University Hospitals Case Medical Center Research Articles

OTHR-15. PATIENTS WITH LIMITED STAGE SMALL CELL LUNG CANCER THAT RECUR WITH ISOLATED BRAIN METASTASES HAVE PROLONGED SURVIVAL

INTRODUCTION: Small cell lung cancer (SCLC) frequently metastasizes to the brain. In patients with limited-stage disease (disease confined to one radiation portal), the incidence of brain metastasis after 3 years is 50–60%. We reviewed patients with SCLC and hypothesized that isolated brain recurrence has a unique natural history. METHODS: 471 adult SCLC patients seen at University Hospitals Case Medical Center from 1998 to 2014 were screened. Patients were separated by those with isolated brain metastases and those with other patterns of metastasis. Demographic data including age, race, sex, smoking history and clinical data such as TNM classification, stage, treatment, and time to relapse and death were collected. Median overall survival (mOS) and progression free survival (mPFS) were compared using log-rank tests and Kaplan-Meier plots were constructed. In a separate cohort of metastatic SCLC we examined differences in next generation sequencing (NGS) of targeted exomes between primary and metastatic sites including the brain. RESULTS: 281 extensive-stage patients and 40 limited-stage patients were included. 12% (30/281) of the extensive-stage patients and 25% (10/40) of limited-stage patients had isolated brain metastases. Patients with limited-stage disease who developed isolated brain metastases had significantly improved mOS as compared to those who developed other sites of metastasis (OS = 38.7 months vs. 20.2 months, p=0.033). Furthermore, mPFS for limited-stage patients with isolated brain metastases was improved compared to other patterns of metastases (PFS = 17.9 months vs. 10.1 months, p = 0.03). NGS demonstrated that NOTCH1 mutations were infrequent in biopsies from all metastatic sites but were common in primary lung tumors. CONCLUSION: In our single center review, patients with limited-stage SCLC who recurred only in the brain had improved survival as compared to those who had other patterns of metastases. Our initial work demonstrates differences in oncogenic gene mutations between the metastatic and primary tumors.

The Necessity and Safety of Resident Involvement in Laparoscopic Colorectal Surgery.

Cleveland, Ohio See “Increased postoperative morbidity associated with prolonged laparoscopic colorectal resections is not increased by resident involvement,” by Kulaylat AS, Hollenbeak CS, Stewart DB, on page 579. Financial Disclosure: None reported. Correspondence: Conor P. Delaney, M.D., M.Ch., Ph.D., F.R.C.S.I., University Hospitals Case Medical Center, Cleveland, OH 44106-5047. E-mail: [email protected]

Creating a Sustainable ObGyn Residency in a Resource-Limited Country Improves Maternal Health Outcomes

BACKGROUND: The 2013 maternal mortality ratio (MMR) in Guyana was 250/100,000 live births according to the WHO, compared to a regional average of 68. Inadequate quality of care, shortage of skilled health care professionals, and systemic limitations are contributing factors. METHODS: In 2012 University Hospitals/Case Medical Center (UHCMC), Georgetown Public Hospital Corporation (GPHC) and University of Guyana collaborated to develop a 4-year ObGyn training program using curriculum formalized at UHCMC, modified to suit local needs. A multi-academic institutional partnership allowed international faculty involvement in training Guyana's first ObGyn residents (MDG-8). Maternal morbidity and mortality outcomes (MDG-5) were prospectively maintained, analyzed, and compared to rates prior to program implementation. RESULTS: Twenty-three residents were trained and five residents completed the program in 2016. Full-time staff are present in Guyana, and 52 faculty from partnering institutions travelled to Guyana to teach and provide patient care. Development of modified evidence-based clinical guidelines improved quality of care and patient safety outcomes. MMR from direct causes decreased country-wide and at GPHC during the 4-year period. Success was due to shared institutional vision, establishment of partner organizations, resident leadership development, and systems-based improvement. Future challenges include trainee retention and continued sustainability. DISCUSSION: Guyana’s first ObGyn residency program can serve as a model for similar endeavors in global health. Creation of sustainable training programs in ObGyn through international partnerships is essential progress toward achieving MDGs 5 and 8.

ATVB Named Lecture Review-Insight Into Author.

ATVB Named Lecture Review-Insight Into Author.

Abstract OT2-01-10: Pilot study of carboplatin, nab-paclitaxel and pembrolizumab for metastatic triple-negative breast cancer (ongoing clinical trial)

Abstract BACKGROUND. Triple-negative breast cancer (TNBC) is associated with an aggressive phenotype and decreased survival. TNBC is characterized by tumor-infiltrating lymphocytes (TIL) which predict for a better prognosis and likely reflect immune recognition of tumor-associated antigens by TIL. However, potent immune suppressive signals exist in the tumor microenvironment such as those mediated by PD-1 with its ligand, PD-L1. Therefore, to test the validity of decreasing PD-1/PD-L1-mediated immune suppression, a Phase Ib study of single-agent pembrolizumab in 32 patients with advanced TNBC showed a partial response of 16.1% and stable disease of 9.7%, thereby attesting to the effectiveness of single-agent pembrolizumab in these patients. Other studies have demonstrated that cytotoxic chemotherapy favorably modulates immunity against cancer and there is therefore a strong rationale to combine chemotherapy with an immune modulator such as pembrolizumab for the treatment of mTNBC. TRIAL DESIGN. This is an investigator-initiated, industry-sponsored (Merck) pilot study of carboplatin (C), nab-paclitaxel (N) and pembrolizumab (P) in 30 patients with metastatic (m) TNBC. Eligible patients will receive 3 cycles of CNP, with each cycle consisting of C (AUC 6 on days 1 of a 21-day cycle), N (100 mg/m2 IV on days 1, 8 and 15 of a 21-day cycle), and P (200 mg IV on day 15 of each cycle). After completion of 3 cycles CNP, patients with responding or stable disease by RECIST 1.1 criteria will be eligible for additional cycle(s) of CNP. ELIGIBILITY CRITERIA. Patients must have radiologically measurable mTNBC, an ECOG performance status of 0-1, must not have received more than 2 prior therapies for this disease, and must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes. A second post-treatment biopsy will be encouraged but will not be mandated. SPECIFIC AIMS. The primary objective is to determine overall response rate (ORR) in patients treated with CNP. The secondary objectives are to determine progression-free survival (PFS) and safety/tolerability of CNP. Correlative objectives include the identification of pathologic and genomic correlates of response to CNP. STATISTICAL METHODS. Clinical response will be scored using RECIST 1.1 criteria. Under the proposed treatment, the expected clinical response is about 35%. With the precision of the 2-sided 95% confidence interval for the response rate set to 0.17 (the distance to the expected response rate of 35%), the sample size required for the study is 30 patients. The true response rate of therapy will be estimated based on the number of responses using a binomial distribution and its confidence intervals will be estimated using Wilson's method. The Kaplan-Meier method will be used to estimate PFS. Factors including pathologic and genomic correlates that predict survival outcomes will be identified by Cox model or extensions of the Cox model. TARGET ACCRUAL. We plan to enroll 30 patients over 2 years, with the first patient expected to be enrolled in September 2016. CONTACT INFORMATION. Joseph Baar, MD, PhD. Seidman Cancer Center of University Hospitals Case Medical Center. E-mail: joseph.baar@uhhospitals.org. Citation Format: Baar J, Abraham J, Silverman P, Budd GT, Vinayak S, Varadan V, Moore H, Montero A, Fu P. Pilot study of carboplatin, nab-paclitaxel and pembrolizumab for metastatic triple-negative breast cancer (ongoing clinical trial) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-10.

Abstract WP409: Impact of Nursing Expertise and Staffing Ratio on Compliance with Post-tPA/Endovascular Patient Monitoring

Introduction: In 2014, the Post-tPA/Endovascular nursing monitoring flow sheet was revised to harmonize with the NIHSS exam. The challenges to performance and documentation compliance posed by the intensity and frequency of assessments have been the focus of an ongoing quality improvement initiative. Methods: All Post-tPA/Endovascular monitoring flow sheets from June 2014- June 2016 at University Hospitals Case Medical Center were reviewed for presence of neurologic assessments, vital signs, and management of hypertension per protocol. Stroke staff conducted in-services on the enhanced assessments and modified NIHSS training and house staff mentored bedside RNs in performing the NIHSS. A tip sheet was developed for staff on the modified NIHSS and real time feedback was given on all outliers. Results: Of 459 patients, compliance with all of the 684 monitoring data points ranged from 67-100% in the Neuroscience ICU (Patient: RN ratio 2:1), 75-100% in the Neuro-Intermediate Unit (Patient: RN ratio 3:1) and 40-100% in the Emergency Department (Patient: RN ratio 4:1). Overall compliance to > 95% of data points was seen in all but 5 patients with missing flow sheets. Symptomatic hemorrhagic complications after IVtPA decreased from 6.5% to 2.7%. Root-cause analysis of missing data points revealed seven areas of opportunity: Interference by diagnostic testing (29%), during patient transportation (22%), and following endovascular treatment (15%) or due to travelling RNs (8%). Missing documentation was most frequent during the q15 minute phase due to the intensity of monitoring (11%)- with the Emergency Department the most vulnerable location- and less during the q30 minute (4%) or q1 hour (3%) assessments. Units with dedicated neuroscience nursing adjusted more rapidly to the revision compared to units that do not routinely perform such assessments. Conclusions: Optimum compliance with nursing assessments and monitoring occur when there is no interference with diagnostic testing or procedures, the patient needs were a high priority and the patient acuity was well matched to the RN staffing ratio. This data supports a care model where a neuroscience trained RN nurse transitions with the patient during the first 24 hours after tPA/Endovascular therapy.

The Impact of a Multidisciplinary Sickle Cell and Gynecology Clinic

Background: Contraception and pregnancy planning are critically important for patients with sickle cell disease (SCD). However, rates of contraceptive utilization are often suboptimal and unplanned pregnancy remains a problem among this patient population. In an effort to improve care, a multidisciplinary hematology and gynecology clinic was initiated at University Hospitals Case Medical Center in which women of reproductive age received comprehensive care in single visits.Objective: To determine the impact on pregnancy, contraception use and sexually transmitted infections (STIs) diagnoses of a multidisciplinary hematology and gynecology clinic for women with SCD.Methods: A retrospective cohort study of women seen in University Hospitals Hematology Clinic for sickle cell disease from 2011 to 2015. Baseline demographics as well as the subsequent outcomes of pregnancies, contraception use and STIs were collected. Total differences in outcomes before and after the multidisciplinary clinical were evaluated with Fisher's exact test. Longitudinal differences in pregnancies and STIs were analyzed with time-to-event analyses. For outcomes of interest p charts were constructed with upper and lower control limits.Results: A total of 133 women total were identified as reproductive age women with sickle cell disease from 2011 to 2015. The percentage of SCD patients using birth control before and after the multidisciplinary clinic increased from 12.3% to 37% (p=0.0001). The p chart for contraception use is provided bellow and was highly significant. No significant differences in pregnancy or STIs were identified in time-to-event analysis and p charts, though the total number of STIs before and after the intervention was limited (eighteen).Conclusion: Incorporating a multidisciplinary approach with combined hematology and gynecology care for women with sickle cell disease has the potential to improve access to contraception use in this population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Historical Perspective: Henry H. Bohlman (1937-2010): The Father of Contemporary Spine Surgery.

The incredible career of Henry H. Bohlman, MD, spanned over four decades at University Hospitals Case Medical Center. He was an innovator and pioneer, designing several techniques for the management of several spinal pathologies while advocating the anterior approach to the spine. Dr. Bohlman's legacy is preserved in his fellows who have become leaders in spine surgery throughout the world.

Disseminated Histoplasmosis in Patients Receiving Tumor Necrosis Factor-α Inhibitors

Abstract Since their introduction in the late 1990s, tumor necrosis factor (TNF)-α inhibitors have proven effective in the treatment of several inflammatory disorders, and their use has become increasingly common. Tumor necrosis factor-α blockade is nonetheless associated with an increase in the risk of infection by intracellular, granuloma-forming pathogens, such as Histoplasma capsulatum. We performed a query of our medical records for all cases of disseminated histoplasmosis in patients receiving TNF-α inhibitors between the years 1999 and 2014 at University Hospitals Case Medical Center in Cleveland, Ohio, an area of moderate histoplasmosis endemicity. A total of 357 cases of disseminated histoplasmosis were identified, 8 (2.2%) of whom were receiving TNF-α inhibitor therapy at the time of diagnosis. Five patients were receiving infliximab, and 3 were receiving adalimumab. All patients had generalized, nonspecific presenting symptoms, and all but one had a complete response to antifungal treatment and the cessation of the inciting TNF-α inhibitor. Five of the patients eventually resumed TNF-α inhibitor therapy a year after their initial diagnosis with disseminated histoplasmosis. The only patient who succumbed to the infection had a delayed diagnosis. The increasing use of TNF-α inhibitors should come with an increased awareness of its association with opportunistic infections including disseminated histoplasmosis and by other endemic fungi. This case series highlights the importance of early diagnosis of such infections to achieve a favorable outcome. Further research will need to focus on determining the best long-term treatment strategies in managing these patients after the resolution of the acute infection.

Computed tomography-guided percutaneous biopsy for vertebral neoplasms: a department's experience and hybrid biopsy technique to improve yield.

OBJECTIVE Recent articles have identified the poor diagnostic yield of percutaneous needle biopsy for vertebral osteomyelitis. The current study aimed to confirm the higher accuracy of CT-guided spinal biopsy for vertebral neoplasms and to identify which biopsy technique provides the highest yield. METHODS Over a 9-year period, the radiology department at University Hospitals Case Medical Center performed 222 CT-guided biopsies of vertebral lesions, of which clinicians indicated a concern for vertebral neoplasms in 122 patients. A retrospective chart review was performed to confirm the higher sensitivity of the percutaneous intervention for vertebral neoplasms. RESULTS A core sample was obtained for all 122 biopsies of concern (100.0%). Only 6 cases (4.9%) were reported as nondiagnostic per histological sampling, and 12 cases (9.8%) were negative for disease. The question of vertebral neoplastic involvement warrants follow-up, and the current study was able to determine the subsequent diagnosis of each lesion. Of the 122 total, 94 (77.0%) core samples provided true-positive results, and the sensitivity of core biopsy measured 87.9%. The technical approach did not demonstrate any significant difference in diagnostic yield. However, when the vertebral cortex was initially pierced with a coaxial bone biopsy system and subsequently a 14-gauge spring-loaded cutting biopsy needle was coaxially advanced into lytic lesions, 14 true positives were obtained with a corresponding sensitivity of 100.0%. CONCLUSIONS This study confirms the higher sensitivity of image-guided percutaneous needle biopsy for vertebral neoplasms. In addition, it demonstrates how the use of a novel cutting needle biopsy approach, performed coaxially through a core biopsy track, provides the highest yield.

Understanding age and race disparities in the application of sentinel lymph node biopsy in breast cancer

Sentinel lymph node biopsy (SLNB) is the standard of care for surgical evaluation of early-stage breast cancer and is being employed as a quality metric for accreditation of breast centers....

Abstract 4963: A distinct AMP-activated protein kinase phosphorylation site is associated with metastasis and castration-resistance in prostate cancer

Abstract AMP-activated protein kinase (AMPK) is a critical regulator of cellular metabolism and plays important role in the development and progression of several human diseases including cancer. We have previously shown that AMPKα activity is significantly inhibited by Ser-485/491 phosphorylation in cell culture and in vivo models of metastatic and castration-resistant prostate cancer. To determine potential translatability, we investigated AMPKα-Ser-485/491 phosphorylation status in clinical prostate cancer specimens and its correlation with metastasis and progression to castration-resistance. Metastasis and matched primary tumor specimens from 45 metastatic prostate cancer patients, 31.1% of which were post-androgen deprivation therapy failure (castration-resistant prostate cancer), and primary tumor specimens from 30 non-metastatic, hormone-dependent prostate cancer patients with undetectable PSA for a mean of 97.1 ± 17.5 months were obtained from the University Hospitals Case Medical Center Pathology Archive. Slides were cut from paraffin blocks, immunostained for p-Ser-485/491 AMPKα and total AMPKα, analyzed by a pathologist, and statistical significance determined by T-test, Kruskal-Wallis test, Fisher's exact test, or Chi-Square test. Mean pre-diagnostic biopsy PSA was 6.5 ng/mL (range 1.20-25.3 ng/mL) in non-metastatic patients and 501.9 ng/mL (range 1.82-3200 ng/mL) in metastatic patients (p < 0.0001). Mean total Gleason score of primary tumors was 6.5 in the non-metastatic group and 8.2 in the metastatic group (p < 0.0001); primary prostate tumor volume (mean ± S.D.) was 22.1 ± 19.5% in the non-metastatic group and 68.1 ± 28.7% in the metastatic group (p < 0.0001). The intensity of overall p-Ser-485/491 AMPKα staining and the number of p-Ser-485/491 AMPKα positively-stained cells was significantly increased in primary prostate tumors (p = 0.0003 and p = 0.0008, respectively) and metastases (p = 0.0011 and p = 0.0062, respectively) of metastatic prostate cancer patients when compared to staining of primary tumor specimens from non-metastatic prostate cancer patients. Further, the intensity of overall p-Ser-485/491 AMPKα staining increased 2.21-fold (p = 0.0050) and the number of p-Ser-485/491 AMPKα positively-stained cells increased 1.77-fold (p = 0.0041) in castration-resistant metastatic prostate cancer specimens compared to androgen-dependent prostate cancer specimens. Therefore, AMPKα Ser-485/491 phosphorylation is associated with metastasis and castration-resistance in clinical prostate cancer and may be a novel target for treatment. Citation Format: Melissa A. Babcook, Mahmut Akgul, Seunghee Margevicius, Gregory T. MacLennan, Pingfu Fu, Robert Abouassaly, Sanjay Gupta. A distinct AMP-activated protein kinase phosphorylation site is associated with metastasis and castration-resistance in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4963.

Parotid melanoma of unknown primary.

Rarely, melanoma is discovered in the parotid gland without an identifiable primary site. It is not known how patients with parotid melanoma of unknown primary (PMUP) compare to those with a known primary (PMKP). As such, we describe the largest series of patients with PMUP to date and compare them to patients with PMKP. We analyzed cases from three sources: (1) the University Hospitals Case Medical Center pathology database (n=45), (2) the Surveillance, Epidemiology, and End Results 18 database (n=33), and (3) a comprehensive literature search (n=32). PMUP patients were predominately male and presented at a mean age of 56years. When compared to PMKP, PMUP cases were more likely to be diagnosed in the parotid parenchyma, present with stage IV disease, and develop distant metastases during follow-up in a shorter amount of time. However, there was no difference in overall survival between patients with PMUP and PMKP presenting with stage-matched disease. Overall survival is similar for stage-matched patients with parotid melanoma presenting with an unknown and known primary site.

New Research

Free AccessNew ResearchJess Levy and Vijayabharathi EkambaramJess LevySearch for more papers by this author and Vijayabharathi Ekambaram1 Child and Adolescent Psychiatry Fellow, University Hospitals Case Medical Center.2 Children's National Medical Center.Search for more papers by this authorPublished Online:August 2016https://doi.org/10.1521/capn.2016.21.2.15PDFPDF PLUS ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations About Previous article Next article FiguresReferencesRelatedDetails Volume 21Issue 2Apr 2016 Information© 2016 Guilford Publications Inc.PDF download

Bilateral Sequential Cochlear Implantation in Patients With Enlarged Vestibular Aqueduct (EVA) Syndrome.

To analyze audiometric outcomes after bilateral cochlear implantation in patients with isolated enlarged vestibular aqueduct (EVA) syndrome and associated incomplete partition (IP) malformations. Secondary objective was to analyze rate of cerebrospinal fluid (CSF) gusher in patients with IP-EVA spectrum deformities and compare this with the existing literature. Retrospective chart review. Thirty-two patients with EVA syndrome who received unilateral or bilateral cochlear implants between June 1999 and January 2014 were identified in the University Hospitals Case Medical Center cochlear implant database. Isolated EVA (IEVA) and Incomplete Partition Type II (IP-II) malformations were identified by reviewing high-resolution computed tomography (HRCT) imaging. Demographic information, age at implantation, surgical details, postimplantation audiometric data including speech reception thresholds (SRT), word, and sentence scores were reviewed and analyzed. Intra- and postoperative complications were analyzed as well and compared with the literature. Seventeen patients (32 implanted ears) had pediatric cochlear implantation for EVA-associated hearing loss. Data from 16 controls (32 implanted ears) were used to compare audiometric and speech outcomes of EVA cohort. Mean age at implantation was 6.8 years for EVA cohort and 6.0 years for controls. There was no statistically significant difference in long-term postoperative SRT, monaurally aided word scores, and binaurally tested word scores between pediatric EVA group and controls. The EVA patients had a long-term mean sentence score of 85.92%. A subset of EVA patients implanted at mean age of 3.18 years (n = 15 ears) had similar audiometric outcomes to another control group with Connexin 26 mutations (n = 20 ears) implanted at a similar age. Further subset analysis revealed no significant differences in age at implantation, SRT, and word scores in patients with IEVA and IP-II malformation. There was no significant association between size of vestibular aqueduct and age at implantation. There was no CSF gusher or other intra- or postoperative complications reported in our series. Bilateral sequential cochlear implantation can be performed safely in patients with EVA. Audiometric outcomes are excellent and comparable to pediatric cochlear implant patients with no malformations. CSF gusher rates can be minimized by trans-round window approach. Further long-term studies are needed to identify differences within IP-EVA spectrum deformities, audiometric outcomes, and proportions of EVA patients who will need cochlear implantation for hearing rehabilitation.

Efficacy of Nutrition Education within a Cardiac Rehabilitation Program on Eliciting Heart Healthy Diet Changes

Purpose: The purpose of this study was to determine if nutrition education classes taught by a Registered Dietitian Nutritionist (RDN) to cardiac rehabilitation patients improved dietary habits, specifically dietary fat intake. Method: This retrospective chart review assessed changes in diet composition of participants enrolled in the cardiac rehabilitation program at University Hospitals Case Medical Center (UHCMC). Participants were offered nutrition education classes and the cardiac program administered the Diet Habit Survey, pre and post education. Participants were separated into groups A, B, C depending on the year they attended cardiac rehabilitation. The data was summarized using means ± standard deviation (SD). One way ANOVA and paired t test were used to compare baseline characteristics, sex and survey scores pre and post within groups. Data was analyzed using the JMP 11.1.1 software. Simple linear regression was used to assess the relationship between change in survey scores and number of classes attended. Spearman’s Rho was used to calculate correlations between pre-survey scores and the number of classes attended. Results: Participant’s baseline characteristics, co-morbidities, entry diagnosis, survey scores and lipid panel were similar among all groups. The post survey scores improved in groups A, B, and C (p ≤ 0.001, 0.007, 0.001) respectively. A change in survey score was not associated with number of classes attended among all groups combined (p = 0.210) nor among individuals assigned to the various participation groups. Categorical changes in % fat were not detected among groups A, B, or C or between sexes (p-value 0.307, 0.349, 0.646 respectively). Conclusion: Nutrition education taught by a RDN can improve dietary habits of participants who attend cardiac rehabilitation programs.

Elevation of Plasma α-Synuclein Levels Is Diagnostic of Malignant or Invasive Central Nervous System Neoplasms

α-synuclein belongs to a family of small proteins and has been described as an important pathologic mediator of neurodegenerative diseases grouped as synucleinopathies such as Parkinson's Disease and Dementia with Lewy Bodies. It is extensively expressed in the central nervous system (CNS); however, its physiologic function is not known though it may involve mediating dopamine neurotransmitter release. Additionally, it is expressed in the hematopoietic system in erythroid precursors and megakaryocytes in bone marrow, as well as erythrocytes and platelets in peripheral blood. More importantly, a recent report has shown that α-synuclein is important for the development and functional response of lymphocytes (both B- and T-cells) and for late stages of hematopoiesis.In this study we set forth to determine the α-synuclein plasma concentration changes that occur during CNS malignancy, due to the potential relationship with destruction of brain tissue. Plasma was isolated from peripheral blood samples collected from patients with benign and malignant CNS neoplasms. All patients provided informed written consent. Five patients from each of the following diagnoses were included: pituitary adenoma, vestibular schwannoma, meningioma grade (G) 1, meningioma G2, oligoastrocytoma G2, oligodendroglioma G3, anaplastic astrocytoma G3, and glioblastoma G4. Tumors were classified according to the World Health Organization criteria. As controls, donated plasma from our regional blood suppliers of different ABO blood types was used. All samples were blinded, thawed and used at 1:5, 1:10 or 1:20 dilutions. α-synuclein concentration was measured using an enzyme-linked immunosorbent assay (ELISA) kit containing a monoclonal antibody to the full length human α-synuclein protein that was performed according to manufacturer's protocols. To quantify total α-synuclein concentration, purified recombinant α-synuclein was assayed in parallel to develop a standard concentration curve. Statistical significance was set at p <0.05 to assess differences in a-synuclein concentration by type of brain tumor diagnosis versus controls. The study was approved by the University Hospitals Case Medical Center institutional review board.Median α-synuclein concentration in healthy plasma donors was 2.25 ng/L. Of the tumors assayed, the median concentration for each tumor was as follows: pituitary adenoma 2.05 ng/L, vestibular schwannoma 2.35 ng/L, meningioma G1 4.70 ng/L, meningioma G2 11.00 ng/L, oligoastrocytoma G2 3.6 ng/L, oligodendroglioma G3 9.4 ng/L, anaplastic astrocytoma G3 4.70 ng/L, and glioblastoma G4 6.20 ng/L. Statistical comparisons between pituitary adenoma, vestibular schwannoma, meningioma G1, oligoastrocytoma G2, and anaplastic astrocytoma G3 neoplasms and normal plasma showed no significant increase of peripheral α-synuclein compared to normal controls. However, there were statistically significant (p <0.05) increases in α-synuclein concentration in meningioma G2, oligoastrocytoma G3, and glioblastoma G4 compared to controls.In summary, our study results show that changes in the plasma concentration of α-synuclein distinctively recognized specific types of CNS neoplasms that are malignant and can lead to brain ischemia. In light of tumor burden and brain tissue destruction, our data indicates that non-malignant brain tumors tend to have α-synuclein concentration in plasma that is similar to that in healthy donors; while some types of malignant brain neoplasms have significantly elevated a-synuclein in plasma. Further research, with higher numbers of patients per tumor group is required before these results can be translated into clinical practice. DisclosuresNo relevant conflicts of interest to declare.

Medical Decision Making for Patients Without Proxies: The Effect of Personal Experience in the Deliberative Process

The number of admissions to hospitals of patients without a proxy decision maker is rising. Very often these patients need fairly immediate medical intervention for which informed consent--or informed refusal--is required. Many have recommended that there be a process in place to make these decisions, and that it include a variety of perspectives. People are particularly wary of relying solely on medical staff to make these decisions. The University Hospitals Case Medical Center recruits community members from its Ethics Committee to serve on a subcommittee, the Patients Without Proxies (PWP) Committee, which works with medical staff during the decision-making process for these patients. Generally, the community members go to the bedside to observe patients. This article looks at how those unused to observing hospitalized patients who are sick and/or dying are affected, comparing them to mock jurors in a research study who are exposed to graphic photographs related to a fabricated crime scene. Judgments made by the mock jurors are affected by viewing such images. The personal experience of witnessing unfamiliar and shocking scenes affects their subsequent judgments. While it may be difficult to tease out whether observing patients causes PWP members to be benefited or harmed, they are affected by what they see. If a variety of perspectives is desirable to reduce possible bias or error, this article argues that at least one community member should refrain from seeing the patient in order to add a different and valuable voice to the decision-making process. Members of the subcommittee base their judgments on the various kinds of information available. Sometimes the things they see, hear, or feel may affect them particularly deeply, and affect their judgments as well. In this article I explore the idea that something like this may be happening in a particular kind of clinical ethics case consultation.

Anthracycline Cardiotoxicity: Strategies for Prevention and Intervention

*Corresponding author: Guilherme H. Oliveira, MD, FACC Associate Professor of Medicine Chief, Heart Failure Section Director, Onco-Cardiology Program Seidman Cancer Center Director, Advanced Heart Failure and Transplantation Center Harrington Heart and Vascular Institute Case Western Reserve University School of Medicine University Hospitals Case Medical Center 11100 Euclid Ave. Cleveland OH 44106, USA E-mail: guilherme.oliveira@uhhospitals.org

Engaging Inner-City Fathers in Breastfeeding Support.

Our objective was to pilot a method of engaging fathers/partners of high-risk inner-city mothers in breastfeeding support. Breast for Success was a breastfeeding promotion initiative with a father engagement component. In collaboration with Community Endeavors, Inc., we organized father-friendly evening programs (one night per week for 3 weeks, repeating quarterly) led by a male facilitator to provide breastfeeding education, with ongoing availability of a resource specialist to link men to community resources relevant to their legal, financial, and health needs. Fathers/partners were recruited from community programs and via our community partner, The City of Cleveland Department of Public Health MomsFirst™ Project, a federally funded Healthy Start program. University Hospitals Case Medical Center Institutional Review Board approved the study. Sixty-six fathers/partners attended eight evening programs, and 30 (45%) attended all three nights. Their median age was 27.5 years (range, 17-64 years), and 49 (74%) self-described themselves as African American. At the start of the groups, 39% (21/54 responding) had a breastfed child, and 64% (39/61 responding) said they were comfortable with breastfeeding for their own child. After Sessions 1, 2, and 3, respectively, 40 (85%), 42 (89%), and 33 (80%) were "more likely" to want their next baby to breastfeed. On average, in 62% of all responses (278/450 possible), men endorsed learning "a lot more" about the 10 breastfeeding curriculum topics presented. Recruitment of inner-city fathers/partners for a breastfeeding education program was feasible, and among men who attended, fathers' perceptions about their breastfeeding knowledge were positively impacted.