Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by ...clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1(+/+) stem cell line do not display the hyperexcitability phenotype. SOD1(A4V/+) ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons can reveal disease-related mechanisms and identify therapeutic candidates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Severe pediatric obesity (class II or higher; body mass index calculated as weight in kilograms divided by height in meters squared ≥120% above the 95th percentile or ≥35) is a national public health ...crisis affecting more than 4.5 million children and adolescents in the United States. The prevalence of severe pediatric obesity has increased from 4.0% in 2000 to 6.0% in 2016.1 For children and adolescents with this disease, metabolic and bariatric surgery (MBS) is effective in achieving long-term weight loss and resolution of comorbidities.2,3 We sought to define contemporary trends in the use of MBS among US children, adolescents, and young adults with severe obesity.
Disparities in health care access, quality, and outcomes for pediatric patients, and their relationship to race and socioeconomic status (SES) have been extensively documented. The underlying causes ...behind such disparities have been less carefully studied, as clinicians and researchers often fail to look past immutable features such as race, into modifiable factors like social determinants of health (SDOH). A child's environment affects their patterns of social engagement, sense of security, and overall well-being. Resources such as affordable housing, access to education, public safety, and availability of healthy foods and safe play spaces impact and enhance quality of life, and have significant influence on both health and health care outcomes. These upstream indicators are often unrecognized or misidentified as health concerns. Few pediatric surgery publications discuss SDOH and their effects on children. This paper aims to introduce the five domains of SDOH (economic stability, education, social and community context, health and healthcare, and neighborhood and built environment) along with strategies to identify and address needs in these domains from a provider, hospital, and health system's perspective. It is anticipated that this information will serve as a foundation for pediatric surgeons to understand and develop processes that ameliorate disparities related to SDOH and improve surgical outcomes and the well-being of all children.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lifestyle modifications focused on diet, physical activity, and behavior have a modest impact on weight reduction in children, adolescents, and young adults (YA) with overweight and obesity. Several ...anti-obesity medications (AOMs) have been approved by the Food and Drug Administration (FDA) for use among adult patients with a body mass index (BMI) ≥27 kg/m
and at least one obesity-related illness. However, only two FDA-approved AOMs are available for use in children and adolescents, which leads to the frequent off-label use of adult AOMs among this population. We sought to investigate current prescribing patterns of AOMs from school age through to young adulthood in a large unified health system. Using a centralized clinical data registry containing the health data of ~6.5 million patients, individuals aged 5-25 years old with overweight and obesity who were taking one of eight commonly prescribed AOMs from 2009 to 2018 were extracted. A total of 1,720 patients were identified, representing 2,210 medication prescribing instances. The cohort was further stratified as children (5-12 years old), adolescents (13-18 years old), and YA (19-25 years old). The mean BMI at the time of medication initiation was 34.0, 39.1, and 39.6 kg/m
, respectively, which corresponded to a BMI
-score (BMIz) of 2.4 and 2.3 for children and adolescents, respectively. Metformin was the most commonly prescribed medication across all ages, including off-label use for weight-loss among children and adolescents. The most commonly off-label prescribed AOM among YA was topiramate. Multivariable analyses demonstrated phentermine was the most effective AOM, with a 1.54% total body weight among YA (
= 0.05) and a 0.12 decrease in BMIz among adolescents (
= 0.003) greater final weight loss when compared to the respective overall frequency-weighted means. Our study demonstrates a statistically significant weight loss among adolescents and young adults on select pharmacotherapy. The small magnitude of this effect should be interpreted carefully, as it is likely an underestimate in the absence of a true control group. Pharmacotherapy should therefore be considered in conjunction with other multimodal therapies such as lifestyle modification and metabolic and bariatric surgery when treating overweight and obesity.
To characterize the rates and variability in substance screening among adult trauma patients in the U.S.
Emergency Department trauma visits provide a unique opportunity to identify patients with ...substance use disorders. Despite the existence of screening guidelines, underscreening and variability in screening practices remain.
Retrospective cohort study including adult trauma patients (18- 64-year-old) from the ACS-TQIP 2017-18 database. Multivariable logistic regressions were performed to adjust for demographics, clinical, and facility factors, and marginal probabilities were calculated using these multivariable models. The primary outcomes were substance screening and positivity, which were defined relative to the observation-weighted grand mean (mean).
2,048,176 patients were contained in the TQIP dataset, 809,878 (39.5%) were screened for alcohol (20.8% positive), and 617,129 (30.1%) were screened for drugs (37.3% positive). After all exclusion criteria were applied, 765,897 patients were included in the analysis, 394,391 (52.9%) were screened for alcohol (22.1% tested positive), and 279,531 (36.5%) were screened for drugs (44.3% tested positive). Among the patients included in our study, significant variability in screening rates existed with respect to demo-graphic, trauma mechanism, injury severity, and facility factors. Furthermore, in several cases, patient subpopulations who were less likely to be screened were in fact more likely to screen positive or vice versa.
Effective substance-screening guidelines should be predicated on achieving universal screening. Current lapses in screening, along with the observed variability, likely affect different patient populations in disparate manners and lead to both under-detection as well as waste of valuable resources.
To review the racial composition of the study populations that the current USPSTF screening guidelines for lung, breast, and colorectal cancer are based on, and the effects of their application ...across non-white individuals.
USPSTF guidelines commonly become the basis for establishing standards of care, yet providers are often unaware of the racial composition of the study populations they are based on.
We accessed the USPSTF screening guidelines for lung, breast, and colorectal cancer via their website, and reviewed all referenced publications for randomized controlled trials (RCTs), focusing on the racial composition of their study populations. We then used PubMed to identify publications addressing the generalizability of such guidelines across non-white individuals. Lastly, we reviewed all guidelines published by non-USPSTF organizations to identify the availability of race-specific recommendations.
Most RCTs used as basis for the current USPSTF guidelines either did not report race, or enrolled cohorts that were not representative of the U.S. population. Several studies were identified demonstrating the broad application of such guidelines across non-white individuals can lead to underdiagnosis and higher levels of advanced disease. Nearly all guideline-issuing bodies fail to provide race-specific recommendations, despite often acknowledging increased disease burden among non-whites.
Concerted efforts to overcome limitations in the generalizability of RCTs are required to provide screening guidelines that are truly applicable to non-white populations. Broader policy changes to improve the pipeline for minority populations into science and medicine are needed to address the ongoing lack of diversity in these fields.
Purpose
For children and adolescents with severe obesity, metabolic and bariatric surgery including laparoscopic sleeve gastrectomy (LSG) is increasingly used to facilitate weight loss and reduce ...associated medical problems. Outcomes of LSG are understudied among patients under age 15 years. We sought to examine surgical complications and weight loss outcomes among children and adolescents who underwent LSG.
Materials and Methods
This is a single-center retrospective cohort analysis at a high-volume metropolitan children’s hospital in the northeast USA between 2011 and 2021. Weight loss was assessed at routine follow-up appointments for up to 36 months postoperatively.
Results
There were 12 patients under 13 years of age (< 13), 45 from 13 up to 15 years of age (13–14), and 57 patients aged 15 years or over (≥ 15). Among all patients, 70% were female, 41% were Hispanic, and 18% were non-Hispanic Black. There were no operative mortalities. Two patients had surgical complications requiring reoperation. Follow-up beyond 6 months occurred for 62% of patients. Weight loss was evident for each group at all time points, and there was no statistically significant difference among groups at any time point. BMI
Z
-score reduction at 6 months was 1.53 for the < 13 group, 0.89 for the 13–14 group, and 0.86 for the ≥ 15 group and at 36 months was 1.79, 1.50, and 1.16, respectively.
Conclusion
These results support that LSG is a safe and effective method of achieving weight loss for young adolescents with severe obesity. Strategies to promote postoperative follow-up are needed.
Graphical Abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Obesity is a significant public health concern in children. The American Academy of Pediatrics recommends the use of metabolic and bariatric surgery (MBS) in children with severe obesity, however; ...MBS remains underutilized in part due to lack of access. This study aims to characterize the prevalence of pediatric obesity and compare this to regional pediatric MBS provider availability.
State-specific prevalence rates of childhood obesity in children aged 10-17 were obtained from the National Survey of Children's Health. The member directory provided by the American Society for Metabolic and Bariatric Surgeons was used to identify all pediatric MBS providers and used to calculate the prevalence of MBS providers by state.
The five states with the highest prevalence rates of childhood obesity were Kentucky, Mississippi, Louisiana, West Virginia, and Alabama. The five states with the highest prevalence (per 100,000 children with obesity) of MBS providers doing pediatric cases were North Dakota, New Jersey, Kansas, New York, and Utah. Notably, there was a negative correlation between the states with the lowest prevalence of pediatric MBS providers and states with the highest prevalence of childhood obesity (r −0.40, ∗P = 0.002).
Our study demonstrates significant state-to-state variation in the prevalence of pediatric obesity and MBS provider availability by state as a proxy for access to surgical care for pediatric obesity. Further work to establish accessible multidisciplinary pediatric weight loss centers is needed to ensure that children and adolescents with obesity receive thorough evaluation and have access to MBS.
•Pediatric and adolescent obesity is a significant public health issue for which all children who meet criteria should be evaluated by a metabolic and bariatric surgeon.•The distribution of metabolic and bariatric surgeons who accept pediatric patients varies widely across the country and is negatively correlated with the population of children with obesity.•Establishment of regionally accessible weight loss centers is critical for meeting the clinical needs of children and adolescents with obesity across the country.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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