United States

Background
Cognitive impairments are common but often neglected in Autism Spectrum Disorder (ASD). These deficits are particularly evident in domains such as working memory, processing speed, and short-term memory. Current pharmacological and behavioral interventions provide only limited improvements in cognition. Emerging research suggests that disrupted brain energy metabolism, including mitochondrial dysfunction and abnormalities in creatine-phosphocreatine systems, may contribute to these impairments. Creatine is a naturally occurring compound that supports ATP regeneration in high-demand brain regions and has shown cognitive benefits in other populations.

Objective
This commentary aimed to evaluate the rationale for using creatine as a cognitive enhancer in ASD by reviewing literature related to brain energy metabolism, creatine’s neurological functions, and cognitive outcomes in both clinical and preclinical studies.

Methods
We conducted a review of literature using PubMed, Google Scholar, and Scopus. Search terms included combinations of “creatine,” “cognition,” “autism,” “ASD,” “mitochondrial dysfunction,” “brain energy,” “working memory,” and “processing speed.” We selected peer-reviewed publications from the past two decades, including preclinical studies, clinical trials, case reports, and mechanistic reviews relevant to creatine and neuroenergetics in ASD.

Results
Multiple studies report that individuals with ASD show signs of mitochondrial dysfunction, altered oxidative stress responses, and reduced cerebral creatine levels. Preclinical models of creatine transporter deficiency replicate several features of ASD and demonstrate cognitive rescue with creatine analogs. In human populations, creatine supplementation has been associated with modest improvements in memory, attention, and processing speed. These effects are especially relevant to the cognitive domains most commonly affected in ASD.

Conclusion
Creatine supplementation may represent a low-risk and mechanistically plausible intervention for improving cognition in ASD. Based on the convergence of preclinical and translational evidence, we propose that future research should explore creatine as a cognitive enhancer in ASD, particularly in individuals with evidence of energy metabolism abnormalities. This commentary provides a foundation to guide the design of pilot studies targeting this promising yet understudied therapeutic pathway.


AMA Research Challenge 2025 

Thinking Creatively about Creatine- A New Direction for Cognitive Enhancement in Autism Spectrum Disorder


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Background: Molar-incisor hypomineralization (MIH) is a developmental enamel defect defined by sharply demarcated opacities and reduced mineralization. On average, 16% of children across many global populations are affected by MIH. Its etiology remains unclear, though abnormal retention of enamel matrix proteins is suspected. Ameloblastin (Ambn), a matrix protein secreted during the secretory stage of amelogenesis, plays a key role in enamel mineralization and structural organization of the hardest tissue in the human body. The goal of this study was to evaluate the effects of Ambn overexpression on enamel morphology and mineral content using a transgenic mouse model.

Methods: Enamel development was examined in six transgenic mouse lines with increasing Ambn overexpression driven by the amelogenin promoter. Continuously growing mandibular incisors were prepared for imaging from early to late stages of enamel formation, including sagittal orientation of the tooth surface and cross-sectional views of the enamel layer. Scanning electron microscopy (SEM) was used to assess cross-sectional and surface enamel morphology. Comparative analysis between wild-type and Ambn-overexpressing incisors included evaluation of the rod-interrod pattern, dentino-enamel junction (DEJ) clarity, enamel thickness, and surface characteristics. Mineral content was assessed using microcomputed tomography (microCT).

Results: Ambn overexpression led to distinct enamel abnormalities. SEM images of wild-type mandibular incisors showed well-defined rod-interrod architecture with a characteristic herringbone pattern and a continuous, glossy surface layer. In contrast, Ambn-overexpressing enamel displayed disrupted rod-interrod boundaries, particularly in the distal outer enamel, where prism-less enamel dominated. Proteinaceous material was visible between rods and along the surface. Cross-sections revealed that enamel thickness (DEJ to surface distance) remained consistent, but the width of the outer enamel zone increased. These defects corresponded to regions of reduced mineral density in microCT reconstructions and suggested impaired proteolytic clearance consistent with prolonged secretory stages. In more severe overexpression lines, the DEJ appeared blurred, and mineralization defects extended from the DEJ to the enamel surface.

Conclusion: Overexpression of Ambn in mice results in enamel defects closely resembling MIH, including opaque appearance, sharply defined lesion boundaries, and hypomineralization. SEM analysis revealed disrupted enamel organization, loss of rod-interrod structure, and abnormal protein retention, particularly in the outer enamel. These structural changes may weaken enamel, increase susceptibility to breakage, and predispose affected children to dental caries. Poor oral health at a young age may influence both overall health and self-confidence.

Disorganized and Hypomineralized Enamel Resembling Molar-Incisor Hypomineralization Induced by Ameloblastin Overexpression in Mice

Background:
Quadratus lumborum (QL) and transversus abdominis plane (TAP) blocks are frequently employed to manage perioperative pain in abdominal surgeries. Recent comparative analyses suggest that QL blocks may provide more effective and longer-lasting analgesia stemming from the spread of local anesthetic into the thoracolumbar fascia and paravertebral space, targeting both somatic and visceral nociception. However, existing studies often fail to account for the influence of adjunct analgesics, such as ketamine, which is known to reduce postoperative opioid needs by modulating central sensitization. This study aimed to (1) compare the effectiveness of QL versus TAP blocks on perioperative opioid use in abdominal surgery, (2) determine whether intraoperative adjunct analgesics mediates this relationship, and (3) determine whether block type moderated the relationship between pain intensity and opioid requirements.
Methods:
We retrospectively analyzed 111 adults who received either a QL (n = 57) or TAP (n = 54) block for abdominal surgery. Groups were matched on age, sex, ASA class, weight, and height. Primary outcomes included intraoperative ketamine dose, opioid requirements (intraoperative and PACU, measured in morphine milligram equivalents [MME]), pain scores (PACU and discharge), and recovery outcomes such as PACU duration, and length of stay. Between-group comparisons were performed using independent t-tests. Mediation and moderation analyses were conducted using PROCESS for SPSS (Models 4 and 1, respectively).
Results:
The TAP group received significantly more intraoperative ketamine [t (81.71) = −2.98, p = .004], while the QL group received significantly more opioids postoperatively in the PACU [t (87.70) = 2.55, p = .012] and overall [t (109) = 2.08, p = .040]. Mediation analysis indicated that intraoperative ketamine dose partially mediated the relationship between block type and total opioid consumption (indirect effect = 1.44 MME; 95% CI [0.03, 3.36]). Additionally, moderation analysis indicated that block type influenced the strength of the pain-opioid relationship (b = 2.86, SE = 1.27; t = 2.26, p = .026, 95% CI [0.35, 5.38]), such that average pain score was a significant positive predictor of total opioid requirements in the QL group [b = 2.45, p = .004], but not the TAP group [b = −0.41, p = .670].
Conclusion:
QL blocks were associated with greater postoperative opioid requirements, partially mediated by lower intraoperative ketamine administration. Moreover, pain intensity more strongly predicted opioid requirements among patients receiving QL blocks, suggesting differential analgesic mechanisms. These findings challenge the assumption that QL blocks are uniformly superior, highlighting the critical role of intraoperative adjuncts when designing individualized, opioid-

QL vs TAP Blocks in Abdominal Surgery: How Pain and Ketamine Influence Postoperative Opioid Use

Background: Risk-stratified lung cancer screening programs identify high-risk smokers but do not account for underlying genetic susceptibility. Many polygenic scores (PGS) have been developed for lung cancer, but it is unclear which, if any, are suitable for identifying high-risk individuals in the general population. 

Methods: We used a systematic review to identify published lung cancer PGS, which were implemented and validated in the UK Biobank (UKB) cohort. Performance (discrimination and accuracy) was compared. Subgroup analyses by sex, ethnicity, and smoking status identified differences across the population. We also divided the cohort into percentiles to assess PGS accuracy at identifying cases across risk categories.

Results: We identified 60 lung cancer PGS published since 2012, most derived from a narrow set of genome-wide association studies (GWAS) with overlapping single nucleotide polymorphisms (SNPs) and limited ethnic diversity (only one included African ancestry). Most scores were associated with lung cancer risk in UKB. Of the 39 evaluated PGS, 33 had a hazard ratio per standard deviation greater than 1.1 and 22 had a C-index greater than 0.55. Discriminative performance did not differ by sex. However, most PGS performed better in smokers than never smokers, although for a few scores (n=8) the reverse is true. Risk threshold analysis showed modest case enrichment, with some PGS identifying more than 25% of cases among the top 20% of the distribution.

Conclusion: Lung cancer PGS remain relatively weak compared to those developed for other cancers, limiting their immediate clinical utility. The predominance of European-derived GWAS and overlapping SNP sources underscores limited diversity and innovation in current development. Selection of a suitable PGS is context-dependent and requires consideration of target population characteristics (such as ethnicity and smoking status). While unlikely to be useful as standalone tools, PGS may provide incremental value when combined with epidemiologic and clinical risk models.

The current state of polygenic scores for the development of lung cancer: a systematic review and validation in UK Biobank

Background
Cardiac masses are rare but remain an important consideration in cardio-oncology
practice. The differentials for cardiac masses vary depending on clinical presentation and include tumors, thrombi, vegetations, and structural abnormalities. Of the heart’s four chambers, right atrial masses pose a diagnostic challenge due to anatomical variations and limitations in imaging modalities. We present a case of a pseudo–right atrial mass. 
Case Presentation
An 81-year-old woman with a past medical history of hypothyroidism, hypertension and erosive esophagitis presented with altered mental status, including dysarthria, weakness, and paresthesia. Initial concern was for a cerebrovascular accident (CVA). CT head and CT angiography showed no ischemia or large vessel occlusion. During hospitalization, a transthoracic echocardiogram (TTE) revealed a large right atrial mass. Review of imaging from two years prior showed no cardiac masses or anatomical abnormalities. Given recent weight loss and neurologic symptoms
concerning for micro-thrombotic lesions, a cardiac tumor was high on the differential. MRI of the brain revealed no acute CVA. Due to the patient’s agitation, transesophageal echocardiogram (TEE) was deferred. A contrast-enhanced CT of the heart was obtained but showed no clear evidence of a right atrial mass; however, the right atrium was poorly opacified, and a large hiatal hernia was noted. The patient's mental status gradually improved, and she was discharged with
outpatient cardiology follow-up. As an outpatient, TEE confirmed the absence of cardiac masses or anatomical abnormalities. The previously suspected right atrial mass was attributed to imaging artifact caused by the large hiatal hernia.
Discussion
Right atrial masses can be challenging to evaluate due to the chamber’s retrosternal position, which limits echocardiographic visualization. Misdiagnosis is possible due to anatomical variants or adjacent structures. This case illustrates how a large hiatal hernia may mimic a right atrial mass on imaging, particularly TTE. Comprehensive evaluation often requires multiple imaging modalities to differentiate true pathology from artifacts before proceeding with invasive workup. This case emphasizes the importance of considering non-cardiac causes, such as large hiatal hernias, in the differential for cardiac masses. Hiatal hernias can affect cardiac function
and rhythm, making their recognition vital in cardiac imaging. Reliance on multimodal imaging allows for a more accurate diagnosis, minimizes unnecessary interventions, and supports improved patient outcomes.

Echo Illusion: Hiatal Hernia Imitating a Right Atrial Mass

Background
Drug-Induced Liver Injury (DILI) is a heterogeneous clinical syndrome potentially caused by many pharmacological agents. DILI is typically benign and transient, improving after drug cessation; few cases progress to chronic liver disease or liver failure. We present a case of DILI following initiation of zoledronate and bicalutamide, resulting in persistent hyperbilirubinemia and acute renal failure due to suspected bile cast nephropathy. 

Case Presentation
An elderly man with metastatic prostate cancer presented with fatigue, dark urine, and jaundice. One month prior he initiated bisphosphonate and anti-androgenic therapy with zoledronate and bicalutamide, respectively. Workup revealed severe transaminitis, elevated alkaline phosphatase (ALP), and rising hyperbilirubinemia. A liver biopsy was obtained and was suggestive of DILI. He was treated with N-acetylcysteine and prednisone and discharged; follow-up labs showed initial improvement in transaminases, ALP, and bilirubin. However, weeks later he was readmitted with progressively increased bilirubin, ALP, and concomitant acute kidney injury. He was managed with fluids, electrolyte replacement, and supportive care. Weeks later, he was hospitalized again with electrolyte derangements, continued renal dysfunction, and persistently elevated bilirubin and ALP. Given persistent cholangiopathy and impending renal failure, with metastatic cancer, the patient enrolled in hospice care and passed away shortly after.
Discussion
Thousands of drugs have been potentially implicated in DILI with wide variations in presentation and severity. Causative drugs are typically identified by the temporal relationship of drug initiation with hepatotoxicity and improvement following cessation. Our patient developed DILI one month after starting zoledronate and bicalutamide, which have both been previously associated with rare reports of hepatotoxicity. Zoledronate has been more commonly implicated in prior reports and is the more likely causative agent – notably, these reports specify transient hepatotoxicity with swift recovery. Our case is unique in that neither bicalutamide nor zoledronate has been previously associated with such severe, prolonged, and progressive liver injury.
Both drugs, particularly zoledronate, have long mechanisms of action and are eliminated slowly – this may help explain the prolonged course of hepatotoxicity seen in our patient. While typical treatment of DILI involves immediate cessation of the offending agent, drugs with long durations of action can present a unique challenge since toxic effects can also persist. We suspect the prolonged period of hyperbilirubinemia resulted in renal failure secondary to bile cast nephropathy, however this was not confirmed with biopsy. Ultimately, the prolonged duration and severity of this case highlight the challenge of managing complex and rare hepatotoxic effects.


Prolonged Cholestatic Drug-Induced Liver Injury with Acute Renal Failure in a Patient with Metastatic Cancer

Background: Microscopic polyangiitis (MPA) is a rare ANCA-associated small vessel vasculitis that primarily affects adults. Pediatric cases are rare and frequently present with non-specific or atypical symptoms. Early recognition can be difficult, as initial symptoms may resemble more common pediatric gastrointestinal or renal conditions.
Case Presentation: A previously healthy 15-year-old male developed progressive vomiting, significant weight loss, and persistent hypertension over several months. Initial outpatient gastrointestinal workup, including imaging and endoscopy, was unrevealing. He was admitted for worsening symptoms and found to have acute kidney injury with abnormal renal ultrasound findings. After temporary improvement with fluid repletion, he was readmitted for recurrent nausea, rising creatinine, and new-onset hematuria and proteinuria. Further history revealed prior episodes of epistaxis and rash. Renal biopsy demonstrated pauci-immune necrotizing and crescentic glomerulonephritis, and serologic testing revealed elevated MPO-positive p-ANCA titers, confirming MPA. He was treated with high dose intravenous steroids and rituximab for induction, with supportive care and antihypertensive therapy. He responded to immunosuppressive treatment with early improvement in symptoms and renal function.
Discussion: This case highlights the diagnostic challenge of MPA in pediatric patients, particularly when presenting with a non-classical, gastrointestinal predominant presentation. ANCA-associated vasculitis should remain on the differential for adolescents with evolving signs of glomerular disease, particularly if early signs are subtle or suggest alternative diagnoses. Early consideration and prompt biopsy confirmation are critical for timely initiation of immunosuppressive therapy and prevention of irreversible organ damage.

Pediatric Microscopic Polyangiitis with Atypical GI-Predominant Presentation

Background: This public health campaign aimed to increase awareness and reduce aggressive driving behaviors among male residents aged 21-35 in Washington, D.C., using self-reported surveys. The campaign sought to develop a protocol for creating and publishing healthcare information on TikTok to effectively influence health behaviors.
Methods: TikTok was the platform used to engage viewers. A TikTok business account was initially created but was converted to a personal account to leverage trending audios and increase visibility. The content creation process involved ideation, video style selection (e.g., lecture-style vs. relatable content), and filming various perspectives, including driver and passenger viewpoints. Captions were crafted to educate and engage viewers. Hashtags such as “#drivesafedc” and “#endaggressivedrivingdc” were consistently used to improve engagement and expand audience reach. Promotion efforts included using TikTok’s paid promotion feature and partnering with influencers and health advocates.
Results: A total of 39 videos were posted over 3 months with a maximum video view count of 21,500 views. The Promote feature substantially increased viewership and engagement. Engagement methods included liking and commenting on the video. Several viewers commented by recounting their own experience with aggressive drivers and even discouraged such behaviors. While it was difficult to regulate spam comments, other viewers created an open space to discuss the impact of aggressive driving. 
Conclusion: The social media campaign effectively raised awareness about aggressive driving, generating significant engagement, particularly through the Promote feature. This engagement fostered meaningful discussions and showcased the potential of social media to connect with audiences on public safety issues. Addressing aggressive driving behavior, such as speeding, tailgating, and road rage, through social media is essential for shifting social norms, promoting positive peer influence, and ultimately reducing the risk of crashes, injuries, and fatalities.

Launching a TikTok Public Health Campaign to Reduce Aggressive Driving in Washington, D.C.: Key Experiences and Lessons

Background 
Pelvic dissection in anatomical education is often limited by inadequate visualization or disruption of critical structures. Traditional anterior approaches obscures deep retropubic anatomy while hemi-sectioning alters spatial relationships. In 2023, Foskey and Loomis introduced a posterior “open-book” method in male donors that preserved in-situ relationships of deep pelvic structures while enabling clear visualization. This study aims to adapt and assess the feasibility of this approach in a female donor, and gain insight about its educational implications and feasibility for medical trainees. 
Methods 
A female cadaver underwent posterior open-book pelvic dissection. One centimeter of the pubic symphysis was excised to create a hinge point. Soft tissue dissection was performed vertically from the coccyx tip through the L4-L5 vertebrae and horizontally across the sacrum and iliac crests. Osteotomies were performed through these same lines to permit controlled separation. Internal rotation of the pelvic halves was stabilized with a headblock underneath the pubic symphysis. Dissection and lateral mobilization of the rectum and surrounding neurovascular bundles, followed by partial dissection of the posterior parietal peritoneum, facilitated unobstructed visualization of intact spatial orientation of the pelvic contents. 
Results 
The posterior open-book approach revealed intact visualization of deep pelvic structures including the bladder, vagina, uterus, uterine tubes, vesicouterine pouch, and rectouterine pouch, while maintaining anatomical continuity. This provided a unique perspective often unavailable with traditional methods. Preserving three-dimensional anatomical relationships enhances spatial-awareness and is crucial for both clinical reasoning and surgical training. The ability to observe these structures without tissue disruption will improve learners’ understanding of this complex anatomical space. These findings highlight the potential of this approach to advance cadaveric education and improve anatomical comprehension in medical curricula. 
Conclusion 
The posterior open-book technique for female pelvic dissection offers a novel and educationally valuable approach that offers superior visualization of deep pelvic structures while preserving native anatomy. By maintaining structural integrity, the technique supports learners’ understanding of complex spatial relationships and may improve anatomical literacy. The approach has promising implications for medical education and anatomic research, particularly for structures traditionally obscured in standard dissection techniques. Integrating an open-book 
dissection alongside traditional prosections may offer a complementary teaching tool that reinforces the in-situ relationships of pelvic anatomy, increases spatial comprehension, and enhances readiness for clinical and surgical applications.

An Open-Book Approach to Female Pelvic Dissection: Feasibility of a Novel Technique

Health inequities persist in rural Nepal due to
socioeconomic factors and challenging geography. The health system faces significant obstacles in meeting the global Sustainable Development Goals (SDGs), with fragmentation and limited resources restricting equitable access.
While some progress has been made, geographical
accessibility remains a key barrier to health equity.
Remote areas struggle to access essential health
services, worsening disparities.
This study examines the impact of an integrated rural
outreach program in a remote Bagmati Province
village. Our goal is to enhance healthcare access,
address inequities, and promote community wellness
through outreach camps, health education, and the
efforts of community health workers (CHWs).

Strengthening Public Health in Remote Settings: The Impact of Integrated Outreach on Health Equity (A
Case Study from Nepal)

Background: Psychological stress is known to exacerbate dermatologic conditions such as acne, eczema, and compulsive skin behaviors. The COVID-19 pandemic introduced a global stressor with widely-experienced psychosocial effects and potential impacts on skin health. This study analyzes U.S. public interest in stress-induced dermatologic conditions and psychodermatologic disorders during pre-pandemic, pandemic, and post-pandemic periods.

Methods: Relative Google search volume (RSV) was used as a proxy for public interest, given the search engine’s 5 trillion annual searches.1 RSV for the terms "skin picking", "trichotillomania", "rash", "eczema", "dermatillomania", and "anxiety skin picking" from 2018 to 2024 was obtained through the Google Trends database. Monthly search interest was normalized and averaged across pre-pandemic (2018-2019), pandemic (2020-2022), and post-pandemic (2023-2024) time periods.

Results: Search interest increased for “skin picking” and “eczema” from 2018 to 2024. “Trichotillomania” RSV increased at least 33.33% from January 2020 to March 2021 relative to 2018-2019. “Dermatillomania” RSV increased 156.41% from April to May 2021. “Anxiety skin picking” RSV increased during the pandemic (2020-2022), with the largest average month-over-month change of 4.99% compared to other search terms. No consistent trend was observed for “rash.”

Conclusion: Public interest in stress-influenced dermatologic conditions increased during the COVID-19 pandemic, suggesting heightened interest or prevalence of psychodermatologic issues during prolonged stress. These findings support the need for more coordinated psychodermatology approaches, particularly in times of stress or societal crisis. The growing intersection of dermatology and mental health underscores the importance of continued research in psychodermatology.

Public Interest in Stress-Induced Dermatologic Conditions and Psychodermatologic Disorders During the COVID-19 Pandemic: A Longitudinal Analysis and Brief Review of Literature

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Disorganized and Hypomineralized Enamel Resembling Molar-Incisor Hypomineralization Induced by Ameloblastin Overexpression in Mice

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