RESUMO
AIM: We investigated the efficacy and safety of durvalumab (D) with or without tremelimumab (T) in addition to single-agent chemotherapy (CT) in patients with platinum-resistant recurrent ovarian cancer (PROC) lacking homologous recombination repair (HRR) gene mutations. PATIENTS AND METHODS: KGOG 3045 was an open-label, investigator-initiated phase II umbrella trial. Patients with PROC without HRR gene mutations who had received ≥2 prior lines of therapy were enrolled. Patients with high PD-L1 expression (TPS ≥25%) were assigned to arm A (D + CT), whereas those with low PD-L1 expression were assigned to arm B (D + T75 + CT). After completing arm B recruitment, patients were sequentially assigned to arms C (D + T300 + CT) and D (D + CT). RESULTS: Overall, 58 patients were enrolled (5, 18, 17, and 18 patients in arms A, B, C, and D, respectively). The objective response rates were 20.0, 33.3, 29.4, and 22.2%, respectively. Grade 3-4 treatment-related adverse events were observed in 20.0, 66.7, 47.1, and 66.7 of patients, respectively, but were effectively managed. Multivariable analysis demonstrated that adding T to D + CT improved progression-free survival (adjusted HR, 0.435; 95% CI, 0.229-0.824; P = 0.011). Favorable response to chemoimmunotherapy was associated with MUC16 mutation (P = 0.0214), high EPCAM expression (P = 0.020), high matrix remodeling gene signature score (P = 0.017), and low FOXP3 expression (P = 0.047). Patients showing favorable responses to D + T + CT exhibited significantly higher EPCAM expression levels (P = 0.008) and matrix remodeling gene signature scores (P = 0.031) than those receiving D + CT. CONCLUSIONS: Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation.
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Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Antígeno B7-H1 , Neoplasias Ovarianas , Humanos , Feminino , Molécula de Adesão da Célula Epitelial , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Choosing an optimal concomitant drug for combination with poly-ADP ribose polymerase (PARP) inhibitor based on patient-specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor-based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub-study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib-based combinations and biomarkers of patients with platinum-resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had BRCA mutations, which were similarly distributed between arms. Grade 3 or 4 treatment-related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD-L1 expression [CPS ≥10], CD8, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era.
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Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Antineoplásicos/uso terapêutico , Biomarcadores , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/induzido quimicamente , Ftalazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Reparo de DNA por Recombinação , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are becoming the standard of care for epithelial ovarian cancer (EOC). Recently, clinical trials of triple maintenance therapy (PARPi+anti-angiogenic agent+anti-PD-1/L1) are actively ongoing. Here, we investigated the immunological effects of PARPi or triple maintenance therapy on T cells and their impact on clinical responses. METHODS: We collected serial blood from EOC patients receiving PARPi therapy (cohort 1: PARPi, n = 49; cohort 2: olaparib+bevacizumab+pembrolizumab, n = 31). Peripheral T cells were analyzed using flow cytometry and compared according to the PARPi response. Progression-free survival (PFS) was assessed according to prognostic biomarkers identified in a comparative analysis. RESULTS: Regulatory T cells (Tregs) were suppressed by PARPi therapy, whereas PD-1 was not significantly changed. Short PFS group exhibited a higher percentage of baseline PD-1+Tregs than long PFS group, and the patients with high percentage of PD-1+Tregs before treatment showed poor PFS in cohort 1. However, the expression of PD-1 on Tregs significantly decreased after receiving triple maintenance therapy, and the reduction in PD-1+Tregs was associated with superior PFS in cohort 2 (P = 0.0078). CONCLUSION: PARPi suppresses Tregs, but does not affect PD-1 expression. Adding anti-PD-1 to PARPi decreases PD-1+Tregs, which have negative prognostic value for PARPi monotherapy.
Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Receptor de Morte Celular Programada 1/uso terapêutico , Linfócitos T Reguladores , Antineoplásicos/uso terapêutico , Poli(ADP-Ribose) PolimerasesRESUMO
OBJECTIVE: We investigated the utility of Positron emission tomography-Computed tomography (PET-CT) in the setting of two different sentinel lymph node (SLN) mapping techniques; the conventional cervical injection method (one-step) and the two-step method, which involves fundal injection followed by cervical injection. METHODS: Patients with endometrial cancer undergoing FDG PET-CT followed by laparoscopic or robotic surgical staging with SLN mapping at the Yonsei Cancer Center between July 2014 and April 2021 were stratified into the PET-positive group (with suspected or likely lymph nodes metastasis) and PET-negative group. A chart review was performed for the number of harvested SLNs, patterns of SLN metastases, and recurrence. RESULTS: Among 466 patients undergoing one-step (n = 276) and two-step (n = 190) SLN mapping, LN metastasis was identified in 21 of 434 PET-negative and 18 of 32 PET-positive patients. The sensitivity and specificity of PET-CT for diagnosing lymph node metastasis were 46.2% and 96.7%, respectively. Among PET-positive patients with LN metastasis, anatomical distribution was concordant in 14/18 patients (77.8%). Among PET-negative patients, four (2.3%) had metastatic para-aortic SLNs, including three (1.7%) with isolated para-aortic metastases; metastatic para-aortic SLNs were exclusively found in the two-step group. Among PET-positive patients, para-aortic SLN metastasis was identified in 35.7% of two-step and 16.7% of one-step group. Among the 21 PET false-negative patients, recurrence was seen in four patients (19%) after a median follow-up of 34 months (range: 7-70 months). CONCLUSIONS: PET-CT served as a useful guide to clinicians with high anatomical concordance rate in patients with LN metastasis. However, despite high specificity, sensitivity was limited. SLN metastasis pattern, especially at the para-aortic level, indicates that the two-step SLN technique might be useful in PET-negative and PET-positive patients.
Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodosRESUMO
OBJECTIVE: This study aimed to determine the incidence of thrombotic events in ovarian cancer patients following a de-escalated prophylactic strategy and to stratify risk groups. METHODS: We reviewed the records of patients who underwent debulking surgery for ovarian cancer at a single institution between January 2007 and May 2019. We identified clinically diagnosed and radiologically confirmed cases of thrombotic events-classified as pulmonary thromboembolism (PE), deep vein thrombosis (DVT), and other thrombotic events-within 6 months of debulking surgery. RESULTS: After excluding 13 patients diagnosed with thromboembolism at the baseline or during neoadjuvant chemotherapy, 799 were analyzed. Since the introduction of medical prophylaxis at our institution in 2009, 482 patients (60%) received medical prophylaxis with subcutaneous injection of low molecular weight heparin for 5 days with mechanical prophylaxis, whereas 317 (40%) received mechanical prophylaxis only. After debulking surgery, thrombotic events occurred in 28 patients (3.5%) including PE (n = 11), DVT (n = 10), and other thrombotic events (n = 7). Multivariable analysis identified age, body mass index (BMI), and operative duration as independent risk factors associated with thrombotic events. A thrombotic event was an independent prognostic factor for overall survival (HR 2.17, 95% CI 1.16-4.1). A cut-off analysis for pre-operative identifiable risk factors showed age < 57 years and BMI < 21 could help define low-risk groups. One patient from 172 low-risk patients (0.58%) experienced a thrombotic event. CONCLUSIONS: The thrombotic event incidence was low in our cohort. A de-escalated prophylaxis strategy may be considered in young (age < 57 years) and lean (BMI < 21) patients.
Assuntos
Neoplasias Ovarianas , Embolia Pulmonar , Trombose Venosa , Anticoagulantes/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controleRESUMO
BACKGROUND: Research assessing the effects of marijuana use on preterm birth has found mixed results, in part, due to lack of attention to the role of maternal tobacco smoking during pregnancy. OBJECTIVES: The study objective was to investigate whether maternal marijuana use was independently associated with gestational age, preterm birth, and two preterm birth subtypes (spontaneous vs clinician-initiated). METHODS: Participants included 8261 mother-newborn pairs from the Boston Birth Cohort. Information on gestational age was collected from electronic medical records. Marijuana use and tobacco smoking during pregnancy were assessed through a standard questionnaire after birth. Linear and log-linear regression models were used to assess associations between marijuana use with and without tobacco smoking during pregnancy and the outcomes of interest. RESULTS: Of the 8261 mothers, 27.5% had preterm births. About 3.5% of mothers with term deliveries and 5.2% of mothers with preterm births used marijuana during pregnancy. Marijuana use and cigarette smoking were independently associated with a decrease in gestational age by 0.50 weeks (95% confidence interval [CI] -0.87, -0.13) and 0.52 weeks (95% CI -0.76, -0.28), respectively. Marijuana use during early or late pregnancy was associated with a similar decrease in gestational age by 0.50 weeks. When we examined the effects on the preterm birth subtypes, simultaneous marijuana use and tobacco smoking were associated with higher risk of spontaneous preterm birth (RR 1.64, 95% CI 1.23, 2.18). The elevated risk was not observed with clinician-initiated preterm birth. CONCLUSIONS: In this high-risk US population, maternal marijuana use and cigarette smoking during pregnancy were independently associated with shorter gestational age. When we examined the effects on preterm birth subtypes, the elevated risk was only observed with spontaneous preterm birth.
Assuntos
Fumar Cigarros , Uso da Maconha , Nascimento Prematuro , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Uso da Maconha/epidemiologia , Mães , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologiaRESUMO
INTRODUCTION: Fluorescence image-guided sentinel lymph node (SLN) biopsy using a two-step mapping technique incorporates sequential injection of indocyanine green into the bilateral uterine cornus, followed by cervical injection. Outcomes were compared with the conventional cervical (one-step) method . METHODS: Patients with FIGO stage I-III endometrial cancer who underwent laparoscopic or robotic staging, including SLN biopsy, from May 2014 to December 2018, were retrospectively reviewed. Patient characteristics, pre-operative imaging, SLN detection pattern, pathologic result, adjuvant, and recurrence locations were analyzed. RESULTS: A total of 199 patients received one-step (n=123) and two-step (n=76) SLN biopsy. Para-aortic SLN were more frequently identified in the two-step group. Lower and upper para-aortic SLN were identified in 67.1% and 38.2%, respectively, in the two-step group and in 18.7% and 5.7% in the one-step group (p<0.001). The number of para-aortic SLN harvested was superior in the two-step group (p<0.001). Metastatic para-aortic SLN were found in 7.9% of the two-step group and 2.4% of the one-step group (p=0.070). In detecting nodal metastasis, the sensitivities of the one- and two-step methods were 91.7% and 100.0%, negative predictive values were 99.0% and 100.0%, false-negative rates were 8.3% and 0%, and accuracy rates were 99.1% and 100.0%, respectively. The one-step method identified only three out of eight para-aortic lymph node metastases and missed five para-aortic lymph node metastases. There was no missed para-aortic lymph node metastasis in the two-step group. Recurrence was observed in two patients (2.6%; vaginal vault and adrenal gland) in the two-step group and seven patients (5.7%) including three nodal recurrences in the one-step group (p=0.307). DISCUSSION: Two-step SLN mapping improved the para-aortic SLN detection rate, a known pitfall of conventional cervical injection. Proper evaluation of aortic nodal status will assist in the tailoring of adjuvant and prevent undertreatment of patients with isolated para-aortic metastasis.
Assuntos
Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Verde de Indocianina , Laparoscopia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Imagem Óptica/métodos , Assistência Perioperatória/métodos , Radioterapia Adjuvante , Procedimentos Cirúrgicos Robóticos , Linfonodo Sentinela/cirurgiaRESUMO
OBJECTIVES: Protests, riots and revolutions have long been a part of human history and are increasing globally, yet their impact on mental health remains largely unknown. We therefore systematically reviewed studies on collective actions and mental health. METHOD: We searched PubMed, Web of Science, PsycINFO and CINAHL Plus for published studies from their inception until 1 January 2018. Study quality was rated using the Newcastle-Ottawa Scale. RESULTS: We identified 52 studies (n = 57,487 participants) from 20 countries/regions. The prevalence of post-traumatic stress disorder ranged from 4% to 41% in riot-affected areas. Following a major protest, the prevalence of probable major depression increased by 7%, regardless of personal involvement in the protests, suggestive of community spillover effects. Risk factors for poorer mental health included female sex, lower socioeconomic status, exposure to violence, interpersonal conflicts, frequent social media use and lower resilience and social support. Nevertheless, two studies suggested that collective actions may reduce depression and suicide, possibly due to a collective cathartic experience and greater social cohesion within subpopulations. CONCLUSION: We present the first systematic review of collective actions and mental health, showing compelling evidence that protests even when nonviolent can be associated with adverse mental health outcomes. Health care professionals therefore need to be vigilant to the mental and psychological sequelae of protests, riots and revolutions. Further research on this emerging sociopolitical determinant of mental health is warranted.
Assuntos
Transtorno Depressivo Maior/epidemiologia , Exposição à Violência/psicologia , Tumultos/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Humanos , Saúde Mental , Fatores de Risco , Fatores Sexuais , Classe SocialRESUMO
BACKGROUND: A fixed-dose combination of ledipasvir/sofosbuvir (LDV/SOF) is efficacious in treating chronic hepatitis C virus (HCV) infection; however, objective adherence to prescribed regimens in real-world clinical settings has not been well studied. OBJECTIVE: This study aimed to evaluate adherence and virologic outcomes in patients with chronic HCV infection treated with LDV/SOF using a novel digital medicine program that directly measures drug ingestion adherence. METHODS: This prospective, observational, open-label, single-arm pilot study was conducted at 2 clinical research sites and followed patients with HCV infection who were prescribed LDV/SOF along with an ingestible sensor. Patients were treated for 8 or 12 weeks. The main outcomes were ingestion adherence, medical interventions, virologic response, safety, and patient satisfaction. RESULTS: Of the 28 patients (mean 59 years, SD 7), 61% (17/28) were male, 61% (17/28) were non-Caucasian, and 93% (26/28) were treatment naïve. All 28 had genotype 1 HCV, and of these, 27 completed an 8- or 12-week treatment. Patients used the digital medicine program for 92% of the expected days; the overall mean ingestion adherence rate was 97%. Providers used the digital medicine program data for same-day medication therapy management in 39% (11/28) of patients. End-of-treatment response was achieved in all the available 21 of 28 patients. Sustained virologic response at 12 weeks or more was achieved in 26 of 28 patients; of the 2 patients who relapsed, one had less than 90% adherence and the other had greater than or equal to 95% adherence, lending insights into reasons for treatment failure. A total of 4 subjects reported nonserious adverse events, which were resolved. CONCLUSIONS: Conclusions: The findings of this study suggest that digital medicines can be used for wirelessly observed therapy to support adherence to antiviral HCV therapy, reduce unnecessary medication wastage and retreatment costs, and potentially optimize sustained virologic response rates, especially in populations at high risk for nonadherence.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Sofosbuvir/farmacologia , Resultado do TratamentoRESUMO
AIM: Predictive accuracy of cervical funneling for successful vaginal delivery prior to labor induction was compared to that of conventional methods such as Bishop score and cervical length. METHODS: Prospective observational study was conducted on nulliparous women at 38 gestational weeks or more with intact membranes who delivered vaginally following labor induction. Transvaginal ultrasound was performed prior to labor induction to evaluate the cervix, to determine the cervical length and to check for the presence of funneling. Following pelvic examinations, the Bishop score was calculated. Predictive accuracy of the three different methods, namely cervical funneling, cervical length and Bishop, were compared. RESULTS: A total of 235 nulliparous women with intact membranes were recruited. Of these, 194 women (82.6%) had successful vaginal deliveries following induction. Cervical funneling was observed in 105 women (44.7%). The rate of successful vaginal delivery was significantly higher in women with cervical funneling than in those without funneling (90.5% vs 76.2%, P < 0.004). Multivariable analysis showed that cervical funneling, similar to traditional measures such as the Bishop score and cervical length, was an independent predictor of successful vaginal delivery following labor induction (odds ratio = 2.95; 95% confidence interval: 1.38-6.47; P = 0.007). CONCLUSIONS: Similar to the conventional methods of cervical evaluation, such as the Bishop score and cervical length, cervical funneling may serve as a useful and valid predictor of successful vaginal deliveries prior to labor induction.
Assuntos
Colo do Útero , Trabalho de Parto Induzido , Colo do Útero/diagnóstico por imagem , Parto Obstétrico , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , UltrassonografiaAssuntos
Neoplasias Ovarianas , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/efeitos adversosRESUMO
PURPOSE OF REVIEW: The consumption of foods and beverages containing non-nutritive sweeteners (NNS) has increased worldwide over the last three decades. Consumers' choice of NNS rather than sugar or other nutritive sweeteners may be attributable to their potential to reduce weight gain. RECENT FINDINGS: It is not clear what the effects of NNS consumption are on glycaemic control and the incidence of type 2 diabetes. This review aims to examine this question in epidemiological, human intervention and animal studies. It is not clear that NNS consumption has an effect on the incidence of type 2 diabetes or on glycaemic control even though there is some evidence for the modification of the microbiome and for interaction with sweet taste receptors in the oral cavity and the intestines' modification of secretion of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), ghrelin and glucose-dependent insulinotropic polypeptide (GIP), which may affect glycaemia following consumption of NNS. In conclusion, long-term studies of NNS consumption are required to draw a firm conclusion about the role of NNS consumption on glycaemic control.
Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Adoçantes não Calóricos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , HumanosRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the fastest-growing chronic liver disease. However, little is known about NAFLD inpatient resource utilization and clinical outcomes. AIMS: The aim of this study was to quantify inpatient NAFLD encounters using patient-level data over time. METHODS: This was a retrospective analysis of de-identified data for NAFLD patients from the California Patient Discharge Database from 2006 to 2013. NAFLD patients were identified by ICD9 codes 571.40, 571.41, 571.49, 571.8, and 571.9. RESULTS: NAFLD patients (n = 91,558) were predominantly female (60%), 45-65 years old (44%), and white (53%). Inpatient encounters increased from 8153 in 2006 to 16,457 in 2013 and were associated with a 207% increase in charges ($686 million in 2006 to $1.42 billion in 2013) and average increase in charges of 9.8% per year adjusting for inflation. Comorbidities (obesity, diabetes, hyperlipidemia, cardiovascular disease, other cancer, and renal disease) increased significantly over time (all P < 0.05). From 2006 to 2011, there were 11,463 deaths (1849 for liver-related hospitalizations) (mean follow-up 4.00 ± 2.13 years). The most significant predictors of death were age > 75 (aHR 3.9, P < 0.0001), male gender (aHR 1.10, P < 0.0001), white race (aHR 1.2, P < 0.0001), decompensated cirrhosis (aHR 2.1, P < 0.0001), and cancer other than HCC (aHR 3.2, P < 0.0001). Within the liver-related hospitalization cohort, mortality predictors were similar, except for Hispanic race (aHR 0.92, P < 0.0096) and renal disease (aHR 1.50, P < 0.0001). CONCLUSIONS: The number of NAFLD inpatient encounters increased significantly from 2006 to 2013, as did the inflation-adjusted inpatient charges. The most significant predictors of death were non-liver cancers (HR 3.11, P < 0.0001, CI 3.06-3.16) and age > 75 years (HR 3.94, P < 0.0001, HR 3.86-4.03).
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Efeitos Psicossociais da Doença , Gastos em Saúde , Preços Hospitalares , Custos Hospitalares , Pacientes Internados , Hepatopatia Gordurosa não Alcoólica/economia , Hepatopatia Gordurosa não Alcoólica/terapia , Admissão do Paciente/economia , Adolescente , Adulto , Fatores Etários , Idoso , California/epidemiologia , Comorbidade , Bases de Dados Factuais , Feminino , Gastos em Saúde/tendências , Preços Hospitalares/tendências , Custos Hospitalares/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/mortalidade , Admissão do Paciente/tendências , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
In pregnancy, uterine natural killer cells (uNK) play essential roles in coordinating uterine angiogenesis, blood vessel remodeling and promoting maternal tolerance to fetal tissue. Deviances from a normal uterine microenvironment are thought to modify uNK function(s) by limiting their ability to establish a healthy pregnancy. While maternal obesity has become a major health concern due to associations with adverse effects on fetal and maternal health, our understanding into how obesity contributes to poor pregnancy disorders is unknown. Given the importance of uNK in pregnancy, this study examines the impact of obesity on uNK function in women in early pregnancy. We identify that uNK from obese women show a greater propensity for cellular activation, but this difference does not translate into increased effector killing potential. Instead, uNK from obese women express an altered repertoire of natural killer receptors, including an imbalance in inhibitory KIR2DL1 and activating KIR2DS1 receptors that favors HLA-C2-directed uNK activation. Notably, we show that obesity-related KIR2DS1 skewing potentiates TNFα production upon receptor crosslinking. Together, these findings suggest that maternal obesity modifies uNK activity by altering the response toward HLA-C2 antigen and KIR2DL1/2DS1-controlled TNFα release. Furthermore, this work identifies alterations in uNK function resulting from maternal obesity that may impact early developmental processes important in pregnancy health.
Assuntos
Células Matadoras Naturais/imunologia , Obesidade/imunologia , Receptores KIR2DL1/metabolismo , Receptores KIR/metabolismo , Útero/imunologia , Adulto , Estudos de Coortes , Citotoxicidade Imunológica , Decídua/citologia , Feminino , Antígenos HLA-C/metabolismo , Humanos , Ativação Linfocitária , Exposição Materna/efeitos adversos , Gravidez , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
The soy isoflavone daidzein is bioconverted to 7,8,4'-trihydroxyisoflavone (7,8,4'-THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)-1 inhibitory properties of 7,8,4'-THIF that arise through the suppression of UVB-induced MMP-1 expression. 7,8,4'-THIF reduced UVB-induced MMP-1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB-induced transcriptional activity of AP-1, a major activator of MMP-1 expression. Additionally, it was observed that the mitogen-activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression, was suppressed by 7,8,4'-THIF. Protein kinase C iota (PKCι) was suspected to be a direct target of 7,8,4'-THIF. The direct interaction between 7,8,4'-THIF and PKCι was confirmed using pull-down assays and immobilized metal ion affinity-based fluorescence polarization assays. Finally, we observed that 7,8,4'-THIF inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4'-THIF, a bioconversion product of daidzein, suppresses UVB-induced MMP-1 expression.
Assuntos
Isoenzimas/antagonistas & inibidores , Isoflavonas/farmacologia , Metaloproteinase 1 da Matriz/metabolismo , Proteína Quinase C/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos , Humanos , Envelhecimento da Pele/efeitos dos fármacos , Raios UltravioletaRESUMO
We developed an innovative home-based HIV self-testing (HIVST) service that included mailing of a free HIVST kit, and providing online real-time instructions and pre-test/post-test counseling (HIVST-OIC). The present parallel-group and non-blinded randomized controlled trial was conducted to evaluate the efficacy of promoting HIVST-OIC in increasing HIV testing rate among 430 men who have sex with men (MSM), with access to online live-chat applications in Hong Kong. At month 6, as compared to the control group, the intervention group reported significantly higher prevalence of HIV testing of any type (89.8 vs. 50.7%; relative risk (RR): 1.77; p < 0.001). Among those who have taken up any HIV testing in the last six months, significant between-group difference was found in multiple male sex partnerships (34.2 vs. 47.7%, RR: 0.72; p = 0.021). HIVST-OIC has a strong potential in increasing prevalence of HIV testing and reducing sexual risk behaviors. Implementation research is warranted.
Assuntos
Sorodiagnóstico da AIDS/métodos , Aconselhamento , Infecções por HIV/diagnóstico , HIV/isolamento & purificação , Promoção da Saúde/métodos , Homossexualidade Masculina , Autocuidado/métodos , Adulto , Infecções por HIV/epidemiologia , Homossexualidade Masculina/psicologia , Hong Kong/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Avaliação de Processos e Resultados em Cuidados de Saúde , Prevalência , Comportamento de Redução do Risco , Autocuidado/psicologia , Testes Sorológicos , Comportamento Sexual , Minorias Sexuais e de GêneroRESUMO
Grassroots non-governmental organizations (NGOs) played pivotal roles in HIV prevention among men who have sex with men (MSM) in China. Their governance and sustainability issues were under-studied. This nation-wide study surveyed leaders of 202 of the HIV related NGOs in China.58.4% of the leaders believed that their NGO would last for ≤5 years; which was negatively associated with perceived good relationship with CDC. 65.3% mentioned ≥3 non-sustainability issues; associated factors included perceived inadequacies in prevention skills, management skills, policy support, technical support, operational support, and CDC's support; a reverse association was found for frequent collaboration with organizations in China. 30.6% of the leaders mentioned ≥7 governance issues; a stepwise model found a positive association with having no office and negative associations with number of full-time staff and core volunteers. These problems would severely limit the effectiveness of HIV prevention among MSM. Related improvements and support are warranted.
Assuntos
Atenção à Saúde/organização & administração , Eficiência Organizacional , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Síndrome da Imunodeficiência Adquirida , Adulto , China , Humanos , Masculino , Organizações , Assunção de Riscos , Minorias Sexuais e de GêneroRESUMO
PURPOSE: Political tension, as expressed by mass movements such as the Occupy Central movement (2014) in Hong Kong, is a potential but understudied structural factor of population mental health. METHODS: A random population-based telephone survey anonymously interviewed 344 Hong Kong Chinese adults aged 18-65 years during the 2 weeks since the termination date of the 2-month-long Occupy Central movement (15/12/2014). Linear regression models were fit using mental distress (depression, anxiety and negative mood) and self-perceived changes in mood/sleeping quality as dependent variables. RESULTS: Prevalence of participation in the movement was 10.5% (self), 17.7% (family members/relatives), and 34.0% (peers); 8.5% had participated for ≥2 days. Young age, but not participation, was associated with mental distress. In adjusted analysis, three types of responses to the movement (worry about safety, negative emotional responses to media reports, and conflicts with peers about the movement) and emotional responses to local political situations were significantly associated with all/some of the dependent variables related to mental distress. The variable on emotions toward local political situations was correlated with the three responses to the movement; it fully mediated the associations between such responses and mental distress. CONCLUSION: Many citizens participated in the movement, which was led by youths and might have increased the general public's mental distress. Negative personal responses to the movement and emotions toward political situations were potential risk factors. As the political tension would last and political pessimism is globally found, politics may have become a regular and persistent structural risk factor negatively affecting population mental health.
Assuntos
Ansiedade/psicologia , Depressão/psicologia , Ativismo Político , Adolescente , Adulto , Idoso , Ansiedade/epidemiologia , Depressão/epidemiologia , Feminino , Hong Kong/epidemiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Telefone , Adulto JovemRESUMO
BACKGROUND: Hypertension and type 2 diabetes mellitus are major modifiable risk factors for cardiac, cerebrovascular, and kidney diseases. Reasons for poor disease control include nonadherence, lack of patient engagement, and therapeutic inertia. OBJECTIVE: The aim of this study was to assess the impact on clinic-measured blood pressure (BP) and glycated hemoglobin (HbA1c) using a digital medicine offering (DMO) that measures medication ingestion adherence, physical activity, and rest using digital medicines (medication taken with ingestible sensor), wearable sensor patches, and a mobile device app. METHODS: Participants with elevated systolic BP (SBP ≥140 mm Hg) and HbA1c (≥7%) failing antihypertensive (≥2 medications) and oral diabetes therapy were enrolled in this three-arm, 12-week, cluster-randomized study. Participants used DMO (includes digital medicines, the wearable sensor patch, and the mobile device app) for 4 or 12 weeks or received usual care based on site randomization. Providers in the DMO arms could review the DMO data via a Web portal. In all three arms, providers were instructed to make medical decisions (medication titration, adherence counseling, education, and lifestyle coaching) on all available clinical information at each visit. Primary outcome was change in SBP at week 4. Other outcomes included change in SBP and HbA1c at week 12, and low-density lipoprotein cholesterol (LDL-C) and diastolic blood pressure (DBP) at weeks 4 and 12, as well as proportion of patients at BP goal (<140/90 mm Hg) at weeks 4 and 12, medical decisions, and medication adherence patterns. RESULTS: Final analysis included 109 participants (12 sites; age: mean 58.7, SD years; female: 49.5%, 54/109; Hispanic: 45.9%, 50/109; income ≤ US $20,000: 56.9%, 62/109; and ≤ high school education: 52.3%, 57/109). The DMO groups had 80 participants (7 sites) and usual care had 29 participants (5 sites). At week 4, DMO resulted in a statistically greater SBP reduction than usual care (mean -21.8, SE 1.5 mm Hg vs mean -12.7, SE 2.8 mmHg; mean difference -9.1, 95% CI -14.0 to -3.3 mm Hg) and maintained a greater reduction at week 12. The DMO groups had greater reductions in HbA1c, DBP, and LDL-C, and a greater proportion of participants at BP goal at weeks 4 and 12 compared with usual care. The DMO groups also received more therapeutic interventions than usual care. Medication adherence was ≥80% while using the DMO. The most common adverse event was a self-limited rash at the wearable sensor site (12%, 10/82). CONCLUSIONS: For patients failing hypertension and diabetes oral therapy, this DMO, which provides dose-by-dose feedback on medication ingestion adherence, can help lower BP, HbA1c, and LDL-C, and promote patient engagement and provider decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT02827630; https://clinicaltrials.gov/show/NCT02827630 (Archived by WebCite at http://www.webcitation.org/6rL8dW2VF).