Basic Science of Autologous Orthobiologics: Part 2. Mesenchymal Stem Cells.

In recent years, autologous biological preparations have emerged as a growing area of medical innovation in interventional orthopedical procedures and surgical interventions. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, like blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC), respectively. In this article, we emphasize and discuss the physiologic variability of autologous prepared BMC and ATC for the delivery of mesenchymal stem cells to support tissue repair processes.

Basic Science of Allograft Orthobiologics.

Orthobiologic procedures are based on altering the microenvironment of musculoskeletal tissues to induce an anti-inflammatory effect and reduce pain, promote healing of these tissues, or provide mechanical support. Allograft tissues have these inherent qualities and can be used as such. This could provide patients whose own autologous tissues may be compromised or have contraindications to harvesting an alternative to treat their orthopedic conditions. Although these allograft therapies are promising, they lack high-quality clinical studies and regulatory guidelines currently limit their use.

Diabetic foot disease: a systematic literature review of patient-reported outcome measures.

PURPOSE: Diabetic foot disease is one of the most serious and expensive complications of diabetes. Patient-reported outcome measures (PROMs) analyse patients' perception of their disability, functionality and health. The goal of this work was to conduct a systematic review regarding the specific PROMs related to the evaluation of diabetic foot disease and to extract and analyse the values of their measurement properties. METHODS: Electronic databases included were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. The search terms used were foot, diabet*, diabetic foot, questionnaire, patient-reported outcome, self-care, valid*, reliabil*. Studies whose did not satisfy the Critical Appraisals Skills Programme (CASP) Diagnostic Study Checklist were excluded. The measurement properties extracted were: Internal Consistency, Test-retest, Inter-rater and Intra-rater, Standard Error of Measurement, Minimum Detectable Measurement Difference, Content Validity, Construct Validity, Criterion Validity and Responsiveness. RESULTS: The PROMs selected for this review were 12 questionnaires. The Diabetic foot self-care questionnaire (DFSQ-UMA) and the Questionnaire for Diabetes Related Foot Disease (Q-DFD) were the PROMs that showed the highest number of completed measurement properties. CONCLUSION: According to the results, it is relevant to create specific questionnaires for the evaluation of diabetic foot disease. It seems appropriate to use both DFSQ-UMA and Q-DFD when assessing patients with diabetic foot disease.

Clinician Assessment Tools for Patients with Diabetic Foot Disease: A Systematic Review.

The amputation rate in patients with diabetes is 15 to 40 times higher than in patients without diabetes. To avoid major complications, the identification of high-risk in patients with diabetes through early assessment highlights as a crucial action. Clinician assessment tools are scales in which clinical examiners are specifically trained to make a correct judgment based on patient outcomes that helps to identify at-risk patients and monitor the intervention. The aim of this study is to carry out a systematic review of valid and reliable Clinician assessment tools for measuring diabetic foot disease-related variables and analysing their psychometric properties. The databases used were PubMed, Scopus, SciELO, CINAHL, Cochrane, PEDro, and EMBASE. The search terms used were foot, ankle, diabetes, diabetic foot, assessment, tools, instruments, score, scale, validity, and reliability. The results showed 29 validated studies with 39 Clinician assessment tools and six variables. There is limited evidence on all of the psychometric characteristics of the Clinician assessment tools included in this review, although some instruments have been shown to be valid and reliable for the assessment of diabetic neuropathy (Utah Early Neuropathy Scale or UENS); ulceration risk (Queensland High Risk Foot Form or QHRFF); diabetic foot ulcer assessment, scoring, and amputation risk (Perfusion, extent, depth, infection and sensation scale or PEDIS and Site, Ischemia, Neuropathy, Bacterial Infection, and Depth score or SINBAD); and diabetic foot ulcer measurement (Leg Ulcer Measurement Tool LUMT).

Instruments of Choice for Assessment and Monitoring Diabetic Foot: A Systematic Review.

Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or clinical instruments that provide objective values for result measurement. The aim of this study was to carry out a systematic review of specific objective clinical outcome measures focused on the assessment and monitoring of diabetic foot disorders. The databases used were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. Search terms used were foot, ankle, diabet*, diabetic foot, assessment, tools, instruments, objective outcome measures, valid*, reliab*. Because of the current published evidence, diabetic neuropathy assessment via sudomotor analysis, cardiovascular autonomic neuropathy and peripheral vascular disease detection by non-invasive electronic devices, wound 3D dimensional measurement, hyperspectral imaging for ulcer prediction and the probe-to-bone test for osteomyelitis diagnosis were highlighted in this study.

Ultrasound Assessment of the Superior Capsular Reconstruction With Dermal Allograft: An Evaluation of Graft Thickness and Vascularity.

PURPOSE: To assess postoperative changes in the thickness of the dermal allograft of the superior capsular reconstruction (SCR) and to evaluate the graft for the presence of intrasubstance pulsatile vessels. METHODS: A retrospective chart review was conducted to identify SCR patients who had ultrasound evaluations between May 2014 and February 2019. Data were collected and stratified based on time from surgery into 2 groups: 0 to 12 months and past the 12-month follow-up. The primary outcome measure was graft thickness at the articular margin-greater tuberosity interface (tuberosity measurement). Secondary measures included midsubstance graft thicknesses 0.5, 1.0, and 1.5 cm medial to the tuberosity measurement; status of lateral graft fixation; presence of pulsatile vessels; and American Shoulder and Elbow Society and visual analog scale scores. RESULTS: Eighteen patients were included for analysis. The tuberosity measurement at final follow-up (mean 25 months, range 12-40 months) was (mean ± standard error [95% confidence interval (CI)]) 4.4 ± 0.2 mm (95% CI 4.0-4.8). This differed significantly from the midsubstance measurements: 0.5 cm: 3.6 ± 0.2 mm (95% CI 3.3-4.0, P = .008); 1.0 cm: 3.1 ± 0.2 mm (95% CI 2.7-3.4, P < .001); and 1.5 cm: 2.9 ± 0.2 mm (95% CI 2.6-3.2, P < .001). Ten constructs (56%) showed signs of pulsatile vessels in the first 12 months and all constructs were intact. ASES scores improved from 49.3 ± 4.0 (95% CI 41.6-57.1) preoperatively to 85.1 ± 2.9 (95% CI 79.4-90.8) (P < .001), and VAS scores decreased from 5.3 ± 0.6 (95% CI 4.2-6.5) preoperatively to 0.9 ± 0.3 (95% CI 0.3-1.5) at final follow-up (P < .001). CONCLUSIONS: The SCR dermal allograft significantly thickens at its lateral aspect, presents with evidence of vasculature in most patients in the first year of implantation, and is not resorbed by the body. LEVEL OF EVIDENCE: Level IV - therapeutic case series.

Prevention, assessment, diagnosis and management of diabetic foot based on clinical practice guidelines: A systematic review.

AIM: Diabetic foot complications are the main reason for hospitalization and amputation in people with diabetes and have a prevalence of up to 25%. Clinical practice guidelines are recommendations based on evidence with the aim of improving health care. The main aim of this study was to carry out a systematic review of the levels of the evaluation and treatment strategies that appear in the clinical practice guidelines focus on diabetic foot or diabetes with diabetic foot section. Another objective of this study was to perform an analysis of the levels of evidence in support of the recommendations made by the selected clinical practice guidelines. METHODS: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and a quality assessment by the Appraisal of Guidelines for Research and Evaluation (AGREE II) were performed. The databases checked were "NICE", "Cinahl", "Health Guide", "RNAO", "Sign", "PubMed", "Scopus" and "NCG". The search terms included were "diabetic foot", "guideline(s)", "practice guideline(s)" and "diabetes." RESULTS: Twelve articles were selected after checked inclusion criteria and quality assessment. A summary and classification of the recommendations was completed. CONCLUSIONS: The heterogeneity of levels of evidence and grades of recommendation of the CPGs included regarding the management, approach and treatment of DF makes it difficult to interpret and assume them in clinical practice in order to select the most correct procedures. Despite this and according to the detailed study of the guidelines included in this work, it can be concluded that the highly recommendable interventions for DF management are debridement (very high level of evidence and strongly recommended), foot evaluation (moderate level of evidence and fairly recommended) and therapeutic footwear (moderate level of evidence and fairly recommended).

Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison.

BACKGROUND: In vivo amniotic fluid is known to contain a population of mesenchymal stem cells (MSCs) and growth factors and has been shown to assist in healing when used as an adjunct in procedures across multiple medical specialties. It is unclear whether amniotic fluid products (AFPs) contain MSCs and, if so, whether the cells remain viable after processing. PURPOSE: To determine whether MSCs, growth factors, and hyaluronan are present in commercially available AFPs. STUDY DESIGN: Descriptive laboratory study. METHODS: Seven commercial companies that provide amniotic fluid were invited to participate in the study; 3 companies (the manufacturers of PalinGen, FloGraft, and Genesis AFPs) agreed to participate and donated AFPs for analysis. The AFPs were evaluated for the presence of MSCs, various growth factors relevant to orthopaedics (platelet-derived growth factor ßß, vascular endothelial growth factor, interleukin 8, bone morphogenetic protein 2, transforming growth factor ß1), and hyaluronan by enzyme-linked immunosorbent assay and culture of fibroblast colony-forming units. These products were compared with unprocessed amniotic fluid and 2 separate samples of MSCs derived from human bone marrow aspirates. All groups used the same culture medium and expansion techniques. Identical testing and analysis procedures were used for all samples. RESULTS: MSCs could not be identified in the commercial AFPs or the unprocessed amniotic fluid. MSCs could be cultured from the bone marrow aspirates. Nucleated cells were found in 2 products (PalinGen and FloGraft), but most of these cells were dead. The few living cells did not exhibit established characteristics of MSCs. Growth factors and hyaluronan were present in all groups at varying levels. CONCLUSION: The AFPs studied should not be considered "stem cell" therapies, and researchers should use caution when evaluating commercial claims that products contain stem cells. Given their growth factor content, however, AFPs may still represent a promising tool for orthopaedic treatment. CLINICAL RELEVANCE: Amniotic fluid has been proposed as an allogenic means for introducing MSCs. This study was unable to confirm that commercial AFPs contain MSCs.

Superior Capsular Reconstruction: Clinical Outcomes After Minimum 2-Year Follow-Up.

Superior capsular reconstruction (SCR) is performed to reduce the pain and disability caused by irreparable supraspinatus rotator cuff tears (RCTs). In this article, we discuss 9 cases of irreparable rotator cuff tears managed with arthroscopic SCR with dermal allograft. At minimum 2-year follow-up (mean, 32.38 months), the patients were prospectively evaluated on the American Shoulder and Elbow Surgeons (ASES) shoulder index, a visual analog scale (VAS) for pain, acromial-humeral distance, and ultrasonography. Patients were compared before and after surgery and against historical controls who underwent repair of massive RCTs. From before surgery to 2 years after surgery, mean ASES score improved significantly (P < .00002), from 43.54 to 86.46, and mean VAS pain score decreased significantly (P < .00002), from 6.25 to 0.38. For the historical controls at final follow-up, mean ASES score was 70.71 (P = .11), and mean VAS pain score was 3.00 (P < .05). Mean acromial-humeral distance improved from 4.50 mm before surgery to 8.48 mm immediately after surgery (P < .0008) and 7.60 mm 2 years after surgery (P < .05). Ultrasonography revealed pulsatile vessels within the allograft tissue between 4 and 8 months after surgery. One patient underwent reverse total shoulder arthroplasty (RTSA) for anterior escape; another had the graft rupture after a motor vehicle accident. Our data showed SCR with dermal allograft effectively restored the superior restraints in the glenohumeral joint and yielded outstanding clinical outcomes even after 2 years, making it an excellent viable alternative to RTSA.

A Guide to Ultrasound of the Shoulder, Part 3: Interventional and Procedural Uses.

Ultrasound is an extremely useful diagnostic tool for physicians, but recent advances have found that ultrasound's greatest utility is in interventional and procedural uses. Numerous studies have demonstrated a significant improvement in outcome and patient satisfaction when using ultrasound guidance for injections. Newer techniques are emerging to use ultrasound as an aid to surgery and interventional procedures. This allows the physician to use smaller incisions and less invasive methods, which are also easier to use for the practitioner and more cost-effective.

A Guide to Ultrasound of the Shoulder, Part 2: The Diagnostic Evaluation.

Ultrasound is becoming an increasingly accessible modality for its easy and accurate evaluation of shoulder pathology. In Part 1 of our series (Am J Orthop. 2016;45(3):176-182), we showed how musculoskeletal ultrasound can be properly coded and reimbursed and can be as effective in evaluating the shoulder as magnetic resonance imaging, yet more economical. With more physicians beginning to incorporate this technology into their practice, we describe the physics of ultrasound and our methods for evaluating the shoulder with ultrasound. In the coming year, new certifications are emerging that may be required to perform and bill for these services. Staying abreast with the current guidelines and protocols being introduced by the American Institute of Ultrasound in Medicine and the American Registry for Diagnostic Medical Sonography will be essential.

The emerging use of platelet-rich plasma in musculoskeletal medicine.

Platelet-rich plasma (PRP) is one of many new developments within the expanding field of regenerative medicine. Specialists in areas such as orthopedics, physical medicine and rehabilitation, and rheumatology have been exploring the benefits of this novel therapy. Although PRP therapy remains controversial and has minimal clinical trial support, the use of orthobiologics such as PRP continues to advance as patients seek nonsurgical approaches to acute and chronic musculoskeletal injury and disease. However, academic acceptance as well as insurance reimbursement remain reliant on solid and repeatable positive results from large clinical trials. The authors summarize the evolution of PRP therapy and report on its status.