Faculty Bibliography

BACKGROUND:As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. OBJECTIVE:To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. METHODS:Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. RESULTS:Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). LIMITATIONS/CONCLUSIONS:The study lacked sufficient representation from Africa and South America. CONCLUSION/CONCLUSIONS:SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence-based treatment recommendations.

BACKGROUND AND OBJECTIVE/OBJECTIVE:The PRESERVE study (NCT04972097) assessed the safety and effectiveness of irreversible electroporation (IRE) with the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). METHODS:. The primary endpoints were the rate of local pathological complete response (negative in-field biopsy) and the incidence, type, and severity of adverse events by 12 mo. The secondary endpoints included PSA kinetics, changes in prostate volume, retreatment, and urinary/sexual function. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Of the 121 patients treated with IRE, the negative in-field biopsy rate at 12 mo was 71% (95% confidence interval [CI]: 62%, 79%). The secondary endpoint of negative in-field biopsy rate defined by the Delphi consensus criterion was 84% (95% CI: 76%, 90%). The time to median PSA nadir was 3.5 mo, and the median percent reduction in PSA at 6 mo was 68.2%. Urinary function outcomes had a mean change from baseline to 12 mo of 3 in the University of California Los Angeles Expanded Prostate Cancer Index Composite urinary domain total score and a mean change of -2 in the International Prostate Symptom Score total symptom score. At 12 mo, 84% of patients with good baseline sexual function maintained erections sufficient for penetration. Fourteen (12%) patients experienced Common Terminology Criteria for Adverse Events grade ≥3 and three experienced procedure-related grade 3 adverse events. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:IRE with the NanoKnife System is safe and effective for prostate tissue ablation.

BACKGROUND:The severity of unilateral cleft lip significantly influences surgical outcomes, yet no standardized system exists to classify cleft severity or assess the impact of presurgical infant orthopedics (PSIO). This study proposes an objective classification system integrating anthropometric measurements with expert evaluations. METHODS:Deidentified pre- and post-PSIO photographs of 50 infants with unilateral cleft lip from the Smile Train Express database were analyzed. Three anthropometric parameters-nostril width ratio (NWR), columellar angle (CA), and subnasale lateral displacement (SN)-were measured. An expert panel of orthodontists and surgeons independently rated cleft severity and PSIO outcomes in a structured three-stage process. Severity thresholds were established through consensus, and interrater agreement was analyzed using weighted kappa. RESULTS:Consensus-derived thresholds categorized NWR, CA, and SN into four severity levels. Interrater agreement for cleft severity improved across stages, reaching near-perfect levels in Stage 3 (weighted kappa = 0.91 pre-PSIO, 0.93 post-PSIO). While pre-PSIO agreement was similar between surgeons and orthodontists, post-PSIO assessments showed greater variability. PSIO had a disproportionate effect on nasal morphology (CA) compared to maxillary segments (NWR, SN), with severe NWR and SN frequently coexisting with mild CA. The proposed classification system demonstrated substantial reliability, aligning at least two parameters within the same severity subclassification. CONCLUSIONS:This study introduces a standardized classification system for cleft severity and PSIO outcomes, demonstrating strong interrater reliability. By integrating anthropometric data with expert assessments, it provides a reproducible framework for clinical and research applications. Further refinements, including intraoral measurements and 3D imaging, may enhance its precision and applicability.

BACKGROUND:Penile cancer is a rare malignancy, the most common subtype of which is squamous cell carcinoma (SCC). Organ-sparing surgery (OSS) is the first-line treatment for early-stage tumors given the quality-of-life impairments of penectomy. However, the rarity of penile SCC has made the large-scale study of the efficacy of surgical approaches difficult. OBJECTIVE:To evaluate the rates of positive margins with the surgical approaches for penile SCC. METHODS:Retrospective cohort study of adult patients with excised penile SCC from the National Cancer Database diagnosed from 2004 to 2019. RESULTS:We found that treatment of penile SCC with OSS resulted in a positive margin rate of 18.8% (SE: 0.7%) versus 9.7% (SE: 0.4%) with partial penectomy and was associated with twice the odds of a positive margin compared with partial penectomy (odds ratio 2.312; p < .001). Positive margins were associated with poorer overall survival on multivariable analysis (hazard ratio 1.528; p < .01). CONCLUSION/CONCLUSIONS:OSS for penile SCC results in high rates of positive margins, which are associated with poorer overall survival. Use of margin-controlled surgery may improve local control for these tumors while minimizing functional damage to an anatomically sensitive organ, allowing for the most optimal quality-of-life outcomes.

BACKGROUND:The purpose of this study was to compare hospital quality and patient outcomes of hip arthroplasty for femoral neck fractures (FNFs) based on the subspecialty training of the treating surgeon: orthopaedic trauma (OT) versus adult reconstruction (AR) fellowship training. METHODS:A retrospective review was conducted on 1,008 elderly patients treated for an FNF with hemiarthroplasty or total hip arthroplasty between 2014 and 2024. Patients were grouped by their surgeon's subspecialty training (OT versus AR). Outcomes analyzed included length of stay, complications, 30-day and 90-day readmissions, dislocations, infections, and 30-day mortality. Statistical significance was set at P < 0.05. RESULTS:Baseline patient demographics were similar between groups, except for a higher proportion of women in the AR cohort (P = 0.008) and Black patients in the OT cohort (P = 0.016). Although age-unadjusted Charlson Comorbidity Index (CCI) was significantly higher in the AR group (P = 0.046), Score for Trauma Triage in the Geriatric and Middle Aged (STTGMA) scores, which take CCI and other health factors into account, were not significantly different (P = 0.59). In-hospital outcomes, including length of stay (P = 0.89) and minor and major complication rates (P = 0.38, P = 0.38), demonstrated no significant differences between groups. Post-discharge outcomes, including readmissions (30-day: P = 0.52, 90-day: P = 0.16), infections (P = 0.25), dislocations (P = 0.89), and 30-day mortality (P = 0.14), were also similar. CONCLUSION/CONCLUSIONS:No differences were identified in any of the outcomes analyzed between OT-trained and AR-trained surgeons in our study. This suggests that when FNFs are treated at high-volume academic institutions, subspecialty training may not substantially influence the short-term results of FNFs treated with hip arthroplasty. These findings highlight the importance of timely surgical intervention rather than waiting for a particularly trained surgeon to be available.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The goal of this study was to develop a highly precise, dynamic machine learning model centered on daily transcranial Doppler ultrasound (TCD) data to predict angiographic vasospasm (AV) in the context of aneurysmal subarachnoid hemorrhage (aSAH). METHODS:A retrospective review of patients with aSAH treated at a single institution was performed. The primary outcome was AV, defined as angiographic narrowing of any intracranial artery at any time point during admission from risk assessment. Standard demographic, clinical, and radiographic data were collected. Quantitative data including mean arterial pressure, cerebral perfusion pressure, daily serum sodium, and hourly ventriculostomy output were collected. Detailed daily TCD data of intracranial arteries including maximum velocities, pulsatility indices, and Lindegaard ratios were collected. Three predictive machine learning models were created and compared: A static multivariate logistics regression model based on data collected on the date of admission (Baseline Model; BM), a standard TCD model using middle cerebral artery flow velocity and Lindegaard ratio measurements (SM), and a machine learning long short term memory (LSTM) model using all data trended through the hospitalization. RESULTS:A total of 424 patients with aSAH were reviewed, 78 of whom developed AV. In predicting AV at any time point in the future, the LSTM model had the highest precision (0.571) and accuracy (0.776), whereas the SM model had the highest overall performance with an F1 score of 0.566. In predicting AV within 5 days, the LSTM continued to have the highest precision (0.488) and accuracy (0.803). After an ablation test removing all non-TCD elements, the LSTM model improved to a precision of 0.824. CONCLUSION/CONCLUSIONS:Longitudinal TCD data can be used to create a dynamic machine learning model with higher precision than static TCD measurements for predicting AV after aSAH.

BACKGROUND AND AIMS/OBJECTIVE:Pre-eclampsia confers increased risks of long-term cardiovascular disease (CVD). However, little is known about CVD risk among patients diagnosed with eclampsia, especially in the post-partum period. The aim of this study was to determine whether patients with eclampsia are at increased risk for readmission for CVD within the first year after delivery. METHODS:Using the Nationwide Readmissions Database from 2010 to 2018, readmissions for CVD events were identified during the calendar year after delivery in patients with eclampsia. Prevalence rates of CVD readmission (per 100 000 deliveries) were determined, and associations between eclampsia and CVD rehospitalization were based on a confounder adjusted hazard ratio (HR) with a 95% confidence interval (CI). A quantitative bias analysis addressed eclampsia misclassification and unmeasured confounding biases. RESULTS:Of over 27 million delivery hospitalizations, 20 478 (74.7 per 100 000) were complicated by eclampsia. CVD readmission rates among the eclampsia and normotensive patients were 854 and 147 per 100 000 delivery hospitalizations, respectively (rate difference 707, 95% CI 473-941; HR 6.9, 95% CI 4.5-10.4). HRs were high for specific heart disease types (range of adjusted HRs 4.8 to 15.5). Eclampsia was associated with a substantially high risk for stroke readmissions (adjusted HR 12.6, 95% CI 6.9-22.8). CONCLUSIONS:Eclampsia is associated with an increased risk for CVD complications compared with normotensive conditions, even as early as the first month following delivery. These data highlight the need for targeted short-term follow-up for CVD complications among patients whose pregnancies are complicated by eclampsia.

BACKGROUND:Anxiety disorders may partly stem from altered neurodevelopment of attention-related networks. Neonatal alterations in resting-state functional connectivity (rsFC) among the dorsal attention (DAN); frontal parietal (FPN); salience (SN); and default mode networks (DMN)) relate to fearful temperament, a risk marker for anxiety. Nevertheless, little research examines development of these networks beyond the first months of life, particularly in fearful infants. This study examines how changes in these networks in the first two years of life relate to fearful temperament. METHODS:Using data from the Baby Connectome Project (from 180 infants across 396 sessions), we conducted independent components analysis to extract rsFC among the DMN, SN, DAN, and FPN. Longitudinal modeling characterized 1) age-related changes (slope) in rsFC through age two; 2) relations between rsFC change (slope) and fearfulness at age 2; 3) relations between rsFC and fearfulness trajectories (slope and intercept) over the first two years of life. RESULTS:Age-related decreases occurred in rsFC in DAN - FPN and DMN - SN. Smaller decreases in DAN - FPN rsFC over time related to greater fear at age 2, and to increases in fearfulness over time. High initial DAN-FPN rsFC and low initial DAN - SN rsFC also related to increasing fearfulness over time. CONCLUSION/CONCLUSIONS:This study provides the first evidence that changes in attention-related brain networks are related to early-life fearfulness, a robust early-life risk marker of anxiety.

BACKGROUND:Spinocerebellar ataxia type 27 B (SCA27B) caused by GAA trinucleotide repeats in the fibroblast growth factor 14 gene is emerging as a common cause of late-onset ataxia. Oscillopsia due to downbeat nystagmus (DBN) and diplopia are common symptoms, yet the causes of diplopia and strabismus patterns are poorly defined. METHODS:Retrospective chart review of 18 patients diagnosed with SCA27B over the past year. RESULTS:Ten of 18 patients had episodic or persistent oscillopsia or diplopia at disease onset, neurologically isolated in 4. Seventeen had detectable DBN, although it was often delayed in onset and was clinically obvious in only 5. Diplopia was present in 14 patients: vertical due to skew deviation (static and or alternating on lateral gaze) (n = 8) and/or horizontal due to vergence dysfunction (n = 11). Symptomatic vergence dysfunction included convergence insufficiency (CI) (n = 4) and divergence insufficiency (n = 5). Thirteen of 16 patients experienced improvement in oscillopsia or imbalance on 4-aminopyridine (4-AP). CONCLUSIONS:Strabismus patterns causing diplopia in patients with SCA27B are, not unexpectedly, largely attributable to cerebellar dysfunction and are not unique to SCA27B. The exceptions to cerebellar localization were CI, sixth nerve palsy, and slow saccades. Careful assessment for DBN in patients presenting with episodic or persistent diplopia from skew deviation or vergence disorders is important, as this may be key to confirming a cerebellar localization, subtle on examination, and guide toward genetic testing and 4-AP treatment.

RATIONALE/BACKGROUND:Excessive stress (distending pressure), strain (volume deformation), and drop in inspiratory alveolar pressure are proposed mechanisms for patient self-inflicted lung injury. OBJECTIVES/OBJECTIVE:To dissect the influence of inspiratory effort, respiratory mechanics, and ventilation mode on lung stress, strain, and drop in inspiratory alveolar pressure; and explore their impact on oxygenation and lung compliance. METHODS:International cohort study analyzing respiratory recordings (esophageal pressure) of patients with acute hypoxemic respiratory failure. Association between muscular pressure (Pmus), surrogates of stress (driving trans-alveolar pressure), strain (tidal volume), and inspiratory alveolar pressure relative to PEEP were explored with mixed-models, including interactions for ventilation mode, respiratory system elastance, and synchrony. Association between these and changes in oxygenation and lung compliance were explored. MEASUREMENTS AND MAIN RESULTS/RESULTS:O, p<0.001). Volume-control ventilation showed less increase in stress and strain surrogates than pressure-targeted modes, but more drop in alveolar pressure (p<0.001, Pmus:mode interaction). Breath-stacking was infrequent and associated with higher stress. Lower inspiratory alveolar pressure relative to PEEP was associated with subsequent worsening oxygenation (p=0.04) and higher stress with worsening lung compliance (p=0.023). CONCLUSION/CONCLUSIONS:Strong efforts are associated with high surrogates for lung stress, strain, and lower inspiratory alveolar pressure relative to PEEP, differently according to the mode of ventilation, being associated with subsequent worsening oxygenation and lung compliance.