Perinatal Tissue-Derived Allografts and Stromal Cells for the Treatment of Knee Osteoarthritis: A Review of Preclinical and Clinical Evidence.

OBJECTIVE: The use of perinatal-derived tissues and mesenchymal stromal cells (MSCs) as alternative treatment options to corticosteroid and hyaluronic acid injections has been gaining popularity. However, their ability to attenuate osteoarthritic (OA) symptoms while also slowing the progression of the disease remains controversial. Thus, the objective of this article is to summarize the results from both preclinical and clinical studies evaluating the efficacy of perinatal-derived tissue allografts and MSCs for the treatment of OA. DESIGN: A comprehensive literature search was conducted on databases including Pubmed, ScienceDirect, and Google Scholar beginning in March 2020 for both preclinical and clinical studies evaluating perinatal-derived tissues and MSCs in OA. Eighteen studies met the inclusion criteria and were used for this review. RESULTS: Both animal models and early human clinical trials demonstrated that perinatal tissues could reduce joint inflammation and pain as well as improve range of motion and function in OA. Perinatal tissue-derived MSCs in animal studies have shown the potential to support chondrocyte proliferation while also decreasing inflammatory gene and protein expression. Limited clinical results suggest perinatal tissue-derived MSC sources may also be a viable alternative or adjunct to hyaluronic acid in reducing pain and symptoms in an arthritic joint. CONCLUSIONS: Perinatal tissue-derived allografts and MSCs have promise as potential therapeutics for mitigating OA progression. However, further research is warranted to fully define the therapeutic mechanism(s) of action and safety of these biological therapies.

Levels of Evidence Supporting the North American and European Perioperative Care Guidelines for Anesthesiologists between 2010 and 2020: A Systematic Review.

BACKGROUND: Although there are thousands of published recommendations in anesthesiology clinical practice guidelines, the extent to which these are supported by high levels of evidence is not known. This study hypothesized that most recommendations in clinical practice guidelines are supported by a low level of evidence. METHODS: A registered (Prospero CRD42020202932) systematic review was conducted of anesthesia evidence-based recommendations from the major North American and European anesthesiology societies between January 2010 and September 2020 in PubMed and EMBASE. The level of evidence A, B, or C and the strength of recommendation (strong or weak) for each recommendation was mapped using the American College of Cardiology/American Heart Association classification system or the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The outcome of interest was the proportion of recommendations supported by levels of evidence A, B, and C. Changes in the level of evidence over time were examined. Risk of bias was assessed using Appraisal of Guidelines for Research and Evaluation (AGREE) II. RESULTS: In total, 60 guidelines comprising 2,280 recommendations were reviewed. Level of evidence A supported 16% (363 of 2,280) of total recommendations and 19% (288 of 1,506) of strong recommendations. Level of evidence C supported 51% (1,160 of 2,280) of all recommendations and 50% (756 of 1,506) of strong recommendations. Of all the guidelines, 73% (44 of 60) had a low risk of bias. The proportion of recommendations supported by level of evidence A versus level of evidence C (relative risk ratio, 0.93; 95% CI, 0.18 to 4.74; P = 0.933) or level of evidence B versus level of evidence C (relative risk ratio, 1.63; 95% CI, 0.72 to 3.72; P = 0.243) did not increase in guidelines that were revised. Year of publication was also not associated with increases in the proportion of recommendations supported by level of evidence A (relative risk ratio, 1.07; 95% CI, 0.93 to 1.23; P = 0.340) or level of evidence B (relative risk ratio, 1.05; 95% CI, 0.96 to 1.15; P = 0.283) compared to level of evidence C. CONCLUSIONS: Half of the recommendations in anesthesiology clinical practice guidelines are based on a low level of evidence, and this did not change over time. These findings highlight the need for additional efforts to increase the quality of evidence used to guide decision-making in anesthesiology.

Retrospective analysis of inpatient polysomnogram characteristics and discharge outcomes in infants with bronchopulmonary dysplasia requiring home oxygen therapy.

RATIONALE: Little is known about the polysomnogram (PSG) characteristics in infants with bronchopulmonary dysplasia (BPD), especially severe BPD, who do not need home ventilatory support but are at increased risk for chronic hypoxia and are vulnerable to its effects. OBJECTIVE: This study aims to assess PSG characteristics and change in discharge outcomes in premature infants with BPD who required oxygen therapy at discharge. METHODS: This is a retrospective chart review of premature infants with BPD who were admitted to a quaternary newborn and infant intensive care unit from January 1, 2012 to December 31, 2015 and who underwent polysomnography before discharge. MEASUREMENTS AND MAIN RESULTS: Data from 127 patients were analyzed. The median gestational age of our patients was 26 weeks and 1 day (interquartile range [IQR]: 24.71, 28.86). The majority of the patients had moderate-to-severe BPD. The median obstructive apnea-hypopnea index was 5.3 events/h (IQR: 2.2, 10.1). The median oxygen desaturation index was 15.7 events/h (IQR: 4.7, 35). Nadir oxygen saturation measured by pulse oximeter was 81% (IQR: 76-86) and the arousal/awakening index was 21.9 (IQR: 13.3-30.9). No statistically significant difference was noted between severe and nonsevere BPD groups for PSG characteristics. However, average end-tidal CO2 was significantly higher in the severe BPD group (p = .0438). Infants in the severe BPD group were intubated longer than infants with nonsevere BPD (p = .0082). The corrected gestational age (CGA) at the time of discharge (CGA-PSG) and PSG (CGA-DC) was higher in severe BPD patients but not statistically different. The majority of premature infants who underwent a PSG were discharged home with oxygen, and 69% required a titration of their level of support based on results from the PSG. CONCLUSION: Our results highlight the presence of abnormal PSG characteristics in BPD patients, as early as 43 weeks CGA. These findings have not been previously described in this patient population prior to initial discharge from the hospital. A severe BPD phenotype tends to be associated with higher respiratory morbidity compared with a nonsevere BPD phenotype for the comparable CGA. PSG, when available, may be helpful for individualizing and streamlining treatment in preparation for discharge home and mitigating the effects of intermittent hypoxic episodes.