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This manuscript seeks to describe diagnostic considerations in individuals with diabetes mellitus presenting to the ED with abdominal pain. It highlights the importance of early investigation with computerised tomography to differentiate aetiologies that compel early surgical intervention from those which may be treated conservatively.
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A man in his 20s was referred by his general practitioner because of the finding of adrenocorticotropic hormone (ACTH)-dependent hypercortisolaemia, discovered as part of investigation of fatigue and alopecia. The man had no other clinical findings suggestive of Cushing syndrome. Further investigation revealed intact diurnal rhythm in cortisol production, normal bone density and excluded assay interference. Further investigation revealed the man's sibling had been labelled as having Cushing syndrome because of similar biochemical abnormalities. A diagnosis of familial primary generalised glucocorticoid resistance syndrome was made. Testing for mutations in the NR3C1 gene is awaited.
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Enfermedades de las Glándulas Suprarrenales , Síndrome de Cushing , Humanos , Hormona Adrenocorticotrópica , Síndrome de Cushing/complicaciones , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/genética , Hidrocortisona , Mutación , Masculino , AdultoRESUMEN
OBJECTIVE: To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients. DESIGN: Retrospective cohort study. SETTING: Eight tertiary-care referral general hospitals in California. METHODS: We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment. RESULTS: For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15-1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, -25%; IQR, -20% to -29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%-105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, -15%; IQR, -14% to -21%) and decreased the SIR at all hospitals (median, -8%; IQR, -4% to -11%). CONCLUSIONS: For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.
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Infecciones por Clostridium/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Servicio de Oncología en Hospital/estadística & datos numéricos , Centros Médicos Académicos , California/epidemiología , Clostridioides difficile , Infecciones por Clostridium/prevención & control , Infección Hospitalaria/prevención & control , Instituciones de Salud , Células Madre Hematopoyéticas , Hospitales Generales , Humanos , Estudios Retrospectivos , Ajuste de Riesgo , Seguridad , Centros de Atención Terciaria , TrasplantesRESUMEN
We undertook a quality improvement project to address challenges with pulmonary artery catheter (PAC) line maintenance in a setting of low-baseline central-line infection rates. We observed a subsequent reduction in Staphylococcal PAC line infections and a trend toward a reduction in overall PAC infection rates over 1 year.
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Bacteriemia/prevención & control , Infecciones Relacionadas con Catéteres/prevención & control , Cateterismo de Swan-Ganz/enfermería , Enfermería/métodos , Paquetes de Atención al Paciente , Infecciones Estafilocócicas/prevención & control , Bacteriemia/microbiología , Vendajes , Infecciones Relacionadas con Catéteres/microbiología , Cateterismo de Swan-Ganz/efectos adversos , Educación Continua en Enfermería , Humanos , Mejoramiento de la CalidadRESUMEN
In patients with ß-lactam allergies, administration of non-ß-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report ß-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured ß-lactam allergy tool, was implemented to improve the utilization of preferred ß-lactam surgical prophylaxis.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Hipersensibilidad a las Drogas/diagnóstico , Tamizaje Masivo/métodos , beta-Lactamas/uso terapéutico , Antibacterianos/efectos adversos , Programas de Optimización del Uso de los Antimicrobianos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mejoramiento de la Calidad , Encuestas y Cuestionarios , beta-Lactamas/efectos adversosRESUMEN
Gain-of-function mutations in the canonical transient receptor potential 6 (TRPC6) gene are a cause of autosomal dominant focal segmental glomerulosclerosis (FSGS). The mechanisms whereby abnormal TRPC6 activity results in proteinuria remain unknown. The ERK1/2 MAPKs are activated in glomeruli and podocytes in several proteinuric disease models. We therefore examined whether FSGS-associated mutations in TRPC6 result in activation of these kinases. In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased ERK1/2 phosphorylation, an effect dependent upon channel function. Pharmacologic inhibitor studies implicated several signaling mediators, including calmodulin and calcineurin, supporting the importance of TRPC6-mediated calcium influx in this process. Through medium transfer experiments, we uncovered two distinct mechanisms for ERK activation by mutant TRPC6, a cell-autonomous, EGF receptor-independent mechanism and a non-cell-autonomous mechanism involving metalloprotease-mediated release of a presumed EGF receptor ligand. The inhibitors KN-92 and H89 were able to block both pathways in mutant TRPC6 expressing cells as well as the prolonged elevation of intracellular calcium levels upon carbachol stimulation seen in these cells. However, these effects appear to be independent of their effects on calcium/calmodulin-dependent protein kinase II and PKA, respectively. Phosphorylation of Thr-70, Ser-282, and Tyr-31/285 were not necessary for ERK activation by mutant TRPC6, although a phosphomimetic TRPC6 S282E mutant was capable of ERK activation. Taken together, these results identify two pathways downstream of mutant TRPC6 leading to ERK activation that may play a role in the development of FSGS.
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Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Mutación , Canales Catiónicos TRPC/fisiología , Animales , Bencilaminas/farmacología , Calcineurina/metabolismo , Calmodulina/metabolismo , Línea Celular , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Inhibidores Enzimáticos/farmacología , Receptores ErbB/metabolismo , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Células HEK293 , Humanos , Immunoblotting , Isoquinolinas/farmacología , Fosforilación/efectos de los fármacos , Podocitos/citología , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sulfonamidas/farmacología , Canales Catiónicos TRPC/genética , Canal Catiónico TRPC6RESUMEN
BACKGROUND: Transient receptor potential canonical (TRPC) channels are non-selective cation channels involved in receptor-mediated calcium signaling in diverse cells and tissues. The canonical transient receptor potential 6 (TRPC6) has been implicated in several pathological processes, including focal segmental glomerulosclerosis (FSGS), cardiac hypertrophy, and pulmonary hypertension. The two large cytoplasmic segments of the cation channel play a critical role in the proper regulation of channel activity, and are involved in several protein-protein interactions. RESULTS: Here we report that SNF8, a component of the endosomal sorting complex for transport-II (ESCRT-II) complex, interacts with TRPC6. The interaction was initially observed in a yeast two-hybrid screen using the amino-terminal cytoplasmic domain of TRPC6 as bait, and confirmed by co-immunoprecipitation from eukaryotic cell extracts. The amino-terminal 107 amino acids are necessary and sufficient for the interaction. Overexpression of SNF8 enhances both wild-type and gain-of-function mutant TRPC6-mediated whole-cell currents in HEK293T cells. Furthermore, activation of NFAT-mediated transcription by gain-of-function mutants is enhanced by overexpression of SNF8, and partially inhibited by RNAi mediated knockdown of SNF8. Although the ESCRT-II complex functions in the endocytosis and lysosomal degradation of transmembrane proteins, SNF8 overexpression does not alter the amount of TRPC6 present on the cell surface. CONCLUSION: SNF8 is novel binding partner of TRPC6, binding to the amino-terminal cytoplasmic domain of the channel. Modulating SNF8 expression levels alters the TRPC6 channel current and can modulate activation of NFAT-mediated transcription downstream of gain-of-function mutant TRPC6. Taken together, these results identify SNF8 as a novel regulator of TRPC6.