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Melanoma's rare capacity to undergo heterologous differentiation can create significant diagnostic challenges. The molecular mechanisms underlying this phenomenon are not well understood. We present an unusual case of subungual melanoma exhibiting extensive cartilaginous differentiation and provide insights into its molecular and cytogenomic features. Histopathologically, the tumor was predominantly composed of nodules of malignant cartilage in association with a smaller population of nested epithelioid to rhabdoid cells. Immunohistochemically, the tumor cells in both components were positive for S100, SOX10, and PRAME, and were negative for Melan‐A and HMB‐45. Molecular analysis by whole exome DNA sequence did not detect any pathogenic variants in genes commonly implicated in melanoma. Additional analysis by SNP chromosomal microarray revealed a complex genome characterized by numerous chromosomal losses and gains, including a homozygous deletion of the CDKN2A locus and a heterozygous deletion of the locus containing EXT2, a tumor suppressor implicated in hereditary multiple osteochondromas and secondary chondrosarcomas. This case underscores the importance of recognizing cartilaginous differentiation as a rare manifestation of melanoma, particularly at subungual sites, and suggests that at least some of these melanomas may be driven by non‐canonical molecular pathways. [ABSTRACT FROM AUTHOR]

Germline genetic evaluation is indicated for all patients with epithelial ovarian cancer (EOC). For testing to have clinical utility, results must be documented within the electronic medical record (EMR) and accessible to providers at the point of care, which can be challenging in the context of current EMR limitations and genetic testing processes. We examined the receipt of genetics services and EMR capture of genetic testing results in patients with EOC. We conducted a retrospective chart review to examine germline genetic evaluations among patients with EOC seen by a gynecologic or medical oncologist at the University of Pennsylvania in 2016. EMRs were reviewed to determine: (1) if patients were referred for genetic evaluation; (2) if genetic testing was performed; (3) if results were documented in office notes, scanned third‐party test reports, and/or the EMR problem list; (4) if provider notes correctly listed the variant classification. Overall, 413 (62%) of patients had documented genetic testing. Genetic testing was documented in almost all provider notes (96%) and the majority of scanned EMR reports (64%). Pathogenic variants were found in 119 (29%) individuals; the majority (70%) had genetic testing documented within EMR problem lists. Provider notes were highly accurate in describing variant classification. In this study, genetic testing was performed and documented in the EMR for most EOC patients. Approximately one‐third of those tested did not have scanned test reports specifying variant found, limiting the utility of test results for cascade testing and therapeutic decisions. [ABSTRACT FROM AUTHOR]

In April 2023, the World Health Organization (WHO) issued new estimates affirming that one in six individuals experience infertility globally. Yet, many states are unclear on their responsibility to prevent infertility, ensure access to treatment, and to end the harm suffered by individuals who are considered infertile. Responding to this uncertainty, in June 2023, the United Nations Office of the High Commissioner on Human Rights (OHCHR) issued a new research paper explaining states' legal obligations regarding infertility. Importantly, OHCHR underscores that states must take steps to prevent infertility by addressing its root causes and ensure access to treatment. Further, states must address the negative consequences of infertility, including stigma and violence, as well as the discriminatory stereotypes that lead to certain groups facing disproportionate harm from infertility. This article provides an overview of the OHCHR report and explains what this means for healthcare providers, who have a critical role to play in providing care and advocating for legal and policy reform necessary to prevent, diagnose, and treat infertility. Synopsis: This article provides an overview of OHCHR's new 2023 research paper on human rights obligations to address the preventable causes and consequences of infertility, and highlights healthcare providers' role in advancing human rights and preventing harm to patients through infertility prevention, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Of note, chlamydia and gonorrhea are now some of the most common STIs, even though dermatologists less frequently screen for these infections.[4] Of the 81 providers, 54% report always or sometimes taking a sexual history, while 46% rarely or never take a sexual history. Dear Editor, The field of dermatology has historical roots in the diagnosis and treatment of sexually transmitted infections (STIs). The results of dermatologist demographics, STIs observed in practice, and STI clinical practice patterns are shown in Tables 1 and 2. [Extracted from the article]

Recent advances in systematic conservation planning make use of modern portfolio theory (MPT)—a framework to construct and select optimal allocation of assets—to address the challenges posed by climate change uncertainty. However, these methods are difficult to implement for fine‐scale conservation planning when the information on future climate scenarios is insufficient. Insufficient information makes the estimators of the key inputs in the optimisation procedure unreliable leading to technical problems for the construction of optimal asset allocation.We identify three statistical methods—constant correlation model, the Ledoit–Wolf approach and the weighted non‐negative least‐squares approach—that can overcome the lack of sufficient information and enable the use of MPT for fine‐scale conservation planning.We illustrate the use of the three methods for identifying efficient portfolio allocation strategies, that is, strategies that give minimum amount of risk for a chosen level of return or maximum return for a chosen level of risk, using case studies of wetland conservation planning in North America and coastal conservation planning in Australia. We compare conservation planning strategies with complete information using standard portfolio theory and with insufficient information using the three methods to highlight their advantages and disadvantages. We find the Ledoit–Wolf and weighted non‐negative least‐squares approaches perform well and can identify risk‐return outcomes that are close to those identified with complete information.The methods presented in this study broaden the range of cases where the application of MPT is possible in conservation planning to enhance its uptake and lead to more efficient allocation of conservation resources. [ABSTRACT FROM AUTHOR]

Background: Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership. Methods: Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class. Results: Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain. Conclusions: Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long‐term risk of heart failure, particularly in those with modest LVEF declines. Modest declines in left ventricular ejection fraction (LVEF) in patients with breast cancer who are treated with cardiotoxic cancer therapy are accompanied by an increased incidence of biochemical and functional abnormalities. This suggests that declines in LVEF that do not reach the conventional thresholds used for the diagnosis of cardiotoxicity could be more clinically important than previously understood. [ABSTRACT FROM AUTHOR]

Climate-change induced uncertainties in future spatial patterns of conservation-related outcomes make it difficult to implement standard conservation-planning paradigms. A recent study translates Markowitz's risk-diversification strategy from finance to conservation settings, enabling conservation agents to use this diversification strategy for allocating conservation and restoration investments across space to minimize the risk associated with such uncertainty. However, this method is information intensive and requires a large number of forecasts of ecological outcomes associated with possible climate-change scenarios for carrying out fine-resolution conservation planning. We developed a technique for iterative, spatial portfolio analysis that can be used to allocate scarce conservation resources across a desired level of subregions in a planning landscape in the absence of a sufficient number of ecological forecasts. We applied our technique to the Prairie Pothole Region in central North America. A lack of sufficient future climate information prevented attainment of the most efficient risk-return conservation outcomes in the Prairie Pothole Region. The difference in expected conservation returns between conservation planning with limited climate-change information and full climate-change information was as large as 30% for the Prairie Pothole Region even when the most efficient iterative approach was used. However, our iterative approach allowed finer resolution portfolio allocation with limited climate-change forecasts such that the best possible risk-return combinations were obtained. With our most efficient iterative approach, the expected loss in conservation outcomes owing to limited climate-change information could be reduced by 17% relative to other iterative approaches. [ABSTRACT FROM AUTHOR]

Rapid conversion of private land for agricultural and urban use has raised concern worldwide over the loss of ecological services. To inform conservation policy, we model privately optimal land use decisions using a real options framework that assumes both the ecological and commercial values of land are stochastic and that land conversion is irreversible. We analyze permanent and temporary land conservation policy incentives using this dynamic framework to guide policy makers interested in designing efficient payment mechanisms to achieve ecological preservation goals. We find that while the financial cost of temporary policy incentives is generally much lower than permanent policy incentives, this difference is very small in scenarios with high discount rates and lower uncertainties in conversion returns and lower expected trend in conservation returns. Alternately, the financial cost of temporary conservation is substantially lower than that of permanent conservation when the expected trend in conservation returns and uncertainties in conservation and conversion returns is high and the discount rate is low. Comparison with net present value and single-source uncertainty models indicates that the presence of a second uncertainty increases the option value of delaying conversion, and shows that permanent and temporary policy incentives based on either of the two simpler models can be seriously misguided if multiple uncertainties are present. We illustrate the analytical results with a case study of tropical deforestation in Indonesia where private landowners can either conserve forests and earn carbon credits, or convert to palm oil agriculture and earn profits from the sale of palm oil. [ABSTRACT FROM AUTHOR]

Background: Biological differences between BRCA-associated breast cancer and sporadic breast cancer may warrant different adjuvant chemotherapy (ACRx) recommendations despite similar phenotypic features. A 21-gene expression profile (Oncotype DX) generates a prognostic recurrence score (RS) that predicts the ACRx benefit in patients with hormone receptor-positive breast cancer. No reports describe assay results for BRCA-associated breast cancer.Methods: A review of Memorial Sloan Kettering Cancer Center databases identified 4908 patients with hormone receptor-positive, node-negative breast cancer who underwent Oncotype DX testing between July 2006 and March 2014. BRCA1/BRCA2 carriers (cases) were identified and matched (1:2) by age at diagnosis and tumor size to noncarrier controls. Two-sample nonparametric tests were used to compare the baseline characteristics, RSs, and risk stratification between BRCA1 and BRCA2 patients. Conditional logistic regression was used to assess these differences by mutational status.Results: Fifty mutation-associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P = .9) and tumor size (P = .6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P = .6) and risk category stratification (P = .3). The median RS was higher for cases versus controls (24 vs 16; P < .0001). Risk stratification also differed by mutational status (P = .0002). Cases had more high-risk disease (28% vs 7%) and intermediate-risk disease (56% vs 36%) and less low-risk disease (16% vs 57%). Cases were more likely than controls to receive ACRx (74% vs 46%; P = .002).Conclusions: Germline BRCA-associated hormone receptor-positive breast cancer may be associated with intrinsically less favorable biology. Few affected carriers have RS indicating a clear absence of benefit from ACRx. The increased use of ACRx and benefit from ACRx in BRCA carriers may mitigate otherwise inferior outcomes. [ABSTRACT FROM AUTHOR]

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A letter to the editor is presented in response to an article about the use of valproic acid (VPA) for the treatment of myeloid malignancies.

Methotrexate is historically recognized as an effective treatment of pemphigus but its utility as a single or alternate steroid-sparing agent was not recognized in recent consensus recommendations in pemphigus management. We aimed to evaluate the efficacy and safety of a treatment course for pemphigus that involves methotrexate as a single or steroid-sparing agent. In a retrospective cohort study, we examined patients with pemphigus vulgaris or pemphigus foliaceus who were on ≥3 months of methotrexate therapy. Efficacy and safety were evaluated by established pemphigus disease endpoints. Of the 34 patients who met inclusion criteria, 25 (73.5%) were on glucocorticoids at time of methotrexate initiation (median follow-up: 5.4 years; median time on methotrexate: 3.7 years). An appreciable proportion achieved disease control (91.2%), with some achieving clinical remission off all systemic therapies (23.5%). For patients on glucocorticoids, median time to control was 42 days, median time to minimal steroid dose tapering (5 mg prednisone) was 161 days, and median time to complete steroid tapering was 308 days. For patients on methotrexate as a single agent, median time to control was 119 days. Among all patients, relapse commonly occurred (88.2%). At last follow-up, 26.5% were managed on topical therapies alone and 11.8% required systemic steroid therapy. Methotrexate was largely tolerated with a low incidence of adverse events leading to treatment discontinuation (2.9%). Methotrexate has the potential to be an effective and well-tolerated option for patients and may be considered for use as an alternate single or steroid-sparing agent for pemphigus., (© 2022 Wiley Periodicals LLC.)