United States

The neuropeptide hormone, endothelin (specially, ET-1) plays an important role in the invasiveness of breast cancer. High ET-1 levels are associated with decreased disease-specific survival. Very few studies highlight the differential expression of ET-1 and its receptors ETAR and ETBR among triple negative breast cancer (TNBC), non-TNBC, and normal phenotypes. The purpose of the present study was to find out whether the expression of ET-1, ETAR and ETBR is higher in TNBC cells versus non-TNBC and normal cells. An association between higher expression of ET-1 axis and promotion of aggressive TNBC phenotype could represent ET-1 axis as useful biomarkers of TNBC prognosis and potential therapeutic targets. Our hypothesis is that expression levels of ET-1 and its receptors might play an important role in the development and progression of TNBC cells as compared to non-TNBC and normal cells. We aimed to assess the possible prognostic and predictive values of ET-1, ETAR and ETBR by studying their mRNA expression and protein levels in TNBC and non-TNBC via formalin fixed paraffin embedded breast tissue from 4 subjects with TNBC and 4 normal subjects, representing non-TNBC. Western blot, immunofluorescent, and immunohistochemical analysis served to quantify the differential expression. Results from Western Blotting showed ET1 levels were 81.6% higher, ETAR levels were 35% higher, and ETBR levels were 30% higher in TNBC vs non-TNBC cell lines. Immunofluorescence revealed greater intensity of ETBR in all cell lines compared to ETAR, greater expression of ET-1 and ETBR in TNBC cell lines, HCC-1806 and MDA- 231, and greater expression of ETBR in the nucleus of all cell lines and of all proteins in MDA- 231. Immunohistochemistry visually depicted greater staining of ET1, ETAR, and ETBR and quantitatively showed approximately 20% higher ET1, 40% higher ETAR, and 20% higher ETBR positive cells in TNBC vs normal breast tissue. Due to the similar results obtained from Western blot analysis with cell lines and immunohistochemical analysis with breast tissue, our hypothesis that expression of ET-1 and its receptors is higher In TNBC than non- TNBC and control is validated and thus could guide subsequent investigations for targeted pharmaceuticals against these biomarkers in TNBC. 

Supported by MVTCP U54CA162069 and Fuji Oil Company, Osaka, Japan, and NIH MeTRC5U5AMD007593.

AMA Research Challenge 2025 

Differential Expression of Endothelial-1 (ET1) and its Receptors, Endothelin Receptor Type A (ETAR), and Endothelin Receptor Type B (ETBR) between Subjects with Normal, Triple Negative, and Non-Triple Negative Breast Cancer

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Purpose:
KCC2, part of the SLC12 family of proteins, is a potassium-chloride cotransporter essential for neuronal function by regulating GABA signaling through chloride gradients. Recent studies suggest that downregulation of KCC2 may contribute to symptoms observed in opioid use disorder (OUD) which sees hyperpolarization of the postsynaptic cleft. While the idea of increasing chloride flux via KCC2 to stabilize the concentration gradient serves as a promising therapeutic target, few small-molecule agonists targeting KCC2 have been identified, and no definitive binding sites have been characterized. This study employs a machine-learning approach to build a model KCC2 protein, identify its possible active sites, and quantitatively characterize the intermolecular interactions with a library of ligands.

Methods:
An in-silico model of KCC2 was generated using published cryo-EM structural data from the RCSB Protein Data Bank. The protein surface was analyzed for potential active sites by evaluating parameters such as size, depth, hydrophobicity, and capacity for intermolecular interactions, including hydrogen bonding and Van der Waals forces. Ligand models for experimental agonists and FDA-approved negative controls were prepared, forming a small-molecule library. This library was screened against the identified binding sites using a rigid docking protocol. Ligand interactions were scored based on parameters including Van der Waals energy, Coulomb energy, hydrophobicity, and hydrogen bonding potential.

Results:
Surface analysis revealed nine potential active sites on KCC2 with SiteScores ranging from 0.895 to 0.979, indicating high reliability in distinguishing drug-binding regions. The highest-scoring site was located in the transmembrane domain encompassing SER896-PHE1090. Common key residue interactions among all agonist candidates involved HIE1051 (Pi-Pi stacking), ASN1086 (hydrogen bonding), and PHE1090 (Pi-Pi stacking). Agonist candidates averaged a more energetically favorable docking score of -4.5228, compared to -3.6087 seen with negative controls, supporting the increased specificity of these binding sites.

Conclusion:
While these findings are promising, it is noted that the docking scores for our library of ligand candidates are not as highly scored as other protein:ligand interactions (ibuprofen covalent binding to cyclooxygenase-2 results in a docking score of -10.3 using the same experimental parameters). Finally, we acknowledge the need for binding and functional assays need to be performed to validate on-target protein:ligand activity. Overall, these findings provide insights for the rational design of novel KCC2-targeted therapeutics, offering avenues for developing treatments optimized for increasing KCC2 activity, and consequently, symptoms associated with OUD.

Machine-Learning-Assisted KCC2 Protein Modeling and Small Molecule Drug Screening for the Rational Design of Therapeutics Against Opioid Use Disorder

Abstract Title
Age, Biological Sex, and Supine Blood Pressure
Background
Blood pressure is a prevalent modifiable risk factor for cardiovascular disease (CVD) and increases with age. Compared with traditional seated brachial blood pressure (BP), supine BP (brachial and aortic) has a greater association with CVD outcomes. However, the significance of biological sex on age-related supine BP is unknown. We hypothesize the relationship between age and supine BP will be sex specific.
Methods
A sample of 316 apparently healthy adults (165 Females, range: 20-84 years; 151 Males, range: 20-87 years) was used to assess the association of biological sex with supine BP. Data were analyzed using bivariate correlations between age and supine brachial and central (aortic) BP. Partial correlations were used to adjust for traditional risk factors (total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides, and blood glucose), body composition (body mass index [BMI], waist circumference), and vascular endpoints (augmentation index (AIx), AIx at heart rate 75, carotid-femoral pulse wave velocity (cfPWV)). Analysis of Variance (ANOVA) was used to compare group mean differences amongst young (18-44 yr), middle age (45-65 yr), and older (65+ yr) females and males.
Results
A positive correlation for age and supine brachial systolic BP (bSBP) and central SBP (cSBP) was identified in females (bSBP, r =.468; cSBP, r =.571, p<.05) and males (bSBP, r =.317; cSBP, r =.577, p<.05). Age remained correlated with supine bSBP and cSBP in females (bSBP, r =.166; cSBP, r =.174, p<.05), but not males (bSBP, r =.067; cSBP, r =.128, p>.05) after adjusting for traditional risk factors, body composition, and vascular endpoints. Supine bSBP of young females (117 ± 2 mmHg) was lower than middle-aged (125 ± 2 mmHg) and older (138 ± 2.8 mmHg) females (p<.05), and young males (126 ± 1 mmHg) was lower than older males (136 ± 2 mmHg, p<.05). Supine bSBP in young females was lower than in young males (p<.05), but not between older females and males (p>.05). A main effect of age (p<.05) was observed with supine cSBP.
Conclusion
Supine brachial and central BP are related to age in females independent of traditional CVD risk factors, but not males. Therefore, utilizing supine blood pressure may provide additional insight for CVD risk assessment in females.

Age, Biologic Sex, and Supine Blood Pressure

Background
Cholangiocarcinoma, a rare but deadly cancer of the bile ducts, has a low incidence in the US, 1.26 cases per 100,000 annually. Often diagnosed at an advanced stage, the median survival of 6 to 7 months may improve with early detection by screening. Our collaborators, van Haag, et al. applied machine learning to UK Biobank data to design a risk assessment score. This “TOP5” model utilizes the 5 most associated factors of cholangiocarcinoma (age, elevated GGT, complications of cirrhosis, cholangitis, and bile duct obstruction) to identify at-risk individuals and improve prognosis. We aimed to utilize TriNetX, an ultra-large scale clinical database, to externally verify this screening tool and evaluate its predictive value.

Methods
TriNetX contains electronic health records from over 150 million de-identified patients. Using GGT values and ICD codes for TOP5 criteria (incorporating age into subsequent analysis), we created three cohorts of interest: a “healthy” population of patients with no identified risk factors for cholangiocarcinoma; an “at-risk” population with at least one general risk factor, but none of the TOP5; and a cohort with one general risk factor plus two of the TOP5 criteria, an elevated GGT lab value plus another, named “GGT +1” cohort. Patients with pancreatic cancer were excluded due to errors in diagnostic overlap with cholangiocarcinoma. Propensity score matching was utilized to reduce the influence of other identified covariates: demographics, BMI, diabetes, etc. Cholangiocarcinoma (ICD: C22.1, C24) must have occurred at least 1 year after the index event, to exclude non-detected cancer at enrollment.

Results
In females, 200 outcomes occurred among ~73,000 “GGT +1” patients, 37 in ~75,000 “at risk,” and ≤10 in ~75,000 “healthy.” In males, 312 outcomes were observed in ~74,000 “GGT +1,” 66 in ~77,000 “at risk,” and ≤10 in ~80,000 “healthy.”
Compared to the “healthy” cohort, “GGT +1” hazard ratios (HR) were 77.1 (95% CI: 24.7-241.2) for females and 95.1 (35.5-255.1) for males. Compared to the “at risk” group, “GGT+1” HRs were 7.6 (5.3-10.7) for females and 6.5 (5.0-8.5) for males.

Conclusion
The GGT +1 group demonstrated a higher incidence of cholangiocarcinoma compared to at-risk and healthy populations. Analyses revealed strong associations, evidenced by high hazard ratios, suggesting the predictive utility of the TOP5 model as a screening tool. Future directions include applying the model to prospectively collected data to further validate predictive performance. This study, limited by reliance on ICD-based data, may prove unreliable from incorrect charting.

Cholangiocarcinoma Risk in a Real-World Population: Validation of a TOP5 Model Derivative

Background: Group A Streptococcal (GAS) pharyngitis is a common cause of sore throat, but complications like post-streptococcal reactive arthritis (PSRA) are less frequently recognized, particularly in adults with atypical presentations. PSRA typically presents with early-onset, nonmigratory joint pain and limited response to NSAIDs. This case highlights an atypical presentation of PSRA in a young adult, emphasizing the difficulty in diagnosing this condition.

Case Presentation: A 28-year-old female who presented with a sore throat, non-pruritic rash, dysuria, and acute left ankle pain that impaired weight-bearing. Initial rapid strep and mononucleosis tests were negative, and she was prescribed cephalexin. The following day, she returned with worsening joint pain and persistent dysuria; a repeat rapid strep test was positive, and treatment was switched to amoxicillin-clavulanate and topical NSAIDs. Laboratory results revealed elevated inflammatory markers (ESR 51 mm/hr, CRP 36 mg/L), normal ASO titer, low MCH/MCHC, mildly elevated TSH, and negative autoimmune and STI panels. Follow-up bloodwork six weeks later showed resolution of TSH without intervention, new-onset normocytic anemia, and vitamin D insufficiency.

Discussion: This case illustrates an atypical manifestation of PSRA in an adult: afebrile, initially false-negative for GAS, and presenting with monoarticular arthritis and dysuria in the absence of urinary infection. The diagnostic course was further complicated by the normal ASO titer and the evolving lab profile. This report underscores the limitations of current diagnostic tools such as RADTs and ASO in identifying streptococcal complications in non-classic cases. Clinical judgment, repeat testing, and ongoing assessment played a critical role in this patient’s care. This case underscores the limitations of current diagnostic tools and highlights the need for improved diagnostic strategies and follow-up in adult patients with evolving symptoms and initial negative testing.


A Diagnostic Challenge: Atypical Streptococcal Infection with Monoarticular Arthritis and Dysuria

Background
Iododerma is a rare cutaneous condition that results from exposure to high levels of iodine, often from imaging contrast, medications like amiodarone, or topical antiseptics. Its nonspecific clinical presentation and histological resemblance to infectious conditions make for a challenging diagnosis.

Case Presentation
A 64-year-old female with multiple chronic conditions, including stage 4 CKD, atrial fibrillation, and HFpEF, was admitted for right lower lobe pneumonia and underwent contrast-enhanced CT imaging. She subsequently developed multiple painful, non-pruritic, purpuric skin lesions, initially appearing on her left arm and later spreading to both upper extremities over 4 days. She was transferred to SLU for rheumatology and dermatology evaluation due to concern for vasculitis. Physical exam revealed purpuric skin lesions, erosions, crusting, and scattered bruising on both forearms and the right posterior arm. Based on this presentation, the initial differentials included several neutrophilic dermatoses, such as Sweet’s syndrome and EED, vasculitis, and deep fungal or atypical mycobacterial infections. The workup included a shave biopsy of lesions from the right posterior upper arm and punch biopsies of lesions from bilateral anterior forearms. Skin biopsies revealed ulceration, necrosis, acanthosis, and dense dermal neutrophilic infiltrates with vacuole-like structures resembling Cryptococcus. However, GMS, tissue Gram, and Fite stains all returned negative. An iodine level was also obtained and returned significantly elevated at 10,074.4 micrograms per liter. In the context of her recent contrast exposure and histological findings, her elevated iodine levels supported the diagnosis of iododerma. The patient was treated with a 30-day course of oral prednisone. There has been no recurrence of the skin lesions after discontinuation of the prednisone.

Discussion
Iododerma can present a diagnostic challenge due to its rarity and histopathological features resembling Cryptococcoid-like structures pointing towards infectious dermatoses. In this case, the clinical picture and histology initially suggested a fungal infection, but negative stains and a history of recent iodine exposure helped guide the diagnostic process towards iododerma. Ultimately, iododerma is a diagnosis of exclusion that requires careful integration of clinical history, histopathological examinations, and other lab testing. Early corticosteroid treatment is the recommended treatment and can lead to favorable outcomes.

Iododerma Mimicking Cryptococcoid Neutrophilic Dermatosis

Background 
Euglycemic diabetic ketoacidosis (DKA) is a unique variant of diabetic ketoacidosis that presents in patients with normal or mildly elevated blood glucose levels, defined as a serum glucose concentration < 250 mg/dL. As euglycemic DKA has an association with newer diabetes treatments, it becomes increasingly important for clinicians to develop an awareness and further recognize its presentation to prevent serious complications and adverse patient outcomes. 
Case Presentation 
A 61-year-old female with type II diabetes and coronary artery disease presented to the emergency department with chest pain, fatigue, and a bilateral upper extremity rash that had worsened over two days. She was afebrile and hemodynamically stable. EKG and troponins were normal. Physical exam was unremarkable except for a bilateral urticarial rash extending from the hands to the forearms. Her initial labs showed a high anion gap metabolic acidosis (bicarbonate 12 mmol/L, anion gap 19 mmol/L) with a glucose of 164 mg/dL. CBC was normal. She was treated with hydroxyzine, methylprednisolone, and famotidine. 
Overnight, her symptoms improved, but her morning labs showed persistent acidosis (anion gap 17 mmol/L, bicarbonate 16 mmol/L) and a glucose of 229 mg/dL. Ketones were 1.49 mmol/L, and venous blood gas revealed pH 7.2, pCO₂ 38 mmHg, HCO₃ 16.7 mmol/L. A diagnosis of euglycemic DKA was made, likely triggered by her use of Dapagliflozin. She was treated with IV insulin, D5W fluids, and discontinuation of her SGLT-2 inhibitor. Her condition stabilized, and she was discharged after three days. 
Discussion 
Despite normal glucose levels, patients with euglycemic DKA exhibit typical DKA features: metabolic acidosis, ketonemia, and an elevated anion gap. The diagnosis is often missed due to the absence of significant hyperglycemia. While traditionally associated with type I diabetes, euglycemic DKA also occurs in type II diabetes, particularly in patients on SGLT-2 inhibitors or those with precipitating factors such as fasting. The mechanism involves insulin deficiency and elevated counterregulatory hormones, leading to increased lipolysis and ketogenesis. Concurrent glycosuria induced by SGLT-2 inhibitors contributes to the misleading euglycemia. 
Symptoms typically include nausea, vomiting, abdominal pain, and general malaise. Treatment consists of IV fluids, insulin, and electrolyte management, with close monitoring of the patient’s clinical and laboratory status. 


Unmasking the Hidden Culprit: A Presentation of Euglycemic DKA

Background:
Chronic subdural hematoma (CSDH) is a common condition in the elderly, often resulting from minor head trauma. While surgical evacuation remains the standard treatment, recurrence rates up to 20% have driven interest in middle meningeal artery (MMA) embolization as a minimally invasive alternative. By targeting the MMA’s role in supplying the neo-membranes associated with CSDH, embolization interrupts the cycle of hemorrhage and inflammation. Although MMA embolization is generally safe, rare complications may occur, including contrast-induced neurotoxicity (CIN), a transient neurological syndrome that arises after iodinated contrast exposure, once other causes have been excluded.

Case Presentation:
An 82-year-old female with a history of hypertension, hyperlipidemia, and ovarian cancer presented with progressive bifrontal headache two months after a fall. Neurological examination was non-focal. Non-contrast head computed tomography (CT) revealed a 1.7 cm left-sided acute-on-chronic subdural hematoma with mass effect. Laboratory evaluation, including coagulation studies, was unremarkable. The patient underwent elective left MMA embolization under conscious sedation.
Approximately one hour post-procedure, she developed sudden-onset expressive aphasia, right-sided weakness, and leftward gaze deviation, with a National Institutes of Health Stroke Scale (NIHSS) score of 16. Emergent non-contrast head CT and CT angiography (CTA) of the head and neck revealed no acute hemorrhage or large vessel occlusion. Brain magnetic resonance imaging (MRI) showed no evidence of acute ischemia. Supportive care with permissive hypertension was initiated. Neurological symptoms resolved completely within 24 hours. Based on the rapid onset and resolution of symptoms, with no imaging abnormalities, CIN was diagnosed. The patient was discharged in stable condition one week later.

Discussion:
MMA embolization is an effective and increasingly utilized treatment for CSDH, particularly in patients with recurrence, high surgical risk, or surgically challenging anatomy. It offers a minimally invasive approach with lower recurrence rates compared to traditional surgery. Although generally safe, CIN is a rare but significant complication of neurointerventional procedures, with reported incidence ranging from 0.15% to 2.5%. It typically presents within hours of contrast exposure with transient neurological symptoms such as encephalopathy, focal deficits, or cortical blindness. Risk factors include advanced age, hypertension, and higher contrast volume. In this case, CIN closely mimicked acute ischemic stroke. Fortunately, it is
typically self-limiting and resolves within 24-72 hours with supportive care. Further research is needed to optimize MMA embolization use and to better understand CIN’s mechanisms and management.

Stroke or Not? Case of Contrast-Induced Neurotoxicity Following Middle Meningeal Artery Embolization

Background
Radiation therapy significantly impacts the success and cosmetic outcome of implant-based breast reconstruction by inducing irreversible alterations in the surrounding tissues. These changes can include fibrosis, radiation dermatitis, tissue damage, and fat necrosis, which collectively impair the reconstructive process. A common complication is the formation of a dense, fibrotic capsule around the implant, known as symptomatic capsular contracture, which can result in breast firmness, asymmetry, and suboptimal aesthetic outcomes. Radiated tissue also demonstrates reduced elasticity, impaired vascularity, and higher susceptibility to wound healing complications such as dehiscence, infection, and implant loss. Reoperation on irradiated pockets is particularly high-risk due to diminished regenerative capacity, increased fibrosis, and poor tissue quality.
Case Presentation
A patient presented with significant post-radiation asymmetry following bilateral implant-based breast reconstruction. The left, radiated breast developed a tight, contracted implant pocket, resulting in a smaller, higher-riding, and firmer breast mound than the contralateral side. Attempts to revise the radiated side were contraindicated due to concerns about implant exposure, infection, and further tissue compromise. To address the asymmetry, reconstructive efforts focused on modifying the non-radiated breast. The original 500 cc implant was replaced with a 480 cc ultra high-profile Mentor MemoryGel implant, which was tightly wrapped in two large perforated acellular dermal matrix (ADM) sheets. These sheets were configured in a bouffant-style to mimic the fibrotic, projected contour of the radiated side. The ADM was anchored high on the chest wall using 2-0 PDS sutures for secure positioning. Additional skin was excised, and the implant capsule was reinforced to prevent bottoming out, ultimately achieving a symmetric result. 
Discussion
This case presentation illustrates the reconstructive challenges posed by radiation therapy, particularly the inability to safely operate on radiated tissue due to compromised vascularity and structural integrity. Instead of correcting the radiated side directly, the surgical team mirrored its shape and projection by modifying the non-radiated breast. The use of ADM provided structural support and allowed precise shaping to achieve symmetry. This strategic approach addressed both aesthetic and functional concerns while minimizing risk. For patients with similar post-radiation asymmetries, individualized planning that avoids direct manipulation of radiated tissue and instead focuses on contralateral adjustments can provide more optimal outcomes.


Achieving Breast Symmetry in Implant Based Reconstruction following Radiation by Manipulating the Non-irradiated Breast


A Rare Case of Iatrogenic Hemothorax Following Thoracentesis Secondary to an Aberrant Posterior Intercostal Artery


Background

Thoracentesis is the initial procedure performed when diagnosing and treating a pleural effusion. The most common complication for this procedure is pneumothorax, with an incidence reported up to 6%, whereas incidence of hemothorax is approximately 1%.


Case Presentation

A 79-year-old female with history of atrial fibrillation, chronic obstructive pulmonary disease, deep vein thrombosis, type 2 diabetes, and early onset myelodysplastic syndrome presented to the emergency department experiencing chest pain and shortness of breath and was admitted to the hospital for atrial fibrillation with rapid ventricular response. Treatment was initiated, including apixaban. Workup revealed a left pleural effusion of unknown origin, so ultrasound-guided diagnostic thoracentesis was successfully performed using a posterolateral approach, and furosemide was initiated.

Within 2 hours, the patient developed extreme dyspnea, becoming hemodynamically unstable, warranting a transfer to intensive care. Repeat chest X-ray revealed a large pleural effusion, so a chest tube was emergently inserted, removing 1 liter of sanguinous fluid.

Given the rapid development of the hemothorax along with the patient’s anticoagulation treatment and recent thoracentesis, a chest computerized tomography angiogram (CTA) was ordered to detect the source of arterial extravasation. It revealed a ruptured aberrant branch of the left 9th intercostal artery coursing inferiorly across the intercostal space and above the 10th rib, which was the cause of the patient’s rapidly developing hemothorax. This artery was treated with coil embolization, which achieved hemostasis and prevented hemothorax recurrence.


Discussion

Hemothorax is a rare complication of thoracentesis when standard technique based on foundational anatomical knowledge is followed. Proper technique involves inserting the needle above the superior rib margin to avoid the neurovascular bundle. Notably, therapeutic anticoagulation is not a contraindication to thoracentesis and has not been shown to increase bleeding risk. The use of imaging guidance reduces the risk of procedural complication; however, anatomical variants and age-related vascular changes, such as increased tortuosity of intercostal vessels, increase the risk. Vessel tortuosity makes medial approaches more hazardous, supporting the recommendation for a posterolateral entry point in the elderly population. 

In the event of suspected vascular injury, as seen in this case, CTA is the diagnostic modality of choice. When active extravasation is identified, coil embolization serves as the preferred intervention to achieve hemostasis and prevent recurrence. This case illustrates a rare and serious complication of thoracentesis secondary to a previously undocumented anatomical variant of the posterior intercostal artery leading to a nearly fatal hemothorax despite appropriate thoracentesis technique.


Safe Technique, Hidden Danger: Post-Thoracentesis Hemothorax from an Intercostal Variant

Background:
The aftermath of whiplash injuries from motor vehicle accidents (MVA) is estimated to cost nearly $4 billion annually in the United States and inflates over sevenfold with litigation costs. In the relationship between whiplash and litigation, prior research cites that no-fault systems generally limit the opportunity for further litigation. However, New York State utilizes a no-fault system that may award plaintiffs further compensation based on a serious injury threshold, for which both injury and treatment are considered. Most MVA do not biomechanically cause disc herniations and are conservatively treated, yet these injuries are frequently litigated. This study examines how treatment of cervical disc herniations claimed in no-fault litigation may impact award compensation, thus evaluating overtreatment as a potential tool to increase compensation.

Methods:
We queried the Thomson Reuters Westlaw database for Jury Verdicts & Settlements in New York that were categorized under “no-fault” and “motor vehicle” and included cervical disc herniation in the claim. 181 of 383 cases from 2005-2011 met the injury criteria and had detailed therapeutic methodology, litigation outcome, and award amount. We categorized cervical disc herniation treatments as surgical or non-surgical. We then separated cases that favored the plaintiff to any degree or were resolved alternatively (Plaintiff Verdict, Settlement, Mediated Settlement, Arbitration, Mixed Verdict) from cases with defendant-oriented outcomes (Defendant Decision and Defendant Verdict). The mean and median true awards (actual value collected by the plaintiff, potentially adjusted by pre-trial high-low agreement) were compared across groups and the Mann-Whitney U Test was used to test significance (p<0.05).

Results:
Of the 181 cases that met our initial query criteria, we included 18 cases describing surgical treatment and 80 cases describing non-surgical treatment that resulted in a plaintiff-oriented outcome. Analysis of included cases demonstrated a significantly greater true award for surgical treatment(s) (n=18, M=$959,257.19, Mdn=$637,500) compared to non-surgical treatment(s) (n=80, M=$195,184.10, Mdn=$74,250, U=141, p<0.001). There was no significant correlation to suggest that either treatment group more often resulted in a defendant or plaintiff-oriented outcome.

Conclusion:
Substantial financial incentives may exist for cervical disc surgical intervention in whiplash compared to more conservative, non-surgical treatment. While neither treatment group resulted in significantly more plaintiff-oriented outcomes, the compensation potential for invasive intervention may still prompt overtreatment. Further work is needed to determine how the medical and legal communities can minimize the economic toll of whiplash while ensuring patients are receiving appropriate care and just compensation.

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