Faculty Bibliography

IMPORTANCE/UNASSIGNED:Chordoma is a rare malignant bone tumor with high local recurrence, metastatic spread in 40% to 60% of patients over the disease course, and significant morbidity. Because of its rarity, anatomical complexity, and prolonged natural history, high-quality evidence to guide management is limited. International consensus guidelines for localized chordoma were first published in 2015; however, advances in pathology, imaging, surgery, radiotherapy, and supportive care since then necessitate updated multidisciplinary recommendations. OBJECTIVE/UNASSIGNED:To update and expand the 2015 consensus recommendations on the diagnosis, treatment, and follow-up of pediatric and adult patients with primary, localized chordoma. EVIDENCE REVIEW/UNASSIGNED:In June 2025, a meeting of the Global Chordoma Consensus Group was held in Milan, Italy, that included experts from all relevant specialties as well as patient representatives. A comprehensive literature review guided structured discussions on the management of primary localized disease. Levels of evidence and grades of recommendation were assigned. FINDINGS/UNASSIGNED:A total of 305 articles were included in the literature review. Management strategies were stratified by anatomical site (skull base, mobile spine, and sacrum). The central principal of care was treatment at experienced, multidisciplinary centers, with maximally safe surgery followed by high-dose, highly conformal radiotherapy. Guidance was provided on diagnosis, surgical approaches, and radiotherapy planning for each anatomical site. Systemic therapy options; long-term, risk-adapted follow-up; and supportive, palliative, and rehabilitative care were also addressed. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This global consensus statement provided updated multidisciplinary guidance for the management of primary, localized chordoma. It aimed to harmonize clinical practice, support shared decision-making, and identify priorities for future collaborative research in this rare and challenging disease.

BackgroundFor many transgender young adults considering gender affirming hysterectomy, discussions may begin prior to the age of 18. However, the extent of their relevant understanding is unclear.ObjectivesDetermining whether transgender men who started testosterone during adolescence correctly understand their reproductive anatomy and the nature and implications of hysterectomy with or without oophorectomy as well as the extent of their recalled counseling and related beliefs.DesignCross-sectional survey.MethodsAn anonymous REDCap survey, sent both through community message boards and the Prolific survey platform, assessing knowledge of and experiences with reproductive and sexual health care in the context of gender affirming care. Analyses were descriptive.ResultsOf 125 respondents, most had initiated testosterone between age 17 and 18 (n=85,67%). Roughly two-thirds (n=80, 64%) wanted or had had a hysterectomy, but only 48% (n=60) wanted or had had an oophorectomy. The majority correctly identified the purpose of the uterus (n=116, 93%) and ovaries (n=88, 70%) ovaries, as well as their physical relationship to each other (n=103, 82%). Fewer correctly defined a hysterectomy (n=78, 64%). Only a third of our respondents reported ever being counseled about the uterus (n=42, 35%) and the ovaries (n=43, 36%). Roughly one-third recalled counseling about testosterone's effects on the uterus and ovaries, primarily by their testosterone prescriber. Most people were uncertain of their knowledge of surgical requirements, but those who felt confident enough to state beliefs tended to be correct.ConclusionMost respondents who started testosterone prior to 18 had basic knowledge of the function and location of the uterus and ovaries, with less knowledge about gender-affirming surgeries. There is a need for clear guidelines to inform clinical counseling in adolescence, as transgender patients may start thinking about hysterectomy for gender affirmation during adolescence, even if the procedure is not accessible until they reach majority.

Individuals with Down syndrome (DS) produce less saliva for unknown reasons resulting in chronic periodontal disease with systemic detrimental effects. Using the (Dp(16)1Yey) mouse model of DS we define the molecular mechanisms of hyposalivation and potential links to periodontal disease. We show that Dp(16)1Yey mice produce less saliva and have a higher immune burden in the salivary glands. We demonstrate that store operated calcium entry (SOCE), required for saliva secretion, is deficient in the salivary glands of Dp(16)1Yey mice. SOCE is also reduced in iPSCs from an individual with DS. We show that the oral and gut microbiomes of Dp(16)1Yey mice have abundant succinate-associated microbes and high succinate levels in the serum. We highlight associations between altered Ca²⁺ handling and hyposalivation, dysbiosis, and periodontal disease in DS. The administration of pilocarpine in Dp(16)1Yey mice increased salivation, suggesting that cholinergic agonists might be useful to improve the oral health of individual with DS.

The September 11, 2001, terrorist attacks on the World Trade Center (9/11) exposed both disaster responders and community members to a complex mixture of environmental contaminants, resulting in long-term health consequences. While clinical and research efforts have characterized health effects among adult survivors (community members) and responders, less is known about individuals who were exposed in utero, during childhood, adolescence, or young adulthood. Recognizing this gap, Congress amended the Public Health Service Act (42 U.S.C. § 300mm-51(c)) to establish a Research Cohort for Emerging Health Impacts on Youth to promote research on those individuals who were 21 years of age or younger at the time of exposure. This Commentary reviews the historical development of post-9/11 monitoring, treatment, and research programs, and discusses the unique challenges of conducting research in such a youth cohort 25 years after the event. A central coordinating center supported by community-based field sites offers a promising approach to promoting research among this cohort and addressing critical gaps in understanding the lifelong impacts of 9/11 exposures.

Obstructive sleep apnea (OSA) is a common but underdiagnosed and undertreated sleep disorder among people with epilepsy (PWE). In PWE, this sleep disorder is often managed as a comorbid condition rather than a contributor to epilepsy outcomes. For many years, OSA has been associated with higher seizure burden and interictal epileptiform discharges. Emerging evidence links OSA to late onset epilepsy (LOE) and increased risk markers for sudden unexpected death in epilepsy (SUDEP). This evidence also suggests that treating OSA with continuous positive airway pressure may improve seizure control. This critical review of the literature posits that OSA should be viewed as a modifiable risk factor for PWE. We apply the Bradford Hill criteria for causation as a framework to appraise the evidence connecting OSA with (1) seizure severity, (2) incident LOE, and (3) SUDEP risk. OSA supports eight of nine Bradford Hill criteria to varying degrees: strength, consistency, temporality, biological gradient, plausibility, coherence, analogy, and experiment, but not specificity. Key limitations include confounding, selection and adherence biases, and limited randomized evidence. However, the evidence supports integrating systematic OSA screening and evidence-based treatment into epilepsy care. Future research should prioritize randomized trials to assess the impact of OSA treatment on epilepsy incidence, severity, and SUDEP risk.

All life-forms can be infected by viruses with double-stranded DNA genomes. Typically, permissive cells support a productive infection, where virus gene expression and DNA replication yield virion progeny resulting in cell death and/or immune clearance. Alternatively, certain viruses, including prokaryotic temperate bacteriophage and herpesviruses that infect multicellular eukaryotes, establish a persistent state in permissive cells (lysogeny in bacteria, latency in eukaryotes) where productive infection is repressed, permitting viral genome maintenance while deferring virus replication and particle assembly until conditions shift to favor productive infection. We compare examples drawn from temperate bacteriophage with more recent developments using the prototypical human α-herpesvirus herpes simplex virus 1 to illustrate mechanisms that control persistence or foster productive infection. Remarkably, despite vast evolutionary distance, similar physiological cues (genome integrity, nutrient status, cell communication signals) govern the switch between persistence and productive infection. Thus, monitoring basic homeostatic indicators determines lysogenic/latent or productive infection outcomes, representing a conserved virus persistence strategy.

PURPOSE/UNASSIGNED:To compare a strategy utilizing testing to guide treatment, also known as selective therapy, to a strategy of initiating interventions without testing, termed empiric therapy, on urinary supersaturation of calcium oxalate and calcium phosphate. MATERIALS AND METHODS/UNASSIGNED:In this single-center trial, adult individuals with recurrent idiopathic calcium stone disease were randomized to either an empiric or selective strategy. Participants received 24-hour urine testing at baseline, 4 weeks, and 8 weeks. Treatment in the empiric arm was comprised of dietary and fluid counseling and pharmacologic treatment with indapamide and potassium citrate irrespective of 24-hour urine results. For the selective arm, diet and pharmacologic treatments, which included indapamide, potassium citrate, and/or allopurinol, were tailored based on urine testing at baseline and 4 weeks. The primary outcome was urinary supersaturation of calcium oxalate and calcium phosphate at 8 weeks. RESULTS/UNASSIGNED:= 0.58). Similarly, there were no significant differences at 8 weeks in urine volume and pH, or in excretion of calcium, oxalate, citrate, uric acid, and sodium. CONCLUSIONS/UNASSIGNED:In this short-term trial among individuals at high-risk for stone recurrence, there was no statistically significant difference in the urinary stone risk comparing an empiric versus selective strategy for kidney stone prevention.

As the prevalence of inflammatory bowel disease (IBD) rises rapidly among older adults, gastroenterologists and other health care providers increasingly face challenges in managing age-related comorbidities, polypharmacy, and functional impairments such as frailty and sarcopenia. This narrative review proposes a dual approach to management by optimizing care for patients aged >60 years while promoting the healthy aging of those aged 40-60 years. For patients aged >60 years, we emphasize prescribing effective corticosteroid-sparing medications to control inflammation, conducting medication reconciliations to assess appropriateness and drug interactions, and evaluating baseline hepatic and renal function for necessary dose adjustments. For patients aged 40-60 years, we advise regular screening and nutritional counseling to delay the onset of age-related comorbidities and recommend targeting endoscopic remission to modify the disease course and reduce complications and disability later in life. Given that patients with IBD receiving long-term immunosuppression are at increased risk of infections, adherence to age-appropriate vaccination schedules is also recommended. A proactive and personalized approach to disease management has the potential to optimize quality of life for older adults with IBD.

Learners who are neurodivergent, including individuals with autism, attention-deficit/hyperactivity disorder, learning disabilities, and related cognitive variations, remain underrecognized and insufficiently supported within medical education. Despite increasing representation, training environments continue to privilege rigid cognitive norms rooted in ableist assumptions and the ideal-physician archetype, reinforcing conformity, endurance, and neurotypical professionalism. This article synthesizes emerging literature on neurodivergence in medical education, highlighting persistent structural gaps in policy implementation, learning environments, and faculty evaluation practices. It examines the consequences of structural ableism, including masking, burnout, mental health strain, and attrition among trainees who are neurodivergent. It further reviews growing physician-led advocacy, mentorship networks, and institutional shifts toward neuroinclusive practices. Pediatrics is uniquely positioned to lead transformation, given its grounding in developmental variability, family-centered care, and communication across cognitive differences. Embracing neurodiversity in pediatric training offers a pathway to more inclusive educational cultures, improved patient care, and a physician workforce that reflects the populations it serves.