STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

Evaluation of Surface-Induced Dissociation Ion Mobility-Mass Spectrometry for Lipid Structural Characterization.

The complexity of the lipidome has necessitated the development of novel analytical approaches for the identification and structural analysis of morphologically diverse classes of lipids. At this time, a variety of dissociation techniques have been utilized to probe lipid decomposition pathways in search of structurally diagnostic fragment ions. Here, we investigate the application of surface-induced dissociation (SID), a fragmentation technique that imparts energy to the target molecule via collision with a coated surface, for the fragmentation of seven lipids across four major lipid subclasses. We have developed a tuning methodology for guiding the efficient operation of a previously developed custom SID device for molecules as small as ca. 300 Da with ion mobility analysis of the fragmentation products. SID fragmentation of the various lipids analyzed was found to generate fragment ions similar to those observed in CID spectra, but fragment ion lab frame onset energies were lower in SID due to the higher energy deposition via a more massive target. For the largest lipid evaluated (cardiolipin 18:1), SID produced chain fragment ions, which yielded analytically useful information regarding the composition of the acyl tails. Ion mobility provided an orthogonal dimension of separation and aided in assigning product ions to their precursors. Overall, the combination of SID and IM-MS is another potential methodology in the analytical toolkit for lipid structural analysis.

Urinary biomarkers associated with acute kidney injury in pediatric mechanical circulatory support patients.

BACKGROUND: In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS: This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS: Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS: Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population-based assessment in seven million children.

BACKGROUND: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. METHODS: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. RESULTS: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). CONCLUSIONS: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.

Female Athlete Research Camp: A Unique Model for Conducting Research in High-Performance Female Athletes.

PURPOSE: The purpose of this study is to describe the implementation of a novel research protocol for conducting research with highly trained female athletes, including characterizing menstrual cycle (MC) function, hormonal profiles and symptoms of the participating athletes. METHODS: Twenty-four Australian First Nation female Rugby League athletes completed this study, which involved 11 wk of cycle tracking, followed by attendance at a 5-wk training camp. Throughout the study, athletes completed a daily survey, reporting their MC function and any associated symptoms. During the training camp, athletes reported to the laboratory on three occasions and provided a venous blood sample, which was analyzed for reproductive hormones. For naturally cycling athletes (athleteNC, n = 11), this included phase 1, 2, and 4 of the menstrual cycle, whereas athletes using hormonal contraception (athleteHC; n = 13) were tested at three equally spaced time points in which consistent exogenous hormone provision occurred. RESULTS: In the athleteNC cohort, just one athlete reached criteria for classification as eumenorrheic, with five athletes showing evidence of MC dysfunction. The prevalence of symptoms on any given day was similar between athleteNC (33.7%) and athleteHC (22.9%; P = 0.376); however, more symptoms were reported in athleteNC, suggesting that they were more likely to report multiple symptoms. Regardless of MC function, there was a significant, positive association between bleeding and symptoms ( P < 0.001), where athletes were more likely to report one or more symptoms on bleeding (50.1%) compared with nonbleeding days (22.0%). CONCLUSIONS: We describe an innovative strategy to investigate the effect of MC function and MC phase in a high-performance sport environment, including approaches to address the challenges of undertaking research with female athletes with MC variability and those using exogenous hormonal therapies.

Measuring herbicide (73.3 % glyphosate) exposure response in Halophila ovalis (previously johnsonii) and Halodule wrightii seagrass.

We evaluated the effects of Roundup QuikPRO™ (73.3 % glyphosate) using real-world herbicide application treatments: (1) overspray (low-dose), (2) powder spill (high-dose), and (3) controls (no-dose). Seagrass and water quality were monitored to observe responses to acute herbicide application. Seagrass shoot densities significantly declined over time in high-dose treatments, whereas seagrass shoot densities in low-dose treatments were comparable to controls. In high-dose treatments, seagrass mortality increased over time, 100 % Halophila ovalis and 81 % Halodule wrightii mortality from day zero to 53. Collectively, glyphosate concentrations were negatively correlated with seagrass shoot densities, and positively correlated with water column nutrients (TN and TP). Based on these results we do not attribute local seagrass declines to low-dose glyphosate exposure, i.e., herbicide overspray events. However, we advise caution against improper herbicide handling, since glyphosate remained detectable in relatively high concentrations (<88 mg/L) after 53 days, resulting in seagrass mortality and increased water column nutrients.

Health Service Utilization and Its Associations with Depression and Sexual Risk Behaviors Among Transgender Women in Shanghai, China.

Purpose: Given the limited research on health care utilization among transgender women in China, we described the use of primary health care and gender-affirming health care, and the associations between utilization of gender-affirming health care and depression and sexual risk behaviors. Methods: We conducted a cross-sectional survey in 2017 among a purposive sample of transgender women in Shanghai, China (N=199). We examined correlates of health care utilization and its association with depression and sexual risk behaviors with Chi-square (χ2), Fisher's exact tests, and analysis of variance. Results: The majority of the sample (78.5%) only had physician appointments when having an illness, while about one-fifth of the sample had physician appointments for yearly checkups. Nineteen out of 199 participants (9.5%) received gender-affirming surgery, among which only five used hormone therapy prescribed by a doctor (26.3%). Receiving some form of gender-affirming surgery was associated with higher depression scores [Welch's F(2, 12.22)=4.16, p=0.04], engagement in sex work (p=0.001), having 7 or more male sexual partners in the last 30 days (p=0.003), lifetime unprotected sex with a man (p=0.050), and unprotected sex with a main partner (p=0.043). Compared with transgender women who received both breast augmentation and vulvo-vaginoplasty (mean=5.86), those who received breast augmentation only (mean=12.33) scored higher on depression (p=0.04). Conclusions: Access to gender-affirming health care is low among transgender women in this study. The utilization of gender-affirming surgery is associated with depression and sexual risk behaviors. Findings suggest China should establish national guidelines on transgender-related health care and set up more clinics to provide consultation and services for the transgender population in China.

Investigating Performance of the SLIM-Based High Resolution Ion Mobility Platform for Separation of Isomeric Phosphatidylcholine Species.

Lipids are structurally diverse molecules that play a pivotal role in a plethora of biological processes. However, deciphering the biological roles of the specific lipids is challenging due to the existence of numerous isomers. This high chemical complexity of the lipidome is one of the major challenges in lipidomics research, as the traditional liquid chromatography-mass spectrometry (LC-MS) based approaches are often not powerful enough to resolve these isomeric and isobaric nuances within complex samples. Thus, lipids are uniquely suited to the benefits provided by multidimensional liquid chromatography-ion mobility-mass spectrometry (LC-IM-MS) analysis. However, many forms of lipid isomerism, including double-bond positional isomers and regioisomers, are structurally similar such that their collision cross section (CCS) differences are unresolvable via conventional IM approaches. Here we evaluate the performance of a high resolution ion mobility (HRIM) system based on structures for lossless ion manipulation (SLIM) technology interfaced to a high resolution quadrupole time-of-flight (QTOF) analyzer to address the noted lipidomic isomerism challenge. SLIM implements the traveling wave ion mobility technique along an ∼13 m ion path, providing longer path lengths to enable improved separation of isomeric features. We demonstrate the power of HRIM-MS to dissect isomeric PC standards differing only in double bond (DB) and stereospecific number (SN) positions. The partial separation of protonated DB isomers is significantly enhanced when they are analyzed as metal adducts. For sodium adducts, we achieve close to baseline separation of three different PC 18:1/18:1 isomers with different cis-double bond locations. Similarly, PC 18:1/18:1 (cis-9) can be resolved from the corresponding PC 18:1/18:1 (trans-9) form. The separation capacity is further enhanced when using silver ion doping, enabling the baseline separation of regioisomers that cannot be resolved when measured as sodium adducts. The sensitivity and reproducibility of the approach were assessed, and the performance for more complex mixtures was benchmarked by identifying PC isomers in total brain and liver lipid extracts.

The Impact of Health Geography on Public Health Research, Policy, and Practice in Canada.

The link between geography and health means that the places we occupy-where we are born, where we live, where we work, and where we play-have a direct impact on our health, including our experiences of health. A subdiscipline of human geography, health geography studies the relationships between our environments and the impact of factors that operate within those environments on human health. Researchers have focused on the social and physical environments, including spatial location, patterns, causes of disease and related outcomes, and health service delivery. The work of health geographers has adopted various theories and philosophies (i.e., positivism, social interactionism, structuralism) and methods to collect and analyze data (i.e., quantitative, qualitative, spatial analysis) to examine our environments and their relationship to health. The field of public health is an organized effort to promote the health of its population and prevent disease, injury, and premature death. Public health agencies and practitioners develop programs, services, and policies to promote healthy environments to support and enable health. This commentary provides an overview of the recent landscape of health geography and makes a case for how health geography is critically important to the field of public health, including examples from the field to highlight these links in practice.

Electronic Structure and Anion Photoelectron Spectroscopy of Uranium-Gold Clusters UAun-, n = 3-7.

A collaborative effort between experiment and theory toward elucidating the electronic and molecular structures of uranium-gold clusters is presented. Anion photoelectron spectra of UAun-(n = 3-7) were taken at the third (355 nm) and fourth (266 nm) harmonics of a Nd:YAG laser, as well as excimer (ArF 193 nm) photon energies, where the experimental adiabatic electron affinities and vertical detachment energies values were measured. Complementary first-principles calculations were subsequently carried out to corroborate experimentally determined electron detachment energies and to determine the geometry and electronic structure for each cluster. Except for the ring-like neutral isomer of UAu6 where one unpaired electron is spread over the Au atoms, all other neutral and anionic UAun clusters (n = 3-7) were calculated to possess open-shell electrons with the unpaired electrons localized on the central U atom. The smaller clusters closely resemble the analogous UFn species, but significant deviations are seen starting with UAu5 where a competition between U-Au and Au-Au bonding begins to become apparent. The UAu6 system appears to mark a transition where Au-Au interactions begin to dominate, where both a ring-like and two heavily distorted octahedral structures around the central U atom are calculated to be nearly isoenergetic. With UAu7, only ring-like structures are calculated. Overall, the calculated electron detachment energies are in good agreement with the experimental values.

Leveling the Battlefield: Development of a Pre-Deployment Vascular Access Curriculum for the Nonsurgical Provider.

INTRODUCTION: Timely vascular access is critical, as hemorrhage is the number one cause of death on the battlefield. Anecdotal evidence in the Military Health System identified an operationally relevant procedural skills gap in vascular access, and data exist in civilian literature showing high rates of iatrogenic injuries when lack of robust procedural opportunity exists. Multiple pre-deployment training courses are available for surgical providers, but no comprehensive pre-deployment vascular access training exists for non-surgical providers. METHODS: This mixed-method review aimed to find relevant, operationally focused, vascular access training publications. A literature review was done to identify both relevant military clinical practice guidelines (CPGs) and full text articles. Reviewers also investigated available pre-deployment trainings for both surgeons and non-surgeons in which course administrators were contacted and details regarding the courses were described. RESULTS: We identified seven full-text articles and four CPGs. Two existing surgical training programs and Army, Navy, and Air Force pre-deployment training standards for non-surgeons were evaluated. CONCLUSION: A cost-effective and accessible pre-deployment curriculum utilizing reviewed literature in a "learn, do, perfect" structure is suggested, building on pre-existing structures while incorporating remotely accessible didactics, hands-on practice with portable simulation models, and live-feedback training.

Female Athlete Representation and Dietary Control Methods Among Studies Assessing Chronic Carbohydrate Approaches to Support Training.

The aim of this audit was to assess the representation of female athletes, dietary control methods, and gold standard female methodology that underpins the current guidelines for chronic carbohydrate (CHO) intake strategies for athlete daily training diets. Using a standardized audit, 281 studies were identified that examined high versus moderate CHO, periodized CHO availability, and/or low CHO, high fat diets. There were 3,735 total participants across these studies with only ∼16% of participants being women. Few studies utilized a design that specifically considered females, with only 16 studies (∼6%) including a female-only cohort and six studies (∼2%) with a sex-based comparison in their statistical procedure, in comparison to the 217 studies (∼77%) including a male-only cohort. Most studies (∼72%) did not provide sufficient information to define the menstrual status of participants, and of the 18 studies that did, optimal methodology for control of ovarian hormones was only noted in one study. While ∼40% of male-only studies provided all food and beverages to participants, only ∼20% of studies with a female-specific design used this approach for dietary control. Most studies did not implement strategies to ensure compliance to dietary interventions and/or control energy intake during dietary interventions. The literature that has contributed to the current guidelines for daily CHO intake is lacking in research that is specific to, or adequately addresses, the female athlete. Redressing this imbalance is of high priority to ensure that the female athlete receives evidence-based recommendations that consider her specific needs.

Intramolecular Proton Transfer in the Radical Anion of Cytidine Monophosphate Sheds Light on the Sensitivities of Dry vs Wet DNA to Electron Attachment-Induced Damage.

Single-strand breaks (SSBs) induced via electron attachment were previously observed in dry DNA under ultrahigh vacuum (UHV), while hydrated electrons were found not able to induce this DNA damage in an aqueous solution. To explain these findings, crossed electron-molecular beam (CEMB) and anion photoelectron spectroscopy (aPES) experiments coupled to density functional theory (DFT) modeling were used to demonstrate the fundamental importance of proton transfer (PT) in radical anions formed via electron attachment. Three molecular systems were investigated: 5'-monophosphate of 2'-deoxycytidine (dCMPH), where PT in the electron adduct is feasible, and two ethylated derivatives, 5'-diethylphosphate and 3',5'-tetraethyldiphosphate of 2'-deoxycytidine, where PT is blocked due to substitution of labile protons with the ethyl residues. CEMB and aPES experiments confirmed the cleavage of the C3'/C5'-O bond as the main dissociation channel related to electron attachment in the ethylated derivatives. In the case of dCMPH, however, electron attachment (in the aPES experiments) yielded its parent (intact) radical anion, dCMPH-, suggesting that its dissociation was inhibited. The aPES-measured vertical detachment energy of the dCMPH- was found to be 3.27 eV, which agreed with its B3LYP/6-31++G(d,p)-calculated value and implied that electron-induced proton transfer (EIPT) had occurred during electron attachment to the dCMPH model nucleotide. In other words, EIPT, subduing dissociation, appeared to be somewhat protective against SSB. While EIPT is facilitated in solution compared to the dry environment, the above findings are consistent with the stability of DNA against hydrated electron-induced SSB in solution versus free electron-induced SSB formation in dry DNA.

Utilizing Latent Class Analysis to Assess the Association of Intersectional Stigma on Mental Health Outcomes Among Young Adult Black, Indigenous, and Sexual Minority Women of Color.

Purpose: Discrimination has detrimental effects on mental health, particularly among Black, Indigenous, and people of color who are also sexual minority women (BIPOC SMW); however, measurement of multiple intersecting forms of discrimination (e.g., race, gender, and sexual identity discrimination among BIPOC SMW) poses methodological challenges. This analysis uses latent class analysis (LCA) to examine the influences of discrimination on mental health in a convenience sample of BIPOC SMW. Methods: Online survey data from BIPOC SMW aged 18-29 years (n = 324) were used to estimate latent classes for discrimination type (race, gender, and sexual identity). Data for this study were collected from July to October 2018. Adjusted linear regressions examined the influences of discrimination profiles on perceived stress and depressive symptoms. Results: Utilizing LCA, the following four classes emerged: (1) low discrimination; (2) mid-level discrimination; (3) high racial, medium gender, and low sexual identity discrimination; (4) high discrimination. Classes 3 and 4 were positively associated with perceived stress and depressive symptoms relative to Class 1 in adjusted models. Conclusion: This analysis highlights the importance of intersectionality and the adverse impact of multiple forms of discrimination on mental health outcomes for BIPOC SMW. Respondents reporting higher levels of racial or multiple forms of discrimination had poorer mental health outcomes. LCA is a promising analytical tool for investigating intersectional stigma and discrimination. There is an urgent need to develop tailored, culturally appropriate intersectional mental health interventions to address the multiple identities and oppressions faced by BIPOC SMW.

Leveraging green infrastructure for efficient treatment of reclaimed water.

Global water scarcity necessitates creative, yet practical, solutions to meet ever-growing demand. Green infrastructure is increasingly used in this context to provide water in environmentally friendly and sustainable ways. In this study, we focused on reclaimed wastewater from a joint gray and green infrastructure system employed by the Loxahatchee River District in Florida. The water system consists of a series of treatment stages for which we assessed 12 years of monitoring data. We measured water quality after secondary (gray) treatment, then in onsite lakes, offsite lakes, landscape irrigation (via sprinklers), and ultimately in downstream canals. Our findings show gray infrastructure designed for secondary treatment, integrated with green infrastructure, achieved nutrient concentrations nearly equivalent to advanced wastewater treatment systems. For example, we observed a dramatic decline in mean nitrogen concentration from 19.42 mg L-1 after secondary treatment to 5.26 mg L-1 after spending an average of 30 days in the onsite lakes. Nitrogen concentration continued to decline as reclaimed water moved from onsite lakes to offsite lakes (3.87 mg L-1) and irrigation sprinklers (3.27 mg L-1). Phosphorus concentrations exhibited a similar pattern. These decreasing nutrient concentrations led to relatively low nutrient loading rates and occurred while consuming substantially less energy and producing fewer greenhouse gas emissions than traditional gray infrastructure-at lower cost and higher efficiency. There was no evidence of eutrophication in canals downstream of the residential landscape whose sole source of irrigation water was reclaimed water. This study provides a long-term example of how circularity in water use can be used to work toward sustainable development goals.

Ethnic-specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high-dose methotrexate.

BACKGROUND: High-dose methotrexate (HD-MTX; 5000 mg/m2 ) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD-MTX in an ethnically diverse population of patients with ALL. METHODS: The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD-MTX at Texas Children's Cancer Center (2010-2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke-like symptoms) occurring within 21 days of HD-MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity. RESULTS: Overall, 351 patients (58.1% Latino) who received 1183 HD-MTX infusions were evaluated. Thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three-fold increased odds (OR, 3.32; 95% CI, 0.98-11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six-fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39-24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%. CONCLUSIONS: The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.

Antineurofascin IgG2-associated paediatric autoimmune nodopathy.

In this case series of four paediatric patients, we present the first described cases of immunotherapy-responsive autoimmune nodopathy with IgG2 antineurofascin antibodies. In three cases, the antineurofascin antibodies were predominantly of the IgG2 subclass, a novel finding in comparison to previously described adult cases where IgG4 and/or IgG1/3 have typically been described. One patient had low signal for IgG2 with predominant IgG1 and IgG4 antibodies, a pattern commonly seen in adult patients. Two patients had antibodies targeting all three neurofascin isoforms (155, 186, and 140), whereas antibodies in the sera from the third targeted only the nodal isoforms 186 and 140, and the fourth patient only neurofascin 155. The three patients with IgG2 predominant antibodies appear to be responsive to intravenous immunoglobulin (IVIG) to varying degrees thus far, whereas the patient with IgG1/4 antibodies had poor response to IVIG but good response to steroids. Although the full clinical significance of IgG2 predominant antineurofascin antibodies in the context of childhood polyneuropathy remains unclear, emerging evidence of serological-phenotypic correlation may inform prognostication and therapeutic decision-making, warranting further study into this area. WHAT THIS PAPER ADDS: Paediatric immunotherapy-responsive nodopathies were associated with antineurofascin antibodies predominantly of the IgG2 subclass in 3 out of 4 patients. Identification of antibodies and understanding their phenotypic relevance could predict response to treatment and guide therapeutic decision-making in children.

Fueling the Female Athlete: Auditing Her Representation in Studies of Acute Carbohydrate Intake for Exercise.

PURPOSE: The aim of this audit was to assess the representation of female athletes within the literature that has led to current guidelines for carbohydrate (CHO) intake in the acute periods surrounding exercise and the quality of this research. METHODS: We conducted a standardized audit of research assessing CHO loading protocols, CHO mouth rinse, and CHO intake before, during, and after exercise. RESULTS: A total of 937 studies were identified in this audit. There were a total of 11,202 participants across these studies, with only ~11% being women. Most studies involved male-only cohorts (~79%), with a mere 38 studies (~4%) involving female-only cohorts and 14 studies (~2%) including a methodological design for comparison of sex-based responses. The frequent use of incorrect terminology surrounding menstrual status and the failure of most studies (~69%) to provide sufficient information on the menstrual status of participants suggests incomplete understanding and concern for female-specific considerations among researchers. Of the 197 studies that included women, only 13 (~7%) provided evidence of acceptable methodological control of ovarian hormones, and no study met all best-practice recommendations. Of these 13 studies, only half also provided sufficient information regarding the athletic caliber of participants. The topics that received such scrutiny were CHO loading protocols and CHO intake during exercise. CONCLUSIONS: The literature that underpins the current guidelines for CHO intake in the acute periods around exercise is lacking in high-quality research that can contribute knowledge specific to the female athlete and sex-based differences. New research that considers ovarian hormones and sex-based differences is needed to ensure that the recommendations for acute CHO fueling provided to female athletes are evidence based.