Department of Obstetrics and Gynecology Medical Student Works

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A Case of Aceruloplasminemia Which Was Not Wilson Disease
(2021-03-26) Williams, Cody; Clemens, Joseph; Wu, Joey; Zimmerman, Michelle
Case: A 58 year old woman presented with 5+ years of fatigue and joint pain as well as recent short term memory concerns. She was evaluated for Lyme disease and was found to have mild anemia with elevated iron and persistently elevated ferritin as high as 2100 ng/ml. An unrelated cardiac scan had the incidental finding of hepatic iron accumulation. No fibrosis was noted on MRI. Liver biopsy was significant for 3-4+ hemochromatosis with sinusoidal dilation and congestion. Labs showed aceruloplasminemia with low urine and serum copper. Eye exam was negative for Kayser Fleischer rings but did show retinal iron deposits and early macular degeneration not supporting Wilson disease. Later genetic testing for CP (ceruloplasmin) gene showed heterozygosity for sequence variant c.2342A>C, predicted to cause amino acid substitution p.Lys781Thr. Conclusion: She is currently awaiting MRI to evaluate possible CNS disease in the setting of aceruloplasminemia but was delayed due to significant COVID-19 risk. Otherwise, she is tolerating deferasirox well. Significance: Our patient had a complex path to diagnosis given that low ceruloplasmin is commonly associated with Wilson disease. However, ceruloplasmin is also a key component in regulating ferric iron binding to transferrin and maintaining copper and iron homeostasis. This case was an exemplar of interdisciplinary diagnosis. Clinical evidence of anemia, ophthalmologic findings, and subjective cognitive dysfunction combined with histology and genetic results contributed to accurate characterization of aceruloplasminemia related hemochromatosis rather than Wilson’s disease. Genetic analysis revealed CP gene c.2342A>C (p.Lys781Thr), a novel mutation not reported elsewhere to our knowledge. Given her heterozygous status for the mutation, further investigation is needed. More importantly for our patient, recognition and treatment at this stage could reduce morbidity from neurodegeneration, pancreatic, and hepatic disease.
Is Operative Diagnosis for Aseptic Revision Total Hip Arthroplasty Related to Patient Reported Outcomes?
(2018-07) Holder, Erik; Ciesielski, Alex; Ziemba-Davis, Mary; Meneghini, R. Michael
Background and Hypothesis: Component loosening and instability are the leading causes of revision total hip arthroplasty (THA). The purpose of this study was to compare patient-reported outcomes after revision THA based on failure etiology. We hypothesized that outcomes would differ based on reason for revision. Project Methods: 187 consecutive revision THAs performed between 2010 and 2017 were retrospectively reviewed. Prospectively collected preoperative and minimum one-year Hip Disability and Osteoarthritis Outcome Score/HOOS Jr., UCLA Activity Level, WOMAC Index, and patient satisfaction were assessed based on failure etiology. Demographic variables and covariates were accounted for including sex, age, BMI, ASA classification, heart disease, lumbar spine pathology, narcotic use, fibromyalgia, depression, and autoimmune arthritis. Results: Latest UCLA activity level did not differ based on failure etiology (p=0.381). However, the degree of improvement in activity level was higher (p= 0.04) in patients revised for loosening, instability, and infection compared to ALTR and polyethylene wear. HOOS Jr (p=0.949) and WOMAC total (p=0.147) scores did not differ based on failure etiology at latest follow-up, although patients revised for loosening had greater WOMAC improvement compared to all other groups except polyethylene wear (p=0.016). Satisfaction did not vary based on failure etiology (p=0.365), and demographic and covariates were unrelated to outcomes (p³0.165). Conclusion and Potential Impact: We observed that patient-reported outcomes following revision THA vary based on revision reason and activity level improvement is mitigated patients revised for ALTR and poly wear. These findings may help surgeons and patients alike set expectations for recovery following revision THA.
Avascular Necrosis of the Hip with Truvada
(2021-01-23) Wu, Joey; Henry, Arnold
Background and Introduction Tenofovir disoproxil fumarate (Truvada) is a common HIV Pre-exposure prophylaxis regimen. Rare side effects such as renal toxicity, bone mineral loss have been reported but well documented relationship between Truvada use and AVN has not been well reported. The patient reported in this case study has no additional risk factor or underlying conditions that predisposes him to AVN of the hip aside from Truvada use. Case presentation 37-year-old gay male who is HIV negative in a monogamous relationship with a male of undetectable HIV viral load on Truvada prophylaxis with goal of decreasing HIV transmission risk. He began taking Truvada in Jan of 2015 and was without complications until Apr 2018 when he presented with left hip/quadricep pain initially diagnosed with IT band syndrome. He failed to improve with multiple courses of physical therapy and pain has been recurrent. He received X-ray of pelvis, bilateral hips, and lumbar spine with 4 views in Jun 2019. Result was significant for avascular necrosis of the left hip. He has no other comorbidities and began taking NSAIDs for pain control. His Truvada was discontinued Jun 2019 and pt began Descovy (Tenofovir alafenamide fumarate) but his ROC visit/imaging in Aug 2020 shows worsening AVN and symptomatic pain. Physical exam also shows significant atrophy of left lower extremity muscle groups and antalgic gait. Conclusion Truvada has been associated with AVN in patients without previous health risks for decreased bone health/density. Previous research have identified improved bone mineral density with discontinuing Truvada and beginning Descovy. However, this patient fails to improve with Descovy and continues to have worsening AVN, perhaps suggesting AVN is not associated with bone mineral loss but possibly other occult reasons.
Predictors of Quality of Life after Liver Transplant
(2020-11-14) Wu, Joey; Desai, Archita
Background and Hypothesis: The impact of chronic liver diseases on patients and their family member is often understated and understudied. Chronic liver diseases can sometimes progress to a need for Liver transplant (LT). While recent studies have described quality of life (QOL) at different stages of liver disease, the impact of the patient’s QOL in LT survivors has not been examined. The importance of studying QOL in patients is due to its effect on the survivorship of LT recipients. We hypothesize that QOL in LT patients is lower than the general population. Our aim was to describe predictors of QOL in a well-described cohort of LT patients. Methods:Patients were enrolled at the Digestive and Liver Disease Liver clinic at Indiana University Hospital. All patients over the age of 18 were approached, if patients consented to the study, they were then enrolled during their liver follow up visit. The PROMIS survey was administered on an iPad and completed during the clinic visit. Survey were then scored and analyzed.Results: The T-scores for post liver transplant patients are lower in physical function, anxiety and depression, but higher in general life satisfaction compared to the general population. LT recipients have similar T-scores in Fatigue, Sleep disturbance, ability to participate in social activities, and pain interference compared to the general population. Conclusion and Potential Impact: Previous diagnosis of PBC, HCC, diagnosis of depression, household income, insurance status, Charlson Comorbid Index and number of non-transplant related medications have the highest association with quality of life. Further enrollment is needed to increase the power of the study. However, this can inform physicians the importance to taking these factors in to consideration in order to improve the QOL in LT recipients.
Is Manipulation Under Anesthesia Effective in Improving Patient Reported Outcomes After Total Knee Arthroplasty? A Matched Cohort Analysis.
(2019-12) Ciesielski, Alex; Holder, Erik; Deckard, Evan; Ziemba-Davis, Mary; Meneghini, R Michael
Introduction: Manipulation under anesthesia (MUA) after total knee arthroplasty (TKA) is considered effective for postoperative stiffness, but strong scientific justification is lacking. This study compared outcomes in two matched cohorts: patients who met criteria and underwent MUA and patients who met criteria but did not undergo MUA. Methods: MUA (experimental) cases had ≤ 90° flexion 4-weeks postoperatively and underwent MUA surgery within 12 weeks of the index TKA. Control cases had ≤ 90° flexion 4-weeks postoperatively and did not undergo MUA. The latter group was alternatively treated with aggressive flexion exercises, frequent follow-up, and pain control modalities per surgeon discretion. 42 MUAs performed by three surgeons between 2011 and 2017 at the same center using the same standardized clinical and rehabilitation protocols were retrospectively reviewed. Six MUAs were excluded for potential confounds. The remaining 36 MUA cases were matched one-to one on sex (p= 1.00), age (p=0.893), race (p=0.938), BMI (p=0.069), and implant manufacturer (p= 1.00) to 36 control cases. Outcome variables included amount of improvement in flexion from preoperative baseline to latest follow-up and standardized PROMS. Covariates potentially affecting outcomes were taken into account. Results: Overall MUA incidence during the time period was 1.9%. Experimental and control groups did not differ on preoperative fibromyalgia, depression, and narcotic use; or intraoperative analgesia (p≥0.084). Four control patients and no experimental patients had inflammatory disease (p=0.054), and six of the former compared to none of the latter had lumbar spine pain or disease (p=0.025). Flexion data are provided in Table 1. Mean pre-primary TKA flexion was significantly greater in experimental patients (112.4 vs. 98.6°, p=0.002). On average, between pre-primary surgery and latest follow-up, experimental patients lost 10.7° of flexion compared to a gain of 12.7° by control patients (p<0.001). Pre-primary to latest follow-up improvement in pain walking on level ground (-3.3 and -4.7 points, p=0.190) and climbing stairs (-3.7 vs. -5.1, p=0.192) did not significantly differ between experimental and control patients respectively. As shown in Figure 1, prior to primary surgery experimental and control patients had similar activity levels (p=0.624). At latest follow-up, however, control patients were significantly more active than experimental patients (Figure 1, p=0.009). Figure 2 shows the proportions of patients in each group who reported their knee never feels normal prior to primary surgery (p=0.580) and at latest follow-up (p=0.0004). Surgery significantly improved this metric for control but not experimental patients. At latest follow-up 88.6% of control patients and 50% of experimental patients were satisfied or very satisfied with their knee surgery (p=0.001). Conclusion: Patients with ≤ 90° flexion 4-weeks after TKA who underwent MUA had significantly worse flexion and PROM scores than matched control patients who did not undergo MUA. These findings question the effectiveness of MUA as a legitimate treatment for postoperative TKA stiffness.
Activation of the oncogene ERG by the Ras/ERK and PI3K/AKT pathways
(2019-08) Willhite, Sydney; Strittmatter, Brady; Hollenhorst, Peter
Background and Hypothesis: The TMPRSS2-ERG re-arrangement occurs in ~50% of prostate cancers and results in aberrant expression of the transcription factor ERG in the prostate. ERG is known to be activated by the Ras/ERK and PI3K/AKT pathways, however, the exact mechanism of this activation is not fully understood. The aim of this project is to identify how activation of these signaling pathways differentially effect transcription of ERG target genes. Experimental Design or Project Methods: In order to test how the Ras/ERK and PI3K/AKT pathways effect ERG target gene transcription, normal prostate epithelial cells (RWPE1) were transfected with constitutively active AKT in combination with phospho-mutants of ERG. These cell lines were then used to conduct Quantitative Reverse Transcription PCR and Western blotting of known downstream ERG target genes to identify how the activation status of these signaling pathways affected transcription and protein production. Results: Overall, our results demonstrate that ERG mediated transcription of the VIM gene, a marker of EMT, was activated by the Ras/ERK pathway and was repressed by the PI3K/AKT pathway. In addition, we found that ERG expression decreased FOXO1 protein expression in our cell lines regardless of Ras/ERK and PI3K/AKT status. Transcription and protein quantification was also measured for ERG target gene VEGFA, a critical regulator of angiogenesis. Conclusion and Potential Impact: This project helps identify the molecular mechanisms by which a common oncogene in prostate cancer is activated. Our results demonstrate how upstream signaling pathways differentially regulate oncogenic transcription and cell transformation. Overall, this project will provide insight to the molecular mechanisms of possible therapeutic targets in prostate cancer, the most common cancer amongst men.
Case description of stroke in a female patient with heterozygous MTHFR C677T mutation: Lessons learned in stroke prevention and the importance of continuity of care for women with multiple risk factors for thrombosis
(2021-03) Bammann, Erin R.; d'Arnaud, Lindsey I.; Willhite, Sydney R.; Carroll, Jourdan G.; Goswami, Amartyadeb
Case Description: A 58 year-old female with a history of antiphospholipid syndrome (APS) with multiple DVTs, spontaneous abortions, hypertension (HTN), hyperlipidemia (HLD), type 2 diabetes mellitus (T2DM), and tobacco use disorder presented to the hospital with dysarthria and headache for three days. Evaluation revealed a left MCA thrombotic CVA. Testing at the time of stroke was negative for antibodies associated with APS, but revealed heterozygous mutation of MTHFR C677T. Prior to this stroke, she had recently established care with a new primary care provider and cardiologist. She reported previously following with a hematologist who managed her APS with folic acid and vitamin D. She was prescribed no anticoagulation therapy and was taking 81 mg aspirin daily at the time of this event. Conclusions: There is mixed evidence regarding the patient’s diagnosis of APS as the underlying factor causing multiple DVTs. Nevertheless, the treatment for APS in the setting of multiple prior DVTs is anticoagulation, which was not part of the patient’s treatment plan prior to her stroke. A more detailed investigation of the patient’s medical history and re-evaluation of appropriate treatment when establishing care would have helped optimize her care and may have prevented her stroke. Clinical significance: Compared to men, women experience worse health outcomes after stroke, including increased mortality. When women are establishing care with new providers, this disruption in continuity of care presents an opportunity for re-evaluation of their risk factors and optimal primary prevention of stroke. This case illustrates how immediate investigation of a patient’s pre-existing diagnoses and treatment plan after a transition of care may help prevent poor health outcomes for women.
An Abscessed Tooth that Wasn't: An Unusual Case of Mumps in an Elderly Patient
(2020-03) Lin, Jenny; Willhite, Sydney; Moore, Hannah; Smith, Maddie; Duncan, Francesca
Case: A 62-year-old African American female with history of self-resolving parotitis initially presented with progressive neck and bilateral facial swelling. She attributed this to an abscessed tooth. CT revealed parotitis with inflammatory changes and mass effect on the hypopharynx and larynx, although the patient denied breathing difficulty. Antibiotics were administered for two days, discontinuing due to lack of abscess. Six days later, the patient presented with worsening facial swelling, sore throat, and dysphagia. She remained afebrile but with a WBC count of 12.8. Antibiotics and steroids were given. MRI displayed retropharyngeal space involvement of 2.6 cm in thickness. ENT performed surgical debridement and culture collection. Upon return from the OR, respiratory distress and inability to manage secretions resulted in intubation via an upright awake fiberoptic approach given concern for impending airway compromise. Finally, a positive IgM antibody to mumps virus was detected from the debridement culture. Discussion: The differential for nonsuppurative parotitis includes viruses, autoimmune disorders, and granulomatous inflammation. Paramyxovirus, specifically mumps, is the most common viral cause, with EBV, HSV, CMV, and HIV as other concerns. Autoimmune causes are Sjogren syndrome and SLE. Mycobacterium species are the likely granulomatous culprit. Though mumps is the most common viral cause of parotitis, it typically occurs in children and young adults, not fitting of the patient described. However, mumps cases have increased recently. MMR vaccination began in 1967 and cases decreased more than 99%; yet, since 2006 there have been outbreaks. Vaccine-induced protection may wane over time. Mumps is highly contagious and complications include meningitis, encephalitis, pancreatitis, and deafness, occurring more commonly in elderly patients. Patients with nonsuppurative parotitis should thus be surveyed for vaccination history and examined for MMR titers.
Don't Always Depend on Your D-Dimer: An Atypical Case of Pulmonary Embolism
(2021-03) Willhite, Sydney; Betts, Aislinn; Lee, Maya; Juloori, Sangeeta
Case: A 35-year-old female patient, with current IV drug use and a history of endocarditis warranting tricuspid valve replacement, presented with dyspnea and chest pain. On physical exam, she was found to have scattered wheezes on expiration with no shortness of breath or LE edema. As the Wells’ score for PE revealed a moderate risk, CTA and D-dimer were obtained. CTA revealed low contrast uptake in the right pulmonary artery, most concerning for a PE. D-dimer and coagulation studies were normal, making DVT unlikely and PE questionable. Therefore, there was high suspicion for endocarditis with septic emboli. On day two, TEE showed no valvular vegetations or thrombus. With no evidence of endocarditis, DVT was reconsidered. Bilateral LE doppler ultrasounds were negative for DVT. However, a repeat D-dimer was found to be elevated (596 ng/mL). Clinical impression on day three was a PE secondary to a small superior venous thrombosis from IV drug use. Conclusions: IV drug use is recognized as a risk factor for SVT and DVT due to endothelial damage of injected veins and/or increased coagulation factors. As a LE DVT was ruled out through ultrasound, this patient likely had an UE thrombus with a secondary PE. However, her low D-dimer in the setting of a PE is puzzling considering the test’s high sensitivity (95%). Given that her subsequent D-dimer was elevated, this suggests that the initial test may have been inaccurate. Clinical Significance: D-dimer is considered to be a useful test to rule out DVT and PE in cases of low or moderate probability. However, a few reasons for false-normal D-dimer have been elicited: small emboli, anticoagulant pretreatment, and symptoms ongoing for ≥ 10 days. In this case with moderate probability, the initial falsely low D-dimer decreased suspicion for thrombosis and was most likely due to small emboli. Therefore, the causes of false-normal D-dimer must be well known and considered in order to avoid misdiagnosis.
Impact of a Daytime Operating Room on Resource Use and Outcomes in Emergency General Surgery
(2020-02-05) Murphy, Patrick; Patterson, Alicia; Holder, Erik; Scifres, Aaron; Rodriguez, Rachel
Introduction: The implementation of acute care surgery (ACS) services has not been standardized. There is no known “best” model or optimal infrastructure required to care for emergency general surgery (EGS) patients. The addition of dedicated daytime operative room (OR) resources may increase patient access and reduce overnight operations. Methods: We performed a retrospective cohort study of patients who underwent emergency appendectomy, cholecystectomy, or hernia repair at a tertiary care center from Feb 1, 2015 to Dec 31, 2018. A daytime ACS room was implemented on Jan 18, 2017, dividing patients into two cohorts: the “Pre-Access” period prior to and “Post-Access” period after implementation. Resources were allocated to the ACS room only if cases were booked by 430 PM the day prior. Outcomes included after-hour ORs (5 pm – 7 am), time to OR, time of scheduled ORs (AM or PM) and relevant patient outcomes. Results: Over 4-years, 925 patients underwent appendectomy (42%), cholecystectomy (50%) or hernia repair (8%) on an emergent basis. There was a 49% increase in volume in the Post-Access period, without an increase in time to OR [14 h, IQR 38 for both groups], after-hours OR (42.1% v 42.1%, p=0.99) or timing of ORs (28.3% v 29.1% AM start and 29.4% v 28.7% PM start, p=0.96). There was no change in hospital length of stay [2 d, IQR 4 v 3 d, IQR 4, p=0.39] or complication rates (14% v 18%, p=0.15). On subgroup analysis, only delayed cholecystectomies for gallstone pancreatitis (GSP) showed a reduction in after-hours ORs (13% v 0%, p=0.03) and an increase in AM OR start times (43% v 71%, p=0.02), suggesting that pre-scheduled cases are most affected by this OR allocation model. Conclusion: Despite a significant increase in volume there was no increase in after-hours resource utilization, hospital length of stay, or worse patient outcomes. The addition of an ACS room improved daytime access for GSP but not for other diagnoses. Dedicated infrastructure results in efficient use of resources and the ability to manage increasing patient volumes. Efficiency may be further improved by dedicated staffing of ACS rooms.

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