Publications by authors named "Hilal M Kremers"

5 Publications

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Trends in Incidence of Adolescent Idiopathic Scoliosis: A Modern US Population-based Study.

J Pediatr Orthop 2021 Jul;41(6):327-332

Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN.

Background: A successful disease screening strategy requires a high incidence of the condition, efficacy of early treatment, and efficient detection. There is limited population-based data describing trends in incidence of adolescent idiopathic scoliosis (AIS) in the United States and potential role of school screening programs on the incidence of AIS. Thus, we sought to evaluate the incidence of AIS over a 20-year period between 1994 and 2013 using a population-based cohort.

Methods: The study population comprised 1782 adolescents (aged 10 to 18 y) with AIS first diagnosed between January 1, 1994 and December 31, 2013. The complete medical records and radiographs were reviewed to confirm diagnosis and coronal Cobb angles at first diagnosis. Age-specific and sex-specific incidence rates were calculated and adjusted to the 2010 United States population. Poisson regression analyses were performed to examine incidence trends by age, sex, and calendar period.

Results: The overall age-adjusted and sex-adjusted annual incidence of AIS was 522.5 [95% confidence interval (CI): 498.2, 546.8] per 100,000 person-years. Incidence was about 2-fold higher in females than in males (732.3 vs. 338.8/100,000, P<0.05). The incidence of newly diagnosed AIS cases with radiographs showing a Cobb angle >10 degrees was 181.7 (95% CI: 167.5, 196.0) per 100,000 person-years. The overall incidence of AIS decreased significantly after discontinuation of school screening in 2004 (P<0.001). The incidence of bracing and surgery at initial diagnosis was 16.6 (95% CI: 12.3, 20.9) and 2.0 (95% CI: 0.5, 3.4) per 100,000 person-years, respectively.

Conclusions: Overall population-based incidence of AIS decreased after school screening was discontinued. However, incidence of patients with a Cobb angle >10 degrees, initiation of bracing and surgery did not change significantly over time. This provides further data to help determine the role of scoliosis screening.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BPO.0000000000001808DOI Listing
July 2021

Intra-articular injection of a substance P inhibitor affects gene expression in a joint contracture model.

J Cell Biochem 2018 02 20;119(2):1326-1336. Epub 2017 Nov 20.

Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota.

Substance P (SP), a neurotransmitter released after injury, has been linked to deregulated tissue repair and fibrosis in musculoskeletal tissues and other organs. Although SP inhibition is an effective treatment for nausea, it has not been previously considered as an anti-fibrotic therapy. Although there are extensive medical records of individuals who have used SP antagonists, our analysis of human registry data revealed that patients receiving these antagonists and arthroplasty are exceedingly rare, thus precluding a clinical evaluation of their potential effects in the context of arthrofibrosis. Therefore, we pursued in vivo studies to assess the effect of SP inhibition early after injury on pro-fibrotic gene expression and contractures in an animal model of post-traumatic joint stiffening. Skeletally mature rabbits (n = 24) underwent surgically induced severe joint contracture, while injected with either fosaprepitant (a selective SP antagonist) or saline (control) early after surgery (3, 6, 12, and 24 h). Biomechanical testing revealed that differences in mean contracture angles between the groups were not statistically significant (P = 0.27), suggesting that the drug neither mitigates nor exacerbates joint contracture. However, microarray gene expression analysis revealed that mRNA levels for proteins related to cell signaling, pro-angiogenic, pro-inflammatory, and collagen matrix production were significantly different between control and fosaprepitant treated rabbits (P < 0.05). Hence, our study demonstrates that inhibition of SP alters expression of pro-fibrotic genes in vivo. This finding will motivate future studies to optimize interventions that target SP to reduce the formation of post-traumatic joint contractures.
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http://dx.doi.org/10.1002/jcb.26256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388635PMC
February 2018

Osteogenic potential of human adipose-tissue-derived mesenchymal stromal cells cultured on 3D-printed porous structured titanium.

Gene 2016 May 13;581(2):95-106. Epub 2016 Jan 13.

Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Department of Biomedical Engineering and Physiology, Mayo Graduate School, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. Electronic address:

Integration of porous metal prosthetics, which restore form and function of irreversibly damaged joints, into remaining healthy bone is critical for implant success. We investigated the biological properties of adipose-tissue-derived mesenchymal stromal/stem cells (AMSCs) and addressed their potential to alter the in vitro microenvironment of implants. We employed human AMSCs as a practical source for musculoskeletal applications because these cells can be obtained in large quantities, are multipotent, and have trophic paracrine functions. AMSCs were cultured on surgical-grade porous titanium disks as a model for orthopedic implants. We monitored cell/substrate attachment, cell proliferation, multipotency, and differentiation phenotypes of AMSCs upon osteogenic induction. High-resolution scanning electron microscopy and histology revealed that AMSCs adhere to the porous metallic surface. Compared to standard tissue culture plastic, AMSCs grown in the porous titanium microenvironment showed differences in temporal expression for genes involved in cell cycle progression (CCNB2, HIST2H4), extracellular matrix production (COL1A1, COL3A1), mesenchymal lineage identity (ACTA2, CD248, CD44), osteoblastic transcription factors (DLX3, DLX5, ID3), and epigenetic regulators (EZH1, EZH2). We conclude that metal orthopedic implants can be effectively seeded with clinical-grade stem/stromal cells to create a pre-conditioned implant.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054723PMC
http://dx.doi.org/10.1016/j.gene.2016.01.015DOI Listing
May 2016

Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee.

J Orthop Res 2016 Feb 29;34(2):177-86. Epub 2015 Dec 29.

Department of Orthopedic Surgery, Mayo Clinic, 200 1st St SW, Rochester, Minnesota 55905.

Like any foreign object, orthopaedic implants are susceptible to infection when introduced into the human body. Without additional preventative measures, the absolute number of annual prosthetic joint infections will continue to rise, and may exceed the capacity of health care systems in the near future. Bacteria are difficult to eradicate from synovial joints due to their exceptionally diverse taxonomy, complex mechanistic attachment capabilities, and tendency to evolve antibiotic resistance. When a primary orthopaedic implant fails from prosthetic joint infection, surgeons are generally challenged by limited options for intervention. In this review, we highlight the etiology and taxonomic groupings of bacteria known to cause prosthetic joint infections, and examine their key mechanisms of attachment. We propose that antimicrobial strategies should focus on the most harmful bacteria taxa within the context of occurrence, taxonomic diversity, adhesion mechanisms, and implant design. Patient-specific identification of organisms that cause prosthetic joint infections will permit assessment of their biological vulnerabilities. The latter can be targeted using a range of antimicrobial techniques that exploit different colonization mechanisms including implant surface attachment, biofilm formation, and/or hematogenous recruitment. We anticipate that customized strategies for each patient, joint, and prosthetic component will be most effective at reducing prosthetic joint infections, including those caused by antibiotic-resistant and polymicrobial bacteria.
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http://dx.doi.org/10.1002/jor.23068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824296PMC
February 2016

Using RxNorm and NDF-RT to classify medication data extracted from electronic health records: experiences from the Rochester Epidemiology Project.

AMIA Annu Symp Proc 2011 22;2011:1089-98. Epub 2011 Oct 22.

Mayo Clinic, Rochester, MN, USA.

RxNorm and NDF-RT published by the National Library of Medicine (NLM) and Veterans Affairs (VA), respectively, are two publicly available federal medication terminologies. In this study, we evaluate the applicability of RxNorm and National Drug File-Reference Terminology (NDF-RT) for extraction and classification of medication data retrieved using structured querying and natural language processing techniques from electronic health records at two different medical centers within the Rochester Epidemiology Project (REP). Specifically, we explore how mappings between RxNorm concept codes and NDF-RT drug classes can be leveraged for hierarchical organization and grouping of REP medication data, identify gaps and coverage issues, and analyze the recently released NLM's NDF-RT Web service API. Our study concludes that RxNorm and NDF-RT can be applied together for classification of medication extracted from multiple EHR systems, although several issues and challenges remain to be addressed. We further conclude that the Web service APIs developed by the NLM provide useful functionalities for such activities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243205PMC
February 2013