Message from Richard A. Walsh, MD

We have over 250 full time faculty, 120 medical housestaff, 80 fellows and 400 support staff working at the CWRU School of Medicine, University Hospitals Case Medical Center and the Cleveland VA Medical Center Wade Park Campus.

We are proud of our premier, extramurally funded research programs, our delivery of high-quality, cost-effective patient care at University Hospitals (ranked as a Top Ten Health Care System by Thompson Reuters) and our VA Hospital (ranked first in the entire VA system for Health Care Delivery Measures).

We are also deeply committed to medical student, graduate student and post graduate training.

Our faculty, trainees and staff are committed to the highest standard of excellence in all of our activities in a collegial, integrated and interactive work environment.

We invite you to navigate our website to learn more about who we are and what we do. Visit us at CWRUmedicine.org
If we can be of help, please contact us.

Richard A. Walsh, MD

Chair, Department of Medicine

Which social tool do you use?

It doesn’t take much effort to see the impact social media is having on almost every avenue of our lives, both professionally and personally. Tools such as LinkedIn, Twitter and Facebook, just to name a few, are changing the way and frequency in which we communicate. It should be no surprise, then, that even Healthcare would find itself impacted by the influence and immediacy that social media provides.

We value your opinion and want to know what tools you use to stay up with the latest news and information. Give us your thoughts. Take our poll on social media in healthcare, and let us know what tool(s) you use.

Take the Poll and see results at CWRUmedicine.org

Cleveland ranked 16 on Real Simple’s Top Time-Saving Cities in America List

The report, in the magazine’s April issue, highlighted urban areas across the nation that offer convenient, timesaving services to residents.

To learn more and review Clevelands scorecard visit us at CWRUmedicine.org

The Survey
Takeout on every corner. Easy access to a doctor. Timed traffic lights. These conveniences can ease even the most chaotic days. To assess which places help you make the most of your precious hours, we sorted through reams of data on dozens of large American cities, ranked each on various criteria in five categories (see below) on a scale of 1 to 5, and added up those categories to get an overall score.

Category 1 :: Getting Around
Includes average commute, walkability, traffic congestion, airport on-time performance.

Category 2 :: Health and Safety
Includes average wait to get a doctor’s appointment, physicians per capita, response times of emergency medical services.

Category 3 :: Information and Technology
Includes broadband and wireless availability, bookstores and libraries per capita, helpful resources such as 311 hotlines.

Category 4 :: Green Time-Savers
Includes recycling access and cost, number of farmers’ markets and community gardens, bike friendliness.

Category 5 :: Lifestyle
Includes number of personal trainers and organizers, restaurants offering takeout per capita, miscellaneous time-saving services.

Learn more at CWRUmedicine.org

New Research Published on Antibiotic resistance determinants in Acinetobacter spp

We explored the association of antibiotic-resistant phenotypes and genotypes in Acinetobacter spp with clinical outcomes and characteristics in 75 patients from a major military treatment facility. Amikacin resistance was associated with nosocomial acquisition of A baumannii, and carbapenem resistance and bla(OXA-23) were associated with the need for mechanical ventilation. The presence of bla(OXA-23) also correlated with longer hospital and ICU stay. Associations between bla(OXA-23) and complexity, duration, and changes made to antibiotic regimens also existed. Copyright 2010.

Learn more at CWRUmedicine.org

Read why Cushing’s syndrome: Why is diagnosis so difficult?

Practicing and perfecting the art of medicine demands recognition that uncertainty permeates all clinical decisions. When delivering clinical care, clinicians face a multiplicity of potential diagnoses, limitations in diagnostic capacity, and “sub-clinical” disease identified by tests rather than by clinical manifestations. In addition, clinicians must recognize the rapid changes in scientific knowledge needed to guide decisions. Cushing’s syndrome is one of several disorders in which there may be considerable difficulty and delay in diagnosis. This article describes a current model of clinical reasoning, some of its challenges, and the application of the principles of clinical epidemiology to meet some of those challenges.

Learn more at CWRUmedicine.org

New Research on Older Patients with Acute Myeloid Leukemia in their first complete remission

“Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome”

McClune BL, Weisdorf DJ, Pedersen TL, da Silva GT, Tallman MS, Sierra J, Dipersio J, Keating A, Gale RP, George B, Gupta V, Hahn T, Isola L, Jagasia M, Lazarus H, Marks D, Maziarz R, Waller EK, Bredeson C, Giralt S.
J Clin Oncol. 2010 Mar 8

PURPOSE:
Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR).

PATIENTS AND METHODS:
We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS).

RESULTS:
Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >/= 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. CONCLUSION: With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Read new research paper from CWRUmedicine Hematology Oncology on Human beta-defensin-2 expression

“Expression of human beta-defensin-2 in intratumoral vascular endothelium and in endothelial cells induced by transforming growth factor beta”
Peptides 2010 Feb
Kawsar HI, Ghosh SK, Hirsch SA, Koon HB, Weinberg A, Jin G.

Human beta-defensin-2 (hBD-2) is a small cationic peptide originally identified from psoriatic skin lesions as an antimicrobial agent of the innate immune system. The expression of hBD-2 is believed to be induced exclusively in epithelial cells by microbial components and certain proinflammatory cytokines, such as interleukin-1 beta (IL-1 beta). In this study, we report, for the first time, that hBD-2 is expressed in vascular endothelial cells associated with oral squamous cell carcinoma (OSCC) and Kaposi’s sarcoma lesions, but not in that of normal stroma. Expression of hBD-2 in vascular endothelial cells was further substantiated by in vitro experiments using cultured human umbilical vein endothelial cells (HUVECs). Transforming growth factor beta1 (TGF beta 1) and IL-1 beta, two well-known tumorigenic inflammatory mediators, induce hBD-2 transcript and peptide expression in HUVECs. However, TGF beta 1 does not stimulate hBD-2 expression in oral epithelial cells. In addition, proinflammatory cytokines and microbial reagents do not induce the expression of hBD-1 and hBD-3 in HUVECs. Since hBD-2 has been shown to modulate migration, proliferation, and tube formation of HUVECs in vitro and participate in immune cell trafficking, its expression in vascular endothelial cells located within malignant lesions may play a role in tumor angiogenesis and cancer metastasis.

Read the full article on CWRUmedicine.org

Happy Doctors Day!

The Department of Medicine would like to wish all physicians and future physicians a very Happy Doctors’ Day!

Each year, March 30th is designated as National Doctors’ Day.  The holiday, while not officially signed into law until the early 1990s, originated in the 1930s by a physician’s wife in North Georgia.

The Department of Medicine at Case Western Reserve Univeristy and University Hospitals Case Medical Center are proud to recognize Doctors Day. As physicians, you sacrifice so much of your life for all the additional years of school and training, plus being on call and taking time away from your families to care for those in need.  Many people don’t realize the level of pressure and stress that physicians deal with, how much debt many of you take on to become a doctor (the average is about $140,000, but many doctors have up to $250,000 in school debt), and the high cost of practicing medicine today.

Therefore, we would like to thank you for all your hard work, sacrifices, and care that you provide to so many people each and every day!  We hope you have a very enjoyable Doctors’ Day! You have more than earned it!

Read about “STAT5 requires the N-domain for suppression of miR15/16, induction of bcl-2, and survival signaling in myeloproliferative disease”

Phosphorylated signal transducer and activator of transcription 5 (STAT5) is a biomarker and potential molecular target for hematologic malignancies. We have shown previously that lethal myeloproliferative disease (MPD) in mice mediated by persistently activated STAT5 (STAT5a(S711F)) requires the N-domain, but the mechanism was not defined. We now demonstrate by retrovirally complementing STAT5ab(null/null) primary mast cells that relative to wild-type STAT5a, STAT5a lacking the N-domain (STAT5aDeltaN) ineffectively protected against cytokine withdrawal-induced cell death. Both STAT5a and STAT5aDeltaN bound to a site in the bcl-2 gene and both bound near the microRNA 15b/16 cluster. However, only STAT5a could effectively induce bcl-2 mRNA and reciprocally suppress miR15b/16 leading to maintained bcl-2 protein levels. After retroviral complementation of STAT5ab(null/null) fetal liver cells and transplantation, persistently active STAT5a(S711F) lacking the N-domain (STAT5aDeltaN(S711F)) was insufficient to protect c-Kit(+)Lin(-)Sca-1(+) (KLS) cells from apoptosis and unable to induce bcl-2 expression, whereas STAT5a(S711F) caused robust KLS cell expansion, induction of bcl-2, and lethal MPD. Severe attenuation of MPD by STAT5aDeltaN(S711F) was reversed by H2k/bcl-2 transgenic expression. Overall, these studies define N-domain-dependent survival signaling as an Achilles heel of persistent STAT5 activation and highlight the potential therapeutic importance of targeting STAT5 N-domain-mediated regulation of bcl-2 family members.

Read the full article on CWRUmedicine.org

Read about “Gab2 Promotes Hematopoietic Stem Cell Maintenance & Self-Renewal with STAT5″

BACKGROUND ::
Grb2-associated binding (Gab) adapter proteins play major roles in coordinating signaling downstream of hematopoietic cytokine receptors. In hematopoietic cells, Gab2 can modulate phosphatidylinositol-3 kinase and mitogen associated protein kinase activities and regulate the long-term multilineage competitive repopulating activity of hematopoietic stem cells (HSCs). Gab2 may also act in a linear pathway upstream or downstream of signal transducer and activator of transcription-5 (STAT5), a major positive regulator of HSC function. Therefore, we aimed to determine whether Gab2 and STAT5 function in hematopoiesis in a redundant or non-redundant manner.

METHODOLOGY & PRINCIPAL FINDINGS ::
To do this we generated Gab2 mutant mice with heterozygous and homozygous deletions of STAT5. In heterozygous STAT5 mutant mice, deficiencies in HSC/multipotent progenitors were reflected by decreased long-term repopulating activity. This reduction in repopulation function was mirrored in the reduced growth response to early-acting cytokines from sorted double mutant c-Kit(+)Lin(-)Sca-1(+) (KLS) cells. Importantly, in non-ablated newborn mice, the host steady-state engraftment ability was impaired by loss of Gab2 in heterozygous STAT5 mutant background. Fetal liver cells isolated from homozygous STAT5 mutant mice lacking Gab2 showed significant reduction in HSC number (KLS CD150(+)CD48(-)), reduced HSC survival, and dramatic loss of self-renewal potential as measured by serial transplantation.

CONCLUSIONS & SIGNIFICANCE ::
These data demonstrate new functions for Gab2 in hematopoiesis in a manner that is non-redundant with STAT5. Furthermore, important synergy between STAT5 and Gab2 was observed in HSC self-renewal, which might be exploited to optimize stem cell-based therapeutics.

Read the full article on CWRUmedicine.org