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Background: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disorder. It is commonly caused by mutations in PTCH1 and chiefly characterized by multiple basal cell carcinomas (BCCs) developing prior to the age of 30 years. In rare cases, NBCCS presents with a late onset of BCC development. Objective: To investigate BCC tumorigenesis in two brothers, who showed characteristic features of NBCCS but developed their first BCCs only after the age of 40 years. Two other siblings did not show signs of NBCCS. Results: We obtained blood samples from four siblings and nine BCCs from the two brothers with NBCCS. Whole exome sequencing and RNA sequencing revealed loss of heterozygosity (LOH) of PTCH1 in eight out of nine tumours that consistently involved the same haplotype on chromosome 9. This haplotype contained a germinal splice site mutation in PTCH1 (NM_001083605:exon9:c.763‐6C>A). Analysis of germline DNA confirmed segregation of this mutation with the disease. All BCCs harboured additional somatic loss‐of‐function (LoF) mutations in the remaining PTCH1 allele which are not typically seen in other cases of NBCCS. This suggests a hypomorphic nature of the germinal PTCH1 mutation in this family. Furthermore, all BCCs had a similar tumour mutational burden compared to BCCs of unrelated NBCCS patients while harbouring a higher number of damaging PTCH1 mutations. Conclusions: Our data suggest that a sequence of three genetic hits leads to the late development of BCCs in two brothers with NBCCS: a hypomorphic germline mutation, followed by somatic LOH and additional mutations that complete PTCH1 inactivation. These genetic events are in line with the late occurrence of the first BCC and with the higher number of damaging PTCH1 mutations compared to usual cases of NBCCS. [ABSTRACT FROM AUTHOR]

Summary: These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert‐based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis. What's already known about this topic? Various symptomatic treatment options exist for congenital ichthyoses, but there are no European guidelines. What does this study add? These European guidelines for the management of congenital ichthyosis may help to improve outcomes and quality of life for patients. Linked Comment:Akiyama. Br J Dermatol 2019; 180:449–450. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert‐based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling. Linked Comment:  Levy. Br J Dermatol 2019; 180:253. [ABSTRACT FROM AUTHOR]

Previous advances have identified immune pathways associated with inflammatory skin diseases, leading to the development of targeted therapies. However, there is a lack of molecular approaches that delineate these pathways at the individual patient level for personalized diagnostic and therapeutic guidance. Here, we conduct a cross-comparison of expression profiles from multiple inflammatory skin diseases to identify gene modules defining relevant immune pathways. Seven modules are identified, representing key immune pathways: Th17, Th2, Th1, Type I IFNs, neutrophilic, macrophagic, and eosinophilic. These modules allow the development of a molecular map with high diagnostic efficacy for inflammatory skin diseases and clinico-pathologically undetermined cases. Aligning dominant modules with treatment targets offers a rational framework for treatment selection, improving response rates in both treatment-naïve patients and non-responders to targeted therapies. Overall, our approach offers precision medicine for inflammatory skin diseases, utilizing transcriptional modules to support diagnosis and guide personalized treatment selection., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: We developed the Hospital-to-Home-Health Transition Quality (H3TQ) Index for skilled home healthcare (HH) agencies to identify threats to safe, high-quality care transitions in real time., Objective: Assess the validity of H3TQ in a large sample across diverse communities., Research Design: A survey of recently hospitalized older adults referred for skilled HH services and their HH provider at two large HH agencies in Baltimore, MD, and New York, NY., Subjects: There were five hundred eighty-seven participants (309 older adults, 141 informal caregivers, and 137 HH providers). Older adults, caregivers, and HH providers rated 747 unique transitions. Of these, 403 were rated by both the older adult/caregiver and their HH provider, whereas the remaining transitions were rated by either party., Measures: Construct, concurrent, and predictive validity were assessed via the overall H3TQ rating, correlation with the care transition measure (CTM), and the Medicare Outcome and Assessment Information Set (OASIS)., Results: Proportion of transitions with quality issues as identified by HH providers and older adults/caregivers, respectively; Baltimore 55%, 35%; NYC 43%, 32%. Older adults/caregivers across sites rated their transitions as higher quality than did providers (P<0.05). H3TQ summed scores showed construct validity with the CTM-3 and concurrent validity with OASIS measures. Summed H3TQ scores were not significantly correlated with 30-day ED visits or rehospitalization., Conclusions: The H3TQ identifies care transition quality issues in real-time and demonstrated construct and concurrent validity, but not predictive validity. Findings demonstrate value in collecting multiple perspectives to evaluate care transition quality. Implementing the H3TQ could help identify transition-quality intervention opportunities for HH patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients requiring skilled home health care (HH) after hospitalization are at high risk of adverse events. Human factors engineering (HFE) approaches can be useful for measure development to optimize hospital-to-home transitions., Objective: To describe the development, initial psychometric validation, and feasibility of the Hospital-to-Home-Health-Transition Quality (H3TQ) Index to identify patient safety risks., Methods: Development : A multisite, mixed-methods study at 5 HH agencies in rural and urban sites across the United States. Testing : Prospective H3TQ implementation on older adults' hospital-to-HH transitions. Populations Studied : Older adults and caregivers receiving HH services after hospital discharge, and their HH providers (nurses and rehabilitation therapists)., Results: The H3TQ is a 12-item count of hospital-to-HH transitions best practices for safety that we developed through more than 180 hours of observations and more than 80 hours of interviews. The H3TQ demonstrated feasibility of use, stability, construct validity, and concurrent validity when tested on 75 transitions. The vast majority (70%) of hospital-to-HH transitions had at least one safety issue, and HH providers identified more patient safety threats than did patients/caregivers. The most frequently identified issues were unsafe home environments (32%), medication issues (29%), incomplete information (27%), and patients' lack of general understanding of care plans (27%)., Conclusions: The H3TQ is a novel measure to assess the quality of hospital-to-HH transitions and proactively identify transitions issues. Patients, caregivers, and HH providers offered valuable perspectives and should be included in safety reporting. Study findings can guide the design of interventions to optimize quality during the high-risk hospital-to-HH transition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Skilled home healthcare (HH) provided in-person care to older adults during the COVID-19 pandemic, yet little is known about the pandemic's impact on HH care transition patterns. We investigated pandemic impact on (1) HH service volume; (2) population characteristics; and (3) care transition patterns for older adults receiving HH services after hospital or skilled nursing facility (SNF) discharge., Methods: Retrospective, cohort, comparative study of recently hospitalized older adults (≥ 65 years) receiving HH services after hospital or SNF discharge at two large HH agencies in Baltimore and New York City (NYC) 1-year pre- and 1-year post-pandemic onset. We used the Outcome and Assessment Information Set (OASIS) and service use records to examine HH utilization, patient characteristics, visit timeliness, medication issues, and 30-day emergency department (ED) visit and rehospitalization., Results: Across sites, admissions to HH declined by 23% in the pandemic's first year. Compared to the year prior, older adults receiving HH services during the first year of the pandemic were more likely to be younger, have worse mental, respiratory, and functional status in some areas, and be assessed by HH providers as having higher risk of rehospitalization. Thirty-day rehospitalization rates were lower during the first year of the pandemic. COVID-positive HH patients had lower odds of 30-day ED visit or rehospitalization. At the NYC site, extended duration between discharge and first HH visit was associated with reduced 30-day ED visit or rehospitalization., Conclusions: HH patient characteristics and utilization were distinct in Baltimore versus NYC in the initial year of the COVID-19 pandemic. Study findings suggest some older adults who needed HH may not have received it, since the decrease in HH services occurred as SNF use decreased nationally. Findings demonstrate the importance of understanding HH agency responsiveness during public health emergencies to ensure older adults' access to care., (© 2024 The American Geriatrics Society.)

Epithelial skin cancers are extremely common, but the mechanisms underlying their malignant progression are still poorly defined. Here, we identify the NRF3 transcription factor as a tumor suppressor in the skin. NRF3 protein expression is strongly downregulated or even absent in invasively growing cancer cells of patients with basal and squamous cell carcinomas (BCC and SCC). NRF3 deficiency promoted malignant conversion of chemically induced skin tumors in immunocompetent mice, clonogenic growth and migration of human SCC cells, their invasiveness in 3D cultures, and xenograft tumor formation. Mechanistically, the tumor-suppressive effect of NRF3 involves HSPA5, a key regulator of the unfolded protein response, which we identified as a potential NRF3 interactor. HSPA5 levels increased in the absence of NRF3, thereby promoting cancer cell survival and migration. Pharmacological inhibition or knock-down of HSPA5 rescued the malignant features of NRF3-deficient SCC cells in vitro and in preclinical mouse models. Together with the strong expression of HSPA5 in NRF3-deficient cancer cells of SCC patients, these results suggest HSPA5 inhibition as a treatment strategy for these malignancies in stratified cancer patients., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: This study explored the key characteristics and needs of midlevel nurse managers (MLNMs) who support and engage clinical nurses (CNs) in scholarly inquiry., Background: Healthcare organizations expect CNs to participate in scholarly inquiry, incorporating evidence-based interventions to improve outcomes and safety. How the MLNM supports and engages CNs in scholarly inquiry remains unclear., Methods: Twelve semistructured interviews of MLNMs occurred at several facilities in the mid-Atlantic region utilizing the institutional review board-acknowledged protocol. Theme interpretation utilized inductive analysis., Results: Four recurrent themes emerged from the interviews related to the value of scholarly inquiry: 1) securing organizational resources to promote scholarly inquiry; 2) knowledge and experience in scholarly inquiry; 3) actions supporting scholarly inquiry; and 4) the value of scholarly inquiry within the organization., Conclusions: Senior nursing leadership and healthcare organizations must recognize the value and provide the infrastructure to support scholarly inquiry. Infrastructure includes education, dedicated time, access to expertise, and resources., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)