Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

HIV-1 DNA and Immune Activation Levels Differ for Long-Lived T-Cells in Lymph Nodes, Compared with Peripheral Blood, during Antiretroviral Therapy.

Elucidating the mechanisms underlying the persistence and location of the HIV reservoir is critical for developing cure interventions. While it has been shown that levels of T-cell activation and the size of the HIV reservoir are greater in rectal tissue and lymph nodes (LN) than in blood, the relative contributions of T-cell subsets to this anatomic difference are unknown. We measured and compared HIV-1 DNA content, expression of the T-cell activation markers CD38 and HLA-DR, and expression of the exhaustion markers programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) in naive, central memory (CM), transitional memory (TM), and effector memory (EM) CD4+ and CD8+ T-cells in paired blood and LN samples among 14 people with HIV who were receiving antiretroviral therapy. HIV-1 DNA levels, T-cell immune activation, and TIGIT expression were higher in LN than in blood, especially in CM and TM CD4+ T-cell subsets. Immune activation was significantly higher in all CD8+ T-cell subsets, and memory CD8+ T-cell subsets from LN had higher levels of PD-1 expression, compared with blood, while TIGIT expression levels were significantly lower in TM CD8+ T-cells. The differences seen in CM and TM CD4+ T-cell subsets were more pronounced among participants with CD4+ T-cell counts of <500 cells/µL within 2 years after antiretroviral therapy initiation, thus highlighting increased residual dysregulation in LN as a distinguishing feature of and a potential mechanism for individuals with suboptimal CD4+ T-cell recovery during antiretroviral therapy. IMPORTANCE This study provides new insights into the contributions of different CD4+ and CD8+ T-cell subsets to the anatomic differences between LN and blood in individuals with HIV who have optimal versus suboptimal CD4+ T-cell recovery. To our knowledge, this is the first study comparing paired LN and blood CD4+ and CD8+ T-cell differentiation subsets, as well as those subsets in immunological responders versus immunological suboptimal responders.

Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study.

BACKGROUND: Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. METHODS: Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). RESULTS: The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44-47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. CONCLUSION: Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44).

Weight History Correlates of Resting Energy Expenditure in Women With Bulimia Nervosa.

OBJECTIVE: Among those with bulimia nervosa, weight suppression has been associated with illness severity and treatment prognosis. Although significant weight loss is known to reduce metabolic rate, the relation between weight suppression and resting energy expenditure (REE) in bulimia nervosa has not been examined. This study tested the hypothesis of an inverse relation between weight suppression and REE in a sample of women with bulimia nervosa (N = 84). METHODS: In primary analyses, linear regressions were conducted between weight suppression and REE, corrected for fat-free mass. In follow-up, exploratory analyses, stepwise linear regressions were conducted to explore the main and interaction effects of weight history and weight suppression on REE. RESULTS: Neither traditional (TWS) nor developmental weight suppression (DWS) correlated with REE. Results from exploratory analyses, however, revealed a medium-to-large inverse relation between several weight history variables and REE (highest past weight, sr2 = 0.05; lowest postmorbid weight, sr2 = 0.07; current weight, sr2 = 0.05). Additionally, DWS interacted with current (sr2 = 0.08) and highest premorbid (sr2 = 0.05) z-BMI to influence REE with a medium-to-large effect. For individuals low in current and premorbid z-BMIs, higher DWS associated with lower REE levels. However, for individuals at higher premorbid z-BMIs, higher DWS unexpectedly associated with greater REE levels. DISCUSSION: In this sample of women with bulimia nervosa, reduced REE associated with higher weights across all timepoints. If the interaction effect between DWS and z-BMI history persists in future studies, this may indicate unique challenges faced by individuals low in z-BMI and high in DWS related to weight gain and normalization of eating.

Physiological, body composition, and body mass measures show that a developmental measure of weight suppression is more valid than the traditional measure.

OBJECTIVE: The traditional measure of weight suppression (TWS; the difference between an individual's highest past weight at adult height and current weight), has been associated with many psychological, behavioral and biological variables in those with eating disorders. A new measure of weight suppression, called developmental weight suppression (DWS), corrects two major problems in the original measure. Initial research indicates that DWS represents a superior operationalization of the construct weight suppression was originally designed to measure (Lowe [1993, Psychol Bull, 114: 100]). This study is the first to examine the relation between both WS measures and weight history, body composition and a variety of metabolic hormones. METHODS: Data were collected in 91 women with bulimia nervosa (BN) or BN-spectrum disorders. RESULTS: Both weight suppression indices were related to multiple hormones. However, multiple regression analyses showed that the independent effects of DWS differed from the independent effects of TWS in that only DWS was negatively related to: (1) current z-BMI, (2) body fat percentage, and (3) insulin, leptin, T3 free, and TSH. This differential pattern also occurred when results were corrected for multiple comparisons. DISCUSSION: Findings provide stronger biological support for the construct validity of DWS than TWS and suggest that: (1) from the perspective of individuals with BN, high DWS embodies success at food restriction and weight loss, (2) elevated DWS may trap individuals with BN in a powerful biobehavioral bind, and (3) DWS is the preferred measure of weight suppression in future research on eating disorders. PUBLIC SIGNIFICANCE: Most individuals with bulimia nervosa lose substantial weight in the process of developing their disorder. Such weight suppression is related to many characteristics of those with the eating disorder bulimia nervosa. This study shows why a new measure of weight suppression, based on an individual's growth during development, is more biologically valid than the traditional measure of weight suppression.

Computing leaky Lamb waves for waveguides between elastic half-spaces using spectral collocation.

In non-destructive evaluation guided wave inspections, the elastic structure to be inspected is often embedded within other elastic media and the ensuing leaky waves are complex and non-trivial to compute; we consider the canonical example of an elastic waveguide surrounded by other elastic materials that demonstrates the fundamental issues with calculating the leaky waves in such systems. Due to the complex wavenumber solutions required to represent them, leaky waves pose significant challenges to existing numerical methods, with methods that spatially discretise the field to retrieve them suffering from the exponential growth of their amplitude far into the surrounding media. We present a spectral collocation method yielding an accurate and efficient identification of these modes, leaking into elastic half-spaces. We discretise the elastic domains and, depending on the exterior bulk wavespeeds, select appropriate mappings of the discretised domain to complex paths, in which the numerical solution decays and the physics of the problem are preserved. By iterating through all possible radiation cases, the full set of dispersion and attenuation curves are successfully retrieved and validated, where possible, against the commercially available software disperse. As an independent validation, dispersion curves are obtained from finite element simulations of time-dependent waves using Fourier analysis.

Is there a basis for a weight cut-off point? A large-scale investigation of atypical anorexia and anorexia nervosa subtypes among patients at a residential treatment centre.

OBJECTIVE: There is debate surrounding how to differentiate between anorexia nervosa (AN) and atypical AN (atypAN) as diagnostic entities, and whether a distinction based on BMI is warranted. Better understanding eating disorder (ED) and emotional symptoms across atypAN and AN subtypes [AN-restricting (AN-R), AN-binge/purge (AN-BP)], with and without controlling for BMI, can elucidate how atypAN differs from AN subtypes and whether there is a basis for a BMI cut-off. METHODS: 1810 female patients at an ED treatment centre completed intake surveys. ANCOVAs assessed differences across AN-R (n = 853), AN-BP (n = 726), and atypAN (n = 231) groups on ED, depressive, and anxiety symptoms, anxiety sensitivity, experiential avoidance, and mindfulness, with and without controlling for BMI. RESULTS: Relative to AN-R, atypAN and AN-BP groups endorsed significantly higher ED and depressive symptoms, anxiety sensitivity, experiential avoidance, and significantly lower mindfulness (all p < 0.001), but atypAN and AN-BP groups did not differ from one another. When controlling for BMI, all previously significant differences between atypAN and AN-R did not remain significant. CONCLUSION: Individuals with atypAN who have a higher BMI experience more pronounced ED and emotional symptoms, suggesting that relying solely on BMI as a marker of illness severity may be problematic.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.

Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/µL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/µL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.

Altered prefrontal activation during the inhibition of eating responses in women with bulimia nervosa.

BACKGROUND: The sense of 'loss of control' (LOC), or a feeling of being unable to stop eating or control what or how much one is eating, is the most salient aspect of binge eating. However, the neural alterations that may contribute to this experience and eating behavior remain poorly understood. METHODS: We used functional near-infrared spectroscopy (fNIRS) to measure activation in the prefrontal cortices of 23 women with bulimia nervosa (BN) and 23 healthy controls (HC) during two tasks: a novel go/no-go task requiring inhibition of eating responses, and a standard go/no-go task requiring inhibition of button-pressing responses. RESULTS: Women with BN made more commission errors on both tasks. BN subgroups with the most severe LOC eating (n = 12) and those who felt most strongly that they binge ate during the task (n = 12) showed abnormally reduced bilateral ventromedial prefrontal cortex (vmPFC) and right ventrolateral prefrontal cortex (vlPFC) activation associated with eating-response inhibition. In the entire BN sample, lower eating-task activation in right vlPFC was related to more frequent and severe LOC eating, but no group differences in activation were detected on either task when this full sample was compared with HC. BN severity was unrelated to standard-task activation. CONCLUSIONS: Results provide initial evidence that diminished PFC activation may directly contribute to more severe eating-specific control deficits in BN. Our findings support vmPFC and vlPFC dysfunction as promising treatment targets, and indicate that eating-specific tasks and fNIRS may be useful tools for identifying neural mechanisms underlying dysregulated eating.

Regional control after precision lymph node dissection for clinically evident melanoma metastasis.

INTRODUCTION: Completion lymph node dissection (CLND) for microscopic lymph node metastases has been replaced by observation; however, CLND is standard for clinically detectable nodal metastases (cLN). CLND has high morbidity, which may be reduced by excision of only the cLN (precision lymph node dissection [PLND]). We hypothesized that same-basin recurrence risk would be low after PLND. METHODS: Retrospective review at four tertiary care hospitals identified patients who underwent PLND. The primary outcome was 3-year cumulative incidence of isolated same-basin recurrence. RESULTS: Twenty-one patients underwent PLND for cLN without synchronous distant metastases. Reasons for forgoing CLND included patient preference (n = 11), comorbidities (n = 5), imaging indeterminate for distant metastases (n = 2), partial response to checkpoint blockade (n = 1), or not reported (n = 2). A median of 2 nodes (range: 1-6) were resected at PLND, and 68% contained melanoma. Recurrence was observed in 33% overall. Only 1 patient (5%) developed an isolated same-basin recurrence. Cumulative incidences at 3 years were 5.0%, 17.3%, and 49.7% for isolated same-basin recurrence, any same-basin recurrence, and any recurrence, respectively. Complications from PLND were reported in 1 patient (5%). CONCLUSIONS: These pilot data suggest that PLND may provide adequate regional disease control with less morbidity than CLND. These data justify prospective evaluation of PLND in select patients.

A comparison of traditional and developmental measures of weight suppression in residential patients with bulimia nervosa.

OBJECTIVE: Weight suppression (WS) is associated with many eating disorder (ED)-related symptoms. However, traditional calculations of WS do not consider the age or height at which one's highest past weight was reached. Lowe et al. (2022) found that developmental WS (DWS) was associated with a wider variety of ED-related symptoms compared with traditional WS (TWS). This study replicated and extended these findings in a larger sample of individuals with bulimia nervosa (BN) at a residential ED treatment center. METHODS: Participants were 1051 female patients with BN. We examined the relations between each WS measure and ED symptoms, emotional symptoms, and weight history variables. RESULTS: TWS and DWS showed a similar number of relations with ED-related symptoms. DWS was positively related to behavioral symptoms (e.g., vomiting), and negatively related to cognitive symptoms (e.g., weight/eating concern). TWS was positively related to highest premorbid, highest postmorbid, and lowest postmorbid weights. DWS was also positively related to highest premorbid z-scored body mass index (zBMI), but negatively related to lowest and highest postmorbid zBMI. CONCLUSIONS: DWS, relative to TWS, may better capture the psychobiological impact of the weight discrepancy that a measure of WS is meant to reflect. PUBLIC SIGNIFICANCE: Weight suppression, the difference between an individual's past highest weight and current weight, is significantly related to many ED-related symptoms. This study found that a new weight suppression measure, based on expected weight-for-height during physical development, relates to ED characteristics in a different manner from the traditional measure of weight suppression, showing positive associations with behavioral symptoms and negative associations with cognitive symptoms.

Neurosyphilis in the Northern Territory of Australia: a clinical guideline.

BACKGROUND: The Northern Territory (NT) of Australia is currently experiencing a syphilis epidemic. Neurosyphilis is commonly considered in the differential diagnosis for patients presenting with neurologic conditions such as dementia and stroke in the NT. AIMS: To explore the local epidemiologic, diagnostic and treatment complexities of neurosyphilis in the NT and produce a guideline for clinical practice. METHODS: A database search was undertaken and local and global neurosyphilis guidelines were analysed. A guideline was created based on findings of the critical review and consultation with local multidisciplinary experts. RESULTS: Neurosyphilis is frequently encountered in the NT but studies suggest it is often undertreated. Dementia is the most common clinical presentation locally. Establishing a diagnosis of neurosyphilis is complex and requires stepwise evaluation of clinical, laboratory and radiological findings. CONCLUSIONS: A clinical guideline and algorithm have been developed for the diagnosis and management of patients with neurosyphilis.

An examination of frontal asymmetry in relation to eating in the absence of hunger and loss-of-control eating.

Loss-of-control (LOC) eating involves a subjective feeling that one cannot stop eating or control one's eating. Individuals with LOC eating may exhibit strong appetitive drives and weak inhibitory control, and these two opposing motivations have been related to EEG measurements of frontal asymmetry or lateralized frontal activation. The present study investigated whether frontal asymmetry is related to hedonic hunger, LOC eating severity and frequency, and eating in the absence of hunger (EAH) in the laboratory. Fifty-nine individuals participated in an ostensible taste study after resting-state electroencephalogram (EEG) recordings. After the EEGs, they were provided a meal to eat until fullness, followed by an array of snacks and instructions to eat as much as they would like. The results indicated that several measures of right-frontal asymmetry were related to greater EAH and greater self-reported LOC eating severity. Although right-frontal asymmetry has been theorized to reflect avoidance motivation, recent evidence suggests it may indicate effortful control during approach-avoidance conflicts. Because individuals with LOC eating presumably experience heightened conflict between drives to eat beyond energy needs and to minimize such eating, those experiencing greater LOC may exert greater effort to manage these conflicting motivations. An integration of these neurobiological correlates of LOC eating may help provide a more comprehensive understanding of LOC eating and inform treatments.

Overlapping and distinct relationships between hedonic hunger, uncontrolled eating, food craving, and the obesogenic home food environment during and after a 12-month behavioral weight loss program.

Hedonic hunger, reward-driven eating outside of biological need, is a newer construct in eating behavior research. During behavioral weight loss (BWL), greater improvements in hedonic hunger are associated with higher weight loss, but it remains unclear if hedonic hunger predicts weight loss independent of more well-established, similar constructs (uncontrolled eating and food craving). Research also is needed to understand how hedonic hunger interacts with contextual factors (e.g., obesogenic food environment) during weight loss. Adults (N = 283) in a 12-month randomized controlled trial of BWL were weighed at 0, 12, and 24 months, and completed questionnaires assessing hedonic hunger, food craving, uncontrolled eating, and the home food environment. All variables improved at 12 and 24 months. Decreases in hedonic hunger at 12 months were associated with higher concurrent weight loss, but not when accounting for improvements in craving and uncontrolled eating. At 24 months, reduction in craving was a stronger predictor of weight loss than hedonic hunger, but improvement in hedonic hunger was a stronger predictor of weight loss than change in uncontrolled eating. Changes to the obesogenic home food environment failed to predict weight loss, regardless of levels of hedonic hunger. This study adds novel information on the individual and contextual factors associated with short- and long-term weight control, which can help refine conceptual models and treatment strategies.

Attenuation of Rayleigh waves due to three-dimensional surface roughness: A comprehensive numerical evaluation.

The phenomenon of Rayleigh wave attenuation due to surface roughness has been well studied theoretically in the literature. Three scattering regimes describing it have been identified-the Rayleigh (long wavelength), stochastic (medium wavelength), and geometric (short wavelength)-with the attenuation coefficient exhibiting a different behavior in each. Here, in an extension to our previous work, we gain further insight with regard to the existing theory, in three dimensions, using finite element (FE) modeling, under a unified approach, where the same FE modeling techniques are used regardless of the scattering regime. We demonstrate good agreement between our FE results and the theory in all scattering regimes. Additionally, following this demonstration, we extend the results to cases that lie outside the limits of validity of the theory.

Prefrontal cortex activation by binge-eating status in individuals with obesity while attempting to reappraise responses to food using functional near infrared spectroscopy.

PURPOSE: Difficulty reappraising drives to consume palatable foods may promote poorer inhibition and binge eating (BE) in adults with obesity, but neural underpinnings of food-related reappraisal are underexamined. METHODS: To examine neural correlates of food-related reappraisal, adults with obesity with and without BE wore a portable neuroimaging tool, functional near-infrared spectroscopy (fNIRS). fNIRS measured activity in the prefrontal cortex while participants watched videos of food and attempt to "resist" the food stimuli (i.e., "consider the negative consequences of eating the food"). RESULTS: Participants (N = 32, 62.5% female; BMI 38.6 [Formula: see text] 7.1; 43.5 [Formula: see text] 13.4 y) had a BMI > 30 kg/m2. Eighteen adults (67.0% female; BMI 38.2 [Formula: see text] 7.6) reported BE (≥ 12 BE-episodes in preceding 3 months). The control group comprised 14 adults who denied BE (64.0% female; BMI 39.2 [Formula: see text] 6.6). Among the entire sample, mixed models showed significant, small hyperactivation during crave and resist compared to watch (relax) condition bilaterally in the medial superior frontal gyrus, dorsolateral areas, and middle frontal gyrus (optodes 5, 7, 9, 10, 11, and 12) in the total sample. No statistically significant differences in neural activation were observed between the BE and control group. Moreover, there were no significant group by condition interactions on neural activation. CONCLUSION: Among adults with obesity, BE status was not linked to differential activation in inhibitory prefrontal cortex areas during a food-related reappraisal task. Future research is needed with larger samples, adults without obesity, and inhibition paradigms with both behavioral and cognitive components. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies. TRIAL REGISTRATION: # NCT03113669, date April 13, 2017.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined. METHODS: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables. RESULTS: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%. CONCLUSIONS: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. METHODS: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. RESULTS: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). CONCLUSIONS: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.