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1.
Medicine (Baltimore) ; 99(36): e22060, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899071

RESUMO

The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Antimetabólitos Antineoplásicos , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas/métodos , Irinotecano/uso terapêutico , Japão/epidemiologia , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Oxaliplatina/uso terapêutico , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X/métodos , Inibidores da Topoisomerase I/uso terapêutico , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico
2.
Lancet ; 396(10254): 839-852, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32888407

RESUMO

BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas. METHODS: We did a seamless design study at 14 cancer centres in the USA. We enrolled adult patients (aged ≥18 years) with relapsed or refractory large B-cell lymphomas. Eligible histological subgroups included diffuse large B-cell lymphoma, high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), diffuse large B-cell lymphoma transformed from any indolent lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B. Patients were assigned to one of three target dose levels of liso-cel as they were sequentially tested in the trial (50 × 106 CAR+ T cells [one or two doses], 100 × 106 CAR+ T cells, and 150 × 106 CAR+ T cells), which were administered as a sequential infusion of two components (CD8+ and CD4+ CAR+ T cells) at equal target doses. Primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate (assessed per Lugano criteria); endpoints were assessed by an independent review committee in the efficacy-evaluable set (comprising all patients who had confirmed PET-positive disease and received at least one dose of liso-cel). This trial is registered with ClinicalTrials.gov, NCT02631044. FINDINGS: Between Jan 11, 2016, and July 5, 2019, 344 patients underwent leukapheresis for manufacture of CAR+ T cells (liso-cel), of whom 269 patients received at least one dose of liso-cel. Patients had received a median of three (range 1-8) previous lines of systemic treatment, with 260 (97%) patients having had at least two lines. 112 (42%) patients were aged 65 years or older, 181 (67%) had chemotherapy-refractory disease, and seven (3%) had secondary CNS involvement. Median follow-up for overall survival for all 344 patients who had leukapheresis was 18·8 months (95% CI 15·0-19·3). Overall safety and activity of liso-cel did not differ by dose level. The recommended target dose was 100 × 106 CAR+ T cells (50 × 106 CD8+ and 50 × 106 CD4+ CAR+ T cells). Of 256 patients included in the efficacy-evaluable set, an objective response was achieved by 186 (73%, 95% CI 66·8-78·0) patients and a complete response by 136 (53%, 46·8-59·4). The most common grade 3 or worse adverse events were neutropenia in 161 (60%) patients, anaemia in 101 (37%), and thrombocytopenia in 72 (27%). Cytokine release syndrome and neurological events occurred in 113 (42%) and 80 (30%) patients, respectively; grade 3 or worse cytokine release syndrome and neurological events occurred in six (2%) and 27 (10%) patients, respectively. Nine (6%) patients had a dose-limiting toxicity, including one patient who died from diffuse alveolar damage following a dose of 50 × 106 CAR+ T cells. INTERPRETATION: Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies. FUNDING: Juno Therapeutics, a Bristol-Myers Squibb Company.


Assuntos
Antígenos CD19/uso terapêutico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Antígenos CD19/administração & dosagem , Antígenos CD19/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/transplante , Síndrome da Liberação de Citocina/epidemiologia , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Infusões Intravenosas , Leucaférese/métodos , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Doenças do Sistema Nervoso/epidemiologia , Neutropenia/epidemiologia , Recidiva , Segurança , Análise de Sobrevida , Trombocitopenia/epidemiologia , Resultado do Tratamento
3.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907923

RESUMO

CONTEXT: Current International Liaison Committee on Resuscitation recommendations on epinephrine administration during neonatal resuscitation were derived in 2010 from indirect evidence in animal or pediatric studies. OBJECTIVE: Systematic review of human infant and relevant animal studies comparing other doses, routes, and intervals of epinephrine administration in neonatal resuscitation with (currently recommended) administration of 0.01 to 0.03 mg/kg doses given intravenously (IV) every 3 to 5 minutes. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and trial registry databases. STUDY SELECTION: Predefined criteria were used for selection. DATA EXTRACTION: Risk of bias was assessed by using published tools appropriate for the study type. Certainty of evidence was assessed by using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Only 2 of 4 eligible cohort studies among 593 unique retrieved records yielded data allowing comparisons. There were no differences between IV and endotracheal epinephrine for the primary outcome of death at hospital discharge (risk ratio = 1.03 [95% confidence interval 0.62 to 1.71]) or for failure to achieve return of spontaneous circulation, time to return of spontaneous circulation (1 study; 50 infants), or proportion receiving additional epinephrine (2 studies; 97 infants). There were no differences in outcomes between 2 endotracheal doses (1 study). No human infant studies were found in which authors addressed IV dose or dosing interval. LIMITATIONS: The search yielded sparse human evidence of very low certainty (downgraded for serious risk of bias and imprecision). CONCLUSIONS: Administration of epinephrine by endotracheal versus IV routes resulted in similar survival and other outcomes. However, in animal studies, researchers continue to suggest benefit of IV administration using currently recommended doses.


Assuntos
Broncodilatadores/administração & dosagem , Epinefrina/administração & dosagem , Ressuscitação/métodos , Animais , Relação Dose-Resposta a Droga , Humanos , Recém-Nascido , Infusões Intravenosas
4.
Medicine (Baltimore) ; 99(35): e21468, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871869

RESUMO

Saline is a commonly used intravenous solvent, however, its excessive infusion may increase drug-induced sodium intake. To investigate the effects of saline infusion on blood pressure variability (BPV) in patients with hypertension, a retrospective study was performed in 1010 patients with hypertension. The patients who received saline infusion before surgery for continuous 3 to 5 days were divided into 2 groups according to the saline infusion volume during the hospitalization, which are >500 mL per day group and <500 mL per day group. The overall incidence of abnormal BPV was 11.58%. As for the incidence of abnormal BPV in the <500 mL per day group with 698 patients was 9.17%, while that in the >500 mL per day group with 312 patients was as high as 16.99%. Additionally, >500 mL of daily saline infusion for continuous 3 to 5 days (P for trend = .004, odds ratio [OR] = 1.911, 95% confidence interval [CI] for OR 1.226-2.977), medical history of diabetes mellitus (P < .001, OR = 4.856, 95% CI for OR 3.118-7.563) and cardiovascular diseases (P < .001, OR = 2.498, 95% CI for OR 1.549-4.029) may be risk factors of abnormal BPV; while anti-hypertensive therapy with diuretics (P < .001, OR = 0.055, 95% CI for OR 0.024-0.125) may be the protective factor. Our study suggests that >500 mL of daily saline infusion for continuous 3 to 5 days may have disadvantages in the blood pressure control for hypertensive patients, especially for the patients with diabetes mellitus and cardiovascular diseases.


Assuntos
Variação Biológica da População/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/epidemiologia , Solução Salina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/tendências , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Procedimentos Ortopédicos/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Solução Salina/administração & dosagem
5.
Emerg Med Clin North Am ; 38(4): 755-769, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981615

RESUMO

There are approximately 350,000 out-of-hospital cardiac arrests and 200,000 in-hospital cardiac arrests annually in the United States, with survival rates of approximately 5% to 10% and 24%, respectively. The critical factors that have an impact on cardiac arrest survival include prompt recognition and activation of prehospital care, early cardiopulmonary resuscitation, and rapid defibrillation. Advanced life support protocols are continually refined to optimize intracardiac arrest management and improve survival with favorable neurologic outcome. This article focuses on current treatment recommendations for adult nontraumatic cardiac arrest, with emphasis on the latest evidence and controversies regarding intracardiac arrest management.


Assuntos
Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Manuseio das Vias Aéreas , Antiarrítmicos/administração & dosagem , Pressão Sanguínea , Dióxido de Carbono/análise , Diástole , Ecocardiografia , Cardioversão Elétrica , Serviço Hospitalar de Emergência , Epinefrina/administração & dosagem , Humanos , Hipotermia Induzida , Infusões Intraósseas , Infusões Intravenosas , Monitorização Fisiológica , Sistemas Automatizados de Assistência Junto ao Leito , Guias de Prática Clínica como Assunto , Vasoconstritores/administração & dosagem
6.
Emerg Med Clin North Am ; 38(4): 795-805, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981618

RESUMO

Successful emergency transfusions require early recognition and activation of resources to minimize treatment delays. The initial goals should focus on replacement of blood in a balanced fashion. There is an ongoing debate regarding the best approach to transfusions, with some advocating for resuscitation with a fixed ratio of blood products and others preferring to use viscoelastic assays to guide transfusions. Whole-blood transfusion also is a debated strategy. Despite these different approaches, it generally is accepted that transfusions should be started early and crystalloid infusions limited. As hemodynamic stability is restored, endpoints of resuscitation should be used to guide the resuscitation.


Assuntos
Transfusão de Sangue , Choque Hemorrágico/terapia , Antifibrinolíticos/uso terapêutico , Tipagem e Reações Cruzadas Sanguíneas , Cateterismo Venoso Central , Tomada de Decisão Clínica , Protocolos Clínicos , Estado Terminal , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Humanos , Hipotensão , Infusões Intraósseas , Infusões Intravenosas , Ressuscitação , Tromboelastografia , Ácido Tranexâmico/uso terapêutico , Ferimentos e Lesões/terapia
7.
Emerg Med Clin North Am ; 38(4): 871-889, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981623

RESUMO

Massive gastrointestinal hemorrhage is a life-threatening condition that can result from numerous causes and requires skilled resuscitation to decrease patient morbidity and mortality. Successful resuscitation begins with placement of large-bore intravenous or intraosseous access; early blood product administration; and early consultation with a gastroenterologist, interventional radiologist, and/or surgeon. Activate a massive transfusion protocol when initial red blood cell transfusion does not restore effective perfusion or the patient's shock index is greater than 1.0. Promptly reverse coagulopathies secondary to oral anticoagulant or antiplatelet use. Use thromboelastography or rotational thromboelastometry to guide further transfusions. Secure a definitive airway and minimize aspiration.


Assuntos
Hemorragia Gastrointestinal/terapia , Manuseio das Vias Aéreas , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticoagulantes/efeitos adversos , Antifibrinolíticos/uso terapêutico , Oclusão com Balão , Fatores de Coagulação Sanguínea/administração & dosagem , Transfusão de Sangue/métodos , Cateteres , Serviço Hospitalar de Emergência , Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Infusões Intraósseas , Infusões Intravenosas , Anamnese , Exame Físico , Inibidores da Bomba de Prótons/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Ressuscitação , Tromboelastografia , Vasoconstritores/uso terapêutico
8.
Ann Palliat Med ; 9(5): 3235-3248, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954754

RESUMO

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-α. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-α and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Betacoronavirus , Estudos de Casos e Controles , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Feminino , Febre/fisiopatologia , Humanos , Infusões Intravenosas , Interleucina-10/imunologia , Interleucina-6/imunologia , Tempo de Internação , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Respiração Artificial , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
9.
Med Klin Intensivmed Notfmed ; 115(7): 550-556, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32880673

RESUMO

Peripheral intravenous lines are indispensable for emergency and intensive medical care. They have a high importance, especially in the context of primary care as well as in the early stages of treatment initiation. This requires in-depth knowledge of the persons being treated. This article describes the most important aspects of the indications, puncture and fixation techniques as well as special features in terms of management and hygiene.


Assuntos
Emergências , Serviço Hospitalar de Emergência , Humanos , Infusões Intravenosas , Injeções Intravenosas
10.
Middle East Afr J Ophthalmol ; 27(2): 134-138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32874049

RESUMO

Nodular posterior scleritis represents a small percentage of all cases of posterior scleritis. Because of the scarcity of nodular posterior scleritis, it may be confused or even misdiagnosed as an intraocular tumor or posterior uveitis. Here, we are reporting a case of nodular posterior scleritis in a 25-year-old medically free male. Furthermore, we reviewed previously reported cases of nodular posterior scleritis. Our patient presented with a choroidal mass of about one disc diameter in size. In addition, the patient had exudative retinal detachment and chorioretinal folds. B scan ultrasonography showed subretinal fluid, macular nodular thickening and underlying echolucent area along with medium internal reflectivity on A scan. Fluorescein angiography revealed early pinpoint areas of hyperfluorescence and late pooling under the detached retina. Indocyanine green angiography demonstrated early diffuse hypofluorescence corresponding to the area of detachment and late multiple pinpoint spots of hyperfluorescence. After intravenous methylprednisolone 1 g for 3 days followed by a course of oral prednisolone along with mycophenolate mofetil, the patient experienced rapid recovery with improvement in vision and complete resolution of subretinal fluid. On further follow-up, the patient regained 20/20 vision. Nodular posterior scleritis is a rare unilateral disease with strong female predominance. Multimodal imaging should be employed to confirm the diagnosis. The disease must be diagnosed correctly to avoid any unnecessary diagnostic work-up and aggressive management. Most cases carry excellent prognosis with no recurrence.


Assuntos
Neoplasias da Coroide/diagnóstico , Melanoma Amelanótico/diagnóstico , Descolamento Retiniano/diagnóstico , Esclerite/diagnóstico , Administração Oral , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Coroide/tratamento farmacológico , Corantes/administração & dosagem , Quimioterapia Combinada , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Verde de Indocianina/administração & dosagem , Infusões Intravenosas , Masculino , Melanoma Amelanótico/tratamento farmacológico , Metilprednisolona/uso terapêutico , Imagem Multimodal , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Descolamento Retiniano/tratamento farmacológico , Esclerite/tratamento farmacológico , Tomografia de Coerência Óptica
11.
N Engl J Med ; 383(12): 1117-1128, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32937045

RESUMO

BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/uso terapêutico , Creatinina/urina , Ciclofosfamida/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão
13.
PLoS One ; 15(8): e0237104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750083

RESUMO

BACKGROUND: Vitamins and minerals are routinely administered by total parenteral nutrition (TPN). However, in Japan, adjustments in iron dosage are difficult because blended mineral preparations are often used. It is therefore unclear whether the iron content is appropriate in cases of long-term TPN. The aim of the study was to assess the influence of iron administration by long-term TPN on iron deposition in post-mortem liver samples isolated from older deceased patients. METHODS: Liver tissues were collected from post-mortem autopsies of 187 patients over a period of 15 years. Samples were stained with Prussian blue and histologically evaluated from Grade 0-V by at least three different observers. Specimens with positive and negative iron staining were compared, and positive samples were grouped according to the level and distribution of the staining. Post-mortem blood obtained from the subclavian vein during autopsy was also analysed. Samples were collected for the measurement of unsaturated serum iron, serum iron, albumin, prealbumin, hepcidin, and IL-6 concentrations. RESULTS: Iron accumulation in the liver was significantly higher in male patients (p = 0.005) with a history of surgery (p = 0.044) or central vein administration of iron (p<0.001). Additionally, the duration of TPN in the iron-positive group was significantly longer than in the iron-negative group (p = 0.038). Serum analysis revealed that unsaturated serum iron was significantly higher in the iron-negative group and that ferritin and serum iron were significantly higher in the iron-positive group. No other statistically significant differences were observed between the two groups. CONCLUSIONS: Chronic intravenous administration of iron was associated with iron deposition in the liver, even when given the minimum recommended dosage. In long-term TPN patients, the iron dose should therefore be carefully considered.


Assuntos
Ferro/administração & dosagem , Fígado/metabolismo , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Infusões Intravenosas , Ferro/sangue , Ferro/metabolismo , Fígado/patologia , Masculino , Nutrição Parenteral
14.
N Engl J Med ; 383(8): 711-720, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32813947

RESUMO

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P<0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was -132.1 mg per deciliter (95% CI, -175.3 to -88.9; P<0.001). The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null-null variants (-43.4% vs. +16.2%) and in those with non-null variants (-49.1% vs. -3.8%). Adverse events were similar in the two groups. CONCLUSIONS: In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.).


Assuntos
Proteínas Semelhantes a Angiopoietina/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/sangue , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/sangue , Criança , Método Duplo-Cego , Feminino , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Infusões Intravenosas , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Mutação , Receptores de LDL/metabolismo , Adulto Jovem
15.
Medicine (Baltimore) ; 99(30): e21303, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791716

RESUMO

The PLEM100 (Inbody Co., Ltd., Seoul, Korea) is a device for measuring phase lag entropy (PLE), a recently developed index for the quantification of consciousness during sedation and general anesthesia. In the present study, we assessed changes in PLE along with the level of consciousness during the induction of general anesthesia using propofol. PLE was compared with the bispectral index (BIS), which is currently the most commonly used index of consciousness.After obtaining Institutional Review Board approval and written informed consent, we enrolled 15 patients (8 men, 7 women; mean age: 37 ±â€Š9 years; mean height: 168 ±â€Š8 cm; mean weight; 68 ±â€Š11 kg) undergoing nasal bone reduction. PLE and BIS sensors were attached simultaneously, and general anesthesia was induced via target-controlled infusion (TCI) of propofol. PLE and BIS scores were recorded when the calculated effect site concentration shown on the TCI pump was equal to the target concentrations of 1.5, 2.0, 2.5, 2.8, 3.0, 3.2, 3.4, and 3.5 µg/mL (and at each 0.1 µg/mL increase, thereafter). Observer's Assessment of Alertness/Sedation (OAA/S) scores were also recorded until unconsciousness was achieved. Throughout the anesthesia period, all pairs of PLE and BIS data were collected using data acquisition software.The partial correlation coefficients between OAA/S scores and PLE, and between OAA/S scores and BIS were 0.778 (P < .001) and 0.846 (P < .001), respectively. Throughout the period of anesthesia, PLE and BIS exhibited a significant positive correlation. The partial correlation coefficient prior to the loss of consciousness was 0.838 (P < .001), and 0.669 (P < .001) following the loss of consciousness. Intra-class correlation between the 2 indices was 0.889 (P < .001) and 0.791 (P < .001) prior and following the loss of consciousness, respectively.PLE exhibited a strong and predictable correlation with both BIS and OAA/S scores. These results suggest that PLE is reliable for assessing the level of consciousness during sedation and general anesthesia.


Assuntos
Anestesia Geral/métodos , Anestésicos Intravenosos/administração & dosagem , Entropia , Propofol/administração & dosagem , Adulto , Estado de Consciência/efeitos dos fármacos , Estado de Consciência/fisiologia , Monitores de Consciência , Eletroencefalografia/instrumentação , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Osso Nasal/cirurgia , Estudos Prospectivos
16.
J Pineal Res ; 69(3): e12683, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32770854

RESUMO

The pharmacological properties of melatonin are well known. However, there is noticeable the lack of clinical trials that confirm the efficacy, security, absence of side effects in the short and long term, and the effective doses of melatonin. This point is especially important in diseases with high morbidity and mortality including COVID-19. There is not treatment for COVID-19, and several anti-inflammatory and antiviral molecules are being tested, and different vaccines are in preparation. Although the SARS-CoV-2 pandemic is apparently improving, it is expected new resurges next fall. Thus, looking for an effective treatment of COVID-19 is mandatory. Melatonin has significant anti-inflammatory, antioxidant, and mitochondrial protective effects, and its efficacy has been demonstrated in multiple experimental models of disease and in a clinical trial in sepsis. Because COVID-19 courses with a severe septic response, multiple reviews proposing melatonin as a treatment for COVID-19 have been published. Nevertheless, there is a lack of experimental and clinical data on the use of melatonin on SARS-CoV-2 infection. Accordingly, we designed a clinical trial with an injectable formulation of melatonin for intravenous perfusion in ICU patients suffering from COVID-19 that has been just approved by the Spanish Agency of Medicines and Medical Devices (AEMPS). The trial will allow by the first time understand the doses and efficacy of melatonin against COVID-19.


Assuntos
Antioxidantes/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Melatonina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Humanos , Infusões Intravenosas , Pandemias
17.
Ann Hematol ; 99(10): 2215-2229, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32856140

RESUMO

The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE® immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígenos CD19/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Subpopulações de Linfócitos B/imunologia , Linfoma de Células B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/economia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Ensaios Clínicos como Assunto , Terapia Combinada , Análise Custo-Benefício , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/prevenção & controle , Custos de Medicamentos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/economia , Infusões Intravenosas , Injeções Subcutâneas , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/imunologia , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Pré-Medicação , Qualidade de Vida , Subpopulações de Linfócitos T/imunologia , Resultado do Tratamento , Carga Tumoral , Evasão Tumoral
18.
Br J Anaesth ; 125(4): 622-628, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32739045

RESUMO

BACKGROUND: Arterial pressure lability is common during the process of replacing syringes used for norepinephrine infusions in critically ill patients. It is unclear if there is an optimal approach to minimise arterial pressure instability during this procedures. We investigated whether 'double pumping' changeover (DPC) or automated changeover (AC) reduced blood pressure lability in critically ill adults compared with quick syringe changeover (QC). METHODS: Patients requiring a norepinephrine infusion syringe change were randomised in a non-blinded trial undertaken in six ICUs. Randomisation was minimised by norepinephrine flow rate at inclusion and centre. The primary outcome was the frequency of increased/decreased mean arterial pressure (defined by 15 mm Hg from baseline measurements) within 15 min of switching the syringe compared with QC. RESULTS: Patients (mean age: 64 (range:18-88)) yr were randomly assigned to QC (n=95), DPC (n=95), or AC (n=96). Increased MAP was the commonest consequence of syringe changeovers. MAP variability was most frequent after DPC (89/224 changeovers; 39.7%) compared with 57/223 (25.6%) changeovers after quick syringe switch and 46/181 (25.4%) in patients randomised to receive automated changeover (P=0.001). Fewer events occurred with QC compared with DPC (P=0.002). Sensitivity analysis based on mixed models showed that performing several changeovers on a single patient had no impact. Both type of changeover and norepinephrine dose before syringe changeover were independently associated with MAP variations >15 mm Hg. CONCLUSIONS: Quick changeover of norepinephrine syringes was associated with less blood pressure lability compared with DPC. The prevalence of MAP variations was the same between AC and QC. CLINICAL TRIAL REGISTRATION: NCT02304939.


Assuntos
Pressão Arterial/efeitos dos fármacos , Cuidados Críticos , Norepinefrina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Seringas , Adulto Jovem
19.
Trials ; 21(1): 746, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847626

RESUMO

OBJECTIVES: To investigate the effect of continuous infusion of the potential endothelial cytoprotective agent prostacyclin (Iloprost) 1 ng/kg/min vs. placebo for 72 hours on pulmonary endotheliopathy in mechanically ventilated COVID-19 patients. TRIAL DESIGN: A multicenter, randomized (1:1, active: placebo), blinded, parallel group exploratory trial PARTICIPANTS: Inclusion criteria are: Adult patients (>18 years); Confirmed COVID-19 infection; Need for mechanical interventions; Endothelial biomarker soluble thrombomodulin >4ng/ml. EXCLUSION CRITERIA: Withdrawal from active therapy; Pregnancy (non-pregnancy confirmed by patient being postmenopausal (age 60 or above) or having a negative urine- or plasma-hCG); Known hypersensitivity to iloprost or to any of the other ingredients; Previously included in this trial or a prostacyclin trial within 30 days; Consent cannot be obtained; Life-threatening bleeding defined by the treating physician; Known severe heart failure (NYHA class IV); Suspected acute coronary syndrome The study is conducted at five intensive care units in the Capital Region of Denmark at Rigshospitalet, Herlev Hospital, Hvidovre Hospital, Bispebjerg Hospital, Nordsjællands Hospital. INTERVENTION AND COMPARATOR: The patients are randomized to 72-hours continuous infusion of either prostacyclin (Iloprost/Ilomedin) at a dose of 1 ng/kg/min or Placebo (normal saline). MAIN OUTCOMES: Primary endpoint: Days alive without mechanical ventilation in the intensive care units within 28 days RANDOMISATION: The randomisation sequence is performed in permuted blocks of variable sizes stratified for trial site using centralised, concealed allocation. The randomisation sequence is generated 1:1 (active/placebo) using the online randomisation software 'Sealed Envelope' ( https://www.sealedenvelope.com/ ). Once generated the randomisation sequence is formatted and uploaded into Research Electronic Data Capture system (REDCap) to facilitate centralised, web-based allocation according to local written instruction. BLINDING (MASKING): The following are blinded: all clinicians, patients, investigators, and those assessing the outcomes including the statisticians. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Forty patients are planned to be randomized to each group, with a total sample size of 80 patients. TRIAL STATUS: Protocol version 1.4 dated May 25, 2020. Recruitment is ongoing. The recruitment was started June 15, 2020 and the anticipated finish of recruitment is February 28, 2021 with 90 days follow up hereafter. TRIAL REGISTRATION: Trial registration at clinicaltrialregisters.eu; EudraCT no. 2020-001296-33 on 3 April 2020 and at ClinicalTrials.gov Identifier: NCT04420741 on 9 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Infecções por Coronavirus/terapia , Iloprosta/uso terapêutico , Pneumonia Viral/terapia , Respiração Artificial , Vasodilatadores/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Dinamarca , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/sangue , Trombomodulina/metabolismo
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