Publications by Year: 2026

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.

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.

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.

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.

BACKGROUND: This study evaluates impact of converting from local to general anesthesia on transcarotid artery revascularization (TCAR) outcomes and identifies risk factors predictive of conversions.

METHODS: A total of 58,960 TCAR cases from the Vascular Quality Initiative (2018-2024) were categorized by anesthesia type: 6,831 local/regional anesthesia (LRA), 51,851 general anesthesia (GA), and 278 conversions from LRA to GA. In-hospital outcomes were compared using multivariate logistic regression, with stroke/death as the primary endpoint. Preoperative predictors of conversion were also assessed.

RESULTS: Converted patients were oldest, more often obese, and more likely to undergo urgent procedures. Compared to LRA, conversion was associated with increased odds of in-hospital stroke/death (adjusted odds ratio [aOR] = 3.01; 95% confidence interval [CI], 1.54-5.36; P < 0.001), stroke/death/MI (aOR = 2.92; 95% CI, 1.58-5.00; P < 0.001), and prolonged hospital stay (aOR = 1.38; 95% CI, 1.05-1.80; P = 0.020). Compared to GA, converted patients had higher odds of stroke/death (aOR = 2.95; 95% CI, 1.55-5.09; P < 0.001) and stroke/death/MI (aOR = 2.75; 95% CI, 1.52-4.57; P < 0.001). Compared to LRA, GA was only associated with longer hospital stay. Age and urgent procedures were significant preoperative predictors of conversion to GA (P < 0.05).

CONCLUSION: Conversion from LRA to GA during TCAR is associated with higher rates of stroke, death, and MI compared to LRA or initial GA. Age and urgent TCAR procedures were identified as critical preoperative factors influencing conversion risk. These findings underscore the importance of meticulous preoperative risk assessment and optimal anesthesia selection to minimize conversions and enhance safety in TCAR.

CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, greatly limiting the range of targetable sequences in a genome. Although engineering strategies to alter PAM specificity exist, they typically require labor-intensive, iterative experimentation. We introduce an evolution-informed deep learning model, Protein2PAM, to efficiently guide the design of Cas protein variants tailored to recognize specific PAMs. Trained on a dataset of over 45,000 CRISPR-Cas PAMs, Protein2PAM rapidly and accurately predicts PAM specificity directly from Cas proteins across type I, II and V CRISPR-Cas systems. Using in silico mutagenesis, the model identifies residues critical for PAM recognition in Cas9 without using structural information. We use Protein2PAM to computationally evolve Nme1Cas9, generating variants with broadened PAM recognition and up to a 50-fold increase in PAM cleavage rates compared to the wild type in vitro. Our machine learning approach allows Cas enzymes to target sequences that were previously inaccessible because of PAM constraints, potentially increasing target flexibility in personalized genome editing.

PURPOSE: Diabetic kidney disease (DKD) in type 1 diabetes has been shown to be strongly associated with insulin resistance, but this has not been previously explored using the euglycemic-hyperinsulinemic clamp. Therefore, we investigated insulin sensitivity in people with type 1 diabetes with and without DKD using M/I-values (mean glucose disposal rates [GDR]/mean plasma insulin) and compared GDRs to estimated GDR (eGDR)-formulae.

METHODS: In this pilot study, we studied 17 adult individuals with type 1 diabetes (ten with and seven without DKD) using euglycemic-hyperinsulinemic clamps and assessed correlations between GDR and eGDR values.

RESULTS: M/I-values were 62.5% lower in individuals with type 1 diabetes and DKD compared to those without DKD, albeit not statistically significant (0.16 ± 0.08 vs. 0.10 ± 0.08 mg/kg/min per mIU/L, P = 0.154). In the whole group (n = 17) eGDR by Williams et al. demonstrated the highest correlation with GDR (r = 0.35, P = 0.167), while eGDR by Januszewski et al. had the highest correlation in the DKD group (n = 10, r = 0.46, P = 0.177).

CONCLUSION: Our pilot study suggests the possibility of increased insulin resistance in people with type 1 diabetes and DKD.

BACKGROUND: Venous thromboembolism (VTE) remains a critical concern in plastic and reconstructive surgery (PRS) due to prolonged operative duration, perioperative immobility, and procedure-specific risks. While low-molecular-weight heparin (LMWH) has been the prophylactic standard, use of direct oral anticoagulants (DOACs) and aspirin (ASA) has been gaining traction. This study summarizes prophylactic practices in PRS.

METHODS: A systematic search of three databases was conducted. Studies evaluating ASA, DOACs, or LMWH prophylaxis in PRS with VTE, bleeding, or 30-day reoperation rates were included. Mixed anticoagulant regimens were excluded. Data on dosage, duration, and complication rates were extracted. A random-effect meta-analysis of proportions was conducted.

RESULTS: Of 884 studies screened, 7 met inclusion criteria, totaling 3,475 patients: ASA (n=402), DOACs (n=2056), and LMWH (n=802). Common regimens included ASA 325mg daily for 5 days and DOAC 10mg daily for 10 days; LMWH dosing varied. VTE rates were low across groups: 1.15% ASA, 0.3% DOACs, and 0.44% LMWH. Hematoma rates were similar for ASA (4.6%) and LMWH (4.5%), while DOACs had a higher rate (8.7%), largely influenced by an outlier. Reoperation rate was highest for ASA (16.9%), followed by DOACs (10.5%) and LMWH (8.0%).

CONCLUSION: Despite comparable VTE rates across agents, variability in bleeding and reoperation highlights the need for procedure-specific, individualized prophylaxis. ASA and LMWH may offer more predictable safety profiles, while DOACs remain promising but warrant further investigation LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .