P4‐026: Use of statins, LDL‐C and incidence of cognitive impairment or dementia in a seven‐year cohort study of older Mexican‐Americans

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152653/1/alzjjalz2008052090.pd

From Bench to Bedside: Review of Gene and Cell-Based Therapies and the Slow Advancement into Phase 3 Clinical Trials, with a Focus on Aastrom’s Ixmyelocel-T

There is a large body of preclinical research demonstrating the efficacy of gene and cellular therapy for the potential treatment of severe (limb-threatening) peripheral arterial disease (PAD), including evidence for growth and transcription factors, monocytes, and mesenchymal stem cells. While preclinical research has advanced into early phase clinical trials in patients, few late-phase clinical trials have been conducted. The reasons for the slow progression of these therapies from bench to bedside are as complicated as the fields of gene and cellular therapies. The variety of tissue sources of stem cells (embryonic, adult bone marrow, umbilical cord, placenta, adipose tissue, etc.); autologous versus allogeneic donation; types of cells (hematopoietic, mesenchymal stromal, progenitor, and mixed populations); confusion and stigmatism by the public and patients regarding gene, protein, and stem cell therapy; scaling of manufacturing; and the changing regulatory environment all contribute to the small number of late phase (Phase 3) clinical trials and the lack of Food and Drug Administration (FDA) approvals. This review article provides an overview of the progression of research from gene therapy to the cellular therapy field as it applies to peripheral arterial disease, as well as the position of Aastrom’s cellular therapy, ixmyelocel-T, within this field

Impact of lipid -lowering agents on the incidence of dementia and type 2 diabetes. A population-based cohort study in older Mexican Americans living in the Sacramento area of California.

Lipid-lowering agents (LLAs) such as statins have been shown to have beneficial effects on cardiovascular events in patients with cardiovascular risk factors. The evidence that statins positively affect the incidence of conditions with outcomes sharing a common pathway with cardiovascular disease, such as dementia and type 2 diabetes, is inconsistent in data collected in clinical intervention and observational studies. This dissertation investigates the effects of lipid-lowering agents, the majority of which are statins, on incidence of dementia, on incidence of dementia in diabetics compared to nondiabetics, and on incidence of type 2 diabetes. The study was based on data from a prospective cohort study (Sacramento Area Latino Study of Aging [SALSA]) in a population comprised of 1789 older (>60 years of age) community-dwelling Mexican Americans. A multistage process was used for the evaluation of dementia and cognitive impairment not demented (CIND). Participants who fell below predetermined scoring results were evaluated clinically by an adjudication team. Dementia was diagnosed using DMS-IV criteria. In the analyses, dementia and CIND were combined into one variable: dementia/CIND. Type 2 diabetes status was determined by (1) fasting plasma glucose level ≥126 mg/dL; or (2) use of an antidiabetic medication; or (3) self-report of a doctor's diagnosis of type 2 diabetes. LLA-use was ascertained at each participant's home annually by direct inspection. Cox Proportional Hazards models were used to assess the association between LLA-use and incidence of dementia/CIND and on incidence of type 2 diabetes. LLA-use was modeled as a time-dependent variable. Results from this cohort study showed that lipid-lowering agents appeared to decrease the risk of dementia/CIND over a 5-year followup period in a population of Mexican Americans. Nondiabetics who used LLAs or statins had the lowest incidence of dementia/CIND compared to all other combinations of diabetes status and LLA-use. Diabetics who did not use LLAs had the highest incidence of dementia/CIND compared to all other combinations of diabetes status and LLA-use. In the evaluation of the association between LLA-use and incidence of type 2 diabetes, LLAs did not impact the incidence of type 2 diabetes over the 5-year followup period in this population of Mexican Americans.Ph.D.EpidemiologyGerontologyHealth and Environmental SciencesHispanic American studiesPublic healthSocial SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126658/2/3276126.pd

Use of statins and incidence of dementia in a population-based cohort study.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60438/1/cramer_statins and incidence of dementia_2008.pd

CEA graft take after combining with a modified MEEK procedure

Resourceful surgical planning for coverage of large burns has led to refinement of early innovative procedures including meshed split thickness skin grafts (STSG), MEEK procedure, and use of cultured epidermal autografts (CEAs). The use of STSG remains standard of care for burn wound coverage; however, manual expansion of STSG is limited due to shortcomings with expansion rates greater than 4:1. The MEEK micrografting method is a method of preparing skin grafts with a device instead of manually with an autograft mesher, allowing reliable expansion rates of autografts up to 9:1. Although the CEA indication for use includes both with and without STSG, use of meshed STSG placed under CEA has been reported to minimize shear forces and hasten graft take. The purpose of this study was to evaluate success of graft take in patients receiving MEEK and CEA for wound coverage in extensive burns at a single burn center experienced in the use of both MEEK and CEA. Data in 15 patients who received both MEEK and CEA for the treatment of large burns (mean total body surface area [TBSA] of 66%) demonstrated a high rate of successful engraftment (87%), and an overall 73% survival rate

Use Of Statins And Incidence Of Dementia And Cognitive Impairment Without Dementia In A Cohort Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62029/1/haan_use of statins_2009.pd

Report of outcomes in burn patients enrolled in the Cultured epidermal autograft prospective Registry

Cultured epidermal autograft (CEA) is a permanent skin replacement indicated for use in adult and pediatric patients with deep dermal or full thickness burns comprising a total body surface area (TBSA) ≥ 30 %. CEA (Epicel®) was approved for use in adults in the United States in 2007 as a Humanitarian Use Device (HUD) under a Humanitarian Device Exemption (HDE) and was approved for pediatric use in 2016. In 2019, a CEA Registry was established with an objective of prospective data collection and analysis of demographic, treatment, and outcome data for the real-world use of CEA. At the time of data cut–off (June 2022), 68 patients (50 adults and 18 children) had completed data in the registry, up through hospital discharge, for this analysis. Mean total body surface area (TBSA) of the burn was 58 % in adults and 56 % in pediatric patients, and almost half had inhalation injury in each group. Approximately 74 % of adults and 67 % of pediatric patients had TBSA ≥ 50 %. Overall survival was 87 % (84 % adults, 94 % pediatric). Mean % graft take (engraftment) of CEA was 81 % in adults and 84 % in pediatric patients. Outcomes from this prospective collection of data in severely burned patients treated with CEA demonstrate favorable engraftment and survival rates and are in general agreement with recent literature

Consensus on Rehabilitation Guidelines among Orthopedic Surgeons in the United States following Use of Third-Generation Articular Cartilage Repair (MACI) for Treatment of Knee Cartilage Lesions

ObjectiveThe aim of this study was to evaluate levels of consensus in rehabilitation practices following MACI (autologous cultured chondrocytes on porcine collagen membrane) treatment based on the experience of an expert panel of U.S. orthopedic surgeons.DesignA list of 24 questions was devised based on the current MACI rehabilitation protocol, literature review, and discussion with orthopedic surgeons. Known areas of variability were used to establish 4 consensus domains, stratified on lesion location (tibiofemoral [TF] or patellofemoral [PF]), including weightbearing (WB), range of motion (ROM), return to work/daily activities of living, and return to sports. A 3-step Delphi technique was used to establish consensus.ResultsConsensus (>75% agreement) was achieved on all 4 consensus domains. Time to full WB was agreed as immediate (with bracing) for PF patients (dependent on concomitant procedures), and 7 to 9 weeks in TF patients. A progression for ROM was agreed that allowed patients to reach 90° by week 4, with subsequent progression as tolerated. The panel estimated that the time to full ROM would be 7 to 9 weeks on average. A range of time was established for release to activities of daily living, work, and sports, dependent on lesion and patient characteristics.ConclusionsGood consensus was established among a panel of U.S. surgeons for rehabilitation practices following MACI treatment of knee cartilage lesions. The consensus of experts can aid surgeons and patients in the expectations and rehabilitation process as MACI surgery becomes more prevalent in the United States