NYU Langone Medical Center

Objectives To review the different analgesic modalities and benefits of non‐opioid pain management options as well as their evidence‐based, established superiority, compared to opioid medications. Materials We review the updated literature about pain management of renal colic, a prevalent and painful urologic condition. Prescribers must know the efficacy, safety and possible ramifications of analgesic selections. Results Commonly prescribed medications in the United States (US) include non‐steroidal anti‐inflammatory drugs (NSAIDs), acetaminophen, and opioids. In the context of the current epidemic of death from overdoses of opioids in the US, the frequency of opioid prescribing for renal colic is likely excessive, problematic and potentially remediable. We also present analgesic modalities revolving around interventions with peri‐procedural pain management for ureteroscopy and percutaneous nephrolithotomy. After touching on the implications of misguided opioid use, especially in the context of kidney stone disease, and despite the evidence and consensus guidelines supporting NSAIDs in renal colic, current evidence has shown that many clinicians continue to prescribe opioids as first‐line treatment. Finally, we highlight current efforts targeted at the reduction of opioid use and prescription in the setting of provider education and decision aids in curbing misguided opioid use in renal colic. Conclusions While the evidence against treating kidney stones with opioids is clear, more work is needed to shift current practices to reflect that renal colic is a non‐opioid‐requiring condition.

Objectives To achieve consensus among expert laser surgeons on standards for the prevention and management of adverse events from fully ablative laser resurfacing of the face. Materials and Methods Delphi study with two rounds of ratings and revisions until consensus was achieved. The draft set of statements was developed by a steering committee based on expert clinical experience. This was followed by two rounds of rating and revisions completed by an expert panel, then a virtual consensus meeting. In both rounds, respondents rated the draft statements on a 9‐point Likert scale (1 = strongly disagree; 9 = strongly agree) and optionally provided comments. The consensus meeting was supplemented by the results of a systematic review of the literature (from 2000 to 2023). Results Two rounds of Delphi survey were completed by 34 participants across four countries. Represented specialties were dermatology, facial plastic surgery, plastic surgery, and oculoplastic surgery. The initial 105 statements from round 1 expanded to 112 in round 2, with 96 statements achieving consensus. These included possible adverse events (11 statements); absolute and relative contraindications to treatment (5 statements); preoperative care and antimicrobial prophylaxis precautions (16 statements); intraoperative precautions (17 statements); postoperative care (21 statements); monitoring for and management of infection (16 statements); management of pigmentation changes (6 statements); and management of scarring and incipient scarring (4 statements). Conclusion An international consensus statement was developed for the prevention and management of complications associated with fully ablative laser resurfacing of the face. While expert practices vary, key factors for optimizing outcomes include careful patient selection, counseling, and meticulous pre‐ and postoperative care. Further research will improve our understanding of this treatment technique.

The authors offer a model for curriculum for education and training in substance-assisted psychotherapy (SAP), that is, psychedelic, psycholytic, and entactogen/MDMA (3,4-methylenedioxymethamphetamine)-assisted psychotherapy, addressing both the detailed contents of training and the question of experiential training. All authors of this model have an abiding interest and extensive experience in both the theory and practical aspects of SAP and questions relating to training. The model curriculum has been written through an international consensus building process and represents a consensus statement about the topic. The model includes an enumeration of theoretical themes and topics, which we suggest for inclusion in an SAP curriculum. The practical part of the curriculum includes experiential training with the following components: (1) apprenticeship observation: learning from observing experienced therapists, (2) ongoing clinical supervision: conducting treatment under direct supervision of experienced SAP therapists, and (3) a proposal for the inclusion of self-experiences for the trainees. Other parts address the use of peer supervision and conventional supervision. The authors are aware of the abiding need for respect of intercultural differences. We are conscious that the proposed model is one largely adapted to western industrialized countries with established graduate level education and training procedures for psychotherapists. However, the model curriculum includes teachings about the use of related substances and treatment techniques in indigenous cultures and traditions. This curriculum model may be valuable to psychedelic researchers, those endeavoring to train therapists for research studies, and those preparing for the clinical work to follow, once SAP is conducted outside of research settings.

Objective Reliable image quality assessment is crucial for evaluating new motion correction methods for magnetic resonance imaging. We compare the performance of common reference-based and reference-free image quality metrics on unique datasets with real motion artifacts, and analyze the metrics’ robustness to typical pre-processing techniques. Materials and methods We compared five reference-based and five reference-free metrics on brain data acquired with and without intentional motion (2D and 3D sequences). The metrics were recalculated seven times with varying pre-processing steps. Spearman correlation coefficients were computed to assess the relationship between image quality metrics and radiological evaluation. Results All reference-based metrics showed strong correlation with observer assessments. Among reference-free metrics, Average Edge Strength offers the most promising results, as it consistently displayed stronger correlations across all sequences compared to the other reference-free metrics. The strongest correlation was achieved with percentile normalization and restricting the metric values to the skull-stripped brain region. In contrast, correlations were weaker when not applying any brain mask and using min-max or no normalization. Discussion Reference-based metrics reliably correlate with radiological evaluation across different sequences and datasets. Pre-processing significantly influences correlation values. Future research should focus on refining pre-processing techniques and exploring approaches for automated image quality evaluation.

Targeted therapies and immunotherapy have improved treatment outcomes for many melanoma patients. However, patients whose melanomas harbor driver mutations in the neurofibromin 1 (NF1) tumor suppressor gene often lack effective targeted treatment options when their tumors do not respond to immunotherapy. In this study, we utilized patient-derived short-term cultures (STCs) and multiomics approaches to identify molecular features that could inform the development of therapies for patients with NF1 mutant melanoma. Differential gene expression analysis revealed that the epidermal growth factor receptor (EGFR) is highly expressed and active in NF1 mutant melanoma cells, where it hyper-activates ERK and AKT, leading to increased tumor cell proliferation, survival, and growth. In contrast, genetic or pharmacological inhibition of EGFR hindered cell proliferation and survival and suppressed tumor growth in patient-derived NF1 mutant melanoma models but not in NF1 wild-type models. These results reveal a connection between NF1 loss and increased EGFR expression that is critical for the survival and growth of NF1 mutant melanoma cells in patient-derived culture and xenograft models, irrespective of their BRAF and NRAS mutation status.

Background Patellofemoral instability is a relatively common condition and is multifactorial in its cause, with both soft tissue and bony components. Trochleoplasty is a newly described surgical procedure to help improve outcomes following patellar restabilization. Indications Trochleoplasty is an emerging surgical technique during patellar stabilization surgery in those patients with underlying trochlear dysplasia. Technique Description Trochleoplasty was performed via an open medial parapatellar arthrotomy. Using a combination of osteotome and guided bur, the subchondral surface was undermined to produce a deeper sulcus. The cartilage surface was then plastically deformed into the newly developed trochlea. Trochleoplasty was then secured with a central triple-loaded interference screw and 3 peripheral interference screws. Medial patellofemoral ligament reconstruction was then performed in standard fashion. Results Postoperative course was complicated by arthrofibrosis, which required manipulation at 4 weeks. Following manipulation, the patient recovered uneventfully and had returned to full activities at 6 months with full strength, range of motion, and minimal pain. Discussion/Conclusion Trochleoplasty with combined soft tissue reconstruction is a viable treatment option in those patients with recurrent patellar instability and underlying trochlear dysplasia. While not without complications, this surgical technique remains a powerful tool in the correctly indicated patient. Appropriate patient selection and adherence to postoperative rehabilitation are crucial for optimal outcomes. Patient Consent Disclosure Statement The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background Hip labral and chondral lesions are commonly found as co-occurring conditions in patients with abductor tendon tears. Concomitant hip arthroscopic surgery for the correction of intra-articular abnormalities and endoscopic abductor tendon repair has therefore emerged as a strategy to address these conditions simultaneously. Purpose To systematically review the existing literature assessing clinical outcomes after endoscopic abductor tendon repair with concomitant hip arthroscopic surgery for the treatment of intra-articular abnormalities. Study Design Systematic review; Level of evidence, 4. Methods Under PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the PubMed, CENTRAL, and Scopus databases were queried in May 2023 to conduct this systematic review using the keywords “hip arthroscopy,”“gluteal,”“abductor,”“gluteus,”“minimus,” and “medius.” Articles were included if they reported preoperative and postoperative patient-reported outcome measure (PROM) scores for patients undergoing endoscopic abductor tendon repair for gluteus medius and/or gluteus minimus tears with concomitant hip arthroscopic surgery for the treatment of labral tears and/or femoroacetabular impingement. We identified a total of 404 articles after our initial search. Title, author, publication date, study design, patient characteristics, preoperative radiographic findings (lateral center-edge angle, alpha angle, and Tönnis grade), concomitant surgical procedures performed, preoperative and postoperative PROM scores, measures of clinical benefit, and secondary surgery performed (revision arthroscopic surgery, revision abductor tendon repair, and conversion to total hip arthroplasty) were recorded. P values were extracted from the articles included in our review, all of which defined statistical significance as P < .05. We were unable to create forest plots for these data, given that no single PROM (preoperative and postoperative scores in means and standard deviations) was reported in ≥3 articles. This also prevented us from further analyzing heterogeneity. We calculated the total rate of secondary surgical procedures by dividing the instances of these events by the total number of patients across the 4 studies that included these outcome measures. Results After duplicate articles were removed, 270 articles entered the abstract screening phase, and 11 full-text articles were reviewed. Overall, 5 articles were included in the systematic review. A total of 223 hips were included, with mean follow-up times ranging from 26 to 74 months. All studies reported a significant improvement ( P < .05) on all reported PROMs from preoperative to latest postoperative time points. There were 2 studies that compared combined endoscopic abductor tendon repair and labral treatment with a matched group undergoing hip arthroscopic surgery alone and found no significant differences ( P > .05) between groups. Among studies reporting secondary surgical procedures, there was 1 case (0.9%) of revision abductor tendon repair and 5 cases (4.3%) of conversion to total hip arthroplasty. Conclusion Our systematic review demonstrated that patients who underwent concomitant endoscopic abductor tendon repair and hip arthroscopic surgery had significant improvements on PROMs with low rates of secondary surgery at a minimum 2-year follow-up. Longer-term studies are needed for us to understand concomitant treatment methods for multiple abnormalities in patients undergoing hip arthroscopic surgery in the future.

This Pillars of Immunology article revisits the landmark 2007 study by Foster, Hargreaves, and Medzhitov—the first to uncover the mechanistic basis of memory in the innate immune system. This pivotal study marks a fundamental shift in our understanding of innate immunity, revealing an epigenetic logic that enables immune memory beyond the adaptive immune system.

Despite significant improvements in survival of patients with multiple myeloma (MM), outcomes remain heterogeneous, and a significant proportion of patients experience suboptimal outcomes. Importantly, traditional prognostic factors based on data from patients treated with older therapies no longer capture prognosis accurately in the contemporary era of novel triplet or quadruplet therapies. Therefore, risk stratification requires refinement in the context of available and investigational treatment options in routine practice and clinical trials, respectively. The current identification of high-risk MM (HRMM) in routine practice is based on the Revised International Staging System, which stratifies patients using a combination of widely available serum biomarkers and chromosomal abnormalities assessed via fluorescence in situ hybridization. In recent years, a substantial body of evidence concerning additional clinical, biological, and molecular/genomic prognostic factors has accumulated, along with new MM risk stratification tools and consensus reports. The International Myeloma Society, along with the International Myeloma Working Group, convened an Expert Panel with the primary aim of revisiting the definition of HRMM and formulating a practical and data-driven consensus definition, based on new evidence from molecular/genomic assays, updated clinical data, and contemporary risk stratification concepts. The Panel proposes the following Consensus Genomic Staging (CGS) of HRMM which relies upon the presence of at least one of these abnormalities: (1) del(17p), with a cutoff of >20% clonal fraction, and/or TP53 mutation; (2) an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32); (3) monoallelic del(1p32) along with 1q+ or biallelic del(1p32); or (4) β2 microglobulin ≥5.5 mg/L with normal creatinine (<1.2 mg/dL).

Neurologists engaged in meaningful and satisfying work are positioned to advance the field through research, education, and patient care. On the other hand, neurologists are at elevated risk for burnout and career dissatisfaction, influenced by personal characteristics but driven primarily by external factors at work unit, organizational, and systemic/societal levels. Recognizing and attending to the full range of factors that influence neurologist well-being is necessary to avoid detrimental consequences on patients, clinicians, organizations, and public health. This discussion will review the current state of well-being in neurology, explore drivers and outcomes, and present strategies for improving career satisfaction.

Background Given the low haemorrhagic risk of intracranial low-grade dural arteriovenous fistulas (dAVFs), the benefits of routine intervention remain controversial. This study compares patient outcomes treated with stereotactic radiosurgery (SRS) versus conservative management. Method Multicentre retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research and the International Radiosurgery Research Foundation data. Inclusion criteria were (1) intracranial low-grade dAVF diagnosed by catheter-based angiography, (2) no prior dAVF-related haemorrhage and (3) management with upfront SRS (intervention group) or conservative management (observation group). The primary outcome was symptomatic improvement. Secondary outcomes included dAVF obliteration, up-conversion, haemorrhage, improvement and favourable modified Rankin Scale (mRS) at follow-up. Results 304 patients with a mean age of 56 years (SD 13.5) and a follow-up of 46.7 months (SD 45.5) were included. 135 (44.4%) were managed conservatively and 169 (55.6%) had upfront SRS. Compared with the observation group, symptomatic and mRS Score improvement (≥1-point decrease in baseline score) was more likely in the intervention group (95.1% vs 58.5%; OR=13.75 (5.61–33.69) and 37.0% vs 24.0%; OR=1.85 (1.09–3.15), respectively). These findings remained significant after multiple imputation and propensity score matching. Remaining outcomes were similar between groups. The all-cause mortality rate was 5.4% (n=16), unrelated to the dAVF or treatment. Five (3.0%) SRS-related complications were reported and resolved during the follow-up period. Conclusions SRS was associated with increased symptomatic and mRS Score improvement for low-grade dAVFs compared with conservative management. SRS had a low complication risk and did not appear to alter dAVF obliteration or haemorrhage. Future prospective trials on SRS as a first-line intervention for symptomatic low-grade dAVFs should be considered.

Response to immune checkpoint inhibitors (ICIs) in metastatic melanoma (MM) varies among patients, and current baseline biomarkers predicting treatment outcomes are limited. As mitochondrial (MT) metabolism has emerged as an important regulator of host immune function, we explored the association of host MT genetics (MT haplogroups) with ICI efficacy in 1,225 ICI-treated patients with MM from the clinical trial CheckMate-067 and the International Germline Immuno-Oncology Melanoma Consortium. We discovered and validated significant associations of MT haplogroup T (HG-T) with resistance to anti-programmed cell death protein-1-based ICI (both single-agent and combination) and have shown that HG-T is independent from established tumor predictors. We also found that patients belonging to HG-T exhibit a unique nivolumab-resistant baseline peripheral CD8⁺ T cell repertoire compared to other MT haplogroups, providing, to our knowledge, the first link between MT inheritance, host immunity and ICI resistance. The study proposes a host blood-based biomarker with stand-alone clinical value predicting ICI efficacy and points to an ICI-resistance mechanism associated with MT metabolism, with clinical relevance in immuno-oncology.

Isocitrate dehydrogenase (IDH) mutant glioma is a malignant primary brain tumor diagnosed in adults. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors. The first targeted IDH-inhibitor was approved by the US Food and Drug Administration in August 2024 for grade 2 gliomas, in light of results of a phase III trial which showed significant advantages in progression-free survival. However, biologic therapy is not curative, and subsequent treatment options offer only limited clinical benefit and often result in long-term toxicities. In addition, targeted treatment options for grade 3 and grade 4 IDH-mutant gliomas are still missing. In this study, we present n=52 patients with glioma (grade 2, 3 and 4) with confirmed IDH1 mutation (mutIDH1) in the newly diagnosed and recurrent setting who, in addition to standard-of-care, received a personalized neoantigen-targeting peptide vaccine. Each tumor was initially analyzed for somatic mutations by whole exome sequencing, and a peptide vaccine containing potential neoepitopes was designed, manufactured and vaccinated. Each vaccine consisted of peptides derived from numerous somatic mutations, including at least one peptide targeting the mutIDH1. Vaccine immunogenicity was determined by intracellular cytokine staining and simultaneous measurement of four T-cell activation markers (Interferon-γ, Tumor Necrosis Factor, Interleukin-2, CD154) after 12-day in vitro expansion of pre and post vaccination peripheral blood mononuclear cells. Extracellular CD154 staining was used to sort mutIDH1-specific CD4+T cells. Immunomonitoring revealed that the vaccines were immunogenic and induced mainly CD4 but also CD8 T cell responses. Vaccine-induced immune responses were robust and polyfunctional. Immunogenicity against mutIDH1 was high (89%). We implemented an assay which allowed us to isolate functional antigen-specific CD4+T cells in an HLA-independent manner. Subsequent T cell receptor (TCR) repertoire sequencing revealed that CD4+T cells reacting on mutIDH1 stimulation were polyclonal. Strikingly, we detected two mutIDH1-specific TCRβ candidate sequences in three different patients. These three patients had the same human leukocyte antigen (HLA) DQA-DQB alleles. The obtained TCRβ sequences could be tracked in autologous ex-vivo single-cell transcriptomic data. Our results provide a rationale for pursuing vaccination and T cell transfer strategies targeting IDH1. Furthermore, our findings indicate that personalized neoantigen-targeting vaccines might be considered for the treatment of IDH1-mutant gliomas.

Recent advances in Artificial Intelligence (AI) methodologies and their application to medical imaging has led to an explosion of related research programs utilizing AI to produce state-of-the-art classification performance. Ideally, research culminates in dissemination of the findings in peer-reviewed journals. To date, acceptance or rejection criteria are often subjective; however, reproducible science requires reproducible review. The Machine Learning Education Sub-Committee of the Society for Imaging Informatics in Medicine (SIIM) has identified a knowledge gap and need to establish guidelines for reviewing these studies. This present work, written from the machine learning practitioner standpoint, follows a similar approach to our previous paper related to segmentation. In this series, the committee will address best practices to follow in AI-based studies and present the required sections with examples and discussion of requirements to make the studies cohesive, reproducible, accurate, and self-contained. This entry in the series focuses on image classification. Elements like dataset curation, data pre-processing steps, reference standard identification, data partitioning, model architecture, and training are discussed. Sections are presented as in a typical manuscript. The content describes the information necessary to ensure the study is of sufficient quality for publication consideration and, compared with other checklists, provides a focused approach with application to image classification tasks. The goal of this series is to provide resources to not only help improve the review process for AI-based medical imaging papers, but to facilitate a standard for the information that should be presented within all components of the research study.

The prevalence of comorbid metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity has increased exponentially over the last several years, with current estimates demonstrating that up to 40% of adults in the United States have MASLD. Metabolic associated steatohepatitis (MASH) is now a leading indication for liver transplantation and rates of obesity and MASLD pre- and post-transplant are on the rise. Our understanding of the physiology of obesity and metabolic disease and the availability of effective obesity treatments has evolved over the same time frame. With the availability of new anti-obesity medications (AOM), there has been a debate over the role of pharmacotherapy versus interventional approaches in the treatment of obesity and MASLD in the liver transplantation population. In October 2024, the American Society of Transplantation (AST) Liver and Intestinal Community of Practice held a virtual Controversies Conference on obesity and liver transplantation. Experts in the field presented the available data and smaller working groups had interactive breakout sessions that identified knowledge gaps and developed recommendations. This perspective prepared on behalf the participants of the AST Controversies Conference on obesity and liver transplant aims to summarize the available evidence for surgical and pharmaceutical treatment in the liver transplantation population.

Background and objectives: Older chronological age is associated with decreased multiple sclerosis (MS) relapse rates and increased risk of progressive disease. Measurement of biological age may be more precise than birthdate in understanding these aging effects. In addition to normal aging, MS-related accelerated aging may contribute. Measurement of biological age in adults may be confounded by the effects of natural aging and age-related comorbidities. Examining age extremes can be informative, and demonstrating accelerated biological aging in children would support a hypothesis of MS driving premature aging. We sought to compare epigenetic age in participants with pediatric-onset MS (POMS) and age-similar controls. Methods: We performed a multicenter case-control analysis of epigenetic age in a prospectively collected set of whole blood DNA samples and clinical data. Quantitative methylation scores were derived for approximately 850,000 cytosine-phosphate-guanine (CpG) sites. Epigenetic age was calculated based on 4 established epigenetic clock algorithms. Epigenetic age and age acceleration residual (AAR) were compared between participants with POMS and age-similar controls using multivariate regression analysis, adjusted for demographic variables. Results: Epigenetic age and AAR were greater in cases (n = 125, mean age 15.7 years [SD = 2.6], 63.2% female) compared with controls (n = 145, mean age 15.3 years [SD = 3.4], 63.5% female) after adjusting for age, sex, body mass index, tobacco exposure, and socioeconomic status. This difference was statistically significant for 2 of the 4 epigenetic clocks used (Horvath β = 0.31 years [CI = -0.32-0.94], p = 0.33; Hannum β = 1.50 years [CI = 0.58-2.42], p = 0.002; GrimAge β = 0.33 years [CI = -0.30-0.96], p = 0.29; PhenoAge β = 1.72 years [CI = 0.09-3.35], p = 0.004). Discussion: We observed greater point estimates of epigenetic age in participants with POMS compared with healthy controls in all epigenetic clocks tested. This difference was statistically significant for the Hannum and PhenoAge clocks after multivariable modeling. These results are consistent with those of studies in adult MS and suggest that accelerated aging may be present even in the youngest people living with MS.

Background: Understanding the relationship between mental and physical health conditions is crucial for developing comprehensive healthcare strategies. The putative existence of a general disease factor (d-factor) that underlies the vulnerability to both physical and mental conditions could have important implications for our approach to health assessment and treatment. Objective: To investigate the presence and characteristics of a general d-factor in children and adolescents. Methods: This Swedish registry-based cross-sectional study included children and adolescents born between 1996 and 2003 with follow-up until 2013. We extracted data on 25 mental and physical health conditions according to the ICD-10 system. To determine the optimal dimensional structure of these conditions, several competing measurement models were tested, including correlated factors, one factor, various bifactor specifications and bifactor exploratory structural equation modelling (ESEM). Findings: The study cohort included 776 667 individuals (mean age 13.96 years, IQR=11.96-16.04; 51% male). The bifactor ESEM model, including a general d-factor and specific mental and physical health factors, provided the best fit to the data compared to alternative models (Comparative Fit Index=0.971, Tucker-Lewis Index=0.962, root mean square error of approximation=0.007 (0.007-0.007)). The d-factor accounted for substantial variance (ωh=0.582, explained common variance (ECV)=0.498), while specific mental (ωhs=0.377, ECV=0.373) and physical (ωhs=0.423; ECV=0.130) factors also indicated additional significant unique contributions. Conclusions: This study provided evidence for a multidimensional structure of health in children and adolescents, characterised by a general d-factor underlying both mental and physical conditions, alongside distinct domain-specific factors. These findings have important implications for clinical practice, providing evidence that suggests the need for more integrated approaches to health assessment and treatment that consider the interconnectedness of mental and physical health.

Purpose: Melanoma brain metastases (MBM) are common in advanced melanoma and linked to poor prognosis. Preventing MBM can improve survival and reduce morbidity. While dual-agent immunotherapy (dIT) improves survival, its role in MBM prevention is unclear. We compared MBM incidence, overall survival (OS), and brain metastasis-free survival (BMFS) between dIT and single-agent immunotherapies (sIT). Experimental Design: A real-world multi-institutional database identified melanoma patients without MBM at immunotherapy (IT) initiation. Patients were stratified by anti-CTLA4, anti-PD1, and combo anti-CTLA4/anti-PD1 (dIT) treatment. MBM incidences were measured within 5 years post-IT initiation and compared with risk ratios (RR). In a complementary single-institution cohort, median OS and BMFS were compared between dIT, anti-CTLA4, and anti-PD1 via log-rank tests and multivariate Cox proportional-hazards models. Results: TriNetX identified 8,287 patients receiving anti-CTLA (3,205), anti-PD1 (3,218), and dIT (1,864). MBM incidence was significantly lower in dIT (8.6%) and anti-PD1 (7.8%) vs. anti-CTLA4 (12.2%) cohorts, (RR[95% CI], 0.72[0.61-0.86] and 0.63[0.57-0.70], respectively). There was no significant difference in MBM incidence between anti-PD1 (7.8%) and dIT (8.6%) (RR[95% CI], 1.13[0.93-1.36]). In the single-institution analysis (n=119), 2-year OS probabilities were 90%, 80%, and 95%, and 2-year BMFS probabilities were 72.7%, 80%, and 95.7%, in the dIT, anti-CTLA4, and anti-PD1 cohorts, respectively. DIT and anti-PD1 showed improved early-phase protection against MBM development. Number of metastatic sites was significantly associated with MBM development (HR 2.36; 95% CI [1.22-4.58]; p=0.01). Conclusions: These findings highlight dIT’s potential role in primary prophylaxis against MBM, with anti-PD1 as the likely work horse agent. Prospective studies are warranted.