RESUMEN
STUDY OBJECTIVE: The primary objective was to quantify postoperative opioid use after laparoscopic surgery for endometriosis or pelvic pain. The secondary objective was to identify patient characteristics associated with greater postoperative opioid requirements. DESIGN: Prospective, survey-based study in which subjects completed 1 preoperative and 7 postoperative surveys within 28 days of surgery regarding medication usage and pain control. SETTING: Tertiary care, academic center. PATIENTS: A total of 100 women with endometriosis or pelvic pain. INTERVENTIONS: Laparoscopic same-day discharge surgery by fellowship-trained minimally invasive gynecologists. MEASUREMENTS AND MAIN RESULTS: A total of 100 patients were recruited and 8 excluded, for a final sample size of 92 patients. All patients completed the preoperative survey. Postoperative response rates ranged from 70.7% to 80%. The mean number of pills (5 mg oxycodone tablets) taken by day 28 was 6.8. The average number of pills prescribed was 10.2, with a minimum of 4 (n = 1) and maximum of 20 (n = 3). Previous laparoscopy for pelvic pain was associated with a significant increase in postoperative narcotic use (8.2 vs 5.6; p = .044). Hysterectomy was the only surgical procedure associated with a significant increase in postoperative narcotic use (9.7 vs 5.4; p = .013). There were no difference in number of pills taken by presence of deep endometriosis or pathology-confirmed endometriosis (all p >.36). There was a trend of greater opioid use in patients with diagnoses of self-reported chronic pelvic pain, anxiety, and depression (7.9 vs 5.7, p = .051; 7.7 vs 5.2, p = .155; 8.1 vs 5.6, p = .118). CONCLUSION: Most patients undergoing laparoscopic surgery for endometriosis and pelvic pain had a lower postoperative opioid requirement than prescribed, suggesting surgeons can prescribe fewer postoperative narcotics in this population. Patients with a previous surgery for pelvic pain, self-reported chronic pelvic pain syndrome, anxiety, and depression may represent a subset of patients with increased postoperative opioid requirements.
Asunto(s)
Endometriosis , Laparoscopía , Trastornos Relacionados con Opioides , Humanos , Femenino , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Prospectivos , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Dolor Pélvico/cirugía , Endometriosis/complicaciones , Endometriosis/cirugía , Endometriosis/tratamiento farmacológico , Laparoscopía/métodosRESUMEN
BACKGROUND: Ischemia and reperfusion (I/R) induces cytokines, and up-regulates inducible nitric oxide synthase (iNOS), interferon regulatory factor-1(IRF1) and p53 up-regulated modulator of apoptosis (PUMA), which contribute to cell death and tissue injury. However, the mechanisms that I/R induces IRF1-PUMA through iNOS/NO is still unknown. METHODS: Ischemia was induced by occluding structures in the portal triad (hepatic artery, portal vein, and bile duct) to the left and median liver lobes for 60 min, and reperfusion was initiated by removal of the clamp. Induction of iNOS, IRF1 and PUMA in response to I/R were analyzed. I/R induced IRF1 and PUMA expression were compared between iNOS wild-type and iNOS knockout (KO) mice. Human iNOS gene transfected-cells were used to determine iNOS/NO signals targeting IRF1. To test whether HDAC2 was involved in the mediation of iNOS/NO-induced IRF1 transcriptional activities and its target gene (PUMA and p21) expression, NO donors were used in vitro and in vivo. RESULTS: IRF1 nuclear translocation and PUMA transcription elevation were markedly induced following I/R in the liver of iNOS wild-type mice compared with that in knock-out mice. Furthermore, I/R induced hepatic HDAC2 expression and activation, and decreased H3AcK9 expression in iNOS wild-type mice, but not in the knock-out mice. Mechanistically, over-expression of human iNOS gene increased IRF1 transcriptional activity and PUMA expression, while iNOS inhibitor L-NIL reversed these effects. Cytokine-induced PUMA through IRF1 was p53 dependent. IRF1 and p53 synergistically up-regulated PUMA expression. iNOS/NO-induced HDAC2 mediated histone H3 deacetylation and promoted IRF1 transcriptional activity. Moreover, treating the cells with romidepsin, an HDAC1/2 inhibitor decreased NO-induced IRF1 and PUMA expression. CONCLUSIONS: This study demonstrates a novel mechanism that iNOS/NO is required for IRF1/PUMA signaling through a positive-feedback loop between iNOS and IRF1, in which HDAC2-mediated histone modification is involved to up-regulate IRF1 in response to I/R in mice.
Asunto(s)
Factor 1 Regulador del Interferón/genética , Hepatopatías/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/metabolismo , Daño por Reperfusión/metabolismo , Activación Transcripcional , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Técnica del Anticuerpo Fluorescente , Humanos , Factor 1 Regulador del Interferón/metabolismo , Hígado/metabolismo , Hígado/patología , Hepatopatías/etiología , Hepatopatías/patología , Ratones , Ratones Noqueados , Modelos Biológicos , Unión Proteica , Transporte de Proteínas , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
OBJECTIVES: To determine ocular outcomes and factors associated with adherence to ophthalmic follow-up in a medically underserved population at a single health centre in Philadelphia. DESIGN: Retrospective chart review. PARTICIPANTS: Patients from a community glaucoma screening program. METHODS: Chart review was conducted for participants who received a complete eye examination at the Philadelphia District Health Center 5 between January 1, 2012 and May 31, 2014 within the Philadelphia Glaucoma Detection and Treatment Project. Multivariate logistic regression was used to determine factors related to ophthalmic follow-up adherence. RESULTS: A total of 249 participants completed an eye examination (mean ageâ¯=â¯57.7 ± 6.9 years). Most were African American (nâ¯=â¯220; 88.4%); female (nâ¯=â¯129; 51.8%). Forty-seven participants (18.9%) received glaucoma-related diagnoses, 20 (8.0%) were prescribed ocular medication, and 26 (10.4%) underwent laser therapy. Ninety (36.1%) attended their recommended follow-up eye examination at the health centre. Glaucoma-related diagnosis (p ≤ 0.001), recommendation of a 4- to 6-week follow-up period (p < 0.001), prescribed eye drops (p < 0.001), or received laser therapy (pâ¯=â¯0.047) were factors most predictive of ophthalmic follow-up adherence. CONCLUSIONS: The collaborative effort of eye care providers and health centres offers an important opportunity to detect, treat, and manage glaucoma and other ocular pathology in medically underserved communities. Having a glaucoma-related diagnosis, initiating treatment, and scheduling regular follow-up visits are the most important factors influencing adherence to follow-up eye appointments.
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Servicios de Salud Comunitaria , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/terapia , Cooperación del Paciente/estadística & datos numéricos , Adulto , Cuidados Posteriores , Anciano , Antihipertensivos/uso terapéutico , Servicios de Salud Comunitaria/métodos , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/fisiología , Coagulación con Láser , Masculino , Área sin Atención Médica , Persona de Mediana Edad , Philadelphia , Estudios Retrospectivos , Tonometría Ocular , Trabeculectomía , Agudeza VisualRESUMEN
Interferon regulatory factor 1 (IRF1) has been found to serve as a tumor suppressor in cholangiocarcinoma, and enabled prediction of clinical progression and prognosis in our previous study. The objective of the current study is to screen and identify valuable microRNAs (miR), which target IRF1 to regulate cholangiocarcinoma cell proliferation, migration, and invasion. High expression of miR-383 was observed in cholangiocarcinoma tissues and cells. Meanwhile, we found the predicted binding site of miR-383 on the IRF1 3'-untranslated region (3'-UTR) according to the miR target database. The miR-383 expression was negatively related to IRF1 messeneger RNA (mRNA) and protein expression in cholangiocarcinoma tissue samples, and miR-383 negatively regulated IRF1 mRNA and protein expression in cholangiocarcinoma cells. Subsequently, we conducted a luciferase reporter assay to prove the predicted binding site miR-383 on IRF1 3'-UTR. Moreover, the results of the rescue study suggested that IRF1 was a functional target of miR-383 involved in regulating cholangiocarcinoma cell proliferation, migration, and invasion. Finally, we evaluated the clinical and prognostic significance of miR-383 in cholangiocarcinoma cases, and found that high expression of miR-383 was correlated with advanced tumor stage, large tumor size, present vascular invasion, and metastasis, and acted as an unfavorable independent prognostic factor. In conclusion, miR-383 serves as a tumor-suppressive miR to regulate cholangiocarcinoma cell proliferation, migration, and invasion via directly targeting IRF1.