United States

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.

AMA Research Challenge 2025 

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

Colleagues and Friends:

I am very happy to welcome you to the 14th annual Canadian Neuroscience Meeting, and to the first virtual edition of our meeting. I want to highlight the important work the CAN meeting chair, **Roger Thompson** and co-chair, **Alyson Fournier**, did to put together the great program we are offering this year. Moving to a virtual format required a complete re-design of the program, and both Roger and Alyson did a splendid job in providing us with an appealing and well adapted program for our first virtual event. I wish to thank them for this very important effort.

Highlights of this year’s scientific meeting include invited speakers **Michael Hausser, Franck Polleux, Gwyneth Card, Magdalena Götz**and Brain Prize winner **Huda Zoghbi**. Plenary and parallel symposia, proposed by our members complete our diverse [scientific program.](https://can-acn.org/meeting-2021/program-2021/)

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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: 
Necrobiosis lipoidica (NL) is a rare, chronic granulomatous skin condition with no FDA- approved therapies. PCS499, an oral deuterated analog of pentoxifylline, has anti-inflammatory and antifibrotic properties that may offer therapeutic benefit. This Phase II open-label study (NCT03698864) evaluated the safety and exploratory efficacy of PCS499 in adults with NL.

Methods: 
Twelve adults with biopsy-confirmed NL were enrolled to receive PCS499 (900 mg orally, twice daily) for 6 months, with an optional 6-month extension. Safety was assessed by adverse event (AE) monitoring, labs, and ECGs. Exploratory efficacy endpoints included lesion characteristics, photography, and validated clinician-and patient-reported outcomes such as Investigator Global Assessment (IGA), NL Color and Ulcer Scale (NLCUS), Physician and Patient Global Assessments (PGA, PtGA), Dermatology Life Quality Index (DLQI), and Skindex-29. Ten subjects completed treatment and were included in the efficacy analysis. Clinical outcomes were summarized descriptively; changes from baseline to month 6 were evaluated using Wilcoxon signed-rank tests (p < 0.05 significant).

Results: 
All subjects were female with a median age of 41; 80% had diabetes mellitus, 20% had ulcerated NL, and mean disease duration was 12.7 years. PCS499 was generally well tolerated. The most common AEs were mild gastrointestinal symptoms. One subject discontinued during the optional extension period due to a treatment-emergent AE of alopecia that was mild and assessed as probably related to the study drug. No serious AEs or clinically significant lab or ECG changes occurred.

Among the two subjects with ulcerated NL, one achieved complete wound healing by day 85 and the other by day 351, with no recurrence through 12 months. Reference ulcer area decreased >75% by month 6 in both cases, and continued treatment through the extension period led to the closure of all remaining ulcers.

In the full cohort, five of ten subjects achieved “clear” or “almost clear” status on the IGA, with a mean time to response of 111 days (range: 54–166). Significant improvements were seen in IGA Activity (Δ −1.3, p = 0.026), PGA (Δ −1.4, p = 0.038), NLCUS inflammation/color (Δ −0.9, p = 0.024), and induration (Δ −0.9, p = 0.037). PtGA and DLQI improved without reaching statistical significance. Skindex-29 scores improved in all domains, with a significant change in the function domain (Δ −10.8, p = 0.045) and trends in symptom and emotion domains.

Conclusion:
PCS499 was safe and well tolerated, with evidence of clinical response and improved quality of life, especially in the ulcerated group. Findings support further investigation in larger controlled trials.


Clinical and Quality of Life Outcomes in a Phase 2 Study of PCS499 for Necrobiosis Lipoidica

Background
Randomized controlled trials (RCTs) are designed to provide the highest levels of evidence for clinical practice; consequently, RCTs are the mainstay for creating guidelines and approving new treatments. It is ethically essential for patients assigned to the control arm in RCTs to receive standard-of-care treatment. This serves to protect patients, optimize adequate treatment, and ensures that RCT findings are compared to current standard-of-care therapy – an ethical imperative of RCT design and implementation. Oncologic medical trials investigating new systemic agents for cancer have a high proportion of RCTs with inadequate control arms (PMID 31046071). It is unknown whether this finding is prevalent in oncologic trials investigating radiation therapy (RT) for cancer.

Methods
We identified registered clinical trials investigating RT in patients with cancer over the past decade. ClinicalTrials.gov was queried for RT as the intervention and cancer and other related terms as the condition between 1/1/13 and 1/1/23. Exclusion criteria included trials with incomplete status or non-oncologic indications. Trials were categorized by indication/primary disease site, first posted date, investigational arm, control arm, and sponsor/collaborator. Each control arm was analyzed, and the standard of care was determined according to National Comprehensive Cancer Center Network (NCCN) guidelines at the time of first posting.

Results
A total of 508 interventional studies with results registered on ClinicalTrials.gov were included. Of these, 360 single-arm studies were excluded. 116 studies investigating a treatment other than RT were excluded. 20 studies that were not completed were excluded. The remaining 12 studies were included in the final analysis. Of the included trials, 2 each investigated RT usage in central nervous system, prostate, head and neck, and breast disease sites, and 1 each for lung, hepatobiliary, rectal, and bone disease sites. A majority of the trials were industry-funded (83%), and over 2/3 of studies took place in the United States (75%). 100% of the trials were found to have an adequate control arm per the corresponding NCCN.

Conclusion
100% of oncologic RCTs investigating radiation therapy for cancer were found to have an adequate control arm. This finding contrasts with medical oncology trials, which have been shown to have a high proportion of RCTs with inadequate control arms. This disparity highlights the importance of designing oncologic RCTs with adequate control arms, which is crucial for providing the highest level of evidence to guide optimal clinical practice and ensure the safety of patients. These findings suggest that adequate control arm treatments are feasible to achieve in trial design, emphasizing both the need for continued focus on improving the quality of ethical oncologic research trials and a possible subspecialty that may serve as an exemplar.

Evaluation of Control Arm Quality in Recent Radiation Oncology Randomized Clinical Trials

Abstract Title
Ovarian Cancer with Gastric Metastasis: A Rare Presentation

Background
Metastatic gastric malignancy is rare, representing 0.7-5.4% of all gastric cancers. The most common tumors metastatic to the stomach are the breast and lung cancer, and melanoma. Gastric metastasis from ovarian serous cancer is extremely rare, accounting for only 0.013% to 1.600% of all gastric metastatic tumors. We present a case of ovarian cancer metastasizing to the stomach presenting with symptomatic anemia.

Case Presentation
A 64-year-old female patient with past medical history of low grade serous ovarian cancer S/P simple hysterectomy and oophorectomy five years ago with metastatic disease to the liver, lung, and peritoneum, S/P Carboplatin and Taxol three months ago and currently receiving BRAF directed therapy (Dabrafenib/Trametinib), presented from medical oncology office after being found with a low hemoglobin of 6.4. Patient also reported symptoms of fatigue, nausea, lightheadedness and shortness of breath. Patient denied any melena or hematochezia. On examination, vital signs were stable and physical examination was unremarkable. CT abdomen
showed intraabdominal mass with progression and likely infiltration into stomach within the lumen. A prior esophagogstroduodenoscopy (EGD) six months ago was normal. Patient received blood transfusion and underwent an EGD which showed a large, fungating, infiltrative, polypoid and ulcerated, partially circumferential (involving one-third of the lumen circumference) mass with no bleeding and no stigmata of recent bleeding in the gastric fundus. Surgical pathology was consistent with serous carcinoma with psammomatous calcification with immunostains positive for PAX8, p16, p53, estrogen receptor and CK7. Patient was treated with
Ribociclib and Fulvestrant and received palliative radiation to the abdomen to control gastrointestinal bleeding and abdominal pain. Therapy was changed from Ribociclib to Trastuzumab deruxtecan as the patient was intolerant to Ribociclib and due to the IHC from the gastric mass being HER2 1+ positive. Subsequent PET CT showed shrinkage of intraabdominal mass and liver lesions.

Discussion
The most common symptoms of ovarian cancer with gastric metastasis are abdominal pain, anemia, vomiting, and melena. It is important to distinguish a primary gastric malignancy from metastatic disease with ovarian origin in a patient with history of ovarian cancer presenting with anemia.

Ovarian Cancer with Gastric Metastasis: A Rare Presentation

Abstract Title
Hypertensive Crisis Unresponsive to Standard Therapy: The Interplay of Pulmonary
Hypertension and Scleroderma Renal Crisis in Systemic Sclerosis
Background
Systemic sclerosis (SSc) is a complex autoimmune disease that can affect nearly every organ system, often leading to serious and sometimes life-threatening complications. Among its most challenging manifestations are pulmonary hypertension (PH) and scleroderma renal crisis (SRC), both of which can dramatically impact patient outcomes. This case report describes a
54-year-old African American woman with a 12-year history of SSc who developed refractory hypertension, right heart failure due to PH, and SRC. Despite aggressive antihypertensive therapy (on seven drugs), her blood pressure remained uncontrolled, highlighting the complexities of managing overlapping pathologies.
Case Presentation
A 54-year-old African American woman with a 12-year history of systemic sclerosis
presented with progressive dyspnea, fatigue, and new-onset lower extremity edema.
Diagnostic workup confirmed pulmonary arterial hypertension (PAH) through right heart catheterization and revealed right ventricular dysfunction on echocardiography. Concurrently, she developed acute kidney injury with a serum creatinine of 3.5 mg/dL and malignant hypertension, consistent with scleroderma renal crisis (SRC). Despite an intensive antihypertensive regimen that included amlodipine, carvedilol, spironolactone, hydrochlorothiazide, clonidine patch, hydralazine, and losartan, her blood pressure remained uncontrolled, averaging 170/105 mmHg. ACE inhibitors, typically the cornerstone treatment
for SRC, were contraindicated due to an allergy. Intravenous prostacyclin therapy was initiated to manage her PAH, but her renal function continued to decline, prompting consideration for renal replacement therapy.
Discussion
Scleroderma renal crisis, characterized by malignant hypertension and rapid renal
deterioration, is a life-threatening complication of SSc. The coexistence of pulmonary hypertension adds another layer of complexity, as therapies for PH may interact with anti-hypertensive agents. Refractory hypertension in this context is driven by endothelial dysfunction and vasculopathy, limiting the efficacy of conventional treatments. Targeted therapies, such as endothelin receptor antagonists and prostacyclin analogs, may offer additional benefits but require careful consideration. This case highlights the critical need for a multidisciplinary approach, involving rheumatology, cardiology, nephrology, and often pulmonology. Close collaboration ensures that care is tailored and responsive to the patient’s dynamic needs. Such complex scenarios remind us of the importance of tailored, patient-focused care and ongoing innovation in the management of systemic sclerosis and its complications. Future research should focus on developing novel therapeutic strategies to address the unique pathophysiology of these intertwined conditions.

Hypertensive Crisis Unresponsive to Standard Therapy: The Interplay of Pulmonary Hypertension and Scleroderma Renal Crisis in Systemic Sclerosis 


Abstract Title: Ivosidenib Therapy for IDH-mutant WHO Grade 4 Astrocytoma

Background:
Isocitrate Dehydrogenase (IDH) is a commonly mutated gene in gliomas, present in approximately 10% of high-grade gliomas. Its oncometabolite, D-2-hydroxyglutarate, has been implicated in promoting gliomagenesis and epileptogenesis. IDH-1 or IDH-2 mutations confer a more favorable prognosis in gliomas than wildtype IDH, leading to the differentiation between IDH-wild type glioblastoma and IDH-mutant WHO Grade 4 astrocytoma. Although IDH-mutant WHO Grade 4 astrocytomas tend to occur in younger patients and show an improved survival, prognosis remains poor and treatment options are limited. Ivosidenib is a small molecule inhibitor of IDH-1 that has shown promise for treating low-grade IDH-mutant glioma. However, little is known about its efficacy in IDH-mutant WHO Grade 4 astrocytoma.

Case Presentation:
We present a retrospective case of a 39-year-old male with a WHO Grade 4 astrocytoma. Molecular characterization revealed that it was IDH-mutant, MGMTp methylated, and 1p/19q intact. It was treated with ivosidenib at second recurrence. He was originally treated with gross total resection, followed by radiation and 6 cycles of adjuvant temozolomide. At the time of 1st progression (approximately 19 months postoperatively), he was treated with lomustine at 90mg/m2 but progressed after 2 cycles. Here we report the effects of off label use of ivosidenib.

Discussion:
Radiological surveillance showed interval decrease in tumor size starting two months after initiation of ivosidenib. The patient remained neurologically intact and no adverse effects were observed. A review of the literature revealed only three studies analyzing the effects of ivosidenib in IDH-mutated WHO Grade 4 astrocytomas with varying results.

The 2023 INDIGO trial showed evidence of efficacy in using an IDH inhibitor for low-grade gliomas. The role of these drugs in high-grade IDH-mutated gliomas is currently unknown. Further studies are needed to assess their efficacy in overall and progression free survival, specifically in IDH-mutated WHO Grade 4 astrocytoma.

Ivosidenib Therapy for IDH-mutant WHO Grade 4 Astrocytoma

Background:
Creutzfeldt-Jakob Disease is a rare, progressive neurodegenerative disease caused by the accumulation of prions and is typically fatal within 6-12 months of onset. MRI of the brain is a crucial part of the diagnostic process, evaluating for disease mimics including tumors, infections, and other neuroinflammatory conditions. A literature search of MRI findings in CJD was performed. Characteristic MRI findings include cortical and basal ganglia hyperintensities on FLAIR and DWI. Contrast-enhancing lesions have not been associated with CJD, prompting evaluation for alternative diagnoses.

Case Presentation:
We present the case of a 77-year-old woman who initially presented to her primary care physician with several months of memory loss and unsteady gait. MRI of the brain showed left temporal lobe FLAIR hyperintensity, suggestive of an underlying neoplastic process. She was lost to follow up, then presented to the hospital two months later with acute altered mental status. Her exam was notable for global aphasia, unresponsiveness, and lack of movement. MRI demonstrated new diffusion restriction in the cortex and left dorsal thalamus, along with a new contrast enhancing lesion in the left temporal lobe. Initial cerebrospinal fluid (CSF) testing showed elevated protein with normal white blood cell count. She received empiric IV methylprednisolone and IVIG for presumed inflammatory etiology, without clinical response. Later CSF testing returned positive for real time quaking-induced conversion (RT-QuIC) and 14-3-3 protein, consistent with CJD. She passed away after discharge.

Discussion:
To the authors’ knowledge, this is the first reported case to demonstrate that contrast-enhancing lesions may be seen with CJD, a neurodegenerative disease with poor prognosis. Therefore, it is critical for clinicians not to exclude CJD in the differential diagnosis of a patient with rapidly progressive neurologic decline with contrast-enhancing lesions, in addition to more characteristic imaging findings. This allows for earlier directed testing, including CSF studies, leading to an earlier probable diagnosis, prioritization of comfort care, and minimization of further unnecessary testing.

A Presentation of Creutzfeldt-Jakob Disease with Contrast Enhancement of the Temporal Lobe

Abstract Title:
Another Subconjunctival Hemorrhage? Unraveling an Unusual Ocular Surface Lesion

Background:
Kaposi’s sarcoma (KS) is a vascular neoplasm associated with immunosuppression, particularly advanced HIV with human herpesvirus 8 (HHV-8) coinfection. Classic presentation includes violaceous, cutaneous and/or mucosal lesions in the setting of a diminished CD4 count; however, reports have also described extracutaneous disease involving visceral organs, and more rarely, ocular structures such as the conjunctiva. We describe herein a rare case of conjunctival KS presenting near the time of initial HIV diagnosis and erroneously regarded as a subconjunctival hemorrhage.

Case Presentation:
A 38-year-old man with newly diagnosed HIV (CD4 18) and a history of oral thrush, cutaneous KS, and recently treated hospital-acquired pneumonia presented to our emergency department with a chief complaint of dyspnea on exertion. He was initially presumed to have a subconjunctival hemorrhage of his right eye, which he reported to have first developed as a red lesion 3 months prior. A subsequent slit-lamp examination in our outpatient ophthalmology clinic unearthed suspicions for a clinical diagnosis of conjunctival KS in addition to HIV retinopathy. An ensuing conjunctival biopsy identified a vascular mass in the substantia propria with positive HHV-8 immunohistochemical staining, confirming the diagnosis of KS. Shortly thereafter, the patient deteriorated clinically and eventually succumbed to complications of advanced HIV, despite initiation of antiretroviral therapy (ART) and linkage to our oncology service for outpatient chemotherapy.

Discussion:
In the era of ART, ocular KS is rare, although not unprecedented due to ART failure, medication nonadherence, or delayed HIV diagnosis influenced by an array of socioeconomic determinants. This case represents the interdisciplinary nature of treating advanced HIV and the importance of recognizing its unconventional ocular manifestations; furthermore, ocular KS can present as a deceptive entity mimicking common clinical findings and appearing as a harbinger of a poor prognosis.


Another Subconjunctival Hemorrhage? Unraveling an Unusual Ocular Surface Lesion

Abstract Title:
Language Matters: Assessing the Role of Interpreter Access in Patient Satisfaction
Background
The United States (U.S) is home to a large and growing immigrant population, with the number
of immigrants reaching 47.8 million in 20231. A 2011 study reported that over 55 million
individuals in the U.S.—both immigrant and U.S.-born—speak a non-English language at home,
with 8.6% considered to have limited English proficiency (LEP)2. LEP may lead to language
barriers which can hinder clear communication between patients and healthcare providers, often
resulting in confusion and dissatisfaction with care. Addressing these barriers is crucial to
enhancing the overall patient experience. The use of trained medical interpreters has been
associated with improved patient satisfaction and communication among LEP individuals2,3,4.
This study aims to evaluate the impact of interpreter services on patient satisfaction among
individuals with LEP in healthcare settings.
Methods
A systematic literature search for peer-reviewed English articles was conducted in PubMed.
Three independent researchers assessed journal eligibility based on publication date,
relevance, and study quality. The search utilized the keywords “interpreter efficiency,”
“healthcare access,” “language barriers,” and “patient satisfaction,” and was limited to
publications from 2000 to 2024, yielding four articles included in this study. The US Census was
used for information on immigration trends.
Results
Current data shows that using trained interpreters increases LEP patients’ satisfaction and trust,
understanding of their medical care, and improves patient outcomes. In contrast, ad hoc
interpreters, such as family members or untrained staff, more frequently lead to clinical
misunderstandings and breaches of confidentiality2,3,4. LEP patients also prefer in-person over
telephone or video interpreters, especially for more sensitive or complex discussions; this builds
better patient-physician rapport and connection5.
However, access to in-person interpreters is inconsistent across different healthcare settings4.
Several studies highlight the need to improve remote interpretation by expanding language
options and prioritizing video formats4,5. Additionally, providers reported greater confidence and
fewer errors when working with professional interpreters3.
Conclusion
Expanding access to trained medical interpreters, preferably in-person, and strengthening
remote services can significantly improve patient satisfaction and health outcomes for
individuals with LEP. Ensuring consistent and high-quality language services across all
healthcare settings is essential to reducing communication barriers. Thus, as the LEP patient
population continues to grow in the U.S., strengthening these services is a crucial step towards
the delivery of more equitable and patient-centered care.

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