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  Trauma Team Time Out: A Pre-Brief and De-Brief Process for Improved Team Dynamics

  Shalmali Mirajkar, Ashlee Mills Duffy, and Zachary Bauman

  Background: The trauma team is one of the most diverse interprofessional and multidisciplinary teams found in the hospital, consisting of emergency medicine physicians, trauma surgeons, bedside nurses, respiratory therapists, advanced practice providers, and more. With many individuals taking care of an individual patient, there can be frustrations and communication challenges that arise, particularly during these emergency and stressful situations. Time-out protocols implemented in the operating room have resulted in improved patient safety and team dynamics. A similar protocol in the trauma bay could carry over similar benefits, allowing for improved communication and trauma team efficiency. The purpose of this study is to identify the challenges in team dynamics at our institution and implement a pre-brief and de-brief system to facilitate interprofessional communication and better teamwork during trauma activations. Methods: A survey based on the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety and Culture (SOPS) was sent out to members of the trauma team at Nebraska Medicine. The survey results highlighted a need for closed-loop communication for questions and concerns, increased transparency, and better follow-up after trauma activations commenced. To address this gap and promote continued improvement of team dynamics, a timeout for a pre-brief and de-brief process were created, supported with two posters outlining the process. These posters were physically hung in the trauma bays. The pre-brief and de-brief processes were created using literature highlighting the necessary elements in the processes. The pre-brief includes roles and responsibilities, things to anticipate given the traumatic mechanism of injury and encoded information, and potential dispositions. The debrief includes discussion about what went well and what could be done better in the future, education from the trauma team leader as to why certain care management decisions were made. It also identifies additional equipment/supplies that might be needed in the future and provides an avenue for people to seek additional emotional/supportive services. Results: Currently the pre-brief and debrief process has been accepted and welcomed with great success. Anecdotally, it has improved team dynamics and communication and provided education to run future trauma activations more efficiently. All team members have loved the education that has come from this process as well. The pilot study is currently ongoing. Conclusion: Implementation of a pre-brief and de-brief system using time-out posters allows for greater communication within the team and has already resulted in improved resuscitations during recent trauma activations. Future directions of this research study include readministering the SOPS survey in a few months to quantify the changes in perceived team dynamics and communication.

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  A Potbellied Problem: A Case of a Mysterious Abdominal Mass

  Shalmali Mirajkar and Martin H. Goodenberger

  88-year-old male presenting for restaging of metastatic renal cell carcinoma. Imaging reveals an anterior abdominal mass that is eventually found to be an extra-adrenal myelolipoma.

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  Syphilis-Related Glomerulopathy: A Rare Presentation of a Common Disease

  Shalmali Mirajkar, Jainaha K. Srikumar, Nichole Regan, Ryan P. Mullane, and Sara Bares

  Background: Syphilis is a preventable and curable sexually transmitted infection (STI) caused by the bacterium Treponema Pallidum. Syphilis has often been described as the “great mimicker” as it can affect multiple organ systems and leads to a wide variety of clinical manifestations. Kidney manifestations are rare, and the most commonly reported glomerular lesion is membranous nephropathy. Herein, we present an unusual case of a rash, membranous nephropathy and cholestatic hepatitis due to secondary syphilis. Case: A 68-year-old male with well-controlled HIV, hypertension, anemia, and depression was admitted to the hospital for evaluation of acute kidney injury and nephrotic-range proteinuria. Three weeks prior, he had experienced flu-like symptoms followed by a generalized pruritic rash. He also noted that his urine had been darker in color. He denied dysuria, hematuria, or foamy urine. He denied any sexual activity in the last year. One week before admission, he sought treatment for his rash at an outpatient dermatology clinic. A punch biopsy was performed, and triamcinolone ointment was prescribed but never utilized. On admission, physical exam revealed bilateral lower extremity edema and a diffuse maculopapular rash that spared the palms and soles. Labs were notable for creatinine of 2.34 mg/dL (up from 1.36 mg/dL six months prior), urine protein/creatinine ratio of 9.2, and alkaline phosphatase of 417 U/L. Renal biopsy exhibited membranous glomerulopathy and skin biopsy demonstrated psoriasiform acanthotic epidermis with moderately dense superficial perivascular lymphoplasmacytic infiltrate and a positive Treponema antibody immunostain. Syphilis treponemal antibody was newly positive and RPR was reactive at 1:128. The patient received 2.4 million units of benzathine penicillin intramuscularly for the treatment of secondary syphilis and was discharged two days later. Two weeks after discharge, the patient was noted to have resolution of his rash and significant improvement in his edema, proteinuria, and serum creatinine. Discussion: Identification and appropriate treatment of secondary syphilis resulted in resolution of this patient’s rash and acute kidney injury. Conclusion: This case highlights the importance of maintaining syphilis on the differential, regardless of reported risk factors, in patients with generalized rashes, cholestatic hepatitis, and/or membranous glomerulopathy as secondary syphilis can have a wide range of clinical manifestations. Checking serology before more invasive diagnostic testing should be considered with uncommon combinations of presenting symptoms.

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  Reactive Aldehyde Species (RASP) Inhibitors Sequester MAA-Adducts and Reduce Pro-Inflammatory Cytokines

  Duncan Works

  Background: Post-translational modifications of self-proteins have been implicated in the pathogenesis of Rheumatoid Arthritis (RA). One of these protein modifications termed malondialdehyde-acetaldehyde-adduct (MAA) has recently gained interest for its involvement in RA. This protein adduct contributes to inflammation by inducing immune cells to generate pro-inflammatory cytokines, T-cell specific responses, responses and circulating autoantibodies. Recently, novel reactive aldehyde species (RASP) inhibitors (ADX-629 and ADX-246) became available that have been shown to prevent the formation of MAA adducts by covalently binding and sequestering MDA and AA in a mouse model of alcoholic liver disease. These inhibitors prevented the release of key inflammatory cytokines and protected animals from progressive liver damage. While these experiments demonstrated the binding of RASP inhibitors to MDA and AA prior to MAA formation, they did not determine the capacity of these agents to scavenge pre-formed MAA protein adducts. Therefore, the purpose of this study was to determine if RASP inhibitors sequester MAA-adducts and block the subsequent cellular release of pro-inflammatory cytokines.
  
  Significance of the problem: MAA modified self-proteins may render harmful effects in patients with RA. Preventing inflammation and inflammation leading to fibrosis by inhibiting cellular binding of could represent significant advancement in the treatment of RA.
  
  Hypothesis: ADX-629 and -246 will prevent MAA protein adducts from binding to macrophage receptors and, as a result, prevent the release of pro-inflammatory cytokines.
  
  Experimental Design: Human monocytic cells (U-937 cell line) were activated to professional macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 hours. Following pre-treatment with decreasing doses of ADX-629 or ADX-246 for 30 minutes, macrophages were incubated with 25µg/mL of fibrinogen (FIB) or MAA-modified fibrinogen (FIB-MAA) for 24 hours. Supernatants were collected for measurement of IL-6 and MCP-1 using commercially available kits. Cells were collected and tested for membrane integrity using a lactate dehydrogenase (LDH) assay.
  
  Results: In the absence of RASP inhibition, FIB-MAA stimulation of cells significantly increased the release IL-6 with mean concentration of approximately 30pg/mL compared to FIB alone 6-fold increase. (p<0.0001). IL-6 release was significantly reduced with only 1 µM of ADX-629 and fell to native FIB levels with drug concentrations exceeding 10 µM (Figure 1A). ADX-246 demonstrated similar results (Figure 1B). Likewise, similar patterns were observed for the release of MCP-1 (data not shown). LDH assays showed no evidence of cellular toxicity regardless of ADX dose.
  
  Conclusions: In addition to confirming the capacity of RASP inhibitors to sequester MAA, results of this study demonstrate that both ADX-629 and ADX-246 attenuate or prevent MAA-modified proteins from initiating the macrophage-mediated release of pro-inflammatory cytokines implicated in RA pathogenesis. These findings support the need for additional in vivo investigations of these RASP inhibitors as novel therapies in in the management of RA and possibly in other conditions wherein MAA adducts mediate tissue damage.

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  SGLT2i Use Potentiates Acute and Chronic Radiation-Induced Side Effects in Prostate Cancer Radiation Therapy

  Duncan Works

  Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and rarely hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months to years after radiation. We herein describe the case of a 65-year-old male with a past medical history of type 2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on Sodium-Glucose Cotransporter-2 inhibitor therapy (Jardiance), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of Ozempic (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

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  A Rare Case of Lightning-Induced Intracerebral Hemorrhage

  Shalmali Mirajkar, Mitchell Floura, Steven Phillips, Daryl Gress, and Subin Mathew

  Objective: Lightning strike is a natural event with devastating consequences. Depending on the intensity, harmful effects can range from mild erythema to severe cardiorespiratory arrest and multi-organ damage. Neurological injuries include loss of consciousness, paresthesia, transient weakness, short/long term cognitive sequelae, visual hallucinations, cluster headache, myelopathy, motor neuron disease, cerebral infarction, and movement disorders. However, intracerebral hemorrhage (ICH) is rarely observed. Here we describe a presentation of ICH secondary to a lightning strike. Background: 45-year-old male was found by bystanders on a rainy morning fallen by a bike trail with a shattered helmet. Intubated at the scene for GCS of 7. Electrocardiogram revealed bradycardia, vitals significant for systolic blood pressure in 200mmHg. A lightning strike to the top of the head was suspected due to scorched hair and burns to scalp (entry wound), upper arms, and shoulders (exit wound). Further examination revealed periorbital swelling and hematoma, right sided hemiplegia, with withdrawal in the left upper and lower extremities. CT/MRI showcased a large left basal ganglia hemorrhage, scattered subarachnoid hemorrhage and stage I diffuse axonal injury. CTA Head/Neck was unremarkable. EEGs revealed moderate to severe encephalopathy with no ictal activity. Follow up CTs continued to be stable, and the patient was discharged to a rehabilitation hospital 5 weeks after presentation. Conclusion: Neurological injuries from lightning strikes are second only to cardiovascular injuries. Lightning can rarely cause basal ganglia ICH. Exact etiology for predilection to basal ganglia ICH remains unknown with few hypotheses. These patients will require aggressive management and can have good outcomes.

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  Associations Between Salience and Frontoparietal Intranetwork Connectivity and Executive Function Tasks in Periadolescent Children

  Shalmali Mirajkar and David E. Warren

  Brain network organization varies between individuals, and individual differences in intrinsic brain networks have been linked to differences in cognitive ability. Individual differences in brain connectivity may be especially evident in brain networks that support executive functions such as cognitive control and attention such as the frontoparietal and salience networks. The frontoparietal network is theorized to play a role in cognitive control, which refers to the selection of thoughts and behaviors in context of task demands. Specifically, the frontoparietal network is necessary to flexibly coordinate behavior in a goal-driven manner. Meanwhile, the salience network has been hypothesized to modulate the relationship between the default mode network, which contributes to self-oriented cognition, and the frontoparietal network. Prior work suggests that the maturation of executive functions during development parallels the integration of the salience networks with the frontoparietal network. Additionally, increased frontoparietal and salience intranetwork connectivity has been associated with development from periadolescence to adulthood. However, associations between frontoparietal or salience intranetwork connectivity and executive functions abilities have not been tested in periadolescent children. Here we tested whether intranetwork connectivity of frontoparietal and salience networks was correlated with executive function measures in periadolescent children. Participants in the NIA-funded Polygenic Risk of Alzheimer’s disease in Nebraska Kids (PRANK) study (N = 94) completed the NIH toolbox cognition battery as well as a functional MRI (fMRI) scan including resting-state data collection. Intranetwork connectivity was measured using the Human Connectome Project’s connectome workbench software. Results of the data analysis indicated a positive correlation between scores on fluid cognition measures and frontoparietal intranetwork connectivity, r(73) = .29, p = .01. A positive correlation was also observed with flanker task scores and frontoparietal intranetwork connectivity, r(73) = .25, p = .03. Finally, we observed a positive correlation with salience intranetwork connectivity and age-adjusted dimensional card sorting task scores, r(91) = .22, p = .03. Our preliminary findings show an association of executive function measures with intranetwork connectivity of two key intrinsic functional networks, and they suggest that frontoparietal and salience intranetwork connectivity may reflect increased efficiency of cognitive control during development.

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  This Case is Out of Hand: A Non-Infectious Mimic of Surgical Site Infection Following Routine Surgery

  Keaton Reed, Shalmali Mirajkar, Alex Lesiak, Sarah L. Lonowski, and Angela L. Hewlett

  Background: Pyoderma gangrenosum is a reactive, non-infectious neutrophilic dermatosis that classically presents as a rapidly progressive, erythematous, ulcerative lesion of the skin and soft tissue, sometimes accompanied by necrosis and purulence. It has been reported following routine surgery, and the shared features with skin and soft tissue infection can lead to treatment with antibiotics and further surgical interventions before diagnosis. Case: A 49-year-old woman presented 6 days after a bilateral carpal tunnel release with 3 days of increased pain, erythema, and swelling of the left surgical site with redness tracking up the arm. Empiric antibiotics were started for presumed surgical site infection, and she underwent irrigation and debridement (I&D) of the left carpal tunnel with extensive purulence visualized intraoperatively. She was treated with cefepime and vancomycin for 2 days then transitioned to doxycycline as wound bacterial cultures were without growth. On post-op day 4, there was increased swelling and erythema of the left surgical site prompting repeat I&D, drain placement and initiation of IV ceftriaxone and daptomycin via peripherally inserted central catheter. Three additional I&Ds of the left wrist were performed over 3 weeks for persistent symptoms. Her right wrist incision developed purulent drainage and the patient underwent 2 right sided I&Ds. A single bacterial culture grew Staphylococcus epidermidis in thioglycolate broth only, while multiple cultures for fungi and acid-fast bacilli were negative. Histopathology demonstrated acute and chronic inflammation with areas of necrosis. Broad range PCR of aspirate from her second left wrist I&D demonstrated Comamonas aquatica prompting exchange of ceftriaxone for levofloxacin and continuation of empiric daptomycin. Six weeks after her initial surgery, the patient was referred to dermatology for persistent wounds. Pyoderma gangrenosum was suspected and a trial of prednisone was initiated. One week later, there was marked improvement with decreased erythema and increased range of motion of both wrists. Antibiotics were discontinued and steroids tapered as her condition improved. Discussion: After bilateral carpal tunnel release, this patient developed suppurative surgical site wounds that were unresponsive to antibiotics and surgical debridement. It is unlikely that either C. aquatica or S. epidermidis contributed to this patient’s condition due to persistence of symptoms with appropriate antibiotics. Rapid improvement was seen with glucocorticoids, consistent with pyoderma gangrenosum. Conclusion: The differential diagnosis for a suppurative post-operative wound should include pyoderma gangrenosum. Failure to improve on antimicrobial therapy with nondiagnostic microbiologic and histopathologic studies should prompt referral to dermatology for evaluation of non-infectious etiologies.

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  Hormonal Reactivity to Social Contexts in Caregivers and Healthy Adults

  Shalmali Mirajkar and Janelle Beadle

  Providing care to older adults with chronic conditions can be emotionally meaningful and stressful. The tend-and-befriend theory highlights the role of affiliation/empathy in stress reduction, but it has not been established whether this theory extends to caregivers for older adults. Addressing this gap, we assessed caregiver empathy and stress through behavioral, hormone, and neuroimaging measures. In Experiment 1, we compared 19 caregivers (Mage=67.1) to 24 non-caregivers (Mage=72.6), and found that caregivers with a greater reduction in cortisol to an empathic context showed greater prosocial behavior (r2=0.3). In experiment 2 (N=32), we examined differences between caregivers and non-caregivers in whole brain resting-state functional connectivity (RSFC) with seed regions of interest (posterior cingulate cortex (PCC); amygdala), and covariation of RSFC with empathy (α=0.05). For emotional empathy, caregivers had stronger connectivity between the PCC seed, medial prefrontal cortex, and right supramarginal gyrus, and between the amygdala seed and the right middle frontal gyrus.

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  Medication Mayhem: A Skin-teresting Consult

  Tiffany Truong, Jonathan H. Ryder, Clayton Mowrer, and Jasmine R. Marcelin

  Introduction: Adverse reactions to medications often present with involvement of the integument. They are characterized by the rapid change of skin appearance (erythema and dryness) and associated symptoms (pruritus) culminating in a visible rash. The challenge for physicians is to determine the etiology of such rashes in order to effectively treat them. Often, cessation of the offending agent resolves the rash. Case Description: A 77-year-old male with lymphedema and over 30 episodes of cellulitis started 250 mg penicillin VK BID for prophylaxis. Eleven days later, he developed a symmetric, erythematous, scaling rash on his buttocks and perineal region with associated pruritus and bleeding. He denied any fevers or chills. The patient tried multiple over the counter medications for the rash without relief. Further medical history included chronic kidney disease, heart failure, hypertension treated with amlodipine, and overall body xerosis. Skin examination demonstrated diffuse lichenified plaques with marked fissures, scaling, and crusting on the buttocks. Dermatology was consulted, and the patient’s symptoms were attributed to symmetrical drug-related intertriginous and flexural exanthem (SDRIFE), a systemic drug-related contact dermatitis characterized by symmetric well-demarcated patches of erythema on the buttocks. This condition is also known as Baboon Syndrome due to its characteristic rash similar to the markings of a baboon. This can be caused by agents such as penicillin, hydroxyzine, and cashews, all of which the patient was exposed to. The Infectious Disease team recommended the discontinuation of Penicillin VK and hydroxyzine. The patient was switched to triamcinolone 0.1% ointment BID and clobetasol 0.05% ointment BID to the affected area with petrolatum for xerosis. A follow-up appointment with Dermatology demonstrated marked improvement. Discussion: Erythema and pruritus following initiation of a new medication is often indicative of an adverse reaction. Rashes from penicillin and hydroxyzine in patients without a history of previous reactions are less common but must also be considered. In this case, correlation of the rash with the administration of penicillin and hydroxyzine, as well as the infrequent ingestion of cashews, prompted cessation of the offending agents. However, diagnosis was delayed until these physical signs became evident. Additionally, the paradoxical reaction of hydroxyzine is typically overlooked as a culprit for erythema and rash given its intended purpose of minimizing pruritus. This case underscores the value of a thorough history and physical in combination with a broad differential in the diagnosis of pruritic rash and highlights the value in understanding polypharmacy and medical reconciliation, rather than adding agents when symptoms continue to arise.

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  The Effect of Maternal Diet on Fetal Outcomes

  Tiffany Truong, Matthew Van Ormer, Tara Nordgren, and Ann Anderson-Berry

  Maternal diet is critical for a successful pregnancy, as well as fetal health outcomes. Recent investigations reveal that dietary fats, such as omega-3 fatty acids, serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM), which have anti-inflammatory and immune-stimulating effects. However, the relationship between maternal omega-3 fatty acid intake and maternal and cord plasma SPM levels in normal weight versus obese pre-pregnancy body mass index (BMI) deliveries is unclear.

  Pre-pregnancy obesity is associated with serious adverse pregnancy outcomes, including an increased risk of miscarriage, caesarean section, pre-eclampsia, and thromboembolism. Along with maternal risk, these complications lead to a four-fold increase in neonatal mortality, attributed to prematurity and macrosomia. Obesity-associated inflammation in early development, from intrauterine, peri-partum, and early childhood insults, may have lifelong impacts on the offspring. Studies are needed to identify modifiable factors in the intrauterine environment and developing fetus that can reduce inflammation and limit the negative consequences of obesity during pregnancy. Recent studies reveal certain omega-3 fatty acid derivatives actively attenuate and resolve pro-inflammatory processes. These SPMs may be key to the beneficial effects of omega-3 fatty acids. While the association between inflammation and obesity is clear, the protective mechanisms of SPMs against complicated birth in maternal-fetal health are a gap in the field. Currently, it is known that SPM production is dependent on intermediates of the omega-3 fatty acid metabolic pathway. However, it is unknown how material SPM production is related to omega-3 fatty acid intake. In recent studies, the Anderson Berry Lab has found strikingly low intakes of omega-3 fatty acids in pregnant woman. Thus, understanding the therapeutic value of omega-3 fatty acid intake and the role of SPMs in maternal-fetal outcomes addresses an unmet need. We hope to achieve two specific aims: 1) to identify the relationship between maternal omega-3 fatty acid intake and maternal and cord plasma SPM levels in normal weight pre-pregnancy BMI and obese pre-pregnancy BMI deliveries and 2) to evaluate similarities and differences in intakes, food security, and transportation security. Dr. Anderson Berry will provide review of the pathophysiology of adverse pregnancy outcomes, teach and assist in a literature search for relevant manuscripts to study, and provide quality assurance for accuracy throughout the data collection process.

  Over a 10-week period, the recruitment of additional subjects to augment current samples was successfully performed. Subject recruitment required the collection of informed consent, preparation of maternal and cord blood, preparation of placental tissue samples, and administration of a validated food frequency questionnaire. Over 100 new subjects were successfully enrolled in the study in this manner. Preliminary evaluation of differences in intakes, food security, and transportation security between obese and normal weight groups was completed. Due to technical equipment challenges and timing inconsistencies in data analysis, utilization of a targeted lipidomics approach to measure SPMs and determine the association between maternal omega-3 fatty acid dietary intake and maternal and cord plasma SPMs is in progress with the mass spectroscopy coil and protocol being fine-tuned on other, less valuable samples.

  In the future, we hope to employ a targeted lipidomics approach to measure SPM levels and determine the association between maternal omega-3 fatty acid dietary intake and maternal and cord plasma SPM levels at the time of delivery. We plan to analyze 80 existing samples (40 mother-infant pairs) consisting of maternal, cord, placental, and neonatal blood and breast milk, 32% of which had a pre-pregnancy BMI >30. Clinical data from these subjects and dietary data measured via a validated food frequency questionnaire have been obtained. Dr. Nordgren will then determine SPM levels in plasma and placental samples via liquid chromatography-tandem mass spectrometry-mediated lipid identification. Key lipids and metabolites to be characterized will include 18- HEPE, 15-HETE, RvE1, RvD1, RvD2, RVD3, RvD5, 17(R)-RvD1, Maresin-1, and protectin-D1. This technique will also allow for determination of the association between maternal and cord serum concentrations of SPMs of obese pre-pregnancy BMI delivery. Levels and associations with clinical pregnancy outcomes will be analyzed. It is hypothesized that in the presence of obesity mediated inflammation, adequate omega-3 fatty acid intake provides a pool of substrates for increased SPM production, minimizing poor pregnancy outcomes.