RESUMEN
ABSTRACT: NUT carcinoma (NC) is a rare and aggressive neoplasm associated with a poor prognosis. NC is characterized by a NUTM1- rearrangement on chromosome 15q14, commonly fused with the BRD4 or BRD3 gene . A rare subset of NC defined by fusion of NUTM1 with the MGA gene has been identified, showing mesenchymal differentiation on histology. Few cases of spindle cell sarcomas harboring MGA::NUTM1 gene fusions have been reported in the literature. We describe a case of spindle cell sarcoma harboring an MGA::NUTM1 fusion in a 6-year-old male patient. In contrast to typical cases of spindle cell carcinomas or NC, NUTM1 fusion-positive sarcomas are associated with a better prognosis. This report highlights the importance of diagnostic workup of undifferentiated neoplasms, as identification of the MGA::NUTM1 fusion in spindle cell sarcoma could be used in treatment algorithms and lead to better outcomes, to the benefit of patients.
Asunto(s)
Carcinoma , Sarcoma , Masculino , Humanos , Niño , Factores de Transcripción/genética , Proteínas de Neoplasias , Proteínas Nucleares/genética , Cuero Cabelludo/patología , Sarcoma/genética , Sarcoma/patología , Fusión Génica , Proteínas de Fusión Oncogénica/genética , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular/genéticaRESUMEN
BACKGROUND: The purpose of this study was to examine the influence of preoperative marijuana use on postoperative opioid use during the first three postoperative days (POD 1-3) after surgery, and on expectations of pain control, resiliency, and quality-of-life scores. METHODS: All patients presenting to a single institution undergoing elective hand or upper extremity outpatient surgery were asked to complete pre- and postoperative questionnaires. Preoperative questionnaires collected information on demographics, marijuana use, tobacco use, procedure type, self-assessed health, pain control expectations, and EuroQol-5D (EQ-5D) scores. At the first postoperative visit, patients self-reported opioid consumption from POD 1-3. Multivariate linear regression analysis was used to determine which patient characteristics were predictive of greater postoperative opioid consumption during POD 1-3. RESULTS: Self-reported marijuana users were younger, less healthy, and more likely to use tobacco compared to non-users. Marijuana users and non-users were comparable in their use of pain medication (including non-opioids), rates of chronic pain diagnoses, and self-reported pain tolerance. EQ-5D scores were lower in marijuana users than non-users (0.64 vs. 0.72). Marijuana users and non-users were prescribed comparable quantities of opioids during the first 14 days after surgery (176 ± 148 vs 115 ± 87). Multiple linear regression analysis revealed that lower preoperative EQ-5D scores, rather than marijuana use, were associated with increased opioid consumption during POD 1-3. CONCLUSIONS: Preoperative marijuana use was not independently associated with increased opioid use during POD 1-3 after elective hand and upper extremity surgery; instead, an association with lower preoperative EQ-5D scores was identified. LEVEL OF EVIDENCE: II, prospective cohort study.
Asunto(s)
Cannabis , Trastornos Relacionados con Opioides , Humanos , Autoinforme , Estudios Prospectivos , Mano/cirugía , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Trastornos Relacionados con Opioides/epidemiología , Analgésicos Opioides/uso terapéutico , Extremidad SuperiorAsunto(s)
Fármacos Dermatológicos , Esclerodermia Localizada , Ustekinumab , Humanos , Ustekinumab/efectos adversos , Ustekinumab/uso terapéutico , Esclerodermia Localizada/inducido químicamente , Esclerodermia Localizada/patología , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Femenino , Psoriasis/tratamiento farmacológico , Persona de Mediana Edad , MasculinoAsunto(s)
Dermatología , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Humanos , Metotrexato/uso terapéutico , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Mucosa Bucal , Instituciones de Atención Ambulatoria , Membrana MucosaAsunto(s)
Colitis Ulcerosa , Diarrea , Colitis Ulcerosa/complicaciones , Diarrea/etiología , HumanosRESUMEN
HIV-1 infection is associated with a progressive loss of T cell functional capacity and reduced responsiveness to antigenic stimuli. The mechanisms underlying T cell dysfunction in HIV-1/AIDS are not completely understood. Multiple studies have shown that binding of program death ligand 1 (PD-L1) on the surface of monocytes and dendritic cells to PD-1 on T cells negatively regulates T cell function. Here we show that neutrophils in the blood of HIV-1-infected individuals express high levels of PD-L1. PD-L1 is induced by HIV-1 virions, TLR-7/8 ligand, bacterial lipopolysaccharide (LPS), and IFNα. Neutrophil PD-L1 levels correlate with the expression of PD-1 and CD57 on CD4+ and CD8+ T cells, elevated levels of neutrophil degranulation markers in plasma, and increased frequency of low density neutrophils (LDNs) expressing the phenotype of granulocytic myeloid-derived suppressor cells (G-MDSCs). Neutrophils purified from the blood of HIV-1-infected patients suppress T cell function via several mechanisms including PD-L1/PD-1 interaction and production of reactive oxygen species (ROS). Collectively, the accumulated data suggest that chronic HIV-1 infection results in an induction of immunosuppressive activity of neutrophils characterized by high expression of PD-L1 and an inhibitory effect on T cell function.
Asunto(s)
Antígeno B7-H1/inmunología , Infecciones por VIH/inmunología , Tolerancia Inmunológica/inmunología , Neutrófilos/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Antígeno B7-H1/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/metabolismo , VIH-1/inmunología , Humanos , Neutrófilos/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Transducción de SeñalRESUMEN
Psoriasis vulgaris, a helper T cell TH1/TH17-mediated inflammatory dermatosis, may be effectively treated with biologic medications such as secukinumab, an IL-17A inhibitor. However, suppression of the TH1-mediated axis may result in the paradoxical appearance of TH2-mediated inflammatory skin conditions, such as atopic dermatitis (AD). Dupilumab, a biologic medication that inhibits IL-4/IL-13-cytokines involved in TH2-mediated inflammation-has demonstrated efficacy in treating AD but may result in phenotypic switching to psoriasis. We describe a patient with psoriasis that was well controlled on secukinumab who developed severe AD that improved with dupilumab. After several months of effective treatment with dupilumab, he subsequently developed re-emergence of psoriatic lesions. This case highlights how pharmacologic interventions targeted at specific immunologic pathways, such as the TH1/TH2 axis, may have unintended consequences.
Asunto(s)
Productos Biológicos , Dermatitis Atópica , Psoriasis , Productos Biológicos/uso terapéutico , Terapia Biológica , Citocinas/metabolismo , Dermatitis Atópica/complicaciones , Dermatitis Atópica/tratamiento farmacológico , Humanos , Masculino , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológicoRESUMEN
Coronal shear fractures of the distal humerus are rare, complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the radial head in a hyper-extended or semi-flexed elbow or from spontaneous reduction of a posterolateral subluxation or dislocation. Due to the small number of soft tissue attachments at this site, almost all of these fractures are displaced. The incidence of distal humeral coronal shear fractures is higher among women because of the higher rate of osteoporosis in women and the difference in carrying angle between men and women. Distal humeral coronal shear fractures may occur in isolation, may be part of a complex elbow injury, or may be associated with injuries proximal or distal to the elbow. An associated lateral collateral ligament injury is seen in up to 40% and an associated radial head fracture is seen in up to 30% of these fractures. Given the complex nature of distal humeral coronal shear fractures, there is preference for operative management. Operative fixation leads to stable anatomic reduction, restores articular congruity, and allows initiation of early range-of-motion movements in the majority of cases. Several surgical exposure and fixation techniques are available to reconstruct the articular surface following distal humeral coronal shear fractures. The lateral extensile approach and fixation with countersunk headless compression screws placed in an anterior-to-posterior fashion are commonly used. We have found a two-incision approach (direct anterior and lateral) that results in less soft tissue dissection and better outcomes than the lateral extensile approach in our experience. Stiffness, pain, articular incongruity, arthritis, and ulnohumeral instability may result if reduction is non-anatomic or if fixation fails.