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Dr. James Young

2142 N Cove Blvd
Toledo OH 43606
419 914-4101
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 35-07-7536
NPI: 1356304349
Taxonomy Codes:
207P00000X

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Publications

The Effect on Surgical Complications of Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer: NRG Oncology/NSABP Protocol B-40. - Annals of surgical oncology
NRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints included rates of surgical complications after surgery in patients who did or did not receive bev.A total of 1206 women with HER2-negative operable breast cancer were randomly assigned to receive one of three different docetaxel-plus-anthracycline-based regimens, without or with bev (15 mg/kg every 3 weeks) for the first 6 of 8 cycles and for 10 doses postoperatively. Surgical complications were assessed from date of surgery through 24 months following study entry.Early surgical complications were significantly more frequent in the bev group (25.4 vs. 18.9%; trend test p = 0.008), but most were grade 1-2. Early noninfectious wound dehiscences were infrequent and not significantly different (5.4 vs. 3.1%; trend test p = 0.15). Long-term noninfectious wound complications were significantly higher for patients receiving bev (11.8 vs. 5.1%; trend test p = 0.0007), but the incidence of grade ≥3 wound dehiscence was low in both groups (<1%). Among 193 patients undergoing expander or implant reconstructions, 19 (19.6%) of 97 in the bev-receiving group versus 10 (10.4%) of 96 in the non-bev group had grade ≥3 complications (Pearson, p = 0.11).Overall, adding bev increased surgical complications, but most serious complications were not significantly increased. In particular, the need for surgical intervention in patients undergoing breast reconstruction with prosthetic implants was higher with bev but was not statistically significantly different. With precautions, bev can be used safely perioperatively in patients undergoing surgery for breast cancer.
An acute session of roller massage prolongs voluntary torque development and diminishes evoked pain. - European journal of applied physiology
Roller massage (RM) has been reported to reduce pain associated with exercise-induced muscle soreness and increase range of motion without force or activation impairments. The objective was to examine RM effects on evoked pain and contractile properties.Twelve men received three sets of 30-s RM at a perceived discomfort level of 7/10 on a visual analogue scale on the ipsilateral (IPSI-R) stimulated plantar flexors (PF), contralateral PF (CONTRA-R), Sham (light rolling on stimulated PF), or Control. At pre-test, post-test, and 5-min post-test, they received evoked maximal twitch, tetanus, and 70% maximal tetanic stimulation, and performed a maximal voluntary isometric contraction (MVIC). Data analysis included perceived pain and contractile properties.The 70% tetanus illustrated significant 9-10% increases in pain perception with Sham and Control at post- and 5-min post-test, respectively (p < 0.01). There was no pain augmentation with IPSI-R and CONTRA-R. There were no main effects or interactions for most contractile properties. However, MVIC force developed in the first 200 ms showed 9.5% (p = 0.1) and 19.1% (p = 0.03) decreases with IPSI-R at post-test and 5-min post-test.Data suggest that RM-induced neural inhibition decreased MVIC F200 and nullified the testing-induced increase in evoked pain associated with 70% tetanic stimulation.
Hematopoietic Cell Transplantation-Specific Comorbidity Index Predicts Outcomes in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Receiving CD34(+) Selected Grafts for Allogeneic Hematopoietic Cell Transplantation. - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
To evaluate the association between the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and the recently developed age-adjusted HCT-CI (HCT-CI/age) and transplant outcomes in the setting of CD34-selected allogeneic HCT, we analyzed a homogeneous population of patients undergoing allogeneic HCT with CD34-selected grafts for acute myeloid leukemia and myelodysplastic syndrome (n = 346). Median HCT-CI and HCT-CI/age scores were 2 (percentile 25 to 75, 1 to 4) and 3 (percentile 25 to 75, 1 to 5), respectively. Higher HCT-CI and HCT-CI/age scores were associated with higher nonrelapse mortality (NRM) and lower overall survival (OS). The HCT-CI distinguished 2 risk groups (0 to 2 versus ≥3), whereas, with the HCT-CI/age, there was a progressive increase in NRM and decrease in OS with increasing scores in all 4 groups (0 versus 1 to 2 versus 3 to 4 versus ≥5). Higher scores in both models were associated with lower chronic graft-versus-host disease relapse-free survival but not with higher relapse. Both models showed a promising predictive accuracy for NRM (c- = .616 for HCT-CI and c- = .647 for HCT-CI/age). In conclusion, the HCT-CI and HCT-CI/age predict transplant outcomes in CD34-selected allo-HCT, including NRM, OS, and chronic graft-versus-host disease relapse-free survival and may be used to select appropriate patients for this approach.Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
CREBBP Inactivation Promotes the Development of HDAC3 Dependent Lymphomas. - Cancer discovery
Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates development of germinal center derived lymphomas in mice. In both human and murine lymphomas CREBBP loss of function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses including class II MHC. Mechanistically, CREBBP regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we find bind extensively to MHC class II loci. HDAC3 loss of function rescued repression of these enhancers and corresponding genes including MHC class II, and more profoundly suppress CREBPP mutant lymphomas in vitro and in vivo. Hence CREBBP loss of function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3 targeted therapy as a precision approach for CREBBP mutant lymphomas.Copyright {copyright, serif}2016, American Association for Cancer Research.
Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation. - Circulation. Heart failure
Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure.A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125-150 mg/dL, 67-85 mg/dL, 32-42 mg/dL, and 97-126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212-0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092-0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support.Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support.© 2016 American Heart Association, Inc.
Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department. - BMJ open
Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage.This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug.This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial.NCT02521415.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme. - European journal of heart failure
We investigated the association between worsening renal function (WRF) that occurs during renin-angiotensin-aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF).We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m(2) with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03-1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality.GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF.© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.
Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation: Delayed CTLA4-Ig Treatment Prevents Memory Alloreactive B-Cell Generation. - Transplantation
The dual role of B cells as drivers and suppressors of the immune responses have underscored the need to trace the fate of B cells recognizing donor major histocompatibility complex class I and class II after allograft transplantation.In this study, we used donor class II tetramers to trace the fate of I-E-specific B cells after immunization with BALB/c spleen cells or cardiac transplantation, in naive or sensitized C57BL/6 recipients. We combined this approach with genetic lineage tracing of memory B cells in activation-induced cytidine deaminase regulated Cre transgenic mice crossed to the ROSA26-enhanced yellow fluorescent protein reporter mice to track endogenous I-E-specific memory B cell generation.Immunization with BALB/c splenocytes or heart transplantation induced an expansion and differentiation of I-E-specific B cells into germinal center B cells, whereas BALB/c heart transplantation into sensitized recipients induced the preferential differentiation into antibody-secreting cells. A 10.8-fold increase in the frequency of I-E-specific memory B cells was observed by day 42 postimmunization. Treatment with CTLA4-Ig starting on day 0 or day 7 postimmunization abrogated I-E-specific memory B cell generation and sensitized humoral responses, but not if treatment commenced on day 14.The majority of donor-specific memory B cells are generated between days 7 and 14 postimmunization, thus revealing a flexible timeframe whereby delayed CTLA4-Ig administration can inhibit sensitization and the generation of memory graft-reactive B cells.
The SLC28 (CNT) and SLC29 (ENT) nucleoside transporter families: a 30-year collaborative odyssey. - Biochemical Society transactions
Specialized nucleoside transporter (NT) proteins are required for passage of nucleosides and hydrophilic nucleoside analogues across biological membranes. Physiologic nucleosides serve as central salvage metabolites in nucleotide biosynthesis, and nucleoside analogues are used as chemotherapeutic agents in the treatment of cancer and antiviral diseases. The nucleoside adenosine modulates numerous cellular events via purino-receptor cell signalling pathways. Human NTs are divided into two structurally unrelated protein families: the SLC28 concentrative nucleoside transporter (CNT) family and the SLC29 equilibrative nucleoside transporter (ENT) family. Human CNTs are inwardly directed Na(+)-dependent nucleoside transporters found predominantly in intestinal and renal epithelial and other specialized cell types. Human ENTs mediate bidirectional fluxes of purine and pyrimidine nucleosides down their concentration gradients and are ubiquitously found in most, possibly all, cell types. Both protein families are evolutionarily old: CNTs are present in both eukaryotes and prokaryotes; ENTs are widely distributed in mammalian, lower vertebrate and other eukaryote species. This mini-review describes a 30-year collaboration with Professor Stephen Baldwin to identify and understand the structures and functions of these physiologically and clinically important transport proteins.© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.
Major advantages and critical challenge for the proposed United States heart allocation system. - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
The proposed new United States allocation system incorporates extensive research into an elegant plan designed to reduce wait list mortality while preserving post-transplant outcomes. All architects are to be congratulated. However, the future cannot be reliably modeled from the past as listing practices will evolve in response to new criteria. The new system should provide a major advance if and only if it is combined with a commitment to limit the number of listed patients overall and within each high priority status to the number that could reasonably undergo timely transplantation.Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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