Complex Regional Pain Syndrome: Updates and Current Evidence

Purpose of Review Complex regional pain syndrome (CRPS) is a debilitating condition that manifests with sensory, neurologic, autonomic, and/or trophic impairment. In addition to manifesting with severe neuropathic pain, CRPS is associated with poor quality of life and higher annual healthcare costs. This systematic review appraises the current body of evidence on all treatment modalities for CRPS. Recent Findings In patients with CRPS-related pain, there is level I evidence supporting modest to moderate improvement in pain intensity from physical therapy, occupational therapy, massage therapy, acupuncture, and transcutaneous electrical nerve stimulation (TENS), although changes in functionality were inconsistent. Topical medications such as eutectic mixture of local anesthetic (EMLA) and ketamine cream were associated with decreased allodynia and hyperalgesia. Inconsistency was present in the current literature in terms of the analgesic effects of gabapentinoids for CRPS. Patients who received intramuscular or intravenous bisphosphonate therapy may achieve modest to moderate improvement in pain intensity and functionality. Systemic steroid and ketamine provided only short-term pain reduction. In terms of interventional therapy, there was an association of modest to moderate improvement in pain with sympathetic ganglion block, sympathectomy, dorsal column spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation, although the level of evidence was limited. Summary In summary, the purpose of this systematic review is to equip the clinician with important updates on conservative, pharmacologic, and interventional treatment modalities for CRPS-related pain

Platelet Rich Plasma and Platelet-Related Products in the Treatment of Radiculopathy—A Systematic Review of the Literature

Back pain with radicular symptoms is associated with detrimental physical and emotional functioning and economic burden. Conservative treatments including physical, pharmacologic and injection therapy may not provide clinically significant or long-standing relief. Regenerative medicine research including Platelet rich plasma (PRP), Platelet lysate (PL) or Plasma rich in growth factors (PRGF) continues to develop, however evidence appraisal for treatment of radicular pain remains lacking. Thus, we performed a systematic review to evaluate the effectiveness of epidural steroid injections containing PRP or related products to treat radicular pain. Embase, PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were queried. Twelve studies were included in qualitative analysis, consisting of three randomized controlled trials and nine observational studies. The primary outcome was pain intensity, and secondary outcomes included functional improvement, anatomical changes on advanced imaging, and adverse events. All studies identified improved pain intensity and functional outcomes after epidural injection of PRP, PRGF and/or PL. Similar or longer lasting pain relief was noted in the PRP cohort compared to the cohort receiving epidural steroid injections with effects lasting up to 12–24 months. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis revealed a very-low certainty of evidence due to risk of bias, indirectness, and imprecision

Brd4 is required for chondrocyte differentiation and endochondral ossification

Differentiation of multi-potent mesenchymal stromal cells (MSCs) is directed by the activities of lineage-specific transcription factors and co-factors. A subset of these proteins controls the accessibility of chromatin by recruiting histone acetyl transferases or deacetylases that regulate acetylation of the N-termini of H3 and H4 histone proteins. Bromodomain (BRD) proteins recognize these acetylation marks and recruit the RNA pol II containing transcriptional machinery. Our previous studies have shown that Brd4 is required for osteoblast differentiation in vitro. Here, we investigated the role of Brd4 on endochondral ossification in C57BL/6 mice and chondrogenic differentiation in cell culture models. Conditional loss of Brd4 in the mesenchyme (Brd4 cKO, Brd4fl/fl: Prrx1-Cre) yields smaller mice that exhibit alteration in endochondral ossification. Importantly, abnormal growth plate morphology and delayed long bone formation is observed in juvenile Brd4 cKO mice. One week old Brd4 cKO mice have reduced proliferative and hypertrophic zones within the physis and exhibit a delay in the formation of the secondary ossification center. At the cellular level, Brd4 function is required for chondrogenic differentiation and maturation of both ATDC5 cells and immature mouse articular chondrocytes. Mechanistically, Brd4 loss suppresses Sox9 levels and reduces expression of Sox9 and Runx2 responsive endochondral genes (e.g., Col2a1, Acan, Mmp13 and Sp7/Osx). Collectively, our results indicate that Brd4 is a key epigenetic regulator required for normal chondrogenesis and endochondral ossification

Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I  2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I  2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results