United States

Background:

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare necrotizing vasculitis affecting small to medium-sized vessels, commonly involving the respiratory tract and kidneys. The disease has a strong association with anti-neutrophil cytoplasmic antibodies (ANCA), particularly c-ANCA directed against proteinase-3. Early diagnosis is challenging due to overlapping symptoms with infections and other inflammatory conditions.

Case Presentation:

A 52-year-old non-diabetic, non-hypertensive female presented with a one-month history of fever with chills, a single episode of haemoptysis, and a recent onset of weight loss, anorexia, and productive cough. On examination, she was pale, tachycardic, and required supplemental oxygen. Auscultation revealed bilateral basal crepitations. Laboratory findings included leukocytosis, elevated CRP (239), and a positive c-ANCA test. Chest X-ray and HRCT thorax revealed multiple cavitary lesions with surrounding consolidation and ground-glass opacities. Despite empirical anti-tubercular and antibiotic therapy, the patient worsened with persistent fever and desaturation. A CT-guided lung biopsy showed granulomatous inflammation with Langhans giant cells and dense lymphoplasmacytic infiltrates, confirming the diagnosis of GPA. She was treated with pulse steroids (IV methylprednisolone 1 g for 3 days), followed by oral corticosteroids, co-trimoxazole, and cyclophosphamide infusions per standard protocol.

Discussion:

The diagnosis was initially confounded by a presumptive diagnosis of pulmonary tuberculosis. However, the absence of microbiological evidence, c-ANCA positivity, constitutional symptoms, and progressive respiratory involvement shifted the suspicion towards GPA with diffuse alveolar hemorrhage. The case highlights the importance of high clinical suspicion, ANCA testing, and timely histopathological confirmation in atypical pulmonary presentations.

Conclusion:

GPA is a life-threatening, multi-system autoimmune vasculitis. Prompt diagnosis and early immunosuppressive therapy with corticosteroids and cyclophosphamide are critical for improving outcomes, especially in cases presenting with diffuse alveolar
hemorrhage. Clinicians must maintain a differential diagnosis of GPA in patients with cavitating lung lesions and systemic symptoms unresponsive to standard antimicrobial therapy.

AMA Research Challenge 2025 

Granulomatosis with Polyangiitis Presenting as Diffuse Alveolar Hemorrhage: A Case Report

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Background
Cancer can recur when a subset of tumor cells, termed persister cells, survive therapy and re-enter the cell cycle. The cellular origins that give rise to persister cells and the mechanisms that confer the persister state remain poorly understood. We hypothesize that an epigenetic signature underlies the drug-tolerant persister state, characterized by transcriptional and chromatin accessibility changes that promote survival of residual cancer following chemotherapy.

Methods
To identify clinically relevant features of persister cells in untreated tumors and residual disease, we performed single-cell multiomic profiling (scRNA+scATAC) on a cohort of treatment-naïve and neoadjuvant chemotherapy (NACT)-treated high-grade serous ovarian cancer (HGSOC) samples. Additionally, we sought to validate the features that give rise to a persister state experimentally by performing single-cell multiomic profiling on HGSOC patient-derived xenograft (PDX) models before and after platinum-based chemotherapy.



Results
We identified differences in gene expression and DNA binding factor - transcription factors (TF) and chromatin regulators - enrichment between naïve and residual patient tumors following chemotherapy. Notably, the changes in chromatin accessibility present in residual NACT tumors were also found in treatment-naive samples from patients who later developed resistance. This suggests that a pre-existing epigenetic signature may be driving the chemotherapy-tolerant state in persister cells. This epigenetic signature independently predicted chemotherapy response in PDX models of HGSOC and in a separate patient cohort of metastatic HGSOC. Cells enriched in the persister state arose from multiple tumor lineages and displayed activation of oncogenic pathways, including altered stress responses, epithelial to mesenchymal transition, and changes to the cell cycle promoting quiescence. Additionally, we identified a subset of genes that are epigenetically primed for expression before treatment and are upregulated after treatment. These genes stay dormant or lowly expressed before chemotherapy but are significantly upregulated after treatment, which could explain the mechanism by which persister cells gain resistance to chemotherapy.

Conclusion
Our study reveals an intrinsic epigenetic program that primes tumor cells towards chemotherapy tolerance and identifies new vulnerabilities that could be exploited to delay or prevent cancer recurrence. The ability of the epigenetic signature to stratify treatment-naïve patient tumors into chemotherapy-sensitive and -resistant groups suggests that epigenetic profiling could be used as a predictive biomarker to guide therapeutic decisions and reduce cancer recurrence.



Single-cell multiomic analysis of HGSOC reveals an epigenetic program driving chemotherapy tolerance

Background
The use of plants as medicine is a tradition that has been around for centuries, dating back nearly 60,000 years. In the mountain regions of southern Appalachia, the Appalachian Cherokee Nation Tribe is known for their innovative use of witch hazel, yarrow, and common rush as anti-inflammatory treatments. Because of the effectiveness within this population, theories regarding the chemical components of these unique plants have abound. One theory suggests that the chemical structures of these plants are comparable to arachidonic acid, an important compound in the arachidonic acid pathway. In this pathway, arachidonic acid binds to cyclooxygenase-2, or COX-2, resulting in the release of prostaglandin 2 (PGG2). This ultimately leads to inflammation and its associated symptoms. When these anti-inflammatory plants are ingested, however, it is believed that the components bind to the active site of COX-2 instead, a strategy known as competitive inhibition. Therefore, the purpose of this study was to determine if these plants inhibit COX-2, a key enzyme responsible for inflammation.

Methods
This goal was achieved by growing, collecting, and preparing witch hazel, yarrow, and
common rush plant specimens. Following this, plant phenols were extracted using boiling water and activity-based fractionation. To test for COX-2 inhibition, the COX-2 Inhibitor Screening Kit (Fluorometric) was employed in conjunction with the SpectraMax M2 Plate Reader and SoftMax Pro Software application. Gas chromatology-mass spectrometry (GC-MS) was used to further identify biochemical compounds present in the samples. Data was inputted and analyzed via Excel using the percent relative inhibition equation outlined in the COX-2 Inhibitor Screening Kit (Fluorometric) instruction manual.

Results
The results from this study found that a 1:10 dilution of witch hazel extract with double distilled water (ddH2O) has a percent relative inhibition of 100.31%, which is greater than a 2.25 M dose of celecoxib (78.96%). Compared to yarrow and common rush, witch hazel demonstrated approximately 30% greater inhibition of COX-2. Results from this study also confirm that there are flavonoids and non-tannin content present in yarrow and common rush, as well as tannins present in witch hazel.

Conclusion
In conclusion, there is scientific basis to support witch hazel, yarrow, and common rush as COX-2 inhibitors. Not only does witch hazel appear to have greater anti-inflammatory properties than yarrow and common rush, but it also shows greater COX-2 inhibition than celecoxib in the laboratory setting. Moving forward, the anti-inflammatory activity of these plants could be compared to pharmaceuticals in clinical trials.

Anti-Inflammatory Activity of Appalachian Cherokee Nation Tribe Medicinal Plants as COX-2 Inhibitors

Sepsis is a life-threatening state of disseminated infection, and treatment requires knowledge of the organism responsible. The gold standard for sepsis diagnosis is blood culture, which requires days of growth. Next-generation sequencing has been proposed as an alternative; however, existing methods may lack sensitivity. We validated the RNA quasi-G-prime classification against cell culture and showed
that RNA quasi-G-primes reliably differentiate septic states from healthy states in humans.

Doing more with less: RNA quasi-G-primes differentiate septic from healthy patients

Background 
Psychiatric comorbidities significantly impact hospital resource utilization in patients hospitalized for heart failure (HF). Mental health conditions such as depression, anxiety, bipolar disorder, post-traumatic stress disorder (PTSD), schizophrenia, and substance use disorders (SUDs) can worsen HF outcomes through mechanisms including increased inflammation, reduced self-care behaviors, and poor medication adherence. These overlapping clinical challenges demand a better understanding of how specific psychiatric diagnoses influence hospital length of stay (LOS) and healthcare costs to inform targeted interventions.

Methods 
We performed a retrospective cohort analysis using the Nationwide Readmissions Database (NRD) from 2016 to 2022. Adults (≥18 years) admitted with a primary diagnosis of HF were included. Psychiatric comorbidities were identified using ICD-10 codes for depression, anxiety, bipolar disorder, PTSD, schizophrenia/psychotic disorders, and SUDs. Outcomes included adjusted hospital LOS and inflation-adjusted hospitalization costs, analyzed using multivariable linear regression controlling for demographic, socioeconomic, and hospital-level factors.

Results 
Among 31,886,859 weighted heart failure hospitalizations, anxiety was associated with increased LOS by 0.84 days (p<0.001) and higher costs by $2,348 (p<0.001). Depression increased LOS by 0.23 days (p<0.001) and decreased costs by $873 (p<0.001). Bipolar disorder had no significant effect on LOS (p=0.19) but was associated with a $2,480 cost reduction (p<0.001). Schizophrenia/psychotic disorders increased LOS by 1.47 days (p<0.001) and decreased costs by $149 (p=0.02). PTSD showed no significant change in LOS (p=0.60) but lowered costs by $752 (p<0.001). SUD was associated with decreased LOS by 0.47 days (p<0.001) and reduced costs by $1,512 (p<0.001). 

Conclusion 
Psychiatric comorbidities have diagnosis-specific effects on hospital resource use in heart failure. Anxiety and depression increased LOS, but only anxiety raised costs. Schizophrenia/psychotic disorders had the largest LOS increase with minimal cost reduction. Bipolar disorder and PTSD reduced costs without affecting LOS, while SUD decreased both. These patterns suggest differing care needs and highlight the importance of tailored, diagnosis-specific strategies to optimize resource use, improve discharge planning, and address potential care gaps in this high-risk population.


Impact of Psychiatric Illness on Hospital Stay and Costs in Heart Failure

Background 
Pituitary adenomas (PA) are common, typically benign tumors with a prevalence of approximately 22%. Endoscopic transsphenoidal (TSS) resection of PAs is the standard of care for large or symptomatic tumors presenting with visual disturbances or endocrinopathies. Postoperative complications include cerebrospinal fluid (CSF) leak, hormonal and visual disturbances, and hematomas leading to acute visual decline. Delayed cyst formation is well-documented and consists largely of arachnoid cysts. Rapid postoperative suprasellar cyst development leading to acute visual deterioration is exceedingly rare, with only 1 case reported in the literature. A cyst composed of normal pituitary gland has not been previously reported. We present the rapid formation of a nonneoplastic pituitary cyst following TSS resection of a large PA. The management and functional outcome are reviewed and the underlying pathogenesis is explored.

Case Presentation
A 63-year-old female presented with a large PA causing significant compression of the optic apparatus. Preoperative evaluation demonstrated normal visual acuity and fields. Gross total resection was achieved via the endoscopic approach and cytological analysis revealed a pituitary gonadotroph, subtype positive for follicle-stimulating hormone. The patient remained neurologically intact and immediate postoperative computed tomography (CT) confirmed complete resection and decompression of the optic apparatus. On postoperative day 6, the patient developed a sudden bitemporal hemianopsia. CT revealed a new suprasellar cystic lesion compressing the optic chiasm. The patient underwent emergent craniotomy and a cyst clearly emanating from the pituitary stalk was identified and resected. The attachment was sharply transected and the stalk was left both anatomically and functionally intact. Pathology demonstrated non-neoplastic anterior pituitary gland. Visual acuity and fields returned to the preoperative baseline. Six months post-resection the patient has normal pituitary function and vision and magnetic resonance imaging demonstrates no evidence of residual or recurrent disease.

Discussion
We present a rare case of a rapidly growing cyst of pituitary origin after TSS resection of a PA. A literature review into postoperative cyst formation after TSS for sellar masses yielded 469 articles, with 6 describing cyst growth within a year of TSS. The fastest developing lesion was a suprasellar arachnoid cyst that presented with acute visual impairment 1 day after surgery. There are no reports of postoperative cysts of pituitary origin. Emergent cyst resection resulted in preservation of vision and pituitary function, supporting surgical management. The pathogenesis of this lesion remains unknown. Future surgical and pathology reports will help identify variables contributing to postoperative cyst formation after PA resection.


Rapid Pituitary Cyst Development After Endoscopic Transsphenoidal Resection of Pituitary Adenoma

Background:
Spinal dural arteriovenous fistulas (SDAVFs) are rare vascular malformations involving an abnormal connection between a dural artery and a medullary vein, leading to venous hypertension and progressive myelopathy. Literature estimates an annual incidence of 5 cases per million, with a strong male predominance between 50-70 years old (~80%), with women accounting for only 20% of cases. This case presents a patient with a proposed novel mechanism for acquired SDAVF through equestrian activity.
Case Presentation:
An 81-year-old woman with hypertension and hypothyroidism presented with bilateral leg paresthesias progressing over three weeks to flaccid lower extremity paralysis, urinary retention, and constipation. She denied back or neuropathic pain. At baseline, she was fully independent and had recently taken up horseback riding.
Lumbar spine MRI revealed multilevel degenerative disc disease and foraminal narrowing. She was discharged to a skilled nursing facility with presumed lumbar radiculopathy. Two weeks later, she re-presented with worsening symptoms: 0/5 strength in the lower extremities, areflexia, T12-L1 sensory level, mute plantar responses, and sphincter dysfunction.
Thoracic spine MRI showed long-segment T2 hyperintensity, cord expansion, and serpentine flow voids. Digital subtraction angiography confirmed an SDAVF at the right T12 intercostal artery. She underwent Onyx-18 embolization with minimal improvement, followed by T11–L1 laminoplasty and direct ligation with nBCA embolization of a residual extradural component.
Postoperatively, she regained movement in hips, knees, and feet but remained Foley- dependent. She is undergoing rehabilitation with gradual improvement.
Discussion:
SDAVFs are acquired lesions often associated with dural sinus thrombosis, trauma, or prior surgery. This patient had none of these risk factors and her only recent change was picking up horseback riding as a new hobby in the last year, which introduced repetitive axial spinal stress. However, with her history of hypertension weakening the arterial walls and the introduction of horseback riding, this could have contributed to the formation of the abnormal connection between arteries and veins that characterizes a SDAVF. This may have triggered angiogenic pathways, particularly vascular endothelial growth factor (VEGF), leading to abnormal arteriovenous shunt formation. Additional mediators such as FGF and IL-6 could have contributed to endothelial injury and neovascularization. No prior literature has linked equestrian activity with SDAVF, making this a novel etiologic consideration. The delay in diagnosis reflects the overlap of symptoms with more common conditions like lumbar stenosis. Clinicians should consider SDAVF in elderly patients with progressive myelopathy and sphincter dysfunction even if the etiology does not follow medical norms for SDAVF’s.

Saddled With A Fistula; A Rare Case of Spinal Dural AVF In An 81 Year Old Equestrian

Background
Chronic abdominal pain (CAP), defined as constant or recurrent pain lasting more than three months, is a common yet diagnostically and therapeutically challenging condition, particularly in patients with overlapping gastrointestinal (GI), musculoskeletal, and connective tissue disorders. Given its multifactorial pathophysiology, CAP often necessitates a multimodal treatment strategy. Osteopathic manipulative treatment (OMT) offers a hands-on, non-pharmacologic approach to address somatic and viscerosomatic dysfunction, but remains underutilized in managing complex CAP.

Case Presentation
This clinical vignette evaluates the effectiveness of OMT, including both somatic and visceral techniques, in managing chronic idiopathic right lower quadrant (RLQ) pain in a patient with complex comorbidities and inconclusive prior workup. The objective is to assess OMT’s therapeutic value and provide clinical insight into a structured, reproducible OMT protocol that may inform future educational and research efforts.

A 25-year-old white woman presented with a two-year history of constant, sharp RLQ pain rated 1- 7/10 in severity. Prior evaluation included a negative abdominal computed tomography (CT) scan in 2023 and an unremarkable transabdominal and ovarian ultrasound during the study period. Her medical history was notable for Ehlers-Danlos syndrome, Celiac disease, irritable bowel syndrome-mixed (IBS-M), reactive hypoglycemia, and post-treatment Lyme disease syndrome. Over nine weeks, she underwent weekly, 20-60 minute OMT sessions. Treatments progressed from somatic-focused techniques (weeks 1–4) to combined somatic-visceral techniques (weeks 5–8) and visceral-focused treatment (week 9). Techniques included muscle energy, counterstrain, and visceral techniques targeting structures such as GI sphincters, fascia of Toldt, and the ileocecal valve. Pre- and post-treatment assessments included positional pain ratings (standing, supine, etc.), somatic dysfunctions (innominate rotation, sacral torsions), and Chapman’s and counterstrain points. 

Initial somatic-focused sessions yielded short-term pain relief (18-48 hours). However, addition of visceral OMT extended symptom relief up to three days. Notable improvements were observed in counterstrain and Chapman’s point tenderness, particularly those corresponding to the pancreas and ileocecal valve. 
By the end of treatment, average pain scores had decreased by 68% (right lateral) and 58% (left lateral), with all positional scores exceeding the common 30% threshold for clinically meaningful improvement.

Discussion
This case illustrates a diagnostic and therapeutic gap frequently encountered in outpatient care to manage chronic abdominal pain despite unremarkable imaging. The structured application of OMT, particularly with visceral integration, revealed clinically relevant dysfunctions not apparent through conventional diagnostics and provided meaningful, though transient, symptom relief. These findings support further exploration of OMT’s role in managing chronic abdominal pain in outpatient settings.

Integrating Somatic & Visceral Osteopathic Techniques to Manage Chronic Abdominal Pain in a Patient with Ehlers-Danlos Syndrome: A Case Study

Background: Computerized Provider Order Entry (CPOE) systems are designed to improve patient safety by allowing providers to electronically enter medication, diagnostic, and treatment orders. Despite widespread recognition of their potential benefits, adoption of CPOE systems across U.S. hospitals remains inconsistent due to complex implementation challenges. Prior studies highlight both the transformative effects of CPOE and the substantial barriers to its integration into clinical workflows. This review aimed to synthesize recent evidence on the benefits and barriers of CPOE implementation in the U.S. hospital setting to inform future systems-level improvements and strategies.

Methods: A hybrid, systematized review was conducted using the MEDLINE Ovid database. MeSH terms including "Medical Records System, Computerized," "Medical Order Entry Systems," and "Medication Errors" were combined with non-MeSH keywords such as "computerized provider order entry," "implementation," "benefits," and "barriers" using Boolean operators. Inclusion criteria required that articles assess either benefits or barriers of CPOE implementation in U.S. hospitals. Studies were excluded if they were not in English, focused on international settings, non-hospital environments, or were non-original research. Of 50 articles screened, 16 met criteria for final inclusion.

Results: The MEDLINE Ovid search yielded n=34,432 articles. Keyword searches for “computerized provider order entry,” “implementation,” “benefits,” “barriers,” and “CPOE” returned n=1,311, n=323,456, n=572,332, and n=1,183 results. After Boolean filtering, 50 articles were screened; 16 met inclusion. Reported benefits included improved test/medication ordering and reduced medication errors (12), fewer adverse drug events (8), shorter stays (6), cost savings (5), and better data access (3). Barriers included provider resistance (9), high costs (8), workflow disruption (6), and usability issues. Studies emphasized leadership engagement, vendor selection, and training as key to overcoming resistance and optimizing CPOE integration.

Conclusion: CPOE systems have demonstrated clear potential to enhance patient safety and hospital efficiency. However, significant implementation barriers persist, particularly related to cost, user adoption, and workflow disruption. Hospitals should prioritize structured implementation strategies that include early stakeholder engagement, targeted training, and efforts to minimize clinical disruption. Future research should focus on department-specific implementations and sustainable models for CPOE integration in resource-variable settings. Addressing these barriers is essential to maximizing the clinical and operational benefits of CPOE technology.

Benefits and Barriers of Computerized Provider Order Entry (CPOE) Implementation in U.S. Hospitals: A Systematized Review

Background 

During the COVID-19 pandemic, health-promoting institutions emphasized the threat of severe COVID-19 symptoms and the increased risk of infection for individuals with pre-existing health conditions. Therefore, public health messaging focused on positive framing of the COVID-19 vaccine to promote vaccine uptake in individuals with chronic health conditions. Using a nationally representative sample of American individuals, this study explores the interplay between chronic illness experience, institutional medical mistrust, and COVID-19 vaccine uptake to better understand perceptions of health promotion messaging. 

Methods
Study participants consisted of a nationally representative sample of 1,151 survey respondents who were enrolled in a parent study that validated the Institutional Medical Mistrust Scale (IMMS). The IMMS measures participants’ perceptions of three types of institutions: 1) health care organizations, 2) local and state government, and 3) federal government. Participants also answered a survey on physical and mental conditions, perceived COVID-19 threat, COVID-19 vaccine behavior, and demographics. Thirteen of the physical conditions and five of the mental conditions that the Centers for Disease Control and Prevention categorized as conclusively carrying a higher risk for severe COVID-19 illness were used in the analysis. 

Results
The average IMMS score was significantly lower for those who received the COVID-19 vaccine compared to those who did not. Age and perceived COVID-19 threat were significantly associated with an increased likelihood of vaccine uptake. Compared to those who felt “not at all” threatened, individuals who felt “very much” or “extremely” threatened were more likely to receive the vaccine. Chronic physical and mental conditions were found not to have significant relationships with vaccine uptake. 

Conclusion
Given that a lower level of institutional medical mistrust and a higher level of perceived COVID-19 threat was found to be associated with greater vaccine uptake, our study highlights the importance of recognizing institutional medical mistrust and perceived health threat as significant motivators for health behaviors. Future investigation to better understand facilitating factors of institutional medical mistrust and perceived health threat will be valuable for improving public health messaging appeal and consequent health-behavior adoption. Our findings provide evidence for health-promoting institutions to tailor their messaging to address these predictive factors when providing health education and messaging.



Navigating COVID-19 Vaccination: The Nuanced Roles of Chronic Illness Experience, Institutional Medical Mistrust and Perceived Health Threat 


TITLE: Impact of Area Deprivation and Pregnancy Intention on Maternal Stress and Anxiety Levels during Early Pregnancy in the Mountain Mama and Baby Cohort
AUTHORS: Emma V Reger, Amna Umer, Elly Marshall, Bethany Barone Gibbs
INTRODUCTION: Young adults living in high deprivation areas experience more stress and anxiety, and higher rates of unintended pregnancy. Though unintended pregnancy may contribute to peripartum stress and anxiety, the extent to which it explains differences in mental health with higher area deprivation is unknown. 
PURPOSE: Determine the relationship between area deprivation, pregnancy intention, and peripartum stress and anxiety. 
METHODS: Participants [n=372, age 27.57 ± 5.55 years (M±SD)] were enrolled in the Mountain Mama and Baby Cohort during their first prenatal visit with WVU Medicine. Participants completed the Perceived Stress Scale (PSS) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires. State deprivation index (SDI) was determined using the participant’s home address (scored 1-10;10 indicating highest deprivation). Pregnancy intention was abstracted from the electronic medical record. Linear regression evaluated relationships between SDI and pregnancy intention with PSS/GAD-7. Logistic regression was used to calculate odds of unintended pregnancy based on SDI. Results were adjusted for pregnancy intention to determine effect on PSS and GAD-7 using percent mediation. 
RESULTS: Higher SDI was associated with greater stress score (+0.26 points, 95% CI [0.023, 0.51]), p=0.028) though anxiety score was not significantly associated (+0.01 points, 95% CI [ -0.05 0.28], p=0.156). Higher SDI was strongly associated with increased odds of unplanned pregnancy by 14.5% (OR=1.15, 95% CI [1.07 1.23], p<0.001). Unplanned pregnancy was associated with greater stress scores (+3.57 points, 95% CI [2.22, 4.94], p<0.001) and anxiety scores (+2.40 points, 95% CI [1.47,3.32], p<0.001). Adjusting for unplanned pregnancy explained 39% of the association between SDI and stress score. 
CONCLUSION: SDI was associated with greater stress during pregnancy; this association was partly explained by unintended pregnancy. Greater peripartum stress associated with unintended pregnancies suggests it is vital to reassess accessibility of contraceptives and quality of sex education to promote mental health, especially in high deprivation areas.

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