United States

Background
Invasive candidiasis is a growing health threat. In the last five years, the WHO has prioritized fungal pathogens, and the CDC has reported a more than 80% increase in nosocomial Candida infections. With resistance to first-line antimycotics also rising, new treatment and prophylactic measures are needed. Glycogen synthase kinase (GSK) is a potential target for fungal pathogens. Some GSK inhibitors have passed Phase 1 clinical trials for indications like bipolar disorder and Alzheimer’s disease. If the safety profiles of potential fungal medication are favorable, or if a potential medication has selectivity for fungal homologs of GSK, fungal GSK could be a novel drug target. Not much is known about the moonlighting functions of Candida GSK. This work screens GSK inhibitors against Candida to examine cell growth inhibition.

Methods
Candida parapsilosis (ATCC 22019) was grown planktonically in YM broth, containing penicillin and streptomycin, at 33°C. GSK inhibitors were purchased from AOBIOUS (Gloucester, MA) and dissolved in DSMO, with a final culture concentration of 0.5% DMSO. Inhibitor screens were run in triplicate in a clear, flat-bottom 96-well plate, and growth/inhibition was monitored by
OD600. Glycogen content in cell cultures was monitored by absorbance at 660 nm after iodine/potassium iodide stain. 

Results
Several GSK inhibitors, including tideglusib, were found to slow or block Candida growth at micromolar concentrations. Some GSK inhibitors had activities comparable to known antifungal agents tested. GSK inhibitors tested encompassed diversity in molecular structure, though some molecules like tideglusib and TDZD-8 shared pharmacophores. Besides inhibiting growth, treatment of GSK inhibitors at sub-MIC concentrations resulted in lower glycogen content.

Conclusion
Our results indicate growth inhibition of Candida with GSK inhibitors. This work is foundation chemical biology studies to elucidate moonlighting functions of fungal GSK. Next steps will be to perform synergy screens to test if the GSK inhibitors increase or decrease bioactivity of known antifungals, and vice versa. Future directions also include pursuing cloning of Candida GSK for biochemical screens of the active compounds.

AMA Research Challenge 2025 

Back to the Fungimentals: Antimycotic Activity of Glycogen Synthase Kinase

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/)

The 2021 Advocacy session, chaired and organized by CAN advocacy committee chair **Karun Singh**, will feature a special lecture and question period with Member of Parliament and past Science Minister **Kirsty Duncan**. This will be followed by a short overview of CAN’s advocacy activities over the last year. We invite you to participate in this session for insight from Dr. Duncan on the workings of Parliament Hill, and to learn more about what CAN has been doing to promote neuroscience research in Canada.

We are also excited to host **Lisa Willis** in the Equity Diversity and Inclusion session, organized by EDI committee chair **Jibran Khokhar**.

A special highlight of our meeting will be the lectures by award-winning young neuroscientists. We are please to host the CAN 2020 Young Investigator Award winner **Mihaela Iordanova**, and CAN 2021 Young Investigator Award winners **Aaron Phillips** and **Tabrez Siddiqui**. Highlights will also include presentation by the top three winners of the CAN-CIHR-INMHA Brain Star Award winners, **Claire Gizowski, Nuria Daviu Abant** and **Lukas Tamayo-Orrego**.

Independently organized satellite symposia complement and complete this exciting program, check them out here: https://can-acn.org/meeting-2021/2021-satellite-symposia/

Some of the most engaging sessions are always the poster sessions featuring the work of our trainees, so make sure to log in to Gather Town during the poster sessions to chat with the presenters.
We hope you enjoy this program, and look forward to welcoming you, virtually.

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14th Canadian Neuroscience Meeting from August 23rd-25th

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Breast cancer remains a leading cause of cancer-related morbidity in women worldwide, yet early detection through optimal imaging remains challenging for many patients. While MRI provides superior soft tissue contrast and sensitivity for detecting small lesions, its clinical utility is often limited by cost and accessibility. Conversely, mammography is widely accessible but offers limited soft tissue differentiation. Recent studies have demonstrated Generative Adversarial Networks’ (GANs) success in medical imaging translation, yet no prior work has validated synthetic breast MRI generation using clinical-grade segmentation tools. This disparity creates a critical gap where patients who could benefit from MRI-quality imaging cannot access it, potentially delaying diagnosis.
To address this clinical challenge, our objective was to develop and clinically validate a CycleGAN framework for generating synthetic breast MRI from mammography. We developed a novel computational framework using CycleGAN-based deep learning to generate synthetic MRI data from standard mammograms. Our approach leverages the shared anatomical features between these modalities while accounting for their distinct imaging characteristics. We trained our model using 500 MRIs from the Duke Breast Cancer MRI dataset and 500 mammograms from the NIH Breast Cancer Screening DBT dataset. By utilizing unpaired image translation techniques, the model eliminates the need for pixel-matched multimodal datasets—a significant barrier in medical AI development.
The synthetic MRI images underwent validation using two clinical-grade segmentation models: MedSAM2 and MONAI. Results demonstrated synthetic tumor regions showing only 0.2% average deviation from ground truth annotations (standard deviation 0.3%). Spatial alignment analysis revealed that 80% of predicted tumor pixels fell within clinically acceptable bounds of radiologist-annotated regions, with an average normalized distance of 7% from tumor boundaries. Additionally, Jacobian determinant analysis revealed comparable local deformation characteristics between synthetic and ground truth images (mean values: MG 1.86 ± 2.7, MRI 2.11 ± 2.7), confirming preservation of anatomical transformation fidelity.
These findings suggest our synthetic MRI approach could democratize access to MRI-quality diagnostic information without the associated costs. The technology addresses the critical scarcity of paired multimodal imaging data while creating new possibilities for enhanced diagnostic workflows. By generating MRI-equivalent representations from readily available mammograms, this framework could particularly benefit underserved populations and resource-limited settings where MRI access remains prohibitive. Our computational approach represents a significant step toward bridging imaging modalities, not only in breast cancer diagnosis, but extrapolation to other diagnoses as well.


Clinical Validation of Synthetic Breast MRI: Multiplatform Segmentation Assessment

Background: Atrial fibrillation affects 38 million individuals worldwide, with dofetilide representing a cornerstone class III antiarrhythmic therapy. Current safety protocols mandate three-day inpatient monitoring for torsades de pointes (TdP) during drug initiation. Traditional risk stratification relies on static baseline QTc measurements, which inadequately predict proarrhythmic susceptibility during incremental dosing. Critically, 24% of TdP cases occur after the initial three-day period, indicating that current approaches fail to identify risk beyond discharge. Improved risk stratification methods are needed for delayed proarrhythmic events. We hypothesized that dynamic QTc changes during dofetilide loading would demonstrate significant predictive accuracy for identifying patients at risk for adverse events.
Methods: We conducted a retrospective cohort study of 101 consecutive atrial fibrillation patients admitted for dofetilide initiation(July 2022-August 2023). The primary composite endpoint included drug discontinuation or adverse ECG parameters (QTc >500ms and/or ventricular arrhythmia). Receiver operating characteristic curve analysis determined optimal QTc change thresholds. Multivariable logistic regression models, adjusted for gender, heart failure status, baseline creatinine clearance, and baseline QTc, assessed predictive value of QTc changes after sequential doses. Study limitations include single-center design and retrospective methodology potentially limiting generalizability.
Results: The cohort demonstrated median age 71.0 years (IQR 63.0-75.0), with 30.7% female participants and mean baseline QTc 440.9±32.6 ms. Forty-six patients (45.5%) experienced the composite endpoint. First-dose absolute QTc increases >48.0ms demonstrated exceptional predictive performance (aOR 17.24, 95% CI 4.34-68.53, p<0.001) with high specificity (83.6%) and overall accuracy (73.3%). First-dose percentage increases >10.54% showed equivalent discriminatory capability (aOR 18.66, 95% CI 4.66-74.75, p<0.001). Cumulative QTc changes from baseline to second dose >50.0ms (aOR 11.01, 95% CI 3.32-36.47, p<0.001) and >11.24% (aOR 10.74, 95% CI 3.23-35.68, p<0.001) maintained robust predictive associations.
Conclusion: Dynamic QTc changes demonstrate superior predictive capability compared to static baseline measurements for identifying high-risk patients, with adjusted odds ratios exceeding 10.0 for clinically actionable thresholds. These threshold-based biomarkers enable precision risk stratification that could facilitate targeted continuous mobile ECG monitoring during the vulnerable post-discharge period. Since nearly one-quarter of TdP cases occur after standard monitoring ends, dynamic QTc-guided algorithms with continuous surveillance may substantially improve patient safety outcomes while optimizing resource allocation. Prospective validation studies are warranted to establish clinical implementation protocols for this precision-based monitoring approach.

ECG QTc Biomarkers Predict Adverse Events During Inpatient Dofetilide Drug Loading

Background: Seborrheic keratoses (SKs) are common benign epidermal tumors that can cause significant cosmetic concerns or irritation. Although non-malignant, their appearance often leads patients to seek removal.

Purpose of Study: The purpose of this study is to provide an updated review of current and emerging treatments for seborrheic keratosis, evaluating their effectiveness, safety profiles, and impact on patient satisfaction to guide personalized, evidence-based management.

Methods: We performed a comprehensive literature review of SK treatments published from 2000 to 2025 using PubMed and major dermatology journals. Key outcomes assessed included treatment effectiveness, recurrence rates, adverse effects, and patient-reported satisfaction.

Results: Traditional treatments—such as cryotherapy, shave excision, and curettage—remain effective but are associated with risks of pigmentary changes or scarring. Recently, non-invasive therapies like topical hydrogen peroxide 40% solution have shown promise in randomized trials, offering comparable clearance rates with minimal downtime. Laser treatments, including Er:YAG and CO₂ lasers, are effective but cost-prohibitive for some patients. Patient satisfaction is highest with treatments that minimize pain, downtime, and post-treatment pigmentation changes.

Discussion: Choice of SK treatment should consider patient skin type, lesion location, cost, and cosmetic goals. Emerging therapies provide effective alternatives to traditional destructive methods, particularly for patients concerned about scarring or dyspigmentation.

Conclusion: Management of SKs is evolving beyond traditional modalities. Newer options, such as hydrogen peroxide 40%, provide effective, well-tolerated alternatives. A personalized approach based on patient preferences and lesion characteristics optimizes outcomes and satisfaction. Further studies comparing long-term efficacy and safety across treatment options are needed.

Advances in Seborrheic Keratosis Treatment Options

Abstract Title
A Cadaveric Study Indicates That Lower Intercostal Nerves (T11 and T12) Have Sufficient Lengths and Diameters for Pudendal Nerve Coaptation

Background
Pudendal nerve injury can cause debilitating bladder and fecal incontinence and sexual dysfunction. It is known that intercostal nerves can be transferred to S2-S3 roots for functional restoration. We sought to determine the feasibility of T11 and T12 intercostal-to-pudendal nerve transfer, using a posterior approach (deep to gluteus maximus). We hypothesized the intercostals would have sufficient tensionless length and diameter for coaptation to pudendal nerves.

Methods
Twenty-one fixed cadavers (9 female, 12 male) were included. With cadavers prone, lower ribs were palpated, and T11/T12 were dissected from deep to erector spinae muscles and followed laterally. After repositioning supine, nerves were followed ventrally, freed, and “transferred” to the ischial spine. Measurements included: distance from intercostal nerve exits from erector spinae to ischial spines and to terminus, and diameters at the same landmarks. Mixed-effects model statistics were used.

Results
Distances from the erector spinae to ischial spines were longer for T11 than for T12; total lengths exceeded the distance to ischial spines; and T11 was longer than T12 (p=0.01). Mean diameters of T11/T12 at ischial spines or termini did not differ. When data was stratified by sex, distances to ischial spines were longer in males, as was T12’s total length. Male T12 nerves were wider at terminus. In cases of multiple terminal branches, at least one branch reached the ischial spine.

Conclusion
Using a posterior access, both T11 and T12 showed sufficient length and diameter to serve as donor nerves for coaptation to pudendal nerves. The diameter of each intercostal nerve at the level of the pudendal was less than the known diameter of the pudendal nerve. We suggest that T11 and T12 could be combined post-transfer for optimal restoration of end-organ function.

A Cadaveric Study Indicates That Lower Intercostal Nerves (T11 and T12) Have Sufficient Lengths and Diameters for Pudendal Nerve Coaptation

Background
Tractional retinal detachment (TRD) is a severe complication of diabetic retinopathy, but its risk factors and impact on mortality in patients with Type I (T1DM) and Type II (T2DM) diabetes remain underexplored. Given the rising prevalence of diabetes, understanding the key contributors to TRD development is critical. This study aims to identify risk factors for TRD and evaluate its effect on survival in individuals with T1DM and T2DM.
Methods
A retrospective study was conducted using the US TriNetX Network database, identifying adults with T1DM and T2DM who were diagnosed with TRD between 2010-2024. Baseline characteristics, including demographics, comorbidities, renal and glycemic labs, and use of antidiabetic medications, were collected within 1 year of diagnosis. Propensity score matching (PSM) of these characteristics was performed to compare T2DM patients with and without TRD, and the same analysis was repeated for T1DM patients. Data were expressed as n (%) or mean (standard deviation). The primary outcome was all-cause mortality over 10 years, analyzed with Kaplan-Meier curves and log-rank tests.
Results
Among 14,701 adults with TRD, 9,820 (66.8%) had T2DM and 3,903 (26.5%) had T1DM. Compared to T2DM patients without TRD (n=3,897,132), the T2DM and TRD cohort had a higher prevalence of Black race (3,172 [32.3%]), HTN (4,624 [47.1%]), adverse SDOH (176 [1.8%)]), higher A1c (8.4 [2.3]%), lower eGFR (53.0 [36.7] mL/min), and higher CRP (42.4 [68.2] mg/L) (p<0.001 for all). Similarly, the T1DM and TRD cohort exhibited higher prevalence of Black race (1,288 [33.0%]), smoking (68 [1.8%]), HTN (2,277 [58.4%]), adverse SDOH (108 [2.8%]), higher A1c (8.6 [2.2]%), and lower eGFR (52.7 [37.7] mL/min) (p<0.001 for all) compared to those with T1DM but without TRD (n=738,984) After PSM, both T2DM and T1DM cohorts with TRD exhibited worse overall survival compared to their respective control groups (log-rank χ2=162.83, p<0.001; log-rank χ2=13.56, p<0.001).
Conclusion
Adults with T1DM and T2DM diagnosed with TRD face significantly higher mortality risk compared to those without TRD, despite adjusting for covariates. Key risk factors that may contribute to TRD development include Black race, hypertension, poor glycemic control, renal dysfunction, and lower socioeconomic status. These findings underscore the need for targeted management strategies to mitigate mortality risk in patients with diabetes and TRD. Future research should assess the effectiveness of interventions addressing TRD risk factors to improve survival outcomes in this high-risk population.

Risk Factors and Mortality Associated with Tractional Retinal Detachment in Type I and Type II Diabetes

Background
Latent autoimmune diabetes in adults (LADA) is an underrecognized slowly progressive form of autoimmune diabetes that presents in adulthood and is frequently misdiagnosed as type 2 diabetes mellitus (T2DM) due to its indolent progression and overlap features of metabolic syndrome. Patients may initially respond to oral hypoglycemic agents but eventually require insulin therapy due to progressive beta-cell failure. Misdiagnosis can lead to suboptimal glycemic control and increased risk of complications, including DKA.
Case Presentation
A 60-year-old woman with asthma, hyperlipidemia, and type 2 diabetes was initially admitted to the ICU for euglycemic DKA. This occurred three weeks after a hospitalization for influenza. A–related respiratory failure. Labs in the ED revealed a high anion gap metabolic acidosis (gap 25, pH 7.2), blood glucose of 140 mg/dL, and moderate ketones, confirming euglycemic DKA. She was compliant with her medications, including empagliflozin/metformin, but was not on
insulin. Her HbA1c was 8.5%. From 2023–2025, she had eight diabetes-focused visits with consistent medication adherence. A prior GLP-1 trial was discontinued due to GI side effects. Despite nutrition counseling and lifestyle changes, her HbA1c remained between 8.5–9.3%. LADA was suspected and confirmed with positive ZnT8 antibodies. She was started on Lantus 10 units nightly and referred to
endocrinology. At follow-up, fasting glucose averaged 150 mg/dL—an improvement from baseline.
Discussion
In 2019, the WHO reclassified LADA as slowly evolving, immune-mediated diabetes in adults. It resembles adult-onset type 1 diabetes but presents with metabolic syndrome features, a single autoantibody (often GAD), and preserved β-cell function. LADA typically affects adults misdiagnosed with T2DM who test positive for pancreatic autoantibodies (GAD, IA-2, or ZnT8).
These patients initially manage without insulin but progress to insulin dependence faster than typical T2DM. The Immunology of Diabetes Society defines LADA by age ≥30, at least one positive diabetes-related autoantibody, and no insulin requirement within six months of diagnosis. C-peptide helps guide therapy: levels ≥0.7 nmol/L may allow for T2DM management, while < 0.3 nmol/L warrants full insulin therapy. SGLT-2 inhibitors, though cardioprotective in T2DM, pose a risk in LADA due to their association with euglycemic DKA. This is believed to result from increased glucagon, hepatic ketogenesis, and impaired ketone clearance. As β-cell function declines, the risk of DKA rises, similar to T1DM. Misdiagnosis of LADA as T2DM often delays appropriate treatment, increasing the likelihood of poor glycemic control and complications like DKA.

Unmasking Latent Autoimmune Diabetes: A case that challenges Type 2 Diabetes

Immune Thrombocytopenia in Pregnancy: Recognition, Risk, Response
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia, which presents unique challenges in pregnancy due to potential bleeding risks and effects on the fetus. It occurs in 1 to 2 of every 1,000 pregnancies, which is a greater rate than in the general population. Thrombocytopenia in pregnancy can be connected to different etiologies, which can have very different consequences and are treated differently. ITP is a diagnosis of exclusion, so early recognition and close monitoring are essential to optimize maternal and neonatal outcomes.
Case Presentation
A 34-year-old G4P3 woman at 14 weeks gestation with a history of Hashimoto’s thyroiditis and gluten intolerance presented with mild fatigue and dyspnea on exertion. She was being evaluated for persistent thrombocytopenia during pregnancy, with laboratory studies revealing a platelet count of 104,000/μL with otherwise normal complete blood count and peripheral smear. She was also found to have iron deficiency without anemia. This was addressed with a trial of IV iron, resulting in improvement. Platelet counts during previous pregnancies, in chronological order, were 116k, 99k, and 92k. The patient denied any
bleeding issues and previous postpartum hemorrhages. Infectious and autoimmune panels were negative, and Von Willebrand disease was ruled out. There was no evidence of vitamin B12 or folate deficiency. A diagnosis of ITP was made based on exclusion and most likely given chronicity and personal medical history of other autoimmune disease processes. Besides closely watching the trend of her platelet count throughout her pregnancy, which stayed >100k and remained asymptomatic, no intervention was needed. Her platelet count was 125k 6 months postpartum.
Discussion
ITP in pregnancy requires careful distinction from gestational thrombocytopenia and more serious etiologies such as HELLP syndrome and preeclampsia. Treatment of ITP during pregnancy is generally the same as that outside of pregnancy and is focused on reducing the risk of bleeding rather than increasing platelet count. Platelet count should be checked at least every 4 weeks up until delivery. First-line therapy is indicated if the platelet count drops to <30k and includes corticosteroids with IVIG, with possible platelet transfusion. Decisions regarding delivery method and timing depend on platelet levels and maternal- fetal status. Platelet count requirements during delivery for the following procedures are: epidural >50-80k, c-section >50k, vaginal >30k. Neonate platelet count should be taken immediately after delivery to determine if therapy is needed. This case highlights the recognition and tailored therapy for ITP in pregnancy to ensure favorable outcomes.

Immune Thrombocytopenia in Pregnancy: Recognition, Risk, Response

Paget-Schroetter Syndrome is a form of upper extremity deep vein thrombosis that typically affects young, healthy individuals following repetitive arm movements or strenuous activity. It results from compression of the subclavian vein at the thoracic outlet, often due to anatomical abnormalities like a cervical rib or hypertrophied muscles. This compression can lead to vein injury and clot formation. Early diagnosis and treatment—including anticoagulation, possible thrombolysis, and surgical decompression—are important to prevent long-term complications.

A 39-year-old woman with a medical history of migraines and who uses a hormonal contraceptive vaginal ring presented to her physician with a swollen, discolored right arm. She reported right arm weakness for the past three months, and over the preceding week, she had noticed increased tightness in her sleeve along with numbness. Due to concern for deep vein thrombosis (DVT), point-of-care ultrasound (POCUS) was performed, revealing a thrombus in the subclavian and axillary veins. A formal ultrasound confirmed an occlusive thrombus in these veins, raising suspicion for Paget-Schroetter Syndrome. A CT scan of the chest was unremarkable. She started apixaban and referred to Interventional Radiology (IR). Venography performed by IR demonstrated high-grade stenosis of the distal subclavian vein at the level of the first rib, confirming the diagnosis. Successful angioplasty was performed. It was at that time that she was referred to vascular surgery. The patient ultimately underwent first rib resection and scalenus anticus resection to address a cervical rib contributing to the compression.

Tight Sleeves and Silent Stenosis: A Vascular Surprise

Clinical Implications of a Left Vertebral Artery Arising from the Aortic Arch
M. Culligan, D. Taneja, A. Charles, K. Thurmann, A. O’Neill, L. Suh, B. Wang, D. Taneja

Background: The left and right vertebral arteries typically originate as the first branches of the left and right subclavian arteries, respectively. Variations in their origin are fairly rare, with the left vertebral artery (LVA) arising as a fourth branch directly off the aortic arch in approximately 3.6-5.5% of the population. LVA abnormalities have the potential to complicate surgical and diagnostic procedures of the neck and surrounding vasculature. 

Case Presentation: During a cadaveric dissection of a 71-year-old female in the anatomy lab at Creighton University School of Medicine - Phoenix, the left vertebral artery was observed originating directly from the aortic arch, between the origins of the left common carotid artery and left subclavian artery. The LVA extended superiorly before entering the transverse foramen of the C5 vertebra. The LVA’s prevertebral length was 93.5mm, compared to 37.8mm for the right vertebral artery (RVA), which entered the spine at C6. The diameters at the base of the LVA and RVA were 2.7mm and 2.1mm, respectively. The brachiocephalic trunk and RVA branching from the right subclavian artery were anatomically unremarkable. Of note, an ependymal cyst in the left parietal lobe was discovered in a previous dissection of this cadaver, who was noted to have a history of epilepsy. 

Discussion: A LVA of aortic arch origin is classified as a Type III aortic arch abnormality. Type III LVAs tend to ascend medially and have a longer course prior to entering the transverse foramen of the vertebrae. This longer, and often more tortuous, prevertebral course can predispose patients to a greater risk of vertebral artery dissection, which presents with headaches and other neurological symptoms. The increased prevertebral, medially-running course also poses increased risk for complications such as hemorrhage, neurological deficits, and even death during anterior approach cervical spinal surgeries. Clinicians unaware of a LVA abnormality while attempting a carotid artery stent or aortic arch procedure could inadvertently occlude the LVA and cause cerebral ischemic effects. In catheterization and other diagnostic studies, a Type III LVA could be incorrectly considered occluded and subject to unnecessary treatment. Obtaining computed tomography angiography or magnetic resonance imaging studies to identify an abnormality prior to a procedure can prevent misdiagnosis and reduce the risk of vertebral artery damage and downstream complications. 


Clinical Implications of a Left Vertebral Artery Arising from the Aortic Arch

Background
Terminal extubation, or palliative or compassionate extubation, is a legally and ethically accepted practice in the US where mechanical ventilation is withdrawn when ongoing life-sustaining treatment no longer aligns with a patient’s goals of care, with nearly 42% of ICU deaths involving withdrawal of such measures. Despite its legal acceptance, it remains a nuanced decision, particularly in patients with spinal cord injury (SCI). Approximately 18,000 new SCIs occur annually in the US, with respiratory failure being the leading cause of death. While extubation protocols exist, there are none specific to the SCI population. Discussions around goals of care and prognosis for patients with SCI may be complicated by quality of life (QOL) concerns and potential ableist bias when physical dependence is misinterpreted as incompatible with meaningful life. Here, we present a case of an older adult with cervical SCI who requested terminal extubation following prolonged hospitalization.

Case Presentation
An 88-year-old male with a history of hypertension and prostate cancer sustained a traumatic high cervical SCI with craniocervical subluxation and multiple associated injuries. He required mechanical ventilation and underwent tracheostomy after developing respiratory failure and pneumonia, and his hospital course was further complicated by pneumonia, pressure injuries, and persistent ventilator dependence. Psychiatric evaluation initially raised concerns for depression and adjustment disorder, though he expressed a consistent, clear expression of a wish not to live ventilator-dependent. Over weeks across multiple care settings, he reaffirmed this wish. After comprehensive interdisciplinary assessment confirming decision-making capacity, and with strong family support, he elected for hospice care. Supported by his family and palliative care team, he was extubated and passed 48 hours later. 

Discussion
This case illustrates the complex intersection of autonomy, capacity, and ethics in end-of-life decisions for patients with SCI. Withdrawal of nonbeneficial life-sustaining treatment is ethically distinct from physician-assisted dying and aligns with guidelines from the American Academy of Hospice and Palliative Medicine, and the patient’s final decision was expressed consistently over time and across settings with concerns about mood disorders impairing decision-making carefully evaluated. SCI presents unique challenges to autonomy, especially when provider bias may influence care framing. QOL judgements must be patient-centered, informed by lived experience rather than assumptions. Physiatry plays a crucial role, offering prognostic insight and advocating for patient-centered goals. As terminal extubation becomes more common in ICU care, cases like this highlight the need for ethical, patient-centered approaches to end-of-life decision making.

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