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2.
Clin Cancer Res ; 29(24): 5008-5011, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37594723

RESUMO

On December 10, 2021, the FDA expanded the indications for ribociclib to include male patients for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Ribociclib is now indicated in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy in adult patients, or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy (ET), in postmenopausal women or in men. The efficacy of ribociclib + AI for male patients was primarily based on previous favorable benefit-risk assessments of ribociclib from MONALEESA-2 and MONALEESA-7 trials, and supported by COMPLEEMENT-1, an open-label, single-arm, multicenter clinical trial, in which 39 male patients (n = 3,246 total patients) received ribociclib + letrozole + goserelin/leuprolide. The overall response rate (ORR) based on confirmed responses in male patients with measurable disease at baseline was 46.9% [95% confidence interval (CI), 29.1-65.3], consistent with an ORR of 43.6% (95% CI, 41.5-45.8) in the overall population. Overall, adverse reactions occurring in male patients were similar to those occurring in female patients treated with ribociclib + ET. The efficacy of ribociclib + fulvestrant for male patients was primarily based on the previous findings of a favorable benefit-risk assessment from the MONALEESA-3 trial, supported by FDA review of clinical data of a limited number of male patients treated in clinical practice receiving ribociclib + fulvestrant. The known mechanism of action, biologic rationale, and clinical information available adequately demonstrate that the efficacy and safety of ribociclib + AI/fulvestrant are similar in male and female patients. This article summarizes the FDA's decision-making and data supporting the approval of ribociclib in male patients with breast cancer, and discusses regulatory insights.


Assuntos
Neoplasias da Mama , Receptores de Estrogênio , Adulto , Feminino , Humanos , Masculino , Letrozol , Fulvestranto/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Aminopiridinas , Inibidores da Aromatase/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor ErbB-2/uso terapêutico
5.
Clin Cancer Res ; 28(8): 1487-1492, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-34916216

RESUMO

On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59-0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA, 13% of patients treated with margetuximab plus chemotherapy reported IRRs, of which 1.5% were grade 3. The most commonly reported adverse drug reactions (>10%) with margetuximab in combination with chemotherapy were fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, IRR, palmar-plantar erythrodysesthesia, and extremity pain. Overall, the favorable risk-benefit profile for margetuximab when added to chemotherapy supported its approval for the intended indication.


Assuntos
Neoplasias da Mama , Adulto , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Aprovação de Drogas , Feminino , Humanos , Receptor ErbB-2/uso terapêutico , Trastuzumab/efeitos adversos
6.
J Eur Acad Dermatol Venereol ; 35(3): 712-720, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32896010

RESUMO

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.


Assuntos
Síndrome de Stevens-Johnson , Alelos , Anticonvulsivantes , Povo Asiático , Antígenos HLA-B/genética , Hong Kong , Humanos , Taiwan
7.
Br J Oral Maxillofac Surg ; 56(9): 841-846, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30293802

RESUMO

Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle has the potential to sag, and because it needs lengthy maxillomandibular fixation. We have therefore introduced a simple method of fixation, and examined its effectiveness and complications. After the osteotomy, the proximal and distal segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in diameter are inserted percutaneously from the proximal to the distal segment while the condyle is positioned in the glenoid fossa. This is followed by a brief period of maxillomandibular fixation. We have reviewed the records of 95 patients who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two patients because excursion of the jaw was either too heavy or too early. The fixations were redone. All other fixations remained stable, including the 20 dual-jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal mouth opening at final follow-up was 44 (7) mm, and in only one patient was it less than 30mm. Numbness of the lip or chin developed in seven patients, five of whom had other anterior mandibular procedures. Four patients had discomfort on palpation of the site of the pins, and one required removal. The new method was effective, and resulted in few complications within its limitations.


Assuntos
Pinos Ortopédicos , Doenças Maxilomandibulares/cirurgia , Técnicas de Fixação da Arcada Osseodentária/instrumentação , Osteotomia Sagital do Ramo Mandibular/instrumentação , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Clin Cancer Res ; 24(13): 2999-3004, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29437768

RESUMO

On March 13, 2017, the FDA approved ribociclib (KISQALI; Novartis Pharmaceuticals Corp.), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer. The approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2). A total of 668 patients were randomized to receive either ribociclib plus letrozole (n = 334) or placebo plus letrozole (n = 334). An improvement in progression-free survival (PFS) was observed in patients receiving ribociclib plus letrozole compared with patients receiving placebo plus letrozole [HR = 0.556; 95% confidence interval (CI), 0.429-0.720]. Overall response rate (ORR) in patients with measurable disease was 52.7% (95% CI, 46.6-58.9) in the ribociclib plus letrozole arm and 37.1% (95% CI, 31.1-43.2) in the placebo plus letrozole arm. Overall survival data were immature. The most common adverse reactions observed in 20% or more of patients taking ribociclib were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. This article summarizes FDA decision-making and data supporting the approval of ribociclib. Clin Cancer Res; 24(13); 2999-3004. ©2018 AACRSee related commentary by Spring and Bardia, p. 2981.


Assuntos
Aminopiridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Aprovação de Drogas , Pós-Menopausa , Purinas/uso terapêutico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Ensaios Clínicos como Assunto , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Purinas/administração & dosagem , Purinas/efeitos adversos , Projetos de Pesquisa , Resultado do Tratamento
9.
Indoor Air ; 28(1): 173-180, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28779498

RESUMO

To improve indoor air quality and to protect public health, Taiwan has enacted the "Indoor Air Quality Act (IAQ Act)" in 2012. For the general public, the indoor air quality in hair salons is important because it is a popular location that people will often visit for hair treatments. However, only a few exposure assessments regarding air pollutants have previously been performed in hair salons. To assess the air quality of hairdressing environments in Taipei, ten hairdressing salons were included for a walk-through survey in this study. In addition, the airborne concentrations of formaldehyde, volatile organic compounds (VOCs), CO2 , and phthalate esters were also determined in 5 salons. Charcoal, XAD-2, and OVS-Tenax tubes were used for the air sampling, while the samples were analyzed with gas chromatography/mass spectrometer. It was found that the products used in hair salons contained various chemicals. In fact, from the walk-through survey, a total of 387 different ingredients were found on 129 hair product labels. The hair salons were not well ventilated, with CO2 levels of 600 to 3576 ppm. The formaldehyde concentrations determined in this study ranged from 12.40 to 1.04 × 103  µg m-3 , and the maximum level was above the permissible exposure limit (PEL) of US Occupational Safety and Health Administration (US OSHA). Additionally, 83% of the samples were with levels higher than the standard regulated by Taiwan's IAQ Act. The concentrations of VOCs and phthalate esters were below the occupational exposure limits (OELs), but higher than what was found in general residential environments. The hair products were considered as the major source of air pollutants because significantly higher concentrations were found around the working areas. The number of perming treatments, the number of workers, and the frequency of using formaldehyde releasing products, were found to be associated with the levels of formaldehyde. This study indicates that efforts are needed to improve the indoor air quality in hairdressing salons in Taipei.


Assuntos
Poluição do Ar em Ambientes Fechados , Formaldeído/análise , Preparações para Cabelo , Compostos Orgânicos Voláteis/análise , Ar/análise , Dióxido de Carbono/análise , Feminino , Humanos , Exposição Ocupacional/análise , Taiwan
10.
Int J Obes (Lond) ; 42(2): 231-243, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28630461

RESUMO

BACKGROUND: Obesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD). METHODS: Male C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored. RESULTS: After 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1ß, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties. CONCLUSIONS: Supplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota.


Assuntos
Antrodia/química , Dieta Hiperlipídica , Disbiose/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/dietoterapia , Obesidade/dietoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Modelos Animais de Doenças , Disbiose/fisiopatologia , Resistência à Insulina/fisiologia , Masculino , Medicina Tradicional , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia
11.
Nutr Metab Cardiovasc Dis ; 27(12): 1136-1142, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29170062

RESUMO

BACKGROUND AND AIMS: There are few studies on the association between HDL-C levels and arterial stiffness (AS). HDL-C levels vary in males and females, and it is not clear whether the relationship between HDL-C levels and AS is influenced by gender. The purpose of this study was to investigate gender differences in the association between HDL-C levels and AS in adults. METHODS AND RESULTS: After excluding subjects using lipid-lowering agent, 7254 subjects were enrolled. The AS was assessed by measuring the brachial-ankle pulse wave velocity (baPWV) value. The quartiles of HDL-C were <38, 38-45, 45-53 and >53 mg/dL in men and <48, 48-57, 57-69 and >68 mg/dL in women, respectively. In subjects aged <50 years, none of the HDL-C quartiles were associated with baPWV values. In subjects aged ≥50 years, the highest quartile of HDL-C (beta: -37.57, 95% CI: -61.61 to -13.54) was negatively related to baPWV values. When considering gender difference in subjects aged ≥50 years, the highest quartile of HDL-C (Q4 beta: -57.22, 95% CI: -95.63 to -18.81) was inversely associated with baPWV values in women, but none of the HDL-C quartiles were related to baPWV values in men. CONCLUSIONS: A high HDL-C level was associated with a lower risk of AS in subjects aged ≥50 years in women but not in men, although this relationship was not apparent in subjects aged <50 years. The association between HDL-C level and AS is thus influenced by gender in people aged ≥50 years.


Assuntos
Doenças Cardiovasculares/fisiopatologia , HDL-Colesterol/sangue , Dislipidemias/sangue , Rigidez Vascular , Adulto , Índice Tornozelo-Braço , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologia , Regulação para Cima
12.
J Hum Hypertens ; 31(10): 616-619, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28660886

RESUMO

Arterial stiffness has similar risk factors to gallstone disease (GSD). However, there are few studies on the association between arterial stiffness and GSD. The aim of this study was to determine the relationship between arterial stiffness and GSD in a Taiwanese population. We enroled 6211 subjects from a health examination centre after excluding those who received medications for diabetes, hypertension and hyperlipidemia or had a history of cardiovascular disease, cerebrovascular disease, cancer, cholecystectomy or ankle-brachial index of ⩽ 0.9 or⩾1.3. Increased arterial stiffness was defined as right brachial-ankle pulse wave velocity (baPWV) ⩾1400 cm s-1. The diagnosis of GSD was based on ultrasonographic findings. The prevalence of increased arterial stiffness was 47.2 and 31.9 % in subjects with and without GSD (P<0.001). A multiple linear regression analysis revealed that GSD, age, systolic blood pressure, fasting plasma glucose and current smoking were positively associated with baPWV, whereas male gender, BMI, habitual exercise and HDL-C were negatively related to baPWV after adjusting for other clinical variables. In conclusion, subjects with GSD are associated with an increased risk of arterial stiffness.


Assuntos
Doenças Cardiovasculares/epidemiologia , Cálculos Biliares/epidemiologia , Rigidez Vascular , Adulto , Índice Tornozelo-Braço , Povo Asiático , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Cálculos Biliares/diagnóstico , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
13.
Bull Entomol Res ; 107(6): 734-741, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28485267

RESUMO

Detrimental effects of ultraviolet (UV) light on living organisms are well understood, little is known about the effects of blue light irradiation. Although a recent study revealed that blue light caused more harmful effects on insects than UV light and blue light irradiation killed insect pests of various orders including Diptera, the effects of blue light on physiology of insects are still largely unknown. Here we studied the effects of blue light irradiation on cuticular melanin in larval and the immune response in adult stage of Bactrocera dorsalis. We also evaluated the effects of blue light exposure in larval stage on various age and mass at metamorphosis and the mediatory role of cuticular melanin in carryover effects of larval stressors across metamorphosis. We found that larvae exposed to blue light decreased melanin contents in their exoskeleton with smaller mass and delayed metamorphosis than insects reared without blue light exposure. Across metamorphosis, lower melanotic encapsulation response and higher susceptibility to Beauveria bassiana was detected in adults that had been exposed to blue light at their larval stage, thereby constituting the first evidence that blue light impaired adult immune function in B. dorsalis as a carryover effect of larval exposure.


Assuntos
Controle de Insetos/métodos , Melaninas/metabolismo , Tephritidae/imunologia , Animais , Beauveria , Terapia de Imunossupressão , Larva/metabolismo , Larva/efeitos da radiação , Tephritidae/metabolismo , Tephritidae/efeitos da radiação
14.
J Fish Dis ; 40(12): 1775-1781, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28493514

RESUMO

This work reports the effect of two DNA vaccines against salmonid alphavirus 3 (SAV3) in Atlantic salmon. Presmolts were vaccinated by intramuscular injection of plasmids encoding the SAV3 structural polyprotein C-E3-E2-6K-E2 (pCSP), E2 only (pE2), or plasmid without insert (pcDNA3.3). E2 is expressed at the surface of cells transfected with pCSP and internally in cells transfected with pE2. A commercial vaccine based on inactivated SAV (NCPD) was used for comparison. At 10 weeks post-vaccination, only fish vaccinated with pCSP showed antibody against E2 and virus-neutralizing activity. Vaccinated fish were infected with SAV3 to determine protection by virus quantitation in serum after 7 days and scoring of pathological changes after 21 days. Fish vaccinated with both pCSP and NCPD vaccines showed significant virus reduction in serum, while fish vaccinated with pE2 did not. All fish vaccinated with pcDNA3.3 and pE2 showed pathological changes in organs typical of PD, 60% of fish vaccinated with NCPD showed PD pathology, while fish vaccinated with pCSP did not show PD pathology. Taken together, DNA vaccination with pCSP provided strong protection for salmon against SAV3 infection, which in part may be due to production of virus-neutralizing antibodies.


Assuntos
Infecções por Alphavirus/veterinária , Formação de Anticorpos , Doenças dos Peixes/prevenção & controle , Salmo salar/virologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Alphavirus/imunologia , Infecções por Alphavirus/prevenção & controle , Animais , Doenças dos Peixes/virologia , Pâncreas/patologia , Pâncreas/virologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
15.
Oncogene ; 36(22): 3193-3206, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28218902

RESUMO

The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARß-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool. Our data reveal that pharmacological concentration of ATRA effectively downregulates PKCζ through activation of miR-200c, leading to a decrease of the stem cell-like populations from non-tumorigenic mammary epithelial cells and non-aggressive breast cancer cells. However, aggressive breast cancer cells that manifest TET2-miR-200c dysregulation sustain a CSC pool highly resistant to ATRA, where inhibition of PKCζ directs the resistant CSCs to the luminal cell-like state and sensitization to tamoxifen, resulting in abrogation of mammary tumor growth and progression. Together, these findings elucidate a novel RARß-TET2-miR-200c-PKCζ signaling pathway that directs cancer cell state changes and also provide previously unidentified therapeutic implications for PKCζ inhibitors in diminishment of breast CSCs to eradicate breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proteínas de Ligação a DNA/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Tretinoína/farmacologia , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dioxigenases , Feminino , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Artigo em Inglês | MEDLINE | ID: mdl-26526411

RESUMO

The quantitative relationship between serum albumin level and surgical outcomes has not been clearly established. This study included 3732 patients with colon cancer who underwent a potentially curative colectomy. Post-operative mortality and morbidity were analysed according to the patients' demographic data, pre-operative comorbidities, and tumour-related factors. Age, asthma, renal impairment, and albumin level were significantly associated with post-operative morbidity and mortality in the multivariate analyses. Logistic regression analysis revealed linear relationships of post-operative morbidity and mortality with albumin level. The morbidity and mortality rates decreased by 7.3% and 15.6%, respectively, for each 0.1 g/dL increase in albumin level. This finding remained significant in the hypoalbuminaemia subgroup but not in the normoalbuminaemia subgroup. That is, the morbidity and mortality rates significantly decreased by 8.7% and 17.7%, respectively (both P < 0.001), in the former group and decreased by 2.7% (P = 0.112) and 11.6% (P = 0.092), respectively, in the latter group. This study demonstrated that serum albumin level linearly predicted the post-operative morbidity and mortality among the colorectal cancer patients. Pre-operative serum albumin level may therefore be used as a continuous rather than a categorical marker of disease severity, especially among patients with hypoalbuminaemia.


Assuntos
Colectomia , Neoplasias Colorretais/cirurgia , Hipoalbuminemia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Albumina Sérica/metabolismo , Fatores Etários , Idoso , Asma/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Comorbidade , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Hipoalbuminemia/metabolismo , Modelos Lineares , Modelos Logísticos , Masculino , Mortalidade , Análise Multivariada , Estadiamento de Neoplasias , Complicações Pós-Operatórias/metabolismo , Período Pré-Operatório , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco
17.
Int J Syst Evol Microbiol ; 66(11): 4766-4771, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27530392

RESUMO

A Gram-stain-negative, nutritionally fastidious bacterium (PLS229T) causing pear leaf scorch was identified in Taiwan and previously grouped into Xylella fastidiosa. Yet, significant variations between PLS229T and Xylellafastidiosa were noted. In this study, PLS229T was evaluated phenotypically and genotypically against representative strains of Xylellafastidiosa, including strains of the currently known subspecies of Xylellafastidiosa, Xylella fastidiosa subsp. multiplex and 'Xylella fastidiosasubsp.pauca'. Because of the difficulty of in vitro culture characterization, emphases were made to utilize the available whole-genome sequence information. The average nucleotide identity (ANI) values, an alternative for DNA-DNA hybridization relatedness, between PLS229T and Xylellafastidiosa were 83.4-83.9 %, significantly lower than the bacterial species threshold of 95 %. In contrast, sequence similarity of 16S rRNA genes was greater than 98 %, higher than the 97 % threshold to justify if two bacterial strains belong to different species. The uniqueness of PLS229T was also evident by observing only about 87 % similarity in the sequence of the 16S-23S internal transcribed spacer (ITS) between PLS229T and strains of Xylellafastidiosa, discovering significant single nucleotide polymorphisms at 18 randomly selected housekeeping gene loci, observing a distinct fatty acid profile for PLS229T compared with Xylellafastidiosa, and PLS229T having different observable phenotypes, such as different susceptibility to antibiotics. A phylogenetic tree derived from 16S rRNA gene sequences showed a distinct PLS229T phyletic lineage positioning it between Xylellafastidiosa and members of the genus Xanthomonas. On the basis of these data, a novel species, Xylella taiwanensis sp. nov. is proposed. The type strain is PLS229T (=BCRC 80915T=JCM 31187T).


Assuntos
Filogenia , Doenças das Plantas/microbiologia , Pyrus/microbiologia , Xylella/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Folhas de Planta/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Xylella/genética , Xylella/isolamento & purificação
18.
Cell Death Dis ; 7: e2298, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27441650

RESUMO

Maintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome activity is inhibited when treated with PD solutions. Proteasome inhibition-mediated activation of salt-inducible kinase 2 (SIK2), an endoplasmic reticulum-resident protein, is important for mesothelial cell viability. SIK2 is mobilized to promote autophagy and protect the cells from apoptosis under PD solution or MG132 treatment. Immunofluorescence staining showed that SIK2 is colocalized with LC3B in the autophagosomes of mesothelial cells treated with PD solution or derived from patients undergoing PD treatment. SIK2 activation is likely via a two-step mechanism, upstream kinases relieving the autoinhibitory conformation of SIK2 molecule followed by autophosphorylation of Thr175 and activation of kinase activity. These results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by PD solutions. Maintaining or boosting the activity of SIK2 may promote peritoneal mesothelial cell viability and evolve as a potential therapeutic target for maintaining or restoring peritoneal membrane integrity in PD therapy.


Assuntos
Soluções para Diálise/farmacologia , Células Epiteliais/efeitos dos fármacos , Diálise Peritoneal , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Cisteína Proteinase/farmacologia , Soluções para Diálise/química , Ativação Enzimática , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Leupeptinas/farmacologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pressão Osmótica , Peritônio/citologia , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Estresse Mecânico
19.
Transplant Proc ; 48(4): 1067-70, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320558

RESUMO

BACKGROUND: Shift in large fluid volumes and massive blood loss during liver transplantation frequently leads to rapid changes in hemoglobin (Hb) concentration; thus, to ensure adequate tissue oxygenation, accurate and rapid determination of Hb concentration is essential in transplant recipients. The Radical-7 Pulse CO-Oximeter provides a noninvasive and continuous way to monitor Hb concentration (SpHb) in real time and is an ideal candidate for use during liver transplantation. In this study, we assessed the relationship between SpHb and total Hb (tHb) obtained from arterial blood samples during surgery. METHODS: Forty patients undergoing liver transplantation were enrolled in this study. tHb and time-matched SpHb were measured at 5 different phases throughout surgery. Paired SpHb and tHb levels were assessed using linear regression, Bland-Altman analysis, and the Critchley polar plot method. RESULTS: A total of 161 paired measurements with sufficient signal quality were analyzed. The correlation between SpHb and tHb was 0.59 (P < .001). Bland-Altman analysis revealed that a bias between SpHb and tHb was 2.28 g/dL, and limits of agreement (LoA) were from -0.78 to 5.34 g/dL. Trending analysis showed that 87% of data were located within the acceptable trending area, indicating that the trending ability was not satisfied. CONCLUSIONS: The Radical-7 Pulse CO-Oximeter was not sufficient to monitor Hb levels and trends during liver transplantation surgery in our cohort. In particular, in critical patients and in those with low Hb levels, invasive Hb measurement should be used for assessment.


Assuntos
Hemoglobinas/análise , Transplante de Fígado/métodos , Monitorização Intraoperatória/métodos , Oximetria/métodos , Adulto , Idoso , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Transplant Proc ; 48(4): 1170-5, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320580

RESUMO

BACKGROUND: Liver transplant recipients often have violent hemodynamic fluctuation during surgery that may be related to perioperative and postoperative morbidity. Because there are some considerations for the risk of the pulmonary arterial catheter (PAC), the conventional invasive device for cardiac output (CO) measurement, a reliable and minimally invasive alternative is required. We validated the reliability of CO measurements with the use of a minimally invasive FloTrac system with the latest fourth-generation algorithm in liver transplant recipients. METHODS: Forty liver transplant recipients without atrial fibrillation, valvular pathology, or intracardiac shunt were recruited in this prospective, observational study. CO values measured by use of PAC with continuous thermodilution method (COTh) and FloTrac devices (COFT) were collected simultaneously throughout the operation for reliability validation. RESULTS: Four hundred pairs of CO data points were collected in total. The linear regression analysis showed a high correlation coefficient (73%, P < .001). However, the percent error between COTh and COFT was 42.2%, which is worse than the established interchangeability criterion of 30%. The concordance rates were calculated at 89% and 59% by 4-quadrant plot and polar plot analysis, respectively. Neither met the preset validation criteria (>92% for the 4-quadrant plot and >90% for polar plot analyses). CONCLUSIONS: Our study demonstrates that the CO measurements in liver transplant recipients by the latest FloTrac system and the PAC do not meet the recognized interchangeability criterion. Although the result showed improvement in linear regression analysis, it failed to display a qualified trending ability.


Assuntos
Débito Cardíaco , Transplante de Fígado , Análise de Onda de Pulso/métodos , Algoritmos , Cateterismo Periférico , Cateterismo de Swan-Ganz/métodos , Feminino , Hemodinâmica , Humanos , Modelos Lineares , Masculino , Estudos Prospectivos , Análise de Onda de Pulso/instrumentação , Reprodutibilidade dos Testes , Termodiluição
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