Faculty Bibliography

There are multiple etiologies for revision anterior cruciate ligament reconstruction (ACLR), including but not limited to infection, arthrofibrosis, and graft failure, which should be distinguished before revision ACLR. Graft failure occurs when the reconstructed ligament does not restore knee stability, and it includes both graft rupture and functional failure in the setting of an intact graft. The causes of graft failure following ACLR can be divided into surgeon-controllable factors (ie, tunnel position, graft choice, alignment) and patient-centric factors (ie, patient age, tissue quality from systemic disease or smoking, compliance/traumatic reruptures). The purpose of this review is to propose an organized, easy-to-remember algorithm for the workup of surgeon-controlled ACLR graft failure etiologies, represented by the acronym "FATAL Graft."

BACKGROUND:Maternal thyroid dysfunction and maternal depression during pregnancy may increase the risk of child behavioral and emotional problems. We sought to investigate the independent and interactive associations of these two risk factors with child behavior problems. METHODS:We combined data from four cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (N = 949). Maternal thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [fT4], thyroid peroxidase autoantibodies [TPO-Ab], fT4/TSH ratio) was measured predominantly during the first half of pregnancy. We harmonized maternal depression into a continuous measure of antepartum depressive symptomatology and a dichotomous measure reflecting (history of) clinical depression. Child internalizing and externalizing problems were harmonized to the T-score metric of the Child Behavior Checklist. We used multiple linear regression and random effects meta-analysis to assess the average relationship between each predictor and outcome, and the variability in these relationships across cohorts. RESULTS:Across cohorts, antepartum depressive symptomatology was positively associated with both internalizing (meta B = 2.879, 95 % CI 1.87-3.89, p < .001) and externalizing problems (meta B = 1.683, 95 % CI 0.67-2.69, p = .001). None of the indicators of maternal thyroid function was associated with child behavior problems across cohorts. TPO-Ab concentrations were positively associated with child externalizing problems only in offspring of depressed mothers (meta B = 3.063, 95 % CI 0.73-5.40, p = .010). CONCLUSIONS:This study supports the importance of maternal antepartum mental health for child behavior across diverse populations. However, we found little empirical evidence for an association between maternal thyroid function within the normal range during pregnancy and child behavioral problems.

This document is an update to the 2014 recommendations for optimizing the adequacy of bowel cleansing for colonoscopy from the US Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy. The US Multi-Society Task Force developed consensus statements and key clinical concepts addressing important aspects of bowel preparation for colonoscopy. The majority of consensus statements focus on individuals at average risk for inadequate bowel preparation. However, statements addressing individuals at risk for inadequate bowel preparation quality are also provided. The quality of a bowel preparation is defined as adequate when standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy. We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient. A same-day regimen is recommended as an acceptable alternative for individuals undergoing afternoon colonoscopy, but we suggest that a same-day regimen is an inferior alternative for individuals undergoing morning colonoscopy. We recommend limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. We suggest the adjunctive use of oral simethicone for bowel preparation before colonoscopy. Routine tracking of the rate of adequate bowel preparations at the level of individual endoscopists and at the level of the endoscopy unit is also recommended, with a target of >90% for both rates.

BACKGROUND/UNASSIGNED:For patients with alpha-1 antitrypsin (AAT) deficiency, AAT augmentation therapy can be an important part of care. However, for those who require a lung transplant (LT), there is currently only limited information to guide the use of AAT augmentation therapy post-LT. METHODS/UNASSIGNED:We identified all LT recipients from 2011-2021 in the Scientific Registry of Transplant Recipients with an AAT deficiency diagnosis. We categorized recipients by use of AAT augmentation therapy post-LT and compared their baseline characteristics using Fisher's exact test and Wilcoxon rank-sum tests. We used Kaplan-Meier analyses and estimated the average treatment effect (ATE) of post-LT AAT augmentation therapy on mortality and all-cause graft failure (ACGF). The ATE measures the observed effect we would see if everyone in the population received the intervention as opposed to just a subset. RESULTS/UNASSIGNED: = 0.02, log-rank test). CONCLUSIONS/UNASSIGNED:In our study, the use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.

Brain excitability is dysfunctional in epilepsy and overlapping neuropsychiatric conditions including autism spectrum disorder (ASD). Epilepsy and ASD are often attributed to malfunctioning coordination between synaptic excitation and inhibition. Dravet syndrome (DS) is a severe form of epilepsy arising from haploinsufficiency of the SCN1A gene that encodes the voltage-gated sodium channel Nav1.1. A DS mouse model (Scn1a^+/-) recapitulated essential features of DS and revealed that sodium current density was profoundly reduced in GABAergic inhibitory interneurons while pyramidal cells were spared, suggesting that DS is an "interneuronopathy." Further studies from the Catterall group and others have expanded this picture: DS symptoms, which include recurrent seizures, ataxia, cognitive impairment, ASD, and premature death, could be assigned in part to brain region-specific effects; the Nav1.1 mutations cause dysfunction in some subtypes of interneurons, not others, and are temporally restricted; DS-causing sodium channel mutations were found throughout SCN1A as well as in SCN1B, encoding the β1 subunit. Interest in therapeutic approaches was sparked by preclinical studies of cannabidiol (CBD) that led to the 2018 US Food and Drug Administration approval for treatment of seizures in patients with DS. Independent evidence showed that CBD antagonized GPR55, a G protein-coupled receptor activated by the lipid signaling molecule lysophosphatidylinositol (LPI). We summarized evidence from our group and others that CBD has a dual mechanism of action, targeting both ion channels and GPR55. CBD quells an epileptogenic vicious cycle: seizures strengthen LPI-GPR55 signaling while LPI-GPR55 signaling elevates the synaptic excitatory-inhibitory ratio, thereby promoting further seizures. SIGNIFICANCE STATEMENT: Modern medicine relies on ion channels and G protein-coupled receptors (GPCRs) as key targets. In studies of Dravet syndrome, a devastating genetic disorder with features of epilepsy and autism, William Catterall connected NaV1.1 mutations to deficient excitability of inhibitory neurons. He and his colleagues explored preclinical interventions using cannabidiol (CBD) and clobazam, opening the way to a current understanding of CBD's therapeutic mechanism. CBD affects both ion channels and GPR55, a GPCR activated by lysophosphatidylinositol, an activity-dependent lipid messenger, readjusting the synaptic excitatory-inhibitory ratio.

BACKGROUND:The primary goal of our study is to assess the national US prevalence of autism spectrum disorder (ASD), along with its socio-demographic characteristics, severity, and co-occurring medical and psychiatric disorders, using data from the 2020-2021 National Survey of Children's Health (NSCH). METHODS:We analyzed 2020-2021 NSCH data to estimate the prevalence of ever-diagnosed and current ASD among 79,182 children and adolescents (3-17 years). Univariate and multivariate regression models were used to examine associations between medical and psychiatric co-morbidities, socio-demographic factors, and ASD severity. RESULTS:< 0.001). CONCLUSIONS:This study provides updated prevalence estimates of ASD and highlights the high burden of co-morbidities, emphasizing the need for comprehensive, multidisciplinary approaches in ASD management. Additionally, our findings emphasize gender differences in ASD presentation, which should be considered in future research and clinical practice to ensure more tailored diagnostic and intervention strategies.

Pregnancy of unknown location is a condition in which a pregnancy test is positive, but no intrauterine or extrauterine pregnancy is visualized using transvaginal ultrasonography. We recommend using standardized nomenclature and definitions to describe intrauterine pregnancy (IUP), probable IUP, pregnancy of unknown location (PUL), probable ectopic pregnancy (probable EP), and ectopic pregnancy (EP) (Best Practice). Among abortion-seeking patients found to have a PUL, the incidence of ectopic pregnancy (EP) is 4-8%. We recommend clinical judgment in assessing the risk for EP in the setting of PUL; the absence of an intrauterine gestational sac (GS) or yolk sac should not delay care (GRADE 1B). In asymptomatic individuals with an undesired PUL who prefer to proceed with immediate treatment (medication or procedural management without delay) and have a low risk of EP, as determined by the clinician based on history, symptoms, and all other available data, we recommend medication management with mifepristone and misoprostol or procedural management via uterine aspiration and clear plans for ensuring pregnancy resolution in a timely fashion (GRADE 1B). While both medication and procedural management of undesired PUL are associated with earlier pregnancy resolution and identification of EP, the two main risks of inadequate follow-up include ongoing pregnancy and missing or delaying a subsequent diagnosis of EP. For individuals with PUL choosing immediate treatment with medication management, we recommend clinicians obtain a baseline serum quantitative hCG at the time of medication provision to aid in diagnosis and follow-up (GRADE 1A). Following medication management of PUL with mifepristone and misoprostol, we suggest a repeat serum quantitative hCG level, with pregnancy resolution defined as either a 50% decline or greater at 48-72 hours after misoprostol or an 80% decline or greater at seven days after mifepristone or 5-10 days after misoprostol (GRADE 2B). We recommend against direct extrapolation of follow-up recommendations from no-test abortion clinical protocols to individuals with a documented PUL treated with mifepristone and misoprostol, given the higher risk of EP among individuals with a known PUL (GRADE 1C). When uterine aspiration is performed at less than 42 days of gestation, including for individuals with PUL or probable IUP, and both chorionic villi and GS are not visualized, we recommend repeat ultrasonography (if an IUP or probable IUP was seen initially), serum quantitative hCG follow-up, or both (GRADE 1B). When both chorionic villi and GS are not visualized after uterine aspiration and serial serum hCG follow-up is warranted, we recommend testing on the day of the procedure and 24-72 hours later, with pregnancy resolution defined as greater than 50% decline 24 hours after aspiration, greater than 70% by 48 hours, or greater than 80% by approximately 72 hours (GRADE 1B).