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1.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541971

RESUMO

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.


Assuntos
Anti-Inflamatórios/efeitos adversos , Dexametasona/efeitos adversos , Viremia/tratamento farmacológico , Idoso , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Automedicação/métodos , Esteroides/efeitos adversos , Esteroides/uso terapêutico , Resultado do Tratamento , Viremia/complicações
2.
Nat Commun ; 12(1): 915, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568665

RESUMO

Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries.


Assuntos
/tratamento farmacológico , Dexametasona/uso terapêutico , /economia , /terapia , Análise Custo-Benefício , Dexametasona/economia , Mortalidade Hospitalar , Hospitalização , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Respiração Artificial , Reino Unido/epidemiologia , Ventiladores Mecânicos
3.
Medicine (Baltimore) ; 100(5): e23992, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592855

RESUMO

BACKGROUND: There have been conflicting results regarding clinical dexamethasone-sugammadex interactions in adults and pediatric patients under general anesthesia. METHODS: This study used a systematic review with meta-analysis of randomized controlled trials and non-randomized studies based on the Cochrane Review Methods. A comprehensive literature search was conducted to identify clinical trials that investigated the effect of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular blockade in surgical patients undergoing general anesthesia. RESULTS: Among the 314 patients in the 6 studies, 147 received intravenous dexamethasone (dexamethasone group), and 167 received intravenous saline or other antiemetics (control group). The primary outcome, the time to recovery after sugammadex administration (the time to recovery of the train-of-four ratio to 0.9 after sugammadex administration; s) was comparable between the 2 groups, the weighted mean difference (95% confidence interval [CI]) being -2.93 (-36.19, 30.33) (I2 = 94%). The time to extubation after sugammadex administration (s) and incidence of postoperative nausea and vomiting was not different between the 2 groups, the weighted mean difference (95% CI) being 23.31 (-2.26, 48.88) (I2 = 86%) and the pooled risk ratio (95% CI) being 0.25 (0.03, 2.11), respectively. The time to recovery after sugammadex administration might be different according to the study design or study region. CONCLUSION: This meta-analysis showed that use of dexamethasone in the perioperative period neither delayed nor facilitated the reversal of rocuronium-induced neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia. However, given that the results showed high heterogeneity, further randomized controlled trials are needed to confirm these findings.


Assuntos
Anestesia Geral/métodos , Dexametasona/farmacologia , Interações Medicamentosas , Bloqueio Neuromuscular/métodos , Rocurônio/farmacologia , Sugammadex/farmacologia , Procedimentos Cirúrgicos Eletivos/métodos , Glucocorticoides/farmacologia , Humanos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Assistência Perioperatória/métodos
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 131-136, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554809

RESUMO

OBJECTIVE: To investigate the efficacy, survival and adverse effects of non-transplanted multiple myeloma (MM) patients treated with bortezomib maintenance. METHODS: A total of 25 newly diagnosed/relapsed non-transplanted MM patients treated in West District of Beijing Chaoyang Hospital from June 2004 to November 2015 were analyzed retrospectively. All patients received PD regimen (bortezomib and dexamethasone), including bortezomib at a dose of 1.3 mg/m2 and dexamethasone 20 mg on days 1, 8, 15, 22 in a 3-month cycle. RESULTS: Till November 1, 2017, 5 patients achieved stringent complete response (sCR), 8 patients achieved complete response (CR), 7 patients achieved very good partial response (VGPR), 4 patients achieved partial reponse (PR), while 1 patient achieved stable disease (SD). After maintenance therapy, 21 patients maintained the efficacy above PR, of which 1 patient was improved from CR to sCR; 4 patients adjusted chemotherapy after disease progressed. Median maintenance therapy was 9 cycles (range from 6 to 31), and the median maintenance time was 27 months (range from 18 to 97). Median follow-up time was 73 months (range from 25 to 171). Median progress-free survival (PFS) time was 30 months (range from 9 to 105) and overall survival (OS) time was 57 months (range from 27 to 160). Till November 1, 2019, 3-year survival rate was 84% (21/25), and 5-year survival rate was 72% (13/18). The most common adverse events were transient leukopenia, thrombocytopenia and peripheral neuropathy, which the patients could tolerate after the prevention and treatment. CONCLUSION: Bortezomib-based maintenance therapy for non-transplanted MM patients can be an option in consideration of its safety and efficacy.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 137-144, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554810

RESUMO

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
6.
Medicine (Baltimore) ; 100(3): e24206, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546038

RESUMO

BACKGROUND: Traumatic brain injury (TBI) constitutes a leading cause of death and disability. Patients with TBI and cerebral contusions developing pericontusional edema are occasionally given dexamethasone on the belief that this edema is similar to that of tumors, in which the beneficial effect of dexamethasone has been demonstrated. METHODS: The DEXCON TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfill the elegibility criteria will be randomized to dexamethasone/placebo in a short and descending course: 4 mg/6 h (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed 1 month and 6 months after TBI. Secondary outcomes are: number of episodes of neurological deterioration; symptoms associated with TBI; adverse events; volume of pericontusional edema before and after 12 days of treatment; results of the neuropsychological tests one month and 6 months after TBI. The main analysis will be on an "intention-to-treat" basis. Logistic regression will estimate the effect of dexamethasone/placebo on GOSE at one month and at 6 months, dichotomized in unfavorable outcome (GOSE 1-6) and favorable outcome (GOSE 7-8). Efficacy will also be analyzed using the 'sliding dichotomy'. An interim and safety analysis will be performed including patients recruited during the first year to calculate the conditional power. A study with 600 patients would have 80% power (2 sided alpha = 5%) to detect a 12% absolute increase (from 50% to 62%) in good recovery. DISCUSSION: This is a confirmative trial to elucidate the therapeutic efficacy of dexamethasone in a very specific group of TBI patients: patients with brain contusions and pericontusional edema. This trial could become an important milestone for TBI patients as nowadays there is no effective treatment in this type of patients. TRIAL REGISTRATION: eudraCT: 2019-004038-41; Clinical Trials.gov: NCT04303065.


Assuntos
Anti-Inflamatórios/uso terapêutico , Contusão Encefálica/tratamento farmacológico , Edema Encefálico/tratamento farmacológico , Dexametasona/uso terapêutico , Contusão Encefálica/complicações , Edema Encefálico/etiologia , Método Duplo-Cego , Humanos , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Yonsei Med J ; 62(2): 137-148, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527793

RESUMO

PURPOSE: In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. MATERIALS AND METHODS: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. RESULTS: CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. CONCLUSION: Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.


Assuntos
Dexametasona/farmacologia , Imunomodulação/efeitos dos fármacos , Linfócitos T/imunologia , Talidomida/farmacologia , Animais , Antígeno CTLA-4/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Citometria de Fluxo , Ativação Linfocitária/efeitos dos fármacos , Teste de Cultura Mista de Linfócitos , Masculino , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/metabolismo , Baço/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
8.
Rinsho Ketsueki ; 62(1): 14-19, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33551419

RESUMO

Although classic Hodgkin's lymphoma (CHL) sometimes develops after treatment for multiple myeloma (MM), simultaneous diagnosis of both malignancies is extremely rare without previous treatment history. Here we describe a case of a 54-year-old female who complained of left cervical lymphadenopathy. Biopsy specimen from the left cervical lymph node revealed mixed-cellularity CHL. Bone marrow aspirate comprised 10.3% plasma cells. She was diagnosed with MM due to involved: uninvolved serum free light chain ratio of >100. She achieved complete response for CHL after 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy along with 30 Gy of involved-field radiotherapy. Three years later, bortezomib, lenalidomide, and dexamethasone (VRd-lite) therapy was initiated for MM. Severe neutropenia during her 1st cycle prompted a dosage reduction of lenalidomide and bortezomib. Partial response was achieved after 4 cycles of VRd-lite followed by high-dose melphalan/autologous stem cell transplantation. No severe adverse events were recorded. This was followed by 4 cycles of carfilzomib, lenalidomide, and dexamethasone therapy, which resulted in complete remission. As the number of elderly people increases, multiple myeloma patients with previous history of other malignancies would increase. Our case has shown that VRd-lite therapy may be suitable for those patients.


Assuntos
Doença de Hodgkin , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Transplante Autólogo
9.
BMJ Case Rep ; 14(1)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504531

RESUMO

Acquired von Willebrand syndrome is a rare bleeding disorder characterised by a later age of onset without a personal or family history of bleeding diathesis. It is vital to discern acquired von Willebrand syndrome from inherited von Willebrand disease and other acquired bleeding disorders as management differs significantly. Acquired von Willebrand syndrome is usually secondary to an underlying disorder such as lymphoproliferative disorder, myeloproliferative neoplasm, solid tumour, cardiovascular disorder, autoimmune disorders or hypothyroidism. Diagnosis is often delayed with a significant risk of morbidity and even mortality. Here we present a case of a 74-year-old man with an acquired bleeding disorder and work up suggestive of acquired von Willebrand syndrome secondary to immunoglobulin G kappa multiple myeloma. He was treated successfully with intravenous immunoglobulin, von Willebrand Factor/Coagulation Factor VIII Complex (human), myeloma directed chemotherapy and autologous stem cell transplantation. We also discuss the management strategies that are largely based on retrospective studies and case reports.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/complicações , Transplante de Células-Tronco , Doenças de von Willebrand/etiologia , Idoso , Bortezomib/administração & dosagem , Angiografia por Tomografia Computadorizada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Erros de Diagnóstico , Combinação de Medicamentos , Embolização Terapêutica , Fator VIII/uso terapêutico , Hemofilia A/diagnóstico , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Nefropatias/etiologia , Nefropatias/terapia , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Transplante Autólogo , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológico , Fator de von Willebrand/uso terapêutico
10.
BMJ Case Rep ; 14(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408106

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder of excessive immune activation. It is mostly seen in the paediatric population and is rarely observed in adults. HLH can be inherited or acquired and is commonly triggered by activation of the immune system by an underlying viral infection or in immune system deficiency such as malignancy or underlying rheumatological disease. HLH is a difficult entity to diagnose due to the rarity of this disorder, variable clinical presentation and non-specific clinical and laboratory findings. HLH carries a high mortality if left untreated, and therefore prompt diagnosis and initiation of immunosuppressive, immunomodulatory and cytostatic medications are critical to improve survival in affected patients. Here, we present a case of lamotrigine-associated HLH. To our knowledge, only eight other cases of lamotrigine-associated HLH have been reported in adult patients.


Assuntos
Anticonvulsivantes/administração & dosagem , Lamotrigina/efeitos adversos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Convulsões/tratamento farmacológico , Adulto , Biópsia , Medula Óssea/patologia , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Etoposídeo/uso terapêutico , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino
11.
Vet Res ; 52(1): 1, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397469

RESUMO

Psoroptic mange is a common disease of livestock, caused by Psoroptes ovis. Compared to Holstein-Friesian (HF) cattle, the Belgian Blue (BB) cattle breed is highly susceptible to the infestation. However, the mechanism for this difference is still unclear. To determine the factors responsible for this breed susceptibility, the immune response to P. ovis was studied in experimentally infested BB and HF cattle, using clinical signs, histology, immunohistochemical profiling and gene expression analysis of skin biopsies. The mite numbers and lesion area of BB cattle were greater than in HF during the whole study period. Significant influxes of eosinophils in the epidermis and dermis were detected in comparison with the pre-infestation samples in both breeds, with significantly higher eosinophils in BB at 6 weeks post infestation (wpi). Mast cell numbers were unaffected at all stages of infestation in HF, but were significantly elevated relative to pre-infestation in BB cattle at 2 and 6 wpi. The more pronounced cutaneous eosinophilia and higher IL-4 levels at 6 wpi in BB cattle suggest that a Th2-type immune response is underlying the higher susceptibility of the BB breed. In naturally infested BB cattle, development of the psoroptic mange lesions and eosinophils and CD3+ T cell areas were severely depressed after anti-inflammatory treatment with dexamethasone. Together, these results suggest that a stronger Th2-type immune response to P. ovis causes the skin lesions in psoroptic mange in BB cattle and that local anti-inflammatory treatment could potentially be an alternative to control the pathology caused by this parasite.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças dos Bovinos/parasitologia , Dexametasona/uso terapêutico , Infestações por Ácaros/veterinária , Psoroptidae , Animais , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/imunologia , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/imunologia , Psoroptidae/imunologia , Pele/imunologia , Pele/parasitologia , Especificidade da Espécie
12.
J Chin Med Assoc ; 84(3): 245-247, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433137

RESUMO

The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a corticosteroid applied in clinical medicine since 1957, especially in immune therapy fields. Herein, we present the characteristics of Dexamethasone, from molecular mechanisms such as genomic and nongenomic pathways by cellular signal regulations, to clinical applications in various phases of the disease. During COVID-19 pandemic, Dexamethasone given to patients who required oxygen or ventilation therapy showed improved life efficacy.


Assuntos
/tratamento farmacológico , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Humanos , Receptores de Glucocorticoides/fisiologia , Transdução de Sinais/fisiologia
13.
Med. clín (Ed. impr.) ; 156(1): 7-12, ene. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-196134

RESUMO

OBJETIVO: Analizar si existe asociación entre el uso de glucocorticoides a dosis altas y la evolución de la SAFI (saturación/fracción inspirada de oxígeno) o el tiempo hasta el alta, en pacientes hospitalizados por COVID-19. MÉTODOS: Estudio observacional sobre una cohorte de 418 pacientes ingresados en 3 hospitales comarcales de Cataluña (España). Como resultados primarios se estudiaron la evolución de la SAFI en las primeras 48h de tratamiento y el tiempo hasta el alta. Los resultados se compararon entre pacientes tratados y no tratados con glucocorticoides (metilprednisolona 1-2mg/kg/día o dexametasona 20-40mg/día), mediante el análisis de subcohortes emparejadas por múltiples factores clínicos y pronósticos, así como mediante modelos multivariantes de Cox, ajustados por diversos factores pronósticos. El uso simultáneo de diferentes tratamientos para la COVID-19 fue tenido en cuenta, tanto en el emparejamiento de subcohortes como en la regresión de Cox. RESULTADOS: Hubo 187 pacientes con glucocorticoides; de ellos, 25 pacientes pudieron ser emparejados con un número equivalente de pacientes control. En las subcohortes emparejadas, no se apreció diferencia en el tiempo hasta el alta (log-rank: p = 0,291), ni en el cambio en la SAFI a las 48h desde la basal (glucocorticoides: −0,04; controles: +0,37; p = 0,095). Los modelos multivariantes mediante regresión de Cox mostraron un tiempo hasta el alta significativamente más largo en pacientes tratados con glucocorticoides (hazard ratio: 7,26; IC 95%: 3,30-15,95). CONCLUSIONES: No hemos encontrado mejoría en la función respiratoria o tiempo hasta el alta, asociado al uso de glucocorticoides a dosis altas


OBJECTIVE: To analyze whether there is an association between the use glucocorticoids at high doses, and the evolution of saturation/fraction of inspired oxygen (SAFI) or time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI in the first 48hours of treatment and the time to discharge. The results were compared between patients treated and untreated with glucocorticoids (methylprednisolone 1-2mg/kg/day o dexamethasone 20-40mg/day) through sub-cohort analyses matched for multiple clinical and prognostic factors, as well as through Cox multivariate models adjusted for prognostic factors. The simultaneous use of different treatments for COVID-19 was taken into account, both in sub-cohorts matching and in Cox regression. RESULTS: There were 187 patients treated with glucocorticoids; of these, 25 patients could be matched with an equivalent number of control patients. In the analysis of these matched sub-cohorts, no significant difference was observed in time to discharge (log-rank: p = 0.291) or the increment in SAFI at 48hours of treatment (glucocorticoides: −0.04; controls: +0.37; p = 0.095). Multivariate models using Cox regression showed a significantly longer time to discharge in patients treated with glucocorticoids (hazard ratio: 7.26; 95% IC: 3.30-15.95). CONCLUSIONS: We have not found improvement in respiratory function or time until discharge, associated with the use of glucocorticoids at high doses


Assuntos
Humanos , Masculino , Feminino , Idoso , Glucocorticoides/administração & dosagem , Alta do Paciente , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Oxigênio/administração & dosagem , Metilprednisolona/administração & dosagem , Dexametasona/administração & dosagem , Síndrome Respiratória Aguda Grave/tratamento farmacológico
14.
BMJ Case Rep ; 14(1)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495184

RESUMO

A 70-year-old man with medical history of IgG kappa multiple myeloma, initially diagnosed in 2017, underwent induction therapy with carfilzomib, lenalidomide and dexamethasone followed by autologous haematopoietic stem cell transplantation. Nine months following transplant, disease relapsed in the form of plasma cell leukaemia. Fluorescent in situ hybridisation of malignant plasma cells revealed t(11;14). A combination therapy including venetoclax was used based on efficacy data for Bcl-2 inhibitor venetoclax from available early-phase clinical trials in patients with relapsed multiple myeloma with t(11;14) and other published case studies. Unfortunately, the disease was primary refractory, and after further ineffective therapies, the patient did not have a successful outcome.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Plasmocitária/tratamento farmacológico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Dexametasona/administração & dosagem , Humanos , Hibridização in Situ Fluorescente , Lenalidomida/administração & dosagem , Leucemia Plasmocitária/diagnóstico por imagem , Leucemia Plasmocitária/genética , Leucemia Plasmocitária/patologia , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Oligopeptídeos/administração & dosagem , Proteínas de Fusão Oncogênica , Translocação Genética , Transplante Autólogo , Falha de Tratamento
15.
BMJ Case Rep ; 14(1)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509883
17.
Mar Drugs ; 19(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513822

RESUMO

Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the MUC5AC gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Dexametasona/farmacologia , Mucina-5AC/biossíntese , Mucina-5AC/efeitos dos fármacos , Quercetina/farmacologia , Células A549 , Anti-Inflamatórios/química , Antioxidantes/química , Dexametasona/química , Depuradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Magnésio/química , Mucina-5AC/genética , Mucinas/biossíntese , Mucinas/química , Nanopartículas , Tamanho da Partícula , Plantas/química , Polifosfatos/química , Quercetina/química , Espécies Reativas de Oxigênio
18.
PLoS One ; 16(1): e0243964, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33507958

RESUMO

OBJECTIVE: Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients. METHODS: This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification. RESULTS: HDCPT showed a statistically significant decrease in mortality (HR = 0.087 [95% CI 0.021-0.36]; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L). CONCLUSIONS: HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.


Assuntos
Corticosteroides/administração & dosagem , Síndrome da Liberação de Citocina/tratamento farmacológico , Adulto , Idoso , /mortalidade , Síndrome da Liberação de Citocina/imunologia , Dexametasona/farmacologia , Feminino , Hospitalização , Humanos , Inflamação/imunologia , Inflamação/prevenção & controle , Masculino , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Taxa de Sobrevida
19.
Niger J Clin Pract ; 24(1): 121-126, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33473037

RESUMO

Aim: To investigate the effect of intravitreal dexamethasone implant on central foveal thickness and choroidal thickness in retinal vein occlusion. Materials and Methods: Clinical records and optical coherence tomography (OCT) scans of 41 naïve patients with retinal vein occlusion (RVO), who were initially treated with intravitreal dexamethasone (DEX) implant between 2016 and 2017 at Kocatepe University Faculty of Medicine, Department of Ophthalmology were investigated. Collected data included age and sex of the patients, crystalline lens status, baseline and final intraocular pressure, and OCT parameters including central foveal thickness and choroidal thickness. Results: Twenty-two (53.7%) female and 19 (46.3%) male patients were enrolled in the study. There were 30 phakic and 11 pseudophakic patients. The intraocular pressure increased significantly from 15.19 mmHg to 17.8 mmHg (P = 0.005), and cataract extraction was performed in two patients who developed cataract after the treatment. There was a significant decrease in the central foveal thickness from 556 µm to 288 µm (P < 0.001). In addition, although there was no statistically significant change in choroidal thickness in the patients with branched retinal vein occlusion (P = 0.423), the patients with central retinal vein occlusion had statistically significant decrease in choroidal thickness measurements (P = 0.049). Conclusion: Therapeutic effect of the DEX implant not only influences retinal layer. Its influence may also extend further to the choroid layer, thereby leading to decrease in the choroidal thickness. Our results were mostly similar to the results of studies in literature which investigated the effects of the DEX implant therapy on the choroidal thickness of the patients with RVO.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Corioide , Dexametasona , Implantes de Medicamento/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Oclusão da Veia Retiniana/tratamento farmacológico , Resultado do Tratamento , Acuidade Visual
20.
Medicine (Baltimore) ; 100(2): e24122, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466183

RESUMO

OBJECTIVE: To assess the impact of intraoperative intravenous dexamethasone on the reduction of postoperative morbidity in children undergoing adenotonsillectomy. METHODS: A double blind randomized controlled trial conducted among children undergoing adenotonsillectomy at a tertiary hospital in Korea from November 2018 to June 2019. Children were randomly assigned to receive dexamethasone (0.5 mg/kg, maximum dose 24 mg) or placebo intravenously after induction of anesthesia. The primary endpoint was the reduction of postoperative pain and postoperative nausea and vomiting (PONV); secondary endpoints were adverse effects like postoperative hemorrhage. RESULTS: The study included 105 children, and 67 were male. Their mean age was 6.2 ±â€Š2.1 years. There was no significant difference between the groups in terms of demographic data or the operation time. The pain scores of the dexamethasone group were lower than those of the control group, but no significant difference was found (all P > .05). The average pain visual analog scale (VAS) during the study period (day 0-7) was 3.67 ±â€Š1.59 and 4.40 ±â€Š2.01 in the dexamethasone group and control group, respectively (P-value = .107). When we compared early pain VAS (day 0-2) and late pain VAS (day 5-7), the dexamethasone group showed significantly lower early mean VAS compared to the control group (4.55 ±â€Š1.78 vs 5.40 ±â€Š2.05, P-value = .046). The mean VAS for PONV was significantly lower in the dexamethasone group than in the control group (1.89 ±â€Š2.22 vs 3.00 ±â€Š2.37, P value = .044). CONCLUSION: In children undergoing adenotonsillectomy, dexamethasone decreased the early postoperative pain and PONV without increasing postoperative hemorrhage.


Assuntos
Adenoidectomia/efeitos adversos , Dexametasona/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Tonsilectomia/efeitos adversos , Adenoidectomia/métodos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Dor Pós-Operatória/etiologia , Pediatria/métodos , Náusea e Vômito Pós-Operatórios/etiologia , República da Coreia , Tonsilectomia/métodos , Escala Visual Analógica
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