Development and Implementation of a Pediatric Nursing Emergency Behavioral Health Assessment Tool.

INTRODUCTION: The national pediatric mental and behavioral health crisis dramatically increased emergency department mental and behavioral health visits and changed emergency nursing practice. Acuity assessment determines patient severity level and supports appropriate resources and interventions. There are no established nursing tools that assess pediatric mental or behavioral health acuity in the emergency department setting. Our goal was to develop and implement the novel pediatric emergency nurse Emergency Behavioral Health Acuity Assessment Tool. METHODS: This quality-improvement project used the plan, do, study, act model to design/refine the Emergency Behavioral Health Acuity Assessment Tool and a non-experimental descriptive design to assess outcomes. The setting was a 47-bed urban level 1 pediatric trauma center with more than 60,000 annual visits. The team designed the tool using published evidence, emergency nurse feedback, and expert opinion. The tool objectively captured patient acuity and suggested acuity-specific nursing interventions. Project outcomes included acuity, length-of-stay, restraint use, and patient/staff injuries. Analyses included descriptive statistics and correlations. RESULTS: With over 3000 annual mental/behavioral-related visits, the emergency department had an average daily census of 23 mental and behavioral health patients. Implementation occurred in August 2021. The Emergency Behavioral Health Acuity Assessment Tool dashboard provided the number of patients, patient location, and acuity. Length-of-stay did not change; however, patient restraint use and patient/staff injuries declined. Number of restraints positively correlated with moderate acuity levels (r = 0.472, P = 0.036). DISCUSSION: For emergency nurses, the Emergency Behavioral Health Acuity Assessment Tool provided an objective measure of patient acuity. Targeted interventions can improve the care of this population.

High-Risk Markers and Infection Rates in Febrile Infants Aged 29 to 60 Days Presenting to an Emergency Department During the COVID-19 Pandemic.

OBJECTIVES: There was an overall decline in pediatric emergency department visits during the COVID-19 pandemic. Caregivers are educated to bring febrile neonates promptly to the emergency department; however, for infants aged 29 to 60 days, there may not be the same urgency especially during a pandemic. There may have been a resultant change in the clinical and laboratory high-risk markers and infection rates in this patient population during the pandemic. METHODS: This was a single-center retrospective cohort study of infants aged 29 to 60 days presenting to the emergency department of an urban tertiary care children's hospital because of fever (>38°C) between March 11 and December 31, 2020, compared with those presenting in the same period during the 3 prior years (2017 through 2019). Patients were categorized as having high-risk criteria on a predetermined definition of ill appearance, white blood cell count, and urinalysis based on our hospital's evidence-based pathway. Information on infection type was also collected. RESULTS: A total of 251 patients were included in the final analysis. Comparison of the prepandemic and pandemic cohorts showed a significant increase in the proportion of patients with urinary tract infections ( P = 0.017) and bacteremia ( P = 0.02) and those presenting with high-risk white blood cell count ( P = 0.028) and urinalysis ( P = 0.034). There was no significant difference in patient demographics or in high-risk ill appearance ( P = 0.208). CONCLUSIONS: This study demonstrates a significant increase in the rates of urinary tract infection and bacteremia in addition to the objective markers used to risk-stratify febrile infants aged 29 to 60 days. This supports the need for attentiveness in evaluating these febrile infants in the emergency department.

Methotrexate for Primary Maintenance Therapy in Mild-to-Moderate Crohn Disease in Children.

OBJECTIVES: Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as "initial" primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors. METHODS: Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission. RESULTS: We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m 2 orally and 12.5 mg/m 2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up. CONCLUSIONS: MTX may have a primary maintenance role in mild/moderate CD.

Trochlear Dysplasia as Shown by Increased Sulcus Angle Is Associated With Osteochondral Damage in Patients With Patellar Instability.

PURPOSE: The primary study objective was to describe the incidence of osteochondral damage (OD) in our cohort of patients with patellar instability (PI). The secondary objective was to assess for associations between patient demographic characteristics, duration of PI, and quantitative radiographic measurements of anatomic risk factors for PI and OD in this cohort. METHODS: A retrospective chart review identified patients treated for PI at a tertiary referral center between 2013 and 2018. Patients were evaluated for osteochondral injury with either magnetic resonance imaging if treated nonoperatively or operative reports if treated surgically. The Caton-Deschamps ratio, proximal tibial tubercle-to-trochlear groove (pTT-TG) distance, distal tibial tubercle-to-trochlear groove (dTT-TG) distance, lateral trochlear inclination (LTI) angle, lateral patellar inclination (LPI) angle, and sulcus angle were calculated from magnetic resonance imaging scans. Trochlear dysplasia is an important risk factor for PI that can be reliability quantified by the pTT-TG distance, dTT-TG distance, LTI angle, sulcus angle, and LPI angle. Demographic data including age at first instability event, sex, body mass index, symptom duration, and number of dislocations were documented. RESULTS: A total of 125 knees in 118 patients (average age, 13.9 ± 3.4 years; 48% female patients) with PI were identified. Within this cohort, 67% were treated surgically and 53% had OD. No association was identified between osteochondral injury and age, sex, body mass index, symptom duration, LTI angle, LPI angle, dTT-TG distance, pTT-TG distance, or number of dislocations. An increased sulcus angle (more dysplasia) showed a statistically significant association with osteochondral pathology (P = .021), and higher sulcus angles were statistically significantly associated with acute osteochondral fracture compared with chondral injury (P = .001). CONCLUSIONS: Using quantitative analysis of trochlear dysplasia, this study identified a significant association between trochlear dysplasia (sulcus angle) and the incidence of OD in our cohort of patients with PI. The frequency of dislocation or subluxation and patient demographic characteristics were not significantly associated with OD. LEVEL OF EVIDENCE: Level III, retrospective prognostic study.

Methodological Challenges in Conducting Research with Refugee Women.

The purpose of this pilot study was to evaluate the acceptability and feasibility of a 10-week community-based, culturally tailored mental health intervention, called Healthy Sudanese Families, with 12 South Sudanese refugee women living in a metropolitan area of the Midwestern United States. This mixed-methods study used the Dinka and Arabic versions of the Hopkins Symptoms Checklist-25 to measure indicators of anxiety and depression and a final focus group to evaluate the women's responses to the intervention. The women found the mental health intervention acceptable and relevant. Methodological challenges encountered in cross-cultural research with refugees are discussed.

Vancomycin Trough and Acute Kidney Injury: A Large Retrospective, Cohort Study.

BACKGROUND: The association between vancomycin trough (VT) and acute kidney injury (AKI) at the recommended doses remains controversial. METHODS: The authors conducted a retrospective, observational cohort study of 500 adult patients who received vancomycin for ≥72 h. Data collected included 2 main predictors: average VT (including only VTs before the occurrence of AKI), first VT and other possible risk factors for AKI. The baseline characteristics/variables between patients with AKI and patients with no AKI were compared. Logistic regression models were used to develop multivariate models. The authors divided the patients into 4 subgroups: (1) VT <10, (2) 10 ≤ VT < 15, (3) 15 ≤ VT < 20 and (4) VT ≥20 µg/ml. All subgroups were compared to subgroup 2 (reference group). RESULTS: AKI occurred in 12.85% of patients while on vancomycin. The incidence of AKI in subgroups 1-4 was 8.02, 13.61, 13.70 and 31.82%, respectively, using the first VT, that is significantly higher in subgroup 4. Using average VT, AKI incidence was 5, 10.38, 19.01 and 25.58%, respectively, that is significantly higher in subgroups 3 and 4. On multivariate logistic regression, average VT, first VT, average VT >15, first VT >15, methicillin-resistant Staphylococcus aureus infection and morbid obesity were significantly associated with increased incidence of AKI. CONCLUSION: Clinicians should be careful when aiming for a VT >15 µg/ml as this is associated with increased incidence of AKI.

Biostatistical and medical statistics graduate education.

The development of graduate education in biostatistics and medical statistics is discussed in the context of training within a medical center setting. The need for medical researchers to employ a wide variety of statistical designs in clinical, genetic, basic science and translational settings justifies the ongoing integration of biostatistical training into medical center educational settings and informs its content. The integration of large data issues are a challenge.

Advancing Newborn Screening Long-Term Follow-Up: Integration of Epic-Based Registries, Dashboards, and Efficient Workflows.

The Connecticut Newborn Screening (NBS) Network, in partnership with the Connecticut Department of Public Health, strategically utilized the Epic electronic health record (EHR) system to establish registries for tracking long-term follow-up (LTFU) of NBS patients. After launching the LTFU registry in 2019, the Network obtained funding from the Health Resources and Services Administration to address the slow adoption by specialty care teams. An LTFU model was implemented in the three highest-volume specialty care teams at Connecticut Children's, involving an early childhood cohort diagnosed with an NBS-identified disorder since the formation of the Network in March 2019. This cohort grew from 87 to 115 over the two-year project. Methods included optimizing registries, capturing external data from Health Information Exchanges, incorporating evidence-based guidelines, and conducting qualitative and quantitative evaluations. The early childhood cohort demonstrated significant and sustainable improvements in the percentage of visits up-to-date (%UTD) compared to the non-intervention legacy cohort of patients diagnosed with an NBS disorder before the formation of the Network. Positive trends in the early childhood cohort, including %UTD for visits and condition-specific performance metrics, were observed. The qualitative evaluation highlighted the achievability of practice behavior changes for specialty care teams through responsive support from the nurse analyst. The Network's model serves as a use case for applying and achieving the adoption of population health tools within an EHR system to track care delivery and quickly fill identified care gaps, with the aim of improving long-term health for NBS patients.

Validating the Modified McGill Thyroid Nodule Score for Assessment of Preoperative Risk of Pediatric Thyroid Malignancy.

OBJECTIVE: The McGill Thyroid Nodule Score (MTNS) is a preoperative tool used to predict the risk for well-differentiated thyroid cancer in adults. It was developed by a multidisciplinary team using established evidence-based risk factors for thyroid cancer. The modified McGill Thyroid Nodule Score (mMTNS) was developed to predict malignancy risk in children. A pilot study suggested the mMTNS was able to assess malignancy risk in children with indeterminate cytology on fine needle aspiration (FNA). This study seeks to validate these findings. METHODS: Retrospective chart review identified subjects who underwent FNA biopsy and subsequent resection. Each patient was assigned a score to compare to final pathology. Statistical analysis was performed with SPSS. All tests were 2-tailed and statistical significance defined p < 0.05. Logistic regression used to determine predictive values of scores. RESULTS: 46 patients ≤21 years of age underwent resection of a thyroid nodule. Female predominance of 85% (n = 39). 78% (n = 36) of patients had palpable nodule. 65% (n = 30) found to have benign pathology and 35% (n = 16) found to have malignancy. Malignant nodules associated with greater mean mMTNS compared to benign [13.63 vs 7.23]. An mMTNS greater >12 had sensitivity of 86.7%, specificity of 90.3%, positive predictive value of 81.3%, and negative predictive value of 93.3%. CONCLUSION: Our data suggests the mMTNS continues to be a useful adjunct in predicting malignancy risk of pediatric thyroid nodules. An mMTNS >12 has a high risk for malignancy, which can aid in counseling and clinical decision making, particularly when there is indeterminate cytology on FNA. LEVEL OF EVIDENCE: IV.

Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.

Fresh frozen plasma and cryoprecipitate: Can we safely reduce their use in the NICU?

OBJECTIVE: To study patterns of use of Fresh Frozen Plasma (FFP) and Cryoprecipitate (CRYO) in a level 4 NICU and assess what proportions were not supported by literature. STUDY DESIGN: single centered retrospective observational. Charts of neonates admitted between 1/1/2010 to 12/31/2017 to CT Children's level 4 NICU were reviewed. Transfusions were assigned as "supported" or "non-supported" based on available evidence. Groups were compared using T-tests and chi-squared analyses. RESULTS: of 4110 total admissions, 197 (4.8%) received a total of 461 transfusions (374 FFP, 87 CRYO). Only 59% of FFP and 60% CRYO were supported by literature. Within the "non-supported" group the largest category was neonates transfused prophylactically. CONCLUSION: A large proportion of transfusions administered to neonates was not evidence-based, suggesting there are opportunities for improvement in use of these products.

Impact of gender in congenital heart surgery: Results from a national survey.

OBJECTIVE: There are limited data regarding the impact of gender within congenital heart surgery. Our aim was to assess gender-related experiences by surgeons in this field. METHODS: A cross-sectional survey was emailed to practicing congenital heart surgeons to ascertain the perception of gender in 5 domains: training, professional career, clinical practice, personal life, and career outlook. RESULTS: The survey response rate was 94% (17/18) for women and 44% (112/257) for men. More than half of women (53%) were discouraged from pursuing congenital heart surgery (P < .001) and reported a negative impact of gender in attaining their first congenital heart surgery job (P < .001) compared with men. Despite similar demographics, women reported lower starting annual salaries ($150K-$250K vs $250K-$400K), lower current annual salaries ($500K-$750K vs $750K-$1M), lower academic ranks (clinical instructor 6% vs 4% [P = .045], assistant professor 35% vs 19% [P = .19], associate professor 41% vs 25% [P = .24], and professor 6% vs 41% [P = .005]) along with lower annual salaries at the associate professor ($500K-$750K vs $1M-$1.25M) and professor levels ($1M-$1.25M vs >$1.5M) compared with men. Sexual harassment was experienced more frequently by women both in training (65% vs 6%, P < .001) and in practice (65% and 4%, P < .001). CONCLUSIONS: This survey highlights many areas of gender-related differences: discouragement due to gender to pursue congenital heart surgery, sexual harassment in training and practice, salary and academic rank differentials, negative gender perception at work, and lower career satisfaction for women. Despite various differences between both genders, the majority in each group would choose to enter this profession again as well as encourage others to do so.

Pilot Study on the Impact of Gratitude Journaling or Cognitive Strategies on Health Care Workers.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the mental well-being of health care workers (HCWs). This study assessed the feasibility, acceptability, and preliminary efficacy of two psychological interventions, gratitude journaling or cognitive strategies, on pediatric HCWs. METHOD: A pilot randomized parallel repeated measures design was used, with a convenience sample of 59 HCWs. Data were collected before and after the intervention period, 2 weeks after, and again 6 months later. Outcomes included depression, anxiety, meaning and purpose, feasibility, and acceptability. RESULTS: Thirty-seven participants completed the study. The majority were nurses (registered nurses and advanced practice registered nurses) and physicians. In both groups, depression and anxiety scores diminished, but changes were not statistically significant. The study was feasible to conduct, and subjects reported high acceptability. DISCUSSION: Gratitude journaling and cognitive strategies may help mental well-being in HCWs; however, future studies with larger samples are needed.

Unpacking the Tibial Tubercle-Trochlear Groove Distance: Evaluation of Rotational Factors, Trochlear Groove and Tibial Tubercle Position, and Role of Trochlear Dysplasia.

BACKGROUND: The tibial tubercle to trochlear groove (TT-TG) distance is often utilized for determining the surgical treatment for patients with patellar instability (PI). It is thought to directly represent the position of the TT on the tibia. Recent work has shown that the measurement of the TT-TG distance is multifactorial. PURPOSE: To investigate the relationship between relative tibial external rotation (rTER) and trochlear dysplasia (TD), as well as the location of the TG and TT in patients with and without PI, and to correlate these and other anatomic measurements with the TT-TG distance. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 89 patients with PI who underwent magnetic resonance imaging were identified with 92 matched control patients. A standardized measurement protocol on axial magnetic resonance imaging determined rTER, the proximal and distal TG lateralization (pTGL and dTGL, respectively) ratios, and the TT lateralization (TTL) ratio. Other measures of interest included the lateral trochlear inclination angle, sulcus angle, and lateral patellar inclination angle. Univariate regression was used to determine the associations of TD (lateral trochlear inclination angle, sulcus angle) with rTER and the TG position, and multivariate regression was used to model associations among all the variables with the proximal and distal TT-TG distances. RESULTS: rTER was significantly higher in the study group (P < .001), and univariate regression showed a significant association between dysplasia measures and rTER (P < .001). The pTGL ratio was lower in the study group (P = .025), but there was no difference in the dTGL ratio (P = .090) or the TTL ratio (P = .098) between the groups. There were no associations between dysplasia measures and the pTGL and dTGL ratios (P > .05). Multivariate regression showed that the proximal TT-TG distance is predicted by the sulcus angle, pTGL ratio, rTER, and TTL ratio (P < .05) and that the distal TT-TG distance is predicted by the lateral patellar inclination angle, dTGL ratio, sulcus angle, rTER, and TTL ratio (P < .05). CONCLUSION: rTER had a significant association with TD. The position of the proximal TG was more medial in patients with PI. There was no significant difference in the TTL ratio between patients with and without PI. The TT-TG distance was associated with multiple anatomic measures and was not solely predicated on the position of the TT.

Comparing Artificial Intelligence and Traditional Methods to Identify Factors Associated With Pediatric Asthma Readmission.

OBJECTIVE: To identify and contrast risk factors for six-month pediatric asthma readmissions using traditional models (Cox proportional-hazards and logistic regression) and artificial neural-network modeling. METHODS: This retrospective cohort study of the 2013 Nationwide Readmissions Database included children 5 to 18 years old with a primary diagnosis of asthma. The primary outcome was time to asthma readmission in the Cox model, and readmission within 180 days in logistic regression. A basic neural network construction with 2 hidden layers and multiple replications considered all dataset variables and potential variable interactions to predict 180-day readmissions. Logistic regression and neural-network models were compared on area-under-the receiver-operating curve. RESULTS: Of 18,489 pediatric asthma hospitalizations, 1858 were readmitted within 180 days. In Cox and logistic models, longer index length of stay, public insurance, and nonwinter index admission seasons were associated with readmission risk, whereas micropolitan county was protective. In neural-network modeling, 9 factors were significantly associated with readmissions. Four overlapped with the Cox model (nonwinter-month admission, long length of stay, public insurance, and micropolitan hospitals), whereas 5 were unique (age, hospital bed number, teaching-hospital status, weekend index admission, and complex chronic conditions). The area under the curve was 0.592 for logistic regression and 0.637 for the neural network. CONCLUSIONS: Different methods can produce different readmission models. Relying on traditional modeling alone overlooks key readmission risk factors and complex factor interactions identified by neural networks.

Percutaneous hamstring lengthening in cerebral palsy: Technique and gait outcomes based on GMFCS level.

BACKGROUND: Increased knee flexion at initial contact and in stance is a common problem for children with cerebral palsy. Surgical correction with percutaneous hamstring lengthening is an alternative to open hamstring lengthening; however, outcomes are less well documented, and there is concern about increasing anterior pelvic tilt. The purpose of this study was to evaluate the short-term outcomes of percutaneous hamstring lengthenings in children with cerebral palsy using comprehensive gait analysis techniques. RESEARCH QUESTION: Does percutaneous hamstring lengthening improve knee function, and do knee and anterior pelvic tilt outcomes vary by GMFCS level? METHODS: A convenience sample of 52 patients with both pre and post-surgical gait analyses was evaluated retrospectively for changes in gait function in terms of temporal-spatial parameters, kinematics and kinetics. Patients were divided into two GMFCS subgroups: GMFCS level I/II and III. RESULTS: The percutaneous hamstring lengthening results in statistically significant improvements in knee function during gait with increased knee extension at initial contact (mean 32° SD 13° to mean 21° SD 11°, p = 0.000) and improved mean knee flexion in stance (mean 23° SD 12° to mean 16° SD 11°, p = 0.000) for the total study cohort. Beneficial changes were found for knee function in both GMFCS level subgroups; however, there was an increase in pelvic tilt pre to post-surgery in the GMFCS level III subgroup (mean 21° SD 8° to mean 26° SD 6°, p = 0.012) but not the GMFCS level I/II subgroup (mean 18° SD 7° to mean 20° SD 8°, p = 0.427). SIGNIFICANCE: Percutaneous hamstring lengthening can improve knee function for all patients; however, the impact on anterior pelvic tilt varies by GMFCS level, with increasing anterior tilt for GMFCS level III only. This study highlights the importance of understanding differences in surgical outcomes by GMFCS level to better predict post-surgical function.

Patellar Height Correlates Modestly With Trochlear Dysplasia: A Magnetic Resonance Imaging Analysis.

Purpose: To evaluate whether there is a correlation between the position of the patella and trochlear morphology in patients with and without patellar instability using exclusively MRI measurements. Methods: MRI scans of knees in patients with patellofemoral instability and knees of patients with an ACL (anterior cruciate ligament) tear as a control group were reviewed. Measurements of patellar position (Canton-Deschamps ratio, Patellar Trochlear Index, and lateral patellar inclination) and trochlear morphology (lateral trochlear inclination and sulcus angle) were obtained from each scan. Bivariate and multivariate analysis was performed to identify correlations between study group, demographics, and patellofemoral joint measurements. Results: There were 70 knees in the patellofemoral instability group and 60 knees in the control group. Bivariate analysis showed a significant difference in all measurements between the patellar instability group and the control group. Multivariate analysis showed modest correlations between patellar position and trochlear morphology. The Caton-Deschamps (CD) ratio correlated with patellar trochlear index (P < .001) and lateral trochlear inclination (P < .001). The respective R-square goodness of fit was 41.1%. Patellar trochlear index correlated with CD ratio (P < .001), lateral trochlear inclination (P < .001), lateral patellar inclination (P < .001), and patellar instability group (P = .011). The R-sq goodness of fit was 37.3%. Lateral patellar inclination correlated with patellar trochlear index (P < .001), Lateral trochlear inclination (P < .001), and age at first dislocation or injury (P = .02). The R-sq goodness of fit was 68.56%. Conclusions: Using MRI-based measurements of the patellofemoral joint, we identified modest, but significant, correlations between measures of patellar height (patellar trochlear index, CD ratio, and lateral patellar inclination) and trochlear dysplasia. This correlation is unclear and is likely multifactorial, but on the basis of this work, a causal relationship between trochlear dysplasia and patella alta cannot be established. Clinical Relevance: Radiographic evaluation of the patella and how it relates to the surrounding boney anatomy provides important information regarding our understanding of patella instability and its treatment.

Antibody Responses to SARS-CoV-2 After Infection or Vaccination in Children and Young Adults With Inflammatory Bowel Disease.

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial. METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 spike protein onto a lentivirus and measures pseudoviral entry into ACE2-angiotensin converting enzyme 2 (ACE2) expressing human embryonic kidney 293 (HEK-293) cells was used. RESULTS: There were 436 patients enrolled (mean age, 17 years, range 2-26 years; 58% male; 71% Crohn's disease, 29% ulcerative colitis, IBD-unspecified). Forty-four (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (n = 33), patients had a 15-fold higher S-RBD antibody response in comparison with natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2. CONCLUSIONS: The lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.

Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis.

BACKGROUND: Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC). METHODS: This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria. Patients were phenotyped by clinical activity per the Pediatric Ulcerative Colitis Activity Index (PUCAI), disease extent, endoscopic/histologic severity, and laboratory markers. In addition, RNA sequencing defined pretreatment rectal gene expression and high density DNA genotyping by the Affymetrix UK Biobank Axiom Array. Coprimary outcomes were colectomy over 3 years and time to colectomy. Generalized linear models, Cox proportional hazards multivariate regression modeling, and Kaplan-Meier plots were used. RESULTS: Four hundred twenty-eight patients (mean age 13 years) started initial theapy with mesalamine (n = 136), oral CS (n = 144), or intravenous CS (n = 148). Twenty-five (6%) underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. Further, 32/35 patients who had colectomy failed infliximab. An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001). A logistic regression model predicting colectomy using the PUCAI, hemoglobin, and erythrocyte sedimentation rate had a receiver operating characteristic area under the curve of 0.78 (95% confidence interval [0.73, 0.84]). Addition of a pretreatment rectal gene expression panel reflecting activation of the innate immune system and response to external stimuli and bacteria to the clinical model improved the receiver operating characteristic area under the curve to 0.87 (95% confidence interval [0.82, 0.91]). CONCLUSIONS: A small group of children newly diagnosed with severe UC still require colectomy despite current therapies. Our gene signature observations suggest additional targets for management of those patients not responding to current medical therapies.

Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.