A Comparison of Demographic Diversity Between Orthopaedic Surgery Residents and ACGME Foot and Ankle Fellows From 2007 to 2022.

Background: Academic medicine emphasizes the need to recruit a diverse workforce in graduate medical education. Orthopaedic surgery residency has demonstrated efforts to model program compositions with evolving US demographics. However, it remains unclear whether orthopaedic fellowships, particularly foot and ankle, also reflect these efforts. Methods: Using the publicly available Accreditation Council for Graduate Medical Education (ACGME) Data Resource Book, a census of the gender and racial/ethnic identities of orthopaedic foot and ankle fellows, as well as active orthopaedic surgery residents, were compiled from 2007 to 2022. Linear trend analysis was conducted to evaluate the trends of orthopaedic residents and foot and ankle fellows, with a Pearson correlation for comparison. Results: Prior analysis demonstrated no significant change in sex and ethnic diversity of fellows from 2006 to 2015. The majority of foot and ankle fellows were White (31%-69%) and male (63%-88%). Linear analysis demonstrated growing diversity in female and non-White active orthopaedic surgery residents. Similarly, there was an increasing number of female foot and ankle fellows (0%-38%) reflective of the trend in orthopaedic residency (12%-20%); however, there was no significant change among racial/ethnic identities. Pearson correlation analysis between the trend of orthopaedic residency residents and foot and ankle fellows suggests moderate correlation among female, Asian, and "Unknown" racial/ethnic categories. Conclusion: The proportion of foot and ankle female fellows in ACGME-accredited fellowships has matched or exceeded the percentage of female orthopaedic residents. Despite increased diversity of orthopaedic surgery residents over the past 2 decades, ACGME-accredited foot and ankle fellowships do not yet reflect similar trends among racial/ethnic minorities. Level of Evidence: Level III, retrospective cohort study.

Treatment of melanoma brain metastases with radiation and immunotherapy or targeted therapy: a systematic review with meta-analysis.

BACKGROUND: Patients with melanoma brain metastases are now frequently treated with immunotherapy(IMT) or targeted therapy (TT). The aim of this systematic review was to determine relative survival outcomes after combining radiotherapy (RT) with IMT or TT. METHODS: 126 studies were identified by searching Medline, Embase and Cochrane CENTRAL(to 7Aug 2023). RESULTS: Multivariable analyses showed that the risk of death was reduced by 30% for combined stereotactic radiosurgery (SRS)+IMT compared to IMT alone, by 65% for patients treated with SRS+anti-PD1 and by 59% for patients treated with SRS+anti-CTLA4 and/or anti-PD1 (HR 0.41, 95%CI 0.31-0.54) compared to SRS alone. Four studies compared SRS+anti-CTLA4 with SRS+anti-PD1, showing a 42% reduction in risk of death with SRS+anti-PD1 treatment. Combined treatment with SRS+TT showed a 59% reduction in risk compared to SRS alone. CONCLUSION: The systematic review suggests a substantial survival benefit for combining SRS with IMT or TT for patients with melanoma brain metastases.

Neurophysiologic Characteristics of the Anterior Nucleus of the Thalamus during Deep Brain Stimulation Surgery for Epilepsy.

INTRODUCTION: Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an increasingly promising treatment option for refractory epilepsy. Optimal therapeutic benefit has been associated with stimulation at the junction of ANT and the mammillothalamic tract (mtt), but electrophysiologic markers of this target are lacking. The present study examined microelectrode recordings (MER) during DBS to identify unique electrophysiologic characteristics of ANT and the ANT-mtt junction. METHODS: Ten patients with medically refractory epilepsy underwent MER during ANT-DBS implantation under general anesthesia. MER locations were determined based on coregistration of preoperative MRI, postoperative CT, and a stereotactic atlas of the thalamus (Morel atlas). Several neurophysiological parameters including single unit spiking rate, bursting properties, theta and alpha power and cerebrospinal fluid (CSF)-normalized root mean square (NRMS) of multiunit activity were characterized at recording depths and compared to anatomic boundaries. RESULTS: From sixteen hemispheres, 485 recordings locations were collected from a mean of 30.3 (15.64 ± 5.0 mm) recording spans. Three-hundred and ninety-four of these recording locations were utilized further for analysis of spiking and bursting rates, after excluding recordings that were more than 8 mm above the putative ventral ANT border. The ANT region exhibited discernible features including: (1) mean spiking rate (7.52 Hz ± 6.9 Hz; one-way analysis of variance test, p = 0.014 when compared to mediodorsal nucleus of the thalamus [MD], mtt, and CSF), (2) the presence of bursting activity with 40% of ANT locations (N = 59) exhibited bursting versus 24% the mtt (χ2; p < 0.001), and 32% in the MD (p = 0.38), (3) CSF-NRMS, a proxy for neuronal density, exhibited well demarcated changes near the entry and exit of ANT (linear regression, R = -0.33, p < 0.001). Finally, in the ANT, both theta (4-8 Hz) and alpha band power (9-12 Hz) were negatively correlated with distance to the ventral ANT border (linear regression, p < 0.001 for both). The proportion of recordings with spiking and bursting activity was consistently highest 0-2 mm above the ventral ANT border with the mtt. CONCLUSION: We observed several electrophysiological markers demarcating the ANT superior and inferior borders including multiple single cell and local field potential features. A local maximum in neural activity just above the ANT-mtt junction was consistent with the previously described optimal target for seizure reduction. These features may be useful for successful targeting of ANT-DBS for epilepsy.

Childhood eczema prevalence in New Zealand using topical corticosteroid dispensing data.

OBJECTIVES: To determine the prevalence of eczema among children in New Zealand. METHODS: Population-based retrospective observational study utilising national pharmaceutical dispensing records for topical corticosteroids and emollients for all New Zealand children aged 0-14 years from 1st January 2006 to 31st December 2019. Data are reported using descriptive statistics, with comparisons between ethnicities and socioeconomic quintiles undertaken with rate ratios. RESULTS: Based on dispensing data, the prevalence of eczema for New Zealand children aged 0-14 years in 2018 was 14.0% (95% CI 14.0%-14.1%), with prevalence decreasing in older age groups (children aged <1 year 26.0% (25.6%-26.4%); children aged 10-14 years 8.8% (8.7%-8.9%)). Prevalence was higher in Pacific children (23.6% (23.3%-24.0%)), but slightly lower in Maori children (13.2% (13.0%-13.3%)). CONCLUSION: Eczema is a common condition affecting a considerable proportion of children in New Zealand. This study provides nationwide paediatric prevalence data for New Zealand, and highlights the increased burden of eczema in Pacific children. Inequity in dispensing of topical corticosteroids is postulated to explain the reduced rates found for Maori children compared to previous studies. These results support the need for further research to determine factors contributing to differing eczema prevalence rates in New Zealand.

Deep brain stimulation for the treatment of substance use disorders: a promising approach requiring caution.

Substance use disorders are prevalent, causing extensive morbidity and mortality worldwide. Evidence-based treatments are of low to moderate effect size. Growth in the neurobiological understanding of addiction (e.g., craving) along with technological advancements in neuromodulation have enabled an evaluation of neurosurgical treatments for substance use disorders. Deep brain stimulation (DBS) involves surgical implantation of leads into brain targets and subcutaneous tunneling to connect the leads to a programmable implanted pulse generator (IPG) under the skin of the chest. DBS allows direct testing of neurobiologically-guided hypotheses regarding the etiology of substance use disorders in service of developing more effective treatments. Early studies, although with multiple limitations, have been promising. Still the authors express caution regarding implementation of DBS studies in this population and emphasize the importance of safeguards to ensure patient safety and meaningful study results. In this perspectives article, we review lessons learned through the years of planning an ongoing trial of DBS for methamphetamine use disorder.

Genetic influence on vascular smooth muscle cell apoptosis.

Vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis play important roles in many physiological processes and pathological conditions. To identify genetic influences on VSMC behavior, we measured these traits and undertook genome-wide association studies in primary umbilical artery-derived VSMCs from >2000 individuals. Although there were no genome-wide significant associations for VSMC proliferation or migration, genetic variants at two genomic loci (7p15.3 and 7q32.3) showed highly significant associations with VSMC apoptosis (P = 1.95 × 10-13 and P = 7.47 × 10-9, respectively). The lead variant at the 7p51.3 locus was associated with increased expression of the GSDME and PALS2 genes in VSMCs. Knockdown of GSDME or PALS2 in VSMCs attenuated apoptotic cell death. A protein co-immunoprecipitation assay indicated that GSDME complexed with PALS2. PALS2 knockdown attenuated activated caspase-3 and GSDME fragmentation, whilst GSDME knockdown also reduced activated caspase-3. These findings provide new insights into the genetic regulation of VSMC apoptosis, with potential utility for therapeutic development.

WonderFlow: Narration-Centric Design of Animated Data Videos.

Creating an animated data video with audio narration is a time-consuming and complex task that requires expertise. It involves designing complex animations, turning written scripts into audio narrations, and synchronizing visual changes with the narrations. This paper presents WonderFlow, an interactive authoring tool, that facilitates narration-centric design of animated data videos. WonderFlow allows authors to easily specify semantic links between text and the corresponding chart elements. Then it automatically generates audio narration by leveraging text-to-speech techniques and aligns the narration with an animation. WonderFlow provides a structure-aware animation library designed to ease chart animation creation, enabling authors to apply pre-designed animation effects to common visualization components. Additionally, authors can preview and refine their data videos within the same system, without having to switch between different creation tools. A series of evaluation results confirmed that WonderFlow is easy to use and simplifies the creation of data videos with narration-animation interplay.

When does a melanoma metastasize? Implications for management.

Selecting which patients with clinically-localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival. Knowing if and when a melanoma is likely to metastasize is therefore of great importance. Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered. Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.

Anti-VEGF Pharmaceutical Prior Authorization in Retina Practices.

Importance: Anti-vascular endothelial growth factor (VEGF) intravitreal injections, a mainstay of treatment for many retinal diseases to optimize visual outcomes, have been included in prior authorization (PA) initiatives. However, if clinicians are extremely accurate in their use of anti-VEGF medications, such administrative burdens may need reconsideration. Objective: To quantify PA for anti-VEGF medications (aflibercept, ranibizumab, and bevacizumab) that were approved and determine associated administrative burdens experienced by retina practices. Design, Setting, and Participants: Prospective multicenter quality improvement study conducted from January 2022 through June 2022, and participants were 9 private retina practices across the US. Main Outcomes and Measures: Overall rate of approval of PA requests, reasons for requesting PA, and overall rate of delay of care resulting from PA procedures. Results: In total, 2365 PA requests were recorded, 2225 of which met inclusion criteria. Overall, 2140 (96.2%) requests were approved. The most common reason for requesting PA, at 64% (1423 of 2225 requests), was reauthorization for a previously utilized medication. Of the 2140 approvals, 59.6% (1277) resulted in a delay in care greater than 24 hours, and 40% (863) were given on the date of service. In a granular analysis of a subset of delayed approvals, 23.9% (173 of 725) were approved within 1 day, 15.9% (115 of 725) were approved within 2 to 3 days, 21.5% (156 of 725) were approved within 4 to 7 days, 26.3% (191 of 725) were approved within 8 to 31 days, and 12.4% (90 of 725) were approved within more than 31 days. Overall, PA denial for step therapy was 2.9% (65 of 2225) of requests and uncovered diagnoses was 0.9% (20 of 2225) of requests. The median staff time spent to obtain a single PA was 100 (range, 0-200) minutes. Conclusions and Relevance: In this study, PA requests were almost always approved but led to a delay in patient care in most patients. The current study suggests that the PA process may not be effective for retina specialists if these results can be generalized to other practices in the US and if less burdensome and less costly approaches could result in similar approval rates. Potential short-term solutions may include eliminating the PA process for bevacizumab and reauthorizations for established patients.

Effect of smoking on melanoma incidence: a systematic review with meta-analysis.

BACKGROUND: There is a strong correlation between cigarette smoking and the development of many cancer types. It is therefore paradoxical that multiple reports have suggested a reduced incidence of melanoma in smokers. This study aimed to analyze all existing studies of melanoma incidence in smokers relative to non-smokers. METHODS: Searches of MEDLINE and Embase were conducted for studies reporting data on melanoma in smokers and never-smokers. No study design limitations or language restrictions were applied. The outcome examined was the association between smoking status and melanoma. Analyses focussed on risk of melanoma in smokers and never-smokers generated from multivariable analyses and these were pooled using a fixed effects model. Risk of bias was assessed using the Newcastle-Ottawa tool. FINDINGS: Forty-nine studies that included 59,429 melanoma patients were identified. Pooled analyses showed that current-smokers had a significantly-reduced risk of melanoma both in males (risk ratio (RR) 0.60, 95%CI_0.56 to0.65, p < .001) and females (RR 0.79- 95%-CI-0.73-to-0.86, p < .001). Male former-smokers had a 16% reduction in melanoma risk compared to never-smokers (RR-0.84,-95%CI-0.77-to-0.93, p < .001), but no risk reduction was observed in female former-smokers (RR-1.0-95%CI-0.92-to-1.08). INTERPRETATION: Current-smokers have a significantly-reduced risk of developing melanoma compared to never-smokers, with a reduction in melanoma risk of 40% in men and 21% in women.

Paediatric opioid poisoning in the UK: a retrospective analysis of clinical enquiries to the National Poisons Information Service.

OBJECTIVE: To evaluate a decade of reported paediatric opioid poisoning cases in the UK. METHODS: The National Poisons Information Service (NPIS) telephone enquiries database (UK Poisons Information Database) was searched for calls regarding opioid poisoning in children under 18 years from 2012 to 2021. The NPIS online clinical guidance database TOXBASE was searched for accesses relating to opioids for both adults and children. The Office of National Statistics provided paediatric data for hospital admissions and deaths in those aged under 20 years old due to opioids. RESULTS: The NPIS received 426 774 telephone enquiries from 2012 to 2021 from across the UK, 3600 in relation to opioid exposures regarding children under 18 years. Annual telephone enquiries regarding paediatric opiate poisoning reduced year on year, from around 450 to 300 calls/year. A rise in all age TOXBASE annual accesses relating to opioids from 71 642 in 2012 to 87 498 in 2021 was noted, a total of 838 455 during the study period. Hospital admissions from opioid poisoning remained consistent, with around 1500 admissions/year. Deaths were uncommon, but averaged 18 deaths annually. Co-codamol was the most reported substance to NPIS, with 1193 calls (36.5%), followed by codeine with 935 (26.1%). CONCLUSIONS: Opioid poisoning in children is not uncommon. There is a general downward trend in telephone enquiries to NPIS, but many childhood exposures may have been dealt with through consultations via TOXBASE, where accesses relating to opioids have increased. Unfortunately, children still die from opioid exposure each year in the UK and this figure has changed little during 2012-2021.

The Effect of Neoadjuvant Systemic Therapy on Surgical Outcomes After Lymph Node Dissections for Stage III Melanoma; An Australian Cohort.

BACKGROUND: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes. METHODS: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database. RESULTS: The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of postoperative complications did not differ between the NAST- and upfront surgery-treated patients (55% vs. 51%; p = 0.643), and steroid treatment for drug toxicity did not influence the complication rate (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.4-3; p = 0.826). No significant differences in postoperative morbidity were observed in terms of seroma (23% vs. 11%; p = 0.570) or lymphedema (36% vs. 51%; p = 0.550). The rate of achieving a textbook outcome was comparable for the two groups (61% vs. 57%; p = 0.641). CONCLUSIONS: The surgical outcomes after lymph node dissections were comparable between the patients who received NAST and those who had upfront surgery, indicating that surgery can be safely performed after NAST with TT or ICI for stage III melanoma.

Impact of an Online Risk Calculator for Sentinel Node Positivity on Management of Patients with T1 and T2 Melanomas.

BACKGROUND: Predicting which patients with American Joint Committee on Cancer (AJCC) T1-T2 melanomas will have a positive sentinel lymph node (SLN) is challenging. Melanoma Institute Australia (MIA) developed an internationally validated SLN metastatic risk calculator. This study evaluated the nomogram's impact on T1-T2 melanoma patient management at MIA. METHODS: SLN biopsy (SLNB) rates were compared for the pre- and post-nomogram periods of 1 July 2018-30 June 2019 and 1 August 2020-31 July 2021, respectively. RESULTS: Overall, 850 patients were identified (pre-nomogram, 383; post-nomogram, 467). SLNB was performed in 29.0% of patients in the pre-nomogram group and 34.5% in the post-nomogram group (p = 0.091). The overall positivity rate was 16.2% in the pre-nomogram group and 14.9% in the post-nomogram group (p = 0.223). SLNB was performed less frequently in T1a melanoma patients in the pre-nomogram group (1.1%, n = 2/177) than in the post-nomogram group (8.6%, n = 17/198) [p ≤ 0.001]. This increase was particularly for melanomas with a risk score ≥ 5%, with an SLN positivity rate of 11.8% in the post-nomogram group (p = 0.004) compared with zero. For T1b melanomas with a risk score of > 10%, the SLNB rate was 40.0% (8/20) pre-nomogram and 75.0% (12/16) post-nomogram (p = 0.049). CONCLUSIONS: In this specialized center, the SLN risk calculator appears to influence practice for melanomas previously considered low risk for metastasis, with increased use of SLNB for T1a and higher-risk T1b melanomas. Further evaluation is required across broader practice settings. Melanoma management guidelines could be updated to incorporate the availability of nomograms to better select patients for SLNB than previous criteria.

Subthalamic nucleus synchronization between beta band local field potential and single-unit activity in Parkinson's disease.

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings. Magnitude of STA-LFP was greater within the STN compared to extra-STN structures along the trajectory path, despite no difference in percentage of the total power. Within the STN, there was a higher percent beta power in dorsal compared to ventral STN but no difference in STA-LFP magnitude. Further refining the comparison to high versus low beta peak power recordings inside the STN to evaluate if single-unit activity synchronized more strongly with beta band activity in areas of high beta power resulted in a significantly higher STA magnitude for areas of high beta power. Overall, these results suggest that STN single units strongly synchronize to beta activity, particularly units in areas of high beta power.