Persistent poverty and incidence-based melanoma mortality in Texas.

PURPOSE: Previous studies have shown that individuals living in areas with persistent poverty (PP) experience worse cancer outcomes compared to those living in areas with transient or no persistent poverty (nPP). The association between PP and melanoma outcomes remains unexplored. We hypothesized that melanoma patients living in PP counties (defined as counties with ≥ 20% of residents living at or below the federal poverty level for the past two decennial censuses) would exhibit higher rates of incidence-based melanoma mortality (IMM). METHODS: We used Texas Cancer Registry data to identify the patients diagnosed with invasive melanoma or melanoma in situ (stages 0 through 4) between 2000 and 2018 (n = 82,458). Each patient's PP status was determined by their county of residence at the time of diagnosis. RESULTS: After adjusting for demographic variables, logistic regression analyses revealed that melanoma patients in PP counties had statistically significant higher IMM compared to those in nPP counties (17.4% versus 11.3%) with an adjusted odds ratio of 1.35 (95% CI 1.25-1.47). CONCLUSION: These findings highlight the relationship between persistent poverty and incidence-based melanoma mortality rates, revealing that melanoma patients residing in counties with persistent poverty have higher melanoma-specific mortality compared to those residing in counties with transient or no poverty. This study further emphasizes the importance of considering area-specific socioeconomic characteristics when implementing place-based interventions to facilitate early melanoma diagnosis and improve melanoma treatment outcomes.

The social vulnerability index as a risk stratification tool for health disparity research in cancer patients: a scoping review.

PURPOSE: The social vulnerability index (SVI), developed by the Centers for Disease Control and Prevention, is a novel composite measure encompassing multiple variables that correspond to key social determinants of health. The objective of this review was to investigate innovative applications of the SVI to oncology research and to employ the framework of the cancer care continuum to elucidate further research opportunities. METHODS: A systematic search for relevant articles was performed in five databases from inception to 13 May 2022. Included studies applied the SVI to analyze outcomes in cancer patients. Study characteristics, patent populations, data sources, and outcomes were extracted from each article. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In total, 31 studies were included. Along the cancer care continuum, five applied the SVI to examine geographic disparities in potentially cancer-causing exposures; seven in cancer diagnosis; fourteen in cancer treatment; nine in treatment recovery; one in survivorship care; and two in end-of-life care. Fifteen examined disparities in mortality. CONCLUSION: In highlighting place-based disparities in patient outcomes, the SVI represents a promising tool for future oncology research. As a reliable geocoded dataset, the SVI may inform the development and implementation of targeted interventions to prevent cancer morbidity and mortality at the neighborhood level.

Effect of selinexor on lipogenesis in virus-positive Merkel cell carcinoma cell lines.

BACKGROUND: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine cutaneous carcinoma aetiologically linked to the Merkel cell polyomavirus (MCPyV). Immune checkpoint inhibitors are currently the first-line therapy for metastatic MCC; however, the treatment is effective in only about half of patients, highlighting the need for alternative therapies. Selinexor (KPT-330) is a selective inhibitor of nuclear exportin 1 (XPO1) and has been shown to inhibit MCC cell growth in vitro, but the pathogenesis has not been established. Decades of research have established that cancer cells significantly upregulate lipogenesis to meet an increased demand for fatty acids and cholesterol. Treatments that inhibit lipogenic pathways may halt cancer cell proliferation. AIM: To determine the effect of increasing doses of selinexor on fatty acid and cholesterol synthesis in MCPyV-positive MCC (MCCP) cell lines and aid in elucidating the mechanism by which selinexor prevents and reduces MCC growth. METHODS: MKL-1 and MS-1 cell lines were treated with increasing doses of selinexor for 72 h. Protein expression quantification was determined using chemiluminescent Western immunoblotting and densitometric analysis. Fatty acids and cholesterol were quantified using free fatty acid assay and cholesterol ester detection kits. RESULTS: Selinexor causes statistically significant reductions of the lipogenic transcription factors sterol regulatory element-binding proteins 1 and 2, and lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase, squalene synthase and 3ß-hydroxysterol Δ-24-reductase in a dose-dependent manner in two MCCP cell lines. Although inhibiting the fatty acid synthesis pathway results in meaningful decreases in fatty acids, the cellular cholesterol levels did not demonstrate such reductions. CONCLUSION: For patients with metastatic MCC refractory to immune checkpoint inhibitors, selinexor may provide clinical benefit through the inhibition of the lipogenesis pathway; however, further research and clinical trials are needed to evaluate these findings.

The Use of a Dehydrated Complete Human Placental Membrane Allograft for Mohs Surgical Defects of the Nose.

BACKGROUND: Repair options for Mohs surgical defects include primary closure, flap or graft, or healing by second intention. These options may not be optimal in all cases. A dehydrated complete human placental membrane (dCHPM) allograft may serve as an alternative repair option. OBJECTIVE: To assess the aesthetic and functional outcomes of an alternative repair technique for Mohs surgical defects of the nose. METHODS: Twenty patients with Mohs surgical defects of the nose repaired with a dCHPM allograft were retrospectively identified. Photographs were used to demonstrate surgical technique and outcomes. Two blinded observers evaluated final outcomes using the Patient and Observer Scar Assessment Scale. RESULTS: Observers rated the scar outcome a combined mean score of 8.4 ± 3.2 (scale 5-50). Patients rated their outcomes a mean of 12.6 ± 7.4 (scale 6-60). The mean "Overall Opinion score" was 2.5 ± 1.8 by patients and 1.9 ± 1.3 by observers (scale 1-10). LIMITATIONS: This was a single institution study with a small sample size. CONCLUSION: Our study demonstrates that dCHPM allografts are a viable alternative repair option for Mohs surgical defects of the nose.

A Pilot Educational Intervention to Support Primary Care Provider Performance of Skin Cancer Examinations.

Educational interventions to support Primary Care Provider (PCP) performance of skin cancer examinations typically train PCPs to "triage and refer," an approach that may result in diagnostic delays in regions without appropriate access to dermatology care. To address the needs of PCPs and patients in regions without appropriate access to dermatology care, we developed a multi-faceted pilot intervention, including a curriculum and telementoring, designed to support PCP performance of skin cancer detection examinations. Our intervention offers two levels of proficiency: "triage and refer" and "diagnose and manage." The pilot intervention was conducted in collaboration with the Texas Tech University of Health Sciences Center El Paso, TX Family and Community Medicine Department (TTUHSC-El Paso). Participation in the intervention was voluntary, and 18-22 family medicine resident physicians completed the intervention tests. The participating family medicine resident physicians demonstrated statistically significant gains in knowledge and self-efficacy at the immediate post-intervention time points. Further adaption of the pilot intervention is needed to meet the needs of practicing PCPs. The pilot tests require further adaption and validation. Translating education delivery from live/synchronous to interactive virtual/asynchronous modules will support greater educational dissemination, and telementoring support is essential to address challenging cases encountered during patient care.

Aortic valve reconstruction surgery using autologous pericardium: The experience in Vietnam.

OBJECTIVE: The study aimed to evaluate the indications and describe the aortic valve reconstruction techniques by Ozaki's procedure in Vietnam and report mid-term outcomes of this technique in Vietnam. METHODS: Between June 2017 and December 2019, 72 patients diagnosed with isolated aortic valve disease, with a mean age of 52.9 (19-79 years old), and a male:female ratio of 3:1 underwent aortic valve reconstruction surgery by Ozaki's technique at Cardiovascular Center, E Hospital, Vietnam. RESULTS: The aortic valve diseases consisted of aortic stenosis (42%), aortic regurgitation (28%), and a combination of both (30%). In addition, the proportion of aortic valves with bicuspid morphology and small annulus (≤21 mm) was 28% and 38.9%, respectively. The mean aortic cross-clamp time was 106 ± 13.8 min, mean cardiopulmonary bypass time was 136.7 ± 18.5 min, and 2.8% of all patients required conversion to prosthetic valve replacement surgery. The mean follow-up time was 26.4 months (12-42 months), the survival rate was 95.8%, the reoperation rate was 2.8%, and rate of postoperative moderate or higher aortic valve regurgitation was 4.2%. Postoperative valvular hemodynamics was favorable, with a peak pressure gradient of 16.1 mmHg and an effective orifice area index of 2.3 cm2 . CONCLUSIONS: This procedure was safe and effective, with favorable valvular hemodynamics and a low rate of valvular degeneration. However, more long-term follow-up data are needed.

Cutaneous Human Polyomavirus Small T Antigens and 4E-BP1 Targeting.

Merkel cell polyomavirus (MCPyV), trichodysplasia spinulosa-associated polyomavirus (TSPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7) are implicated in the pathogeneses of distinct hyperproliferative cutaneous growths and encode small tumor (sT) antigens. The current study demonstrates that the four sT antigens differentially regulate 4E-binding protein 1 (4E-BP1) serine 65 hyperphosphorylation. MCPyV and HPyV7 sT antigens were found to promote the presence of the hyperphosphorylated 4E-BP1-δ isoform, while TSPyV and HPyV6 sT antigens had no significant effects. Given that hyperphosphorylated 4E-BP1 is associated with an aggressive cancer phenotype, our findings confirm the previously reported pathogenicity of MCPyV sT and highlight a novel mechanism by which HPyV7 sT may mediate oncogenesis.

The New Media Landscape and Its Effects on Skin Cancer Diagnostics, Prognostics, and Prevention: Scoping Review.

BACKGROUND: The wide availability of web-based sources, including social media (SM), has supported rapid, widespread dissemination of health information. This dissemination can be an asset during public health emergencies; however, it can also present challenges when the information is inaccurate or ill-informed. Of interest, many SM sources discuss cancer, specifically cutaneous melanoma and keratinocyte cancers (basal cell and squamous cell carcinoma). OBJECTIVE: Through a comprehensive and scoping review of the literature, this study aims to gain an actionable perspective of the state of SM information regarding skin cancer diagnostics, prognostics, and prevention. METHODS: We performed a scoping literature review to establish the relationship between SM and skin cancer. A literature search was conducted across MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from January 2000 to June 2023. The included studies discussed SM and its relationship to and effect on skin cancer. RESULTS: Through the search, 1009 abstracts were initially identified, 188 received full-text review, and 112 met inclusion criteria. The included studies were divided into 7 groupings based on a publication's primary objective: misinformation (n=40, 36%), prevention campaign (n=19, 17%), engagement (n=16, 14%), research (n=12, 11%), education (n=11, 10%), demographics (n=10, 9%), and patient support (n=4, 3%), which were the most common identified themes. CONCLUSIONS: Through this review, we gained a better understanding of the SM environment addressing skin cancer information, and we gained insight into the best practices by which SM could be used to positively influence the health care information ecosystem.

The effect of selinexor on prostaglandin synthesis in virus-positive Merkel cell carcinoma cell lines.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with high rates of metastasis and mortality. In vitro studies suggest that selinexor (KPT-330), an inhibitor of exportin 1, may be a targeted therapeutic option for MCC. This selective inhibitor prevents the transport of oncogenic mRNA out of the nucleus. Of note, 80% of MCC tumors are integrated with Merkel cell polyomavirus (MCPyV), and virally encoded tumor-antigens, small T (sT) and large T (LT) mRNAs may require an exportin transporter to relocate to the cytoplasm and modulate host tumor-suppressing pathways. To explore selinexor as a targeted therapy for MCC, we examine its ability to inhibit LT and sT antigen expression in vitro and its impact on the prostaglandin synthesis pathway. Protein expression was determined through immunoblotting and quantified by densitometric analysis. Statistical significance was determined with t-test. Treatment of MCPyV-infected cell lines with selinexor resulted in a significant dose-dependent downregulation of key mediators of the prostaglandin synthesis pathway. Given the role of prostaglandin synthesis pathway in MCC, our findings suggest that selinexor, alone or in combination with immunotherapy, could be a promising treatment for MCPyV-infected MCC patients who are resistant to chemotherapy and immunotherapy.

Current treatments and emerging therapies of human polyomavirus-associated skin diseases: a comprehensive review.

Since Merkel cell polyomavirus (MCPyV) was linked as the predominant etiology of Merkel cell carcinoma (MCC) in 2008, three additional human polyomaviruses (HPyV) have been definitively linked to cutaneous diseases-trichodysplasia spinulosa virus (TSPyV) and human polyomavirus 6 and 7 (HPyV6, HPyV7). TSPyV contributes to the development of trichodysplasia spinulosa (TS), and HPyV6/7 is associated closely with the eruption of pruritic and dyskeratotic dermatoses (PDD). Clinically, MCC is treated with surgical excision and radiation with adjuvant chemotherapy, although newer treatment options include immune checkpoint inhibition. These novel immunotherapies hold promise for the treatment of metastatic MCC, but resistance and side effects prevent a significant proportion of patients from realizing their benefits. Based on previous case reports, the standard of care for the less deadly but disfiguring cutaneous disease TS include immunosuppressant (IS) reduction, the use of antivirals such as cidofovir (CDV) or valganciclovir (VGCV), or a combination of these treatments. Similar treatments were attempted for PDD, but oral acitretin was found to be most effective. As MCC, TS, and PDD are rare diseases, further research is required for effective treatments. In this review, we summarize clinical trials, preclinical studies, and case reports that present outcomes and side effects of current and emerging treatments for HPyV-associated cutaneous diseases, offering a comprehensive resource for clinical application and prospective clinical trials.

The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: a comprehensive review.

PURPOSE: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor's efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors. METHODS: Pertinent literature searches in PubMed and the Karyopharm Therapeutics website for selinexor and non-hematologic malignancies preclinical and clinical trials. RESULTS: This review provides evidence that selinexor is a promising agent used alone or in combination with other anticancer medications in non-hematologic malignancies. CONCLUSION: Further clinical investigation of selinexor treatment for solid malignancies is warranted.

Expert Consensus Statement on Proficiency Standards for Dermoscopy Education in Primary Care.

BACKGROUND: Primary care providers (PCPs) frequently address dermatologic concerns and perform skin examinations during clinical encounters. For PCPs who evaluate concerning skin lesions, dermoscopy (a noninvasive skin visualization technique) has been shown to increase the sensitivity for skin cancer diagnosis compared with unassisted clinical examinations. Because no formal consensus existed on the fundamental knowledge and skills that PCPs should have with respect to dermoscopy for skin cancer detection, the objective of this study was to develop an expert consensus statement on proficiency standards for PCPs learning or using dermoscopy. METHODS: A 2-phase modified Delphi method was used to develop 2 proficiency standards. In the study's first phase, a focus group of PCPs and dermatologists generated a list of dermoscopic diagnoses and associated features. In the second phase, a larger panel evaluated the proposed list and determined whether each diagnosis was reflective of a foundational or intermediate proficiency or neither. RESULTS: Of the 35 initial panelists, 5 PCPs were lost to follow-up or withdrew; 30 completed the fifth and last round. The final consensus-based list contained 39 dermoscopic diagnoses and associated features. CONCLUSIONS: This consensus statement will inform the development of PCP-targeted dermoscopy training initiatives designed to support early cancer detection.

Antibiotic overuse and resistance in dermatology.

Antibiotics have a significant role in dermatology, treating a wide range of diseases, including acne, rosacea, inflammatory skin conditions and skin structure infections, such as cellulitis, folliculitis, carbuncles, and furuncles. Because of their consistent use, utility, and availability, antibiotics are susceptible to overuse within the medical practice, and, specific to this discussion, in the dermatologic setting. The issue of continuously increasing risk of antibiotic resistance remains an important concern to the dermatologist. The scope of this review will be to provide an overview of the common antibiotics used in the dermatologic setting with an emphasis on identifying areas of overuse, reported bacterial resistance, and discussion of clinical management aimed at decreasing antibiotic resistance.

Ingenol mebutate: potential for further development of cancer immunotherapy.

Ingenol mebutate is a diterpene ester derived from the plant Euphorbia peplus and is FDA approved for the topical treatment of actinic keratoses (AK). Shown to be efficacious with as little as a 3-day trial, this compound is being further tested for the topical treatment of other nonmelanoma skin cancers with promising preclinical data. In an effort to elucidate the molecular mechanism of this novel drug, Stahlhut et al. (2012) suggest a role for calcium and apoptosis. Further studies are needed to evaluate the intracellular mechanisms of ingenol mebutate-mediated cytotoxicity. Additionally, studies such as this not only shed light on the mechanism of ingenol mebutate and its derivatives, but also pave the way for evaluating the involvement of the immune system in eliminating drug-treated cells and tissues. This has important implications for the development of novel topical immune modulatory products and the field of topical immunotherapy.

Innovative techniques of left atrial exposure in minimally invasive mitral valve repair.

Various atrial retractors have been developed to achieve optimal exposure of mitral valve in minimally invasive surgery. We introduce our technique of only using retraction sutures to expose mitral valve. This method is simple, efficient, and provides good exposure of the left atrium without causing traumatic injury.

Theory-Based Approaches to Support Dermoscopic Image Interpretation Education: A Review of the Literature.

Introduction: Efficient interpretation of dermoscopic images relies on pattern recognition, and the development of expert-level proficiency typically requires extensive training and years of practice. While traditional methods of transferring knowledge have proven effective, technological advances may significantly improve upon these strategies and better equip dermoscopy learners with the pattern recognition skills required for real-world practice. Objectives: A narrative review of the literature was performed to explore emerging directions in medical image interpretation education that may enhance dermoscopy education. This article represents the first of a two-part review series on this topic. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaborative (ISIC) assembled a 12-member Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of emerging directions in image interpretation education. The following theory-based approaches will be discussed in this first part: whole-task learning, microlearning, perceptual learning, and adaptive learning. Conclusions: Compared to traditional methods, these theory-based approaches may enhance dermoscopy education by making learning more engaging and interactive and reducing the amount of time required to develop expert-level pattern recognition skills. Further exploration is needed to determine how these approaches can be seamlessly and successfully integrated to optimize dermoscopy education.

Instructional Strategies to Enhance Dermoscopic Image Interpretation Education: a Review of the Literature.

Introduction: In image interpretation education, many educators have shifted away from traditional methods that involve passive instruction and fragmented learning to interactive ones that promote active engagement and integrated knowledge. By training pattern recognition skills in an effective manner, these interactive approaches provide a promising direction for dermoscopy education. Objectives: A narrative review of the literature was performed to probe emerging directions in medical image interpretation education that may support dermoscopy education. This article represents the second of a two-part review series. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaborative (ISIC) assembled an Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of theory-based approaches, as discussed in the first part of this series. The group also acknowledged the role of motivation, metacognition, and early failures in optimizing the learning process. Other promising teaching tools included gamification, social media, and perceptual and adaptive learning modules (PALMs). Conclusions: Over the years, many dermoscopy educators may have intuitively adopted these instructional strategies in response to learner feedback, personal observations, and changes in the learning environment. For dermoscopy training, PALMs may be especially valuable in that they provide immediate feedback and adapt the training schedule to the individual's performance.

Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Understanding the distinct genetic and epigenetic changes contributing to the establishment and growth of metastatic lesions is crucial for the development of novel therapeutic strategies. In a search for key regulators of colorectal cancer metastasis establishment, we have found that the serine/threonine kinase Akt2, a known proto-oncogene, is highly expressed in late-stage colorectal cancer and metastatic tumors. Suppression of Akt2 expression in highly metastatic colorectal carcinoma cells inhibits their ability to metastasize in an experimental liver metastasis model. Overexpression of wild-type Akt1 did not restore metastatic potential in cells with downregulated Akt2, thus suggesting non-redundant roles for the individual Akt isoforms. In contrast, Akt2 overexpression in wild-type PTEN expressing SW480 colorectal cancer cells led to the formation of micrometastases; however, loss of PTEN is required for sustained formation of overt metastasis. Finally, we found that the consequence of PTEN loss and Akt2 overexpression function synergistically to promote metastasis. These results support a role for Akt2 overexpression in metastatic colorectal cancer and establish a mechanistic link between Akt2 overexpression and PTEN mutation in metastatic tumor establishment and growth. Taken together, these data suggest that Akt family members have distinct functional roles in tumor progression and that selective targeting of the PI3K/Akt2 pathway may provide a novel treatment strategy for colorectal cancer metastasis.

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma.

Although basal cell carcinoma (BCC) is often managed successfully with surgery, patients with locally advanced BCC (laBCC) or metastatic BCC (mBCC) who are not candidates for surgery or radiotherapy have limited treatment options. Most BCCs result from aberrant Hedgehog pathway activation in keratinocyte tumor cells, caused by sporadic or inherited mutations. Mutations in the patched homologue 1 gene that remove its inhibitory regulation of Smoothened homologue (SMO) or mutations in SMO that make it constitutively active, lead to Hedgehog pathway dysregulation and downstream activation of GLI1/2 transcription factors, promoting cell differentiation and proliferation. Hedgehog inhibitors (HHIs) block overactive signaling of this pathway by inhibiting SMO and are currently the only approved treatments for advanced BCC. Two small-molecule SMO inhibitors, vismodegib and sonidegib, have shown efficacy and safety in clinical trials of advanced BCC patients. Although these agents are effective and tolerable for many patients, HHI resistance occurs in some patients. Mechanisms of resistance include mutations in SMO, noncanonical cell identity switching leading to tumor cell resistance, and non-canonical pathway crosstalk causing Hedgehog pathway activation. Approaches to managing HHI resistance include switching HHIs, HHI and radiotherapy combination therapy, photodynamic therapy, and targeting Hedgehog pathway downstream effectors. Increasing understanding of the control of downstream effectors has identified new therapy targets and potential agents for evaluation in BCC. Identification of biomarkers of resistance or response is needed to optimize HHI use in patients with advanced BCC. This review examines HHI resistance, its underlying mechanisms, and methods of management for patients with advanced BCC.