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    Revisiting Ferritin Reference Ranges: A Case for Addressing Iron Deficiency in Women with Symptom-Driven Standards
    (2025) Amstutz, Julia; Bhadouriya, Ritika; Coffey, Gillian; Milhouse, Wynne; Mehta, Rakesh
    Iron deficiency (ID), even without anemia, is an insidious condition which reduces quality of life through diverse symptoms. Women are particularly susceptible due to menstruation, pregnancy, and childbirth, resulting in nearly 1 in 5 affected under current thresholds. ID is typically investigated when ferritin levels are below the lower limit of normal (LLN.) Apart from fatigue, many symptoms like hair loss, restless leg syndrome (RLS), angular cheilitis, and impaired cognition are rarely evaluated, furthering dependence on ferritin values for diagnosis. Foundational studies defining normal ferritin did not screen for symptoms or risk factors of ID, resulting in iron-deficient women in control groups. This has led to an erroneously low mean LLN of 9ng/mL for females amongst the five most used commercial laboratories. Many specialty societies and national guidelines target ferritin >30ng/ml for both sexes due to evidence of clinical ID below this level. A 31-year-old woman with a history of three pregnancies all requiring postpartum iron supplementation presented with fatigue, palpitations, and restless legs. She did not endorse pica, reflux, or nail changes. Her menstrual cycles are four days, regular, and include occasional penny-sized clots. Testing revealed normal hemoglobin and a ferritin of 22ng/ml (normal 10-106ng/ml). She was started on oral iron with a goal of ferritin >75ng/ml as per Sleep Medicine RLS treatment guidelines. At initial follow-up, fatigue was already markedly reduced with her ferritin up to 30ng/ml, a 36% increase. New reference ranges for ferritin with LLNs of at least 30ng/mL are required to better facilitate early diagnosis of ID, especially in high risk groups like menstruating women. Current ferritin reference ranges are bred from inappropriate studies that exclude symptoms and risk factors necessary to characterize ID. By redefining normal ferritin ranges, women can better receive care for symptoms that have perennially gone untreated.
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    The Use of Dialectical Behavior Therapy in Patients with Suicidal Ideation
    (2023) Gallagher, Clare; Sivamohan, Anjali; Andrews, Madeline; Coffey, Gillian; Raza, Mubashra
    Background: Dialectical behavior therapy (DBT) is a psychotherapeutic approach that aims to reduce incidences of self-harm and suicidal ideations through use of skills-based training and individualized psychotherapy. While DBT has been applied to patients with borderline personality disorder (BPD), it can potentially be used in anyone with a history of self-harm or attempted suicide. We investigated whether DBT is an effective therapy in the treatment of patients with repeat suicidal ideation regardless of a BPD diagnosis. Case Description: A 31-year-old female veteran with a history of substance use disorders, post-traumatic stress disorder, BPD, and multiple suicide attempts presented to the emergency department (ED) for suicidal ideation (SI). She has had at least 7 hospitalizations in the past year for SI. While inpatient, the patient had daily therapy, motivational interview, and pharmacological management. She denied SI upon discharge and was sent home on her previous medication regimen and follow-up with substance use recovery and DBT. Conclusion: Few studies have looked at the effectiveness of DBT in treating SI or self-harm without exclusively looking at BPD. However, the studies that have evaluated DBT for suicidal ideation, it was seen to be effective in reducing incidence of self-harm and suicidal attempts including a meta-analysis of 18 clinical trials found DBT reduced self-directed violence and frequency of psychiatric crisis. One point found during our literature search worth exploring further is whether DBT is offered more to female patients compared to male patients due to the association of BPD as every study reviewed had a female majority. Clinical significance: Per CDC, suicide is the 12th leading cause of death. In 2020, there were an estimated 1.20M suicide attempts and 45,979 Americans died by suicide. DBT therapy should be considered as a standard of care in patients with suicidal ideation as current literature suggests it can be beneficial in reducing suicidal attempts and incidence of self-harm.
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    Comparison of Postoperative Outcomes of Surgical Techniques in Basilar Thumb Reconstruction: Trapeziectomy with FiberLock InternalBrace Reconstruction and Tenodesis versus Ligament Reconstruction and Tendon Interposition.
    (2025-02-26) Malik, Hanna; Yocum, Derek; Fuller, Sam; Mencias, Adelbert
    HYPOTHESIS: FiberLock suture suspenionplasty will yield superior post-operative outcomes at both 6 weeks and 6 months following BTR in terms of patient-reported outcome measures (PROMIS), functional disability (QuickDASH), pain levels (painVAS), and surgery satisfaction compared to trapeziectomy with ligament reconstruction and tendon interposition (LTRI) in patients with thumb CMC joint osteoarthritis. METHODS: Retrospective data was collected on patients with thumb carpometacarpal (CMC) arthritis who underwent trapeziectomy and either LRTI or Arthrex FiberLockTM Suspension Implants (Arthrex, Naples, FL, USA) InternalBrace suspensionplasty with side-to-side flexor carpi radialis tendon transfer. Outcomes were measured using the Visual Analogue Scale (VAS) for pain, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire, and Patient-Reported Outcomes Measurement Information System (PROMIS) v1.2 Upper Extremity (UE) item bank. Patient reports of surgery satisfaction and demographic data were recorded. Patients without completed questionnaires were excluded from analysis. At 6 weeks there were 74 LRTI and 74 FiberLock patients, while at 6 months, 65 patients remained in each group. Multiple Imputation by Chained Equations was utilized for missing data fields within surveys. Wilcoxon Rank Sum Test with Bonferroni correction were utilized to compare outcome scores of each group at 6-weeks and 6-months. RESULTS: No significant (all p > 0.05) differences between groups for any outcome (VAS Pain 24 Hours, VAS Pain When Resting, VAS Pain When Active, PROMIS Upper Extremity, Quick DASH, and surgery satisfaction). SUMMARY: The surgical techniques provide similar outcomes in pain, function, and patient satisfaction at both short-term (6 weeks) and medium-term (6 months) follow-ups, suggesting that the newer FiberLock procedure may yield comparable patient outcomes to the standard LRTI. Our study is limited by incomplete survey data, as some patients either skipped questions or missed surveys entirely, which was addressed by employing multiple imputation and pooling techniques before analysis. Further research involving larger cohorts and extended follow-up periods is necessary to enhance our understanding of the potential advantages of FiberLock suspensionplasty versus LRTI in managing basilar thumb arthritis.
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    Comparison of Postoperative Outcomes of Surgical Techniques in Basilar Thumb Reconstruction: Trapeziectomy with FiberLock InternalBrace Reconstruction and Tenodesis versus Ligament Reconstruction and Tendon Interposition
    (2025-04-05) Malik, Hanna; Yocum, Derek; Fuller, Sam; Adelbert, Mencias
    HYPOTHESIS: FiberLock suture suspenionplasty will yield superior post-operative outcomes at both 6 weeks and 6 months following BTR in terms of patient-reported outcome measures (PROMIS), functional disability (QuickDASH), pain levels (painVAS), and surgery satisfaction compared to trapeziectomy with ligament reconstruction and tendon interposition (LTRI) in patients with thumb CMC joint osteoarthritis. METHODS: Retrospective data was collected on patients with thumb carpometacarpal (CMC) arthritis who underwent trapeziectomy and either LRTI or Arthrex FiberLockTM Suspension Implants (Arthrex, Naples, FL, USA) InternalBrace suspensionplasty with side-to-side flexor carpi radialis tendon transfer. Outcomes were measured using the Visual Analogue Scale (VAS) for pain, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire, and Patient-Reported Outcomes Measurement Information System (PROMIS) v1.2 Upper Extremity (UE) item bank. Patient reports of surgery satisfaction and demographic data were recorded. Patients without completed questionnaires were excluded from analysis. At 6 weeks there were 74 LRTI and 74 FiberLock patients, while at 6 months, 65 patients remained in each group. Multiple Imputation by Chained Equations was utilized for missing data fields within surveys. Wilcoxon Rank Sum Test with Bonferroni correction were utilized to compare outcome scores of each group at 6-weeks and 6-months. RESULTS: No significant (all p > 0.05) differences between groups for any outcome (VAS Pain 24 Hours, VAS Pain When Resting, VAS Pain When Active, PROMIS Upper Extremity, Quick DASH, and surgery satisfaction). SUMMARY: The surgical techniques provide similar outcomes in pain, function, and patient satisfaction at both short-term (6 weeks) and medium-term (6 months) follow-ups, suggesting that the newer FiberLock procedure may yield comparable patient outcomes to the standard LRTI. Our study is limited by incomplete survey data, as some patients either skipped questions or missed surveys entirely, which was addressed by employing multiple imputation and pooling techniques before analysis. Further research involving larger cohorts and extended follow-up periods is necessary to enhance our understanding of the potential advantages of FiberLock suspensionplasty versus LRTI in managing basilar thumb arthritis.
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    Novel Technique for Suture Suspension Arthroplasty of the Thumb using the Locking "Nice" Knot
    (2025-06-13) Callahan, Kyle; Lovins, Sydney; Sibai, Tarek
    Osteoarthritis (OA) of the first carpometacarpal (CMC) joint is common and often presents as pain, weakness, or sense of instability in the joint. A common surgical technique for treatment is suture suspension arthroplasty, which was first described in 2009 by DelSignore et al with successful long term follow up reported in 2023. This technique involves piercing the flexor carpi radialis (FCR) tendon, which poses a risk of tendon rupture. Many adjustments to the original technique have been proposed, including modified suture patterns, suture buttons, and awake surgeries to avoid overtightening. The purpose of this paper is to discuss a novel modification to the original technique that eliminates the need to pierce the FCR tendon by utilizing the “Nice” knot. In addition, this technique tunnels suture through the base of the first CMC, pierces the distal abductor pollicis longus (APL) and finally ties remaining suture together, eliminating the need for a suture anchor. We believe these changes lead to lower rates of FCR tendon rupture, improved suspensionoplasty stability, and decreased time and cost of procedure, thus maximizing value-based care.
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    Treatment of Metastatic Her2Neu+ Breast Cancer with Oligoprogressive Disease
    (2024-03-23) Pelton, Sarah; Ayub, Jinan; Kenyon, Taylor; Ramchandani, Muskaan; Newton, Erin
    Background Information: In treating metastatic Her2Neu+ breast cancer, trastuzumab-based chemotherapy regimens typically result in fairly durable tumor control. Historically, when there was any disease progression, the systemic therapy was changed, but it has recently been recognized that “oligoprogressive disease” (when only a limited number of metastatic sites progress) might be approached differently. This heterogeneous response to treatment is due to variation in tumor cell phenotypes, which confer drug resistance. Oligoprogressive disease is often treated with local therapy, such as stereotactic body radiotherapy (SBRT), or resection, and determination of optimal treatment regimens remains a challenge. Case Description: We report a case of a 37-year-old, premenopausal female with locally advanced, Her2Neu+ right breast cancer with de novo metastases to the liver and bone. First line systemic therapy was well-tolerated and resulted in disease control. Unfortunately, she had symptomatic progression in her primary breast tumor, which was treated with mastectomy while continuing the same systemic therapy. Later, she developed a painful, right infraclavicular metastasis; surgical resection was ultimately declined due to local edema and the tumor’s proximity to significant neurovasculature. She elected to receive palliative radiation therapy for pain control via SBRT, and her systemic therapy remained unchanged. Currently, she shows no signs of progression and continues to have excellent tolerance of her systemic therapy. Clinical Significance: Oligoprogression is a clinically significant concept for numerous cancers, but the best methods of control have not been elucidated. This case contributes to the limited knowledge base as an example of treating Her2Neu+ breast cancer-associated oligoprogressive disease with local therapy.
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    Social Determinants of Health and Clinical Outcomes in Children With Cystic Fibrosis
    (2024-05-20) de Laosa, Mary; Ayub, Jinan; Bilinski, Sarah; Fultz, Megan; Petit, Rebecca; Chmiel, James; Sanders, Don
    Rationale: Among children with cystic fibrosis (CF), clinical outcomes vary among genetically similar patients, in part due to the contributions of social determinants of health (SDOH). Changes to patient assistance programs and Medicaid re-enrollment requirements may further impact people affected by SDOH. This project aimed to identify socially vulnerable patients and evaluate the impacts of SDOH on clinical outcomes. Methods: From January to July 2023, SDOH questionnaires were distributed to families of children with CF at Riley Hospital for Children. Patients were categorized by SDOH vulnerability and associations with clinical outcomes were analyzed using the Chi-squared test of independence. Results: 193 screeners were analyzed: the mean age was 9.2 years; 53% were males, 2.6% identified as non-White race, 3.6% reported Hispanic ethnicity, 51.6% were enrolled in Medicaid, and 70.5% were taking either ivacaftor or elexacaftor-tezacaftor-ivacaftor (ETI), consistent with the overall CF Center population. Overall, 100 (51.8%) screened positive for at least one SDOH (SDOH+): 60 screened positive for 1, 25 for 2, and 13 for 3+ SDOH. Of the SDOH+ patients, 64% were affected by the medical needs of another family member, 30% by food insecurity, 28% by difficulties affording utilities or rent, 22% by transportation needs, 11% by housing, and 9% by medication costs. In addition, 16 (8.3%) reported being negatively affected by changes to patient assistance programs and 7 (3.6%) by difficulties with Medicaid re-enrollment; 12 (75%) and 3 (43%) of whom were SDOH+, respectively. Of those who were SDOH+, 62% received immediate social work intervention.Mean (SD) FEV1 among SDOH+ patients was 5.8 (5.2)% predicted lower than their 2022 mean, vs 3.5 (5.0)% lower for SDOH- patients, p=0.001. A higher proportion of SDOH+ patients were 35% predicted below their 2022 mean FEV1 (24% vs 13% for SDOH-, p=0.037) and to have been hospitalized for a pulmonary exacerbation in the prior 12 months (21% vs 10% for SDOH-, p=0.030). There were no differences in mean BMI percentile, CFRD, or P. aeruginosa. Conclusions: Half of our CF Center population that completed a questionnaire screened positive for at least one SDOH. Some of these were not previously known by the CF Center team and this information provided opportunities to support families. SDOH+ patients have benefited from support from the multidisciplinary team, which may have mitigated negative impacts on clinical outcomes of insurance/payment assistance program changes. We will continue to routinely track SDOH, and changes to patient assistance programs and Medicaid.
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    Investigation of the Oncogenic Properties of Phosphatase of Regenerating Liver 3
    (2021-04-12) Ayub, Jinan; Amarasinghe, Ovini; Zhang, Zhong-Yin
    Phosphatase regenerating liver (PRL) is an enzymatic phosphatase whose oncogenic properties warrant its investigation as a therapeutic drug target. Specifically, it is well understood that PRL3 overexpression can be directly linked to cancer, as the phosphatase can activate PI3K/AKT pathways and downregulate PTEN levels, promoting metastasis and epithelial-mesenchymal transition (EMT). The purpose of this project was to further investigate mutated PRL3 proteins in order to assess whether mutations, rather than overexpression, of PRL3 can lead to cancer. Furthermore, whether these mutations specifically caused a gain-of-function or loss-of-function in PRL3 activity was examined. This study began by investigating common point mutations associated with PRL3 using the cBioPortal for Cancer Genomics database, through which R138 was identified as the most commonly mutated site. The four most frequent PRL3 mutations were created using QuikChange® site-directed mutagenesis. After sequencing the DNA to confirm mutagenesis, the recombinant proteins were purified to investigate their biochemical properties in vitro, such as their trimerization ability and phosphatase activity. Results indicated the most common mutation, R138C, had similar trimerization ability compared to wild-type PRL3, however, the other three mutants had lower trimerization ability. Interestingly, all four oncogenic mutants showed decreased kinetic activity and lower binding affinity for the pNPP substrate. Although these results imply that these oncogenic mutations are indeed loss-of-function, further in vivo experimentation should be conducted to confirm the applicability of these results in transfected human cell lines.
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    Pediatric Postpartum Gallstone Pancreatitis: A Case Study
    (2023-03-24) Sullivan, Megan; Ayub, Jinan; Jauregui, Alexa; Brian, Gray; Burns, Catherine
    Background Hospitalizations in the United States for biliary tract pathology, mainly gallstone disease, affect 0.5% of peripartum and postpartum patients. Complications include significant disability, preterm delivery, and time away from the newborn due to surgery. Symptoms of gallstone pancreatitis are often dismissed as normal peripartum symptoms. Case Presentation A 12-year-old female, 2 months postpartum, presented with 1 day of epigastric pain and vomiting. Labs showed elevated lipase (>2000). Computed Tomography (CT) showed acute pancreatitis, and choledocholithiasis was noted on ultrasound (US). She underwent endoscopic retrograde cholangiopancreatography, followed by laparoscopic cholecystectomy. Review of records revealed 3 previous visits for vomiting and abdominal pain. Gallstones were not suspected due to missed follow-up or suspicion of pregnancy-related diagnoses. Social history was complex due to immigration and socioeconomic status (SES). A 17-year-old female presented similarly, at 2 months postpartum, with epigastric pain. She was discharged with a presumed urinary tract infection. Later diagnostic tests revealed acute pancreatitis (CT) and gallstones (US). After treatment, lipase remained elevated (>6000), but other labs suggested passage of the previously obstructing gallstone. She underwent laparoscopic cholecystectomy. Care was delayed due to insurance barriers. Conclusion Patients <20 years are at greatest risk for postpartum gallstone pathology. This differential should be prioritized in young patients with epigastric or right upper quadrant pain, especially in the presence of risk factors such as low SES. Clinical significance It is typical for gallstone acute pancreatitis to have symptoms prior to presentation, but it is unclear if preceding symptoms in postpartum patients are misdiagnosed and attributed to pregnancy, or if acute presentation is more common. Increased awareness about gallstones in postpartum pediatric patients can mitigate the dangerous sequelae of gallstones including acute pancreatitis.
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    Relationship between Neighborhood-Level Socioeconomic Status and Relapsed Pediatric B-Acute Lymphoblastic Leukemia Treated with CAR-T19 Therapy in Indiana
    (2025-03-29) Ayub, Jinan; Walker, Alyssa; Grischke, Tyra; Garcia, Gloria; Skiles, Jodi; Spiegel, Courtney; Batra, Sandeep
    Background/Purpose: There is paucity of studies investigating the relationship between socioeconomic status and outcomes for patients receiving chimeric antigen receptor T-cell therapy (CART19) for refractory or relapsed B-ALL. Area Deprivation Index (ADI) serves as a measurement of socioeconomic disadvantage based on theoretical income, education, employment, and quality of housing. Methods: A retrospective chart review of 27 patients with relapsed B-ALL treated with CART19 at a non-profit children’s hospital from 2018-2024 was conducted. Using a public institution’s Neighborhood Atlas database, ADI scores (range 1-10) were recorded for each patient based on ZIP code of residence in Indiana. A low ADI score (0-5) indicates affluence and higher SES, while a high ADI score (6-10) indicates deprivation and a lower SES. Comparisons between groups were done using Chi-square tests for categorical variables. The Kaplan-Meier method was used to analyze relapse free survival (RFS) using the log rank test to compare groups. Results: The patients (age range 2-25 years) were stratified into two groups: low ADI or high SES (≤5, n = 10 (37%); 2.9 ± 1.4; range, 1-5)) and high ADI or low SES (>5, n = 17 (63%); 8.5 ± 1.5; range, 6-10). Seventeen identified as white (63%) and 10 (37%) as Hispanic. Three patients received CART19 infusions twice, and one patient received multiple CART19-directed products. In the high ADI group, 3-month, 6-month, and 1-year RFS post-CART therapy was 82%, 76%, 60% respectively compared to 100%, 71%, 57% in the low ADI group (p=0.9). Conclusion: Most patients who received CART therapy at our tertiary center resided in low SES areas but did not experience worse RFS compared to patients residing in more affluent areas. Further studies with larger sample sizes are needed to better understand the heath inequalities among patients with relapsed leukemia in Indiana and to identify challenges faced by patients from disadvantaged communities with limited resources.