Brandon Michael Henry

The Influence of Aging on the Regenerative Potential of Human Adipose Derived Mesenchymal Stem Cells

Tissue regeneration using human adipose derived mesenchymal stem cells (hASCs) has significant potential as a novel treatment for many degenerative bone and joint diseases. Previous studies have established that age negatively affects the proliferation status and the osteogenic and chondrogenic differentiation potential of mesenchymal stem cells. The aim of this study was to assess the age-related maintenance of physiological function and differentiation potential of hASCs in vitro. hASCs were isolated from patients of four different age groups: (1) >20 years (n = 7), (2) >50 years (n = 7), (3) >60 years (n = 7), and (4) >70 years (n = 7). The hASCs were characterized according to the number of fibroblasts colony forming unit (CFU-F), proliferation rate, population doubling time (PDT), and quantified parameters of adipogenic, chondrogenic, and osteogenic differentiation. Compared to younger cells, aged hASCs had decreased proliferation rates, decreased chondrogenic and osteogenic potential, and increased senescent features. A shift in favor of adipogenic differentiation with increased age was also observed. As many bone and joint diseases increase in prevalence with age, it is important to consider the negative influence of age on hASCs viability, proliferation status, and multilineage differentiation potential when considering the potential therapeutic applications of hASCs.

Methods of Evidence-Based Anatomy: a guide to conducting systematic reviews and meta-analysis of anatomical studies.

Evidence-Based Anatomy (EBA) is the concept of applying evidence-based principles and research methods to the anatomical sciences. While narrative reviews are common in the anatomical sciences, true systematic reviews (SR) and meta-analysis (MA) are only beginning to grow in popularity. In order to enhance the quality of future EBA studies, and ensure the clinical reliability of their results, a uniform methodology is needed. In this paper, we present a step-by-step methodological guide for performing SRs and MAs of anatomical studies. We address the EBA-specific challenges in each step of the SR and MA process, and discuss methods and strategies to overcome these difficulties. Furthermore, we discuss in detail the statistical methods used in MA of anatomical data, including multi-categorical and single-categorical pooled prevalence estimates, as well as pooled means of one group. Lastly, we discuss the major limitations of EBA, including the lack of a proper quality assessment tool for anatomical studies. The methods described in this paper present a uniform road map for future EBA studies.

Development of the Anatomical Quality Assurance (AQUA) checklist: Guidelines for reporting original anatomical studies

The rise of evidence‐based anatomy has emphasized the need for original anatomical studies with high clarity, transparency, and comprehensiveness in reporting. Currently, inconsistencies in the quality and reporting of such studies have placed limits on accurate reliability and impact assessment. Our aim was to develop a checklist of reporting items that should be addressed by authors of original anatomical studies. The study steering committee formulated a preliminary conceptual design and began to generate items on the basis of a literature review and expert opinion. This led to the development of a preliminary checklist. The validity of this checklist was assessed by a Delphi procedure, and feedback from the Delphi panelists, who were experts in the area of anatomical research, was used to improve it. The Delphi procedure involved 12 experts in anatomical research. It comprised two rounds, after which unanimous consensus was reached regarding the items to be included in the checklist. The steering committee agreed to name the checklist AQUA. The preliminary AQUA Checklist consisted of 26 items divided into eight sections. Following round 1, some of the items underwent major revision and three new ones were introduced. The checklist was revised only for minor language inaccuracies after round 2. The final version of the AQUA Checklist consisted of the initial eight sections with a total of 29 items. The steering committee hopes the AQUA Checklist will improve the quality and reporting of anatomical studies. Clin. Anat. 30:14–20, 2017.

Development of the anatomical quality assessment (AQUA) tool for the quality assessment of anatomical studies included in meta‐analyses and systematic reviews

Critical appraisal of anatomical studies is essential before the evidence from them undergoes meta‐epidemiological synthesis. However, no instrument for appraising anatomical studies with inherent applicability to different study designs is available. We aim to develop a generic yet comprehensive tool for assessing the quality of anatomical studies using a formal consensus method. The study steering committee formulated an initial conceptual design and generated items for a preliminary tool on the basis of a literature review and expert opinion. A Delphi procedure was then adopted to assess the validity of the preliminary tool. Feedback from the Delphi panelists was used to improve it. The Delphi procedure involved 12 experts in anatomical research. It comprised two rounds, after which unanimous consensus was reached about the items to be included. The preliminary tool consisted of 20 items, which were phrased as signaling questions and organized into five domains: 1. Aim and subject characteristics, 2. Study design, 3. Characterization of methods, 4. Descriptive anatomy, and 5. Results reporting. Each domain was set to end with a risk of bias question. Following round 1, some of the items underwent major revision, although agreement was reached regarding inclusion of all the domains and signaling questions in the preliminary tool. The tool was revised only for minor language inaccuracies after round 2. The AQUA Tool was designed to assess the quality and reliability of anatomical studies. It is currently undergoing a validation process. Clin. Anat. 30:6–13, 2017.

The Prevalence of Anatomical Variations of the Median Nerve in the Carpal Tunnel: A Systematic Review and Meta-Analysis

Background and Objective The course and branches of the median nerve (MN) in the wrist vary widely among the population. Due to significant differences in the reported prevalence of such variations, extensive knowledge on the anatomy of the MN is essential to avoid iatrogenic nerve injury. Our aim was to determine the prevalence rates of anatomical variations of the MN in the carpal tunnel and the most common course patterns and variations in its thenar motor branch (TMB). Study Design A systematic search of all major databases was performed to identify articles that studied the prevalence of MN variations in the carpal tunnel and the TMB. No date or language restrictions were set. Extracted data was classified according to Lanzs classification system: variations in the course of the single TMB—extraligamentous, subligamentous, and transligamentous (type 1); accessory branches of the MN at the distal carpal tunnel (type 2); high division of the MN (type 3); and the MN and its accessory branches proximal to the carpal tunnel (type 4). Pooled prevalence rates were calculated using MetaXL 2.0. Results Thirty-one studies (n = 3918 hands) were included in the meta-analysis. The pooled prevalence rates of the extraligamentous, subligamentous, and transligamentous courses were 75.2% (95%CI:55.4%-84.7%), 13.5% (95%CI:3.6%-25.7%), and 11.3% (95%CI:2.4%-23.0%), respectively. The prevalence of Lanz group 2, 3, and 4 were 4.6% (95%CI:1.6%-9.1%), 2.6% (95%CI:0.1%-2.8%), and 2.3% (95%CI:0.3%-5.6%), respectively. Ulnar side of branching of the TMB was found in 2.1% (95%CI:0.9%-3.6%) of hands. The prevalence of hypertrophic thenar muscles over the transverse carpal ligament was 18.2% (95%CI:6.8%-33.0%). A transligamentous course of the TMB was more commonly found in hands with hypertrophic thenar muscles (23.4%, 95%CI:5.0%-43.4%) compared to those without hypertrophic musculature (1.7%, 95%CI:0%-100%). In four studies (n = 423 hands), identical bilateral course of the TMB was found in 72.3% (95%CI:58.4%-84.4%) of patients. Conclusions Anatomical variations in the course of the TMB and the MN in the carpal tunnel are common in the population. Thus, we recommend an ulnar side approach to carpal tunnel release, with a careful layer by layer dissection, to avoid iatrogenic damage to the TMB.

The role of serum procalcitonin in the diagnosis of bacterial meningitis in adults: a systematic review and meta-analysis

OBJECTIVE Clinically, it is often difficult to differentiate between bacterial and viral aetiologies in adults with suspected meningitis. Several studies have demonstrated the potential use of serum procalcitonin (PCT) in making this differentiation. The aim was to pool these studies into a meta-analysis to determine the diagnostic accuracy of PCT. METHODS Major electronic databases were searched for articles studying the use of serum PCT in the differentiation of bacterial and viral meningitis in adult patients. No date or language restrictions were applied. Data analysis was performed using Meta-DiSc 1.4 and MIX 2.0. RESULTS Nine studies (n=725 patients) were included in the meta-analysis. Serum PCT was found to be a highly accurate test for diagnosing meningitis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) for PCT were 0.90 (95% confidence interval (CI) 0.84-0.94), 0.98 (95% CI 0.97-0.99), 27.3 (95% CI 8.2-91.1), 0.13 (95% CI 0.07-0.26), and 287.0 (95% CI 58.5-1409.0), respectively. PCT was found to be far superior to C-reactive protein, which had a pooled DOR of only 22.1 (95% CI 12.7-38.3). CONCLUSIONS Serum PCT is a highly accurate diagnostic test that can be used by physicians for rapid differentiation between bacterial and viral causes of meningitis in adults.

Median and Ulnar Nerve Anastomoses in the Upper Limb: A Meta-Analysis.

The most frequently described anomalous neural connections between the median and ulnar nerves in the upper limb are: Martin‐Gruber anastomosis (MGA), Marinacci anastomosis (MA), Riche‐Cannieu anastomosis (RCA), and Berrettini anastomosis (BA). The reported prevalence rates and characteristics of these anastomoses vary significantly between studies.

Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo.

Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine.

Procalcitonin as a Serum Biomarker for Differentiation of Bacterial Meningitis From Viral Meningitis in Children: Evidence From a Meta-Analysis

Several studies have explored the use of serum procalcitonin (PCT) in differentiating between bacterial and viral etiologies in children with suspected meningitis. We pooled these studies into a meta-analysis to determine the PCT diagnostic accuracy. All major databases were searched through March 2015. No date or language restrictions were applied. Eight studies (n = 616 pediatric patients) were included. Serum PCT assay was found to be very accurate for differentiating the etiology of pediatric meningitis with pooled sensitivity and specificity of 0.96 (95% CI = 0.92-0.98) and 0.89 (95% CI = 0.86-0.92), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) for PCT were 7.5 (95% CI = 5.6-10.1), 0.08(95% CI = 0.04-0.14), 142.3 (95% CI = 59.5-340.4), and 0.97 (SE = 0.01), respectively. In 6 studies, PCT was found to be superior than CRP, whose DOR was only 16.7 (95%CI = 8.8-31.7). Our meta-analysis demonstrates that serum PCT assay is a highly accurate and powerful test for rapidly differentiating between bacterial and viral meningitis in children.

Anatomical variations of the formation and course of the sural nerve: A systematic review and meta-analysis

INTRODUCTION The sural nerve (SN) is a sensory nerve in the lower extremity which branches to supply the skin on the distal posterolateral third of the lower limb. Typically, the medial sural cutaneous nerve (MSCN) and the peroneal communicating nerve (PCN) unite to form the SN. Other variations in the formation, course, and morphometry of the SN have also been described in the literature. OBJECTIVE To study anatomical variations in the formation and course of the SN and establish a new classification system for formation patterns of the SN. METHODS A systematic search of all major databases identified articles that studied the prevalence of variations in the formation of the SN. No date or language restrictions were set. Anatomical data was extracted according to our new classification system where the SN is formed by: union of the MSCN and the PCN (Type 1); union of the MSCN and the Lateral Sural Cutaneous Nerve (LSCN) (Type 2); continuation of the MSCN with absent PCN (Type 3); the PCN alone (Type 4); the LSCN (Type 5); or the Sciatic Nerve (SCN) directly (Type 6). Pooled prevalence rates were calculated using MetaXL 2.0. RESULTS A total of 39 studies (n=3974 limbs) were included in the meta-analysis. The most common patterns were Type 1, Type 3, and Type 2 with a pooled prevalence of 51.5% (95% CI: 0.293-0.591), 31.2% (95% CI: 0.143-0.410), and 13.8% (95% CI: 0.035-0.234), respectively. The rest of the patterns were rare, with pooled prevalence of Types 4, 5, and 6 calculated to be 1.8% (95% CI: 0-0.063), 1.1% (95% CI: 0-0.050), and 0.7% (95% CI: 0-0.041), respectively. In 83.7% (95% CI: 0.765-0.899) of limbs, the site of union was in the lower half of the lower extremity. The pooled mean length of the SN from the formation to the lateral malleolus was 14.78 (±5.76) cm, while the mean diameter of the SN was 0.28 (±0.03) cm. CONCLUSIONS Anatomical variations in the formation and course of the SN are common in the population. Clinicians, especially surgeons, should be aware of these variations to avoid iatrogenic injury to the nerve during operative procedures.