To loop or not to loop? CNS-28 is the answer.

Regulation of interferon-γ is critical to constrain inflammation and mount effective responses to infection and anti-tumor immunity. In this issue of Immunity, Cui et al. identify a distal silencer element that disrupts promoter-enhancer looping, regulating IFN-γ expression and preventing inappropriate inflammation.

Considerations for Lumbar Medial Branch Nerve Radiofrequency at Spinal Motion Segments Adjacent to a Fusion Construct.

Instrumented lumbar spinal fusion is common and results in biomechanical changes at adjacent spinal segments that increase facet load bearing. This can cause facet-mediated pain at levels adjacent to the surgical construct. Medial branch nerve radiofrequency ablation (RFA) exists as a treatment for some cases. It is important to acknowledge that the approach and instrumentation used during some specific lumbar fusion approaches will disrupt the medial branch nerve(s). Thus, the proceduralist must consider the fusion approach when determining which medial branch nerves are necessary to anesthetize for diagnosis and then to potentially target with RFA. This article discusses the relevant technical considerations for preparing for RFA to denervate lumbosacral facet joints adjacent to fusion constructs.

Gone Viral: A Cross-Sectional Analysis of Contact Lens-Related Videos on TikTok.

OBJECTIVES: To evaluate the content, sources, and quality of contact lens (CL)-related videos on TikTok, the fastest growing social media platform worldwide. METHODS: TikTok was queried on October 25, 2021 for the top 200 posts with the hashtag "#contactlenses." Posts meeting inclusion criteria were characterized and assessed for quality with DISCERN, a validated scoring instrument for the appraisal of consumer health information (score range 1-5 with a higher score indicating a higher quality video). RESULTS: The included 113 posts showed a mean quality of 1.94±0.44. Content included product displays (42%), patient experiences (23%), educational (22%), and comedy (12%). Most product displays featured decorative lenses (98%). Although videos by eye-care providers (ECPs) accounted for most educational content (52%) and showed significantly higher mean quality compared with posts by non-ECPs (2.57±0.18 vs. 1.85±0.13, P <0.001), they were a minority (12%) and showed poor overall quality. Contact lens representation was greatly skewed toward decorative lenses (74%), whereas only 3.5% of videos promoted seeing an ECP. CONCLUSIONS: Poor quality and skewed representation of posts indicate that CL-related information on TikTok has serious shortcomings. These findings are particularly concerning given that most TikTok users are adolescents and young adults, the same population who tend to be decorative lens wearers and who are at increased risk of CL-related complications. Eye-care providers, professional organizations, and regulatory agencies should be urged to increase their engagement with the platform, especially regarding educational content creation and CL marketing oversight.

Radiofrequency Ablation for Chronic Posterior Sacroiliac Joint Complex Pain: A Comprehensive Review.

Radiofrequency ablation of the sacral lateral branches targets the innervation of the posterior sacroiliac ligaments and posterior portion of the sacroiliac joint. These structures are also collectively referred to as the posterior sacroiliac joint complex. This review will discuss current diagnostic block paradigms and selection criteria for sacral lateral branch radiofrequency ablation, varying techniques and technologies utilized for sacral lateral branch radiofrequency ablation, and updates on the clinical outcome literature. The current evidence suggests that sacral lateral branch radiofrequency ablation can provide relief for posterior sacroiliac joint complex pain, but the literature is limited by variability in selection criteria, the specific nerves targeted by radiofrequency ablation, and the types of radiofrequency ablation technology and techniques utilized in clinical outcome studies.

Conservative Care in Lumbar Spine Surgery Trials: A Descriptive Literature Review.

OBJECTIVE: To evaluate the degree to which conservative care and failure were specifically defined in studies comparing nonoperative treatment versus surgery for low back pain (LBP) conditions in adults. DATA SOURCES: A comprehensive literature search was conducted by an experienced librarian using MEDLINE (PubMed), Embase, Google Scholar, and CENTRAL from January 2003 to June 2014. Endnote bibliographic management application was used to remove duplicates and organize the citations. STUDY SELECTION: Prospective, randomized, or cohort trials comparing surgery versus conservative intervention for patients with LBP conditions. Study selection was conducted by 2 independent reviewers. DATA EXTRACTION: Three independent reviewers extracted data from each article using a structured data extraction form. Data extracted included type of study, participant characteristics, sample size, description, and duration of conservative care and whether failed conservative care criterion was defined. DATA SYNTHESIS: A total of 852 unique records were screened for eligibility; of those, 72 articles were identified for further full-text review. Thirty-four full texts were excluded based on the exclusion criteria, and 38 articles, representing 20 unique studies, were included for qualitative synthesis. Fifteen of the 20 studies defined the duration of conservative care. Only 3 studies defined the dosage of physical therapy sessions, including total number of visits and visit duration. Two studies described medication usage, including the duration and type. No studies specifically defined what constituted failed conservative therapy. CONCLUSIONS: This literature review suggests conservative care is poorly defined in randomized trials, which can lead to ambiguity of research procedures and unclear guidelines for clinicians. Future studies should increase transparency and explicitly define conservative care.

Effects of Off-Axis Elliptical Training on Reducing Pain and Improving Knee Function in Individuals With Patellofemoral Pain.

OBJECTIVE: To examine whether an off-axis elliptical training program reduces pain and improves knee function in individuals with patellofemoral pain (PFP). DESIGN: Controlled laboratory study, pretest-posttest. SETTING: University rehabilitation center. PARTICIPANTS: Twelve adult subjects with PFP. INTERVENTIONS: Subjects with PFP completed an exercise program consisting of 18 sessions of lower extremity off-axis training using a custom-made elliptical trainer that allows frontal plane sliding and transverse plane pivoting of the footplates. MAIN OUTCOME MEASURES: Changes in knee pain and function posttraining and 6 weeks after training were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) scores. Lower extremity off-axis control was assessed by pivoting and sliding instability, calculated as the root mean square (RMS) of the footplate pivoting angle and sliding distance during elliptical exercise. Subjects' single-leg hop distance and proprioception in detecting lower extremity pivoting motion were also evaluated. RESULTS: Subjects reported significantly greater KOOS and IKDC scores (increased by 12-18 points) and hop distance (increased by 0.2 m) after training. A significant decrease in the pivoting and sliding RMS was also observed after training. Additionally, subjects with PFP demonstrated improved pivoting proprioception when tested under a minimum weight-bearing position. CONCLUSIONS: An off-axis elliptical training program was effective in enhancing lower extremity neuromuscular control on the frontal and transverse planes, reducing pain, and improving knee function in persons with PFP. CLINICAL RELEVANCE: This study provides a novel intervention approach to enhance the control of the frontal and transverse plane motions of the lower extremities during functional weight-bearing activities. This novel off-axis elliptical training may be incorporated with other common treatment options currently available for PFP to augment the effects of musculoskeletal rehabilitation for the PFP population.

A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results.

Therapeutic vaccines that elicit cytotoxic T cell responses targeting tumor-specific neoantigens hold promise for providing long-term clinical benefit to patients with cancer. Here we evaluated safety and tolerability of a therapeutic vaccine encoding 20 shared neoantigens derived from selected common oncogenic driver mutations as primary endpoints in an ongoing phase 1/2 study in patients with advanced/metastatic solid tumors. Secondary endpoints included immunogenicity, overall response rate, progression-free survival and overall survival. Eligible patients were selected if their tumors expressed one of the human leukocyte antigen-matched tumor mutations included in the vaccine, with the majority of patients (18/19) harboring a mutation in KRAS. The vaccine regimen, consisting of a chimp adenovirus (ChAd68) and self-amplifying mRNA (samRNA) in combination with the immune checkpoint inhibitors ipilimumab and nivolumab, was shown to be well tolerated, with observed treatment-related adverse events consistent with acute inflammation expected with viral vector-based vaccines and immune checkpoint blockade, the majority grade 1/2. Two patients experienced grade 3/4 serious treatment-related adverse events that were also dose-limiting toxicities. The overall response rate was 0%, and median progression-free survival and overall survival were 1.9 months and 7.9 months, respectively. T cell responses were biased toward human leukocyte antigen-matched TP53 neoantigens encoded in the vaccine relative to KRAS neoantigens expressed by the patients' tumors, indicating a previously unknown hierarchy of neoantigen immunodominance that may impact the therapeutic efficacy of multiepitope shared neoantigen vaccines. These data led to the development of an optimized vaccine exclusively targeting KRAS-derived neoantigens that is being evaluated in a subset of patients in phase 2 of the clinical study. ClinicalTrials.gov registration: NCT03953235 .

Gastroenteropancreatic Neuroendocrine Tumor Metastasis to the Heart: Evaluation of Imaging Manifestations.

Neuroendocrine tumors (NET) may affect the heart by cardiac metastasis or carcinoid heart disease. NET metastasis to the heart is rare, with limited data characterizing it. We sought to evaluate 68Ga-DOTATATE PET scan imaging features and associated cardiac imaging characteristics where available in those with NET cardiac metastases. 68Ga-DOTATATE positron emission tomography (PET)/CT scans performed on patients with gastroenteropancreatic (GEP) NET at our institution were reviewed for cardiac involvement. Those identified with cardiac metastases had their electronic medical record, transthoracic echocardiogram (TTE) and cardiac magnetic resonance imaging (MRI) reviewed for characterization. From a total of 1426 68Ga-DOTATATE PET/CT scans performed on patients with GEP-NET, 25 (1.75%) had cardiac uptake consistent with metastasis. Of these, 22 had myocardial metastases (29 distinct myocardial lesions: left ventricle - 16, right ventricle - 6, and ventricular septum -7) and 3 had periradial lymph node involvement only. NET patients with cardiac metastases as identified by DOTATATE scan did not appear to have any hemodynamically significant TTE features, aside from those (2/25) who had concomitant carcinoid heart disease. Of the 14 patients who had available TTE for review, only one with high metastatic cardiac tumor burden had detectable cardiac mass. Of the 6 cases who had available MRI, all had metastatic cardiac lesions seen with excellent correlation with tumor localization on 68Ga-DOTATATE PET scan. 68Ga-DOTATATE PET has excellent capability for the diagnosis of cardiac NET metastasis. Cardiac MRI may provide further anatomic and tissue characterization evaluation. Those with myocardial NET metastases without carcinoid heart disease did not have significant hemodynamic effect based on echocardiographic criteria.

Cognitive Behavioral Immersion for Substance Use Disorders: A Feasibility and Pilot Study of a Peer-Based Coaching Program in the Metaverse.

Introduction: Cognitive Behavioral Immersion (CBI) is a novel cognitive-behavioral skills program delivered by lay coaches in the metaverse through immersive virtual reality technology. Objectives: The objective for this study was to run a feasibility and pilot study of CBI for individuals in recovery from a substance use disorder. Methods: Data from 48 participants were used and program usage was assessed. Participants were asked to complete questionnaires assessing affect, perceived online social support, and group therapy alliance throughout their participation in the program. Structured qualitative interviews were also conducted with a subset of participants (n = 11) to understand the feasibility of the novel program. Results: Participants experienced a significant increase in their positive affect and non-significant decrease in their negative affect during their most recently attended session. Participants also experienced a nonsignificant increase in online social support across their participation in the program. Structured qualitative interviews revealed eight primary themes, including both advantages (community, psychoeducational impact, immersion, comparability with other interventions, coping in the pandemic, and anonymity) and areas of improvement (challenges and technological usability) of the program. Conclusion: This study provides preliminary support for the feasibility and potential effects of CBI and its incorporation of lay coaches to lead cognitive-behavioral skills groups in the metaverse. Future research is encouraged to examine the feasibility and efficacy of this program for a broader array of clinical presentations.

Sacroiliac Joint Interventions.

The sacroiliac joint complex (SIJC) is composed of complex anatomy of numerous potential pain generators that demonstrate varying pathophysiology and differing innervations. This heterogeneity has been a challenge to advancing research and clinical care. Moving forward, individualized approaches taking these factors into account may be a path forward to improved outcomes. Thus, as we move toward precision medicine in interventional spine care, it is imperative to investigate more targeted diagnostic and therapeutic approaches to the SIJC.

Development of a Cadaver Laboratory Curriculum for Interventional Spine Procedures for Physical Medicine and Rehabilitation Residents.

ABSTRACT: There is no standardized curriculum for teaching interventional spine procedures during residency. The objective of this protocol was to share a curriculum using a cadaver laboratory for teaching Physical Medicine and Rehabilitation residents interventional spine procedures, which can be an effective and safe medium to train residents. This protocol provides a checklist that can guide the residents while they are in the cadaver laboratory with a focus on some of the most common lumbar procedures. Twelve physical medicine and rehabilitation resident's confidence in their ability to maneuver the x-ray image intensifier (C-arm), identify spine anatomy under fluoroscopy, and drive the needle improved after the training curriculum (P < 0.005). Although the cadaver laboratory curriculum is not a replacement for the required Accreditation Council for Graduate Medical Education training, it may serve as a tool to improve resident preparedness for spine procedures.

The Complementary Role of 68Ga-DOTATATE PET/CT in Diagnosis of Recurrent Meningioma.

Introduction: Contrast-enhanced brain MRI is the choice of imaging modality in diagnosis and posttreatment evaluation, its role is limited in distinguishing recurrent lesion from postoperative change. 68Ga-DOTATATE is a somatostatin analog PET tracer which has high affinity to meningioma expressing somatostatin receptor. Methods and subjects: In this case series review, we described 8 patients with brain MRI suspected of recurrent meningioma who underwent focused 68Ga-DOTATATE PET/CT scan for radiation treatment planning. Results: The combined brain MRI and PET/CT allowed improved conspicuity of the lesions and aided radiation treatment planning. The time from the initial surgery to PET/CT scans varied widely ranging from 1 year to 12 years. Three patients had PET/CT shortly after the initial surgery (1-3 years) and underwent targeted radiation therapy. Subsequent imaging showed no evidence of recurrence. Four patients had prolonged time between the PET/CT and the initial surgery (7-12 years) which showed extensive tumor burden. All four patients expired shortly after the last PET/CT scan. Conclusion: 68Ga-DOTATATE PET shows promising complementary role in detection and treatment planning of recurrent meningioma.

Identification of metabolic pathways underlying FGF1 and CHIR99021-mediated cardioprotection.

Acute myocardial infarction is a leading cause of death worldwide. We have previously identified two cardioprotective molecules - FGF1 and CHIR99021- that confer cardioprotection in mouse and pig models of acute myocardial infarction. Here, we aimed to determine if improved myocardial metabolism contributes to this cardioprotection. Nanofibers loaded with FGF1 and CHIR99021 were intramyocardially injected to ischemic myocardium of adult mice immediately following surgically induced myocardial infarction. Animals were euthanized 3 and 7 days later. Our data suggested that FGF1/CHIR99021 nanofibers enhanced the heart's capacity to utilize glycolysis as an energy source and reduced the accumulation of branched-chain amino acids in ischemic myocardium. The impact of FGF1/CHIR99021 on metabolism was more obvious in the first three days post myocardial infarction. Taken together, these findings suggest that FGF1/CHIR99021 protects the heart against ischemic injury via improving myocardial metabolism which may be exploited for treatment of acute myocardial infarction in humans.

Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results.

Checkpoint inhibitor (CPI) therapies provide limited benefit to patients with tumors of low immune reactivity. T cell-inducing vaccines hold promise to exert long-lasting disease control in combination with CPI therapy. Safety, tolerability and recommended phase 2 dose (RP2D) of an individualized, heterologous chimpanzee adenovirus (ChAd68) and self-amplifying mRNA (samRNA)-based neoantigen vaccine in combination with nivolumab and ipilimumab were assessed as primary endpoints in an ongoing phase 1/2 study in patients with advanced metastatic solid tumors (NCT03639714). The individualized vaccine regimen was safe and well tolerated, with no dose-limiting toxicities. Treatment-related adverse events (TRAEs) >10% included pyrexia, fatigue, musculoskeletal and injection site pain and diarrhea. Serious TRAEs included one count each of pyrexia, duodenitis, increased transaminases and hyperthyroidism. The RP2D was 1012 viral particles (VP) ChAd68 and 30 µg samRNA. Secondary endpoints included immunogenicity, feasibility of manufacturing and overall survival (OS). Vaccine manufacturing was feasible, with vaccination inducing long-lasting neoantigen-specific CD8 T cell responses. Several patients with microsatellite-stable colorectal cancer (MSS-CRC) had improved OS. Exploratory biomarker analyses showed decreased circulating tumor DNA (ctDNA) in patients with prolonged OS. Although small study size limits statistical and translational analyses, the increased OS observed in MSS-CRC warrants further exploration in larger randomized studies.

Factors Influencing Fellowship Decision Making During Physical Medicine & Rehabilitation Residency.

ABSTRACT: Previous surveys have demonstrated an increasing trend among graduating physiatry residents who desired to pursue a subspecialty fellowship. There has been sparse information on whether residents start their training with a subspecialty interest in mind and what factors influenced them to choose a fellowship. This article describes a prospective survey in the 2019-2020 academic year in which 175 responses were collected representing 65 (78.3%) of the 83 physical medicine and rehabilitation programs with graduating residents. Nearly 3 in 4 (73.7%, 129/175) reported matching into a fellowship, and among those, 79.8% (103/129) had matched into a pain, spine, or sports medicine fellowship. At the start of residency, 62.3% (109/175) were planning to pursue a fellowship, with 54.9% (96/175) planning to focus on either pain, sports, or spine medicine. Most respondents (72.2%) did not change their initial subspecialty focus during their residency training. Forty-six percent agreed that their anticipated subspecialty influenced their choice of residency program. The results of this survey demonstrate that most graduating residents are matriculating into fellowship training with pain, spine, and/or sports medicine being among the top choices. These results underscore the importance of subspecialty interests of trainees at the start of their residency and how training may influence their subspecialty interest.

Complications Associated With Electromyography: A Systematic Review.

OBJECTIVES: The aims of the study were to systematically review the available literature concerning complications due to electromyography and to review those associated with nerve conduction studies. DESIGN: A systematic review was undertaken of Medline and Cochrane Central Register of Controlled Trials. Any complication related to clinical electromyography written in English was included, and all bibliographies were scanned for missed articles. RESULTS: A total of 27 articles fit the inclusion criteria, with two observational studies, and the rest case series or case studies; 42 patients were reported. Of these, 28 patients required hospitalization and 22 required surgery or a procedure, with zero deaths reported. Needle-related complications were the most prevalent (18 patients reported), with 17 related to pneumothoraces. Disorders of hemostasis were identified in 13 patients (many were asymptomatic) and cutaneous disorders were identified in 11 patients. Only one complication was identified in the narrative review related to nerve conduction studies. CONCLUSIONS: This systematic review identified a variety of complications related to electromyography. Although the incidence of these occurrences cannot be elucidated from the case series and case study-predominant literature, adverse events seem to be rare but can cause significant morbidity. Electromyographers should be aware of all reported complications; this review outlines all reported occurrences that fit the inclusion criteria.

Low-profile elastic exosuit reduces back muscle fatigue.

We investigated the extent to which an un-motorized, low-profile, elastic exosuit reduced the rate of fatigue for six lumbar extensor muscles during leaning. Six healthy subjects participated in an A-B-A (withdrawal design) study protocol, which involved leaning at 45º for up to 90 s without exosuit assistance (A1), then with assistance (B), then again without assistance (A2). The exosuit provided approximately 12-16 Nm of lumbar extension torque. We measured lumbar muscle activity (via surface electromyography) and assessed fatigue rate via median frequency slope. We found that five of the six subjects showed consistent reductions in fatigue rate (ranging from 26% to 87%) for a subset of lumbar muscles (ranging from one to all six lumbar muscles measured). These findings objectively demonstrate the ability of a low-profile elastic exosuit to reduce back muscle fatigue during leaning, which may improve endurance for various occupations.

Ultrasound neuromodulation depends on pulse repetition frequency and can modulate inhibitory effects of TTX.

Ultrasound is gaining traction as a neuromodulation method due to its ability to remotely and non-invasively modulate neuronal activity with millimeter precision. However, there is little consensus about optimal ultrasound parameters required to elicit neuromodulation and how specific parameters drive mechanisms that underlie ultrasound neuromodulation. We address these questions in this work by performing a study to determine effective ultrasound parameters in a transgenic mouse brain slice model that enables calcium imaging as a quantitative readout of neuronal activity for ultrasound neuromodulation. We report that (1) calcium signaling increases with the application of ultrasound; (2) the neuronal response rate to ultrasound is dependent on pulse repetition frequency (PRF); and (3) ultrasound can reversibly alter the inhibitory effects of tetrodotoxin (TTX) in pharmacological studies. This study offers mechanistic insight into the PRF dependence of ultrasound neuromodulation and the nature of ultrasound/ion channel interaction.

Image-Guided Sacroiliac Joint Injections: an Evidence-based Review of Best Practices and Clinical Outcomes.

Injections into the intraarticular sacroiliac joint (SIJ) are commonly done for both diagnostic and therapeutic reasons. Injection of an anesthetic can aid in the diagnosis of SIJ pain. Corticosteroids can be administered with the goal of providing a therapeutic effect. This article summarizes the literature regarding the diagnostic and therapeutic effects of these injections. It includes a review of the various imaging modalities including fluoroscopy, ultrasound, and computed tomography guidance, as well as a discussion on the prevalence data and other variables that may affect the reported outcomes.