Background: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality. Results: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84–0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72–0.97 for Latinx). Female sex and age >75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race. Conclusions: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.

We designed and validated a Visual Index for Ichthyosis Severity for scale and erythema that provides (1) written descriptions of the features characteristic of each level of severity, (2) visual standards for four body sites, and (3) two distinct standards to account for different types of scale. We tested the Visual Index for Ichthyosis Severity for reliability and reproducibility using two different settings: one that utilized scoring of 60 test photographs by 10 dermatologists, and one with in-person evaluations on 85 subjects by 12 dermatologists at the Foundation for Ichthyosis and Related Skin Types conference. The validation process revealed high reliability and reproducibility for both scale and erythema. The interrater and intrarater intraclass correlation coefficients for scale were consistently near or greater than 0.7 in both settings. By contrast, the interrater reliability for erythema was higher during in-person validation compared with validation on test photographs. Our analysis indicates that the Visual Index for Ichthyosis Severity performs better in person than with photographs, an important consideration in the design of clinical trials. Power analysis predicts that a 1-point difference on this 5-step scale would be detectable with 12 subjects in each of two defined groups. This index provides a tool for clinical phenotyping and assessment of therapeutic response for many disorders of keratinization.

The ichthyoses, also known as disorders of keratinization (DOK), encompass a heterogeneous group of skin diseases linked by the common finding of abnormal barrier function, which initiates a default compensatory pathway of hyperproliferation, resulting in the characteristic clinical manifestation of localized and/or generalized scaling. Additional cutaneous findings frequently seen in ichthyoses include generalized xerosis, erythroderma, palmoplantar keratoderma, hypohydrosis, and recurrent infections. In 2009, the Ichthyosis Consensus Conference established a classification consensus for DOK based on pathophysiology, clinical manifestations, and mode of inheritance. This nomenclature system divides DOK into two main groups: nonsyndromic forms, with clinical findings limited to the skin, and syndromic forms, with involvement of additional organ systems. Advances in next-generation sequencing technology have allowed for more rapid and cost-effective genetic analysis, leading to the identification of novel, rare mutations that cause DOK, many of which represent phenotypic expansion. This review focuses on new findings in syndromic and nonsyndromic ichthyoses, with emphasis on novel genetic discoveries that provide insight into disease pathogenesis.

Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI. OBJECTIVE To expand the genotypic spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to use BSI genotypes to draw inferences about the temperature sensitivity of TGM1 mutations. DESIGN, SETTING, AND PARTICIPANTS A total of 16 participants with BSI from 13 kindreds were identified from 6 academic medical centers. A detailed clinical history was obtained from each participant, including phenotypic presentation at birth and disease course. Each participant underwent targeted sequencing of TGM1. MAIN OUTCOMES AND MEASURES Phenotypic and genotypic characteristics in these patients from birth onward. RESULTS Of the 16 participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39 years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8 TGM1 missense mutations that to our knowledge have not been previously reported in BSI: 5 have been previously described in non-temperature-sensitive forms of congenital ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations. Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating that these mutations are temperature sensitive. Seven of 10 probands with a compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315, providing evidence that mutations at these sites are temperature sensitive and highlighting the importance of these residues in the pathogenesis of BSI. CONCLUSIONS AND RELEVANCE Our findings expand the genotypic spectrum of BSI and the understanding of temperature sensitivity of TGM1 mutations. Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1 ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.

Nonbacterial thrombotic endocarditis (NBTE) associated with malignancy is rare; its infrequency and similarity to other diagnoses make it a significant diagnostic challenge. A 63-year-old woman on rivaroxaban for prior deep vein thrombosis presented with left upper extremity weakness and left facial droop with imaging demonstrating multiple strokes. Echocardiograms revealed mitral and aortic valve vegetations. The patient was switched to apixaban and started on vancomycin and ceftriaxone for presumed culture-negative endocarditis. Despite continuing apixaban, her hospital course was complicated by new acute embolic infarcts. Workup confirmed nonmucinous metastatic biliary adenocarcinoma. The patient was placed on a heparin drip then switched to low molecular weight heparin without further embolic events and was discharged to a rehabilitation facility in stable condition with plans for chemotherapy as an outpatient. These clinical, imaging, and histologic findings were consistent with a rare case of NBTE associated with primary non-mucinous gallbladder malignancy complicated by recurrent strokes in which direct oral anticoagulants did not provide adequate anticoagulation.

The objective is to describe a previously unclassified syndrome and to document potential associated mutations. We performed chart review and genetic testing with high-resolution chromosome analysis, subtelomeric probes, comparative genomic hybridization, SNP array, whole exome sequencing, and specific testing for mutations in Lamin A and ZMPSTE24. The patient is an 11-year-old female with craniosynostosis and clinical findings of anodontia, adermatoglyphia, hyponychia, hypopigmented and hyperpigmented atrophic linear patches in a Blaschkonian distribution, acral skin changes and tapered fingers, sparse and wiry scalp hair, sparse lateral eyebrows, dysmorphic facial features including a beaked nose and prominent chin, and hyperlipidemia. Her presentation primarily involves tissues of ectodermal origin, but her constellation of findings do not fit with any of the known features of ectodermal dysplasias or progeroid syndromes. Genetic testing of Lamin A and ZMPSTE24 were normal. Chromosome analysis, subtelomeric probes, comparative genomic hybridization, and SNP array have also been normal. On the other hand, whole exome sequencing identified a heterozygous sequence change in the ZAK gene (c.850_851+1delAGG mutation). This mutation is of unknown clinical significance, but ZAK protein belongs to the MAPKKK family of signal transduction molecules (OMIM: 609479), which has been shown to play a role in regulating chondrogenesis in mice. To our knowledge, this is the only case with this constellation of findings in the setting of ZAK mutation. This analysis may provide insight into the possible function of the ZAK gene and further our understanding of the MAPKKK signal transduction pathway.

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The prevalence of atopic dermatitis (AD) in adults remains to be established. The objective of this cross-sectional study was to define the prevalence and impact on Health-Related Quality of Life (HRQoL) of AD in US adults. Disease severity was categorized as clear/mild, moderate or severe based on the Patient Oriented Eczema Measure (POEM). The impact of AD on HRQoL was assessed using Dermatology Life Quality Index (DLQI) and depression and anxiety using the Hospital Anxiety and Depression scale (HADS). Logistic regression was used to analyze the association between risk factors for AD and HRQoL. 2,137 subjects were invited to participate (response rate¼59.80%). The prevalence of AD was 7.3% (CI: 5.9-8.8%). 60.1% of subjects were classified as clear/mild, 28.9% moderate; and 11.0% severe disease. In adjusted models, only female (OR¼1.65; CI:1.05-2.61), Hispanic/biracial (OR¼3.36;