ABSTRACT
Skin cancer mortality rates continue to rise, and survival analysis is increasingly needed to understand who is at risk and what interventions improve outcomes. However, current statistical methods are limited by inability to synthesize multiple data types, such as patient genetics, clinical history, demographics, and pathology and reveal significant multimodal relationships through predictive algorithms. Advances in computing power and data science enabled the rise of artificial intelligence (AI), which synthesizes vast amounts of data and applies algorithms that enable personalized diagnostic approaches. Here, we analyze AI methods used in skin cancer survival analysis, focusing on supervised learning, unsupervised learning, deep learning, and natural language processing. We illustrate strengths and weaknesses of these approaches with examples. Our PubMed search yielded 14 publications meeting inclusion criteria for this scoping review. Most publications focused on melanoma, particularly histopathologic interpretation with deep learning. Such concentration on a single type of skin cancer amid increasing focus on deep learning highlight growing areas for innovation; however, it also demonstrates opportunity for additional analysis that addresses other types of cutaneous malignancies and expands the scope of prognostication to combine both genetic, histopathologic, and clinical data. Moreover, researchers may leverage multiple AI methods for enhanced benefit in analyses. Expanding AI to this arena may enable improved survival analysis, targeted treatments, and outcomes.
ABSTRACT
Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered.
Subject(s)
Monoclonal Gammopathy of Undetermined Significance , Skin Diseases , Humans , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/pathology , Female , Male , Aged , Middle Aged , Skin Diseases/etiology , Skin Diseases/diagnosis , Skin Diseases/pathology , Aged, 80 and over , Adult , Skin/pathologySubject(s)
Monoclonal Gammopathy of Undetermined Significance , Multiple Myeloma , Humans , Retrospective Studies , Male , Female , Aged , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Middle Aged , Multiple Myeloma/drug therapy , Aged, 80 and over , Drug Eruptions/etiology , Drug Eruptions/epidemiology , Drug Eruptions/pathology , AdultABSTRACT
ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.
Subject(s)
Herpes Simplex , Lymphohistiocytosis, Hemophagocytic , Pityriasis Lichenoides , Skin Neoplasms , Skin Ulcer , Female , Humans , Young Adult , Blister , Fever/etiology , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Necrosis , Pityriasis Lichenoides/complications , Pityriasis Lichenoides/diagnosis , Skin Neoplasms/complications , Skin Ulcer/pathologySubject(s)
Dermatology , Physician-Patient Relations , Truth Disclosure , Humans , Dermatology/history , History, 20th CenturyABSTRACT
BACKGROUND: Fellowship directors (FDs) play a key role in shaping Mohs micrographic surgery (MMS). Studies characterizing director trends are lacking and may provide a framework for improving gender diversity. OBJECTIVE: To explore characteristics of FDs and trends in gender of both fellows and FDs over time. MATERIALS AND METHODS: The authors compiled a comprehensive list of FDs and fellows for all Accreditation Council for Graduate Medical Education-accredited Micrographic Surgery & Dermatologic Oncology programs from 1996 to 2023. Publicly available data from various internet sources from February 1, 2023 to May 30, 2023 were used to assess characteristics of MMS FDs. RESULTS: The percentage of female FDs increased from 6% to 25% from 1996 to 2023. Female directors were more likely to select female fellows than male directors ( p = .0002) and had fewer years between fellowship completion and FD appointment (9.1 ± 4.7 years) compared with male directors (13.6 ± 8.8 years; p = .036). H-index, program type, and academic rank were similar between male and female directors. CONCLUSION: Although gender parity among MMS trainees has been achieved, discrepancies remain in the gender composition of FDs. Further studies are required to determine why women are underrepresented as FDs.
Subject(s)
Fellowships and Scholarships , Internship and Residency , Humans , Male , Female , Leadership , Mohs Surgery , Education, Medical, Graduate , AccreditationABSTRACT
INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is a heterogenous group of non-Hodgkin lymphomas. Similar presentation to benign conditions, significant genetic variation, and lack of definitive biomarkers contributes to diagnostic delay. The etiology of CTCL is unknown, and environmental exposures, such as geographic, occupational, chemicals, sunlight, and insects have been investigated. EVIDENCE ACQUISITION: Review of the literature for CTCL and exposures was performed in PubMed and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews. This search yielded 193 total results, which were initially screened with defined inclusion and exclusion criteria. The 45 remaining articles were reviewed and classified by exposure type. EVIDENCE SYNTHESIS: The most frequently investigated CTCL exposure type was geographic (13/45 articles, 29%). Chemical exposures were commonly discussed (10/45 articles, 22%), along with occupational (10/45 articles, 22%). Insect exposures (6/45, 13%) and sun exposure (3/45, 7%) were also reviewed, along with articles describing multiple exposure types (3/45, 7%). Article types ranged from cases to systematic reviews and case-control studies. Evidence linking CTCL and these exposures was mixed. Limitations of this investigation include reliance on patient reporting and frequent speculation on disease association versus causality. CONCLUSIONS: This investigation synthesizes the current literature on exposures potentially implicated in the pathogenesis of CTCL, while offering guidance on patient history-taking to ensure potential exposures are captured. Awareness of these possible associations may improve understanding of disease pathogenesis and diagnosis. Moreover, these insights may help with public health decision-making and disease mitigation.
Subject(s)
Lymphoma, Non-Hodgkin , Lymphoma, T-Cell, Cutaneous , Skin Neoplasms , Humans , Delayed Diagnosis , Lymphoma, T-Cell, Cutaneous/epidemiology , Lymphoma, T-Cell, Cutaneous/etiology , Environmental Exposure/adverse effects , Skin Neoplasms/epidemiology , Skin Neoplasms/etiologyABSTRACT
BACKGROUND: This study aimed to determine the impact of preoperative opioid use on outcomes of patients undergoing ankle or hindfoot arthrodesis, or total ankle arthroplasty (TAA). METHODS: We conducted a retrospective review of 190 patients undergoing an ankle or hindfoot arthrodesis (n=122) or TAA (n=68) between December 2015 and September 2020 with a single fellowship-trained orthopaedic foot and ankle surgeon at an academic medical center. Data collected included demographics, medical comorbidities, treatment history, complications and reoperation rates, patient-reported outcome measures (PROMs) (eg, Foot and Ankle Outcome Score [FAOS]), and opioid use. RESULTS: Patients with preoperative opioid use were more likely to continue usage at 90 (r = 0.931, P < .001) and 180 (r = 0.940, P < .001) days postoperatively. For the entire cohort, complication and reoperation rates were 48.9% and 13.2%, respectively. While preoperative opioid use groups did not differ in the overall complication rate, users had significantly more infections (user = 12.5%, nonuser = 3.3%; P = .036) and reoperations (user = 22.5%, nonuser = 10.7%; P = .049). When analyzing postoperative opioid prescriptions, there were many significant correlations with preoperative PROMs, mainly FAOS, such that increased postoperative opioid use was associated with worse subjective outcomes. CONCLUSION: Preoperative opioid users are more likely to continue postoperative opioid use, experience infections, and undergo reoperations. LEVEL OF EVIDENCE: Level III: Retrospective cohort study.
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The adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in prepubertal, 3-week-old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle 3 weeks later. Unilateral loss of maxillary molars led to significant, robust, bilateral changes, primarily in condylar morphology, including anteroposterior narrowing of the condylar head and neck and increased convexity at the condylar surface, as determined by geometric morphometric analysis. Furthermore, both condyles in experimental mice exhibited a degenerative phenotype, which included decreased bone volume and increased mineral density near the condylar head surface compared to control mice. Changes in condylar morphology and mineralized tissue composition were associated with alterations in the cellular architecture of the mandibular condylar cartilage, including increased expression of markers for mature (Col2a1) and hypertrophic (Col10a1) chondrocytes, suggesting a shift toward differentiating chondrocytes. Our results show significant bilateral condylar morphological changes, alterations in tissue composition, cellular organization, and molecular expression, as well as degenerative disease, in response to the unilateral loss of teeth. Our study provides a relatively simple, tractable mouse tooth extraction system that will be of utility in uncovering the cellular and molecular mechanisms of condylar and mandibular adaptation in response to altered occlusion. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Background: Scientific publication and original articles remain the primary method of sharing scientific findings and advancing the knowledge base of that subject. Despite the value of these publications, little research has surveyed what topics are being published. This study aims to identify and characterize the most common topics in current foot and ankle literature. Methods: We reviewed all 1514 published articles in a 5.5-year period (January 2014-June 2019) in 2 foot and ankle-specific journals: Foot & Ankle International (FAI) and Foot and Ankle Surgery (FAS). The articles were sorted into different topic domains to identify the 3 most common categories of publication. The top 3 domains were further characterized by level of evidence (LOE) as well as citations. Results: The 3 most published topics in foot and ankle literature were hallux valgus (8.3%), total ankle arthroplasty (TAA) (8.3%), and ankle fracture (6.6%). These 3 subjects accounted for 351 articles (23.2%). Other common topics were patient-reported outcomes (5.0%), osteochondritis dissecans (3.9%), syndesmotic injury (3.8%), ankle instability (3.7%), hallux rigidus (3.0%), and anatomy (2.8%). The average LOE for articles on hallux valgus, TAA, and ankle fracture was 3.27 from FAI, and the average number of annual citations for a given article in both journals was 3.05. Based on our study, there is no correlation between LOE and number of overall citations, but there is a significant, negative linear correlation in ankle fracture data. We also found that articles on TAA had the highest impact factor and that articles from FAI were cited more often than articles from FAS. Conclusion: The 3 most published topics in foot and ankle literature comprise only 23.2% of all articles. This finding is indicative of the wide variety of cases performed by orthopaedic foot and ankle surgeons. High-quality data are still needed in all topics. Level of Evidence: Level III, retrospective cohort study.
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The National Antimicrobial Prescribing Survey (NAPS) is a web-based qualitative auditing platform that provides a standardized and validated tool to assist hospitals in assessing the appropriateness of antimicrobial prescribing practices. Since its release in 2013, the NAPS has been adopted by all hospital types within Australia, including public and private facilities, and supports them in meeting the national standards for accreditation. Hospitals can generate real-time reports to assist with local antimicrobial stewardship (AMS) activities and interventions. De-identified aggregate data from the NAPS are also submitted to the Antimicrobial Use and Resistance in Australia surveillance system, for national reporting purposes, and to strengthen national AMS strategies. With the successful implementation of the programme within Australia, the NAPS has now been adopted by countries with both well-resourced and resource-limited healthcare systems. We provide here a narrative review describing the experience of users utilizing the NAPS programme in Canada, Malaysia and Bhutan. We highlight the key barriers and facilitators to implementation and demonstrate that the NAPS methodology is feasible, generalizable and translatable to various settings and able to assist in initiatives to optimize the use of antimicrobials.
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Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.
Subject(s)
Biomarkers, Tumor/metabolism , Meningioma/classification , Meningioma/metabolism , Proteogenomics , DNA Methylation , Data Analysis , Drug Discovery , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Meningioma/drug therapy , Meningioma/genetics , Mutation , RNA-Seq , Reproducibility of Results , Single-Cell AnalysisABSTRACT
Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)-Cas9 RNP] to target the critical gene interleukin-1 receptor accessory protein (IL1RAP) in human LSCs. To enhance LSC targeting, we loaded LNP-Cas9 RNP and the chemokine CXCL12α onto mesenchymal stem cell membrane-coated nanofibril (MSCM-NF) scaffolds mimicking the bone marrow microenvironment. In vitro, CXCL12α release induced migration of LSCs to the scaffolds, and LNP-Cas9 RNP induced efficient gene editing. IL1RAP knockout reduced LSC colony-forming capacity and leukemic burden. Scaffold-based delivery increased the retention time of LNP-Cas9 in the bone marrow cavity. Overall, sustained local delivery of Cas9/IL1RAP sgRNA via CXCL12α-loaded LNP/MSCM-NF scaffolds provides an effective strategy for attenuating LSC growth to improve AML therapy.
Subject(s)
CRISPR-Cas Systems , Leukemia, Myeloid, Acute , Gene Editing , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/therapy , RNA, Guide, Kinetoplastida/genetics , Ribonucleoproteins/genetics , Tumor MicroenvironmentABSTRACT
INTRODUCTION: Tyrosine kinase inhibitors (TKI) targeting epidermal growth factor receptor (EGFR) are approved for use in metastatic non-small cell lung cancer (NSCLC). CASE PRESENTATION: Here we present a case of a African American patient with stage IIIA NSCLC treated with osimertinib in the neoadjuvant setting with concurrent radiation, followed by resection. The patient remains disease-free 4 months after surgery. CONCLUSION: This case report suggests that osimertinib may be effective as neoadjuvant therapy in resectable stage III disease. Additionally, we provide a summary of previous case reports and ongoing clinical trials for neoadjuvant EGFR inhibition in stage III NSCLC patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Acrylamides , Aniline Compounds , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Mutation , Neoadjuvant Therapy , Protein Kinase Inhibitors/therapeutic useABSTRACT
INTRODUCTION: Asian immigrants to the U.S. smoke at higher rates than U.S.-born Asians. However, few programs exist to help these immigrants quit and little is known about their real-world effectiveness. The Centers for Disease Control and Prevention funded the Asian Smokers' Quitline to serve Chinese, Korean, and Vietnamese immigrants nationwide. This study examines service utilization and outcomes from the first 7 years of the program. METHODS: From August 2012 to July 2019, the Asian Smokers' Quitline enrolled 14,073 Chinese-, Korean-, and Vietnamese-speaking smokers. Service utilization rates and cessation outcomes were compared with those of an earlier trial (conducted 2004-2008) that demonstrated the efficacy of an Asian-language telephone counseling protocol. Data were analyzed in 2019. RESULTS: Asian Smokers' Quitline participants came from all 50 states and the District of Columbia. The main referral sources were Asian-language newspapers (37.2%), family and friends (16.4%), healthcare providers (11.9%), and radio (11.9%). Overall, 37.6% were uninsured, 38.8% had chronic health conditions, and 15.4% had mental health conditions. Compared with participants in the earlier trial, Quitline participants received 1 fewer counseling session (3.8 vs 4.9, p<0.001) but were more likely to use pharmacotherapy (73.6% vs 20.9%, p<0.001). More than 90% were satisfied with the services they received. Six-month prolonged abstinence rates were higher in the Quitline than in the trial (complete case analysis: 28.6% vs 20.0%, p<0.001; intention-to-treat analysis: 20.5% vs 16.4%, p=0.005). CONCLUSIONS: The Asian Smokers' Quitline was utilized by >14,000 Asian-language-speaking smokers across the U.S. in its first 7 years. This quitline could serve as a model for delivering other behavioral services to geographically dispersed linguistic minority populations.
Subject(s)
Smokers , Smoking Cessation , Counseling , District of Columbia , Hotlines , HumansABSTRACT
Systemic lupus erythematosus may present with several distinct autoimmune phenomena simultaneously. We report a patient presenting with three serious hematologic disorders: thrombotic thrombocytopenic purpura, catastrophic antiphospholipid syndrome, and warm-type IgG red cell autoantibodies. The case is an example of the complex clinical nature of lupus and the importance of accurately identifying individual complications in order to optimize management.
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While fluid replacement therapy is a primary treatment modality used in vaso-occlusive crises for sickle cell disease, data is limited on its safety, efficacy, and variability. We performed a retrospective analysis on 157 unique patient encounters from 49 sickle cell patients hospitalized with a vaso-occlusive episode at our institution from 2013 to 2017. The median length of hospital stay was 4 days (IQR 2-7). The mean total amount of intravenous fluid administered during the hospitalization was 7.4 L (Std 9.6). The mean total amount of fluid intake including intravenous fluids, blood transfusions, and oral fluids was 14.2 L (Std 18.2). Multivariate analyses revealed significant associations between the development of any adverse event (including a new oxygen requirement, acute chest syndrome, aspiration event, other hospital-acquired infection, acute kidney injury, and intensive care unit transfer) and the following variables: intravenous fluid administered in the first 24 h (p = 0.001, OR 1.899, 95% CI 1.319-2.733), total amount of intravenous fluid administered (p = 0.005, OR 1.081, 95% CI 1.023-1.141), and total amount of fluid intake including oral fluids, blood transfusions, and intravenous fluids (p = 0.009, OR 1.046, 95% CI 1.011-1.081). Other factors found to be significantly associated with any adverse event were dialysis dependence prior to admission (p < 0.001, OR 12.984, 95% CI 3.660-46.056) and admission to an inpatient service versus an emergency room or observation unit (p = 0.008, OR 3.201, 95% CI 1.346-7.612). While fluid administration may theoretically slow the sickling process, this data suggests that fluid administration during a vaso-occlusive episode, and especially total volume given in the first 24 h, may also lead to adverse events.
Subject(s)
Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/therapy , Fluid Therapy/trends , Pain Management/trends , Pain/epidemiology , Administration, Intravenous , Adult , Anemia, Sickle Cell/diagnosis , Female , Fluid Therapy/methods , Hospitalization/trends , Humans , Male , Pain/diagnosis , Pain Management/methods , Retrospective Studies , Treatment OutcomeABSTRACT
Mechanical testing machines used in cadaveric spine biomechanics research vary between labs. It is a necessary first step to understand the capabilities and limitations in any testing machine prior to publishing experimental data. In this study, a reproducible protocol that uses a synthetic spine was developed and used to quantify the inherent rotation error and the ability to apply loads in a single physiologic plane (pure-moment) of a custom spine biomechanics simulator. Rotation error was evaluated by comparing data collected by the test machine and the data collected by an optical motion capture system. Pure-moment loading was assessed by comparing the out-of-plane loads to the primary plane load. Using synthetic functional spine units previously shown to have mechanics similar to the cadaveric human spine, the simulator was evaluated using a dynamic test protocol reflective of its future use in the study of cadaveric spine specimens. Rotation errors inherent in the test machine were <0.25° compared to motion capture. Out of plane loads were <4.0% of the primary plane load, which confirmed pure-moment loading. The authors suggest that a standard validation protocol for biomechanical spine testing machines is needed for transparency and accurate field-wide data interpretation and comparison. We offer recommendations based on the reproducible use of a synthetic spinal specimen for consideration.