United States

Background: Female reproductive aging remains a significant challenge in reproductive medicine and is characterized by a decline in oocyte quantity and quality, as well as uterine and cervical dysfunction, all of which contribute to infertility, pregnancy complications, and congenital defects. As maternal age continues to rise worldwide, there is a pressing need to prevent age-associated infertility and pregnancy complications. The molecular mechanisms underlying female reproductive aging are complex and not yet fully understood. We have recently demonstrated that the Spag17 gene is a key regulator of female reproductive aging. To better understand its mechanism of action, the objective of this research was to investigate the effects of Spag17 loss of function in stromal cells from cervical tissue at the molecular level.

Methods: Stromal cells and cervical tissue were isolated from wild-type and Spag17 knockout mice and used to assess the activation of molecules involved in profibrotic, inflammatory, and senescence signaling pathways by immunofluorescence and immunohistochemistry. Image analysis was conducted using Zen 10 and ImageJ software. Statistical analysis was performed using GraphPad Prism 10.

Results: Profibrotic signaling markers such as SMAD2/3 for the TGF-β pathway, YAP1 for the Hippo pathway, procollagen as a marker of collagen synthesis, and ASMA as a myofibroblast marker, were found constitutively activated in knockout cells. Additionally, a higher number of infiltrating immune cells (CD45⁺ and F4/80⁺) were observed in knockout cervical samples. Activation of these molecules led to the nuclear translocation and activation of the senescence-associated proteins P16, P21, and P53, as evidenced by increased nuclear-to-cytoplasmic ratios.

Conclusions: Our results reveal that Spag17 influences female reproductive aging by regulating the activation of profibrotic, inflammatory, and senescence-related molecular signaling pathways.

AMA Research Challenge 2025 

Female reproductive aging is associated with loss of Spag17 gene function

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Objective: Tears of the gluteus medius tendon are a well-recognized cause of lateral hip pain and gait dysfunction, especially in older adults. Although surgical repair has demonstrated favorable clinical outcomes, persistent challenges such as gap formation, suture pull through, and inadequate healing continue to contribute to repair failure. BioBrace is a bioinductive scaffold composed of collagen and PLLA microfilaments designed to provide early mechanical support while facilitating tissue regeneration. This study aims to biomechanically evaluate the effectiveness of BioBrace augmentation in gluteus medius tendon repair using a cadaveric model.
Methods: Twelve fresh-frozen human cadaveric hips from six matched pairs will be used in this controlled biomechanical study. Specimens will be randomized to receive either standard double-row suture anchor repair or BioBrace-augmented repair. All constructs will utilize ConMed Revo anchors and Hi-Fi sutures in a standardized suture bridge configuration. In the augmentation group, a 40 × 60 × 3 mm BioBrace
scaffold will be secured medially and laterally within the construct. Biomechanical testing will consist of cyclic tensile loading (10–125 N for 150 cycles) followed by load-to-failure testing using a servohydraulic testing system. Outcome measures will include gap formation, ultimate failure load, linear stiffness, and failure mode. Statistical analysis will be performed using paired t-tests or Wilcoxon signed-rank tests based on data distribution.
Results: While results are currently pending, this study has secured $50,000 in funding and testing is actively underway. Based on prior biomechanical research in rotator cuff repair, we hypothesize that BioBrace augmentation will result in reduced gap formation, higher ultimate load to failure, and increased construct stiffness when compared to non-augmented repairs. The collagen matrix and PLLA
reinforcement of the scaffold are designed to both distribute force and provide early mechanical strength, which may reduce the incidence of suture pull through, a common failure mode in tendon repair. Using a matched-pair design will help minimize inter-specimen variability, strengthening the internal validity of our biomechanical comparisons. If the hypotheses are confirmed, this study will offer
the first cadaveric biomechanical evidence supporting the use of BioBrace in gluteus medius repairs. These data may justify future translational or clinical studies and support incorporation of biologic scaffolds in technically demanding abductor tendon reconstructions.
Conclusion: This study represents a critical step in evaluating the mechanical benefits of BioBrace augmentation for gluteus medius tendon repair. With dedicated funding and testing in progress, we anticipate our results will support the integration of bioinductive scaffolds into the surgical armamentarium for managing complex abductor tendon tears.

Biomechanical Evaluation of BioBrace Augmentation in Gluteus Medius Tendon Repair: A Cadaveric Study

Background
Acanthamoeba keratitis (AK) is a rare but serious eye infection caused by the opportunistic protozoan pathogen Acanthamoeba castellanii. AK can also lead to disseminated disease and encephalopathy in immunocompromised individuals. First-line treatment is has a prolonged schedule, due to weak antiamoebal medicines and limited therapeutic options; and sometimes, even with pharmacological intervention, surgery may be needed and patients can still lose their sight. New effective treatments are needed. Protein kinases make up a significant portion of the A. castellanii proteome, suggesting that protein kinase inhibitors (PKIs), already developed for other indications like cancer and autoimmune diseases, may be viable for repurposing if selective against pathogen targets.
Methods
PKIs were obtained from AOBIOUS (Gloucester, MA) and reconstituted in DMSO. These compounds were screened in vitro against A. castellanii (Neff strain, ATCC 30100) cultured in YPG media in 96-well plates. Trophocidal activity was quantified using a Resazurin fluorescence. Protein alignments were performed via UniProt to assess sequence identity between known human tyrosine kinases and putative kinases in A. castellanii.
Results
Initial screening at 20 μM revealed multiple PKIs with inhibitory activity against A. castellanii trophozoites. Dose-response curves demonstrated micromolar EC50 values for compounds TUN-00048 and TUN-00055. Sequence alignment showed approximately 27% identity between two putative A. castellanii tyrosine kinases and the human Abl1/Abl2 kinases, the known targets of the active PKIs.
Conclusion
These preliminary findings support the potential utility of repurposing PKIs as therapeutic agents against AK. Continuing studies will expand the compound library and will clone and express A. castellanii tyrosine kinases for detailed structure-activity relationship and profiling for selectivity for amoebal kinases over patient kinases. Such work could lay the foundation for novel, targeted therapies for this difficult-to-treat infection.

PKIdnapped: Hijacking Cancer Drugs to Fight Acanthamoeba

Background
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset disorder caused by somatic mutations in the UBA1 gene. It primarily affects older men and is characterized by systemic inflammation and hematologic abnormalities. Despite growing interest in VEXAS, the literature remains limited to case reports and small series, with no comprehensive synthesis of U.S. cases to date. This scoping review addresses this gap by describing the clinical features, diagnostic pathways, treatment outcomes, and management strategies in U.S. patients, offering key insights for clinicians.

Methods
We searched PubMed, Web of Science, and CINAHL through April 2025 to identify case reports and series of U.S. patients diagnosed with VEXAS syndrome. Articles were eligible if they reported a UBA1 mutation consistent with VEXAS syndrome and included sufficient clinical detail for data extraction. Non-U.S. cases, reviews, commentaries, and abstracts without full reports were excluded.

Results
Of 194 citations screened, 105 underwent full-text review, and 31 articles met inclusion criteria, describing 43 unique male patients. The median reported age at diagnosis was 66 years. The p.Met41Leu variant was identified in 25/43 patients (58%), making it the most common UBA1 mutation. Macrocytic anemia was reported in 41/43 patients (95%), and bone marrow vacuolization in all cases. Cutaneous findings were noted in 38/43 patients (88%), including Sweet syndrome or neutrophilic dermatoses in 18/43 (42%) and histiocytoid variants in 5 cases. These were often misclassified as lupus or vasculitis, causing diagnostic delays of 1-3 years. Other features included fever, chondritis, and inflammatory arthritis. Myelodysplastic syndrome was diagnosed in about half of patients. All patients were treated with corticosteroids, and among the 31 with tapering data, 24/31 (77%) experienced symptom flares when prednisone was reduced below 20-30 mg daily. Immunosuppressants and biologics showed limited benefit.

Conclusions
U.S. cases of VEXAS syndrome consistently reveal a pattern of relapsing inflammation, diagnostic delays, and prolonged corticosteroid use, underscoring the need for more effective treatments and earlier diagnosis. Most steroid-sparing agents provided limited benefit, though some targeted therapies showed improvement in selected patients. Earlier recognition may be supported by awareness of hallmark features like cutaneous inflammation, macrocytic anemia, and cytopenias in older males, leading to timely diagnoses and better outcomes. Genetic testing for UBA1 mutations should be considered for early diagnosis and to guide targeted therapies.

Clinical Characteristics and Reported Cases of VEXAS Syndrome in the United States: A Scoping Review

Empowering Diabetics Through Structured Blood Glucose Logging: A Community-Based Quality Improvement Initiative
Background
Diabetes affects over 537 million adults globally, with projections rising to 783 million by 2045. In underserved communities like East Trenton, glycemic control remains a major challenge due to low health literacy, limited access to glucometers, and lack of patient engagement. Many patients on insulin or sulfonylureas are not routinely tracking blood glucose levels, leading to delayed therapeutic adjustments and increased risk of complications.

Objective
To increase the proportion of diabetic patients on hypoglycemic agents (insulin or sulfonylureas) maintaining structured blood glucose logs from a baseline of 25–30% in August 2023 to at least 75% by May 2024.

Methods
This resident-led QI initiative was conducted at East Trenton Clinic from August 2023 to May 2024. Patients on insulin or sulfonylureas were identified and educated on the frequency and timing of glucose monitoring based on ADA guidelines. A standardized logbook template was distributed. During follow-up visits, providers reviewed logs, reinforced lifestyle counseling, and made timely medication adjustments. Focused walk-in visits were also arranged for patients with poor glycemic control. Barriers such as cost, literacy, and documentation format were addressed iteratively.

Results
By May 2024, over 75% of target patients had begun maintaining structured glucose logs. Patient engagement improved, with many reporting increased understanding of their disease and actively participating in their care. Clinic teams were able to identify trends earlier, allowing for prompt medication changes. Despite improvements, challenges included financial constraints, literacy issues, and time limitations during routine visits.

Conclusions
This QI initiative demonstrated that structured glucose logging can significantly improve patient engagement and glycemic monitoring in underserved populations. Empowering patients with the tools and education to manage their diabetes fosters more timely clinical decision-making. Future efforts will focus on integrating log templates into the EHR, expanding focused diabetes visits, and tracking corresponding improvements in HbA1c.


Empowering Diabetics Through Structured Blood Glucose Logging: A Community-Based Quality Improvement Initiative

Abstract Title: 
Avoiding the scalpel: Implementation of radiologic and clinical markers to reduce the need for biopsy in tumefactive MS

Background:
Tumefactive multiple sclerosis (TMS) is a rare subtype of MS characterized by large (>2 cm) demyelinating lesions that often mimic brain tumors or abscesses. Symptoms can range from visual changes, aphasia, cognitive changes, paresthesia, incontinence, etc—often raising concern for malignancy, stroke, or infection.
TMS affects approximately 1–3 per 1,000 MS cases, typically in young adults aged 20–40. Lesions are often enhancing, edematous, and radiographically similar to lymphoma, glioma, or abscess, frequently leading to brain-biopsy for diagnosis. However, emerging literature highlights distinct imaging and clinical patterns that may allow for confident, noninvasive diagnosis—potentially avoiding unnecessary procedures and reducing patient risk.

Methods:
This study retrospectively reviewed four patients (2018–2025) who presented to a metropolitan emergency department, were ultimately diagnosed with TMS, and are now followed at the same MS specialty clinic. For each case the presenting symptoms, early diagnostic impressions, MRI findings (lesion size, enhancement pattern, ring-like features, mass effect, midline shift, diffusion restriction), CSF results (glucose, cytology, oligoclonal bands), response to corticosteroids, and the input of a multidisciplinary tumor board were all compared to investigate possible patterns.

Results:
Presenting symptoms included visual field deficits, aphasia, dysarthria, cognitive decline, loss of motor control, rapid-onset-weakness, and hemiparesis. All four patients were initially suspected of neoplasm (specifically low-grade-glioma). One patient underwent open craniotomy/biopsy after imaging revealed an incompletely enhancing lesion with moderate vasogenic edema, mild mass effect, notable midline shift, and CSF studies were negative for oligoclonal bands. However, this patient returned to the ED following discharge with worsening headaches; subsequent imaging demonstrated lesion expansion and increased edema.

Of the remaining three patients, two were scheduled for biopsy but deferred following tumor board reassessment. The fourth was diagnosed with TD relatively quickly compared to other cohort members. Shared features among these non-biopsied patients included open/incomplete ring enhancement without necrosis, minimal or no mass effect or midline shift, presence of oligoclonal bands, and clinical/radiographic improvement with corticosteroids.
All four patients have since stabilized or improved on immunotherapy

.Conclusion:
While brain-biopsy remains necessary in select cases, specific imaging and CSF features—alongside steroid responsiveness—may support noninvasive diagnosis of tumefactive demyelination. In this cohort, pattern recognition enabled safe avoidance of biopsy in most cases. These findings may inform evolving diagnostic strategies in neurology and neuro-surgery/oncology, improving care for patients with atypical demyelinating lesions.

Avoiding the scalpel: Implementation of radiologic and clinical markers to reduce the need for biopsy in tumefactive MS

Background: Within osteopathic medical education, understanding men’s perspectives on depression is crucial for developing more inclusive and effective interventions. This study explored how male medical students at Noorda College of Osteopathic Medicine (Noorda-COM) perceive, experience, and respond to depression.

Methods: We conducted a qualitative interview study with 33 male Noorda-COM students across multiple graduating classes. Participants completed semi-structured interviews that addressed perceptions of depression, stigma, willingness to seek care, and relationships with healthcare providers. Interviews were transcribed, coded, and thematically analyzed to identify shared perspectives and recurrent themes.

Results: Three primary themes emerged:

Money/Time Constraint: Most participants answered their biggest inhibitor to obtaining health being either not enough time or too expensive. Accessibility continues to be the most common answer amongst our participants as research and interviews continue.

Stigma – Mixed Results: While some participants endorsed progress toward greater openness, others described internalized stigma and family pressures that perpetuated silence. Depression was sometimes equated with weakness, creating barriers to acknowledging symptoms and seeking care.

Relationships With Providers: Strong, trusting provider relationships were repeatedly identified as a key factor in willingness to seek help. Participants emphasized the importance of feeling understood and respected, with several noting that without this trust, they would not disclose symptoms.

Conclusion: Findings highlight how masculine identity, stigma, and the perception of competing responsibilities intersect to influence men’s willingness to engage in care. Although awareness of depression has improved, significant barriers remain—particularly around access and vulnerability with their provider. Provider rapport and empathetic communication emerged as critical facilitators of seeking help. These insights can inform targeted mental health interventions, medical education, and institutional wellness programs aimed at normalizing depression treatment and reducing stigma among male medical students.

Men's Perception of Depression: A Qualitative Interview Study

Background
The evaluation of readily measurable biomarkers, such as platelet-to-albumin ratio (PAR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and neutrophil-to-lymphocyte ratio (NLR), has gained prominence as an effective method for predicting outcomes in various inflammatory diseases. Rheumatoid Arthritis (RA) is characterized by chronic inflammation and requires a comprehensive therapeutic approach that changes depending on the severity of the disease. Upadacitinib is an FDA-approved medication for the treatment of moderate-to-severe rheumatoid arthritis and its mechanism of action includes inhibition of Janus Kinase (JAK), a key player in the inflammatory cascade. This study aims to evaluate the response to Upadacitinib in moderate to severe rheumatoid arthritis by assessing the ratios between PAR, NLR, PLR and PNR.

Methods
We identified patients on Upadacitinib via Epic’s Slicer Dicer function. Patients with incomplete or duplicated information were excluded and we obtained a final cohort of 53 patients. Data collected included demographic information, treatment length, and response to treatment. We reported continuous variables as mean (range) and categorical variables as number (percent). Between-group differences for continuous variables were analyzed using Student’s T-test. We consulted previously published studies and created our own receiver operating characteristic (ROC) curve to determine cut-off values for the ratios.

Results
We analyzed a total of 53 patients receiving Upadacitinib. The overall mean age was 62.4, with treatment responders being slightly younger at 61.8 and treatment non-responders/partial responders slightly older at 63.6. Overall sex distribution was 28.30% males and 71.70% females. The body mass index (BMI) difference was clinically negligible. The mean length of treatment (LOT) was 21.8 months overall, with a significant difference between treatment responders at 61.8 months and treatment non-responders/partial responders at 12.6 months. Treatment responders displayed a lower PAR at 67.56 ±20.46, compared to partial/non-responders at 81.33 ±21.97 with a p-value of 0.021. PNR exhibited a similar tendency with treatment responders at 61.31 ±27.73 and partial/non-responders at 72.36 ±23.60 with a p-value of 0.028. ROC analysis and Youden’s J-point suggested optimal cut-off values for PAR at 83.53 (AUC: 0.683, p = 0.0243) and for PNR at 58.05 (AUC: 0.0.672, p = 0.025), with a resulting 83.3% sensitivity and 47.06% specificity for PAR and 61.11% sensitivity and 70.59% specificity for PNR.

Conclusion
PAR and PNR demonstrated a statistically significant difference in moderate to severe RA patients that responded to treatment with Upadacitinib compared to similar patients with partial or no response.

Role of platelet-to-albumin ratio, platelet-to lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to- lymphocyte ratio to predict response to Upadacitinib treatment in moderate to severe rheumatoid arthritis

Background: Renal cell carcinoma (RCC) presenting with extension of tumor thrombus into the inferior vena cava (IVC) and right atrium is a rare, life-threatening condition that requires surgical treatment with the simultaneous involvement of multiple surgical subspecialties.
Case Description: We present a case of a 65-year-old male who presented to the hospital with syncope, and was subsequently diagnosed with a level four cavoatrial sinus tumor thrombus extending from a primary renal mass. The patient had no concerning physical exam and electrocardiogram (EKG) findings, however, transthoracic and transesophageal echocardiography revealed severely reduced systolic function with a hyperechoic, vascular, and cystic mass extending from the IVC into the right atrial cavity that originated from a renal mass that involved the right renal vein and IVC.
Conclusions: The purpose of this case is to highlight the critical importance of early recognition and timely intervention in patients who present with nonspecific symptoms, such as syncope, which may signal underlying fatal conditions. This case illustrates RCC with tumor thrombus extending into the IVC and right atrium. This rare but serious manifestation highlights the need for a high index of suspicion and comprehensive evaluation when faced with vague clinical presentations. Early recognition not only facilitates appropriate management but can also alter the patient’s prognosis and survival outcomes.

The Atrial Mass without an Auscultatory “Plop”: Renal Cell Carcinoma
Presenting with Cardiac Syncope

Background: Dieulafoy lesions are a relatively uncommon but important cause of gastrointestinal (GI) bleeding, accounting for around 5% of gastrointestinal bleeds. Characterized by a dilated, aberrant submucosal artery that erodes through overlying mucosa, these lesions can result in life-threatening hemorrhage. Small intestinal Dieulafoy lesions are exceedingly rare and often evade early detection due to location and their intermittent bleeding pattern. In this report, a rare case of massive and recurrent hematochezia caused by a Dieulafoy lesion in the terminal ileum is presented.
Case Presentation: A 68-year-old female with a complex medical history including chronic kidney disease stage V on intermittent hemodialysis, type 2 diabetes, severe aortic stenosis post aortic valve replacement, systolic heart failure, chronic hypoxic respiratory failure, and chronic anemia was transferred to a quaternary medical center for evaluation of severe, recurrent hematochezia. Hemoglobin on presentation was 5.2 g/dL (baseline 8.5–9.5). Prior to transfer, the patient underwent extensive diagnostic evaluation, including esophagogastroduodenoscopy (EGD), colonoscopy, tagged RBC scan, and CT angiography of the abdomen and pelvis, all of which failed to localize a source of bleeding.

Subsequent capsule endoscopy reported active small bowel bleeding from an undetermined source. Double balloon retrograde enteroscopy demonstrated blood throughout the colon and distal ileum, but without an obvious culprit lesion. Due to continued overt hematochezia requiring ongoing transfusions, repeat CT angiography was performed, which suggested possible arterial extravasation but subsequent angiography by interventional radiology team again failed to localize the source.

A final effort at identifying the lesion with repeat retrograde push enteroscopy successfully encountered a solitary Dieulafoy lesion in the terminal ileum with active pulsatile bleeding. Durable hemostasis was achieved with argon plasma coagulation, PuraStat application, and the placement of two hemostatic clips. In total, the patient received 33 units of packed red blood cells, in addition to five units of other blood products prior to achieving hemostasis. 

Discussion: This case highlights the diagnostic complexity and multidisciplinary approach required in managing life-threatening lower GI bleeding secondary to Dieulafoy lesions. A high index of suspicion is required for Dieulafoy lesions in patients with recurrent GI bleeding of unknown origin. It is crucial to consider deep enteroscopy and capsule endoscopy in cases of small intestine bleeding. Moreover, procedures may need to be repeated due to Dieulafoy lesions' sporadic, severe bleeding pattern. We emphasize the importance of further research on optimal timing and sequencing of diagnostic modalities regarding small intestinal Dieulafoy lesions.

Terminal Ileal Dieulafoy Lesion Resulting in Massive Hematochezia

Background 
Rhinoplasty is a surgical procedure that focuses on the nasal structure, enhancing both the appearance and function of the nose. Managing a cleft palate is incomplete without addressing secondary nasal deformities. An important aspect of correcting a cleft nose is addressing depressed and hypoplastic cartilage frameworks, which is key to the success of secondary rhinoplasty. 
Facial recognition is used to verify individuals based on their unique facial features, which is used for unlocking phones, conducting transactions, security purposes, and more. 
This case highlights emerging challenges at the intersection of modern technology and medicine. 
Case Presentation 
A 20-year-old Indian man with a previously operated right cleft lip & palate before 18 years, had a depressed right nostril, nasal tip, hypoplastic alar cartilage, and columella deviated to the left side. He underwent open rhinoplasty, right alar cartilage hitching to opposite upper lateral cartilage, and conchal cartilage graft to augment alar depression. This secondary rhinoplasty was performed for the aesthetic congenital deformity of the nose that is almost always associated with grade III cleft lip & palate deformity. After the operation, his face was unrecognizable to his latest smartphone, which made it difficult for him to get access to his phone as he did not know the backup password. This issue persisted for nearly 20 days, resolving once the swelling and inflammation subsided. 
Discussion 
This case highlights an unexpected challenge between modern technology and facial surgeries like rhinoplasty and smartphone facial recognition. With a lot of use of facial biometrics recently, in unlocking phones, accessing personal data, or authorizing payments, even a small problem like this can cause a lot of inconvenience. In this case, the patient was unable to access the mobile phone due 
to not remembering the backup password. 
This emphasizes the importance of patients’ preoperative counselling regarding possible problems with facial surgeries or rhinoplasty. Patients should be advised to disable facial recognition features or guarantee password access before surgery. These minor actions can make the patient stress-free from unnecessary issues. 
This case promotes a more comprehensive, technologically conscious method of surgery planning and patient education. 
As the world and technology emerge, interactions between cosmetic surgeries and digital systems are going to increase, further discussions and research would be needed for surgeries and their effects on new digital systems, and how to improve them.

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