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BACKGROUND: Physician malpractice lawsuits are climbing, and the reasons underlying litigation against dermatologists are unclear. OBJECTIVE: To determine the reasons patients pursue litigation against dermatologists or dermatology practices. MATERIALS AND METHODS: A retrospective analysis of all state and federal cases between 2011 and 2022 was performed after a query using "Dermatology" and "dermatologist" as search terms on 2 national legal data repositories. RESULTS: The authors identified a total of 48 (37 state and 11 federal) lawsuits in which a practicing dermatologist or dermatology group practice was the defendant. The most common reason for litigation was unexpected harm (26 cases, 54.2%), followed by diagnostic error (e.g. incorrect or delayed diagnoses) (16 cases, 33.3%). Six cases resulted from the dermatologist failing to communicate important information, such as medication side effects or obtaining informed consent. Male dermatologists were sued at a rate 3.1 times higher than female dermatologists. CONCLUSION: Although lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed diagnoses and ensure critical information is shared with patients to safeguard against easily avoidable litigation.
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Dermatólogos , Mala Praxis , Humanos , Estudios Retrospectivos , Estados Unidos , Mala Praxis/legislación & jurisprudencia , Mala Praxis/estadística & datos numéricos , Masculino , Femenino , Dermatólogos/estadística & datos numéricos , Dermatólogos/legislación & jurisprudencia , Dermatología/legislación & jurisprudencia , Dermatología/estadística & datos numéricos , Errores Diagnósticos/legislación & jurisprudencia , Errores Diagnósticos/estadística & datos numéricos , Consentimiento Informado/legislación & jurisprudenciaRESUMEN
Despite the more than 500 interns graduating into dermatology residency each year across the United States, there is little insight on what to expect during this transition. The shift from an intern year largely defined by acute generalized inpatient medicine to an outpatient specialty can be challenging, requiring a new framework for patient care and self-study. This article highlights the main contrasts between the intern year and dermatology residency to better prepare dermatology-bound interns as they enter their chosen specialty.
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Dermatología , Humanos , Medios de Contraste , Etnicidad , Pacientes AmbulatoriosRESUMEN
Residency is both physically and mentally taxing. Although some tout these struggles as a rite of passage to practice medicine, rates of physician burnout and suicide unfortunately remain higher than the general population. Limitations on work hours, mandatory reporting of work hour violations, and resident wellness programs have aimed to improve these statistics, but the time constraints and physical demands of residency offer little room for trainees to focus on their mental health. In 2020, the COVID-19 pandemic tested an already strained health care system, bringing to light the prevalence of depression and anxiety among residents. This article explores this prevalence and highlights several modalities available to residents who are seeking to prioritize their mental health.
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Agotamiento Profesional , COVID-19 , Internado y Residencia , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , COVID-19/epidemiología , Humanos , Salud Mental , Pandemias , Encuestas y CuestionariosRESUMEN
COVID-19 was declared a global pandemic by the World Health Organization on March 11, 2020, and within the following 2 months, most states had issued mandatory stay-at-home orders, leaving many patients without access to outpatient care. Similar to many other outpatient-based specialties, dermatology quickly adopted telemedicine into clinical practice, and this expansion of virtual communication provided (1) increased access for patients living in remote areas, (2) ease of multidisciplinary collaboration, and (3) new opportunities for training and education. This article highlights the caveats of teledermatology, such as the need for excellent visual diagnostic skills and the vulnerability of patient privacy and protected information. Additionally, as teledermatology is poised to further expand in the future, it is critical to reflect on patient safety as well as its clinical efficacy in comparison to in-person evaluation.
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COVID-19 , Dermatología , Enfermedades de la Piel , Telemedicina , Humanos , SARS-CoV-2 , Enfermedades de la Piel/diagnósticoAsunto(s)
Mutación , Sarcoma/genética , Neoplasias Cutáneas/genética , Xantomatosis/genética , Anciano , Anciano de 80 o más Años , Humanos , Pérdida de Heterocigocidad , Masculino , Sarcoma/patología , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/genética , Secuenciación del Exoma , Xantomatosis/patologíaRESUMEN
BACKGROUND: Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis. OBJECTIVE: To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis. METHODS: We enrolled a series of 5 porokeratosis patients,1 with disseminated superficial actinic porokeratosis, 2 with porokeratosis palmaris et plantaris disseminata, and 2 with linear porokeratosis. Patients were genotyped before initiation of therapy. Patients then applied topical cholesterol/lovastatin twice daily to a unilaterally defined treatment area for up to 3 months. The response was evaluated and patients photographed at every visit. RESULTS: Three patients had MVD mutations, and 2 patients had PMVK mutations. Treatment with topical cholesterol/lovastatin (but not cholesterol alone) resulted in near complete clearance of disseminated superficial actinic porokeratosis lesions after 4 weeks of therapy and moderate improvement of porokeratosis palmaris et plantaris disseminata lesions and linear porokeratosis lesions. There were no adverse events. LIMITATIONS: Case series design with a small number of patients. CONCLUSION: Topical cholesterol/lovastatin is an effective and well-tolerated therapy for porokeratosis that underscores the utility of a pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic precursors.
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Anticolesterolemiantes/administración & dosificación , Carboxiliasas/genética , Colesterol/administración & dosificación , Lovastatina/administración & dosificación , Poroqueratosis/tratamiento farmacológico , Poroqueratosis/genética , Administración Cutánea , Adulto , Preescolar , Combinación de Medicamentos , Genotipo , Humanos , Persona de Mediana Edad , Mutación , Pomadas , Fosfotransferasas (Aceptor del Grupo Fosfato)/genética , Adulto JovenRESUMEN
We describe unrelated individuals with ichthyosis, failure to thrive, thrombocytopenia, photophobia, and progressive hearing loss. Each have bi-allelic mutations in AP1B1, the gene encoding the ß subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 ß subunit is lost, and the γ subunit is greatly reduced, demonstrating destabilization of the AP-1 complex. Affected cells and tissue contain an abundance of abnormal vesicles and show hyperproliferation, abnormal epidermal differentiation, and derangement of intercellular junction proteins. Transduction of affected cells with wild-type AP1B1 rescues the vesicular phenotype, conclusively establishing that loss of AP1B1 function causes this disorder.
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Complejo 1 de Proteína Adaptadora/genética , Subunidades beta de Complejo de Proteína Adaptadora/genética , Sordera/genética , Genes Recesivos/genética , Ictiosis/genética , Mutación/genética , Fotofobia/genética , Diferenciación Celular/genética , Proliferación Celular/genética , Femenino , Pérdida Auditiva/genética , Humanos , Masculino , Fenotipo , Subunidades de Proteína/genética , Transporte de Proteínas/genética , Trombocitopenia/genéticaRESUMEN
Tufted angioma (TA) is a rare vascular tumor characterized by histologic tufts of proliferating capillaries that occurs in infancy or early childhood, with a poorly understood pathogenesis. Though benign, TA can be associated with the Kasabach-Merritt phenomenon (KMP), a life-threatening consumptive coagulopathy and thrombocytopenia. Here, we explored the genetic mechanism underlying a case of TA associated with KMP via targeted sequencing of laser capture micro-dissected lesion and blood DNA, and identified a somatic, activating GNA14 mutation specific to the tumor. Our findings support aberrant GNA14 activation underlies the pathogenesis of TA associated with KMP.
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Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Hemangioma/patología , Síndrome de Kasabach-Merritt/diagnóstico , Mutación , Neoplasias Cutáneas/patología , Hemangioma/congénito , Hemangioma/genética , Humanos , Recién Nacido , Síndrome de Kasabach-Merritt/genética , Masculino , Neoplasias Cutáneas/congénito , Neoplasias Cutáneas/genéticaRESUMEN
Importance: Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because linear porokeratosis manifests in the lines of Blaschko representing the dorsoventral migration patterns of keratinocyte precursors, it has been suggested that postzygotic somatic mutation underlies the disease. However, no genetic evidence has supported this hypothesis to date. Objective: To identify genetic mutations associated with linear porokeratosis. Design, Setting, and Participants: Paired whole-exome sequencing of affected skin and blood/saliva samples from 3 participants from 3 academic medical centers with clinical and histologic diagnoses of linear porokeratosis. Interventions or Exposures: Whole-exome sequencing of paired blood/saliva and affected tissue samples isolated from linear porokeratosis lesions. Main Outcomes and Measures: Germline and somatic genomic characteristics of participants with linear porokeratosis. Results: Of the 3 participants, 2 were male. Participant ages ranged from 5 to 20 years old. We found a combination of a novel germline mutation and a novel somatic mutation within affected tissue in all cases. One participant had a germline heterozygous PMVK c.329G>A mutation and a somatic copy-neutral loss of heterozygosity confined to the lesional skin, while a second had a germline heterozygous PMVK c.79G>T mutation and an additional PMVK c.379C>T mutation in the lesional skin. In a third participant, there was a germline splice-site mutation in MVD (c.70 + 5G>A) and a somatic deletion in MVD causing frameshift and premature codon termination within the lesional skin (c.811_815del, p.F271Afs*33 frameshift). Conclusions and Relevance: Our findings suggest that linear porokeratosis is associated with the presence of second-hit postzygotic mutations in the genes that encode enzymes within the mevalonate biosynthesis pathway, and provide further evidence that the mevalonate pathway may be a potential target for therapeutic intervention in porokeratosis.
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Variaciones en el Número de Copia de ADN/genética , Mutación de Línea Germinal/genética , Fosfotransferasas (Aceptor del Grupo Fosfato)/genética , Poroqueratosis/genética , Centros Médicos Académicos , Preescolar , Análisis Mutacional de ADN , Humanos , Masculino , Muestreo , Sensibilidad y Especificidad , Secuenciación del Exoma , Adulto JovenAsunto(s)
Malformaciones Arteriovenosas/tratamiento farmacológico , Malformaciones Arteriovenosas/patología , Proteínas Asociadas a Microtúbulos/genética , Terapia Molecular Dirigida/métodos , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Malformaciones Arteriovenosas/genética , Niño , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Proteínas Asociadas a Microtúbulos/efectos de los fármacos , Índice de Severidad de la Enfermedad , Pared Torácica , Resultado del TratamientoRESUMEN
Investigation of genetic determinants of Mendelian skin disorders has substantially advanced understanding of epidermal biology. Here we show that mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma. Heterozygosity for a C-terminal truncation, which produces a protein that appears to be unstably incorporated into desmosomes, causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds. Homozygosity for an N-terminal truncation ablates expression and causes widespread erythrokeratoderma, with expansion of epidermal differentiation markers. Both exhibit epidermal hyperproliferation, immature desmosomes lacking a dense midline observed via electron microscopy, and impaired intercellular adhesion upon mechanical stress. Localization of other desmosomal components appears normal, which is in contrast to other conditions caused by mutations in genes encoding desmosomal proteins. These discoveries highlight the essential role of PERP in human desmosomes and epidermal homeostasis and further expand the heterogeneous spectrum of inherited keratinization disorders.
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Desmosomas/patología , Epidermis/patología , Queratodermia Palmoplantar/genética , Proteínas de la Membrana/genética , Adulto , Adhesión Celular/genética , Niño , Preescolar , Codón sin Sentido , Análisis Mutacional de ADN , Desmosomas/ultraestructura , Epidermis/ultraestructura , Exones/genética , Femenino , Mutación del Sistema de Lectura , Genes Supresores de Tumor , Heterocigoto , Homocigoto , Humanos , Queratodermia Palmoplantar/patología , Masculino , Proteínas de la Membrana/metabolismo , Microscopía Electrónica , Adulto JovenAsunto(s)
Actinas/genética , Astrocitoma/diagnóstico , Astrocitoma/genética , Cementoma/diagnóstico , Cementoma/genética , Mutación , Preescolar , Estudios de Asociación Genética , Pruebas Genéticas , Humanos , Imagen por Resonancia Magnética , Masculino , Fenotipo , Tomografía Computarizada por Rayos X , Secuenciación del ExomaRESUMEN
Genetic mosaicism arises when a zygote harbors two or more distinct genotypes, typically due to de novo, somatic mutation during embryogenesis. The clinical manifestations largely depend on the differentiation status of the mutated cell; earlier mutations target pluripotent cells and generate more widespread disease affecting multiple organ systems. If gonadal tissue is spared-as in somatic genomic mosaicism-the mutation and its effects are limited to the proband, whereas mosaicism also affecting the gametes, such as germline or gonosomal mosaicism, is transmissible. Mosaicism is easily appreciated in cutaneous disorders, as phenotypically distinct mutant cells often give rise to lesions in patterns determined by the affected cell type. Genetic investigation of cutaneous mosaic disorders has identified pathways central to disease pathogenesis, revealing novel therapeutic targets. In this review, we discuss examples of cutaneous mosaicism, approaches to gene discovery in these disorders, and insights into molecular pathobiology that have potential for clinical translation.
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Regulación del Desarrollo de la Expresión Génica , Mosaicismo , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Enfermedades Cutáneas Genéticas/genética , Ectodermo/metabolismo , Ectodermo/patología , Embrión de Mamíferos , Endodermo/metabolismo , Endodermo/patología , Humanos , Queratina-1/genética , Queratina-1/metabolismo , Queratina-10/genética , Queratina-10/metabolismo , Captura por Microdisección con Láser , Mesodermo/metabolismo , Mesodermo/patología , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Enfermedades Cutáneas Genéticas/metabolismo , Enfermedades Cutáneas Genéticas/patología , Factores de Tiempo , Secuenciación del ExomaRESUMEN
Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual's lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this "natural gene therapy".
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Mosaicismo , Mutación/genética , Enfermedades de la Piel/genética , Epidermis/patología , Humanos , Queratinas/genética , Fenotipo , Enfermedades de la Piel/terapiaRESUMEN
Herein, we demonstrate the synthesis of a bicyclic carbonate monomer of a d-glucal derivative, which originated from the natural product d-glucose, in an efficient three-step procedure and its ring-opening polymerization (ROP), initiated by 4-methylbenzyl alcohol, via organocatalysis. The ROP behavior was studied as a function of time, catalyst type, and catalyst concentration by using size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR) spectroscopy. Using a cocatalyst system of 1,8-diazabicyclo[5.4.0]undec-7-ene and 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexyl-2-thiourea (5 mol %) afforded poly(d-glucal-carbonate) (PGCC) with almost complete monomer conversion (ca. 99%) within 1 min, as analyzed by 1H NMR spectroscopy, and a monomodal SEC trace with dispersity of 1.13. The resulting PGCCs exhibited amorphous characteristics with a relatively high glass transition temperature at ca. 69 °C and onset decomposition temperature at ca. 190 °C, as analyzed by differential scanning calorimetry and thermogravimetric analysis, respectively. This new type of potentially degradable polymer system represents a reactive functional polymer architecture.
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Ichthyosis with confetti is a rare, autosomal dominant disorder caused by frameshift mutations in KRT10 or KRT1 and characterized by the development of white, genetically revertant macules in red, diseased skin. All cases result from mutations affecting the tail domains of keratin-10 or keratin-1, and Suzuki et al. expand the mutation spectrum for ichthyosis with confetti caused by mutations in KRT1, showing that a polyarginine frameshift in the keratin-1 tail can also cause this disorder.
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Ictiosis/genética , Queratina-10/genética , Humanos , Ictiosis Lamelar , Queratina-1/genética , MutaciónRESUMEN
Vascular tumors are among the most common neoplasms in infants and children; 5%-10% of newborns present with or develop lesions within the first 3 months of life. Most are benign infantile hemangiomas that typically regress by 5 years of age; other vascular tumors include congenital tufted angiomas (TAs), kaposiform hemangioendotheliomas (KHEs), and childhood lobular capillary hemangiomas (LCHs). Some of these lesions can become locally invasive and unresponsive to pharmacologic intervention, leading to significant complications. Recent investigation has revealed that activating mutations in HRAS, KRAS, NRAS, GNAQ, and GNA11 can cause certain types of rare childhood vascular tumors, and we have now identified causal recurrent somatic activating mutations in GNA14 by whole-exome and targeted sequencing. We found somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations in one KHE, one TA, and one LCH and a GNA11 c.547C>T (p.Arg183Cys) mutation in two LCH lesions. We examined mutation pathobiology via expression of mutant GNA14 or GNA11 in primary human endothelial cells and melanocytes. GNA14 and GNA11 mutations induced changes in cellular morphology and rendered cells growth-factor independent by upregulating the MAPK pathway. Our findings identify GNA14 mutations as a cause of childhood vascular tumors, offer insight into mechanisms of oncogenic transformation by mutations affecting Gaq family members, and identify potential targets for therapeutic intervention.
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Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación/genética , Neoplasias Vasculares/congénito , Neoplasias Vasculares/genética , Células Cultivadas , Preescolar , Activación Enzimática , Subunidades alfa de la Proteína de Unión al GTP/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Lactante , Recién Nacido , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Melanocitos/metabolismo , Melanocitos/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Vasculares/enzimología , Neoplasias Vasculares/patologíaRESUMEN
BACKGROUND: We recently demonstrated multilineage somatic mosaicism in cutaneous skeletal hypophosphatemia syndrome (CSHS), which features epidermal or melanocytic nevi, elevated fibroblast growth factor (FGF)-23, and hypophosphatemia, finding identical RAS mutations in affected skin and bone. OBJECTIVE: We sought to: (1) provide an updated overview of CSHS; (2) review its pathobiology; (3) present a new patient with CSHS; and (4) discuss treatment modalities. METHODS: We searched PubMed for "nevus AND rickets," and "nevus AND hypophosphatemia," identifying cases of nevi with hypophosphatemic rickets or elevated serum FGF-23. For our additional patient with CSHS, we performed histopathologic and radiographic surveys of skin and skeletal lesions, respectively. Sequencing was performed for HRAS, KRAS, and NRAS to determine causative mutations. RESULTS: Our new case harbored somatic activating HRAS p.G13 R mutation in affected tissue, consistent with previous findings. Although the mechanism of FGF-23 dysregulation is unknown in CSHS, interaction between FGF and MAPK pathways may provide insight into pathobiology. Anti-FGF-23 antibody KRN-23 may be useful in managing CSHS. LIMITATIONS: Multilineage RAS mutation in CSHS was recently identified; further studies on mechanism are unavailable. CONCLUSION: Patients with nevi in association with skeletal disease should be evaluated for serum phosphate and FGF-23. Further studies investigating the role of RAS in FGF-23 regulation are needed.