Physiotherapy practices in the clinical assessment of lateral elbow tendinopathy: An international survey.

BACKGROUND AND PURPOSE: Understanding physiotherapy practices is important to identify variations from empirical evidence and highlight requirements for training. This survey explored international physiotherapy practices for assessment of lateral elbow tendinopathy (LET). METHODS: Two hundred ninety-nine surveyed physiotherapists from eight member countries of the International Federation of Manual and Orthopaedic Physical Therapists completed the survey. Respondents rated their frequency of use (never, rarely, sometimes, often, and always) for items related to: patient history; diagnostic tests; grip and upper limb strength; cervical and neurological assessment; and medical imaging. To establish practices, the five response categories were dichotomised into routine practice (often, always) and not-routine practice (sometimes, rarely, never). A response rate of ≥70% for each dichotomy was used to determine whether an assessment item was deemed routine practice or not, with items not meeting either criterion considered neither routine nor not-routine practice. RESULTS: Most respondents were from United States (63%). The 'chair pick up test', 'cervical special tests', and 'plain radiograph' met our criteria for not routine practice (i.e., 70%, 72%, and 71%, respectively). All other assessment items did not meet the criteria to be considered routine or not-routine practice. CONCLUSION: The chair pick-up test, cervical spine special tests (e.g., Spurling's test), and plain radiography appear to not be routinely used in the assessment of LET. The finding that no assessment technique met the criteria for routine use may imply that physiotherapists adopt a nuanced approach to selecting clinical assessment items as opposed to routinely applying tests.

Patterning optimization for device realization of patterned GaAsSbN nanowire photodetectors.

Vertically grown nanowires (NWs) are a research interest in optoelectronics and photovoltaic applications due to their high surface to volume ratio and good light trapping capabilities. This study presents the effects of process and design parameters on self-catalyzed GaAsSbN NWs grown by plasma-assisted molecular beam epitaxy on patterned silicon substrates using electron beam lithography. Vertical alignment of the patterned NWs examined via scanning electron microscopy show the sensitivity of patterned NW growth to the parameters of NW diameter, pitch, dose time, etching techniques and growth plan. Diameters range from 90 nm to 250 nm. Pitch lengths of 200 nm, 400 nm, 600 nm, 800 nm, 1000 nm, and 1200 nm were examined. Dry etching of the oxide layer of the silicon substrate and PMMA coating is performed using reactive ion etching (RIE) for 20 s and 120 s respectively. Comparisons of different HF etch durations performed pre and post PMMA removal are presented. Additionally, the report of an observed surfactant effect in dilute nitride GaAsSbN NWs in comparison to non-nitride GaAsSb is presented. Optimizations to patterning, RIE, and HF etching are presented to obtain higher vertical yield of patterned GaAsSbN NWs, achieving ∼80% of the expected NWµm2. Room temperature and 4 K photoluminescence results show the effect of nitride incorporation for further bandgap tuning, and patterned pitch on the optical characteristics of the NWs which gives insights to the compositional homogeneity for NWs grown at each pitch length.

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.

Simulation of ultrasound backscatter coefficient measurement using the finite element method.

Ultrasound backscatter coefficient (BSC) measurement is a method for assessing tissue morphology that can inform on pathologies such as cancer. The BSC measurement is, however, limited by the accuracy with which the investigator can normalise their results to account for frequency dependent effects of diffraction and attenuation whilst performing such measurements. We propose a simulation-based approach to investigate the potential sources of error in assessing the BSC. Presented is a tool for the 2D Finite Element (FE) simulation mimicking a BSC measurement using the planar reflector substitution method in reduced dimensionality. The results of this are verified against new derivations of BSC equations also in reduced dimensionality. These new derivations allow computation of BSC estimates based on the scattering from a 2D scattering area, a line reference reflector and a theoretical value for the BSC of a 2D distribution of scatterers. This 2D model was designed to generate lightweight simulations that allow rapid investigation of the factors associated with BSC measurement, allowing the investigator to generate large data sets in relatively short time scales. Under the conditions for an incoherent scattering medium, the simulations produced BSC estimates within 6% of the theoretical value calculated from the simulation domain, a result reproduced across a range of source f-numbers. This value of error compares well to both estimated errors from other simulation based approaches and to physical experiments. The mathematical and simulation models described here provide a theoretical and experimental framework for continued investigation into factors affecting the accuracy of BSC measurements.

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).

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.

Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis.

BACKGROUND: Recent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall survival (OS) among patients with metastatic melanoma and non-small cell lung cancer. These data are in line with growing preclinical evidence that the adaptive immune response may be more effectively stimulated earlier in the day. We sought to determine the impact of time-of-day ICI infusions on outcomes among patients with metastatic renal cell carcinoma (mRCC). METHODS: The treatment records of all patients with stage IV RCC who began ICI therapy within a multicenter academic hospital system between 2015 and 2020 were reviewed. The associations between the proportion of ICI infusions administered prior to noon (denoting morning infusions) and PFS and OS were evaluated using univariate and multivariable Cox proportional hazards regression. RESULTS: In this study, 201 patients with mRCC (28% women) received ICIs and were followed over a median of 18 months (IQR 5-30). The median age at the time of ICI initiation was 63 years (IQR 56-70). 101 patients (50%) received ≥20% of their ICI infusions prior to noon (Group A) and 100 patients (50%) received <20% of infusions prior to noon (Group B). Across the two comparison groups, initial ICI agents consisted of nivolumab (58%), nivolumab plus ipilimumab (34%), and pembrolizumab (8%). On univariate analysis, patients in Group A had longer PFS and OS compared with those in Group B (PFS HR 0.67, 95% CI 0.48 to 0.94, Punivar=0.020; OS HR 0.57, 95% CI 0.34 to 0.95, Punivar=0.033). These significant findings persisted following multivariable adjustment for age, sex, performance status, International Metastatic RCC Database Consortium risk score, pretreatment lactate dehydrogenase, histology, and presence of bone, brain, and liver metastases (PFS HR 0.70, 95% CI 0.50 to 0.98, Pmultivar=0.040; OS HR 0.57, 95% CI 0.33 to 0.98, Pmultivar=0.043). CONCLUSIONS: Patients with mRCC may benefit from earlier time-of-day receipt of ICIs. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.

Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node.

Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a CD8+ PD-1+ Tcf-1+ stem-like T cell subset in the tumor-draining lymph node (TdLN). Using murine melanoma models, we found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. Our data indicate that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor.

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.

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.

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

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.

Association Between Helicobacter pylori Infection and Migraine: A Systematic Review.

Migraine is a highly debilitating disease affecting humans worldwide. Despite having known this disease for a long time, not many studies have been done to search for a chronic infectious cause of migraine. The goal of this study was to look for an association between migraine and Helicobacter pylori infection. Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) standards, we conducted the analysis and literature search using PubMed, Google Scholar and Cochrane databases. After applying the inclusion and exclusion criteria, the search technique produced a total of 10 articles including one cross-sectional study, two randomized controlled trials (RCTs), one cohort study, five case-control studies and one meta-analysis. Analysis of these studies revealed that there could be an association between Helicobacter pylori infection and migraine, especially in the Asian population. However, the mechanism by which the infection could possibly cause this extra-gastric disorder needs further research and analysis.

FcγRIIB expressed on CD8+ T cells limits responsiveness to PD-1 checkpoint inhibition in cancer.

Checkpoint inhibition using Fc-containing monoclonal antibodies has emerged as a powerful therapeutic approach to augment antitumor immunity. We recently showed that FcγRIIB, the only inhibitory IgG-Fc receptor, is expressed on a population of highly differentiated effector CD8+ T cells in the tumors of mice and humans, raising the possibility that CD8+ T cell responses may be directly modulated by checkpoint inhibitor binding to T cell-expressed FcγRIIB. Here, we show that despite exhibiting strong proliferative and cytokine responses at baseline, human FcγRIIBpos CD8+ T cells exhibited reduced responsiveness to both PD-1 and CTLA-4 checkpoint inhibition as compared with FcγRIIBneg CD8+ T cells in vitro. Moreover, frequencies of FcγRIIBpos CD8+ T cells were reduced after treatment of patients with melanoma with nivolumab in vivo. This reduced responsiveness was FcγRIIB dependent, because conditional genetic deletion of FcγRIIB on tumor-specific CD8+ T cells improved response to checkpoint blockade in B16 and LLC mouse models of cancer. The limited responsiveness of FcγRIIBpos CD8+ T cells was also dependent on an intact Fc region of the checkpoint inhibitor, in that treatment with Fc-devoid anti-PD-1 F(ab) fragments resulted in increased proliferation of FcγRIIBpos CD8+ T cells, without altering the response of FcγRIIBneg CD8+ T cells. Last, the addition of FcγRIIB blockade improved efficacy of PD-1 checkpoint inhibition in mouse models of melanoma, lung, and colon cancer. These results illuminate an FcγRIIB-mediated, cell-autonomous mechanism of CD8+ T cell suppression, which limits the efficacy of checkpoint inhibitors during antitumor immune responses in vivo.

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.

Emerging Therapies for the Management of Pain and Vaso-Occlusive Crises in Patients With Sickle Cell Disease: A Systematic Review of Randomized Controlled Trials.

Sickle cell disease (SCD) is an inherited disorder that impairs red blood cells (RBCs) and disrupts the delivery of oxygen to tissues. There is currently no cure. Symptoms can appear as early as six months of age and include anemia, acute episodes of pain, swelling, infections, delayed growth, and vision problems. A growing number of therapies are being investigated for reducing these episodes of pain, also known as vaso-occlusive crises (VOCs). The research literature evidence, however, currently includes far more approaches that have not shown superiority versus placebo than ones that have been proven effective. The purpose of this systematic review is to evaluate the body of randomized controlled trials (RCTs) to determine the quality of support for and against the use of a variety of current and emerging therapies for treading SCD VOCs. Several important new papers have emerged since previous systematic reviews with similar objectives were published. This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and focused on PubMed exclusively. Only RCTs were sought, and no other filters, except for a five-year historical timeline cut-off, were used. Of the 46 publications that were returned in response to the query, 18 were ultimately accepted as meeting the pre-established inclusion criteria. The Cochrane risk-of-bias tool was utilized as a quality assessment measure, and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework was used to assess the certainty of the evidence. Among the included publications, five out of 18 featured positive results with superiority and statistical significance versus placebo for either reduction in pain score or number/duration of VOCs. The approaches featured therapies ranging from de novo molecules to currently available drugs approved for other indications to naturally occurring metabolites such as amino acids and vitamins. A single therapy, arginine, was supported for both clinical endpoints: pain score reduction and shortened VOC duration. Currently, two therapies are approved by the United States Food and Drug Administration (FDA) and are commercially available (crizanlizumab, ADAKVEO and L-glutamine, Endari). All other therapies are investigational only in nature. Several studies included measurement of biomarker endpoints as well as clinical outcomes. Generally, beneficial outcomes related to improving biomarker levels did not also translate into statistically significant reduction of pain scores or number/duration of VOCs. While measuring biomarkers may contribute to the understanding of pathophysiology, it does not appear to directly offer predictive value toward treatment success clinically. It can be concluded that there exists a specific opportunity to design, fund, and execute investigations that both compare emerging and existing therapies versus one another and compare combinational therapies versus placebo.

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.).