Citations

Background: Lyme disease is the most common vector-borne disease in United States children. It was traditionally thought to be limited to the Northeast and upper Midwest due to the prevalence of tick and deer vectors in these regions. We hypothesize that as Lyme disease cases in children continue to increase throughout the country, nontraditional regions such as the Midwest and South may have an increased rate of Lyme disease compared with the Northeast region. Methods: The Pediatric Health Information System (PHIS) database was queried for patients 19.0 years or younger who were treated for Lyme disease between 2004 and 2019 through Emergency Department and in-patient records using ICD coding. Data from 49 pediatric hospitals was included and the centers were split into 4 regions based on geographic location. The data was separated into 2 time periods: 2004 to 2014 and 2015 to 2019. Slopes were compared using a general linear model with interaction to determine if annual rates of Lyme disease were statistically different between the 2 time periods. The data was then split by geographic region and again the annual rate of Lyme disease was compared between the 4 regions. A P -value <0.008 was considered significant to adjust for multiple comparisons. Results: Between 2004 and 2019, 7,572 cases of Lyme disease were reported with a mean age of 9.5 years (range: 0.08 to 19.00 y) and 58% male. From 2004 to 2019, there was an annual increase of 46.5 cases. When separated by region from 2004 to 2019, the Midwest had a higher increased annual rate of Lyme disease (30.7 additional cases/year) compared with the Northeast (10.0 additional cases/y), the South (3.6 additional cases/y), and the West (2.2 additional cases/y). Conclusions: Lyme disease continues to show an increased rate across the United States. The annual increase in cases in the Midwest was significantly higher than the other regions from 2004 to 2019. There does appear to be a significant regional spread, particularly in the Midwest. Awareness of the increased rate and spread of Lyme disease across the US is crucial in helping to identify national and regional strategies to diagnose and treat this disease in children. Level of Evidence: Level IV.

Background: Spasticity is common in spinal cord injury (SCI) and multiple sclerosis (MS), and it can manifest as repeated, rhythmic muscle contractions called clonus. The spontaneous nature of clonus can disrupt independent performance of activities of daily living and negatively impact overall health and quality of life. Objectives: To quantify biomarkers of clonus and explore management of clonus in individuals with SCI or progressive MS using epidural spinal cord stimulation (ES) or dorsal root stimulation (DRS). Methods: Four male participants were included in this case series study: 3 with SCI and 1 with MS. All participants underwent temporary percutaneous ES lead placement over the dorsolateral thoracolumbar region of the spinal cord. Participants with SCI were also implanted with DRS leads at the L4 dorsal root. Clonus was elicited mechanically at the ankle while recording electromyography of the soleus muscle synchronized to direct spinal cord field potential recordings from ES and DRS percutaneous leads. Results: Clonus was evident as a prominent band (5-8 Hz) in recordings from ES leads, DRS leads, soleus muscle, and accelerometry. In 4 participants, percutaneous spinal stimulation reduced median clonus duration and cycle count. Clonus was immediately suppressed upon activation of spinal cord stimulation, and the suppression persisted even when clonus was reinitiated after turning off the stimulation. Conclusion: The use of objective biomarkers, including spinal cord potentials, to quantify clonus in real time combined with the immediate and reversible effects of stimulation highlight the potential of neuromodulation as a therapeutic tool for managing clonus. These data demonstrate preliminary efficacy of ES and DRS for clonus monitoring and treatment in 4 participants.

ABSTRACT Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial ( n = 384, 53%) or total ( n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy ( RT ) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively ( RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates ( RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates ( RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.

Abstract Oxygen deprivation within large or poorly vascularized bone defects remains a key barrier to successful regeneration, especially during the early postimplantation period before vascular ingrowth. Here, the development of COSnPPOD (CaO 2 –Silica NP Platform for Osteogenic Development) is reported, a visible light digital light processing‐printed hydrogel scaffold that integrates oxygen‐releasing nanoparticles (NPs) within a Primitive‐type triply periodic minimal surface architecture. The scaffold combines a gelatin methacrylate‐poly(ethylene glycol) diacrylate matrix with calcium peroxide (CaO 2 )‐loaded hollow silica NPs, enabling localized, short‐term oxygen release while preserving structural fidelity. COSnPPOD scaffolds demonstrate favorable degradation kinetics, tunable stiffness, and increased protein adsorption in vitro. In a preosteoblast model, COSnPPOD maintains cell viability and supports osteogenic gene expression without cytotoxic effects. While overall gene expression is comparable to controls, a 16‐fold increased expression of phosphoprotein 1 (Spp1) suggests scaffold‐driven activation of matrix remodeling pathways. In vivo, COSnPPOD scaffolds enhance bone regeneration in a murine calvarial defect model, with significantly greater bone formation and collagen deposition than untreated defects and hydrogel controls. Additionally, vascular endothelial growth factor immunostaining is increased within the defect, consistent with a proangiogenic response, and no systemic toxicity is observed. These findings establish COSnPPOD as a promising scaffold system that combines sustained oxygenation with biomimetic geometry to support localized bone regeneration.

Spinal cord stimulation (SCS) is effective for some pain syndromes, but inappropriate referrals can frustrate patients and misuse resources. This retrospective study reviewed 370 patients referred to a Neuromodulation for Pain Program (NPP) from July 2022 to June 2024. Of these, 241 were deemed appropriate for SCS. The SCS-appropriate group had higher pain intensity, more neuropathic pain, and lower opioid use. Inappropriate referrals were often from family physicians. Key factors associated with inappropriateness included low pain intensity, lack of neuropathic features, and high opioid use. Enhancing referral quality through targeted education may improve care and system efficiency.

Abstract BACKGROUND Tau‐derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid‐beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long‐term anti‐Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them. METHODS A post‐hoc analysis of the DIAN‐TU‐001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab ( n = 50), gantenerumab ( n = 52), or placebo ( n = 40). High‐resolution mass spectrometry quantified CSF tau species over four years. RESULTS Phosphorylated tau (p‐tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab‐mediated Aβ plaque reduction. Nearly a decade later, MTBR‐tau243 and p‐tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION Initially changing soluble p‐tau species track Aβ plaque reduction, while ptau205 and MTBR‐243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. Highlights p‐tau217 and p‐tau231 correlate with Aβ‐PET and respond to Aβ‐plaque lowering therapies. Aβ immunotherapy trials support a direct link between p‐tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT‐related biomarkers. Blood‐based p‐tau217 assays may provide a non‐invasive tool to monitor Aβ therapies. MTBR‐tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT‐targeting therapies.

Abstract Background The past two decades have witnessed tremendous growth in the appreciation and treatment of sacroiliac joint (SIJ) complex pain, including anatomical dissections that shed light on innervation, an appreciation for the contribution of extra-articular components to SIJ complex pain, the advent of radiofrequency ablation (RFA) and a host of minimally invasive surgical techniques. Yet, there is no standardization on diagnosis and treatment paradigms. Methods In February 2023, the Boards of Directors for the American Academy of Pain Medicine (AAPM) and American Society of Regional Anesthesia & Pain Medicine (ASRA-PM) approved the development of multispecialty guidelines on SIJ complex pain. Thirty partner organizations with clinical and scientific interests in SIJ complex pain were identified, and formal letters of request-for-participation were sent to each, along with a request for nominees to serve on the committee. Twenty five organizations agreed to participate in addition to the Departments of Defense and Veterans Affairs. A steering committee developed 21 questions, which spanned criteria for diagnosis, non-interventional and interventional treatments including surgery, technical parameters on how to optimize results, and what constitutes positive outcomes. Questions were methodically assigned to specialized modules comprising 4-5 members with complementary expertise, who collaborated with the Subcommittee Lead and one of three Committee Chairs to develop preliminary drafts. Following thorough revisions, these drafts were subsequently submitted to the full committee for comprehensive review. A modified Delphi method was used in which the answers to questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was achieved. During a committee meeting before commencement, it was agreed that recommendations would be noted when there was &gt;50% agreement among committee members, but that a formal recommendation would require ≥75% consensus. Results Twenty-one organizations formally endorsed the guidelines. The American Society of Anesthesiologists, and American Academy of Physical Medicine & Rehabilitation, and the North American Spine Society affirmed the benefit of the guidelines but did not officially endorse them. The American Academy of Neurology declined to affirm the benefit of the guidelines citing “lack of relevance to their membership.” Per policies, while the Departments of Defense and Veterans Affairs did not formally review the guidelines for endorsement, their representatives approved them. In addition to being endorsed or the benefit affirmed by all voting organizations, complete consensus from committee members was obtained on all 21 questions. On 2 recommendations, there were dissensions from 3 societies who thought that selecting patients for sacral lateral branch RFA and minimally invasive fusion should be based on ≥75% relief from 2 blocks instead of at least 50% relief from a single block before RFA, and greater than 50% pain relief with documented functional improvement after a single block before fusion. One additional society (Latin American Society of Regional Anesthesia) abstained on the statement that the evidence is stronger for extra-articular than intra-articular injections. The committee found that a battery of physical exam tests has reasonable sensitivity, but lower specificity, for identifying intra-articular but not extra-articular pathology, with negative tests having greater predictive value than positive ones. Intra-articular injections have diagnostic validity for SIJ intra-articular, but not extra-articular pain. There is unclear or negative evidence for imaging. The prevalence rates of intra-articular and extra-articular pathology are comparable, with both intra- and extra-articular steroid injections providing at least 4 weeks of relief in well-selected patients. However, the evidence is slightly stronger for extra-articular corticosteroid injections to provide short-term relief. The evidence base for non-interventional therapies is indirect, extrapolated mostly from low back pain studies. There is weak evidence supporting dextrose-based prolotherapy and platelet-rich plasma to provide at least 3 months of pain relief. There is strong evidence for sacral lateral branch RFA to provide relief for at least 6 months in individuals with extra-articular pathology, with face validity and indirect evidence from randomized trials supporting sacral lateral branch blocks as a prognostic tool. There is stronger evidence for larger lesions or more aggressive lesioning strategies than for less stringent techniques. There is weak evidence to support non-steroidal anti-inflammatory drugs to prevent neuritis after RFA, and in most cases anticoagulation does not require cessation in the periprocedural perioid. With an aggressive lesioning strategy, sensory stimulation provides minimal therapeutic benefit, with weak, extrapolated evidence that motor stimulation can provide safety benefit. The cutoff to designate diagnostic or prognostic blocks as positive is most commonly set at 50%, with higher values not shown to improve outcomes for more definitive procedures; for therapeutic treatment outcomes, the evidence supports a lower threshold of ≥30% pain relief or meaningful benefit on non-pain outcomes (eg, opioid cessation) for designation of a positive response. For carefully selected patients with intra-articular SIJ complex pain based on controlled blocks who have failed conservative therapies, there is weak or very weak evidence that minimally invasive SIJ fusion can provide benefit for at least one year. Conclusions SIJ complex pain remains an underappreciated source of chronic low back pain, affecting between 15% and 30% of patients with axial pain predominantly below L5. Answers to many questions were limited by low-quality evidence, indicating the need for better research. SIJ complex pain is a multifarious condition (ie, pain can be from different portions of both the intra- and extra-articular components of the joint) for which an interdisciplinary, multimodal treatment plan can optimize treatment outcomes.

ABSTRACT Precision medicine approaches have gained attention for their potential to more effectively manage obesity by tailoring diagnosis and treatment strategies to individual characteristics, including genetic background, phenotypes, metabolic profiles, and environmental exposures. The current review evaluates the evidence for precision medicine in weight management by summarizing the proceedings of a Pennington Biomedical Scientific Symposium titled “Precision Prevention, Diagnostics, and Treatment of Obesity: Pipedream or Reality?” This review discusses the extent to which we can classify and predict obesity risk based on individual‐level factors; whether we have the diagnostic capability to prospectively identify people who will benefit most from specific interventions; whether prospective trials demonstrate superior prevention and treatment of obesity when precision approaches are applied; and whether evidence is sufficient to guide policy decisions. Expert opinions were presented on the current evidence of precision medicine for obesity to collectively evaluate key barriers and opportunities for implementation of precision approaches in clinical and public health settings.