Medicine and Health Sciences Commons^™

Periprosthetic Joint Infection Increases The Risk Of One-Year Mortality., Benjamin Zmistowski, Joseph A. Karam, M.D., Joel B Durinka, David S Casper, Md, Javad Parvizi Md

Rothman Institute Faculty Papers

BACKGROUND: Periprosthetic joint infection continues to potentially complicate an otherwise successful joint replacement. The treatment of this infection often requires multiple surgical procedures associated with increased complications and morbidity. This study examined the relationship between periprosthetic joint infection and mortality and aimed to determine the effect of periprosthetic joint infection on mortality and any predictors of mortality in patients with periprosthetic joint infection.

METHODS: Four hundred and thirty-six patients with at least one surgical intervention secondary to confirmed periprosthetic joint infection were compared with 2342 patients undergoing revision arthroplasty for aseptic failure. The incidence of mortality at thirty days, ninety …

Neuropathy, Neuropathic Pain, And Sickle Cell Disease., Samir K. Ballas, Deepika S Darbari

Cardeza Foundation for Hematologic Research

No abstract provided.

Clinical Phenotypes And Abcc6 Gene Mutations In Brazilian Families With Pseudoxanthoma Elasticum., Caroline Silvério Faria, Qiaoli Li, Haitao Guo, Jouni Uitto, Sylvia Satomi Takeno, Marilia De Arruda Cardoso Smith, Dertia Villalba Freire-Maia

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE; OMIM 264800) manifests with characteristic skin lesions of yellowish papules which coalesce into plaques of inelastic and leathery skin on the predilection sites (1). The ocular findings consist of angioid streaks, choroidal neovascularization and subretinal hemorrhages resulting in loss of visual acuity and occasional blindness. Cardiovascular problems include hypertension, intermittent claudication, and occasional myocardial infarcts and stroke. The prevalence of PXE is estimated to be in the range of 1:50,000-70,000 and to be more frequent in females than in males. The diagnosis can be challenging to clinicians due to late-onset of clinical manifestations and considerable heterogeneity. PXE …

Inverse Lichen Planus, Michael D Lee, Laurel R Schwartz

Department of Dermatology and Cutaneous Biology Faculty Papers

A Case of Inverse Lichen Planus

Lichen planus (LP) is a pruritic, papular eruption characterized by its violaceous color and polygonal shape. It is most commonly found on the flexor surfaces of the upper extremities, on the genitalia, and on the mucous membranes. We herein report a classic case of LP in an inverse distribution.

Phenotypic Parameters Predict Time To Normalization In Infants With Hypogammaglobulinemia., Robert C. Van Winkle, Walter W. Hauck, Stephen J. Mcgeady

Department of Pediatrics Faculty Papers

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy.

METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization.

RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile …

Predictors Of Perioperative Blood Loss In Total Joint Arthroplasty., Jai Hyung Park, Mohammad R Rasouli, S M Javad Mortazavi, Anthony T Tokarski, Mitchell G Maltenfort, Javad Parvizi

Rothman Institute Faculty Papers

UNLABELLED: UPDATE The print version of this article has errors that have been corrected in the online version of this article. In the Materials and Methods section, the sentence that reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 mg/dL or a hematocrit level of at least 33%." in the print version now reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Generating Hypotheses About Care Needs Of High Utilizers: Lessons From Patient Interviews., Dawn B Mautner, Hauchie Pang, Jeffrey C Brenner, Judy A Shea, Kennen S Gross, Rosemary Frasso, Carolyn C Cannuscio

Department of Family & Community Medicine Faculty Papers

Informed by a largely secondary and quantitative literature, efforts to improve care and outcomes for complex patients with high levels of emergency and hospital-based health care utilization have offered mixed results. This qualitative study identifies psychosocial factors and life experiences described by these patients that may be important to their care needs. Semi-structured interviews were conducted with 19 patients of the Camden Coalition of Healthcare Providers' Care Management Team. Investigators coded transcripts using a priori and inductively-derived codes, then identified 3 key themes: (1) Early-life instability and traumas, including parental loss, unstable or violent relationships, and transiency, informed many participants' …

Patients With Atrial Fibrillation Undergoing Total Joint Arthroplasty Increase Hospital Burden., Vinay K Aggarwal, Eric H Tischler, Zachary D Post, Ian Kane, Fabio R Orozco, Alvin Ong

Rothman Institute Faculty Papers

BACKGROUND: More than 3 million people in the United States have atrial fibrillation, most of whom are being managed with anticoagulation therapy for life. The goal of the present study was to examine the effect of chronic anticoagulation therapy on patients with atrial fibrillation who undergo total joint arthroplasty.

METHODS: We retrospectively reviewed all patients undergoing aseptic primary or revision total joint arthroplasty at our facility from March 2007 to August 2011. One hundred and sixty-one patients with atrial fibrillation (Group A) were compared with 161 matched controls (Group B). A total of 112 hips and 210 knees underwent 239 …

The Effect Of Malnutrition On Patients Undergoing Elective Joint Arthroplasty., Ronald Huang, Md, Max Greenky, Bs, Glenn J. Kerr, Md, Mathew S. Austin, Md, Javad Parvizi, Md, Frcs

Rothman Institute Faculty Papers

Malnutrition has been linked to serious complications in patients undergoing elective total joint arthroplasty (TJA). This study prospectively evaluated 2,161 patients undergoing elective TJA for malnutrition as defined by either an abnormal serum albumin or transferrin. The overall incidence of malnutrition was 8.5% (184 of 2,161) and the rate of overall complications in the malnourished group was 12% as compared to 2.9% in patients with normal parameters (P55years-old undergoing TJA and is associated with a significant increase in post-operative complications.

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …

Occupational Exposure To Hepatitis C Virus: Early T-Cell Responses In The Absence Of Seroconversion In A Longitudinal Cohort Study., Theo Heller, Jens Martin Werner, Fareed Rahman, Eishiro Mizukoshi, Yuji Sobao, Ann Marie Gordon, Arlene Sheets, Averell H. Sherker, Ellen Kessler, Kathleen S. Bean, Steven K. Herrine, M'Lou Stevens, James Schmitt, Barbara Rehermann

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.

METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.

RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell …

Spinal Anesthesia: Should Everyone Receive A Urinary Catheter?: A Randomized, Prospective Study Of Patients Undergoing Total Hip Arthroplasty., Adam G Miller, James Mckenzie, Max Greenky, Erica Shaw, Kishor Gandhi, William J Hozack, Javad Parvizi

Rothman Institute Faculty Papers

BACKGROUND: The objective of this randomized prospective study was to determine whether a urinary catheter is necessary for all patients undergoing total hip arthroplasty under spinal anesthesia.

METHODS: Consecutive patients undergoing total hip arthroplasty under spinal anesthesia were randomized to treatment with or without insertion of an indwelling urinary catheter. All patients received spinal anesthesia with 15 to 30 mg of 0.5% bupivacaine. The catheter group was subjected to a standard postoperative protocol, with removal of the indwelling catheter within forty-eight hours postoperatively. The experimental group was monitored for urinary retention and, if necessary, had straight catheterization up to two …

Spinal Anesthesia: Should Everyone Receive A Urinary Catheter?: A Randomized, Prospective Study Of Patients Undergoing Total Hip Arthroplasty., Adam G Miller, Md, James Mckenzie, Bs, Max Greenky, Ba, Erica Shaw, Rnp, Kishor Gandhi, Md, William J Hozack, Md, Javad Parvizi, Md, Frcs

Rothman Institute Faculty Papers

BACKGROUND: The objective of this randomized prospective study was to determine whether a urinary catheter is necessary for all patients undergoing total hip arthroplasty under spinal anesthesia.

METHODS: Consecutive patients undergoing total hip arthroplasty under spinal anesthesia were randomized to treatment with or without insertion of an indwelling urinary catheter. All patients received spinal anesthesia with 15 to 30 mg of 0.5% bupivacaine. The catheter group was subjected to a standard postoperative protocol, with removal of the indwelling catheter within forty-eight hours postoperatively. The experimental group was monitored for urinary retention and, if necessary, had straight catheterization up to two …

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …

Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina

Kimmel Cancer Center Faculty Papers

No abstract provided.

Erosive Arthritis And Hepatic Granuloma Formation Induced By Peptidoglycan Polysaccharide In Rats Is Aggravated By Prasugrel Treatment., Analia E Garcia, Mario C Rico, Elisabetta Liverani, Raul A Dela Cadena, Paul F. Bray, Satya P Kunapuli

Cardeza Foundation for Hematologic Research

Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS) in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with …

Altered Drainage Patterns In Patients With Melanoma And Previous Axillary Dissection., Caitlyn M. Johnson, Charles Intenzo, Michael Mastrangelo, Kendra Feeney, Adam C. Berger

Department of Surgery Faculty Papers

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously …

An Old Problem With A New Therapy: Gastrointestinal Bleeding In Ventricular Assist Device Patients And Deep Overtube-Assisted Enteroscopy., Konrad Sarosiek, Linda J Bogar, Mitchell I Conn, Brendan O'Hare, Hitoshi Hirose, Md, Phd, Nicholas C. Cavarocchi, Md

Department of Surgery Faculty Papers

Conventional algorithms for diagnosis and treatment of gastrointestinal bleeding (GIB) in patients with nonpulsatile ventricular assist devices (VADs) may take days to perform while patients require transfusions. We developed a new algorithm based on deep overtube-assisted enteroscopy (DOAE) to facilitate a rapid diagnosis and treatment. From 2004 to 2012, 84 patients who underwent VAD placement in our institution, were evaluated for episodes of GIB. Our new algorithm for the management of GIB using DOAE was evaluated by dividing the episodes into three groups: group A (traditional management without enteroscopy), group B (traditional management with enteroscopy performed >24 hours after presentation), …

Common Peroneal Nerve Palsy Following Total Hip Arthroplasty: Prognostic Factors For Recovery., Jai Hyung Park, Bryan Hozack, Peter Kim, Robert Norton, Steven Mandel, Camilo Restrepo, Javad Parvizi

Rothman Institute Faculty Papers

BACKGROUND: Common peroneal nerve palsy, although rare, is a serious complication of total hip arthroplasty. Although several publications have dealt with the risk factors for peroneal nerve palsy, there is little literature regarding the time it takes for the nerve to recover and the factors that influence its recovery. The purpose of this study was to elucidate the clinical course of this injury and identify prognostic factors for recovery.

METHODS: From January 2000 to December 2007, 7969 primary and 1601 revision total hip arthroplasties were performed at our institution. Common peroneal nerve palsy developed following thirty-one (0.32%) of these procedures. …

Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md

Department of Surgery Faculty Papers

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.

METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and …

Functional And Quality-Of-Life Outcomes In Geriatric Patients With Type-Ii Dens Fracture., Alexander R Vaccaro, Christopher K Kepler, Branko Kopjar, Jens Chapman, Christopher Shaffrey, Paul Arnold, Ziya Gokaslan, Darrel Brodke, John France, Mark Dekutoski, Rick Sasso, S Tim Yoon, Christopher Bono, James Harrop, Michael G Fehlings

Rothman Institute Faculty Papers

BACKGROUND: Dens fractures are relatively common in the elderly. The treatment of Type-II dens fractures remains controversial. The aim of this multicenter prospective cohort study was to compare outcomes (assessed with use of validated clinical measures) and complications of nonsurgical and surgical treatment of Type-II dens fractures in patients sixty-five years of age or older.

METHODS: One hundred and fifty-nine patients with a Type-II dens fracture were enrolled in a multicenter prospective study. Subjects were treated either surgically (n = 101) or nonsurgically (n = 58) as determined by the treatment preferences of the treating physicians and the patients. The …

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

Cultural Diversity And Views On Alzheimer Disease In Older African Americans., Barry W. Rovner, Robin J. Casten, Lynn F. Harris

Department of Psychiatry and Human Behavior Faculty Papers

Cultural constructs prevalent in older African Americans may influence their risk perceptions and knowledge of Alzheimer disease (AD). To examine this issue, we administered 3 sociocultural scales, the AD Knowledge Scale, and a Risk Perception questionnaire to 271 older African Americans who were recruited from a large community senior center and local churches. Higher Present Time Orientation was significantly related to perceptions of having little control over risks to health (P=0.004), God's Will in determining AD (P=0.001), and lower AD knowledge (P

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Department of Medicine Faculty Papers

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …

Distribution Of Dyssynchrony In Subjects With No Known Cardiac Disease And Comparison Of Velocity Vector Imaging To Color-Coded Tissue Doppler Imaging., Anoop C Parameswaran, Bhaskar Purushottam, Aman Amanullah, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Data on the distribution of dyssynchrony in subjects with normal ejection fraction (EF) and normal QRS are scarce. We studied 100 subjects with no known cardiac disease (52% male, mean age 60 ± 17 years) using velocity vector imaging (VVI). Seventeen percent had septal to lateral (S-L) wall longitudinal delay >75 msec, 63% of subjects had S-L wall radial delay >75 msec, and 25% had a circumferential opposing wall delay >100 msec. Those with circumferential opposing wall delay of >100 msec had a lower EF (57 ± 5% vs. 62 ± 5%, P < 0.05). In an additional group of 33 patients, we compared the longitudinal dyssynchrony parameters as assessed by VVI and tissue Doppler imaging (TDI) and found them to be comparable. In conclusion, we find significant variation in time to peak velocities in subjects with no known cardiac disease, who had a normal left ventricular ejection fraction and QRS duration. VVI is comparable to TDI.

Inflammatory Biomarker Changes And Their Correlation With Framingham Cardiovascular Risk And Lipid Changes In Antiretroviral-Naive Hiv-Infected Patients Treated For 144 Weeks With Abacavir/Lamivudine/Atazanavir With Or Without Ritonavir In Aries., Benjamin Young, Kathleen E Squires, Lisa L Ross, Lizette Santiago, Louis M Sloan, Henry H Zhao, Brian C Wine, Gary E Pakes, David A Margolis, Mark S Shaefer

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of

Major Perioperative Morbidity Does Not Affect Long-Term Survival In Patients Undergoing Esophagectomy For Cancer Of The Esophagus Or Gastroesophageal Junction., Brent T Xia, Ernest L Rosato, Karen A Chojnacki, Albert G. Crawford, Benny Weksler, Adam C. Berger

Department of Surgery Faculty Papers

INTRODUCTION: The incidence of cancer of the esophagus/GE junction is dramatically increasing but continues to have a dismal prognosis. Esophagectomy provides the best opportunity for long-term cure but is hampered by increased rates of perioperative morbidity. We reviewed our large institutional experience to evaluate the impact of postoperative complications on the long-term survival of patients undergoing resection for curative intent.

METHODS: We identified 237 patients who underwent esophagogastrectomy, with curative intent, for cancer between 1994 and 2008. Complications were graded using the previously published Clavien scale. Survival was calculated using Kaplan-Meier methodology and survival curves were compared using log-rank tests. …

Synchronous And Asynchronous Theta And Gamma Activity During Episodic Memory Formation., John F Burke, Kareem A Zaghloul, Joshua Jacobs, Ryan B Williams, Michael R Sperling, Ashwini D Sharan, Michael J Kahana

Department of Neuroscience Faculty Papers

To test the hypothesis that neural oscillations synchronize to mediate memory encoding, we analyzed electrocorticographic recordings taken as 68 human neurosurgical patients studied and subsequently recalled lists of common words. To the extent that changes in spectral power reflect synchronous oscillations, we would expect those power changes to be accompanied by increases in phase synchrony between the region of interest and neighboring brain areas. Contrary to the hypothesized role of synchronous gamma oscillations in memory formation, we found that many key regions that showed power increases during successful memory encoding also exhibited decreases in global synchrony. Similarly, cortical theta activity …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …