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1.
N Engl J Med ; 381(13): 1201-1214, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553833

RESUMO

BACKGROUND: The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS: We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS: The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. CONCLUSIONS: Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Indução , Infusões Intravenosas , Injeções Subcutâneas , Quimioterapia de Manutenção , Masculino , Gravidade do Paciente , Indução de Remissão/métodos , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
2.
N Engl J Med ; 381(13): 1215-1226, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553834

RESUMO

BACKGROUND: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking. METHODS: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52. RESULTS: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years. CONCLUSIONS: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Adalimumab/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Indução de Remissão/métodos
3.
Nihon Shokakibyo Gakkai Zasshi ; 116(9): 732-738, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31511459

RESUMO

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as the operation of choice for refractory ulcerative colitis (UC), UC with dysplasia or cancer, or familial adenomatous polyposis. Pouchitis is the most frequent complication after IPAA for UC. Although the pathogenesis of pouchitis remains unclear, current evidence suggests that dysbiosis and mucosal immune response are important mechanisms. Antibiotics are the first-line treatment for the condition, but some patients develop chronic refractory pouchitis. Such cases can be treated with regimens such as longer courses of antibiotic combinations, mesalazine, corticosteroids, probiotics, or biologics. But if pouch inflammation is not ameliorated, a permanent ileostomy may be required. A 40-year-old man had undergone IPAA for UC and was diagnosed with pouchitis according to the Pouchitis Disease Activity Index. Antibiotics, mesalazine, and corticosteroids were given, but the inflammation was difficult to control. He developed chronic refractory pouchitis associated with perianal abscesses and anal fistulae. Following a seton procedure for fistulae, adalimumab (ADA) was administered. After 42 weeks, the ulcers in the pouch became scarred, and the anal fistulae were closed endoscopically. After remission was induced, it has been maintained. ADA is a fully human anti-tumor necrosis factor-α (TNF-α) monoclonal antibody that has been successfully used to treat refractory Crohn disease of the ileoanal pouch. Although some studies report that infliximab, a chimeric anti-TNF-α monoclonal antibody, is efficacious in patients with refractory pouchitis, clinical evidence for the use of ADA is limited. This case illustrates achievement of induction and maintenance of remission of refractory pouchitis with ADA. It is possible that patients with this condition can avoid a permanent ileostomy with anti-TNF-α therapy. In the near future, further study of long-term clinical outcomes of anti-TNF-α therapy is expected.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/cirurgia , Pouchite/diagnóstico , Proctocolectomia Restauradora , Adulto , Humanos , Masculino , Fator de Necrose Tumoral alfa
4.
Chem Biol Interact ; 311: 108790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31400342

RESUMO

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Interferon gama/metabolismo , Nociceptividade/efeitos dos fármacos , Receptores Opioides/metabolismo , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/genética , Edema/tratamento farmacológico , Edema/patologia , Comportamento Exploratório/efeitos dos fármacos , Pé/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Interferon gama/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/tratamento farmacológico , Dor/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/genética , Testes de Toxicidade Aguda , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Medicine (Baltimore) ; 98(34): e15852, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441836

RESUMO

BACKGROUND: The purpose of this study was to investigate the benefits and harm of combined administration of tranexamic acid (TXA) and dexamethasone (Dexa) in total knee arthroplasty (TKA). METHODS: A total of 88 consecutive patients undergoing TKA for knee osteoarthritis were stratified in 2 groups. All surgeries were performed under general anesthesia. Brief, patients in the TXA + Dexa group (n = 45) received 10 mg Dexa just after the anesthesia, and repeated at 24 hours after the surgery; and patients in the TXA group (n = 43) received 2 ml of normal saline solution at the same time. The measured outcomes were the C-reactive protein (CRP) and interleukin-6 (IL-6) from preoperatively to postoperatively, and postoperative nausea and vomiting (PONV), fatigue, range of motion (ROM), length of stay (LOS), and the analgesic and antiemetic rescue consumption RESULTS:: The level of CRP and IL-6 in the TXA + Dexa group were lower than that in the TXA group at 24 hours (P < .001, P < .001), 48 hours (P < .001, P < .001), and 72 hours (P < .001, P < .001) after the surgery. The pain scores in the TXA + Dexa group were lower during walking at 24 hours (P < .001), 48 hours (P < .001), and 72 hours (P < .001) and at rest at 24 hours (P = .022) after the surgery. Patients in the TXA + Dexa group had a lower nausea score, the incidence of PONV, fatigue, and the analgesic and antiemetic rescue consumption, and had a greater ROM than that in the TXA group. No significant differences were found in LOS and complications. CONCLUSION: The combined administration of TXA + Dexa significantly reduced the level of postoperative CRP and IL-6, relieve postoperative pain, ameliorate the incidence of POVN, provide additional analgesic and antiemetic effects, reduce postoperative fatigue, and improve ROM, without increasing the risk of complications in primary TKA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/métodos , Dexametasona/uso terapêutico , Ácido Tranexâmico/uso terapêutico , Idoso , Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antieméticos/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Proteína C-Reativa/efeitos dos fármacos , Dexametasona/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Amplitude de Movimento Articular , Ácido Tranexâmico/administração & dosagem
7.
Medicine (Baltimore) ; 98(35): e16985, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464947

RESUMO

RATIONALE: Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis (AEM) in infants is a very rare but fatal disease. Utilization of genetic assay to detect the cerebral parasite plays an important role for the treatment of the infection. PATIENT CONCERNS: Two infants (<2 years) presented with cough, intermittent fever, mental fatigue, and poor diet. DIAGNOSIS: The patients were under clinical examination and laboratory test including cardiac ultrasound, chest X-ray, blood or cerebrospinal fluid (CSF) cell counting, serum enzyme-linked immunosorbent assay (ELISA), head magnetic resonance imaging (MRI) and next-generation sequencing (NGS) on DNA from CSF. Due to hypereosinophils in patients' peripheral blood and CSF, and abundant DNA sequences from A cantonensis in CSF, the patients were diagnosed with Angiostrongylus eosinophilic meningoencephalitis. INTERVENTIONS: The patients were treated with albendazole to deworm, and methylprednisolone to reduce inflammation. OUTCOME: The patients were completely recovered from AEM without relapse after 10-day treatment. LESSONS: ELISA and MRI are not sufficiently accurate for the diagnosis of AEM in infants. NGS can specify the infection by the cerebral parasite and offers a new effective approach for the early and precise diagnosis of AEM in infants.


Assuntos
Eosinofilia/complicações , Meningoencefalite/complicações , Meningoencefalite/diagnóstico , Meningoencefalite/parasitologia , Infecções por Strongylida/diagnóstico , Albendazol/uso terapêutico , Angiostrongylus cantonensis , Animais , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Meningoencefalite/tratamento farmacológico , Metilprednisolona/uso terapêutico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia
8.
Medicine (Baltimore) ; 98(35): e17001, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464954

RESUMO

RATIONALE: Acute retinal necrosis (ARN), which is characterized by peripheral necrotizing retinitis, severe retinal arteritis, and progressive inflammatory reaction in the vitreous and anterior chambers, has been reported in cases with herpes simplex encephalitis (HSE). It is a relatively rare complication secondary to HSE. However, cases presented with viral encephalitis following ARN were seldom reported. PATIENT CONCERNS: A 43-year-old immunocompetent male patient manifested the aforesaid reverse situation. He developed HSE following 3-day systemic steroid therapy for abrupt ocular pain and rapidly decreased visual acuity, which was later diagnosed as ARN. Polymerase chain reaction (PCR) analysis of vitreous specimen verified herpes simplex virus-1 (HSV-1) infection. DIAGNOSIS: HSE associated with ARN. INTERVENTIONS: The patient was treated with intravenous acyclovir (500 mg every 8 h) for 21 days. A pulse of intravenous methylprednisolone, 500 mg/d for 5 days was given as an anti-inflammatory therapy, followed by prednisone taper. OUTCOMES: The patient's neurological symptoms got improved very soon after the therapy, but his vision acuity remained no perception of light in both eyes. LESSONS: The present case indicates that ARN can also be a risk factor for HSE. Once ARN was suspected, corticosteroid should be applied with caution and in combination with antiviral treatment to avoid progressive duplication of virus and its spread to the brain.


Assuntos
Encefalite por Herpes Simples/complicações , Herpesvirus Humano 1 , Síndrome de Necrose Retiniana Aguda/complicações , Aciclovir/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , DNA Viral/análise , Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Masculino , Metilprednisolona/uso terapêutico , Reação em Cadeia da Polimerase , Síndrome de Necrose Retiniana Aguda/diagnóstico , Síndrome de Necrose Retiniana Aguda/tratamento farmacológico
9.
Vasc Health Risk Manag ; 15: 209-220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371977

RESUMO

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.


Assuntos
Aterosclerose , Colesterol/sangue , Embolia de Colesterol , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cristalização , Embolia de Colesterol/sangue , Embolia de Colesterol/diagnóstico , Embolia de Colesterol/epidemiologia , Embolia de Colesterol/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Interleucina-1/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Síndrome
10.
Life Sci ; 234: 116773, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422095

RESUMO

AIMS: NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM. MAIN METHODS: A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12 weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35 mM). KEY FINDINGS: Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ɑ, interleukin-1ß, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells. SIGNIFICANCE: Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM.


Assuntos
Diabetes Mellitus Experimental/imunologia , Cardiomiopatias Diabéticas/imunologia , Glucuronidase/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/uso terapêutico , Cardiotônicos/imunologia , Cardiotônicos/uso terapêutico , Linhagem Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Glucuronidase/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Ratos , Espécies Reativas de Oxigênio/imunologia
11.
Int J Cardiovasc Imaging ; 35(9): 1745-1753, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312997

RESUMO

No data exist whether statins have robust anti-inflammatory effects of atherosclerotic plaques primarily during the early treatment period or continuously throughout use. This prospective three time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study of the carotid artery assessed anti-inflammatory effects of statin during the early treatment period (initiation to 3 months) and late treatment period (3 months to 1 year) and their correlation with lipid and inflammatory profile changes during a year of therapy. Nine statin-naïve stable angina patients with inflammatory carotid plaques received 20 mg/day atorvastatin after undergoing initial 18F-FDG PET/CT scanning of carotid arteries and ascending thoracic aorta, and then completed serial 18F-FDG PET/CT imaging at 3 and 12 months whose data were analyzed. The primary outcome was the inter-scan percent change in target-to-background ratio (ΔTBR) within the index vessel. At 3 months of atorvastatin treatment, mean serum low-density lipoprotein cholesterol (LDL-C) level decreased by 36.4% to < 70 mg/dL (p = 0.001) and mean serum high-density lipoprotein cholesterol level increased to > 40 mg/dL (p = 0.041), with both maintained with no further reduction up to 1 year (p = 0.516 and 0.715, respectively) while mean serum high sensitivity C-reactive protein level only numerically decreased (p = 0.093). The index vessel ΔTBR showed continuous plaque inflammation reduction over 1 year, by 4.4% (p = 0.015) from the initiation to 3rd months and 6.2% (p = 0.009) from 3rd months to 1 year, respectively, without correlation with lipid profile changes. The ΔTBR of the bilateral carotid arteries and ascending aorta also continuously decreased from 3 months to 1 year. Three time point 18F-FDG PET/CT imaging demonstrates that statin's anti-inflammatory effect continues throughout its use up to 1 year, even though yielding stable below-target plasma LDL-C levels at 3 months.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/tratamento farmacológico , Fluordesoxiglucose F18/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Rev Soc Bras Med Trop ; 52: e20180229, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31340353

RESUMO

Sarcoidosis is a rare multisystem chronic inflammatory disease in children. We present a case of a five-year-old child with clinical features mimicking several diseases, including tuberculosis. After failure of treatment based on the suspected diagnosis, an axillary lymph node biopsy showed noncaseating granulomas compatible with sarcoidosis and appropriate treatment was then started.


Assuntos
Sarcoidose/diagnóstico , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Biópsia , Brasil , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Linfoma/diagnóstico , Prednisolona/uso terapêutico , Sarcoidose/tratamento farmacológico , Tiabendazol/uso terapêutico , Tomografia Computadorizada por Raios X , Tuberculose/diagnóstico
13.
Rev Med Chil ; 147(3): 384-389, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344178

RESUMO

Fibrodysplasia ossificans progressiva (FOP) or myositis ossificans, is a genetic disease, with a prevalence of 1 in 2.000.000. It is caused by pathogenic variants in ACVR1 gene and characterized by soft tissue heterotopic ossification, starting in the second decade of life. It is associated to early mortality caused by respiratory complications. It evolves in flare-ups, triggered by soft tissue injuries; therapy is symptomatic, using analgesia, steroids and diphosphonates. We report a 12-year-old female with left renal agenesis, hallux valgus and intellectual disability, presenting with a six months history of thoracic kyphosis, tender nodules in the thorax, and rigidity of right elbow and left knee. Clinical examination revealed dysmorphic facial features. A magnetic resonance showed heterotopic ossification nodules, which was confirmed with spinal radiography. These findings prompted the diagnosis of FOP. Pain treatment was started, and prednisone was used during flare-ups. The ACVR1 gene was analyzed and a pathogenic variant, p. Arg206His, was found, confirming the diagnosis of FOP.


Assuntos
Miosite Ossificante/diagnóstico por imagem , Anti-Inflamatórios/uso terapêutico , Criança , Chile , Feminino , Humanos , Imagem por Ressonância Magnética , Miosite Ossificante/tratamento farmacológico , Miosite Ossificante/genética , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/tratamento farmacológico , Ossificação Heterotópica/genética , Prednisona/uso terapêutico
14.
Medicine (Baltimore) ; 98(28): e16372, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305435

RESUMO

BACKGROUND: Acute graft-vs-host disease (aGVHD) is a common complication of allogenic hematopoietic stem-cell transplantation (allo-HSCT) and skin is the most common and often the 1st site at which aGVHD develops. Cutaneous aGVHD is usually treated with oral and/or topical corticosteroids as the 1st-line treatment; however, steroid-refractory aGVHD not only impairs patients' quality of life but also causes significant morbidity and mortality after allo-HSCT. Narrow-band ultraviolet B (NB-UVB) phototherapy has been utilized for a wide range of immunologic inflammatory skin diseases, but there is limited information on the efficacy, safety, and biomarkers for response prediction of NB-UVB for cutaneous aGVHD. AIMS: The purpose of this study is to investigate the efficacy and safety of NB-UVB phototherapy for steroid-refractory cutaneous aGVHD. PATIENTS AND METHODS: A total of 40 subjects aged from 16 to 70 years with steroid-refractory cutaneous aGVHD after allo-HSCT will be included in the trial. Patients with worse than stage 2 intestine/liver aGVHD will be excluded. Eligible patients will undergo NB-UVB phototherapy until resolution or further worsening of rash or occurrence of an unmanageable adverse event. The primary endpoint is the overall response rate. The secondary outcomes include rates for complete response, partial response, stable disease, progressive disease, duration of response, sparing effect on calcineurin inhibitors and/or corticosteroids, safety, and predictive biomarkers for treatment response. ETHICS AND DISSEMINATION: The protocol has been approved by the institutional Clinical Research Review Board of Kyoto Prefectural University of Medicine. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Trial registration numbers UMIN000032426 and jRCTs052180005.


Assuntos
Ensaios Clínicos Fase II como Assunto , Doença Enxerto-Hospedeiro/terapia , Dermatopatias/terapia , Transplante de Células-Tronco , Terapia Ultravioleta , Doença Aguda , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Resistência a Medicamentos , Humanos , Pessoa de Meia-Idade , Retratamento , Dermatopatias/etiologia , Esteroides/uso terapêutico , Transplante Homólogo , Terapia Ultravioleta/efeitos adversos , Terapia Ultravioleta/métodos , Adulto Jovem
15.
Cochrane Database Syst Rev ; 7: CD001915, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31271656

RESUMO

BACKGROUND: The reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used in this respect to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review; however, due to the lack of research in this area, we do not envisage undertaking any further updates. OBJECTIVES: To assess the effectiveness of taking regular inhaled corticosteroids compared to not taking them in children and adults with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.Date of most recent search of the Group's Trials Register: 19 November 2018. SELECTION CRITERIA: Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS: The searches identified 35 citations, of which 27 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 525 people with cystic fibrosis aged between 6 and 55 years. One was a withdrawal trial in 171 individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information.Objective measures of airway function were reported in most trials but were often incomplete and reported at different time points. We found no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) % predicted in any of the trials, although the quality of the evidence was low due to risks of bias within the included trials and low participant numbers. We are uncertain whether inhaled corticosteroids result in an improvement in exercise tolerance, bronchial hyperreactivity or exacerbations as the quality of the evidence was very low. Data from one trial suggested that inhaled corticosteroids may make little or no difference to quality of life (low-quality evidence).Three trials reported adverse effects, but the quality of the evidence is low and so we are uncertain whether inhaled corticosteroids increase the risk of adverse effects. However, one study did show that growth was adversely affected by high doses of inhaled corticosteroids. AUTHORS' CONCLUSIONS: Evidence from these trials is of low to very low quality and insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Fibrose Cística/tratamento farmacológico , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Criança , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Capacidade Vital , Adulto Jovem
16.
Medicine (Baltimore) ; 98(30): e16632, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348314

RESUMO

BACKGROUND: This study aims to systematically explore the efficacy and safety of mometasone furoate (MTF) for patients with nasal polyps (NP). METHODS: We will search MEDLINE, Cochrane Library, PubMed, Springer, Web of Science, Ovid, Wangfang and Chinese Biomedical Literature Database from their inception to April 30, 2019 without language restrictions. All randomized controlled trials (RCTs) of MTF for the treatment of NP will be considered for inclusion. RevMan 5.3 software will be used for data synthesis, subgroup analysis, sensitivity analysis, as well as the meta-analysis. RESULTS: Primary outcomes include change in symptom scores (as measured by any symptom scores), and polyp size (as assessed by any Polyp size scores or tools). Secondary outcomes consist of polyp recurrence, change in nasal air flow, quality of life outcomes (as measured by any quality of life scales, such as Short Form Health Survey is a 36-item), and adverse events. CONCLUSION: This study will provide evidence for judging whether MTF is an effective and safe treatment for NP or not. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019134037.


Assuntos
Anti-Inflamatórios/uso terapêutico , Furoato de Mometasona/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Administração Intranasal , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Projetos de Pesquisa
17.
Chem Biol Interact ; 310: 108729, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31255636

RESUMO

A nutraceutical product can be defined as a substance that has a physiological benefit or provides protection against chronic diseases. The term nutraceutical is a hybrid term derived from the union of "nutrition" and "pharmaceutical". The list of studied nutraceuticals is constantly changing and reflects ongoing market developments, research and consumer interest. Spices, in addition to giving color and taste to foods, are also important nutraceutical. Spices have been an integral part of human diets and commerce for millennia but recently, the recognition of the link between health and nutrition has strengthened their importance in the food sector and sparked the interest of researchers who increasingly engage in trying to determine the mechanisms of action of spices and the countless beneficial properties attributed to them. Among the many existing spices, turmeric is one of the most studied for its antioxidant, anti-inflammatory, antibacterial and anticancer properties. The purpose of this review is to briefly summarize the fundamental characteristics of turmeric and give an overview of the use of this spice in several diseases.


Assuntos
Curcuma/fisiologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Especiarias
18.
Pan Afr Med J ; 32: 189, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312301

RESUMO

Diffuse Idiopathic Skeletal Hyperostosis (DISH) also known as Forestier's disease, is a musculoskeletal disorder characterized by the calcification of ligaments essentially the vertebral longitudinal anterior ligament. Men are generally affected. It is often asymptomatic. The most common extra-spinal clinical manifestation of this disease presents as dysphagia followed by respiratory disturbances such as dyspnea and sleep apnea. In this paper we discuss two cases where the patients have experienced progressive dysphagia. Radiological findings were compatible with DISH. The management was based on diet modification and anti-inflammatory medication.


Assuntos
Anti-Inflamatórios/uso terapêutico , Transtornos de Deglutição/etiologia , Hiperostose Esquelética Difusa Idiopática/diagnóstico , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Hiperostose Esquelética Difusa Idiopática/complicações , Hiperostose Esquelética Difusa Idiopática/terapia , Masculino , Pessoa de Meia-Idade
19.
Medicina (B Aires) ; 79(3): 204-207, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31284256

RESUMO

Susac syndrome is a rare disorder caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear. These occlusions lead to a characteristic clinical triad of central nervous system dysfunction, visual disturbances and vestibule-cochlear deficits. The diagnosis is based on clinical manifestations and complementary studies, which demonstrate the involvement of three systems. There are different treatments that include various immunosuppressive drugs combinations such as corticosteroids, intravenous immunoglobulin, mycophenolate mofetil, among others. We present the case of a 26-year-old woman with left hearing loss, tinnitus and episodes of recurrent vertigo, four weeks after bilateral blurred vision, cerebellar ataxia and encephalopathy. Magnetic resonance imaging of the brain showed multiple rounded hyperintense lesions in t2 and fluid-attenuated inversion recovery (FLAIR), hypointense in t1, at the middle level of the corpus callosum, internal capsule, cerebellum and right middle cerebellar peduncle. The audiometry evidenced bilateral perceptual hearing loss, predominantly in the left ear. Angiography by optical coherence tomography showed obstruction in the deep layer retina arteries. The Susac syndrome was diagnosed and treatment started with methylprednisolone pulses therapy, intravenously 1000 mg/day for 5 days, followed by maintenance with mycophenolate, which completely reversed the encephalopathy, with persistence of mild ataxia and hearing loss. It is important to know the clinical triad characteristic and the complementary studies necessary to arrive at the diagnosis, since immunosuppressive treatment can often be delayed. Our case had an excellent response to corticosteroids.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Síndrome de Susac/complicações , Síndrome de Susac/diagnóstico por imagem , Vertigem/diagnóstico , Anti-Inflamatórios/uso terapêutico , Encefalopatias/tratamento farmacológico , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Fármacos Neuroprotetores , Prednisolona/uso terapêutico , Gravidez , Síndrome de Susac/tratamento farmacológico
20.
Bull Cancer ; 106(9): 776-783, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31178070

RESUMO

Mucositis, an acute inflammation of the digestive mucosa, is one of the main toxicities secondary to oncological treatments. Among its consequences, mucositis-related pain is an important complication due to its intensity and repercussion, especially on quality of life. Treatment of pain plays a central role in management of mucositis. It must be multimodal, combining local and general opioid or non-opioid treatments, adapted to pain intensity and based on international recommendations updated in 2014. A systemic analgesic treatment with morphine with a patient-controlled analgesia device is often necessary in severe mucositis. In case of insufficient analgesia, use of co-analgesics (paracetamol, ketamine, anticonvulsants, and antidepressants) can improve analgesic control and reduce morphine doses. Non-drug strategies (distraction, relaxation, hypnosis) and preventive measures must be a major concern. Among them, laser therapy using a low power athermal laser beam, is a promising therapeutic strategy whose effectiveness is based on its analgesic, anti-inflammatory, and healing properties. Despite many available studies, there is a limited number of clinically effective therapies. New therapeutic agents for the prevention and treatment of mucositis and its pain, based on the biological phenomena involved, must be further developed to improve the efficacy of analgesia.


Assuntos
Analgésicos/uso terapêutico , Mucosite/complicações , Manejo da Dor/métodos , Dor/etiologia , Analgesia Controlada pelo Paciente , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Humanos , Terapia a Laser , Terapia de Alvo Molecular , Morfina/uso terapêutico , Doenças da Boca/complicações , Doenças da Boca/terapia , Mucosite/terapia , Neoplasias/terapia , Medição da Dor/métodos , Guias de Prática Clínica como Assunto
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