A Comprehensive Analysis of Metastatic Disease following Surgery for Clinically Localized Cutaneous Melanoma.

INTRODUCTION: The NCCN considers "baseline staging" (whole body CT or PET scan +/- brain MRI) for all asymptomatic melanoma patients with a positive sentinel lymph node biopsy. The true yield of these workups is unknown. METHODS: We created cohorts of adult malignant melanoma patients, using the National Cancer Database (2012-2020) to mimic three common scenarios: (1) clinically node negative, with positive sentinel lymph node(s) (SLNB[+]); (2) clinically node negative, with negative sentinel lymph node(s) (SLNB[-]); (3) clinically node positive with confirmed lymph node metastases (cN[+] and pN[+]). Multivariable regression, supervised decision trees, and nomograms were constructed to assess the risk of metastases based on key features. RESULTS: 10,371 patients were SLNB[+], 55,172 were SLNB[-], and 4,012 were cN[+] and pN[+]. The proportion of patients with any metastatic disease (brain metastases) were as follows: SLNB[+]: 1.4% (0.3%); SLNB[-] 0.3% (<0.1%); cN[+] and pN[+] 11.6% (1.6%). On multivariable regression, Breslow depth > 4, ulceration, and lymphovascular invasion were associated with greater risk of metastatic disease. A supervised decision tree for SLNB[+] and SLNB[-] patients found the only groups with >2% risk of metastases were T4 tumors or T2/T3 tumors with ulceration and LVI. Most groups had a negligible risk (<0.1%) of brain metastases. CONCLUSION: This is the first large analysis to guide the use of imaging for cutaneous melanoma. Among clinically node negative patients, metastatic disease is uncommon and brain metastases are exceedingly rare. Further investigation could promote a tailored approach to metastatic workups guided by individual risk factors.

A global assessment of large terrestrial carnivore kill rates.

Through killing and instilling fear in their prey, large terrestrial carnivores shape the structure and function of ecosystems globally. Most large carnivore species have experienced severe range and population declines due to human activities, and many are now threatened with extinction. Consequently, the impacts of these predators on food webs have been diminished or lost completely from many ecosystems. Kill rates provide a fundamental metric for understanding large carnivore ecology and assessing and comparing predation within and across ecological communities. Our systematic review of large terrestrial mammalian carnivore kill rates reveals significant positive geographic (North America, Europe, and Africa) and taxonomic (grey wolf Canis lupus, puma Puma concolor, lion Panthera leo, and Eurasian lynx Lynx lynx) bias, with most studies apparently motivated by human-carnivore conflict over access to ungulate prey and wildlife management objectives. Our current understanding of the behaviour and functional roles of many large carnivore species and populations thus remains limited. By synthesising and comparing kill rates, we show that solitary carnivores (e.g. brown bears Ursus arctos and most felids) exhibit higher per capita kill rates than social carnivores. However, ungulate predation by bears is typically limited to predation of neonates during a short period. Lower per capita kill rates by social carnivores suggests group living significantly reduces energetic demands, or, alternatively, that group-living carnivores defend and consume a greater proportion of large prey carcasses, or may acquire more food through other means (e.g. scavenging, kleptoparasitism) than solitary hunters. Kill and consumption rates for Canidae - measured as kilograms of prey per kilogram of carnivore per day - are positively correlated with body mass, consistent with increasing energy costs associated with a cursorial hunting strategy. By contrast, ambush predators such as felids show an opposite trend, and thus the potential energetic advantage of an ambush hunting strategy for carnivores as body mass increases. Additionally, ungulate kill rates remain relatively constant across solitary felid body sizes, indicative of energetic constraints and optimal foraging. Kill rate estimates also reveal potential insights into trophic structuring within carnivore guilds, with subordinate carnivores often killing more than their larger counterparts, which may be indicative of having to cope with food losses to scavengers and dominant competitors. Subordinate carnivores may thus serve an important role in provisioning food to other trophic levels within their respective ecosystems. Importantly, kill rates also clarify misconceptions around the predatory behaviour of carnivores (e.g. spotted hyaenas Crocuta crocuta and wolverines Gulo gulo are often considered scavengers rather than the capable hunters that they are) and thus the potential impacts of various carnivore species on their ecological communities. Despite the importance of kill rates in understanding predator-prey interactions, their utility is not widely recognised, and insufficient research limits our ability to fully appreciate and predict the consequences of modified predation regimes, justify current management actions affecting carnivores, or inform effective conservation measures. Together with other important research on predator-prey interactions, robust kill rate studies that address the research deficiencies we highlight will provide a deeper understanding of the foraging behaviours and potential ecosystem impacts of many of the world's carnivores, thus aiding effective conservation and management actions.

Update on Recommendations for Cancer Screening and Surveillance in Children with Genomic Instability Disorders.

Genomic instability disorders are characterized by DNA or chromosomal instability resulting in various clinical manifestations including developmental anomalies, immunodeficiency, and increased risk to develop cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association of Cancer Research held the second Childhood Cancer Predisposition Workshop where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article will discuss childhood cancer risks and surveillance recommendations for the group of genomic instability disorders with predominantly recessive inheritance, including the DNA repair disorders ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, Xeroderma Pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome, as well as the telomere biology disorders and mosaic variegated aneuploidy. Recognition of children with genomic instability disorders is important in order to make the proper diagnosis, enable genetic counseling, and inform cancer screening, cancer risk reduction, and choice of anti-cancer therapy.

Perfusion Strategies for Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma.

Cytoreductive surgery (CRS) with heated intraoperative intraperitoneal chemotherapy (HIPEC) has been shown to improve survival for patients with malignant peritoneal mesothelioma (MPM). Presently, there is no standardized HIPEC protocol with respect to chemotherapeutic agent, dose, administration temperature, or duration and limited literature comparing outcomes in different regimens. In this study, we analyze common practices and outcomes of published HIPEC regimens to gain insight into current practice to inform future directions of study. We conducted a literature search for investigational studies of CRS and HIPEC for MPM treatment in adults and identified 35 such articles. These studies were analyzed for institution type and location, drug regimens, perfusion temperatures and time, and study outcomes including median survival, complication rates, and perioperative mortality rates. On review, there is significant heterogeneity in HIPEC regimens and outcome reporting metrics, suggesting a need for multi-institutional standardized study protocols to better determine the safest and most efficacious treatment regimen.

Reasons for Surgical Attrition Among Nonmetastatic Upper Gastrointestinal Cancer Patients: A Single Institutional Experience.

INTRODUCTION: Upper gastrointestinal (UGI) cancers require multidisciplinary treatment, but surgery provides the only potentially curative option. We sought to understand reasons for attrition before surgery within our regional hospital network. METHODS: We performed chart reviews of patients (age 18-80) with stage I-III UGI cancers (gastroesophageal junction, gastric, and hepatopancreatobiliary adenocarcinomas) in our multihospital cancer registry from 2015 to 2021. Our primary outcome was reasons for surgical attrition. Univariable analysis identified factors related to surgical attrition and the Kaplan-Meier method estimated overall survival based on surgery receipt. RESULTS: Seven hundred and ninety-two patients were included in our analysis, of whom 107 (13.5%) did not undergo curative surgery. Reasons for not undergoing surgery included medical comorbidities (30.8%), patient preference/nonmedical barriers (24.3%, which included: not interested without further explanation, worried about complications, nonadherence to appointments, insurance issues, did not wish for blood transfusion, lack of social support, preferring home care, and worried about recurrence), psychosocial (5.6%), progression while on neoadjuvant therapy or waiting for transplant (15.0% and 7.5%), poor performance status (3.7%), side effects of neoadjuvant therapy (3.7%), and death unrelated to treatment or unknown cause (9.4%). Nonsurgical management was not associated with race, socioeconomic status, or distance traveled for care. Survival was greatly improved for patients who underwent surgery (158 vs. 63 weeks, p < 0.05). CONCLUSION: Nearly one in seven patients (18-80 years old) with UGI cancers evaluated at our academic cancer center did not undergo surgical resection. Reasons for surgical attrition included potentially modifiable issues, and addressing these barriers could help overcome inequities in cancer treatment and survival.

Orbital preservation in the treatment of acute invasive fungal sinusitis.

Acute invasive fungal sinusitis (AIFS) is an aggressive disease with significant mortality and morbidity. Surgical debridement is a mainstay of treatment. However, orbital involvement may limit its efficacy and is an independent risk factor for mortality. Traditionally, orbital exenteration has been utilized in cases with orbital invasion and ophthalmoplegia or vision loss. Retrobulbar liposomal amphotericin B injection may improve disease control and has the potential to spare the morbidity associated with exenteration. In this video article, we document the use of serial endonasal debridement with retrobulbar injections to salvage the eye in a patient with significant orbital involvement. A 28-year-old immunocompromised female patient presented with acute onset restricted right extraocular movement, progressive orbital pain, V2 trigeminal numbness, and 20/40 vision. The patient underwent recurrent debridement and retrobulbar injections of liposomal amphotericin B. Her serial exams, including changes in extraocular muscle appearance and gradual improvement in extraocular movement, were documented. The exam six months after initial presentation demonstrated 20/20 vision, minimal extraocular movement restriction, and proper healing of the orbit and ethmoid. The salvage of the patient's orbit suggests that liposomal amphotericin B injections with debridement may be a viable treatment alternative in patients with acute invasive fungal sinusitis and orbital involvement.

Neighbourhood environments and cognitive health in the longitudinal Personality and Total Health (PATH) through life study: A 12-year follow-up of older Australians.

BACKGROUND: Urban neighbourhood environments may impact older adults' cognitive health. However, longitudinal studies examining key environmental correlates of cognitive health are lacking. We estimated cross-sectional and longitudinal associations of neighbourhood built and natural environments and ambient air pollution with multiple cognitive health outcomes in Australian urban dwellers aged 60+ years. METHODS: The study included 1160 participants of the PATH Through Life study (60+ cohort) who were followed up for 12 years (four assessments; 2001/02 to 2013/15) and with data on socio-demographics, health, cognitive functions and diagnoses, and full residential address. Neighbourhood environmental features encompassed population and street-intersection densities, non-commercial land use mix, transit points, presence of blue space, percentages of commercial land, parkland and tree cover, and annual average PM2.5 and NO2 concentrations. All exposures except for tree cover were assessed at two time points. Generalised additive mixed models estimated associations of person-level average, and within-person changes in, exposures with cognitive functions. Multi-state hidden Markov models estimated the associations of neighbourhood attributes with transitions to/from mild cognitive impairment (MCI). RESULTS: Dense, destination-rich neighbourhoods were associated with a lower likelihood of transition to MCI and reversal to no MCI. Positive cross-sectional and longitudinal associations of non-commercial land use mix, street intersection density and percentage of commercial land were observed especially with global cognition and processing speed. While access to parkland and blue spaces were associated with a lower risk of transition to MCI, the findings related to cognitive functions were mixed and supportive of an effect of parkland on verbal memory only. Higher levels of PM2.5 and NO2 were consistently associated with steeper declines and/or decreases in cognitive functions and worse cognitive states across time. CONCLUSION: To support cognitive health in ageing populations, neighbourhoods need to provide an optimal mix of environmental complexity, destinations and access to the natural environment and, at the same time, minimise ambient air pollution.

A Ketogenic Diet Sensitizes Pancreatic Cancer to Inhibition of Glutamine Metabolism.

Pancreatic cancer is the third leading cause of cancer death in the United States, and while conventional chemotherapy remains the standard treatment, responses are poor. Safe and alternative therapeutic strategies are urgently needed 1 . A ketogenic diet has been shown to have anti-tumor effects across diverse cancer types but will unlikely have a significant effect alone. However, the diet shifts metabolism in tumors to create new vulnerabilities that can be targeted (1). Modulators of glutamine metabolism have shown promise in pre-clinical models but have failed to have a marked impact against cancer in the clinic. We show that a ketogenic diet increases TCA and glutamine-associated metabolites in murine pancreatic cancer models and under metabolic conditions that simulate a ketogenic diet in vitro. The metabolic shift leads to increased reliance on glutamine-mediated anaplerosis to compensate for low glucose abundance associated with a ketogenic diet. As a result, glutamine metabolism inhibitors, such as DON and CB839 in combination with a ketogenic diet had robust anti-cancer effects. These findings provide rationale to study the use of a ketogenic diet with glutamine targeted therapies in a clinical context.

Association of Maternal Air Pollution Exposure and Infant Lung Function Is Modified by Genetic Propensity to Oxidative Stress.

BACKGROUND AND OBJECTIVE: The association between air pollution and poor respiratory health outcomes is well established. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. This study investigated maternal exposure to air pollution during pregnancy and oxidative stress (OS), inflammation, and infant lung function at 4 weeks of age. METHODS: Data from the Barwon Infant Study were available for 314 infants. The exposure to NO2 and PM2.5 were estimated. Infant lung function (4 weeks) was measured by multiple-breath washout. Glycoprotein acetyls (GlycA) (36 weeks prenatal), cord blood, and OS biomarkers were measured in maternal urine (28 weeks). A genetic pathway score for OS (gPFSox) was calculated. Linear regression was used and potential modification by the OS genotype was tested. RESULTS: There was no relationship between maternal exposure to air pollution and infant lung function, or with GlycA or OS during pregnancy. We found an association in children with a genetic propensity to OS between NO2 and a lower functional residual capacity (FRC) (ß = -5.3 mls, 95% CI (-9.3, -1.3), p = 0.01) and lung clearance index (LCI) score (ß = 0.46 turnovers, (95% CI 0.10, 0.82), p = 0.01). CONCLUSION: High prenatal exposure to ambient NO2 is associated with a lower FRC and a higher LCI score in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.

The Increasing Medicolegal Cost in the Care of High-Level Athletes.

BACKGROUND: Medical malpractice represents a significant economic cost in healthcare. Increasingly large damage claims by professional athletes against physicians have raised concerns about the medicolegal challenges in caring for high-level athletes. METHODS: An online proprietary legal research database was queried for lawsuits related to malpractice in the care of professional and amateur athletes from 1992-2023. Demographics of plaintiffs and defendants, details of lawsuit filings and damages claimed were recorded for all cases, settlements, and jury verdicts. Descriptive statistics, linear regression, as well as univariate analysis of demographic factors and damage claims in inflation-adjusted 2023 dollars was performed. RESULTS: Eighty-eight lawsuits were recorded from 1992-2023. The sum of indemnities exceeded 186 million in 2023 inflation-adjusted United States Dollars. Football players were the most commonly represented athletes (n=26) and represented 49% of total financial awards. Fourteen cases (16%) involved treatment of the upper extremity. Professional and collegiate level of play was associated with higher damages in favor of plaintiffs when compared to other levels of play. No other demographic was associated with higher financial awards. Linear regression showed a significant positive trend with an increasing inflation-adjusted compensation for plaintiff verdicts in the last 30 years. CONCLUSIONS: There is an increasing medicolegal financial risk associated with the care of athletes. This is higher in collegiate and professional levels of play. As physicians, insurers and institutions adjust to these financial risks, care must be taken to avoid ramifications on the availability and quality of care provided to athletes. Shoulder and elbow surgeons may consider additional preoperative counseling, legal waiver forms regarding malpractice claims and advocacy for medical malpractice reforms in the care of athletes with high earning potential to mitigate these increasing financial risks.

Dynamic assemblies of parvalbumin interneurons in brain oscillations.

Brain oscillations are crucial for perception, memory, and behavior. Parvalbumin-expressing (PV) interneurons are critical for these oscillations, but their population dynamics remain unclear. Using voltage imaging, we simultaneously recorded membrane potentials in up to 26 PV interneurons in vivo during hippocampal ripple oscillations in mice. We found that PV cells generate ripple-frequency rhythms by forming highly dynamic cell assemblies. These assemblies exhibit rapid and significant changes from cycle to cycle, varying greatly in both size and membership. Importantly, this variability is not just random spiking failures of individual neurons. Rather, the activities of other PV cells contain significant information about whether a PV cell spikes or not in a given cycle. This coordination persists without network oscillations, and it exists in subthreshold potentials even when the cells are not spiking. Dynamic assemblies of interneurons may provide a new mechanism to modulate postsynaptic dynamics and impact cognitive functions flexibly and rapidly.

Elucidating and Optimizing the Photochemical Mechanism of Coumarin-Caged Tertiary Amines.

Photoactivatable or "caged" pharmacological agents combine the high spatiotemporal specificity of light application with the molecular specificity of drugs. A key factor in all optopharmacology experiments is the mechanism of uncaging, which dictates the photochemical quantum yield and determines the byproducts produced by the light-driven chemical reaction. In previous work, we demonstrated that coumarin-based photolabile groups could be used to cage tertiary amine drugs as quaternary ammonium salts. Although stable, water-soluble, and useful for experiments in brain tissue, these first-generation compounds exhibit relatively low uncaging quantum yield (Φu < 1%) and release the toxic byproduct formaldehyde upon photolysis. Here, we elucidate the photochemical mechanisms of coumarin-caged tertiary amines and then optimize the major pathway using chemical modification. We discovered that the combination of 3,3-dicarboxyazetidine and bromine substituents shift the mechanism of release to heterolysis, eliminating the formaldehyde byproduct and giving photolabile tertiary amine drugs with Φu > 20%─a 35-fold increase in uncaging efficiency. This new "ABC" cage allows synthesis of improved photoactivatable derivatives of escitalopram and nicotine along with a novel caged agonist of the oxytocin receptor.

Texture perception at the foot sole: comparison between walking, sitting, and to the hand.

We frequently interact with textured surfaces with both our feet and hands. Like texture's importance for grasping, texture perception via the foot sole might provide important signals about the stability of a surface, aiding in maintaining balance. However, how textures are perceived by the foot, and especially under the high forces experienced during walking, is unknown. The current study builds on extensive research investigating texture perception at the hand by presenting everyday textures to the foot while stepping onto them, exploring them with the foot while sitting, and exploring them with the hand. Participants rated each texture along three perceptual dimensions: roughness, hardness, and stickiness. Participants also rated how stable their posture felt when standing upon each texture. Results show that perceptual ratings of each textural dimension were highly correlated across conditions. Hardness exhibited the greatest consistency and stickiness the weakest. Moreover, correlations between stepping and exploration with the foot were lower than those between exploration with the foot and exploration with the hand, suggesting that mode of interaction (high vs. low force) impacts perception more than body region used (foot vs. hand). On an individual level, correlations between conditions were higher than those between participants, suggesting that differences are greater between individuals than between mode of interaction or body region. When investigating the relationship to perceived stability, only hardness contributed significantly, with harder surfaces rated as more stable. Overall, tactile perception appears consistent across body regions and interaction modes, although differences in perception are greater during walking.NEW & NOTEWORTHY We frequently interact with textured surfaces using our feet, but little is known about how textures on the foot sole are perceived as compared with the hand. Here, we show that roughness, hardness, and stickiness ratings are broadly consistent when stepping on textures, exploring them with the foot sole, or with the hand. Hardness also contributes to perceived stability.

Charcot-Marie-Tooth Disease and Hearing Loss: A Systematic Review With Meta-Analysis.

OBJECTIVE: To characterize the pattern of hearing loss in Charcot-Marie-Tooth (CMT) disease to help guide clinical management. DATABASES REVIEWED: CINAHL, PubMed, and Scopus. METHODS: Two independent investigators selected studies on CMT patients with pure-tone average (PTA) and auditory brainstem response (ABR) data. Case reports, case series <5 patients, and data that overlapped with another study were excluded. Investigators performed data extraction, quality rating, and risk-of-bias assessment using the Newcastle-Ottawa Scale. Meta-analysis of mean difference using fixed/random effects models was used. Also, data were analyzed using a weighted one-way analysis of variance, with post-hoc Tukey's test for comparison. RESULTS: Ultimately, 6 prospective studies (N = 197) were included. The most common demyelinating subtype (CMT1A) had significantly prolonged ABR latency values across wave III (0.20 ms, 95% confidence interval [CI]: 0.05-0.35), wave V (0.20 ms, 95% CI: 0.01-0.39), waves I-III (0.20 ms, 95% CI: 0.01-0.39), and waves I-V (0.20 ms, 95% CI: 0.01-0.39) when compared to matched controls. The autosomal recessive demyelinating subtype (CMT4C) had significantly worse PTA when compared to the most common subtype (CMT1A) (Δ 28.93 dB, 95% CI 18.34-39.52) and nondemyelinating subtype (CMT2A) (Δ 28.3 dB, 95% CI: 15.98-40.62). CONCLUSIONS: Patients with CMT can present with a variety of phenotypes depending on the causative mutation. The ABR interpeak latency values for the most common demyelinating form of CMT are delayed when compared to matched controls. Most subtypes have normal hearing thresholds, apart from CMT4C, which presents with mild hearing loss on average.

The Utility of Sentinel Lymph Node Biopsy in Elderly Patients with Melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is performed less often for older patients with melanoma. We investigated the association of SLNB and melanoma-specific survival (MSS) in the elderly. METHODS: We retrospectively reviewed the Surveillance, Epidemiology, and End Results (SEER: 2010-2019) for patients ≥ 70 years with cT2-4N0M0 melanoma. We used multivariable Cox proportional hazard models to evaluate the impact of SLNB performance and SLN status on MSS at increasing age cutoffs. In addition, we evaluated the association of different factors with SLNB performance using multivariable logistic regression. RESULTS: We identified 11,548 patients. Sentinel lymph node biopsy occurred in 6754 (58.5%) patients, 1050 (15.5%) of whom had a positive SLN. On adjusted SEER analysis, a negative SLN was independently associated with improved MSS (overall hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.63-0.67) for patients up to 87 years old. Positive SLNB was independently associated with inferior MSS (HR 1.71, 95% CI 1.93-1.98). Increasing age groups were significantly associated with decreased SLNB performance. CONCLUSIONS: Sentinel lymph node biopsy is associated with cancer-specific survival and adds prognostic information for elderly patients with melanoma. Sentinel lymph node biopsy performance should not be eliminated in elderly patients based on age alone, unless justified by poor performance status, patient preference, or other surgical contraindications. Decreased SLNB performance with increasing age in our cohort may indicate a missed therapeutic opportunity in the care of elderly patients with melanoma.

Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy.

Children with certain germline gene variants have an increased risk of developing myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM), such as leukemias and lymphomas. Recent studies have identified an expanding number of these predisposition genes, with variants most prevalent in children with MDS but also found in other HM. For some hematopoietic malignancy predisposition (HMP) disorders, specifically those with a high risk of MDS, early intervention through hematopoietic stem cell transplantation (HSCT) can favorably impact overall survival, providing a rationale for rigorous surveillance. A multidisciplinary panel of experts at the 2023 AACR Childhood Cancer Predisposition Workshop reviewed the latest advances in the field and updated prior 2017 surveillance recommendations for children with HMP. In addition to general guidance for all children with HMP, which includes annual physical examination, education about the signs and symptoms of HM, consultation with experienced providers, and early assessment by an HSCT specialist, the panel provided specific recommendations for individuals with a higher risk of MDS based on the affected gene. These recommendations include periodic and comprehensive surveillance for individuals with those syndromes associated with higher risk of MDS, including serial bone marrow examinations to monitor for morphologic changes and deep sequencing for somatic changes in genes associated with HM progression. This approach enables close monitoring of disease evolution based on the individual's genetic profile. As more HMP-related genes are discovered and the disorders' natural histories are better defined, these personalized recommendations will serve as a foundation for future guidelines in managing these conditions.

Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.

Melanoma metabolism can be reprogrammed by activating BRAF mutations. These mutations are present in up to 50% of cutaneous melanomas, with the most common being V600E. BRAF mutations augment glycolysis to promote macromolecular synthesis and proliferation. Prior to the development of targeted anti-BRAF therapies, these mutations were associated with accelerated clinical disease in the metastatic setting. Combination BRAF and MEK inhibition is a first line treatment option for locally advanced or metastatic melanoma harboring targetable BRAF mutations. This therapy shows excellent response rates but these responses are not durable, with almost all patients developing resistance. When BRAF mutated melanoma cells are inhibited with targeted therapies the metabolism of those cells also changes. These cells rely less on glycolysis for energy production, and instead shift to a mitochondrial phenotype with upregulated TCA cycle activity and oxidative phosphorylation. An increased dependence on glutamine utilization is exhibited to support TCA cycle substrates in this metabolic rewiring of BRAF mutated melanoma. Herein we describe the relevant core metabolic pathways modulated by BRAF inhibition. These adaptive pathways represent vulnerabilities that could be targeted to overcome resistance to BRAF inhibitors. This review evaluates current and future therapeutic strategies that target metabolic reprogramming in melanoma cells, particularly in response to BRAF inhibition.