Maja Artandi, MD

All Publications

• Evaluation of video visit appropriateness for common symptoms seen in primary care: A retrospective cohort study. Journal of telemedicine and telecare Chen, D., Gonzales, E., Winget, M., Shaw, J., Artandi, M., Tsai, S. A., Nelligan, I. 2024: 1357633X231224094

  Abstract

  INTRODUCTION: Little is known about which conditions seen in primary care are appropriate for video visits. This study evaluated video visits compared to office visits for six conditions: abdominal pain, joint pain, back pain, headache, chest pain, and dizziness.METHODS: Six hundred charts of adult patients from our institution's same-day outpatient clinic were reviewed in this study. Charts for video visits evaluating the aforementioned chief complaints that occurred between August and October 2020 were reviewed and compared with charts for office visits that occurred from August to September 2019. Frequencies of 3-week follow-up visits, Emergency Room visits, imaging, and referrals for office and video visits were measured. Reasons for in-person evaluation for patients seen by video were determined by review of clinician notes.RESULTS: Three-week in-person follow-up was more frequent for patients presenting with chest pain (52% vs 18%, p=0.0007) and joint pain (24% vs 8%, p=0.05) after video evaluation, relative to an office evaluation. Three-week in-person follow-up was also more frequent for patients presenting with dizziness (38% vs 28%) and low back pain (24% vs 14%); however, this difference was not statistically significant. Patients presenting with headache and abdominal pain did not have a higher rate of follow-up.DISCUSSION: Based on the frequency of in-person follow-up, this study suggests that video visits are generally adequate for evaluating headache and abdominal pain. Patients with dizziness and chest pain have the highest frequency of in-person and Emergency Room follow-up within 3 weeks when first seen by video compared to other conditions evaluated and may be less suitable for an initial video visit. Institutions can consider these findings when scheduling and providing guidance to patients on what type of visit is most appropriate for their symptoms.

  View details for DOI 10.1177/1357633X231224094

  View details for PubMedID 38254267

• IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition. Nature communications Haslund-Gourley, B. S., Woloszczuk, K., Hou, J., Connors, J., Cusimano, G., Bell, M., Taramangalam, B., Fourati, S., Mege, N., Bernui, M., Altman, M. C., Krammer, F., van Bakel, H., IMPACC Network, Maecker, H. T., Rouphael, N., Diray-Arce, J., Wigdahl, B., Kutzler, M. A., Cairns, C. B., Haddad, E. K., Comunale, M. A., Ozonoff, A., Ehrlich, L. I., Melamed, E., Sesma, A. F., Simon, V., Pulendran, B., Nadeau, K. C., Davis, M. M., McCoey, G. A., Sekaly, R., Baden, L. R., Levy, O., Schaenman, J., Reed, E. F., Shaw, A. C., Hafler, D. A., Montgomery, R. R., Kleinstein, S. H., Becker, P. M., Augustine, A. D., Calfee, C. S., Erle, D. J., DeBakey, M. E., Corry, D. B., Kheradmand, F., Atkinson, M. A., Brakenridge, S. C., Higuita, N. I., Metcalf, J. P., Hough, C. L., Messer, W. B., Kraft, M., Bime, C., Peters, B., Milliren, C. E., Syphurs, C., McEnaney, K., Barton, B., Lentucci, C., Saluvan, M., Chang, A. C., Hoch, A., Albert, M., Shaheen, T., Kho, A. T., Liu, S., Thomas, S., Chen, J., Murphy, M. D., Cooney, M., Hayati, A. N., Bryant, R., Abraham, J., Jayavelu, N. D., Presnell, S., Jancsyk, T., Maguire, C., Qi, J., Lee, B., Fourati, S., Esserman, D. A., Guan, L., Gygi, J., Pawar, S., Brito, A., Fragiadakis, G. K., Patel, R., Overton, J. A., Vita, R., Westendorf, K., Shannon, C. P., Tebbutt, S. J., Thyagarajan, R. V., Rousseau, J. F., Wylie, D., Triplett, T. A., Kojic, E., Chinthrajah, S., Ahuja, N., Rogers, A. J., Artandi, M., Geng, L., Yendewa, G., Powell, D. L., Kim, J. N., Simmons, B., Goonewardene, I. M., Smith, C. M., Martens, M., Sherman, A. C., Walsh, S. R., Issa, N. C., Salehi-Rad, R., Dela Cruz, C., Farhadian, S., Iwasaki, A., Ko, A. I., Anderson, E. J., Mehta, A. K., Sevransky, J. E., Seyfert-Margolis, V., Leligdowicz, A., Matthay, M. A., Singer, J. P., Kangelaris, K. N., Hendrickson, C. M., Krummel, M. F., Langelier, C. R., Woodruff, P. G., Corry, D. B., Kheradmand, F., Anderson, M. L., Guirgis, F. W., Drevets, D. A., Brown, B. R., Siegel, S. A., Lu, Z., Mosier, J., Kimura, H., Khor, B., van Bakel, H., Rahman, A., Stadlbauer, D., Dutta, J., Xie, H., Kim-Schulze, S., Gonzalez-Reiche, A. S., van de Guchte, A., Carreno, J. M., Singh, G., Raskin, A., Tcheou, J., Bielak, D., Kawabata, H., Kelly, G., Patel, M., Nie, K., Yellin, T., Fried, M., Sullivan, L., Morris, S., Sieg, S., Steen, H., van Zalm, P., Fatou, B., Mendez, K., Lasky-Su, J., Hutton, S. R., Michelotti, G., Wong, K., Jha, M., Viode, A., Kanarek, N., Petrova, B., Zhao, Y., Bosinger, S. E., Boddapati, A. K., Tharp, G. K., Pellegrini, K. L., Beagle, E., Cowan, D., Hamilton, S., Ribeiro, S. P., Hodder, T., Rosen, L. B., Lee, S., Wilson, M. R., Dandekar, R., Alvarenga, B., Rajan, J., Eckalbar, W., Schroeder, A. W., Tsitsiklis, A., Mick, E., Guerrero, Y. S., Love, C., Maliskova, L., Adkisson, M., Siles, N., Geltman, J., Hurley, K., Saksena, M., Altman, D., Srivastava, K., Eaker, L. Q., Bermudez-Gonzalez, M. C., Beach, K. F., Sominsky, L. A., Azad, A. R., Mulder, L. C., Kleiner, G., Lee, A. S., Do, E., Fernandes, A., Manohar, M., Hagan, T., Blish, C. A., Din, H. N., Roque, J., Yang, S., Sigal, N., Chang, I., Tribout, H., Harris, P., Consolo, M., Edwards, C., Lee, E., Lin, E., Croen, B., Semenza, N. C., Rogowski, B., Melnyk, N., Bell, M. R., Furukawa, S., McLin, R., Schearer, P., Sheidy, J., Tegos, G. P., Nagle, C., Smolen, K., Desjardins, M., van Haren, S., Mitre, X., Cauley, J., Li, X., Tong, A., Evans, B., Montesano, C., Licona, J. H., Krauss, J., Chang, J. B., Izaguirre, N., Rooks, R., Elashoff, D., Brook, J., Ramires-Sanchez, E., Llamas, M., Rivera, A., Perdomo, C., Ward, D. C., Magyar, C. E., Fulcher, J. A., Pickering, H. C., Sen, S., Chaudhary, O., Coppi, A., Fournier, J., Mohanty, S., Muenker, C., Nelson, A., Raddassi, K., Rainone, M., Ruff, W. E., Salahuddin, S., Schulz, W. L., Vijayakumar, P., Wang, H., Wunder, E. J., Young, H. P., Rothman, J., Konstorum, A., Chen, E., Cotsapas, C., Grubaugh, N. D., Wang, X., Xu, L., Asashima, H., Bristow, L., Hussaini, L., Hellmeister, K., Samaha, H., Wimalasena, S. T., Cheng, A., Spainhour, C., Scherer, E. M., Johnson, B., Bechnak, A., Ciric, C. R., Hewitt, L., Carter, E., Mcnair, N., Panganiban, B., Huerta, C., Usher, J., Vaysman, T., Holland, S. M., Abe-Jones, Y., Asthana, S., Beagle, A., Bhide, S., Carrillo, S. A., Chak, S., Ghale, R., Gonzalez, A., Jauregui, A., Jones, N., Lea, T., Lee, D., Lota, R., Milush, J., Nguyen, V., Pierce, L., Prasad, P. A., Rao, A., Samad, B., Shaw, C., Sigman, A., Sinha, P., Ward, A., Willmore, A., Zhan, J., Rashid, S., Rodriguez, N., Tang, K., Altamirano, L. T., Betancourt, L., Curiel, C., Sutter, N., Paz, M. T., Tietje-Ulrich, G., Leroux, C., Thakur, N., Vasquez, J. J., Santhosh, L., Song, L., Nelson, E., Moldawer, L. L., Borresen, B., Roth-Manning, B., Ungaro, R. F., Oberhaus, J., Booth, J. L., Sinko, L. A., Brunton, A., Sullivan, P. E., Strnad, M., Lyski, Z. L., Coulter, F. J., Micheleti, C., Conway, M., Francisco, D., Molzahn, A., Erickson, H., Wilson, C. C., Schunk, R., Sierra, B., Hughes, T. 2024; 15 (1): 404

  Abstract

  The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

  View details for DOI 10.1038/s41467-023-44211-0

  View details for PubMedID 38195739

• Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study. Nature communications Ozonoff, A., Jayavelu, N. D., Liu, S., Melamed, E., Milliren, C. E., Qi, J., Geng, L. N., McComsey, G. A., Cairns, C. B., Baden, L. R., Schaenman, J., Shaw, A. C., Samaha, H., Seyfert-Margolis, V., Krammer, F., Rosen, L. B., Steen, H., Syphurs, C., Dandekar, R., Shannon, C. P., Sekaly, R. P., Ehrlich, L. I., Corry, D. B., Kheradmand, F., Atkinson, M. A., Brakenridge, S. C., Higuita, N. I., Metcalf, J. P., Hough, C. L., Messer, W. B., Pulendran, B., Nadeau, K. C., Davis, M. M., Sesma, A. F., Simon, V., van Bakel, H., Kim-Schulze, S., Hafler, D. A., Levy, O., Kraft, M., Bime, C., Haddad, E. K., Calfee, C. S., Erle, D. J., Langelier, C. R., Eckalbar, W., Bosinger, S. E., Peters, B., Kleinstein, S. H., Reed, E. F., Augustine, A. D., Diray-Arce, J., Maecker, H. T., Altman, M. C., Montgomery, R. R., Becker, P. M., Rouphael, N. 2024; 15 (1): 216

  Abstract

  Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

  View details for DOI 10.1038/s41467-023-44090-5

  View details for PubMedID 38172101

  View details for PubMedCentralID PMC10764789

• A quality-improvement approach to urgent-care antibiotic stewardship for respiratory tract infections during the COVID-19 pandemic: Lessons learned. Infection control and hospital epidemiology Ong'uti, S. K., Artandi, M., Betts, B., Weng, Y., Desai, M., Lentz, C., Nelligan, I., Ha, D. R., Holubar, M. K. 2023: 1-6

  Abstract

  OBJECTIVE: We investigated a decrease in antibiotic prescribing for respiratory illnesses in 2 academic urgent-care clinics during the coronavirus disease 2019 (COVID-19) pandemic using semistructured clinician interviews.METHODS: We conducted a quality-improvement project from November 2020 to May 2021. We investigated provider antibiotic decision making using a mixed-methods explanatory design including interviews. We analyzed transcripts using a thematic framework approach to identify emergent themes. Our performance measure was antibiotic prescribing rate (APR) for encounters with respiratory diagnosis billing codes. We extracted billing and prescribing data from the electronic medical record and assessed differences using run charts, p charts and generalized linear regression.RESULTS: We observed significant reductions in the APR early during the COVID-19 pandemic (relative risk [RR], 0.20; 95% confidence interval [CI], 0.17-0.25), which was maintained over the study period (P < .001). The average APRs were 14% before the COVID-19 pandemic, 4% during the QI project, and 7% after the project. All providers prescribed less antibiotics for respiratory encounters during COVID-19, but only 25% felt their practice had changed. Themes from provider interviews included changing patient expectations and provider approach to respiratory encounters during COVID-19, the impact of increased telemedicine encounters, and the changing epidemiology of non-COVID-19 respiratory infections.CONCLUSIONS: Our findings suggest that the decrease in APR was likely multifactorial. The average APR decreased significantly during the pandemic. Although the APR was slightly higher after the QI project, it did not reach prepandemic levels. Future studies should explore how these factors, including changing patient expectations, can be leveraged to improve urgent-care antibiotic stewardship.

  View details for DOI 10.1017/ice.2023.8

  View details for PubMedID 36815249

• Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study. EBioMedicine Ozonoff, A., Schaenman, J., Jayavelu, N. D., Milliren, C. E., Calfee, C. S., Cairns, C. B., Kraft, M., Baden, L. R., Shaw, A. C., Krammer, F., van Bakel, H., Esserman, D. A., Liu, S., Sesma, A. F., Simon, V., Hafler, D. A., Montgomery, R. R., Kleinstein, S. H., Levy, O., Bime, C., Haddad, E. K., Erle, D. J., Pulendran, B., Nadeau, K. C., Davis, M. M., Hough, C. L., Messer, W. B., Higuita, N. I., Metcalf, J. P., Atkinson, M. A., Brakenridge, S. C., Corry, D., Kheradmand, F., Ehrlich, L. I., Melamed, E., McComsey, G. A., Sekaly, R., Diray-Arce, J., Peters, B., Augustine, A. D., Reed, E. F., Altman, M. C., Becker, P. M., Rouphael, N. 2022; 83: 104208

  Abstract

  Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.NIH.

  View details for DOI 10.1016/j.ebiom.2022.104208

  View details for PubMedID 35952496

• Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome. JCI insight Jia, X., Cao, S., Lee, A. S., Manohar, M., Sindher, S. B., Ahuja, N., Artandi, M., Blish, C. A., Blomkalns, A. L., Chang, I., Collins, W. J., Desai, M., Din, H. N., Do, E., Fernandes, A., Geng, L. N., Rosenberg-Hasson, Y., Mahoney, M. R., Glascock, A. L., Chan, L. Y., Fong, S. Y., Phelps, M., Raeber, O., Purington, N., Röltgen, K., Rogers, A. J., Snow, T., Wang, T. T., Solis, D., Vaughan, L., Verghese, M., Maecker, H., Wittman, R., Puri, R., Kistler, A., Yang, S., Boyd, S. D., Pinsky, B. A., Chinthrajah, S., Nadeau, K. C. 2022; 7 (13)

  Abstract

  BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.

  View details for DOI 10.1172/jci.insight.156713

  View details for PubMedID 35801588

• Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19. Cell reports. Medicine Feyaerts, D., Hédou, J., Gillard, J., Chen, H., Tsai, E. S., Peterson, L. S., Ando, K., Manohar, M., Do, E., Dhondalay, G. K., Fitzpatrick, J., Artandi, M., Chang, I., Snow, T. T., Chinthrajah, R. S., Warren, C. M., Wittman, R., Meyerowitz, J. G., Ganio, E. A., Stelzer, I. A., Han, X., Verdonk, F., Gaudillière, D. K., Mukherjee, N., Tsai, A. S., Rumer, K. K., Jacobsen, D. R., Bjornson-Hooper, Z. B., Jiang, S., Saavedra, S. F., Valdés Ferrer, S. I., Kelly, J. D., Furman, D., Aghaeepour, N., Angst, M. S., Boyd, S. D., Pinsky, B. A., Nolan, G. P., Nadeau, K. C., Gaudillière, B., McIlwain, D. R. 2022: 100680

  Abstract

  The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC]training = 0.799, p = 4.2e-6; multi-class AUCvalidation = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.

  View details for DOI 10.1016/j.xcrm.2022.100680

  View details for PubMedID 35839768

• A 360 degree mixed-methods evaluation of a specialized COVID-19 outpatient clinic and remote patient monitoring program. BMC primary care Vilendrer, S., Lestoquoy, A., Artandi, M., Barman, L., Cannon, K., Garvert, D. W., Halket, D., Holdsworth, L. M., Singer, S., Vaughan, L., Winget, M. 2022; 23 (1): 151

  Abstract

  BACKGROUND: Our goals are to quantify the impact on acute care utilization of a specialized COVID-19 clinic with an integrated remote patient monitoring program in an academic medical center and further examine these data with stakeholder perceptions of clinic effectiveness and acceptability.METHODS: A retrospective cohort was drawn from enrolled and unenrolled ambulatory patients who tested positive in May through September 2020 matched on age, presence of comorbidities and other factors. Qualitative semi-structured interviews with patients, frontline clinician, and administrators were analyzed in an inductive-deductive approach to identify key themes.RESULTS: Enrolled patients were more likely to be hospitalized than unenrolled patients (N=11/137 in enrolled vs 2/126 unenrolled, p=.02), reflecting a higher admittance rate following emergency department (ED) events among the enrolled vs unenrolled, though this was not a significant difference (46% vs 25%, respectively, p=.32). Thirty-eight qualitative interviews conducted June to October 2020 revealed broad stakeholder belief in the clinic's support of appropriate care escalation. Contrary to beliefs the clinic reduced inappropriate care utilization, no difference was seen between enrolled and unenrolled patients who presented to the ED and were not admitted (N=10/137 in enrolled vs 8/126 unenrolled, p=.76). Administrators and providers described the clinic's integral role in allowing health services to resume in other areas of the health system following an initial lockdown.CONCLUSIONS: Acute care utilization and multi-stakeholder interviews suggest heightened outpatient observation through a specialized COVID-19 clinic and remote patient monitoring program may have contributed to an increase in appropriate acute care utilization. The clinic's role securing safe reopening of health services systemwide was endorsed as a primary, if unmeasured, benefit.

  View details for DOI 10.1186/s12875-022-01734-7

  View details for PubMedID 35698064

• Improving the physical exam: a new assessment and evaluation tool for physical examination skills. Diagnosis (Berlin, Germany) Artandi, M., Norcini, J., Garibaldi, B., Thadaney Israni, S., Kugler, J., Kumar, A., Russell, S. 2022

  View details for DOI 10.1515/dx-2022-0014

  View details for PubMedID 35303765

• Approach to the telemedicine physical examination: partnering with patients. The Medical journal of Australia Russell, S. W., Artandi, M. K. 1800

  View details for DOI 10.5694/mja2.51398

  View details for PubMedID 35118688

• Sustained Reduction in Urgent Care Antibiotic Prescribing During the Coronavirus Disease 2019 Pandemic: An Academic Medical Center's Experience. Open forum infectious diseases Ha, D., Ong'uti, S., Chang, A., Mui, E., Nelligan, I., Betts, B., Lentz, C., Alegria, W., Fox, E., Meng, L., Stenehjem, E., Hersh, A. L., Deresinski, S., Artandi, M., Holubar, M. 1800; 9 (2): ofab662

  Abstract

  We compared antibiotic prescribing before and during the -coronavirus disease 2019 (COVID-19) pandemic at 2 academic urgent care clinics and found a sustained decrease in prescribing driven by respiratory encounters and despite transitioning to telemedicine. Antibiotics were rarely prescribed during encounters for COVID-19 or COVID-19 symptoms. COVID-19 revealed opportunities for outpatient stewardship programs.

  View details for DOI 10.1093/ofid/ofab662

  View details for PubMedID 35111874

• Training Internal Medicine Residents in Difficult Diagnosis: A Novel Diagnostic Second Opinion Clinic Experience. Journal of medical education and curricular development Testa, S., Joshi, M., Lotfi, J., Lin, B., Artandi, M., Chiang, K. F., Chang, K., Singh, B., Geng, L. N. 2022; 9: 23821205221091036

  Abstract

  Background: In primary care clinics, time constraints and lack of exposure to highly complex cases may limit the breadth and depth of learning for internal medicine residents. To address these issues, we piloted a novel experience for residents to evaluate patients with puzzling symptoms referred by another clinician.Objective: To increase internal medicine residents' exposure to patients with perplexing presentations and foster a team-based approach to solving diagnostically challenging cases.Methods: During the academic year 2020-2021, residents participating in their 2-week primary care "block" rotation were given protected time to evaluate 1-2 patients from the Stanford Consultative Medicine clinic, an internist-led diagnostic second opinion service, and present their patients at the case conference. We assessed the educational value of the program with resident surveys including 5-point Lickert scale and open-ended questions.Results: 21 residents participated in the pilot with a survey response rate of 66.6% (14/21). Both the educational value and overall quality of the experience were rated as 4.8 out of 5 (SD 0.4, range 4-5; 1:"very poor"; 5:"excellent"). Residents learned about new diagnostic tools as well as how to approach complex presentations and diagnostic dilemmas. Residents valued the increased time devoted to patient care, the team-based approach to tackling difficult cases, and the intellectual challenge of these cases. Barriers to implementation include patient case volume, time, and faculty engagement.Conclusions: Evaluation of diagnostically challenging cases in a structured format is a highly valuable experience that offers a framework to enhance outpatient training in internal medicine.

  View details for DOI 10.1177/23821205221091036

  View details for PubMedID 35372696

• New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nature communications Chang, S. E., Feng, A., Meng, W., Apostolidis, S. A., Mack, E., Artandi, M., Barman, L., Bennett, K., Chakraborty, S., Chang, I., Cheung, P., Chinthrajah, S., Dhingra, S., Do, E., Finck, A., Gaano, A., GeSSner, R., Giannini, H. M., Gonzalez, J., Greib, S., Gundisch, M., Hsu, A. R., Kuo, A., Manohar, M., Mao, R., Neeli, I., Neubauer, A., Oniyide, O., Powell, A. E., Puri, R., Renz, H., Schapiro, J., Weidenbacher, P. A., Wittman, R., Ahuja, N., Chung, H., Jagannathan, P., James, J. A., Kim, P. S., Meyer, N. J., Nadeau, K. C., Radic, M., Robinson, W. H., Singh, U., Wang, T. T., Wherry, E. J., Skevaki, C., Luning Prak, E. T., Utz, P. J. 2021; 12 (1): 5417

  Abstract

  COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

  View details for DOI 10.1038/s41467-021-25509-3

  View details for PubMedID 34521836

• New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19 Chang, S., Feng, A., Meng, W., Apostolidis, S., Mack, E., Artandi, M., Barman, L., Bennett, K., Chakraborty, S., Chang, I., Cheung, P., Chinthrajah, S., Dhingra, S., Do, E., Finck, A., Gaano, A., Gessner, R., Giannini, H., Gonzalez, J., Greib, S., Gundisch, M., Hsu, A., Kuo, A., Manohar, M., Mao, R., Neeli, I., Neubauer, A., Oniyide, O., Powell, A., Puri, R., Renz, H., Schapiro, J., Weidenbacher, P., Wittman, R., Ahuja, N., Chung, H., Jagannathan, P., James, J., Kim, P., Meyer, N., Nadeau, K., Radic, M., Robinson, W., Singh, U., Wang, T., Wherry, J., Skevaki, C., Prak, E., Utz, P. WILEY. 2021: 3202-3205

  View details for Web of Science ID 000744545206097

• A Specialized Acute COVID-19 Outpatient Clinic at an Academic Medical Center. American journal of medical quality : the official journal of the American College of Medical Quality Artandi, M., Barman, L., Srinivasan, M., Thomas, S., Singh, J., Asch, S. M., Vilendrer, S. 2021

  Abstract

  Health systems are challenged to provide equitable access to coronavirus disease 2019 (COVID-19) outpatient care during the pandemic. Infected patients may have difficulties accessing regular care and rely on emergency rooms. With the goal to improve system efficiencies and access to care, Stanford launched a designated outpatient COVID-19 "Care and Respiratory Observation of Patients With Novel Coronavirus" clinic in April 2020 in which all adult Stanford patients with newly diagnosed severe acute respiratory syndrome coronavirus 2 were offered follow-up for 2-3 weeks through video, telephone, and in-person encounters. Patients were triaged into risk categories and received home pulse oximeters based on a standardized protocol. Between April 15, 2020, and March 26, 2021, the Care and Respiratory Observation of Patients With Novel Coronavirus clinic enrolled 1317 patients. The clinic provided evaluation of Patients under Investigation, management of acute COVID-19 symptoms, care for COVID-19 patients after hospital discharge, clinical advice, and opportunities for research. The authors share crucial implementation lessons related to team agility, care personalization, and resource optimization.

  View details for DOI 10.1097/JMQ.0000000000000006

  View details for PubMedID 34310381

• Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19. Allergy Eggert, L. E., He, Z., Collins, W., Lee, A. S., Dhondalay, G., Jiang, S. Y., Fitzpatrick, J., Snow, T. T., Pinsky, B. A., Artandi, M., Barman, L., Puri, R., Wittman, R., Ahuja, N., Blomkalns, A., O'Hara, R., Cao, S., Desai, M., Sindher, S. B., Nadeau, K., Chinthrajah, R. S. 2021

  Abstract

  BACKGROUND: It is unclear if asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2.METHODS: All patients over 28 days oldtesting positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms.RESULTS: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p=0.40). Among SARS-CoV-2 positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared to non-allergic asthma (OR 0.52 (0.28, 0.91), p=0.026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared to patients with mild or asymptomatic disease, independent of asthma status (p=0.0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms.CONCLUSIONS: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared to non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms three months post-infection.

  View details for DOI 10.1111/all.14972

  View details for PubMedID 34080210

• Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19. bioRxiv : the preprint server for biology Feyaerts, D., Hédou, J., Gillard, J., Chen, H., Tsai, E. S., Peterson, L. S., Ando, K., Manohar, M., Do, E., Dhondalay, G. K., Fitzpatrick, J., Artandi, M., Chang, I., Snow, T. T., Chinthrajah, R. S., Warren, C. M., Wittman, R., Meyerowitz, J. G., Ganio, E. A., Stelzer, I. A., Han, X., Verdonk, F., Gaudillière, D. K., Mukherjee, N., Tsai, A. S., Rumer, K. K., Jiang, S., Valdés Ferrer, S. I., Kelly, J. D., Furman, D., Aghaeepour, N., Angst, M. S., Boyd, S. D., Pinsky, B. A., Nolan, G. P., Nadeau, K. C., Gaudillière, B., McIlwain, D. R. 2021

  Abstract

  The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

  View details for DOI 10.1101/2021.02.09.430269

  View details for PubMedID 33594362

  View details for PubMedCentralID PMC7885914

• Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19 European Journal of Allergy and Clinical Immunology Eggert, L. E., He, Z., Collins, W., Lee, A. S., Nadeau, K., Chinthrajah, R. 2021

  View details for DOI 10.1111/all.14972

• Connecting tobacco users in the primary care setting to comprehensive tobacco treatment: a quality improvement initiative JOURNAL OF PUBLIC HEALTH-HEIDELBERG Kendra, M. S., Dang, J., Artandi, M., Vemuri, M. 2020

  View details for DOI 10.1007/s10389-020-01401-0

  View details for Web of Science ID 000580437800001

• Qualitative Assessment of Rapid System Transformation to Primary Care Video Visits at an Academic Medical Center. Annals of internal medicine Srinivasan, M. n., Asch, S. n., Vilendrer, S. n., Thomas, S. C., Bajra, R. n., Barman, L. n., Edwards, L. M., Filipowicz, H. n., Giang, L. n., Jee, O. n., Mahoney, M. n., Nelligan, I. n., Phadke, A. J., Torres, E. n., Artandi, M. n. 2020

  Abstract

  The coronavirus disease 2019 pandemic spurred health systems across the world to quickly shift from in-person visits to safer video visits.To seek stakeholder perspectives on video visits' acceptability and effect 3 weeks after near-total transition to video visits.Semistructured qualitative interviews.6 Stanford general primary care and express care clinics at 6 northern California sites, with 81 providers, 123 staff, and 97 614 patient visits in 2019.Fifty-three program participants (overlapping roles as medical providers [n = 20], medical assistants [n = 16], nurses [n = 4], technologists [n = 4], and administrators [n = 13]) were interviewed about video visit transition and challenges.In 3 weeks, express care and primary care video visits increased from less than 10% to greater than 80% and from less than 10% to greater than 75%, respectively. New video visit providers received video visit training and care quality feedback. New system workflows were created to accommodate the new visit method.Nine faculty, trained in qualitative research methods, conducted 53 stakeholder interviews in 4 days using purposeful (administrators and technologists) and convenience (medical assistant, nurses, and providers) sampling. A rapid qualitative analytic approach for thematic analysis was used.The analysis revealed 12 themes, including Pandemic as Catalyst; Joy in Medicine; Safety in Medicine; Slipping Through the Cracks; My Role, Redefined; and The New Normal. Themes were analyzed using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to identify critical issues for continued program utilization.Evaluation was done immediately after deployment. Although viewpoints may have evolved later, immediate evaluation allowed for prompt program changes and identified broader issues to address for program sustainability.After pandemic-related systems transformation at Stanford, critical issues to sustain video visit long-term viability were identified. Specifically, technology ease of use must improve and support multiparty videoconferencing. Providers should be able to care for their patients, regardless of geography. Providers need decision-making support with virtual examination training and home-based patient diagnostics. Finally, ongoing video visit reimbursement should be commensurate with value to the patients' health and well-being.Stanford Department of Medicine and Stanford Health Care.

  View details for DOI 10.7326/M20-1814

  View details for PubMedID 32628536

• Reinvigorating the clinical examination for the 21st century. Polish archives of internal medicine Garibaldi, B. T., Zaman, J. n., Artandi, M. K., Elder, A. T., Russell, S. W. 2019; 129 (12): 907–12

  Abstract

  At its most fundamental level, the clinical encounter between a patient and their doctor seeks to solve a mystery. Clinicians uncover clues through the history, physical examination, and ancillary tests to arrive at a diagnosis and develop a management plan. Despite advances in technology, the majority of clinical diagnoses are still reached through the history and physical examination without the use of laboratory and imaging tests. However, in the modern American hospital, clinicians spend as little as 12% of their time in direct contact with patients and their families. This has led to a decline in clinical examination skills and contributes to diagnostic error. There is a growing movement to return clinicians and trainees back to the bedside. In 2017, we formed the Society of Bedside Medicine to encourage innovation, education, and research on the role of the clinical encounter in 21st century medicine. Over the last 3 years, we have embraced the following 6 strategies to reinvigorate the practice of the clinical examination: 1) be present with the patient; 2) practice an evidence‑based approach to the physical exam; 3) create opportunities for intentional practice of the physical exam; 4) recognize the power of the physical examination beyond diagnosis; 5) use point‑of‑care technology to aid in diagnosis and reinforce skills; and 6) seek and provide specific feedback on physical examination skills. By employing these strategies in both teaching and practice, clinicians can maximize the value of time spent with patients and renew the importance of the clinical examination in 21st century practice.

  View details for DOI 10.20452/pamw.15073

  View details for PubMedID 31777402

• The Outpatient Physical Examination MEDICAL CLINICS OF NORTH AMERICA Artandi, M. K., Stewart, R. W. 2018; 102 (3): 465-+

  Abstract

  The physical examination in the outpatient setting is a valuable tool. Even in settings where there is lack of evidence, such as the annual physical examination of an asymptomatic adult, the physical examination is beneficial for the physician-patient relationship. When a patient has specific symptoms, the physical examination-in addition to a thorough history-can help narrow down, or in many cases establish, a diagnosis. In a time where imaging and laboratory tests are easily available, but are expensive and can be invasive, a skilled physical examination remains an important component of patient evaluation.

  View details for PubMedID 29650068

• The Five-Minute Moment. American journal of medicine Chi, J., Artandi, M., Kugler, J., Ozdalga, E., Hosamani, P., Koehler, E., Osterberg, L., Zaman, J., Thadaney, S., Elder, A., Verghese, A. 2016; 129 (8): 792-795

  Abstract

  In today's hospital and clinic environment, the obstacles to bedside teaching both for faculty and trainees are considerable. As Electronic Health Records (EHR) systems become increasingly prevalent, trainees are spending more time performing patient care tasks from computer workstations, limiting opportunities to learn at the bedside. Physical examination skills are rarely emphasized and low confidence levels, especially in junior faculty, pose additional barriers to teaching the bedside exam.

  View details for DOI 10.1016/j.amjmed.2016.02.020

  View details for PubMedID 26972793

• Conceptual basis and clinical rationale for the development of a multidisciplinary weight management center. International journal of obesity supplements Artandi, M. K. 2012; 2: S43-S46

  Abstract

  Overweight (body mass index (BMI) 25 kg m(-2)) or obesity (BMI 30>kg m(-2)) affects more than two-thirds of Americans. Overweight and obesity are commonly associated with multiple coexisting conditions, such as hypertension, diabetes, dyslipidemia, cardiovascular disease, obstructive sleep apnea and cancer. Lifestyle modification can induce a modest weight loss, which is associated with the prevention or improvement of many of these comorbidities. A combination of diet, exercise and behavioral therapy is considered the cornerstone of treatment for all overweight and obese individuals. As the etiology and therapy of obesity is complex, what is needed for these patients is a multidisciplinary clinic where specialists from different disciplines share their knowledge and participate in the treatment of the obese patient.

  View details for PubMedID 25018870

• TERT promotes epidermal proliferation through transcriptional control of a Myc- and Wnt-related developmental program. PLoS Genet Choi, J., Southworth, Sarin, K., Venteicher, A.S., Ma, W., Chang, W., Cheung, P., Jun, S., Artandi, M.K., Shah, N., Kim, S 2008: (4) 1
• Conditional telomerase induction causes proliferation of hair follicle stem cells NATURE Sarin, K. Y., Cheung, P., Gilison, D., Lee, E., Tennen, R. I., Wang, E., Artandi, M. K., Oro, A. E., Artandi, S. E. 2005; 436 (7053): 1048-1052

  Abstract

  TERT, the protein component of telomerase, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells, but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.

  View details for DOI 10.1038/nature03836

  View details for Web of Science ID 000231263900057

  View details for PubMedID 16107853

  View details for PubMedCentralID PMC1361120

• Irinotecan combined or alternated with bolus 5-fluorouracil and folinic acid versus the Mayo clinic regimen in the first line therapy of advance colorectal cancer Oncol Rep Graeven U.,, Ridwelski K., Artandi M., Espana P., Scholmerich J et al 2005: 13 (4) 681-8
• Constitutive telomerase expression promotes mammary carcinomas in aging mice PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Artandi, S. E., Alson, S., Tietze, M. K., Sharpless, N. E., Ye, S., Greenberg, R. A., Castrillon, D. H., Horner, J. W., Weiler, S. R., Carrasco, R. D., DePinho, R. A. 2002; 99 (12): 8191-8196

  Abstract

  Telomerase is up-regulated in the vast majority of human cancers and serves to halt the progressive telomere shortening that ultimately blocks would-be cancer cells from achieving a full malignant phenotype. In contrast to humans, the laboratory mouse possesses long telomeres and, even in early generation telomerase-deficient mice, the level of telomere reserve is sufficient to avert telomere-based checkpoint responses and to permit full malignant progression. These features in the mouse provide an opportunity to determine whether enforced high-level telomerase activity can serve functions that extend beyond its ability to sustain telomere length and function. Here, we report the generation and characterization of transgenic mice that express the catalytic subunit of telomerase (mTERT) at high levels in a broad variety of tissues. Expression of mTERT conferred increased telomerase enzymatic activity in several tissues, including mammary gland, splenocytes, and cultured mouse embryonic fibroblasts. In mouse embryonic fibroblasts, mTERT overexpression extended telomere lengths but did not prevent culture-induced replicative arrest, thus reinforcing the view that this phenomenon is not related to occult telomere shortening. Robust telomerase activity, however, was associated with the spontaneous development of mammary intraepithelial neoplasia and invasive mammary carcinomas in a significant proportion of aged females. These data indicate that enforced mTERT expression can promote the development of spontaneous cancers even in the setting of ample telomere reserve.

  View details for DOI 10.1073/pnas.112515399

  View details for Web of Science ID 000176217700071

  View details for PubMedID 12034875

  View details for PubMedCentralID PMC123043

• Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas HEPATO-GASTROENTEROLOGY Kubicka, S., Rudolph, K. L., Tietze, M. K., Lorenz, M., Manns, M. 2001; 48 (39): 783-789

  Abstract

  Patients with advanced unresectable hepatobiliary carcinomas have a dismal prognosis. The efficacy of systemic chemotherapy in these patients is negligible and often, in particular in patients with hepatocellular carcinomas, the toxicity of chemotherapy outweighs the potential palliative effect of antineoplastic agents. Gemcitabine is a new anticancer agent with a mild toxicity profile, which has demonstrated antineoplastic activity in many solid tumors. Therefore we investigated the effect of gemcitabine in patients with advanced nonresectable hepatocellular and cholangiocellular carcinomas in a phase II study.Twenty-three patients with cholangiocellular carcinoma and 20 patients with hepatocellular carcinoma were enrolled into the study. Eighteen of the 20 patients with hepatocellular carcinomas had liver cirrhosis. Gemcitabine was administered once weekly over 30 min for 3 consecutive weeks out of every 4 weeks. Patients with cholangiocellular carcinomas received gemcitabine also in the forth week of the first cycle with no rest to the following cycle. Disease status was assessed every 4 weeks.Overall the regimen was well tolerated. The median number of gemcitabine administration was 15 (range, 3-37) in the group of patients with cholangiocellular carcinomas and 7.6 (range, 3-21) in the group of patients with hepatocellular carcinomas. In the group of patients with hepatocellular carcinomas thrombocytopenia was the most frequent side effect (30% grade 3/4). Among the patients with cholangiocellular carcinomas nausea and neutropenia were the most commonly observed side effects. The overall response rate of hepatocellular carcinomas was only 5% and chemotherapy generally did not improve the tumor symptoms of the patients in this group. In contrast, in the group of cholangiocellular carcinomas, seven patients achieved a partial response (overall response rate 30%). Eleven patients with cholangiocellular carcinomas revealed tumor symptoms before the onset of gemcitabine treatment. Seven of these patients developed a treatment related clinical benefit as defined as a relief of tumor symptoms or gain of weight.Our results indicate that the treatment of cholangiocarcinomas with gemcitabine is effective and should be further evaluated in phase III studies. In contrast, palliative chemotherapy with gemcitabine cannot be recommended in patients with hepatocellular carcinoma and liver cirrhosis.

  View details for Web of Science ID 000169631600042

  View details for PubMedID 11462924

• Murine models of malignant melanoma MOLECULAR MEDICINE TODAY Tietze, M. K., Chin, L. 2000; 6 (10): 408-410

  View details for Web of Science ID 000089768000010

  View details for PubMedID 11006531

• I kappa B alpha gene therapy in tumor necrosis factor-alpha- and chemotherapy-mediated apoptosis of hepatocellular carcinomas CANCER GENE THERAPY Tietze, M. K., Wuestefeld, T., Paul, Y., Zender, L., Trautwein, C., Manns, M. P., Kubicka, S. 2000; 7 (10): 1315-1323

  Abstract

  The transcription factor nuclear factor kappaB (NFkappaB) is an essential antagonist of apoptosis during liver regeneration and embryonal development of hepatocytes. Several reports have indicated that NFkappaB may also inhibit the programmed cell death induced by cytokines, ionizing radiation, or cytotoxic drugs in some cancer cell lines. Because hepatocellular carcinomas (HCCs) are one of the most resistant tumors to systemic chemotherapy, we investigated the activation of NFkappaB and the consequence of its inhibition by an IkappaBalpha-super repressor during tumor necrosis factor alpha (TNFalpha)- and chemotherapy-induced apoptosis in HCC cell lines. We demonstrate that both TNFalpha and adriamycin activate NFkappaB in hepatoma cells. Activation of NFkappaB could be blocked through an adenoviral vector expressing the IkappaBalpha super repressor, regardless of the activating agent. Inhibition of NFkappaB enhanced the apoptosis induced by TNFalpha, whereas IkappaBalpha had an anti-apoptotic effect on chemotherapy-induced programmed cell death. A strong inhibition of chemotherapy- and TNFalpha-induced apoptosis by dominant-negative Fas-associated death domain indicated an essential contribution of death receptor-mediated apoptosis. To elucidate the different role of NFkappaB in chemotherapy-induced apoptosis, we investigated the expression of Fas (CD95) and Fas ligand (CD95 ligand), which have been described as important mediators of chemotherapy-induced cell death and as target genes of NFkappaB. However, our investigations demonstrated that in hepatoma cells, the chemotherapy-induced up-regulation of Fas (CD95) and Fas ligand (CD95 ligand) is not transcriptionally mediated through NFkappaB. Thus, other molecular mechanisms must account for the anti-apoptotic effect of IkappaBalpha in adriamycin-induced death of hepatoma cells. In summary, our investigations indicate that the activation of NFkappaB in response to cytotoxic drugs, in contrast to TNFalpha, exerts a pro-apoptotic stimulus rather than an anti-apoptotic function, which has implications for therapy of HCCs.

  View details for Web of Science ID 000090073200004

  View details for PubMedID 11059688

• Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area Liver Kubicka S.,, Rudolph KL., Hanke T., Tietzke MK., Tillmann H.., Trautwein C., Manns M. 2000: 20 (4):312-8
• NfkB mediates apoptosis through transcriptional activation of Fas (CD95) in adenoviral hepatitis J Biol Chem Kuehnel F.,, Zender L., Paul Y., Tietzke MK., Trautwein C., Manns M., Kubicka S. 2000: 275:6421-7