Outcomes of High Tibial Osteotomy With Versus Without Mesenchymal Stem Cell Augmentation: A Systematic Review and Meta-analysis.

BACKGROUND: The outcomes after high tibial osteotomy (HTO) with augmentation of intra-articular mesenchymal stem cell (MSCs) for medial tibiofemoral osteoarthritis remain controversial. PURPOSE: To pool existing studies to compare the outcomes of HTO with versus without intra-articular MSC augmentation when performed for medial tibiofemoral osteoarthritis. STUDY DESIGN: Systematic review; Level of evidence, 3. METHODS: The systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included were clinical studies that compared the outcomes of HTO with intra-articular MSC augmentation (MSC group) versus without (control group). Pre- and postoperative outcomes were compared between groups from measures including the Lysholm score, International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score, Hospital for Special Surgery Knee Rating Scale, Tegner score, visual analog scale for pain, arthroscopic and histological grading scales, femorotibial angle, weightbearing line, and posterior tibial slope. RESULTS: We reviewed 4 studies with a total of 224 patients. The MSC group demonstrated significantly greater improvement versus controls in the pooled Lysholm score (weighted mean difference [WMD], 6.64; 95% CI, 0.90 to 12.39) and pooled IKDC score (WMD, 9.21; 95% CI, 4.06 to 14.36), which were within or close to the minimal clinically important difference. Radiological outcomes were similar in both groups, including the femorotibial angle (WMD, -0.01; 95% CI, -1.10 to 1.09), weightbearing line, and posterior tibial slope. The studies were homogeneous, and no publication bias was noted. CONCLUSION: Intra-articular MSC augmentation for HTO may modestly improve functional outcomes as compared with HTO alone. However, adequate data are lacking to make definitive conclusions regarding the effect of MSC augmentation on pain or arthroscopic and histologic grading.

Intra-articular Injections of Mesenchymal Stem Cells Without Adjuvant Therapies for Knee Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: While many reviews have been performed to attempt to provide conclusive evidence regarding the outcomes of mesenchymal stem cells (MSCs) in osteoarthritis treatment, the evidence for MSC treatment in osteoarthritis remains contentious, as these reviews have been limited by the heterogeneous evidence available. PURPOSE: To pool the results of treatment using intra-articular injections of MSCs without any adjuvant therapies for osteoarthritis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All clinical trials of level 1 or 2 evidence that reported clinical outcomes of patients with osteoarthritis of the knees treated using intra-articular injections of MSCs without any adjuvant therapies were included. RESULTS: A total of 19 studies with 440 knees were included. All studies reported an improvement in the outcomes after intervention. The standardized mean differences (SMDs) for the visual analog scale (VAS) for pain at rest and upon exertion were -1.48 (95% CI, -1.85 to -1.11) and -2.25 (95% CI, -2.64 to -1.85), respectively. The SMDs for the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and total Knee injury and Osteoarthritis Outcome Score were -1.19 (95% CI, -1.53 to -0.84) and 0.88 (95% CI, 0.66-1.10), respectively. Only the source of MSCs and whether the MSCs were cultured or uncultured were clinically important and statistically significant moderators of the treatment outcome. The use of bone marrow MSCs reduced the VAS for pain by 1.50 (95% CI, 0.04-2.96; P = .04) and reduced the total WOMAC by 23.2 (95% CI, 10.0-36.4; P < .01) as compared with adipose MSCs. The use of cultured MSCs reduced the VAS for pain by 2.19 (95% CI, 0.57-3.81; P < .01) and reduced the total WOMAC by 14.4 (95% CI, 1.21-27.5; P = .03) as compared with uncultured MSCs. CONCLUSION: Intra-articular injections of MSCs without any adjuvant therapies improves pain and function for osteoarthritis. Significantly better outcomes were obtained with the use of bone marrow MSCs as compared with adipose MSCs and with the use of cultured MSCs as opposed to uncultured MSCs.

The impact of death and dying on the personhood of medical students: a systematic scoping review.

BACKGROUND: The re-introduction of medical students into healthcare systems struggling with the COVID-19 pandemic raises concerns as to whether they will be supported when confronted with death and dying patients in resource-limited settings and with reduced support from senior clinicians. Better understanding of how medical students respond to death and dying will inform educationalists and clinicians on how to best support them. METHODS: We adopt Krishna's Systematic Evidence Based Approach to carry out a Systematic Scoping Review (SSR in SEBA) on the impact of death and dying on medical students. This structured search process and concurrent use of thematic and directed content analysis of data from six databases (Split Approach) enhances the transparency and reproducibility of this review. RESULTS: Seven thousand six hundred nineteen were identified, 149 articles reviewed and 52 articles included. The Split Approach revealed similar themes and categories that correspond to the Innate, Individual, Relational and Societal domains in the Ring Theory of Personhood. CONCLUSION: Facing death and dying amongst their patients affect how medical students envisage their personhood. This underlines the need for timely, holistic and longitudinal support systems to ensure that problems faced are addressed early. To do so, there must be effective training and a structured support mechanism.