Safety of bone marrow derived mesenchymal stem cell extracellular vesicle injection for lumbar facet joint pain.

Aim: A 3-month pilot study to evaluate the safety of injecting a bone marrow-derived mesenchymal stem cell extracellular vesicle advanced investigational product (IP) into the lumbar facet joint space as a treatment for chronic low back pain. Methods: 20 healthy adults were treated with IP injections (0.5 ml/joint) and evaluated by three functional assessments 1, 3, 7, 14, 30, 60 and 90 days later. Results: No adverse effects or complications occurred across the 3-month follow-up. There were no reports of worsening pain. After 3 months group average scores improved significantly (p < 0.0001) in the Severity Index (65.04%), Interference Index (72.09%) and Oswestry Disability Index (58.43%) assessments. Conclusion: IP injections were safe and associated with significant functional improvements.

What is this article about? Bone marrow mesenchymal stem cell derived extracellular vesicles (BM-MSC EV), a novel biologic therapeutic candidate, are a safe and promising therapeutic intervention for patients with lumbar facet joint pain, a malady that manifests as persistent low back pain (LBP). 20 adult subjects with lumbar facet joint pain received a single injection of BM-MSC EV investigational product in the lumbar facet joint space. What were the results? Follow-up was conducted through in-office and virtual visits that included outcome measures to determine the safety and efficacy of this therapy. By the 3-month end point, follow-up was successful, and no complications or adverse events were noted. Significant improvements in all three assessments of pain and disability occurred throughout the study. What do the results of the study mean? The results are promising and suggest that BM-MSC EV may represent a revolutionary treatment option with durable efficacy and minimal safety risks. Randomized, controlled clinical studies into the application of BM-MSC EV in lumbar facet joint pain should be pursued to confirm the potential benefits of this novel intervention.

Interventional Mental Health: A Transdisciplinary Approach to Novel Psychiatric Care Delivery.

Mental health disorders are among the most common health conditions in the United States. Traditional clinical treatments rely on psychiatric counseling and, in many cases, prescription medications. We propose an innovative model, Interventional Mental Health, which employs a combination of modalities through a multifaceted approach to treat conditions that have exhibited limited responsiveness to traditional methods and individuals afflicted with multiple comorbidities simultaneously. We hypothesize that creating a unique treatment algorithm combining current therapeutic modalities such as Stellate Ganglion Blocks (SGB), Transcranial Magnetic Stimulation (TMS) therapy, and ketamine therapy, within a consolidated timeframe, will yield synergistic outcomes among patients presenting with comorbid post-traumatic stress disorder (PTSD), depression, and/or anxiety.

Pulsed Radiofrequency-Enhanced Dual Sympathetic Block for the Treatment of Post-Traumatic Stress Disorder.

Dual sympathetic blocks (DSBs) have been shown to provide significant symptom relief in individuals with post-traumatic stress disorder (PTSD). However, despite the clinical significance of DSB in PTSD treatment, a subset of patients experience the recurrence of somatic symptoms of PTSD and trauma-induced anxiety. The purpose of this case report is to describe our experience with the successful treatment of acute symptoms of PTSD by using serial DSBs and DSBs with pulsed radiofrequency (PRF). An 18-year-old male who had suffered multiple childhood traumatic events presented with severe and persistent symptoms consistent with a diagnosis of PTSD. The patient had been previously treated with myriad, multiple-year trials of psychotropic medications and psychotherapy as well as lifestyle modifications involving art therapy and physical exercise. Despite these psychiatric and psychological interventions, his symptoms persisted. The patient underwent a total of four bilateral DSBs, three of which were enhanced with PRF, over a period of 15 months at our clinic, with intervals of three, four, and six months between appointments, respectively. At the two-week follow-up after the initial bilateral stellate ganglion block (SGB) procedure, a major improvement in the patient's PTSD symptoms was observed, specifically symptoms of anxiety and a heightened sense of danger. These results were confirmed by a reduction in PTSD Checklist Version 5 (PCL-5) scores from 73 to 50. However, three months later, some of his symptoms returned. The patient elected to proceed with a bilateral PRF-enhanced DSB, and he subsequently reported that his PTSD and general anxiety symptoms subsided by 80%, which was confirmed by a reduction in PCL-5 scores from 50 to 42. This significant symptom relief persisted for four months, and the patient returned for his second bilateral PRF-enhanced DSB. The patient's PCL-5 score further dropped from 42 to 22 and he reported an 80% reduction in symptoms, which persisted for six months. The patient elected to undergo a third bilateral PRF-enhanced DSB, which was successful in further reducing his symptoms as demonstrated by a self-reported 80% symptom relief and a drop in PCL-5 scores from 22 to 20, which has persisted for over six months.  We highlight the fact that the addition of PRF in a selective blockade of the stellate ganglion via injection reduced our patient's PTSD symptoms to below the PTSD diagnostic threshold. Furthermore, we report that the clinical efficacy of bilateral PRF-enhanced DSB may be additive over successive procedures. We also provide a theoretical exposition of our findings.

Botox-Enhanced Stellate Ganglion Blockade for the Treatment of Post-traumatic Stress Disorder.

Emerging evidence promotes stellate ganglion blocks (SGB) as a treatment for post-traumatic stress disorder (PTSD) in individuals who have not fully responded to conventional therapies. Ongoing research aims to assess the reliability and sustainability of this intervention. A 36-year-old female presented to our clinic complaining of severe and persistent symptoms since childhood, consistent with a diagnosis of PTSD and trauma-induced anxiety. The patient tried traditional psychological therapies and psychotropic medications for multiple years without optimal symptom relief. The patient underwent two sets of bilateral SGB: one set of standard injections performed with 0.5% bupivacaine and one set performed with the addition of botulinum toxin (Botox) injected into the stellate ganglion. After the initial standard bilateral SGB procedures, the patient experienced a significant reduction in PTSD symptoms. Two months later, however, the somatic symptoms of PTSD and trauma-induced anxiety returned, including hypervigilance, nightmares, insomnia, hyperhidrosis, and muscle tension. The patient elected to proceed with a set of Botox-enhanced SGB, and the results demonstrated profound relief as quantified by a drop in PTSD Checklist Version 5 (PCL-5) scores from 57 to 2. At a six-month follow-up since the initial injections, the patient reported significant and sustained relief from her PTSD symptoms. We report that the addition of Botox in a selective blockade of the stellate ganglion reduced our patient's PTSD symptoms to below the PTSD diagnostic threshold for a sustained period while providing additional benefits of reduced anxiety, hyperhidrosis, and pain. We provide a reasonable explanation for our findings.

Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome.

Many acute COVID-19 convalescents experience a persistent sequelae of infection, called post-acute COVID-19 syndrome (PACS). With incidence ranging between 31% and 69%, PACS is becoming increasingly acknowledged as a new disease state in the context of SARS-CoV-2 infection. As SARS-CoV-2 infection can affect several organ systems to varying degrees and durations, the cellular and molecular abnormalities contributing to PACS pathogenesis remain unclear. Despite our limited understanding of how SARS-CoV-2 infection promotes this persistent disease state, mitochondrial dysfunction has been increasingly recognized as a contributing factor to acute SARS-CoV-2 infection and, more recently, to PACS pathogenesis. The biological mechanisms contributing to this phenomena have not been well established in previous literature; however, in this review, we summarize the evidence that NAD+ metabolome disruption and subsequent mitochondrial dysfunction following SARS-CoV-2 genome integration may contribute to PACS biological pathogenesis. We also briefly examine the coordinated and complex relationship between increased oxidative stress, inflammation, and mitochondrial dysfunction and speculate as to how SARS-CoV-2-mediated NAD+ depletion may be causing these abnormalities in PACS. As such, we present evidence supporting the therapeutic potential of intravenous administration of NAD+ as a novel treatment intervention for PACS symptom management.

Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.

INTRODUCTION: There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. MATERIALS AND METHODS: We conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs. RESULTS: We identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs. CONCLUSIONS: Similar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.

The risk of false-positive results in orthopaedic surgical trials.

The risk of concluding that the results of a particular study are true, when, in fact, they really are attributable to chance (or random sampling error) is underappreciated by investigators. This erroneous false-positive conclusion is designated as a Type I or alpha error. The extent to which randomized trials in surgery risk Type I errors is unclear. The current authors hand-searched four orthopaedic journals, six general surgery journals, and five medical journals to identify recently published randomized trials (within the past 2 years). Information on outcomes and statistical adjustment for multiple outcomes was recorded for each study. The risk of a Type I error was calculated for each study that did not explicitly state a primary outcome measure for the main statistical comparison. One hundred fifty-nine studies met the inclusion criteria for the study: 60 studies from orthopaedic journals, 49 studies from nonorthopaedic surgical journals, and 50 studies from medical journals. Of the trials that did not state a primary outcome measure, the risk of Type I errors (false-positive results) in orthopaedic and nonorthopaedic surgery journals (mean 37.3% +/- 13.3% and 37.6% +/- 10.5%, respectively) were significantly greater than medical journals (10.1% +/- 1.9%). In the current review of randomized trials in surgery and medicine, the following is reported: (1) reporting of primary outcomes in trials was inadequate; (2) one in three trials in surgery and one in 10 trials in medicine risked false-positive results; and (3) few trials in surgery and medicine considered adjustment for multiple comparisons.