Publications by Year: 2026

Systemic lupus erythematosus (SLE) presents with diverse clinical manifestations originating from multiple contributing factors employing a complex array of pathogenetic pathways. Understanding the origin of the disease is stifled by the assumption that a set of classification criteria represent one disease. Efforts to continuously refine the SLE classification criteria over the last 50 years have been based on the assumption that they will solve core aspects of SLE. Yet, this optimism has failed to deliver, because it is not possible to conquer a complex disease through criteria which are arbitrarily selected, but not supported by causal mechanisms. We propose to reconsider the value of SLE classification criteria and contemplate the development of diagnostic criteria directed by causality to bolster research and treatment efforts. This communication proposes that SLE diagnostic criteria should replace SLE classification criteria, at which point SLE will be studied within the context of causality. Such an accomplishment will optimize SLE research and the care of patients with SLE.

Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD) are characterized by core approach and avoidance (AA) motivational system dysfunction. However, patterns of AA motivation dysfunction in mood disorders are markedly heterogeneous across studies, which is inconsistent with a singular pattern of AA motivation dysfunction in mood disorders. Thus, we utilized hierarchical cluster analysis (HCA) to classify multiple, distinct AA motivational profiles in both healthy control samples (Study 1: n = 427 and n = 462) and patients with MDD or BD (Study 2: n = 111). In both healthy control and clinical samples, we identified and replicated three distinct AA motivational profiles that were generally characterized as: 1). High Approach + Moderate Avoid, 2). Low Approach + Low Avoid, or 3). Low Approach + High Avoid. In both studies, AA motivational profiles were further characterized by multivariate, non-linear differences in self-reported reward and threat sensitivity. Compared to healthy controls, patients with mood disorders exhibited AA motivation dysfunction that systematically varied in severity across AA motivational profiles. Together, these results suggest that mood disorders may be more accurately characterized by multiple, distinct patterns of AA motivational dysfunction, which may ultimately be useful towards informing precision-medicine frameworks.

The increase in HIV pre-exposure prophylaxis (PrEP) uptake presents both challenges and opportunities. The process of initiating and continuing PrEP brings the medical care establishment into direct and ongoing contact with a young population that is often otherwise unengaged with health-care systems. The groups at highest risk for HIV acquisition, including PrEP recipients, have high rates of tobacco use, which remains the leading cause of preventable death in the world. However, there has been little attention paid to tobacco use and cessation treatment in the context of PrEP care. PrEP guidelines and tobacco use treatment guidelines do not mention the issue of tobacco use in PrEP recipients, and medical literature pertaining to this subject is virtually non-existent. Public health investments that focus on reducing the immediate risk of HIV acquisition have not been accompanied by sufficient investment aimed at mitigating the long-term harms of tobacco use within the same target population. This Viewpoint discusses easy and efficient strategies that might be used to promote tobacco use cessation in PrEP care settings and encourages health-care providers and policy makers to seize this opportunity.

INTRODUCTION: Greater Occipital Nerve (GON) neurolysis, based on the original description of the procedure, is followed by elevation of a subcutaneous fat flap that is wrapped around the nerve for cushioning. However, this technique places the nerve in a more superficial and exposed position, and may increase the susceptibility to mechanical stimuli and traction, with risk for recurrent pain or injury. More recently, techniques to bury the nerve under the trapezius or semispinalis muscle have been employed to position the nerve beneath protective soft tissues. In this article, both techniques are discussed and postoperative results are compared.

METHODS: Patients who underwent primary GON decompression surgery at three centers were included. Pain frequency, intensity and duration was collected preoperatively and postoperatively in a prospective fashion. Manual chart review was performed to collect data regarding type of flap used, complications and reoperations.

RESULTS: 391 patients underwent GON decompression surgery. A fat flap was used in 203 (52%) and a muscle flap in 188 (48%) patients. Postoperative complications were similar between groups (p=0.116). The reoperation rate was significantly higher in the fat flap group as compared to the muscle flap group (n=26 (13%) vs n=9 (4.7%); p=0.007). Postoperative pain characteristics between the fat and the muscle flap group after the last intervention were not significantly different (p>0.05).

CONCLUSION: In comparing fat versus muscle flap techniques for GON decompression, both methods effectively reduced pain. However, the muscle flap approach resulted in a lower reoperation rate, suggesting this option may provide better long-term pain relief.

INTRODUCTION: Targeted Muscle Reinnervation (TMR) can prevent and treat neuropathic pain in amputees, but the degree of success varies. This study developed a Machine Learning (ML) model to predict the likelihood of sustained pain mitigation following primary and secondary TMR based on patient characteristics.

METHODS: Patients who underwent TMR at a tertiary care center (2017-2024) were included. Patients were categorized as achieving good or poor pain outcomes based on predefined criteria: ≥3/10-point reduction (Numeric Rating Scale) for secondary TMR, or pain scores ≤3/10 for ≥3 months for primary TMR. Three ML architectures (lasso logistic regression, random forest classifier, and relevance vector machine (RVM)) were tested. Model performance was evaluated using area under the receiver operating characteristic (AUROC) curve; feature importance was quantified using Shapley additive explanations (SHAP).

RESULTS: In total, 77 primary TMR and 101 secondary TMR patients were included (median follow-up: 2.0 years). The RVM model achieved test prediction accuracy scores of 0.74±0.12 for both primary and secondary TMR, with AUROC scores of 0.78±0.13 and 0.80±0.05, respectively. For primary TMR, pre-operative opioid use, male sex, and history of depression showed strong negative impacts. For secondary TMR, pre-operative smoking, elevated pain scores, and history of anxiety were strong negative predictors. The model significantly outperformed traditional statistical approaches.

DISCUSSION: This novel custom ML model achieved strong predictive capability for TMR outcomes, demonstrating proof of concept of a practical tool for surgical planning and patient selection. The identification of several key modifiable risk factors suggests opportunities for pre-operative optimization to improve surgical outcomes.

Despite decades of research, no vaccine has been approved for herpes simplex virus-2 (HSV-2). While HSV-2 subunit vaccines have been more extensively studied, various HSV-2 mutants have also been tested. We compared three types of HSV-2 mutant viruses (replication-defective, single-cycle replication, and replication-competent) using five routes of vaccination (intramuscular, subcutaneous at two different sites, intrarectal, or intravaginal) for their ability to protect mice from intravaginal challenge with HSV-2. The replication-competent virus vaccine gave the best protection compared to the other vaccines after intravaginal vaccination of mice resulting in complete prevention of disease, and 90 % of the animals had no detectable shedding after challenge despite very low serum neutralizing titers. The replication-competent virus vaccine was also superior to the other vaccines when given intrarectally, although less effective than when given intravaginally. In contrast, when given subcutaneously in the scruff of the neck, the replication-defective vaccine was more effective than the replication-competent vaccine and the replication-defective vaccine tended to be more effective than the live vaccine when given intramuscularly. The highest levels of serum neutralizing antibody were observed with the replication-defective and single-cycle replication vaccines given intramuscularly. Thus, excellent protection from genital herpes was obtained after intravaginal vaccination with the replication-competent vaccine providing evidence that a replication-competent vaccine given by the natural route of HSV-2 infection is superior to replication-defective or single-cycle replication vaccines to reduce virus infection and spread in the genital mucosa.

BACKGROUND: Recent analysis of epidural procedure utilization has demonstrated significant shifts over the past 25 years. Utilization increased substantially until 2004, continued with modest growth through 2011, and then gradually declined through 2019 among the Medicare population. Influences from the COVID-19 pandemic, the Affordable Care Act (ACA), and economic pressures have continued to contribute to declining utilization patterns.

OBJECTIVE: The present investigation provides an updated evaluation of epidural procedure utilization for chronic pain management in the U.S. Medicare population, focusing on the time periods of 2000 to 2010, 2010 to 2019, and 2019 to 2024.

STUDY DESIGN: A retrospective cohort study evaluating utilization patterns and variables for epidural injections in the fee-for-service (FFS) traditional Medicare population in the U.S. from 2000 to 2024.

METHODS: A retrospective longitudinal analysis of Medicare Part B data from 2000 through 2024 was completed. Epidural injection services included cervical/thoracic and lumbar/caudal interlaminar injections, and cervical/thoracic and lumbar/sacral transforaminal injections, identified using procedure codes in the study database. A procedure or service represented all interventions performed during a treatment episode, incorporating add-on codes and bilateral services. Episodes were defined as one unit regardless of bilateral or additional services, reflecting the number of times patients received treatment. Utilization was assessed through counts, rates per 100,000 beneficiaries, geometric mean changes, and percent changes across key intervals (2000-2010, 2010-2019, 2019-2024). Trends by provider's specialty and place of service were also evaluated.

RESULTS: From 2000 to 2010, services, episodes, and rates per 100,000 beneficiaries increased 144.3%, 126.1%, and 103%. From 2010 to 2019, this pattern shifted to declining utilization, with reductions of 9.5% in services, 0.4% in episodes, and 9% in rates per 100,000. From 2019 to 2024, procedural rates declined 13%, episodes declined 22.6%, and episode rates declined 11.9%, corresponding to average annual reductions of 2.8%, 4.3%, and 2.6%.Comparative analysis showed that from 2000 to 2010, interlaminar epidural rates increased 43.8%, whereas transforaminal epidural rates increased 579.1%. From 2010 to 2019, interlaminar rates declined 18.4%, while transforaminal rates increased 5%. From 2019 to 2024, interlaminar rates declined 14.6% compared to 8.7% for transforaminal procedures. By 2024, interventional pain specialists performed over 92% of all epidural injections, while other specialties showed decreasing participation. A continued shift toward office settings and ambulatory surgery centers (ASCs) was also observed.

LIMITATIONS: The study includes data only through 2024 and is limited to the FFS Medicare population, excluding Medicare Advantage beneficiaries who accounted for 54% of Medicare enrollment by 2024. Limitations inherent to retrospective claims data also apply.

CONCLUSION: Epidural injection utilization has shifted substantially over the last 25 years, driven by changes in clinical practice, regulatory and economic influences, and pandemic-related disruptions. The increasing concentration of procedure utilization among interventional pain specialists, together with the continued expansion of transforaminal techniques, underscores the progressive specialization and refinement of interventional pain management within the Medicare population.

The hallmark of ERCC6L2 disease (ED) is a highly penetrant progression from bone marrow failure (BMF) to erythroid-predominant, TP53-mutated myeloid malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option, but concerns exist regarding transplant-related toxicities due to the underlying DNA repair defect. This is the first study to report a systematic analysis of HSCT in ED. We conducted a retrospective multicenter study involving 45 patients with ED who underwent HSCT in 2004-2024. The primary outcomes were overall survival (OS), transplant-related toxicity, and non-relapse mortality (NRM). The 1-year and 3-year OS were 79% (95% confidence interval [CI], 66-91) and 54% (95% CI, 35-73), respectively. Prior history of excess blasts significantly predicted inferior survival (hazard ratio [HR], 6.8; 95% CI, 2.2-20.3; P<0.001), with a median survival of 12 months (95% CI, 0-24). Grade 3-5 endothelial toxicities occurred in 27% of patients and were associated with higher NRM (HR, 7.7; 95% CI, 1.5-38.8; P=0.016). The use of non-treosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared to reduced-intensity conditioning (RIC) (HR, 4.9; 95% CI, 1.1-22.0; P=0.040), whereas outcomes with treosulfan-based MAC were comparable to RIC. In summary, allogeneic HSCT is a viable curative strategy for ED when performed before transformation to an aggressive malignancy i.e. myelodysplasia with excess blasts or acute myeloid leukemia. However, the elevated incidence of endothelial toxicity highlights the importance of optimizing conditioning intensity and enhancing peritransplant monitoring in this population.

BACKGROUND: Celiac plexus block (CPB) and celiac plexus neurolysis (CPN) are interventions used to treat chronic abdominal pain, particularly in cancer patients with pancreatic malignancy and patients who have chronic pancreatitis. Both CPB and CPN have been shown to significantly improve pain in patients with abdominal cancers while decreasing opioid consumption and side effects. Existing data on the technical variations and complications associated with both CPB and CPN are limited.

OBJECTIVES: We sought to examine the technical factors, patient demographic data, and intra- and post-operative complications and side effects of CBP and CPN.

STUDY DESIGN: We conducted a retrospective analysis of all patients at our institution who underwent CPB and/or CPN between September 2017 and February 2023. The study primarily included a chart review of patient data followed by statistical analysis.

METHODS: Computed tomography-guided imaging was used for all patients' CPB and/or CPN procedures, which included injections of either lidocaine or ethanol, respectively. Data were collected on patient demographics and baseline disease status, procedural indications, procedural technique, and intra- and post-procedural complications. Patients were stratified based on malignant and nonmalignant pain indications.

RESULTS: Of the 141 patients included in the study, 70.2% of were found to have undergone treatment for malignancy-related pain. When assessing needle position, there were no significant differences in technical data between groups. Rates of side effects, including hypotension, diarrhea, and localized pain, were overall low and similar to those reported in meta-analyses. There was a subjective improvement in pain in 67.4% of all patients.

LIMITATIONS: This study is limited by its retrospective observational nature and the inability to perform standardized pain scoring pre- and post-procedurally. Data on opioid use and consumption was inferred from prescribing data, which might not have accurately reflected real-world use. Despite these issues, this study provides insight into key patient data around CPB and/or CPN.

CONCLUSIONS: This study bridges a gap in the literature to address both technical variables and procedural complications of the CPB for patients with malignant and nonmalignant pain.