Establishment of a conditionally reprogrammed primary eccrine sweat gland culture for evaluation of tissue-specific CFTR function.

BACKGROUND: Sweat chloride concentration is used both for CF diagnosis and for tracking CFTR modulator efficacy over time, but the relationship between sweat chloride and lung health is heterogeneous and informed by CFTR genotype. Here, we endeavored to characterize ion transport in eccrine sweat glands (ESGs). METHODS: First, ESGs were microdissected from a non-CF skin donor to analyze individual glands. We established primary cultures of ESG cells via conditional reprogramming for functional testing of ion transport by short circuit current measurement and examined cell composition by single-cell RNA-sequencing (scRNA-seq) comparing with whole dissociated ESGs. Secondly, we cultured nasal epithelial (NE) cells and ESGs from two people with CF (pwCF) to assess modulator efficacy. Finally, NEs and ESGs were grown from one person with the CFTR genotype F312del/F508del to explore genotype-phenotype heterogeneity. RESULTS: ESG primary cells from individuals without CF demonstrated robust ENaC and CFTR function. scRNA-seq demonstrated both secretory and ductal ESG markers in cultured ESG cells. In both NEs and ESGs from pwCF homozygous for F508del, minimal baseline CFTR function was observed, and treatment with CFTR modulators significantly enhanced function. Notably, NEs from an individual bearing F312del/F508del exhibited significant baseline CFTR function, whereas ESGs from the same person displayed minimal CFTR function, consistent with observed phenotype. CONCLUSIONS: This study has established a novel primary culture technique for ESGs that allows for functional ion transport measurement to assess modulator efficacy and evaluate genotype-phenoytpe heterogeneity. To our knowledge, this is the first reported application of conditional reprogramming and scRNA-seq of microdissected ESGs.

Integrating skin color assessments into clinical practice and research: A review of current approaches.

Skin color classification can have importance in skin health, pigmentary disorders, and oncologic condition assessments. It is also critical for evaluating disease course and response to a variety of therapeutic interventions and aids in accurate classification of participants in clinical research studies. A panel of dermatologists conducted a literature review to assess the strengths and limitations of existing classification scales, as well as to compare their preferences and utilities. We identified 17 skin classification systems utilized in dermatologic settings. These systems include a range of parameters such as UV light reactivity, race, ethnicity, and degree of pigmentation. The Fitzpatrick skin type classification is most widely used and validated. However it has numerous limitations including its conflation with race, ethnicity, and skin color. There is a lack of validation data available for the remaining scales. There are significant deficiencies in current skin classification instruments. Consensus-based initiatives to drive the development of validated and reliable tools are critically needed.

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.

Effects of safe handling education on cognition, compliance and stress handling of antineoplastic drugs in clinical nurses.

To evaluate the effects of safe-handling education on the cognition, practice and stress handling of antineoplastic drugs in clinical nurses. This study uses a quasi-experimental, non-equivalent control group pre-test and post-test design. The experimental and control groups had 30 nurses each, who handled antineoplastic drugs from three institutions. This study examines the safe handling of antineoplastic drugs six times, for two hours each over two weeks. To verify the homogeneity of the experimental and control groups and the effectiveness of safe-handling education about antineoplastic drugs, a chi-square test and independent samples t-test were performed. The results were statistically significant in both groups (cognition [t = 6.84, p < 0.001], practice [t = 5.86, p < 0.001], and the stress of handling antineoplastic drugs [t = 5.15, p < 0.001]). Education on ways to safely handle antineoplastic drugs improves cognition, practice and stress handling of these drugs; moreover, proper education minimizes exposure.

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis.

Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease that disproportionately affects black patients. However, the pathogenesis of PN is poorly understood. We performed single-cell transcriptomic profiling, ligand receptor analysis and cell trajectory analysis of 28,695 lesional and non-lesional PN skin cells to uncover disease-identifying cell compositions and genetic characteristics. We uncovered a dysregulated role for fibroblasts (FBs) and myofibroblasts as a key pathogenic element in PN, which were significantly increased in PN lesional skin. We defined seven unique subclusters of FBs in PN skin and observed a shift of PN lesional FBs towards a cancer-associated fibroblast (CAF)-like phenotype, with WNT5A+ CAFs increased in the skin of PN patients and similarly so in squamous cell carcinoma (SCC). A multicenter PN cohort study subsequently revealed an increased risk of SCC as well as additional CAF-associated malignancies in PN patients, including breast and colorectal cancers. Systemic fibroproliferative diseases were also upregulated in PN patients, including renal sclerosis and idiopathic pulmonary fibrosis. Ligand receptor analyses demonstrated increased FB1-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV, suggesting a fibroblast-neuronal axis in PN. Type I IFN responses in immune cells and increased angiogenesis/permeability in endothelial cells were also observed. As compared to atopic dermatitis (AD) and psoriasis (PSO) patients, increased mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype between atopic dermatitis and psoriasis. These findings identify a pathogenic role for CAFs in PN, including a novel targetable WNT5A+ fibroblast subpopulation and CAF-associated malignancies in PN patients.

Sex-specific differences in oxidative stress markers and collagen expression in perioral skin wrinkling.

Wrinkling is the hallmark of skin ageing. We previously reported that perioral wrinkling is more severe in females; however, the molecular basis is unknown. This study assessed sex differences in the molecular expression of key ageing regulators in perioral skin. Twelve subjects (n = 6 male/female) were enrolled in this cross-sectional study and biopsies were taken from the perioral and periocular regions. RNA expression of collagen I, collagen III, cysteine-rich angiogenic inducer 61 (CYR61) and insulin-like growth factor 1 (IGF-1) was assessed by qPCR. There was no difference between females' and males' Griffith's grades (6 and 5.67, respectively, p = 0.092) or periocular wrinkling grades (3.2 and 2.6, p = 0.421), but females had more severe perioral wrinkling grades than males (6.2 and 2.8, p = 0.020). Females not only expressed significantly more CYR61 (p = 0.018) in the perioral region than malesm but also expressed more collagen III (p = 0.016). There was no difference in collagen I (p = 0.115) or IGF-1 (p = 0.124) expression in the perioral region between sexes. In the periocular region, there were no significant differences between sexes in the expression of all four markers. The significant molecular differences in the perioral region between the sexes may contribute to the greater perioral skin wrinkling seen clinically in females.

N6-methyladenosine RNA Methylation Correlates with Immune Microenvironment and Immunotherapy Response of Melanoma.

RNA methylation normally inhibits the self-recognition and immunogenicity of RNA. As such, it is likely an important inhibitor of cancer immune recognition in the tumor microenvironment, but how N6-methyladenosine (m6A) affects prognosis and treatment response remains unknown. In eight independent melanoma cohorts (1,564 patients), the modification patterns of 21 m6A gene signatures were systematically correlated with the immune cell infiltration of melanoma tumor microenvironment. m6A modification patterns for each patient were quantified using the principal component analysis method, yielding an m6Ascore that reflects the abundance of m6A RNA modifications. Two different m6A modification patterns were observed in patients with melanoma, separated into high and low m6Ascores that correlated with survival and treatment response. Low m6Ascores were characterized by an immune-inflamed phenotype, with 61.1% 5-year survival. High m6Ascores were characterized by an immune-excluded phenotype, with 52.2% 5-year survival. Importantly, lower m6Ascores correlated with more sensitive anti-PD-1 and anti-CTLA4 treatment responses, with 90% of patients with low m6Ascore responding, whereas 10% of those with high m6Ascore nonresponding (in cohort GSE63557). At single-cell and spatial transcriptome resolution, m6Ascore reflects melanoma malignant progression, immune exhaustion, and resistance to immune checkpoint blockade therapy. Hence, the m6Ascore correlates to an important facet of tumor immune escape as a tool for personalized medicine to guide immunotherapy in patients with melanoma.

Association of Early Clinical Response to Laser Rejuvenation of Photoaged Skin with Increased Lipid Metabolism and Restoration of Skin Barrier Function.

Laser resurfacing treatments for photoaged skin have improved dramatically over the past decades, but few studies have examined the molecular mechanisms underlying differences in clinical response. Seventeen white female participants with moderate-to-severe photoaging received nonablative fractional laser treatment on the face and forearm once monthly for 6 months. Biopsies for microarray analysis were performed at baseline and 7 days after facial treatment and at baseline and 1, 7, 14, and 29 days after forearm treatment in each participant, resulting in 119 total samples. Participants were stratified into fast (n = 11) and slow (n = 6) responders on the basis of the presence of clinical improvement after the first treatment. Microarray analysis revealed the upregulation of genes associated with matrix metalloproteinases, collagen and extracellular components, TGF-ß signaling, double-stranded RNA signaling, and retinoic acid synthesis after treatment that did not differ significantly between fast and slow responders. Cluster and enrichment analyses suggested significantly greater activation of lipid metabolism and keratinocyte differentiation in fast responders, who showed greater upregulation of acyltransferases, fatty acid elongases, fatty acid 2-hydroxylase, fatty acid desaturases, and specific keratins that may contribute to epidermal barrier function. These results create, to our knowledge, a previously unreported atlas of molecular changes that correlate with improvements in photoaging after laser therapy.

Skin type specific photobiological response to visible light is mediated by constitutional melanin.

BACKGROUND: Visible light (VL) induces varying photobiological responses between skin types, likely influenced by inherent melanization. Individual typology angle (ITA) objectively measures skin types. We hypothesize that epidermal melanin content and distribution determine VL response. OBJECTIVES: This study describes clinical and histologic responses to VL and examines the potential role of melanin in the underlying mechanistic pathways. METHODS: We grouped enrolled participants by ITA (Light = 5, Intermediate = 4, Dark = 7) per colorimetry (CR-400, Konica Minolta). Photoprotected sites were exposed daily to 480 J/cm2 of VL (Fiber-Lite High Intensity Illuminator, Series 180, Dolan Jenner Industries Inc.) for 4 days (total = 1920 J/cm2 ), as tolerated. Treated and control sites were biopsied 96 h after first exposure. We used hematoxylin and eosin and Fontana-Mason to assess histological changes and melanin deposition, respectively. p53 and Ki67 immunohistochemical stains were done to assess DNA damage and proliferation. Matrix metalloproteinase (MMP)-1 expression was detected by immunohistochemical staining and immunofluorescence microscopy. RESULTS: Darker skin did not tolerate the full VL regimen with blistering occurring in most subjects at doses of 220-880 J/cm2 . Intermediate and Dark skin showed tanning. Light skin developed erythema. p53 counts were highest in Intermediate, followed by Light skin, although this was not statistically significant. VL treatment led to MMP-1 expression and nuclear localization in keratinocytes in Dark and Intermediate but not in Light skin, however differences between groups were not statistically significant. CONCLUSIONS: Skin types demonstrate unique biological responses to VL. The role of melanin in photoprotection is well-defined. However, given the pro-apoptotic function of nuclear MMPs, we suggest a potential mechanism by which melanin may mediate VL-induced phototoxicity.

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.

Autoantibodies Present in Hidradenitis Suppurativa Correlate with Disease Severity and Promote the Release of Proinflammatory Cytokines in Macrophages.

Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti-human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.

A Role for NRF2-Signaling in the Treatment and Prevention of Solar Lentigines.

BACKGROUND: Photoaging is premature skin aging resulting from oxidative stress generated by exposure to solar radiation. A key clinical feature is solar lentigines, areas of hyperpigmentation on sun-exposed skin. Skin pigmentation is determined by cross-talk between keratinocytes and melanocytes, which is exquisitely sensitive to oxidative stress. Toll-like receptor (TLR) signaling and NF-E2-related factor 2 (NRF2) signaling, an endogenous antioxidant system, serve as a bridge between the oxidative stress response and immune regulation. Moreover, TLR-mediated induction of IL-6 production has been shown to prevent ultraviolet (UV)-induced hyperpigmentation. METHODS: Shave biopsies of solar lentigines were obtained from 14 individuals. An additional 7 subjects applied broccoli sprout extract (BSE) containing sulforaphane daily or vehicle on photodamaged skin. Immunofluorescence staining was used to determine total and phosphorylated NRF2 in the lentiginous skin. Dermoscopy and Fontana & Masson staining were used to assess the effect of topical BSE on UV-induced pigmentation. Similar topical treatments were performed in a mouse model of UVB-induced hyperpigmentation utilizing WT, Nrf2-/-, or K14-Cre-ERT2IL-6Rαfl/fl C57BL/6 mice. RESULTS: NRF2 expression is altered in solar lentigines, and UV-induced skin pigmentation in humans could be ameliorated with topical BSE. Corresponding mouse models replicated the authors' clinical findings and identified a potential mechanistic link to IL-6Rα signaling in keratinocytes. CONCLUSION: The authors' findings suggest that dysregulation of NRF2 signaling is involved in the pathogenesis of UV-induced skin pigmentation and pharmacological activation of NRF2 may represent a potential therapeutic target in photoaging.

Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization.

Prurigo nodularis (PN) is an understudied, chronic inflammatory skin disease that disproportionately affects African Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize the immune dysregulation in PN, PBMCs and skin biopsies were obtained from patients with PN and healthy subjects (majority African American) matched by age, race, and sex. Flow cytometric analysis of functional T-cell response comparing patients with PN with healthy subjects identified increased γδT cells (CD3+CD4-CD8-γδTCR+) and Vδ2+ γδT enrichment. Activated T cells demonstrated uniquely increased IL-22 cytokine expression in patients with PN compared with healthy controls. CD4+ and CD8+ T cells were identified as the source of increased circulating IL-22. Consistent with these findings, RNA sequencing of lesional PN skin compared with nonlesional PN skin and biopsy site‒matched control skin demonstrated robust upregulation of T helper (Th) 22‒related genes and signaling networks implicated in impaired epidermal differentiation. Th22‒related cytokine upregulation remained significant, with stratifications by race and biopsy site. Importantly, the expression of the IL-22 receptors IL22RA1 and IL22RA2 was significantly elevated in lesional PN skin. These results indicate that both systemic and cutaneous immune responses in patients with PN are skewed toward a Th22/IL-22 profile. PN may benefit from immunomodulatory therapies directed at Th22‒mediated inflammation.

Noninflammatory comedones have greater diversity in microbiome and are more prone to biofilm formation than inflammatory lesions of acne vulgaris.

BACKGROUND: The ability of Cutibacterium acnes strains to form biofilms has been correlated with their virulence. OBJECTIVE: This study examined biofilm and skin microbiota in acne patients in order to understand their role in the development of acne lesions. METHODS: Thin sections of punch biopsy specimens of (i) uninflamed comedones, (ii) inflammatory lesions, and (iii) uninvolved adjacent skin of acne patients were examined. Epiflourescence and confocal laser scanning microscopy were used for biofilm detection, and pyrosequencing with taxonomic classification of 16s rRNA gene amplicons was used for microbiota analysis. RESULTS: Of the 39 skin specimens from patients with mild-moderate acne (n = 13) that were studied, nine (23%) contained biofilm. Among these specimens, biofilm was most frequently detected in comedones (55.6%) and less frequently in inflammatory papules (22.2%) and uninvolved skin (22.2%). Comedones demonstrated the highest mean alpha diversity of all the lesion subtypes. The relative abundance of Staphylococcus was significantly higher in comedones (11.400% ± 12.242%) compared to uninvolved skin (0.073% ± 0.185%, P = 0.024). CONCLUSIONS: The microenvironment of the comedone differs from that of inflammatory lesions and unaffected skin. The increased frequency of biofilm in comedones may account for the lack of host inflammatory response to these lesions.

The association of photo-induced collagen degeneration and the development of telangiectasias in rosacea.

Rosacea is a chronic, often progressive disorder characterized by facial erythema, telangiectasias, papules, pustules, and/or rhinophyma. In this study, we investigated the tissue structure in rosacea compared to controls. We performed a case-control study between five patients with mild-to-moderate erythematotelangiectatic rosacea (ETR) and five matched controls. Facial biopsy samples from rosacea patients and controls were stained with picrosirius red for collagen and CD31 for microvessel identification. Mean collagen content was significantly greater in control samples (19.603% ±8.821%) compared to rosacea samples (16.812% ± 7.787%, p = 0.030). In contrast, mean microvessel density was significantly higher in rosacea patients (4.775 E-5 ± 1.493 E-5 µm-3 ) compared to controls (2.559 E-5 ± 8.732 E-6 µm-3 , p = 0.004). Mean microvessel lumen area was also significantly higher in rosacea patients (491.710 ± 610.188 µm2 ) compared to controls (347.879 ± 539.624 µm2 , p = 0.003). We identified a correlation between decreased collagen content and increased microvessel size and density in rosacea patients that was not observed in controls. These structural changes to the dermal matrix may contribute to the characteristic vessel growth and dilation in rosacea.

Comparison of the skin microbiota in acne and rosacea.

Acne and rosacea, despite their similar clinical presentations, follow distinct clinical courses, suggesting that fundamental differences exist in their pathophysiology. We performed a case-control study profiling the skin microbiota in rosacea and acne patients compared to matched controls. Nineteen rosacea and eight acne patients were matched to controls by age ± 5 years, sex and race. DNA was extracted from facial skin swabs. The V3V4 region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq and analysed using QIIME/Metastats 2.0 software. The mean relative abundance of Cutibacterium acnes in rosacea with inflammatory papules and pustules (20.454% ±16.943%) was more similar to that of acne (19.055% ±15.469%) than that of rosacea without inflammatory papules and pustules (30.419% ±21.862%). C acnes (P = .048) and Serratia marcescens (P = .038) were significantly enriched in individuals with rosacea compared to acne. Investigating the differences between the skin microbiota in acne and rosacea can provide important clues towards understanding the disease progression in each condition.

Association of the Psoriatic Microenvironment With Treatment Response.

Importance: The ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well. Objective: To develop a bioinformatic gene signature score derived from skin mRNA to predict psoriasis treatment outcomes for a variety of therapies. Design, Setting, and Participants: In this decision analytical model using 1145 skin samples from different cohorts of 12 retrospective psoriasis studies, samples were analyzed using the CIBERSORT algorithm to define the immune landscape of psoriasis lesions and controls. Random forest classification and principal component analysis algorithms were used to estimate psoriatic microenvironment (PME) signature genes and construct a PME score. Overall, 85 and 421 psoriasis lesions from 1 and 4 independent cohorts were used as discovery and validation studies, respectively. Among them, 157, 71, 89, and 90 psoriasis lesions were treated with etanercept, tofacitinib, adalimumab, and methotrexate, respectively. Main Outcomes and Measures: Number of weeks after treatment initiation when responders and nonresponders could be predicted. Results: Overall, 22 immune cell subtypes formed infiltration patterns that differentiated psoriasis lesions from healthy skin. In psoriasis lesions, the expression of 33 PME signature genes defined 2 immune phenotypes and in aggregate could be simplified to a numerical PME score. A high PME score, characterized by keratinocyte differentiation, correlated with a better treatment response (Psoriasis Area and Severity Index [PASI] reduction, 75.8%; 95% CI, 69.4% to 82.2%; P = .03), whereas a low PME score exhibited an immune activation signature and was associated with a worse response (PASI reduction, 53.5%; 95% CI, 45.3% to 61.7%; P = .03). The PME score at week 4 after treatment initiation correlated with future responder vs nonresponder to treatment status 8 to 12 weeks earlier than PASI reduction for etanercept, methotrexate plus adalimumab, and tofacitinib. Conclusions and Relevance: The PME score is a biometric score that may predict clinical efficacy of systemic psoriasis therapy in advance of clinical responses. As an application of personalized medicine, it may reduce the exposure of patients with psoriasis to ineffective and expensive therapies.

The Relationship of Perceptions of Hospice and Palliative Care With Emotional Intelligence and Cognitive Empathy in Nursing Students.

This study aimed to identify the relationships of perception of hospice and palliative care with emotional intelligence and cognitive empathy in nursing students. The participants were 458 nursing students. Data were collected using structured questionnaires and analyzed with Pearson correlation coefficients, independent-samples t test, and binary logistic regression. Perception of hospice and palliative care was significantly and positively correlated with emotional intelligence (r = 0.224, P < .001) and cognitive empathy (r = 0.311, P < .001). Mean score differences of perception of hospice and palliative care by emotional intelligence and cognitive empathy were statistically significant (t = -3.973, P < .001; t = -4.109, P < .001, respectively). Logistic regression yielded an odds ratio of 1.860 (P < .001; 95% confidence interval, 1.283-2.698) between the perception of hospice and palliative care and emotional intelligence and an odds ratio of 2.028 (P < .001; 95% confidence interval, 1.394-2.951) between the perception of hospice and palliative care and cognitive empathy. Emotional intelligence and cognitive empathy should be cultivated to raise nursing students' perception of hospice and palliative care and must be included when developing related curricula and extracurricular programs.