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Abstract Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by drug‐resistant seizures and developmental slowing. Although cognitive and executive function deficits have been described, their early trajectory is not well understood. Methods The prospective ENVISION natural history study (NCT04537832) assessed cognitive, executive, and adaptive function in children younger than 5 years of age with SCN1A + DS every 6 months for up to 2 years using Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID‐III), Wechsler Preschool & Primary Scale of Intelligence, 4th Edition (WPPSI‐IV), Vineland Adaptive Behavior Scales, 3rd Edition (VABS‐3), Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF‐P), and Pediatric Evaluation of Disability Inventory (PEDI). Results Fifty‐eight children were enrolled, with 47% younger than age 2 years. At least 80% of children did not achieve age‐appropriate milestones. Mean BSID‐III Cognitive raw scores increased minimally, with age‐equivalent gains of only 3 months over 1.5 years. Mean Cognitive Composite scores declined significantly by Month 12 (from 81.6 to 72.2; change: –11.0, 95% confidence interval [CI]: −15.3 to −6.8), signaling a widening gap compared with neurotypical development. Executive function worsened, with mean BRIEF‐P Global Executive Composite T‐scores increasing by 3.2 points/year. For some participants, scores were 5 standard deviations (SD) above the normative mean, reflecting abilities profoundly below age expectations (bottom .00003% of the population). Adaptive functioning worsened, with mean VABS‐3 Adaptive Behavior Composite decreasing from 78.7 to 68.1 over 1.5 years (change: –9.0, 95% CI: −11.9 to −6.1) and greater decline among children <2 years at enrollment, with scores decreasing by ~15 points (1 SD). Over half of children >3 years could not remove clothing independently; and when placed on a toilet, 48% could not use it. Significance Infants and young children with SCN1A + DS show significant and progressive developmental slowing across several domains, highlighting urgent need for therapies to mitigate the devastating impact on individuals and families.

OBJECTIVE Surgical site infection (SSI) is a leading cause of morbidity following posterior spine surgery. The optimal choice of skin closure technique depending on patient- and procedure-specific characteristics remains to be elucidated. METHODS The Neurosurgery Enterprise Registry (NER) at Mayo Clinic was queried for patients who underwent posterior spine surgery from 2017 to 2023. Propensity matching was performed to match patients on the basis of the development of SSI and baseline characteristics, including age, sex, race, and comorbidities. Perioperative outcomes were analyzed using data from the NER and medical records. RESULTS A total of 18,842 cases of posterior spine surgery were identified in the NER, and SSI was observed in 154 cases (0.8%). Of these patients, 308 patients were included in the 1:1 propensity score–matched cohort analysis, with 154 patients included in each group. Sutures were used in 224 patients (72.7%) and staples in 84 patients (27.3%) (p < 0.01). Female patients comprised 45.1% of the sutures group and 46.4% of the staples group (p = 0.8). The mean ± SD age was 59.8 ± 15.4 years in the sutures group and 60.8 ± 11.9 years in the staples group (p = 0.6). Fusion was performed in 27.2% of patients in the sutures group and 44% in the staples group (p < 0.01). Multilevel fusion comprised 68.9% of fusion cases in the sutures group and 67.6% in the staples group (p = 0.8). Comorbidities, such as diabetes (p = 0.6), hypertension (p = 0.1), and the use of disease-modifying antirheumatic drugs (DMARDs) (p = 0.5) and immunosuppressants (p = 0.2), did not differ between groups. Univariate analysis performed in the propensity score–matched cohort showed that SSI was observed in 53.6% of patients in the sutures group and 40.5% in the staples group (p = 0.04). No significant differences were noted regarding 30-day (p = 0.3), 90-day (p = 0.2), and 1-year (p = 0.3) readmissions and 30-day (p = 0.7), 90-day (p = 0.8), and 1-year (p = 0.8) reoperations. On multivariable logistic regression, SSI was not significantly associated with the choice of skin closure technique (p = 0.3). CONCLUSIONS After adjustment for spinal fusion, number of fused levels, the use of immunosuppressants, and other risk factors, SSI development was not significantly associated with the use of sutures versus staples following posterior spine surgery in our institution. Additionally, no significant differences were observed regarding baseline characteristics and other perioperative outcomes. The authors’ analysis shows that skin closure technique did not significantly affect SSI rates and other outcomes in these patients.

OBJECTIVE Patient-reported outcome measures (PROMs) are standardized questionnaires used to evaluate patients’ quality of life and health status before and after medical procedures. While worse preoperative health is often associated with worse postoperative outcomes, the role of baseline PROMs in predicting postoperative dysphagia following cervical surgery has been unexplored with Eating Assessment Tool–10 (EAT-10) scores. This study aimed to investigate the relationship between baseline PROMs and the incidence of postoperative dysphagia. METHODS A prospectively collected multi-institutional quality registry of patients undergoing anterior cervical spine surgery was retrospectively reviewed. Eight baseline PROMs were assessed: Neck Disability Index (NDI), modified Japanese Orthopaedic Association scale, EQ-5D questionnaire, EuroQol visual analog scale, visual analog scales for neck pain (NP-VAS) and arm pain, and 10-item Patient-Reported Outcomes Measurement Information System Global Physical Health and Global Mental Health. Including baseline dysphagia as a fixed effect, multivariable logistic regressions were performed to examine the impact of patient-reported baseline PROMs on the incidence of dysphagia. RESULTS Baseline PROMs were collected from 1706 patients. When assessing baseline PROMs independently in multivariable analyses, worse baseline NDI score (OR 1.04, p = 0.001) was a significant predictor of dysphagia at 12 months after surgery, while other PROMs were not. When assessing baseline PROMs together in multivariable analysis, worse baseline NDI score (OR 1.07, p < 0.001) and better NP-VAS score (OR 0.88, p = 0.006) were significant predictors of dysphagia at 12 months, while other PROMs were not. Patients in the severe or complete disability NDI categories (NDI score ≥ 25; 465/1466 patients without baseline dysphagia) experienced significantly more new dysphagia at 1 month (65% vs 50%, p < 0.001), 3 months (30% vs 21%, p < 0.001), and 12 months (32% vs 14%, p < 0.001) after anterior cervical spine surgery. These patients also had no significant difference in baseline EAT-10 scores (0.103 ± 0.386 vs 0.115 ± 0.405, p = 0.6), yet experienced significantly worse EAT-10 score changes between baseline and 12 months (3.369 ± 5.954 vs 1.208 ± 3.332, p < 0.001). CONCLUSIONS Baseline NDI score appears to be the strongest independent predictor of the 8 PROMs in determining whether patients have dysphagia at 12 months after anterior cervical surgery.

OBJECTIVE This study examined the extent to which preoperative depression predicts dysphagia after cervical spine surgery. METHODS A prospectively collected multi-institutional quality registry was retrospectively reviewed. Patients undergoing cervical surgery were categorized based on preoperative depression, and correlations with pre- and postoperative Eating Assessment Tool-10 (EAT-10) dysphagia questionnaire scores were assessed. Mixed-effects logistic regressions were performed to assess the impact of preoperative depression on the incidence of dysphagia. RESULTS Of 2002 patients meeting inclusion criteria, 524 (26%) reported having preoperative depression. Depression was associated with a higher incidence of dysphagia at baseline (25% vs 12%, p < 0.001) and at 1 (62% vs 54%, p = 0.038), 3 (36% vs 26%, p < 0.001), and 12 months (36% vs 22%, p < 0.001) postoperatively. Including baseline dysphagia as a fixed effect, multivariable analysis revealed that depression is not a significant independent predictor of postoperative dysphagia at 1 (OR 1.14, p = 0.5), 3 (OR 1.09, p = 0.6), or 12 months (OR 1.27, p = 0.2). Patients with depression and no baseline dysphagia (395 of 524) were significantly more likely to report new dysphagia at 12 months (26% vs 18%, p = 0.006), but not at 1 (53% vs 52%, p = 0.7) or 3 months (28% vs 22%, p = 0.06). The average change in EAT-10 scores between baseline and 12 months was significantly worse in patients with preoperative depression and no baseline dysphagia (2.552 [SD 5.041] vs 1.634 [SD 4.095], p < 0.001). Post hoc multivariable analyses excluding those with baseline dysphagia did not significantly affect the results. CONCLUSIONS Although patients with preoperative depression report dysphagia more often at baseline and at 1, 3, and 12 months after cervical surgery, preoperative depression is not an independent predictor of postoperative dysphagia. Preoperative depression may be valuable to consider as a risk factor for developing dysphagia after cervical surgery, but the heightened dysphagia risk in patients with depression may be attributed to secondary factors associated with depression such as comorbid conditions.

ABSTRACT Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder causing hypogammaglobulinemia. Although rare, nodular regenerative hyperplasia is the most common liver complication in CVID, which can progress to noncirrhotic portal hypertension. We report a case of a young male with CVID presenting with recurrent parastomal bleeding secondary to noncirrhotic portal hypertension from CVID-associated nodular regenerative hyperplasia.

Abstract Two recent studies suggested that the APOE ε4 haplotype was associated with increased α-synuclein pathology in cell and mouse models. Genetic variants in the SNCA region have strong association with Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and idiopathic REM sleep behaviour disorder (iRBD), while APOE is a genetic risk determinant for only DLB. To determine if genetic-level interactions between SNCA and APOE exists that can explain the protein-level association, we investigated the genotypic interaction of APOE and SNCA in cohorts of PD, DLB and iRBD. We analysed genome-wide association study (GWAS) data from 5229 PD patients and 5480 controls, 2610 DLB patients and 1920 controls, and 1055 iRBD patients and 3667 controls. We used logistic regression interaction models across all three cohorts independently between the (i) top GWAS signals of SNCA single nucleotide polymorphisms (SNPs) and APOE haplotypes and (ii) SNP×SNP and three-way SNP interaction across the entire coding region plus 200 kb flanking each gene. No significant interactions were found to be associated with any of the synucleinopathies after correction for multiple testing. Our results do not support a role for genetic interactions between APOE and SNCA across PD, DLB and iRBD. Since the tested genetic variants affect the expression and function of these proteins, it is likely that any interactions between them do not affect the risk of PD, DLB and iRBD.

ABSTRACT Background Critically ill patients may be overexposed to valproate because altered protein binding leads to a disproportionate free valproate fraction. The Fraser equation was derived and internally validated to estimate critically ill patients' free valproate concentrations, but it requires external validation. Methods Adult intensive care unit (ICU) patients at two academic centers with concurrently measured free and total valproate concentrations were included. Free valproate concentrations were estimated using the Fraser equation which includes total valproate, albumin and BUN concentration, and whether the patient received propofol or aspirin. The primary outcome was Fraser equation performance, assessed using Bland–Altman methods. Comparative performance against estimates from the Doré equation (an alternative predictive equation), therapeutic concordance using a target free valproate range of 5–15 mg/L, and equation improvements were explored. Results Overall, 315 patients and 556 free‐total valproate concentration pairs were included. The mean (±SD) age was 58 (±17) years and 90 (29%) patients were on valproate prior to hospital admission. The Fraser equation estimated free valproate concentrations were correlated with measured concentrations ( r = 0.728) with a negative bias (mean bias −2.77 mg/L, 95% LOA –18.9, 13.4). The Fraser equation increasingly underestimated measured concentrations as measured concentrations increased. 71% of Fraser equation estimates were therapeutically concordant (e.g., estimate and measured both within reference range) compared to 61.9% of Doré estimates ( p = 0.001). Fraser equation modifications led to minor performance improvements but did not overcome worsening underestimation with higher measured free valproate concentrations. Conclusion The Fraser equation was moderately accurate and corresponded with an appropriate interpretation for 71% of free valproate concentrations. Worse underestimation with higher measured free valproate concentrations suggests direct measurement of free valproate concentrations is warranted. While the Fraser equation could complement therapeutic decision making at centers where direct free valproate measurements are unavailable or slow to return, its accuracy is currently insufficient to replace direct measurement.

Abstract Introduction Penile augmentation or penis enlargement surgery refers to any technique aimed at enhancing penile length or girth. These male enhancement surgical techniques can increase total penile length, either flaccid or erect, while others add to the penile shaft’s girth and/or glans size. Proposed strategies include physical methods such as various penile exercises, mechanical traction devices, and medical therapy, while surgical interventions include cosmetic and phallic reconstructive techniques and use of fillers, sleeves, grafts, and flaps to augment penile size. Objectives The International Consultation on Sexual Medicine (ICSM) consensus statements provide evidence-based recommendations and aim to guide a clinical framework in penile aesthetic and augmentation. Methods A comprehensive literature search was conducted to identify published literature relevant to penile augmentation or enhancement. Preliminary consensus was presented to the delegates attending the 5th ICSM meeting, and feedback was incorporated into the final document. Results Twenty new recommendations are provided with corresponding levels of evidence and grades of recommendation. Conclusions Due to the controversies and lack of longer-term data regarding penile augmentation and cosmetic procedures, comprehensive assessments and careful patient counseling weighing the pros and cons, as well as potential complications, are mandatory before embarking on any treatment. Surgeons should be experienced in anatomy and various surgical techniques, and it is important to individualize surgical options based on patient condition(s) and needs, surgeon expertise, and local resources.

Abstract Introduction There is no ideal treatment for Peyronie’s Disease (PD) since every patient has different needs with varying perceived risks versus benefits of individual treatment options, coupled with the degree of impact relating to PD on sexual function and beyond. Objectives The 5th International Consultation on Sexual Medicine (ICSM) guideline on PD provides an update to the previous ICSM with an aim to provide a clinical framework and best-evidenced consensus recommendations to assist clinicians in managing PD. Methodology Available literature was reviewed, and a modified Delphi consensus was undertaken by leading sexual medicine experts to achieve a set of Quality of Evidence and strength of recommendations. This guideline was developed as an authoritative best-evidenced consensus incorporating state-of-the-art knowledge and contemporary literature. Results A total of thirty-one recommendations were made on PD guidelines. New updates to the 4th ICSM on PD have been made in definition, pathophysiology, and treatment strategies. The presence of penile pain with erection could occur in the chronic phase due to torque or stretch on the penile scar and surrounding tissue. Oral therapy works best during the acute phase and should be provided concurrently with other treatment modalities. Penile traction therapy can reduce penile deformity as monotherapy or may be offered as part of a multimodal therapy approach. There is no convincing evidence supporting cellular-based therapy. The type of plication procedure used depends on the surgeon and patient preference, although excision of the tunica followed by plication may have a higher complication rate. There is currently no ideal graft, and graft contracture can occur postoperatively. Adjunctive procedures such as penile modeling, tunical plication, plaque incision/excision and grafting can be performed when penile deformity and/or penile curvature persist following penile prosthesis implantation. Conclusions The management of PD should be individualized based on the patient’s needs and preferences while balancing the benefits and risks of each treatment option.

Abstract Background DNA methylation profiling can be used to robustly predict postsurgical outcomes and response to radiotherapy (RT) for meningioma patients. To allow for seamless integration of these complementary models into clinical practice, a practical framework is needed. Methods We leveraged a cohort of nearly 2000 surgically-treated meningiomas with DNA methylation profiling and clinical outcomes data. Existing methylation-based prediction models were dichotomized to yield four risk groups: low and high recurrent risk, each with RT sensitive and resistant subgroups. Risk groups were correlated with progression-free survival in the context of existing biomarkers including extent of resection and WHO grade. Results We first demonstrated that all risk groups benefit from gross total resection. All “high-risk, RT sensitive” tumors (n = 306, 15.7%) also benefited from adjuvant RT: after GTR, median PFS increased from 4.68 (4.13-9.48) years to not reached (P = .003); after subtotal resection (STR), from 2.12 (1.59-3.02) to 4.09 (3.41-not reached) years (P = .004). “Low-risk, RT sensitive cases” (n = 1207, 61.8%) also benefited from RT after STR (median PFS 7.39 (6.66-12.8) vs. 16.53 (10.35-not reached) years, P = .03), suggesting that RT be considered in these patients. Neither “low-risk RT resistant” (n = 84, 4.3%) nor “high-risk RT resistant” (n = 356, 18.2%) cases benefited from RT, and the latter group was associated with universally poor outcomes. Conclusions We identify methylation-defined risk groups of meningioma for which additional benefit is gained from adjuvant RT, leading to a clinical decision-making framework for straightforward integration of molecular models into clinical practice.