was a strong correlation in the proportion of women as presenters for oral abstracts, expert panelists, and miscellaneous moderators between the years but no correlation in scientific session moderators and named lecturers/keynote speakers. Of the 45 named lecturers/keynote speakers in the programs tracked, only 2 were women. CONCLUSIONS AND RELEVANCE: In this study, from 2007 to 2019, the presence of women at ANHS has increased overall, reflecting the changing demographic characteristics of those entering in head and neck oncology and microvascular surgery fellowships. However, a strong disparity continues to exist for preeminent speaking opportunities.

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Background:Characterization of, and evaluation of strategies to mitigate, the effects of sub-concussive impacts (SCI) on brain structure and function are crucial to understanding potential long-term neurological risks associated with sports participation.Objectives:To evaluate the efficacy of a jugular vein compression collar for preserving functional and structural measures of brain network organization in a cohort of female high school soccer players throughout a season of competitive play.Methods:Athletes were assigned to a collar (N= 72) or non-collar (N= 56) group before engaging in a season of play, during which head impact data were recorded via accelerometer for every practice and competition. Participants completed neuroimaging sessions before and following the season. A graph theoretical framework was applied to the functional and structural connectivity measures computed from resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data.Results:Non-collar-wearing athletes exhibited significantly increased rs-fMRI-derived global clustering coefficients (p= 0.032) and DTI-derived modularity (p= 0.042), compared to collar-wearing athletes. No longitudinal changes in any graph measures were observed for the collar group (p> 0.05).Conclusion:The observed increase in graph measures in the non-collar group is congruent with previous studies of SCI and is similar to graph theoretical studies of traumatic brain injury. The absence of alterations in graph metrics in the collar group indicates a potential ameliorating effect of the collar device against network reorganization, in line with previous literature.

ObjectiveTo evaluate the ability of four objectively defined, cortical maturation features—surface area, gyrification index, sulcal depth and curvature—from structural MRI at term-equivalent age (TEA) to independently predict cognitive and language development at 2 years corrected age in very preterm (VPT) infants.DesignPopulation-based, prospective cohort study. Structural brain MRI was performed at term, between 40 and 44 weeks postmenstrual age and processed using the developing Human Connectome Project pipeline.SettingMulticentre study comprising four regional level III neonatal intensive care units in the Columbus, Ohio region.Patients110 VPT infants (gestational age (GA) [Formula]31 weeks).Main outcome measuresCognitive and language scores at 2 years corrected age on the Bayley Scales of Infant and Toddler Development, Third Edition.ResultsOf the 94 VPT infants with high-quality T2-weighted MRI scans, 75 infants (80%) returned for Bayley-III testing. Cortical surface area was positively correlated with cognitive and language scores in nearly every brain region. Curvature of the inner cortex was negatively correlated with Bayley scores in the frontal, parietal and temporal lobes. In multivariable regression models, adjusting for GA, sex, socioeconomic status, and injury score on MRI, regional measures of surface area and curvature independently explained more than one-third of the variance in cognitive and language scores at 2 years corrected age in our cohort.ConclusionsWe identified increased cortical curvature at TEA as a new prognostic biomarker of adverse neurodevelopment in very premature infants. When combined with cortical surface area, it enhanced prediction of cognitive and language development. Larger studies are needed to externally validate our findings.

Objectives:To identify risk factors and evaluate the impact of various facial fractures and reconstruction surgeries on postoperative weight change. Methods:Retrospective, monocentric study was performed at a tertiary care center. Medical history, type and mechanism of fracture, operative factors, and postoperative weights at follow-up appointments for 145 adult patients undergoing surgical repair for maxillofacial fractures were collected. Further information was obtained on postoperative diet and whether patients received maxillomandibular fixation (MMF). Univariate and multivariate analyses were utilized to evaluate effects of surgical reconstruction after facial trauma on postoperative weight loss. Results:Patients lost 3.2 ± 4.9 kg (95% confidence interval = 2.7-4.1, P< .0001) on average, with maximum loss between date of surgery and first follow-up. Univariate analysis demonstrated that intensive care unit admission (5.9 kg, SD 5.4, P= .001), nasogastric tube placement (5.1 kg, SD 4.6, P= .012), and MMF (4.4 kg, SD 5.4, P< .0001) were associated with more severe weight loss. Multivariate analyses showed that only MMF remained a significant risk factor for increased weight loss (avg. 6.0, standard error 1.93, tvalue 3.11, P= .0024). Conclusions:We report significant weight loss following facial trauma and reconstruction, which emphasizes the need to perform further studies on nutrition protocols for this patient population to optimize wound healing.

PurposeTo (1) quantify white matter (WM) alterations in female high school athletes during a soccer season and characterise the potential for normalisation during the off-season rest period, (2) determine the association between WM alterations and exposure to repetitive subconcussive head impacts, and (3) evaluate the efficacy of a jugular vein compression collar to prevent WM alterations associated with head impact exposure.MethodsDiffusion tensor imaging (DTI) data were prospectively collected from high school female soccer participants (14–18 years) at up to three time points over 9 months. Head impacts were monitored using accelerometers during all practices and games. Participants were assigned to a collar (n=24) or non-collar group (n=22). The Tract-Based Spatial Statistics approach was used in the analysis of within-group longitudinal change and between-group comparisons.ResultsDTI analyses revealed significant pre-season to post-season WM changes in the non-collar group in mean diffusivity (2.83%±2.46%), axial diffusivity (2.58%±2.34%) and radial diffusivity (3.52%±2.60%), but there was no significant change in the collar group despite similar head impact exposure. Significant correlation was found between head impact exposure and pre-season to post-season DTI changes in the non-collar group. WM changes in the non-collar group partially resolved at 3 months off-season follow-up.DiscussionMicrostructural changes in WM occurred during a season of female high school soccer among athletes who did not wear the collar device. In comparison, there were no changes in players who wore the collar, suggesting a potential prophylactic effect of the collar device in preventing changes associated with repetitive head impacts. In those without collar use, the microstructural changes showed a reversal towards normal over time in the off-season follow-up period.

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood–brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile‐onset systemic lupus erythematosus (SLE). In this cross‐sectional, case–control study, capillary permeability was measured as a marker of blood–brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion‐weighted brain MRI. Regional gray matter volume was measured by voxel‐based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood–brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P= 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P< 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood–brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood–brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study.

Post-implant variability in oral language outcomes is difficult to predict in young cochlear implant recipients. The authors aimed to identify neuroimaging biomarkers of post-implant oral language performance in these children before implantation, using functional magnetic resonance imaging. They used auditory stimuli such as spoken narratives and narrow band noise to study brain activation. They identified four brain regions that correlated positively with behavioral measures of oral language abilities administered two years post-implantation. The results suggest that in spite of auditory deprivation, pre-implant fMRI with appropriate auditory stimulation may predict oral language outcome following early implantation.

Background:Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls.Methods:Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups.Results:Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants.Conclusion:Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates.

Objective.Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein overexpressed in certain inflammatory diseases. Our objective was to correlate FSTL-1 levels with gene expression, known biomarkers, and measures of disease activity in systemic juvenile idiopathic arthritis (sJIA), including macrophage activation syndrome (MAS).Methods.FSTL-1 serum levels were measured by ELISA in 28 patients with sJIA, including 7 patients who developed MAS, and 30 healthy controls. Levels were correlated with erythrocyte sedimentation rate (ESR), ferritin, and soluble interleukin-2 receptor-α (sIL-2Rα). Gene expression based on FSTL-1 levels was analyzed in peripheral blood mononuclear cells (PBMC).Results.Serum levels of FSTL-1 were elevated at time of presentation of sJIA (mean 200.7 ng/ml) and decreased to normal (mean 133.7 ng/ml) over 24 months (p < 0.01). FSTL-1 levels were markedly elevated during acute MAS (mean 279.8 ng/ml) and decreased to normal following treatment (p < 0.001). FSTL-1 levels correlated with serum markers of inflammation, including sIL-2Rα and ferritin. Ferritin/ESR ratio was superior to ferritin, sIL-2Rα, and FSTL-1 in discriminating MAS from new-onset sJIA. PBMC from patients with FSTL-1 levels > 200 ng/ml showed altered expression of genes related to innate immunity, erythropoiesis, and natural killer cell dysfunction. Two patients with the highest FSTL-1 levels at disease onset (> 300 ng/ml) ultimately developed MAS.Conclusion.Elevated pretreatment serum FSTL-1 levels in sJIA are associated with dysregulated gene expression suggestive of occult MAS, and may have utility in predicting progression to overt MAS. Ferritin/ESR ratio may be superior to ferritin alone in discriminating overt MAS from new-onset sJIA.

AbstractBackground:Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form.Design and Methods:This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother–infant pairs from Cincinnati, OH and 277 mother–infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n= 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot.Results:In the population studies, initial milk adiponectin was 24.0 ± 8.6 μg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (−0.20 ± 0.04, p< 0.0001) and weight-for-length Z-score (−0.29 ± 0.08, p= 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form.Conclusions:Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.

To determine whether differences exist in the descriptors used in letters of recommendations for Otolaryngology - Head and Neck Surgery (OHNS) residency candidates, comparing race and gender as depicted in visual letters of recommendation (VLORs) from the 2014 and 2019 application cycles.

The kappa statistic is frequently used as a measure of agreement among two or more raters. Although considerable research on statistical inferences for this statistic has been published for the case of two raters and a binary outcome, relatively little work has appeared on inference problems for the case of multiple raters and/or polytomous nominal outcome categories. In this paper we propose a new procedure for constructing inferences for the kappa statistic that may be applied to this general case. The procedure is based on a chi‐square goodness‐of‐fit test as applied to the Dirichlet multinomial model, and is a natural extension of previously proposed procedures that apply to more restricted cases. A simulation study shows that the new procedure provides confidence interval coverage levels and type I error rates close to nominal over a wide range of parameter combinations. We also present a sample size formula which may be used to determine the required number of subjects and raters for a given number of outcome categories. Copyright © 2001 John Wiley & Sons, Ltd.

Summary. We propose a new procedure for constructing inferences about a measure of interobserver agreement in studies involving a binary outcome and multiple raters. The proposed procedure, based on a chi‐square goodness‐of‐fit test as applied to the correlated binomial model (Bahadur, 1961, in Studies in Item Analysis and Prediction, 158–176), is an extension of the goodness‐of‐fit procedure developed by Donner and Eliasziw (1992, Statistics in Medicine11, 1511–1519) for the case of two raters. The new procedure is shown to provide confidence‐interval coverage levels that are close to nominal over a wide range of parameter combinations. The procedure also provides a sample‐size formula that may be used to determine the required number of subjects and raters for such studies.

Introduction: Femoral neck fractures in the elderly are increasingly common as a result of a growing geriatric population with 1-year mortality rates approaching 35%. While preoperative medical optimization and early time to surgery have reduced morbidity and mortality, patients with numerous medical comorbidities remain high risk for death in the perioperative period. Identifying those with greatest risk with a scoring system or nomogram may assist multidisciplinary teams in reducing mortality following hemiarthroplasty.Purpose: Identify predictors of 30-day mortality in elderly patients who underwent hemiarthroplasty for a femoral neck fracture to generate a predictive nomogram to determine the probability of post-operative mortality.Methods: Retrospective evaluation using data from the ACS-NSQIP database from 2005 to 2014 with CPT code 27125 for hip hemiarthroplasty. Multiple factors including demographics and comorbidities were compared in patients who experienced 30-day mortality and those who did not. T-test and chi-square tests were used to analyze data and a multivariate model was generated using logistic regression.Results: Advanced age (odds ratio (OR) 1.04), underweight BMI (OR 1.55), male sex (OR 1.80), reduced functional status (OR 2.04), heart failure within 30 days prior to surgery (OR 2.22), American Society of Anesthesiologists grade > 2 (OR > 2.50), disseminated cancer (OR 3.43) were all found to have statistically significant odds ratios for 30-day mortality following hemiarthroplasty.Conclusion: A tool based on easily identifiable risk factors, demographics, and comorbidities was developed that can help predict elderly patients who will experience mortality within 30 days of following hemiarthroplasty. In addition to identifying high risk patients, the nomogram can serve as a counseling tool for physicians to use with patients and their families to assist with better understanding of perioperative mortality risk.

Background: To measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple bvalues and investigate relationships of those measures with neurocognitive function and disease activity. Methods: In this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls. These markers of microvascular and microstructural integrity were derived by diffusion-weighted brain MRI and intravoxel incoherent motion (IVIM) modeling. Formal neurocognitive testing was completed focused on the domains of attention, visuoconstructional ability, working memory, and psychomotor speed. Test scores and measures of disease severity were regressed against regional microvascular integrity parameters among cSLE patients. Results: Formal cognitive testing confirmed normal cognitive ability among all cSLE patients included in the analysis (n= 11). Nevertheless, reduction in blood volume fraction coincided with increased effective diffusion and flow parameters in cSLE patients vs. controls in posterior brain regions including the cuneus and precuneus. Regional microvascular measures correlated (|r| = 0.54–0.66) with neuropsychiatric scores and disease activity among cSLE patients. Conclusions: There is imaging evidence, using IVIM, of degraded microvascular integrity in cSLE patients with normal cognitive ability. The observed regional changes correspond with posterior vascular border zones. These outcomes appear consistent with regional gray matter volume loss previously observed in cSLE patients with overt neurocognitive deficits, supporting the notion that adverse vascular changes precede loss of cognitive ability in cSLE. Longitudinal studies are needed to confirm the findings of this initial study.

To test the hypothesis that human milk fucosyloligosaccharides are part of an innate immune system, we addressed whether their expression (1) depends on maternal genotype and (2) protects breastfed infants from pathogens. Thus the relationship between maternal Lewis blood group type and milk oligosaccharide expression and between variable oligosaccharide expression and risk of diarrhea in their infants was studied in a cohort of 93 Mexican breastfeeding mother–infant pairs. Milk of the 67 Lea–b+ mothers contained more LNF-II (Lea) and 3-FL (Lex) (oligosaccharides whose fucose is exclusively α1,3- or α1,4-linked) than milk from the 24 Lea−b− mothers; milk from Lea−b− mothers contained more LNF-I (H-1) and 2′-FL (H-2), whose fucose is exclusively α1,2-linked. The pattern of oligosaccharides varied among milk samples; in each milk sample, the pattern was summarized as a ratio of 2-linked to non-2-linked fucosyloligosaccharides. Milks with the highest ratios were produced primarily by Lea−b− mothers; those with the lowest ratios were produced exclusively by Lea–b+ mothers (p<0.001). Thus maternal genetic polymorphisms expressed as Lewis blood group types are expressed in milk as varied fucosyloligosaccharide ratios. The four infants who developed diarrhea associated with stable toxin of Escherichia coli were consuming milk with lower ratios (4.4 ± 0.8 [SE]) than the remaining infants (8.5 ± 0.8; p<0.001). Furthermore, the 27 infants who developed moderate to severe diarrhea of any cause were consuming milk with lower ratios (6.1 ± 0.9) than the 26 who remained healthy (10.5 ± 1.9; p = 0.042). Thus, milk with higher 2-linked to non-2-linked fucosyloligosaccharide ratios affords greater protection against infant diarrhea. We conclude that specific oligosaccharides constitute a major element of an innate immune system of human milk.