BackgroundIndividuals with spinal cord injury (SCI) are at high risk for developing neurogenic bladder or neurogenic lower urinary tract dysfunction (NLUTD), which can lead to severe complications and negatively impact quality of life. Despite the critical need for timely urologic care, barriers to access remain poorly understood, particularly in resource-limited settings. This study aims to identify systemic and perceived barriers to urologic follow-up for individuals with SCI treated at an academic medical center. MethodsA single-center, observational study was conducted on individuals presenting with a diagnosis code indicative of complete SCI at an academic hospital between October 2015 and October 2023. Data were extracted from electronic medical records using ICD-10 codes for SCI, and phone interviews were conducted to assess symptoms, quality of life, and perceived barriers to care. Descriptive statistics summarized the findings. Univariate and multivariate Firth logistic regression analyses were performed to analyze for possible covariates impacting the odds of follow-up or having obtained a urodynamics study. ResultsOf 213 records, 136 met the inclusion criteria. Among them, only 17 (13%) received a urology consultation during their hospital stay, and 28 (21%) had been seen in a urology clinic post-injury. Phone interviews with 42 patients revealed that 93% reported NLUTD symptoms, with a mean quality of life impact score of 7.3. Barriers identified included availability (71%), accessibility (45%), accommodation (69%), affordability (43%), and acceptability (31%) barriers. Firth logistic regression demonstrated that male sex was associated with lower odds (OR = 0.205, 95% CI: 0.048, 0.772, p = 0.02) of having obtained a urodynamics study. ConclusionSignificant gaps in urologic care for individuals with SCI exist. Statistically significant variation in management via Firth logistic regression analyses also demonstrates potential disparities in follow-up and management. Addressing these challenges requires improved discharge planning, increased healthcare accessibility, and innovative care models such as telemedicine. Future research should explore broader geographic regions and interventions to improve outcomes.

This series of Fact Finders presents a brief summary of the evidence and outlines recommendations regarding the injection of preservative-containing steroid formulations in the epidural space and the practice of swabbing newly opened vial tops before drawing up injectate.The evidence in support of the following facts is presented: (1) No adverse events have been documented from the administration of preservative-containing steroids into the epidural space; however, neurological injuries have been reported following intrathecal injection of these preservatives. (2) Swabbing newly opened vial tops before drawing up an injectate has been a standard procedure in healthcare settings. However, the evidence supporting its efficacy is mixed. While a recent study has found no significant benefit, guidelines from the American Society of Anesthesiologists (ASA), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO) still recommend this practice. (3) Greater than 60% isopropyl alcohol is not universally effective against all pathogens.

Background Basivertebral nerve ablation (BVNA) is a minimally invasive intraosseous radiofrequency procedure for vertebrogenic chronic low back pain (CLBP). Although randomized controlled trials have established its efficacy, real-world safety data remain limited. Purpose Post-market adverse event (AE) characterization associated with BVNA using the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database. Study design Retrospective analysis of a national medical device adverse event database. Methods The MAUDE database was queried for all reports involving FDA-cleared BVNA systems from inception to 2025. Reports were manually reviewed, deduplicated, and coded for AE type, severity, timing, and outcome. Frequencies were summarized with descriptive statistics. Results A total of 96 unique medical device reports were analyzed. Vertebral compression fracture was the most frequently reported AE, occurring in 21.9% (21/96) of reports. Among the 21 VCF-containing reports, timing was documented in 12 (57.1%): 6 occurred within 30 days post-procedure (range: 4-21 days) and 6 occurred beyond 30 days (range: 33-294 days). Timing was not reported in the remaining 9 reports. An additional 2 reports described posterior element fractures and are reported separately (2.1%, 2/96). Other common AEs included increased low back pain (10.4%), superficial bleeding (2.1%), and emergency department visits (7.3%). Severe AEs were infrequent, including hospitalization (9.4%), retroperitoneal hematoma (7.3%), and death (2.1%). Both deaths were associated with anesthesia-related events rather than the BVNA device or procedure. No cases of infection, spinal/epidural hematoma, or major neurologic injury were identified. Most reports were manufacturer-submitted, with few voluntary reports or device returns. Conclusions This MAUDE-based review complements clinical trial data by characterizing the distribution of post-market adverse event reports associated with BVNA. Vertebral fracture was the most frequently reported event, with variable timing ranging from the day of the procedure to nearly 300 days post-BVNA; no consistent temporal pattern could be established. These findings do not permit conclusions about incidence or causality but identify vertebral fracture and pain as the most represented post-market signals, and highlight the need for prospective registries with standardized follow-up, pre-procedural bone health documentation, and detailed AE capture to more precisely define the long-term safety profile of BVNA.

The t-test is a mainstay statistical test that allows researchers to use the observed averages (arithmetic means) of data samples to draw evidence-supported conclusions about the corresponding averages in the populations they represent. This article serves as an introduction to this common and useful technique for clinicians with a limited statistical background, who seek to deepen their understanding of the t-test, its reasoning, and its implications in clinical research. We describe the three basic forms of the t-test, its applications and alternatives, and some related concepts while avoiding technical concepts and jargon as much as possible.

ABSTRACT:Opioids are among the most widely prescribed treatments for pain; however, prolonged use leads to adverse effects, including tolerance and opioid-induced hyperalgesia. Neurons that detect noxious stimuli (nociceptors) within the dorsal root ganglion (DRG) are critical for both the analgesic and adverse effects of opioids. Although post-transcriptional RNA control is critical for DRG function, the role of circular RNAs (circRNAs), an evolutionarily conserved and highly stable class of RNA, in nociceptive processes remains largely unexplored. Furthermore, the effect of opioids on the circRNA landscape of human DRG (hDRG) is unknown. To address these gaps, we performed high-coverage total RNA sequencing on hDRG tissue obtained from opioid-exposed donors and compared circRNA and linear transcriptomic profiles to age- and sex-matched controls. Opioid exposure was associated with a global reduction in circRNA abundance, as well as specific alterations in 43 differentially expressed circRNAs. Parallel analysis of linear transcripts (mRNAs) revealed 349 differentially expressed transcripts, including genes involved in neuronal signaling and immune responses. Integrative circRNA-mRNA network analyses suggest that opioid-responsive circRNAs may modulate nociceptor gene expression through miRNA- and RNA-binding protein-binding mechanisms. Among opioid-associated circRNAs, circNTRK2 , derived from NTRK2 , the tyrosine kinase B receptor gene, was downregulated in both opioid-exposed hDRG tissue and a repeat morphine exposure paradigm in nociceptor-like cell line. Collectively, these findings establish the landscape of circRNAs in hDRG, reveal opioid-associated circRNA dysregulation, and highlight circRNAs as potential modulators of post-transcriptional gene expression in nociceptors.

Spinal cord injury typically leads to neurogenic bladder dysfunction, often including detrusor-sphincter dyssynergia. Sacral anterior root stimulation can empty the neurogenic bladder, but this emptying can be impeded by reflex contractions of the urethral sphincter. The sacral sensory roots are typically transected (rhizotomy) to reduce these reflex contractions, but this rhizotomy also impairs desirable reflexes (e.g., sexual function) and sacral sensation, if present. Preclinical experiments have shown that sacral nerve stimulation at 600 Hz can promote bladder emptying while reducing urethral sphincter activity. In this proof-of-concept study, we tested 600-Hz sacral nerve stimulation to limit urethral sphincter activity in individuals with spinal cord injury who were already implanted with a sacral anterior root stimulation device. Bladder pressure, urethral pressure, rectal pressure, anal pressure, and pelvic floor electromyogram were measured in response to stimulation at 20 or 600 Hz. Stimulation was feasible and well-tolerated, and frequency appeared to have an effect on lower urinary tract and bowel function. In one participant, stimulation at 600 Hz produced a significant decrease in urethral pressure compared to 20-Hz stimulation. Further work is needed to explore the potential for this approach to improve bladder emptying efficiency for individuals with spinal cord injury and detrusor-sphincter dyssynergia.

Primary sensory neurons of the dorsal root ganglion (DRG) express mu-type opioid receptors and undergo plasticity that can contribute to both analgesia and maladaptive outcomes such as opioid tolerance and opioid-induced hyperalgesia. Most mechanistic work has relied on rodent models, which may not fully capture the repertoire of opioid-responsive pathways present in humans. In this study, we tested whether morphine exposure reshapes gene expression programs in human nociceptors. Human induced pluripotent stem cell (hiPSC)-derived nociceptors were exposed to morphine (3.5 μM) acutely (1h, 16h) or repeatedly (2–3 days; daily 16h exposure separated by 8h washout) and profiled by time-series RNA sequencing. The transcriptional response to morphine included the induction of a small set of genes across exposure paradigms. P2RY11, encoding the purinergic G protein-coupled receptor P2Y11, was the most robustly induced transcript across the time course, and genes involved in purinergic signaling pathways exhibited coordinated expression dynamics. Since P2RY11 lacks a mouse/rat ortholog, its contribution to nociceptor biology and opioid responses has remained largely underexplored. Using human DRG tissue and primary human DRG cultures from organ donors, we detected P2RY11 mRNA and P2Y11 protein in neuronal populations. We observed increased P2Y11 expression in peripherin-positive neurons after morphine exposure in vitro, corroborating our sequencing results. These findings identify P2RY11/P2Y11 as a morphine-responsive purinergic receptor in DRG neurons and nominate purinergic signaling as a candidate pathway contributing to opioid-driven peripheral plasticity.

OBJECTIVE:To evaluate the effectiveness of genicular nerve radiofrequency ablation (GnRFA) for chronic knee pain via a systematic review and Bayesian network meta-analysis. METHODS:Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched through November 2, 2025, for studies of adults ≥18 years of age with chronic knee pain due to osteoarthritis or persistent postsurgical pain who received the intervention GnRFA. Comparison groups received sham, chemoneurolysis, other active treatments, or no comparator. Outcomes were the proportions of individuals with numeric rating scale or visual analog rating scale reductions of ≥50% or ≥2 points at 1, 3, 6, and 12 months. Bayesian network meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was reported according to the PRISMA guidelines. For risk-of-bias assessment, Cochrane Risk of Bias 2, Risk of Bias In Non-Randomized Studies of Interventions, and National Heart, Lung, and Blood Institute quality-assessment tools were used. RESULTS:The search identified 1740 records, with 358 full texts reviewed and 29 studies included (13 randomized controlled trials and 16 observational studies, totaling 2285 participants). GnRFA was most likely to be the highest-ranked treatment for chronic knee pain relief at 1 month (86.3%), 3 months (75.3%), 6 months (74.3%), and 12 months (75.0%) when compared with sham, intra-articular joint injections, and chemical neurolysis. CONCLUSIONS:GnRFA serves as an effective treatment for chronic knee pain from either osteoarthritis or persistent postsurgical pain for at least 12 months. Additionally, it was found to be more effective than sham for at least 6 months. STUDY REGISTRATION:The study protocol was registered in the systematic review registry PROSPERO (https://www.crd.york.ac.uk/PROSPERO; ID1179765).

Neuropathic pain affects approximately 10% of the adult population and is commonly treated with gabapentin (GBP), a repurposed anticonvulsant drug. Despite its widespread use, GBP's effectiveness varies significantly among patients, highlighting the need to better understand its functional and molecular impacts on human nociceptors. Here we characterized the electrophysiological and transcriptomic effects of GBP on primary neurons derived from the dorsal root ganglia (DRGs) of ethically consented human donors. Using patch-clamp electrophysiology, we demonstrated that GBP treatment reduced neuronal excitability, with more pronounced effects in multi-firing vs. single-firing neurons. Notably, significant donor-specific variability was observed in electrophysiological responsiveness to GBP treatment in vitro. RNA sequencing of DRG tissue from the donor that was more responsive to GBP revealed differences in transcriptome-wide expression of genes associated with ion transport, synaptic transmission, inflammation, and immune response. Cross-transcriptomic analyses further showed that GBP treatment counteracted these alterations, rescuing aberrant gene expression at the pathway level and for several key genes. This study provides a comprehensive electrophysiological and transcriptomic profile of the effects of GBP on human DRG neurons. These findings enhance our understanding of GBP's mechanistic actions on peripheral sensory neurons and could help optimize its use for managing neuropathic pain.

OBJECTIVE:To evaluate the effectiveness of genicular nerve radiofrequency ablation (GnRFA) for chronic knee pain due to osteoarthritis or persistent post-surgical knee pain (PPSP). METHODS:Population: Adults ≥ 18 years with chronic knee pain due to osteoarthritis (OA) or PPSP. Intervention: GnRFA. Comparison: Sham, placebo, active treatments, or no comparator. Outcomes: Proportion of individuals with pain score reductions of ≥ 50% or ≥ 2 points or ≥ 30% improvement in functional measures at 1, 3, 6, 12, 18, and 24 months. Search Strategy and Risk of Bias Assessment: Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched through April 2024 (PROSPERO ID CRD42024552068). Cochrane Risk of Bias 2, Risk of Bias In Non-Randomized Studies-of Interventions and National Heart, Lung, and Blood Institute quality assessment tools were used accordingly. RESULTS:The search identified 1,849 records, with 226 full-texts reviewed and 28 studies included (11 randomized controlled trials and 17 observational studies, totaling 2,218 participants). Pooled success rates for ≥50% pain reduction in both OA and PPSP were 51% (95% CI : 49-54%) at 6 months, 43% (95% CI : 40-47%) at 12 months, and 58% (95% CI : 48-67%) at 24 months. Large lesions showed higher pooled success rates compared to small lesions at 12 months (55% (95%CI : 51-59%) vs. 34% (95%CI : 26-43%)). CONCLUSIONS:GnRFA is effective in reducing knee pain in the majority of patients with osteoarthritis when large lesion techniques are used with moderate-certainty evidence, according to GRADE. Alternatively, there is low quality evidence that GnRFA results in treatment benefit for individuals with PPSP. These conclusions, however, are limited by small subgroup sample sizes and the lack of a meta-analysis.

INTRODUCTION:Existing literature has highlighted disparities in acute pain management across racial and sex groups in both emergency department and pre-hospital settings. This study aimed to evaluate prescribing patterns among physicians and advanced practice providers for patients with upper tract urolithiasis in an academic emergency department. MATERIALS AND METHODS:Retrospective chart review of patients diagnosed with upper tract urolithiasis was performed to evaluate age, sex, race, ethnicity, stone size and location, presence of hydronephrosis, admission status, history of prior nephrolithiasis, medications administered in the emergency department (ED), requests for urology consult or referral, and discharge medications. RESULTS AND CONCLUSIONS:In this single-center, propensity-matched analysis, we found no significant sex, race, or provider level of training-based differences in prescribing patterns for patients presenting with renal colic secondary to upper urinary tract stones in our academic emergency department.

Opioids are among the most widely prescribed treatments for pain; however, prolonged use leads to adverse effects, including reduced analgesic efficacy (tolerance) and paradoxically heightened pain sensitivity (opioid-induced hyperalgesia, OIH). Neurons that detect noxious stimuli within the dorsal root ganglion (DRG), referred to as nociceptors, mediate both the beneficial and maladaptive effects of opioids. Although post-transcriptional regulation is critical for DRG function, the role of circular RNAs (circRNAs), an evolutionarily conserved and highly stable class of RNA, in nociceptive processes remains largely unexplored in humans. Further, how opioids might alter the circRNA landscape of human DRG (hDRG) is unknown. To address this gap, we performed high-coverage RNA sequencing on hDRG tissue obtained from opioid-positive organ donors and compared these profiles with those from age- and sex-matched opioid-negative controls. The circRNA expression profiles were analyzed using the CIRI2/CIRIquant pipeline, and parallel measurements were made for the linear transcriptome (e.g. mRNA). Our data revealed a significant overall decrease in circRNA abundance in the opioid-exposed group. Among the top differentially expressed circRNAs were circSH3D19, circSMARCA5, circHLA-A, and circAMY2B, with an additional 39 circRNAs altered in opioid-exposed tissue. To explore potential interactions with the linear transcriptome, we constructed a competing endogenous RNA (ceRNA) network using established pipelines and databases (circAtlas, miRanda, TargetScan, PITA, and miRDB). Gene Ontology enrichment analysis of predicted mRNA targets of these circRNAs identified overrepresented pathways related to neuronal development, synaptic signaling, inflammatory processes, and pain perception. These findings suggest that circRNAs may play a key regulatory role in the DRG response to opioid exposure and modulation of pain. Future studies will investigate the spatial and temporal dynamics and functional and behavioral effects of these circRNA. ### Competing Interest Statement The authors have declared no competing interest.

Categorical variables are an integral part of clinical research. This article introduces their uses and most common analyses for clinicians seeking additional statistics exposure to more critically engage with literature and refine their own research endeavors. We describe and demonstrate the two most common tests of association for categorical variables: chi-square and Fisher's exact tests, along with their underlying logic, result interpretations, and relative strengths and weaknesses. We also introduce and explain two of the most common measurements of effect size in analyses of categorical outcomes: relative risk (RR) and odds ratio (OR).

BACKGROUND:Lumbar radicular pain is often treated with interlaminar epidural particulate corticosteroid injection (ILEPSI). However, little literature exists on epidural tissue changes post ILEPSI. Investigating these potential tissue changes is valuable because of their possible clinical implications. OBJECTIVE:To report gross and histological epidural tissue changes after ILEPSI following spinal decompression surgery and compare the observed changes to those previously reported in the literature. DESIGN:A retrospective case series and systematic literature review were conducted. Surgeons were blinded to the details of corticosteroid injections and the study's specific aims. PARTICIPANTS:Patients who underwent spinal decompression surgery and through retrospective chart review were found to have had ILEPSI prior to surgery. METHODS:Four consecutive patients undergoing spinal decompression surgery were included in a convenience sample, all exhibiting abnormal epidural tissue formation. A retrospective chart review showed that each patient had received ILEPSI at the same spinal level before surgery. A systematic literature review, registered in International Prospective Register of Systematic Reviews, was subsequently conducted based on this novel finding. RESULTS:Surgical biopsies from four patients undergoing spinal decompression after ILEPSI showed "granulomatous-like reactions" in the epidural space. A systematic literature review found no similar epidural reactions but did find comparable findings in dermatology literature. CONCLUSION:The epidural "granulomatous-like reactions" observed after ILEPSI are a novel finding, resembling tissue reactions from particulate corticosteroid administration. This suggests a potential link between ILEPSI and these reactions.