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1.
Cardiooncology ; 9(1): 37, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37891699

ABSTRACT

BACKGROUND: Millions of cancer survivors are at risk of cardiovascular diseases, a leading cause of morbidity and mortality. Tools to potentially facilitate implementation of cardiology guidelines, consensus recommendations, and scientific statements to prevent atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases are limited. Thus, inadequate utilization of cardiovascular medications and imaging is widespread, including significantly lower rates of statin use among cancer survivors for whom statin therapy is indicated. METHODS: In this methodological study, we leveraged published guidelines documents to create a rules-based tool to include guidelines, expert consensus, and medical society scientific statements relevant to point of care cardiovascular disease prevention in the cardiovascular care of cancer survivors. Any overlap, redundancy, or ambiguous recommendations were identified and eliminated across all converted sources of knowledge. The integrity of the tool was assessed with use case examples and review of subsequent care suggestions. RESULTS: An initial selection of 10 guidelines, expert consensus, and medical society scientific statements was made for this study. Then 7 were kept owing to overlap and revisions in society recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples. CONCLUSION: A simple rules-based application was designed to provide a potential format to deliver critical cardiovascular disease best-practice prevention recommendations at the point of care for cancer survivors. A version of this tool may potentially facilitate implementing these guidelines across clinics, payers, and health systems for preventing cardiovascular diseases in cancer survivors. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.

2.
Eur J Cancer ; 194: 113354, 2023 11.
Article in English | MEDLINE | ID: mdl-37827067

ABSTRACT

BACKGROUND: Recent studies have shown that approximately 20% of patients have 4-5 year progression free survival (PFS) on BRAF/MEK inhibitors. The long-term safety and efficacy in these patients with more durable responses have not been studied. METHODS: This retrospective multicenter cohort study assessed response, progression, and adverse events in patients from eight institutions in four countries with >4-year PFS following BRAF/MEK inhibitors. RESULTS: Among 146 patients, 112 (76.7%) remained progression-free at median follow-up of 7.8 years from treatment start; 131 (89.7%) were alive. Among progressors (n = 34), 21 (62%) were on treatment at progression. Among those who discontinued treatment for reasons other than progression (toxicity, preference, etc.) (n = 68, with median 49 months treatment duration), 13 (19%) progressed (median 15.3 months from treatment cessation to progression). Surgery or radiation for single-organ progression resulted in durable benefit in 11 of 22 patients (50%). Subsequent systemic therapy included immune therapy (24% responded) and BRAF/MEK rechallenge (56% responded). Thirteen (8.9%) patients had ongoing toxicities at last follow-up, 10 (77%) of which remained on active treatment; all cardiac adverse events had resolved (n = 9). Twenty-four (16.4%) patients developed any new primary cancer, and 28 (19%) patients experienced other major health events. CONCLUSIONS: Over 75% of patients with 4-year PFS from BRAF/MEK inhibitors had continued durable antitumor responses after nearly 8-year median follow-up, with similar results in patients who discontinued therapy for reasons other than progression. Long-term toxicities were uncommon and low-grade. These findings highlight the often-favourable outcomes in patients with extended benefit from BRAF/MEK inhibitors.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/pathology , Proto-Oncogene Proteins B-raf/genetics , Cohort Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Melanoma/pathology , Protein Kinase Inhibitors/adverse effects , Mitogen-Activated Protein Kinase Kinases , Mutation
3.
JAMA Netw Open ; 6(10): e2336483, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37782499

ABSTRACT

Importance: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency. Objective: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information. Design, Setting, and Participants: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes or no) or descriptive answers. The physicians then graded the chatbot-generated answers to these questions for accuracy (6-point Likert scale with 1 being completely incorrect and 6 being completely correct) and completeness (3-point Likert scale, with 1 being incomplete and 3 being complete plus additional context). Scores were summarized with descriptive statistics and compared using the Mann-Whitney U test or the Kruskal-Wallis test. The study (including data analysis) was conducted from January to May 2023. Main Outcomes and Measures: Accuracy, completeness, and consistency over time and between 2 different versions (GPT-3.5 and GPT-4) of chatbot-generated medical responses. Results: Across all questions (n = 284) generated by 33 physicians (31 faculty members and 2 recent graduates from residency or fellowship programs) across 17 specialties, the median accuracy score was 5.5 (IQR, 4.0-6.0) (between almost completely and complete correct) with a mean (SD) score of 4.8 (1.6) (between mostly and almost completely correct). The median completeness score was 3.0 (IQR, 2.0-3.0) (complete and comprehensive) with a mean (SD) score of 2.5 (0.7). For questions rated easy, medium, and hard, the median accuracy scores were 6.0 (IQR, 5.0-6.0), 5.5 (IQR, 5.0-6.0), and 5.0 (IQR, 4.0-6.0), respectively (mean [SD] scores were 5.0 [1.5], 4.7 [1.7], and 4.6 [1.6], respectively; P = .05). Accuracy scores for binary and descriptive questions were similar (median score, 6.0 [IQR, 4.0-6.0] vs 5.0 [IQR, 3.4-6.0]; mean [SD] score, 4.9 [1.6] vs 4.7 [1.6]; P = .07). Of 36 questions with scores of 1.0 to 2.0, 34 were requeried or regraded 8 to 17 days later with substantial improvement (median score 2.0 [IQR, 1.0-3.0] vs 4.0 [IQR, 2.0-5.3]; P < .01). A subset of questions, regardless of initial scores (version 3.5), were regenerated and rescored using version 4 with improvement (mean accuracy [SD] score, 5.2 [1.5] vs 5.7 [0.8]; median score, 6.0 [IQR, 5.0-6.0] for original and 6.0 [IQR, 6.0-6.0] for rescored; P = .002). Conclusions and Relevance: In this cross-sectional study, chatbot generated largely accurate information to diverse medical queries as judged by academic physician specialists with improvement over time, although it had important limitations. Further research and model development are needed to correct inaccuracies and for validation.


Subject(s)
Artificial Intelligence , Physicians , Humans , Cross-Sectional Studies , Reproducibility of Results , Software
4.
JMIR Dermatol ; 6: e48998, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37676716

ABSTRACT

BACKGROUND: Environmental vinyl chloride (VC) exposure may result in serious acute and chronic dermatological conditions. Because existing literature largely focuses on exposures in occupational settings, a gap persists in our understanding of the medical consequences of large-scale chemical spills. OBJECTIVE: This study aims to examine the potential dermatological manifestations of VC exposure in the context of industrial spills and other environmental disasters and to highlight the public health and justice implications of such releases. METHODS: In this narrative review, relevant evidence-based, peer-reviewed scientific sources, gray literature, and media reports were identified via searches of search PubMed and Google using predetermined keyword search terms related to VC, VC spills and releases, train derailment, cutaneous disease, public health, and vulnerable and marginalized populations. RESULTS: Contact dermatitis and frostbite may arise acutely, highlighting the importance of swift decontamination. Long-term manifestations from chronic VC exposure due to persistence in environmental reservoirs include Raynaud disease, sclerodermatous skin changes, acro-osteolysis, and cutaneous malignancies. The clinical severity of cutaneous manifestations is influenced by individual susceptibility as well as duration, intensity, and route of exposure. Additionally, chemical releases of VC more frequently impact Communities of Color and those of lower socioeconomic status, resulting in greater rates of exposure-related disease. CONCLUSIONS: With environmental release events of hazardous chemicals becoming increasingly common and because the skin has increased contact with environmental toxins relative to other organs, an urgent need exists for a greater understanding of the overall short- and long-term health impacts of large-scale, toxic exposures, underscoring the need for ongoing clinical vigilance. Dermatologists and public health officials should also aim to better understand the ways in which the disproportionate impacts of hazardous chemical exposures on lower-income and minority populations may exacerbate existing health disparities. Herein, we describe the health implications of toxic releases with particular consideration paid to marginalized and vulnerable populations. In addition to legal and regulatory frameworks, we advocate for improved public health measures, to not only mitigate the risk of environmental catastrophes in the future, but also ensure timely and effective responses to them.

5.
Animals (Basel) ; 13(18)2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37760351

ABSTRACT

Ranaviruses are global multi-host pathogens that infect ectothermic vertebrates and cause mass mortality events in some species. In 2021-2022, we surveyed two species of aquatic turtles in a Virginia site where previous research found ranavirus in lizards (Sceloporus undulatus) and turtles (Chrysemys picta picta and Terrapene carolina carolina). We sampled tissues from 206 turtles and tested 249 samples (including recaptures) for ranavirus using qPCR. We detected trace amounts of ranavirus DNA in 2.8% of Common Musk Turtles (Sternotherus odoratus). We did not detect the virus in Eastern Painted Turtles (C. p. picta). The Ct values from animals carrying ranavirus corresponded to positive controls with a concentration of one copy of ranavirus DNA per microliter and likely reflect DNA in the environment rather than ranavirus infection in turtles. Turtles carrying ranavirus DNA came from only one pond in one year. The amount of ranavirus in our study site, as indicated by tissue samples from turtles, appears to have dropped dramatically since previous research conducted over a decade ago. This study represents the first report of ranavirus detected in S. odoratus and contributes to the scarce literature on longitudinal surveys of ranavirus in wild chelonians. We emphasize the need for large sample sizes and multi-year sampling to detect this pathogen in wild populations.

7.
JAMA Netw Open ; 6(8): e2327145, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37535354

ABSTRACT

Importance: Anti-programmable cell death-1 (anti-PD-1) improves relapse-free survival when used as adjuvant therapy for high-risk resected melanoma. However, it can lead to immune-related adverse events (irAEs), which become chronic in approximately 40% of patients with high-risk melanoma treated with adjuvant anti-PD-1. Objective: To determine the incidence, characteristics, and long-term outcomes of chronic irAEs from adjuvant anti-PD-1 therapy. Design, Setting, and Participants: This retrospective multicenter cohort study analyzed patients treated with adjuvant anti-PD-1 therapy for advanced and metastatic melanoma between 2015 and 2022 from 6 institutions in the US and Australia with at least 18 months of evaluable follow-up after treatment cessation (range, 18.2 to 70.4 months). Main Outcomes and Measures: Incidence, spectrum, and ultimate resolution vs persistence of chronic irAEs (defined as those persisting at least 3 months after therapy cessation). Descriptive statistics were used to analyze categorical and continuous variables. Kaplan-Meier curves assessed survival, and Wilson score intervals were used to calculate CIs for proportions. Results: Among 318 patients, 190 (59.7%) were male (median [IQR] age, 61 [52.3-72.0] years), 270 (84.9%) had a cutaneous primary, and 237 (74.5%) were stage IIIB or IIIC at presentation. Additionally, 226 patients (63.7%) developed acute irAEs arising during treatment, including 44 (13.8%) with grade 3 to 5 irAEs. Chronic irAEs, persisting at least 3 months after therapy cessation, developed in 147 patients (46.2%; 95% CI, 0.41-0.52), of which 74 (50.3%) were grade 2 or more, 6 (4.1%) were grade 3 to 5, and 100 (68.0%) were symptomatic. With long-term follow-up (median [IQR], 1057 [915-1321] days), 54 patients (36.7%) experienced resolution of chronic irAEs (median [IQR] time to resolution of 19.7 [14.4-31.5] months from anti-PD-1 start and 11.2 [8.1-20.7] months from anti-PD-1 cessation). Among patients with persistent irAEs present at last follow-up (93 [29.2%] of original cohort; 95% CI, 0.25-0.34); 55 (59.1%) were grade 2 or more; 41 (44.1%) were symptomatic; 24 (25.8%) were using therapeutic systemic steroids (16 [67%] of whom were on replacement steroids for hypophysitis (8 [50.0%]) and adrenal insufficiency (8 [50.0%]), and 42 (45.2%) were using other management. Among the 54 patients, the most common persistent chronic irAEs were hypothyroid (38 [70.4%]), arthritis (18 [33.3%]), dermatitis (9 [16.7%]), and adrenal insufficiency (8 [14.8%]). Furthermore, 54 [17.0%] patients experienced persistent endocrinopathies, 48 (15.1%) experienced nonendocrinopathies, and 9 (2.8%) experienced both. Of 37 patients with chronic irAEs who received additional immunotherapy, 25 (67.6%) experienced no effect on chronic irAEs whereas 12 (32.4%) experienced a flare in their chronic toxicity. Twenty patients (54.1%) experienced a distinct irAE. Conclusions and Relevance: In this cohort study of 318 patients who received adjuvant anti-PD-1, chronic irAEs were common, affected diverse organ systems, and often persisted with long-term follow-up requiring steroids and additional management. These findings highlight the likelihood of persistent toxic effects when considering adjuvant therapies and need for long-term monitoring and management.


Subject(s)
Adrenal Insufficiency , Antineoplastic Agents, Immunological , Immune System Diseases , Melanoma , Female , Humans , Male , Middle Aged , Adrenal Insufficiency/chemically induced , Antineoplastic Agents, Immunological/adverse effects , Cohort Studies , Follow-Up Studies , Immune System Diseases/drug therapy , Melanoma/drug therapy , Melanoma/surgery , Retrospective Studies , Aged
8.
Immunol Rev ; 318(1): 157-166, 2023 09.
Article in English | MEDLINE | ID: mdl-37470280

ABSTRACT

Immune checkpoint inhibitors have transformed cancer therapy, but their optimal use is still constrained by lack of response and toxicity. Biomarkers of response may facilitate drug development by allowing appropriate therapy selection and focusing clinical trial enrollment. However, aside from PD-L1 staining in a subset of tumors and rarely mismatch repair deficiency, no biomarkers are routinely used in the clinic. In addition, severe toxicities may cause severe morbidity, therapy discontinuation, and even death. Here, we review the state of the field with a focus on our research in therapeutic biomarkers and toxicities from immune checkpoint inhibitors.


Subject(s)
Brain Neoplasms , Colorectal Neoplasms , Neoplastic Syndromes, Hereditary , Humans , Immune Checkpoint Inhibitors/adverse effects , Biomarkers , Immunotherapy/adverse effects , Biomarkers, Tumor
10.
Oncologist ; 28(9): e839-e842, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37338166

ABSTRACT

The management of metastatic melanoma patients that fail multiple lines of systemic therapy remains a significant challenge. There is limited literature regarding combination of anti-PD-1 and temozolomide, or of other chemotherapy agents, in melanoma. Here, we present a series of 3 patients with metastatic melanoma and their responses to nivolumab and temozolomide combination therapy after progression on several local/regional therapies, combination immune checkpoint inhibitors, and/or targeted therapies. The novel combinatory strategy led to remarkable responses in all 3 patients shortly after initiating treatment with tumor remission and symptomatic improvement. The first patient has had ongoing response 15 months after initiating treatment, although he has since discontinued temozolomide due to intolerance. The remaining 2 patients show ongoing response after 4 months, with good tolerability. This case series suggests that nivolumab and temozolomide may be a promising option in the setting of advanced melanoma refractory to standard treatments, and warrants further investigation in larger series.


Subject(s)
Antineoplastic Agents , Melanoma , Male , Humans , Nivolumab/pharmacology , Nivolumab/therapeutic use , Temozolomide/pharmacology , Temozolomide/therapeutic use , Salvage Therapy , Melanoma/pathology , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ipilimumab/therapeutic use
11.
NeuroRehabilitation ; 53(1): 61-70, 2023.
Article in English | MEDLINE | ID: mdl-37248918

ABSTRACT

BACKGROUND: There is equivocal evidence regarding the effectiveness of robotic guidance on the (re)learning of voluntary motor skills. Robotic guidance can improve the performance of continuous/ tracking skills, although being seldom more effective than unassisted practice alone. However, most of the previous studies employed robotic guidance on all intervention trials. Recently, we showed that mixing robotic guidance with unassisted practice (i.e., mixed practice) can significantly improve the learning of a golf putting task. Yet, these mixed practice studies involved self-paced movements in a standing posture, thus less applicable to rehabilitation contexts. OBJECTIVE: The current study aimed to investigate the influence of mixed practice on the timing accuracy of an upper-limb, rhythmic, sequential task. The goal was to assess the feasibility of integrating mixed practice with music-based interventions. METHODS: Two groups of participants performed circle-drawing sequences in synchrony with rhythmic auditory signals. They completed a pre-test and an acquisition phase, followed by immediate retention and transfer tests. One group received robotic guidance on 50% of the acquisition trials (i.e., mixed practice), whereas another group always practiced unassisted. The pre-test, retention, and transfer tests were performed unassisted. RESULTS: Both groups significantly improved their timing accuracy and precision between the pre-test and the retention test. CONCLUSION: This study provides further evidence that mixed practice can facilitate the (re)learning of voluntary actions, especially with the type of externally paced upper-limb movements employed in music-based interventions.


Subject(s)
Music , Robotic Surgical Procedures , Robotics , Humans , Feasibility Studies , Upper Extremity , Motor Skills
12.
Res Sq ; 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36909565

ABSTRACT

Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 - completely incorrect to 6 - completely correct) and completeness (3-point Likert scale; range 1 - incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; p<0.01). Conclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.

13.
Med ; 4(3): 139-140, 2023 03 10.
Article in English | MEDLINE | ID: mdl-36905924

ABSTRACT

Goodman et al. discuss how AI technologies like the natural language processing model Chat-GPT could potentially transform healthcare through knowledge dissemination and personalized patient education. Before these tools can be safely integrated into healthcare, research and development of robust oversight mechanisms are necessary to ensure their accuracy and reliability.


Subject(s)
Artificial Intelligence , Natural Language Processing , Humans , Reproducibility of Results , Delivery of Health Care , Health Facilities
14.
Clin Cancer Res ; 29(14): 2580-2587, 2023 07 14.
Article in English | MEDLINE | ID: mdl-36648402

ABSTRACT

Despite revolutionizing cancer management, immunotherapies dysregulate the immune system, leading to immune-mediated adverse events. These common and potentially dangerous toxicities are often treated with corticosteroids, which are among the most prescribed drugs in oncology for a wide range of cancer and noncancer indications. While steroids exert several mechanisms to reduce immune activity, immunotherapies, such as immune checkpoint inhibitors (ICI), are designed to enhance the immune system's inherent antitumor activity. Because ICI requires an intact and robust immune response, the immunosuppressive properties of steroids have led to a widespread concern that they may interfere with antitumor responses. However, the existing data of the effect of systemic steroids on immunotherapy efficacy remain somewhat conflicted and unclear. To inform clinical decision-making and improve outcomes, we review the impact of steroids on antitumor immunity, recent advances in the knowledge of their impact on ICI efficacy in unique populations and settings, associated precautions, and steroid-sparing treatment approaches.


Subject(s)
Neoplasms , Humans , Neoplasms/drug therapy , Immunosuppressive Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Immunotherapy/adverse effects
15.
J Sex Res ; : 1-12, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36519736

ABSTRACT

Job stress is pervasive in today's workforce and has negative implications for employees' mental and physical well-being and job performance. Recovery activities outside of work can reduce strain and improve work outcomes; however, little is known about pleasurable intimate recovery experiences and their influence on work outcomes, even though these experiences are important parts of most people's lives outside of work. The present study examined sexual activity that is shared either with a relationship partner or oneself (masturbation) and how pleasure specifically predicts well-being and work outcomes to induce recovery. Results suggest that pleasurable sexual activity, with a partner or alone, is related to perceived recovery from work stress, job satisfaction, work engagement, and life satisfaction. Moreover, perceived recovery from work mediated the relationship between pleasurable sex and work outcomes. Gender moderated this relationship such that pleasurable sex was a stronger predictor of recovery for women (compared to men) in the context of sex within committed relationship partners (but not masturbation). Theoretical and practical implications are discussed.

16.
Curr Atheroscler Rep ; 24(12): 901-913, 2022 12.
Article in English | MEDLINE | ID: mdl-36441421

ABSTRACT

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of mortality in adult women in the USA, yet CVD is underrecognized in women. Disparities in care are further pronounced in women of racial/ethnic minority backgrounds. In this review, we discuss the role of social media (SoMe) as a tool to (i) promote women's cardiovascular (CV) health and (ii) address and potentially reduce gaps in care, particularly in general cardiology (targeting atherosclerotic cardiovascular disease), cardio-oncology, and cardio-obstetrics. We also briefly discuss women's CV health as a common, although not unique, focus of women in cardiology on SoMe. RECENT FINDINGS: Studies have suggested the utility of social media to help advance subspecialties of cardiology. Leaders within general cardiology, cardio-oncology, and cardio-obstetrics have curated social media strategies to advance their respective fields and call attention to cardiovascular health disparities in female populations and racial/ethnic minorities. In addition to these types of uses, women in cardiology also frequently use SoMe to encourage a career in cardiology and to share experiences, challenges, and resources for support and career advancement as healthcare professionals; men in cardiology and especially those who are allies for sex and racial/ethnic minorities also use SoMe for these means. Herein, we highlight the role and myriad applications of social media in the promotion of women's cardiovascular health. We discuss five primary roles of social media: increasing public awareness, disseminating medical literature in a rapid and accessible fashion, facilitating professional networking, serving as a platform for medical conferences, and empowering patients. These core strategies are discussed through the lens of general cardiology, cardio-oncology, and cardio-obstetrics. We also demonstrate how these applications can be leveraged to increase representation of women in cardiology, also supporting an increased focus on women's cardiovascular health.


Subject(s)
Cardiovascular Diseases , Social Media , Adult , Pregnancy , Male , Female , Humans , Cardiovascular Diseases/therapy , Ethnicity , Minority Groups , Women's Health
17.
Curr Treat Options Oncol ; 23(10): 1428-1442, 2022 10.
Article in English | MEDLINE | ID: mdl-36125618

ABSTRACT

OPINION STATEMENT: While most skin malignancies are successfully treated with surgical excision, advanced and metastatic skin malignancies still often have poor long-term outcomes despite therapeutic advances. Antibody-drug conjugates (ADCs) serve as a potentially promising novel therapeutic approach to treat advanced skin cancers as they combine antibody-associated antigen specificity with cytotoxic anti-tumor effects, thereby maximizing efficacy and minimizing systemic toxicity. While no ADCs have gained regulatory approval for advanced skin cancers, several promising agents are undergoing preclinical and clinical investigation. In addition to identifying and validating skin cancer antigen targets, the key to maximizing therapeutic success is the careful development of each component of the ADC complex: antibodies, cytotoxic drugs, and linkers. It is the optimization of each of these components that will be integral in overcoming resistance, maximizing safety, and improving long-term clinical outcomes.


Subject(s)
Antineoplastic Agents , Immunoconjugates , Melanoma , Skin Neoplasms , Antineoplastic Agents/therapeutic use , Humans , Immunoconjugates/adverse effects , Melanoma/drug therapy , Skin Neoplasms/drug therapy
18.
Curr Atheroscler Rep ; 24(6): 443-456, 2022 06.
Article in English | MEDLINE | ID: mdl-35441347

ABSTRACT

PURPOSE OF REVIEW: Cardiovascular disease (CVD) and cancer are the first and second most common causes of death within the USA. It is well established that a diagnosis of cancer increases risk and predisposes the patient to CVD, and vice versa. Despite these associations, cancer is not yet incorporated into current CVD risk calculators, necessitating additional CV risk markers for improved stratification in this at-risk population. In this review, we consider the utility of breast arterial calcification (BAC), coronary artery calcification (CAC), clonal hematopoiesis of indeterminate potential (CHIP), and cancer and cancer treatment in CVD risk assessment. RECENT FINDINGS: There is evidence supporting the use of BAC, CAC, CHIP, and cancer and cancer treatment for improved CV risk stratification in patients with cancer and those who are being screened for cancer. BAC has been shown to predict CAC, coronary atherosclerotic plaque on coronary CTA, coronary artery stenosis on coronary angiography, and CVD events and accordingly enhances CVD risk stratification beyond the atherosclerotic CVD (ASCVD) risk pooled cohort equation. Additionally, CAC visualized on CT utilized for lung cancer screening, radiation planning, and cancer staging is predictive of coronary artery disease (CAD). Furthermore, CHIP can also be utilized in risk stratification, as the presence of CHIP carries a 40% increase in CV risk independent of traditional CV risk factors. Finally, cancer and many oncologic therapies confer a lifelong increased risk of CVD. We propose an emerging set of tools to be incorporated into the routine continuum of CVD risk assessment in individuals who have been treated for cancer or who are being screened for cancer development. In this review, we discuss BAC, CAC, CHIP, and cancer and cancer treatment as emerging risk markers in cardiovascular health assessment. Their effectiveness in predicting and influencing the burden of CVD will be discussed, along with suggestions on their incorporation into preventive cardio-oncology practice. Future research will focus on short- and long-term CVD outcomes in these populations.


Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Lung Neoplasms , Vascular Calcification , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Coronary Angiography , Coronary Artery Disease/therapy , Early Detection of Cancer , Humans , Lung Neoplasms/complications , Risk Assessment , Risk Factors , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology
20.
Viruses ; 13(8)2021 07 23.
Article in English | MEDLINE | ID: mdl-34452306

ABSTRACT

Ranaviruses are an important wildlife pathogen of fish, amphibians, and reptiles. Previous studies have shown that susceptibility and severity of infection can vary with age, host species, virus strain, temperature, population density, and presence of environmental stressors. Experiments are limited with respect to interactions between this pathogen and environmental stressors in reptiles. In this study, we exposed hatchling red-eared slider turtles (Trachemys scripta elegans) to herbicide and ranavirus treatments to examine direct effects and interactions on growth, morbidity, and mortality. Turtles were assigned to one of three herbicide treatments or a control group. Turtles were exposed to atrazine, Roundup ProMax®, or Rodeo® via water bath during the first 3 weeks of the experiment. After 1 week, turtles were exposed to either a control (cell culture medium) or ranavirus-infected cell lysate via injection into the pectoral muscles. Necropsies were performed upon death or upon euthanasia after 5 weeks. Tissues were collected for histopathology and detection of ranavirus DNA via quantitative PCR. Only 57.5% of turtles exposed to ranavirus tested positive for ranaviral DNA at the time of death. Turtles exposed to ranavirus died sooner and lost more mass and carapace length, but not plastron length, than did controls. Exposure to environmentally relevant concentrations of herbicides did not impact infection rate, morbidity, or mortality of hatchling turtles due to ranavirus exposure. We also found no direct effects of herbicide or interactions with ranavirus exposure on growth or survival time. Results of this study should be interpreted in the context of the modest ranavirus infection rate achieved, the general lack of growth, and the unplanned presence of an additional pathogen in our study.


Subject(s)
DNA Virus Infections/veterinary , Herbicides/toxicity , Ranavirus , Turtles/physiology , Turtles/virology , Animals , Atrazine/toxicity , DNA Virus Infections/epidemiology , DNA Virus Infections/mortality , Environmental Exposure , Glycine/analogs & derivatives , Glycine/toxicity , Turtles/growth & development , Glyphosate
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