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PPARγ agonists delay age-associated metabolic disease and extend longevity
Xu, Lingyan; Ma, Xinran; Verma, Narendra; Perie, Luce; Pendse, Jay; Shamloo, Sama; Marie Josephson, Anne; Wang, Dongmei; Qiu, Jin; Guo, Mingwei; Ping, Xiaodan; Allen, Michele; Noguchi, Audrey; Springer, Danielle; Shen, Fei; Liu, Caizhi; Zhang, Shiwei; Li, Lingyu; Li, Jin; Xiao, Junjie; Lu, Jian; Du, Zhenyu; Luo, Jian; Aleman, Jose O; Leucht, Philipp; Mueller, Elisabetta
Aging leads to a number of disorders caused by cellular senescence, tissue damage, and organ dysfunction. It has been reported that anti-inflammatory and insulin-sensitizing compounds delay, or reverse, the aging process and prevent metabolic disorders, neurodegenerative disease, and muscle atrophy, improving healthspan and extending lifespan. Here we investigated the effects of PPARγ agonists in preventing aging and increasing longevity, given their known properties in lowering inflammation and decreasing glycemia. Our molecular and physiological studies show that long-term treatment of mice at 14 months of age with low doses of the PPARγ ligand rosiglitazone (Rosi) improved glucose metabolism and mitochondrial functionality. These effects were associated with decreased inflammation and reduced tissue atrophy, improved cognitive function, and diminished anxiety- and depression-like conditions, without any adverse effects on cardiac and skeletal functionality. Furthermore, Rosi treatment of mice started when they were 14 months old was associated with lifespan extension. A retrospective analysis of the effects of the PPARγ agonist pioglitazone (Pio) on longevity showed decreased mortality in patients receiving Pio compared to those receiving a PPARγ-independent insulin secretagogue glimepiride. Taken together, these data suggest the possibility of using PPARγ agonists to promote healthy aging and extend lifespan.
PMCID:7681041
PMID: 33219735
ISSN: 1474-9726
CID: 4679992
Incidence of Osteomyelitis in Sacral Decubitus Ulcers and Recommendations for Management
Crespo, Alexander; Stevens, Nicole M; Chiu, Ernest; Pham, Vinh; Leucht, Philipp
PMID: 33006456
ISSN: 2329-9185
CID: 4615872
Modification of a Validated Risk Stratification Tool to Characterize Geriatric Hip Fracture Outcomes and Optimize Care in a Post-COVID-19 World
Konda, Sanjit R; Ranson, Rachel A; Solasz, Sara J; Dedhia, Nicket; Lott, Ariana; Bird, Mackenzie L; Landes, Emma K; Aggarwal, Vinay K; Bosco, Joseph A; Furgiuele, David L; Gould, Jason; Lyon, Thomas R; McLaurin, Toni M; Tejwani, Nirmal C; Zuckerman, Joseph D; Leucht, Philipp; Ganta, Abhishek; Egol, Kenneth A
OBJECTIVES:(1) To demonstrate how a risk assessment tool modified to account for the COVID-19 virus during the current global pandemic is able to provide risk assessment for low-energy geriatric hip fracture patients. (2) To provide a treatment algorithm for care of COVID-19 positive/suspected hip fractures patients that accounts for their increased risk of morbidity and mortality. SETTING:One academic medical center including 4 Level 1 trauma centers, 1 university-based tertiary care referral hospital, and 1 orthopaedic specialty hospital. PATIENTS/PARTICIPANTS:One thousand two hundred seventy-eight patients treated for hip fractures between October 2014 and April 2020, including 136 patients treated during the COVID-19 pandemic between February 1, 2020 and April 15, 2020. INTERVENTION:The Score for Trauma Triage in the Geriatric and Middle-Aged ORIGINAL (STTGMAORIGINAL) score was modified by adding COVID-19 virus as a risk factor for mortality to create the STTGMACOVID score. Patients were stratified into quartiles to demonstrate differences in risk distribution between the scores. MAIN OUTCOME MEASUREMENTS:Inpatient and 30-day mortality, major, and minor complications. RESULTS:Both STTGMA score and COVID-19 positive/suspected status are independent predictors of inpatient mortality, confirming their use in risk assessment models for geriatric hip fracture patients. Compared with STTGMAORIGINAL, where COVID-19 patients are haphazardly distributed among the risk groups and COVID-19 inpatient and 30 days mortalities comprise 50% deaths in the minimal-risk and low-risk cohorts, the STTGMACOVID tool is able to triage 100% of COVID-19 patients and 100% of COVID-19 inpatient and 30 days mortalities into the highest risk quartile, where it was demonstrated that these patients have a 55% rate of pneumonia, a 35% rate of acute respiratory distress syndrome, a 22% rate of inpatient mortality, and a 35% rate of 30 days mortality. COVID-19 patients who are symptomatic on presentation to the emergency department and undergo surgical fixation have a 30% inpatient mortality rate compared with 12.5% for patients who are initially asymptomatic but later develop symptoms. CONCLUSION:The STTGMA tool can be modified for specific disease processes, in this case to account for the COVID-19 virus and provide a robust risk stratification tool that accounts for a heretofore unknown risk factor. COVID-19 positive/suspected status portends a poor outcome in this susceptible trauma population and should be included in risk assessment models. These patients should be considered a high risk for perioperative morbidity and mortality. Patients with COVID-19 symptoms on presentation should have surgery deferred until symptoms improve or resolve and should be reassessed for surgical treatment versus definitive nonoperative treatment with palliative care and/or hospice care. LEVEL OF EVIDENCE:Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.
PMID: 32815845
ISSN: 1531-2291
CID: 4574902
Can lessons learned about preventing cardiac muscle death be applied to prevent skeletal muscle death?
Buchalter, Daniel B; Kirby, David J; Egol, Kenneth A; Leucht, Philipp; Konda, Sanjit R
PMCID:7376282
PMID: 32728425
ISSN: 2046-3758
CID: 4540372
Transcription Error Rates in Retrospective Chart Reviews
Feng, James E; Anoushiravani, Afshin A; Tesoriero, Paul J; Ani, Lidia; Meftah, Morteza; Schwarzkopf, Ran; Leucht, Philipp
Electronic health record (EHR) technologies have improved the ease of access to structured clinical data. The standard means by which data are collected continues to be manual chart review. The authors compared the accuracy of manual chart review against modern electronic data warehouse queries. A manual chart review of the EHR was performed with medical record numbers and surgical admission dates for the 100 most recent inpatient venous thromboembolic events after total joint arthroplasty. A separate data query was performed with the authors' electronic data warehouse. Data sets were then algorithmically compared to check for matches. Discrepancies between data sets were evaluated to categorize errors as random vs systematic. From 100 unique patient encounters, 27 variables were retrieved. The average transcription error rate was 9.19% (SD, ±5.74%) per patient encounter and 11.04% (SD, ±21.40%) per data variable. The systematic error rate was 7.41% (2 of 27). When systematic errors were excluded, the random error rate was 5.79% (SD, ±7.04%) per patient encounter and 5.44% (SD, ±5.63%) per data variable. Total time and average time for manual data collection per patient were 915 minutes and 10.3±3.89 minutes, respectively. Data collection time for the entire electronic query was 58 seconds. With an error rate of 10%, manual chart review studies may be more prone to type I and II errors. Computer-based data queries can improve the speed, reliability, reproducibility, and scalability of data retrieval and allow hospitals to make more data-driven decisions. [Orthopedics. 2020;43(x):xx-xx.].
PMID: 32602916
ISSN: 1938-2367
CID: 4504072
DHEA in bone: the role in osteoporosis and fracture healing
Kirby, David J; Buchalter, Daniel B; Anil, Utkarsh; Leucht, Philipp
Dehydroepiandrosterone (DHEA) is a metabolic intermediate in the biosynthesis of estrogens and androgens with a past clouded in controversy and bold claims. It was once touted as a wonder drug, a fountain of youth that could cure all ailments. However, in the 1980s DHEA was banned by the FDA given a lack of documented health benefits and long-term use data. DHEA had a revival in 1994 when it was released for open market sale as a nutritional supplement under the Dietary Supplement Health and Safety Act. Since that time, there has been encouraging research on the hormone, including randomized controlled trials and subsequent meta-analyses on various conditions that DHEA may benefit. Bone health has been of particular interest, as many of the metabolites of DHEA are known to be involved in bone homeostasis, specifically estrogen and testosterone. Studies demonstrate a significant association between DHEA and increased bone mineral density, likely due to DHEA's ability to increase osteoblast activity and insulin like growth factor 1 (IGF-1) expression. Interestingly, IGF-1 is also known to improve fracture healing, though DHEA, a potent stimulator of IGF-1, has never been tested in this scenario. The aim of this review is to discuss the history and mechanisms of DHEA as they relate to the skeletal system, and to evaluate if DHEA has any role in treating fractures.
PMID: 32504237
ISSN: 1862-3514
CID: 4477592
Increased Mortality and Major Complications in Hip Fracture Care During the COVID-19 Pandemic: A New York City Perspective
Egol, Kenneth A; Konda, Sanjit R; Bird, Mackenzie L; Dedhia, Nicket; Landes, Emma K; Ranson, Rachel A; Solasz, Sara J; Aggarwal, Vinay K; Bosco, Joseph A; Furgiuele, David L; Ganta, Abhishek; Gould, Jason; Lyon, Thomas R; McLaurin, Toni M; Tejwani, Nirmal C; Zuckerman, Joseph D; Leucht, Philipp
OBJECTIVES/OBJECTIVE:To examine one health system's response to the essential care of its hip fracture population during the COVID-19 pandemic and report on its effect on patient outcomes. DESIGN/METHODS:Prospective cohort study SETTING:: Seven musculoskeletal care centers with New York City and Long Island. PATIENTS/PARTICIPANTS/METHODS:138 recent and 115 historical hip fracture patients. INTERVENTION/METHODS:Patients with hip fractures occurring between February 1, 2020 and April 15, 2020 or between February 1, 2019 and April 15, 2019 were prospectively enrolled in an orthopedic trauma registry and chart reviewed for demographic and hospital quality measures. Patients with recent hip fractures were identified as COVID positive (C+), COVID suspected (Cs) or COVID negative (C-). MAIN OUTCOME MEASUREMENTS/METHODS:Hospital quality measures, inpatient complications and mortality rates. RESULTS:Seventeen (12.2%) patients were confirmed C+ by testing and another 14 (10.1%) were suspected (Cs) of having had the virus but were never tested. The C+ cohort, when compared to Cs and C- cohorts, had: an increased mortality rate (35.3% vs 7.1% vs 0.9%), increased length of hospital stay, a greater major complication rate and a greater incidence of ventilator need postoperatively. CONCLUSIONS:COVID-19 had a devastating effect on the care of hip fracture patients during the pandemic. Although practice patterns generally remained unchanged, treating physicians need to understand the increased morbidity and mortality in hip fracture patients complicated by COVID-19. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.
PMID: 32482976
ISSN: 1531-2291
CID: 4468782
Can Glucose-Insulin-Potassium Prevent Skeletal Muscle Ischemia-Reperfusion Injury?
Buchalter, Daniel B; Kirby, David J; Egol, Kenneth A; Leucht, Philipp; Konda, Sanjit R
ORIGINAL:0014636
ISSN: 2642-1747
CID: 4428922
Free Tissue Transfer with Distraction Osteogenesis and Masquelet Technique Is Effective for Limb Salvage in Patients with Gustilo Type IIIB Open Fractures
Abdou, Salma A; Stranix, John T; Daar, David A; Mehta, Devan D; McLaurin, Toni; Tejwani, Nirmal; Saadeh, Pierre B; Levine, Jamie P; Leucht, Philipp; Thanik, Vishal D
Osteocutaneous reconstruction can be challenging because of concomitant injuries and limited donor sites. There is a paucity of data on limb salvage outcomes following combined soft-tissue reconstruction and bone transport or Masquelet procedures. The authors reviewed a consecutive series of open tibia fracture patients undergoing soft-tissue reconstruction with either distraction osteogenesis or Masquelet technique. Endpoints were perioperative flap complications and bone union. Fourteen patients with Gustilo type IIIB open tibia fractures were included. Half of the group received muscle flaps and the remaining half received fasciocutaneous flaps. Ten patients (71.4 percent) underwent distraction osteogenesis and the remaining patients underwent Masquelet technique. Average bone gap length was 65.7 ± 31.3 mm (range, 20 to 120 mm). In the bone transport group, the average external fixation duration was 245 days (range, 47 to 686 days). In the Masquelet group, the average duration of the first stage of this two-stage procedure (i.e., time from cement spacer placement to bone grafting) was 95 days (range, 42 to 181 days). Bone union rate, as determined by radiographic evidence, was 85.7 percent. There was one complete flap failure (7.1 percent). One patient underwent below-knee amputation after failing bone transport and developing chronic osteomyelitis and subsequent infected nonunion. Our case series demonstrates that nonosteocutaneous flap methods of limb reconstruction are a viable option in patients with segmental long bone defects, with a bone union rate of 85 percent and a limb salvage rate over 90 percent in patients with Gustilo type IIIB fractures. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.
PMID: 32221236
ISSN: 1529-4242
CID: 4369902
Author Correction: Hox gene expression determines cell fate of adult periosteal stem/progenitor cells
Bradaschia-Correa, Vivian; Leclerc, Kevin; Josephson, Anne M; Lee, Sooyeon; Palma, Laura; Litwa, Hannah P; Neibart, Shane S; Huo, Jason C; Leucht, Philipp
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PMID: 32066822
ISSN: 2045-2322
CID: 4312062