Craig C Weinkauf

Interests

Research

Carotid artery diseaseBrain healthMRI

Courses

Scholarly Contributions

Chapters

• Weinkauf, C. C. (2017). Difficult Decisions in Vascular Surgery. In Decisions in Surgery: An Evidence-Based Approach.. Switzerland: Springer International.
• Weinkauf, C. C. (2015). Technological Advances in Endovascular Surgery. In Technological Advances in Surgery, Trauma & Critical Care. New York, New York: Springer.

Journals/Publications

• French, S. R., Arias, J. C., Bolakale-Rufai, I. K., Serrano, G. E., Beach, T. G., Reiman, E. M., & Weinkauf, C. C. (2024). Abstract TP238: Blood Brain Barrier Injury Detected in the Serum of Patients With a History of Stroke and Transient Ischemic Attack. Stroke, 55(Suppl_1). doi:10.1161/str.55.suppl_1.tp238
• Mori, M., Sakamoto, A., Kawakami, R., Guo, L., Slenders, L., Mosquera, J., Ghosh, S., Wesseling, M., Shiraki, T., Bellissard, A., Shah, P., Weinkauf, C., Konishi, T., Sato, Y., Cornelissen, A., Kawai, K., Jinnouchi, H., Xu, W., Vozenilek, A., , Williams, D., et al. (2024). CD163+Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma. Circulation Research, 135(2). doi:10.1161/CIRCRESAHA.123.324082
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  BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa β) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.
• Tan, T., Tolson, J., Arias Aristizabal, J., Urbina, D., Fermawi, S., Weinkauf, C., Marrero, D., & Armstrong, D. (2024). Association of Preulcerative Foot Care and Outcomes of Diabetic Foot Ulceration. Journal of the American Podiatric Medical Association, 114(2). doi:10.7547/22-071
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  Background: The purpose of this study was to determine the association of preulcerative foot care and outcomes of diabetic foot ulcerations (DFUs). Methods: This retrospective cohort study using the Mariner all-payers claims data set included participants with a new DFU from 2010 to 2019. Patients were stratified into two cohorts (foot care and control) based on whether they had received any outpatient foot care within 12 months before DFU. Adjusted comparison was performed by propensity matching for age, sex, and the Charlson Comorbidity Index (1:2 ratio). Kaplan-Meier estimates and logistic regression examined the association between foot care and outcomes of DFUs. Results: Of the 307,131 patients in the study cohort, 4.7% (n 5 14,477) received outpatient preulcerative foot care within the 12-month period before DFU. The rate of major amputation was 1.8% (foot care, 1.2%), and 9.0% of patients had hospitalizations for foot infection within 12 months after DFU (foot care, 7.8%). In the study cohort, patients who received pre-DFU foot care had greater major amputation-free survival (P < .001) on Kaplan-Meier estimate. In both the study and matched cohorts, multivariable analysis demonstrated that foot care was associated with lower odds of major amputation for both study (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.48–0.66) and matched (OR, 0.61; 95% CI, 0.51–0.72) cohorts, and lower odds of hospitalizations for a foot infection in both study (OR, 0.91; 95% CI, 0.86–0.96) and matched (OR, 0.88, 95% CI, 0.82–0.94) cohorts. Conclusions: Among patients with a new DFU, those who received outpatient preulcerative foot care within 12 months of diagnosis had lower risks of major amputation and hospitaliza tions for foot infection.
• Vitali, F., Torrandell-Haro, G., Branigan, G., Aristizabal, J., Reiman, E., Bedrick, E., Brinton, R., & Weinkauf, C. (2024). Asymptomatic carotid artery stenosis is associated with increased Alzheimer’s disease and non-Alzheimer’s disease dementia risk. Stroke and Vascular Neurology. doi:10.1136/svn-2024-003164
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  Background In the absence of a cerebrovascular accident, whether asymptomatic extracranial carotid atherosclerotic disease (aECAD) affects Alzheimer’s disease (AD) and non-AD dementia risk is not clear. Understanding whether aECAD is associated with an increased risk for AD is important as it is present in roughly 10% of the population over 60 and could represent a modifiable risk factor for AD and non-AD dementia. Methods This retrospective cohort study analysed Mariner insurance claims. Enrolment criteria included patients aged 55 years or older with at least 5 years of data and no initial dementia diagnosis. Subjects with and without aECAD were evaluated for subsequent AD and non-AD dementia diagnoses. Propensity score matching was performed using confounding factors identified by logistic regression. χ2 tests and Kaplan-Meier survival curves were used to evaluate the impact of aECAD diagnosis on AD and non-AD dementia risk over time. Results 767 354 patients met enrolment criteria. After propensity score matching, 62 963 subjects with aECAD and 62 963 subjects without ECAD were followed through data records. The aECAD cohort exhibited an increased relative risk of 1.22 (95% CI 1.15 to 1.29, p
• Bolakale-Rufai, I. K., Thompson, M. R., Concha-Moore, K., Jett, S., Awasthi, S., Cuccia, D. J., Mazhar, A., & Weinkauf, C. C. (2023). Assessment of revascularization impact on microvascular oxygenation and perfusion using spatial frequency domain imaging. Journal of surgical case reports, 2023(7), rjad382.
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  The microvasculature (with vessels
• Patel, N., Tan, T. W., Weinkauf, C., Rice, A. H., Rottman, A. M., Pappalardo, J., Goshima, K., & Zhou, W. (2022). Economic value of podiatry service in limb salvage alliance. Journal of vascular surgery, 75(1), 296-300.
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  Over the past decade, multidisciplinary "toe and flow" programs have gained great popularity, with proven benefits in limb salvage. Many vascular surgeons have incorporated podiatrists into their practices. The viability of this practice model requires close partnership, hospital support, and financial sustainability. We intend to examine the economic values of podiatrists in a busy safety-net hospital in the Southwest United States.
• Weise, L., Chiapaikeo, D., Tan, T. W., Weinkauf, C., Goshima, K. R., & Zhou, W. (2022). Role of late renal revascularization in functional renal salvage. Journal of vascular surgery cases and innovative techniques, 8(1), 121-124.
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  The duration that renal parenchyma will tolerate ischemia has continued to be debated. We have reported the cases of three patients who had undergone revascularization procedures with successful return of baseline renal function after prolonged renal artery occlusion of 14 days to 3 months. These cases highlight that aggressive revascularization can lead to successful renal salvage in selected patients. We examined the characteristics of these patients and those of others in the literature and reviewed the factors favoring recovery.
• Arias, J. C., Edwards, M., Vitali, F., Beach, T. G., Serrano, G. E., & Weinkauf, C. C. (2021). Extracranial carotid atherosclerosis is associated with increased neurofibrillary tangle accumulation. Journal of vascular surgery.
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  We sought to determine whether extracranial carotid atherosclerotic disease (ECAD) is associated with increased key neurodegenerative pathology such as neurofibrillary tangle (NFT), beta-amyloid plaque, or cerebral amyloid angiopathy (CAA) accumulation, findings associated with Alzheimer's disease (AD) and other dementias.
• Bilgin, A., Weinkauf, C. C., Winegar, B., Altbach, M. I., Rosado-Toro, J. A., Keerthivasan, M. B., Guzman Perez-Carrillo, G., & Umapathy, L. (2020). A Stacked Generalization of 3D Orthogonal Deep Learning Convolutional Neural Networks for Improved Detection of White Matter Hyperintensities in 3D-FLAIR Images. American Journal of Neuroradiology.
• Harris, D. T., Badowski, M., Jernigan, B., Sprissler, R., Edwards, T., Cohen, R., Paul, S., Merchant, N., Weinkauf, C. C., Bime, C., Erickson, H. E., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., Campion, J., , Chopra, M., et al. (2021). SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus. Biomedicines, 9(5).
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  SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.
• Jett, S., Thompson, M. R., Awasthi, S., Cuccia, D. J., Tan, T. W., Armstrong, D. G., Mazhar, A., & Weinkauf, C. C. (2021). Stratification of Microvascular Disease Severity in the Foot Using Spatial Frequency Domain Imaging. Journal of diabetes science and technology, 19322968211024666.
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  Microvascular disease (MVD) describes systemic changes in the small vessels (~100 um diameter) that impair tissue oxygenation and perfusion. MVD is a common but poorly monitored complication of diabetes. Recent studies have demonstrated that MVD: (i) is an independent risk factor for ulceration and amputation and (ii) increases risk of adverse limb outcomes synergistically with PAD. Despite the clinical relevance of MVD, microvascular evaluation is not standard in a vascular assessment.
• Pandit, V., Zeeshan, M., Nelson, P. R., Hamidi, M., Jhajj, S., Lee, A., Trinidad, B., Goshima, K., Horst, V., Weinkauf, C., Zhou, W., & Tan, T. W. (2020). Frailty Syndrome in Patients with Carotid Disease: Simplifying How We Calculate Frailty. Annals of vascular surgery, 62, 159-165.
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  Frailty syndrome is an established predictor of adverse outcomes after carotid surgery. Recently, a modified 5-factor National Surgical Quality Improvement Program frailty index has been used; however, its utility in vascular procedures is unclear. The aim of our study was to compare the 5-factor modified frailty index (mFI-5) with the 11-factor modified frailty index (mFI-11) regarding value and predictive ability for mortality, postoperative infection, and unplanned 30-day readmission.
• Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., Aini, T. E., Rischard, F., , Campion, J., et al. (2020). Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. medRxiv : the preprint server for health sciences.
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  We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
• Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., , Campion, J., et al. (2020). Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity, 53(5), 925-933.e4.
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  We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.
• Altbach, M. I., Bilgin, A., Martin, D. R., Weinkauf, C. C., Fu, Z., Saranathan, M., Johnson, K., & Keerthivasan, M. B. (2019). An Efficient 3D Stack-of-Stars TSE Pulse Sequence for Simultaneous T2-weighted Imaging and T2 Mapping. Magnetic Resonance in Medicine, 82(1), 326-341.
• Keerthivasan, M. B., Saranathan, M., Johnson, K., Fu, Z., Weinkauf, C. C., Martin, D. R., Bilgin, A., & Altbach, M. I. (2019). An efficient 3D stack-of-stars turbo spin echo pulse sequence for simultaneous T2-weighted imaging and T2 mapping. Magnetic resonance in medicine, 82(1), 326-341.
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  To design a pulse sequence for efficient 3D T2-weighted imaging and T2 mapping.
• Pandit, V., Lee, A., Zeeshan, M., Goshima, K., Tan, T. W., Jhajj, S., Trinidad, B., Weinkauf, C., & Zhou, W. (2019). Effect of frailty syndrome on the outcomes of patients with carotid stenosis. Journal of vascular surgery.
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  Frailty syndrome confers a greater risk of morbidity and mortality after operative interventions. The aim of the present study was to assess the effect of frailty on the outcomes after carotid interventions, including both carotid endarterectomy (CEA) and carotid artery stenting (CAS).
• Sabat, J., Bock, D., Hsu, C. H., Tan, T. W., Weinkauf, C., Trouard, T., Perez-Carrillo, G. G., & Zhou, W. (2019). Risk factors associated with microembolization after carotid intervention. Journal of vascular surgery.
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  Microembolization after carotid artery stenting (CAS) and carotid endarterectomy (CEA) has been documented and may confer risk for neurocognitive impairment. Patients undergoing stenting are known to be at higher risk for microembolization. In this prospective cohort study, we compare the microembolization rates for patients undergoing CAS and CEA and perioperative characteristics that may be associated with microembolization.
• Sabat, J., Hsu, C. H., Samra, N., Chu, Q., Weinkauf, C., Goshima, K., Zhou, W., & Tan, T. W. (2019). Length of Stay and ICU Stay Are Increased With Repair of Traumatic Superior Mesenteric Vein Injury. The Journal of surgical research, 242, 94-99.
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  Traumatic superior mesenteric vein (SMV) injury is rare, and the ideal treatment is controversial. We compared the outcomes of ligation versus repair of SMV injury using the National Trauma Databank.
• Weinkauf, C., Mazhar, A., Vaishnav, K., Hamadani, A. A., Cuccia, D. J., & Armstrong, D. G. (2019). Near-instant noninvasive optical imaging of tissue perfusion for vascular assessment. Journal of vascular surgery.
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  Noninvasive vascular tests are critical for identifying patients who may benefit from surgical revascularization, but current tests have significant limitations in people with diabetes. This study aimed to evaluate the ability of spatial frequency domain imaging (SFDI), an optical imaging method capable of measuring tissue oxygen saturation (StO) and tissue hemoglobin, to assess lower extremity blood supply.
• Yanquez, F. J., Peterson, A., Weinkauf, C., Goshima, K. R., Zhou, W., Mohler, J., Ehsani, H., & Toosizadeh, N. (2019). Sensor-Based Upper-Extremity Frailty Assessment for the Vascular Surgery Risk Stratification. The Journal of surgical research.
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  Available methods for determining outcomes in vascular surgery patients are often subjective or not applicable in nonambulatory patients. The purpose of the present study was to assess the association between vascular surgery outcomes and a previously validated upper-extremity function (UEF) method, which incorporates wearable motion sensors for the physical frailty assessment.
• Moccetti, F., Weinkauf, C. C., Davidson, B. P., Belcik, J. T., Marinelli, E. R., Unger, E., & Lindner, J. R. (2018). Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress. Ultrasound in medicine & biology, 44(6), 1155-1163.
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  The aim of this study was to evaluate a panel of endothelium-targeted microbubble (MB) ultrasound contrast agents bearing small peptide ligands as a human-ready approach for molecular imaging of markers of high-risk atherosclerotic plaque. Small peptide ligands with established affinity for human P-selectin, VCAM-1, LOX-1 and von Willebrand factor (VWF) were conjugated to the surface of lipid-stabilized MBs. Contrast-enhanced ultrasound (CEUS) molecular imaging of the thoracic aorta was performed in wild-type and gene-targeted mice with advanced atherosclerosis (DKO). Histology was performed on carotid endarterectomy samples from patients undergoing surgery for unstable atherosclerosis to assess target expression in humans. In DKO mice, CEUS signal for all four targeted MBs was significantly higher than that for control MBs, and was three to sevenfold higher than in wild-type mice, with the highest signal achieved for VCAM-1 and VWF. All molecular targets were present on the patient plaque surface but expression was greatest for VCAM-1 and VWF. We conclude that ultrasound contrast agents bearing small peptide ligands feasible for human use can be targeted against endothelial cell adhesion molecules for inflammatory cells and platelets for imaging advanced atherosclerotic disease.
• Trinidad, B., Weinkauf, C., & Hughes, J. (2018). Perigraft air mimicking infection on CT angiography following open abdominal aortic aneurysm repair. Radiology case reports, 13(2), 343-346.
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  Aortic graft infection is a feared complication after open abdominal aortic aneurysm repair secondary to its high mortality. Perigraft air is a common finding after open aortic aneurysm repair; however, it is also associated with aortic graft infection. Delineating between graft infection and common postoperative finding is a challenge. This is further complicated by use of hemostatic agents such as Gelfoam, which is also documented to cause perigraft air. Correct diagnosis has crucial implications in management of potential aortic graft infection, which is a vascular emergency. We report a case of perigraft air in a patient status after open aortic aneurysm repair with associated clinical manifestations of infection in whom conservative management and surveillance was selected for treatment. We then discuss the timeline of perigraft air, potential causation, importance of history, and physical examination, and finally, we discuss how specific findings on computed tomography imaging for infection in other areas may be useful in aortic graft infection.
• Weinkauf, C. C., Concha-Moore, K., Lindner, J. R., Marinelli, E. R., Hadinger, K. P., Bhattacharjee, S., Berman, S. S., Goshima, K., Leon, L. R., Matsunaga, T. O., & Unger, E. (2018). Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging. Journal of vascular surgery, 68(6S), 105S-113S.
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  Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging.
• Weinkauf, C., George, E., & Zhou, W. (2017). Open versus endovascular aneurysm repair trial review. Surgery, 162(5), 974-978.
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  The Open versus Endovascular Aneurysm Repair trial is the only randomized controlled trial that is funded by the federal government to evaluate the treatment outcomes of infrarenal abdominal aortic aneurysms. Since the initial publication, multiple post-hoc analyses have become available. This review summarizes these data, focusing on the primary outcome measures (ie, overall survival) and several key secondary outcomes including aneurysm-related death, age consideration, secondary procedures, and endoleaks. Cost-effectiveness of each treatment modality and the limitations of OVER trial also are discussed critically in this review.
• Umiker, B. R., Andersson, S., Fernandez, L., Korgaokar, P., Larbi, A., Pilichowska, M., Weinkauf, C. C., Wortis, H. H., Kearney, J. F., & Imanishi-Kari, T. (2014). Dosage of X-linked Toll-like receptor 8 determines gender differences in the development of systemic lupus erythematosus. European journal of immunology, 44(5), 1503-16.
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  Systemic lupus erythematosus (SLE) is an autoimmune disease with a high incidence in females and a complex phenotype. Using 564Igi mice, a model of SLE with knock-in genes encoding an autoreactive anti-RNA Ab, we investigated how expression of Toll-like receptors (TLRs) in B cells and neutrophils affects pathogenesis. We established that TLR signaling through MyD88 is necessary for disease. Autoantibody was produced in mice with single deletions of Tlr7, Tlr8, or Tlr9 or combined deletions of Tlr7 and Tlr9. Autoantibody was not produced in the combined absence of Tlr7 and Tlr8, indicating that TLR8 contributes to the break in tolerance. Furthermore, TLR8 was sufficient for the loss of B-cell tolerance, the production of class-switched autoantibody, heightened granulopoiesis, and increased production of type I IFN by neutrophils as well as glomerulonephritis and death. We show that dosage of X-linked Tlr8 plays a major role in the high incidence of disease in females. In addition, we show that the negative regulation of disease by TLR9 is exerted primarily on granulopoiesis and type I IFN production by neutrophils. Collectively, we suggest that individual TLRs play unique roles in the pathogenesis of systemic lupus erythematosus, suggesting new targets for treatment.
• Weinkauf, C., McPhillips, S., Krouse, R., & Levine, I. (2014). Autoimmune Gastrointestinal Paralysis: Failure of Conventional Treatment without Immunomodulation. Case reports in surgery, 2014, 180654.
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  The treatment of the rare enteric nervous system (ENS) manifestations of paraneoplastic syndromes, which are most frequently associated with small cell lung cancer (SCLC), is poorly understood and described. Patients with neuroendocrine-derived tumors can develop B-cell reactivity towards the tumor with cross-reactivity for neurons located in the submucosal and myenteric ganglia of the ENS. The ensuing autoimmune neuritis causes aperistalsis and severe gastrointestinal (GI) dysfunction. Immune-directed therapy is not the standard of care but may be paramount for patient recovery. Our patient, a 63-year-old man with recent symptoms of esophageal dysmotility and newly diagnosed SCLC was hospitalized with nausea, emesis, and constipation. After an extensive work-up that included laparoscopy and celiotomy with bowel resection, we diagnosed what we refer to as Autoimmune Paraneoplastic Chronic Intestinal Pseudoobstruction (AP-CIPO). Unlike the few clinically similar reports, SCLC and AP-CIPO were diagnosed in our patient within weeks of each other, which presented the dilemma of treating the two processes simultaneously. In this report, we review the relevant literature and describe our patient's course. We believe standard chemotherapy is not effective treatment for AP-CIPO. Based on evidence discussed herein, we suggest initiating autoimmune-directed therapy before or simultaneous with cancer-directed therapy.
• Weinkauf, C., Salvador, R., & Pereiraperrin, M. (2011). Neurotrophin receptor TrkC is an entry receptor for Trypanosoma cruzi in neural, glial, and epithelial cells. Infection and immunity, 79(10), 4081-7.
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  Trypanosoma cruzi, the agent of Chagas' disease, infects a variety of mammalian cells in a process that includes multiple cycles of intracellular division and differentiation starting with host receptor recognition by a parasite ligand(s). Earlier work in our laboratory showed that the neurotrophin-3 (NT-3) receptor TrkC is activated by T. cruzi surface trans-sialidase, also known as parasite-derived neurotrophic factor (PDNF). However, it has remained unclear whether TrkC is used by T. cruzi to enter host cells. Here, we show that a neuronal cell line (PC12-NNR5) relatively resistant to T. cruzi became highly susceptible to infection when overexpressing human TrkC but not human TrkB. Furthermore, trkC transfection conferred an ∼3.0-fold intracellular growth advantage. Sialylation-deficient Chinese hamster ovarian (CHO) epithelial cell lines Lec1 and Lec2 also became much more permissive to T. cruzi after transfection with the trkC gene. Additionally, NT-3 specifically blocked T. cruzi infection of the TrkC-NNR5 transfectants and of naturally permissive TrkC-bearing Schwann cells and astrocytes, as did recombinant PDNF. Two specific inhibitors of Trk autophosphorylation (K252a and AG879) and inhibitors of Trk-induced MAPK/Erk (U0126) and Akt kinase (LY294002) signaling, but not an inhibitor of insulin-like growth factor 1 receptor, abrogated TrkC-mediated cell invasion. Antibody to TrkC blocked T. cruzi infection of the TrkC-NNR5 transfectants and of cells that naturally express TrkC. The TrkC antibody also significantly and specifically reduced cutaneous infection in a mouse model of acute Chagas' disease. TrkC is ubiquitously expressed in the peripheral and central nervous systems, and in nonneural cells infected by T. cruzi, including cardiac and gastrointestinal muscle cells. Thus, TrkC is implicated as a functional PDNF receptor in cell entry, independently of sialic acid recognition, mediating broad T. cruzi infection both in vitro and in vivo.
• Weinkauf, C., & Pereiraperrin, M. (2009). Trypanosoma cruzi promotes neuronal and glial cell survival through the neurotrophic receptor TrkC. Infection and immunity, 77(4), 1368-75.
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  Trypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFRalpha). However, these receptors are expressed by only a subset of neurons and at low levels or not at all in glial cells. Thus, T. cruzi might exploit an additional neurotrophic receptor(s) to maximize host-parasite equilibrium in the nervous system. We show here that T. cruzi binds TrkC, a neurotrophic receptor expressed by glial cells and many types of neurons, and that the binding is specifically inhibited by neurotrophin-3, the natural TrkC ligand. Coimmunoprecipitation and competition assays show that the trans-sialidase/parasite-derived neurotrophic factor (PDNF), previously identified as a TrkA ligand, mediates the T. cruzi-TrkC interaction. PDNF promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite outgrowth, and survival of genetically engineered PC12 neuronal cells and glial Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic receptor that T. cruzi engages to promote the survival of neuronal and glial cells. The results raise the possibility that T. cruzi recognition of TrkC underlies regenerative events in nervous tissues of patients with Chagas' disease.
• Theoharides, T. C., Weinkauf, C., & Conti, P. (2004). Brain cytokines and neuropsychiatric disorders. Journal of clinical psychopharmacology, 24(6), 577-81.

Proceedings Publications

• Umapathy, L., Guzman Perez-Carrillo, G., Keerthivasan, M., Altbach, M. I., Winegar, B., Weinkauf, C. C., & Bilgin, A. (2020, August). StackGen-Net: A Stacked Generalization of 3D Orthogonal Convolutional Neural Networks for Improved Detection of White Matter Hyperintensities. In Annual Meeting of the International Society for Magnetic Resonance in Medicine.
• Altbach, M. I., Weinkauf, C. C., Bilgin, A., Johnson, K., & Keerthivasan, M. B. (2019, May). Efficient T2 Mapping of the Carotid Artery using a 3D Stack-of-Stars Variable Flip Angle TSE Pulse Sequence. In 2019 Annual Meeting of the ISMRM, Montreal, QC, Canada.
• Weinkauf, C. C., Trouard, T. P., Chou, Y., Chen, N., Guzman Perez-Carrillo, G., Ryan, T. L., Altbach, M. I., Johnson, K., Bruck, D., Ugonna, C., McKinnon, A., Bernstein, A. S., & Lindley, M. (2019, Spring). Functional and Microstructural Changes in the Brain After Carotid Endarterectomy. In International Society for Magnetic Resonance in Medicine.
• Altbach, M. I., Bilgin, A., Martin, D. R., Weinkauf, C. C., Saranathan, M., Johnson, K., & Keerthivasan, M. B. (2018, June). An Optimized 3D Stack-of-Stars TSE Pulse Sequence for Simultaneous T2-weighted Imaging and T2 Mapping. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
• Weinkauf, C. C., Bilgin, A., Becker, J., Keerthivasan, M. B., Li, Z., Johnson, K., Mandava, S., & Altbach, M. I. (2018, June). Rapid Carotid Artery T2 and T1 Mapping Using a Radial TSE and IR-FLASH Approach. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
• Weinkauf, C. C., Trouard, T. P., Guzman Perez-Carrillo, G., Chou, Y., Chen, N., Ryan, L., Altbach, M. I., Johnson, K., Bruck, D., Ugonna, C., Bernstein, A., & Lindley, M. (2018, June). Impact of Carotid Endarterectomy on Functional Connectivity. In Joint International Society for Magnetic Resonance in Medicine & The European Society for Magnetic Resonance in Medicine and Biology (ISMRM-ESMRMB) Annual Meeting, 5562.

Presentations

• Zhou, W., Weinkauf, C. C., & Tan, T. (2021, October). Association of Preventive Foot Care and Outcome of New Diabetic Foot Ulceration. 2021 American Public Health Association (APHA) Annual Meeting. Denver, CO: American Public Health Association.
• Weinkauf, C. C. (2019, January 2019). Quantitative Evaluation of Cognition and Brain function in the Treatment of Extracranial Carotid Atherosclerosis. Banner Alzheimer’s Institute. Phoenix, AZ.
• Weinkauf, C. C. (2019, May 2019). Vertebrobasilar Insufficiency. Vascular Surgery Teaching Conference. College of Medicine: University of Arizona.
• Weinkauf, C. C. (2018, December). Introduction to Non-Cardiac Vascular Surgery Emergencies. Medicine Grand Rounds. College of Medicine: University of Arizona.