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1.
J Am Acad Dermatol ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243946

RESUMEN

BACKGROUND: Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity. OBJECTIVE: Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS). METHODS: Patients with CHNM and CMOS diagnosed between 2000-2018 were included. Locoregional control (LRC), distant metastasis-free survival (DMFS), melanoma-specific survival (MSS), and overall survival (OS) were described using the Kaplan-Meier method. Cox regression analyses were performed to examine associations between prognostic factors and outcomes. Additional analyses of survival from time of stage IV disease diagnosis were undertaken, stratified by receipt of BRAF-targeted therapy and immune checkpoint inhibitor (ICI) immunotherapy. RESULTS: Of 3007 CHNM and 10637 CMOS patients, CHNM had more adverse pathological features (median age 65.9 vs. 58.5, p<0.001, median Breslow thickness 1.7mm vs. 1.2mm, p<0.001, ulceration 21.2% vs. 18.2%, p<0.001). CHNM had worse LRC (HR 1.17, p<0.001) and DMFS (HR 1.25, p<0.001) but there were no significant differences in MSS or OS. Amongst stage IV patients who received ICI, CHNM had better MSS (HR 0.56, p=0.001) and OS (HR 0.57, p<0.001) on multivariable analyses. LIMITATIONS: Retrospective study, offset by prospective data collection. CONCLUSION: CHNM is associated with a distinct clinicopathological and prognostic profile.

2.
J Natl Cancer Inst ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39245462

RESUMEN

The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the four AJCC 8th Edition T-categories by analyzing Australian registry data for 210,042 melanoma patients diagnosed from 1982-2014. The 30-year incidence rates of death due to melanoma and non-melanoma causes (with 95% confidence intervals) were 7.1% (CI 6.9-7.3%) and 32.8% (CI 32.3-33.3%), respectively. For T2 melanomas, the corresponding rates were 21.6% (CI 21.0-22.3%) and 35.6% (CI 34.7-36.6%), for T3 melanomas 34.2% (CI 33.4-35.1%) and 39.6% (CI 38.5-40.8%), and for T4 melanomas 44.3% (CI 43.2-45.3%) and 39.6% (CI 38.3-41.0%). A plateau in melanoma-related deaths occurred in T4 patients after 20 years but there were ongoing melanoma-related deaths for the other T-categories beyond 30 years. A progressive rise in the risk of death from other causes occurred across all T-categories.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39311581

RESUMEN

BACKGROUND AND OBJECTIVES: As the aging population increases, the incidence of chronic subdural hematomas (cSDHs) is expected to rise. Surgical evacuation, though effective, sees up to 30% recurrence. Middle meningeal artery (MMA) embolization, particularly with n-butyl cyanoacrylate (n-BCA) glue diluted in D5W for distal penetration, has shown promise in reducing recurrences. Limited reports have investigated the safety and technical feasibility of n-BCA as a primary liquid embolic agent using the D5W push technique in cSDH. This series is the largest in the literature investigating the outcomes of this technique in cSDH. METHODS: A multicenter retrospective database analysis was conducted on consecutive patients who underwent MMA embolization using n-BCA embolisate. Data collected included patient demographics, procedural information, angiographic data, and periprocedural complications. RESULTS: The study included 269 patients with a median age of 76 years. Nearly half of the patients had previous surgeries, and 93 underwent contralateral embolization for bilateral cSDH. Successful MMA embolization with effective distal penetration was achieved in all cases. The complication rate was 2.2%. Significant improvements were noted at a 60-day follow-up, with a median reduction in cSDH diameter of 40.6% (P < .001) and 53% of patients showing neurological improvement. No recurrent cSDH or need for retreatment was observed in patients who underwent follow-up. CONCLUSION: MMA embolization using n-BCA with the D5W push technique is safe and technically feasible. It can be used adjunctively or as an alternative to surgery in patients with cSDH, resulting in decreased recurrence, high technical success, improved distal penetration, and low complication rates.

4.
Crit Rev Oncol Hematol ; 202: 104462, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39097248

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Inmunoterapia , Melanoma , Terapia Molecular Dirigida , Humanos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidad , Terapia Combinada , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Melanoma/terapia , Melanoma/patología , Melanoma/mortalidad , Radiocirugia/métodos
5.
NPJ Parkinsons Dis ; 10(1): 150, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122725

RESUMEN

Oscillatory activity within the beta frequency range (13-30 Hz) serves as a Parkinson's disease biomarker for tailoring deep brain stimulation (DBS) treatments. Currently, identifying clinically relevant beta signals, specifically frequencies of peak amplitudes within the beta spectral band, is a subjective process. To inform potential strategies for objective clinical decision making, we assessed algorithms for identifying beta peaks and devised a standardized approach for both research and clinical applications. Employing a novel monopolar referencing strategy, we utilized a brain sensing device to measure beta peak power across distinct contacts along each DBS electrode implanted in the subthalamic nucleus. We then evaluated the accuracy of ten beta peak detection algorithms against a benchmark established by expert consensus. The most accurate algorithms, all sharing similar underlying algebraic dynamic peak amplitude thresholding approaches, matched the expert consensus in performance and reliably predicted the clinical stimulation parameters during follow-up visits. These findings highlight the potential of algorithmic solutions to overcome the subjective bias in beta peak identification, presenting viable options for standardizing this process. Such advancements could lead to significant improvements in the efficiency and accuracy of patient-specific DBS therapy parameterization.

6.
Foot Ankle Orthop ; 9(3): 24730114241263056, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39086379

RESUMEN

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.

8.
Stereotact Funct Neurosurg ; : 1, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008968

RESUMEN

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.

9.
Australas J Dermatol ; 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39003644

RESUMEN

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.

10.
Front Psychiatry ; 15: 1435109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071229

RESUMEN

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.

12.
Arch Dis Child ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937064

RESUMEN

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.

13.
J Natl Cancer Inst ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913874

RESUMEN

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.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38857128

RESUMEN

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.

16.
Oncotarget ; 15: 374-378, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870033

RESUMEN

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.


Asunto(s)
Melanoma , Humanos , Melanoma/secundario , Melanoma/terapia , Metástasis de la Neoplasia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia
17.
Cell Death Dis ; 15(6): 402, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851795

RESUMEN

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.


Asunto(s)
Apoptosis , Músculo Liso Vascular , Miocitos del Músculo Liso , Apoptosis/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Humanos , Miocitos del Músculo Liso/metabolismo , Estudio de Asociación del Genoma Completo , Caspasa 3/metabolismo , Caspasa 3/genética , Proliferación Celular/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Movimiento Celular/genética , Células Cultivadas
18.
Surg Oncol ; : 102094, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38830788
19.
JAMA Ophthalmol ; 142(8): 716-721, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38935350

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis , Bevacizumab , Inyecciones Intravítreas , Autorización Previa , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Enfermedades de la Retina , Factor A de Crecimiento Endotelial Vascular , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Estudios Prospectivos , Proteínas Recombinantes de Fusión/uso terapéutico , Ranibizumab/uso terapéutico , Ranibizumab/administración & dosificación , Enfermedades de la Retina/tratamiento farmacológico , Autorización Previa/estadística & datos numéricos , Mejoramiento de la Calidad , Estados Unidos
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