Caitlin Parmer-Chow

All Publications

• Association between emergency department disposition and mortality in patients with COVID-19 acute respiratory distress syndrome. Journal of the American College of Emergency Physicians open Lebold, K. M., Moore, A. R., Sanchez, P. A., Pacheco-Navarro, A. E., O'Donnell, C., Roque, J., Parmer, C., Pienkos, S., Levitt, J., Collins, W. J., Rogers, A. J., Wilson, J. G. 2024; 5 (3): e13192

  Abstract

  Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission to hospital wards with subsequent transfer to intensive care unit (ICU) is associated with worse outcomes. We hypothesized that initial admission to the ward may affect outcomes in patient with COVID-19 ARDS.This was a retrospective study of consecutive adults admitted for COVID-19 ARDS between March 2020 and March 2021 at Stanford Health Care. Mortality scores at hospital admission (Coronavirus Clinical Characterization Consortium Mortality Score [4C score]) and ICU admission (Simplified Acute Physiology Score III [SAPS-III]) were calculated, as well as ROX index for patients on high flow nasal oxygen. Patients were classified by emergency department (ED) disposition (ward-first vs. ICU-direct), and 28- and 60-day mortality and highest level of respiratory support within 1 day of ICU admission were compared. A second cohort (April 2021‒July 2022, n = 129) was phenotyped to validate mortality outcome.A total of 157 patients were included, 48% of whom were first admitted to the ward (n = 75). Ward-first patients had more comorbidities, including lung disease. Ward-first patients had lower 4C and similar SAPS-III score, yet increased mortality at 28 days (32% vs. 17%, hazard ratio [HR] 2.0, 95% confidence interval [95% CI] 1.0‒3.7, p = 0.039) and 60 days (39% vs. 23%, HR 1.83, 95% CI 1.04‒3.22, p = 0.037) compared to ICU-direct patients. More ward-first patients escalated to mechanical ventilation on day 1 of ICU admission (36% vs. 14%, p = 0.002) despite similar ROX index. Ward-first patients who upgraded to ICU within 48 h of ED presentation had the highest mortality. Mortality findings were replicated in a sensitivity analysis.Despite similar baseline risk scores, ward-first patients with COVID-19 ARDS had increased mortality and escalation to mechanical ventilation compared to ICU-direct patients. Ward-first patients requiring ICU upgrade within 48 h were at highest risk, highlighting a need for improved identification of this group at ED admission.

  View details for DOI 10.1002/emp2.13192

  View details for PubMedID 38887225

  View details for PubMedCentralID PMC11180691

• DON'T GET LOST IN TRANSLATION: IMPROVING CARE OF PATIENTS WITH LIMITED ENGLISH PROFICIENCY (LEP) Wang, S., Caton, J., Parmer-Chow, C. M., Parker, J. SPRINGER. 2024: S987

  View details for Web of Science ID 001433572703119

• LANGUAGE EQUITY NOW: A CURRICULAR NEED IN GRADUATE MEDICAL EDUCATION Parmer-Chow, C. M., Parker, J., Wang, S. SPRINGER. 2024: S855-S856

  View details for Web of Science ID 001433572702321

• Right Ventricular Dysfunction Patterns Among Patients with COVID-19 in the Intensive Care Unit - a Retrospective Cohort Analysis. Annals of the American Thoracic Society Sanchez, P. A., O'Donnell, C. T., Francisco, N., Santana, E. J., Moore, A. R., Pacheco-Navarro, A., Roque, J., Lebold, K. M., Parmer, C. M., Pienkos, S. M., Celestin, B. E., Levitt, J. E., Collins, W. J., Lanspa, M. J., Ashley, E. A., Wilson, J. G., Haddad, F., Rogers, A. J. 2023

  Abstract

  Right ventricular (RV) dysfunction is common among patients hospitalized with COVID-19; however, its epidemiology may depend on the echocardiographic parameters used to define it.To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among COVID-19 patients admitted to the intensive care unit, as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality.Retrospective cohort study of COVID-19 ICU patients between March 4th,2020 to March 4th, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation respectively defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at time of TTE and APACHE II score.116 patients were included, of which 69% had RV dysfunction by > 1 parameter and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction included: Presence of 3 abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RVFAC (24% vs 36%, p = 0.001), worse RVFWS (16.3% vs 19.1%, p = 0.005), higher RVSP (45mmHg vs 31mmHg, p = 0.001) but similar TAPSE (13mm vs 13mm, p = 0.30) compared to those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (OR 2.91, 95% CI 1.01 - 9.44), as was the presence of at least 2 parameter abnormalities.ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

  View details for DOI 10.1513/AnnalsATS.202303-235OC

  View details for PubMedID 37478340

• Obeticholic Acid Decreases Intestinal Content of Enterococcus in Rats With Cirrhosis and Ascites HEPATOLOGY COMMUNICATIONS Yan, K., Hung, A., Parmer, C., Yang, H., Jain, D., Lim, B., Goodman, A. L., Garcia-Tsao, G. 2021; 5 (9): 1507-1517

  Abstract

  The intestinal microbiome and bacterial translocation (BT), the passage of microorganisms from the gut lumen to mesenteric lymph nodes and other extra-intestinal sites, are main mechanisms implicated in liver injury and further decompensation in patients with cirrhosis. We hypothesized that obeticholic acid (OCA), a semisynthetic bile acid, would change the microbiome composition and reduce bacterial translocation in experimental cirrhosis. Rats with cirrhosis induced by carbon tetrachloride inhalation (a nonseptic model) with ascites present for at least 7 days were randomized to receive a 14-day course of OCA at a dose of 5 mg/kg/day (n = 34) or placebo (n = 34). Stool was collected at days 1 (randomization), 8, and 14 (sacrifice) for analysis of intestinal microbiome using the V4 hypervariable region of the bacterial 16S gene amplified by polymerase chain reaction. Bacteriological cultures of mesenteric lymph nodes, blood, and ascites were performed at end of study. Twenty-four animals in each group reached the end of study. Compared with placebo, rats treated with OCA had decreased relative abundance of Enterococcus in both ileum content (P = 0.02) and in stool (P < 0.001). BT from pathogenic bacteria was not different between groups. At end of treatment, rats on OCA had a significantly lower aspartate aminotransferase (AST) (266 vs. 369 IU/L; P < 0.01) and higher serum albumin (0.9 vs. 0.7 g/dL; P < 0.01) than rats on placebo. Conclusion: Although OCA did not appear to reduce BT by pathogenic bacteria, the reduction in intestinal content of Enterococcus, which has been associated with hepatocyte death, in OCA-treated animals is consistent with our observed improvements in AST and in liver function, as evidenced by higher serum albumin.

  View details for DOI 10.1002/hep4.1740

  View details for Web of Science ID 000659492600001

  View details for PubMedID 34510838

  View details for PubMedCentralID PMC8435275

• Fine needle aspiration cytology of peripancreatic myelolipoma DIAGNOSTIC CYTOPATHOLOGY Huang, Q., Parmer, C., Muniraj, T., Aslanian, H. R., Cai, G. 2020; 48 (5): 491-493

  View details for DOI 10.1002/dc.24399

  View details for Web of Science ID 000523332100012

  View details for PubMedID 32150351

• Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease. Vascular medicine (London, England) Parmer, C. n., De Sousa-Coelho, A. L., Cheng, H. S., Daher, G. n., Burkart, A. n., Dreyfuss, J. M., Pan, H. n., Prenner, J. C., Keilson, J. M., Pande, R. n., Henkin, S. n., Feinberg, M. W., Patti, M. E., Creager, M. A. 2020: 1358863X20947467

  Abstract

  Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) was PLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR; PLA2G16 was downregulated by 68% in patients with PAD (p < 0.001). Expression of Pla2g16 was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression of Pla2g16 in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.

  View details for DOI 10.1177/1358863X20947467

  View details for PubMedID 32853041

• Resolvin D2 Enhances Postischemic Revascularization While Resolving Inflammation CIRCULATION Zhang, M. J., Sansbury, B. E., Hellmann, J., Baker, J. F., Guo, L., Parmer, C. M., Prenner, J. C., Conklin, D. J., Bhatnagar, A., Creager, M. A., Spite, M. 2016; 134 (9): 666-680

  Abstract

  Resolvins are lipid mediators generated by leukocytes during the resolution phase of inflammation. They have been shown to regulate the transition from inflammation to tissue repair; however, it is unknown whether resolvins play a role in tissue revascularization following ischemia.We used a murine model of hind limb ischemia (HLI), coupled with laser Doppler perfusion imaging, microcomputed tomography, and targeted mass spectrometry, to assess the role of resolvins in revascularization and inflammation resolution.In mice undergoing HLI, we identified resolvin D2 (RvD2) in bone marrow and skeletal muscle by mass spectrometry (n=4-7 per group). We also identified RvD2 in skeletal muscle biopsies from humans with peripheral artery disease. Monocytes were recruited to skeletal muscle during HLI and isolated monocytes produced RvD2 in a lipoxygenase-dependent manner. Exogenous RvD2 enhanced perfusion recovery in HLI and microcomputed tomography of limb vasculature revealed greater volume, with evidence of tortuous arterioles indicative of arteriogenesis (n=6-8 per group). Unlike other treatment strategies for therapeutic revascularization that exacerbate inflammation, RvD2 did not increase vascular permeability, but reduced neutrophil accumulation and the plasma levels of tumor necrosis factor-α and granulocyte macrophage colony-stimulating factor. In mice treated with RvD2, histopathologic analysis of skeletal muscle of ischemic limbs showed more regenerating myocytes with centrally located nuclei. RvD2 enhanced endothelial cell migration in a Rac-dependent manner, via its receptor, GPR18, and Gpr18-deficient mice had an endogenous defect in perfusion recovery following HLI. Importantly, RvD2 rescued defective revascularization in diabetic mice.RvD2 stimulates arteriogenic revascularization during HLI, suggesting that resolvins may be a novel class of mediators that both resolve inflammation and promote arteriogenesis.

  View details for DOI 10.1161/CIRCULATIONAHA.116.021894

  View details for Web of Science ID 000382288200012

  View details for PubMedID 27507404

  View details for PubMedCentralID PMC5214591

• Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus ACTA DIABETOLOGICA Milian, J., Goldfine, A. B., Zuflacht, J. P., Parmer, C., Beckman, J. A. 2015; 52 (4): 709-715

  Abstract

  Vascular disease is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). We previously demonstrated that patients with T1DM have impaired endothelial function, a forme fruste of atherosclerosis, as a result of increased oxidative stress. Bilirubin has emerged as a potent endogenous antioxidant with higher concentrations associated with lower rates of myocardial infarction and stroke.We tested the hypothesis that increasing endogenous bilirubin using atazanavir would improve cardiometabolic risk factors and vascular function in patients with T1DM to determine whether targeting bilirubin may be a novel therapeutic approach to reduce cardiovascular disease risk in this population. In this single-arm, open-label study, we evaluated blood pressure, lipid profile, and conduit artery function in fifteen subjects (mean age 45 ± 9 years) with T1DM following a 4-day treatment with atazanavir.As anticipated, atazanavir significantly increased both serum total bilirubin levels (p < 0.0001) and plasma total antioxidant capacity (p < 0.0001). Reductions in total cholesterol (p = 0.04), LDL cholesterol (p = 0.04), and mean arterial pressure (p = 0.04) were also observed following atazanavir treatment. No changes were seen in either flow-mediated endothelium-dependent (p = 0.92) or nitroglycerine-mediated endothelium-independent (p = 0.68) vasodilation, measured by high-resolution B-mode ultrasonography at baseline and post-treatment.Increasing serum bilirubin levels with atazanavir in subjects with T1DM over 4 days favorably reduces LDL and blood pressure but is not associated with improvements in endothelial function of conduit arteries.

  View details for DOI 10.1007/s00592-014-0708-6

  View details for Web of Science ID 000358085800009

  View details for PubMedID 25563478

  View details for PubMedCentralID PMC4496330

• New Insights into the Role of Plg-R-KT in Macrophage Recruitment INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 309 Miles, L. A., Lighvani, S., Baik, N., Parmer, C. M., Khaldoyanidi, S., Mueller, B. M., Parmer, R. J., Jeon, K. W. 2014; 309: 259-302

  Abstract

  Plasminogen (PLG) is the zymogen of plasmin, the major enzyme that degrades fibrin clots. In addition to its binding and activation on fibrin clots, PLG also specifically interacts with cell surfaces where it is more efficiently activated by PLG activators, compared with the reaction in solution. This results in association of the broad-spectrum proteolytic activity of plasmin with cell surfaces that functions to promote cell migration. Here, we review emerging data establishing a role for PLG, plasminogen receptors and the newly discovered plasminogen receptor, Plg-RKT, in macrophage recruitment in the inflammatory response, and we address mechanisms by which the interplay between PLG and its receptors regulates inflammation.

  View details for DOI 10.1016/B978-0-12-800255-1.00005-3

  View details for Web of Science ID 000333377700005

  View details for PubMedID 24529725

  View details for PubMedCentralID PMC4060795

• The Plasminogen Receptor, Plg-R-KT, and Macrophage Function JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY Miles, L. A., Lighvani, S., Baik, N., Andronicos, N. M., Chen, E. I., Parmer, C. M., Khaldoyanidi, S., Diggs, J. E., Kiosses, W. B., Kamps, M. P., Yates, J. R., Parmer, R. J. 2012: 250464

  Abstract

  When plasminogen binds to cells its activation to plasmin is markedly enhanced compared to the reaction in solution. Thus, cells become armed with the broad spectrum proteolytic activity of plasmin. Cell-surface plasmin plays a key role in macrophage recruitment during the inflammatory response. Proteins exposing basic residues on the cell surface promote plasminogen activation on eukaryotic cells. We have used a proteomics approach combining targeted proteolysis with carboxypeptidase B and multidimensional protein identification technology, MudPIT, and a monocyte progenitor cell line to identify a novel transmembrane protein, the plasminogen receptor, Plg-R(KT). Plg-R(KT) exposes a C-terminal lysine on the cell surface in an orientation to bind plasminogen and promote plasminogen activation. Here we review the characteristics of this new protein, with regard to membrane topology, conservation of sequence across species, the role of its C-terminus in plasminogen binding, its function in plasminogen activation, cell migration, and its role in macrophage recruitment in the inflammatory response.

  View details for DOI 10.1155/2012/250464

  View details for Web of Science ID 000310018100001

  View details for PubMedID 23125524

  View details for PubMedCentralID PMC3484331

• Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-R-KT, a major regulator of cell surface plasminogen activation BLOOD Andronicos, N. M., Chen, E. I., Baik, N., Bai, H., Parmer, C. M., Kiosses, W. B., Kamps, M. P., Yates, J. R., Parmer, R. J., Miles, L. A. 2010; 115 (7): 1319-1330

  Abstract

  Activation of plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin, is markedly promoted when plasminogen is bound to cell surfaces, arming cells with the broad spectrum proteolytic activity of plasmin. In addition to its role in thrombolysis, cell surface plasmin facilitates a wide array of physiologic and pathologic processes. Carboxypeptidase B-sensitive plasminogen binding sites promote plasminogen activation on eukaryotic cells. However, no integral membrane plasminogen receptors exposing carboxyl terminal basic residues on cell surfaces have been identified. Here we use the exquisite sensitivity of multidimensional protein identification technology and an inducible progenitor cell line to identify a novel differentiation-induced integral membrane plasminogen receptor that exposes a C-terminal lysine on the cell surface, Plg-R(KT) (C9orf46 homolog). Plg-R(KT) was highly colocalized on the cell surface with the urokinase receptor, uPAR. Our data suggest that Plg-R(KT) also interacts directly with tissue plasminogen activator. Furthermore, Plg-R(KT) markedly promoted cell surface plasminogen activation. Database searching revealed that Plg-R(KT) mRNA is broadly expressed by migratory cell types, including leukocytes, and breast cancer, leukemic, and neuronal cells. This structurally unique plasminogen receptor represents a novel control point for regulating cell surface proteolysis.

  View details for DOI 10.1182/blood-2008-11-188938

  View details for Web of Science ID 000274669200004

  View details for PubMedID 19897580

  View details for PubMedCentralID PMC2826757