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1.
Nat Commun ; 12(1): 5954, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642329

RESUMO

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamento farmacológico , Ipilimumab/administração & dosagem , Carcinomatose Meníngea/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Anorexia/induzido quimicamente , Anorexia/mortalidade , Anorexia/patologia , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Colite/induzido quimicamente , Colite/mortalidade , Colite/patologia , Exantema/induzido quimicamente , Exantema/mortalidade , Exantema/patologia , Fadiga/induzido quimicamente , Fadiga/mortalidade , Fadiga/patologia , Feminino , Febre/induzido quimicamente , Febre/mortalidade , Febre/patologia , Hepatite/etiologia , Hepatite/mortalidade , Hepatite/patologia , Humanos , Ipilimumab/efeitos adversos , Masculino , Carcinomatose Meníngea/mortalidade , Carcinomatose Meníngea/patologia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/mortalidade , Náusea/patologia , Nivolumabe/efeitos adversos , Análise de Sobrevida
2.
Curr Oncol ; 28(5): 3537-3553, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34590600

RESUMO

The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome has the potential to worsen and can result in hypotension secondary to dehydration and associated organ-related complications. Furthermore, premature treatment discontinuation may result in a reduction in progression-free and overall survival. Despite existing guidance, there is still a wide variety of therapeutic approaches suggested in the literature for both the definition and management of dabrafenib and trametinib-related pyrexia. This is reflected in the practice variation of its prevention and treatment within and between Canadian cancer centres. A Canadian working group was formed and consensus statements were constructed based on evidence and finalised through a two-round modified Delphi approach. The statements led to the development of a pyrexia treatment algorithm that can easily be applied in routine practice. The Canadian working group consensus statements serve to provide practical guidance for the management of dabrafenib and trametinib-related pyrexia, hopefully leading to reduced discontinuation rates, and ultimately improve patients' quality of life and cancer-related outcomes.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Canadá , Consenso , Febre/induzido quimicamente , Febre/tratamento farmacológico , Humanos , Imidazóis , Mutação , Oximas , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas , Pirimidinonas
3.
J Postgrad Med ; 67(3): 158-163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34427280

RESUMO

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a severe, potentially life-threatening drug-induced hypersensitivity reaction characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with eosinophilia and elevated liver enzymes. The severity and potential organ damage associated with DRESS mandates withdrawing the offending drug and provide a suitable replacement. We report a 55-year-old man who developed prolonged fever, generalized maculopapular rash and facial edema after 3 weeks of starting imatinib for chronic myeloid leukemia (CML). A diagnosis of DRESS was confirmed by eosinophilia and skin biopsy findings, along with a consistent RegiSCAR score. Imatinib was stopped and he was initiated on low-dose steroids, which led to complete resolution of rash and eosinophilia. A rechallenge with imatinib was positive, and he was switched to dasatinib for further therapy, following which he attained an optimal molecular response. DRESS following imatinib has only been reported in eight patients so far. In this report we summarize the current evidence for managing DRESS and its impact on the treatment of CML.


Assuntos
Antineoplásicos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Angioedema/induzido quimicamente , Eosinofilia/induzido quimicamente , Exantema/induzido quimicamente , Febre/induzido quimicamente , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
J Korean Med Sci ; 36(27): e196, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34254475

RESUMO

BACKGROUND: This is an observational study to analyze an emergency department (ED) utilization pattern of coronavirus disease 2019 (COVID-19) vaccinated in-hospital healthcare workers (HCWs). METHODS: We included 4,703 HCWs who were administered the first dose of the COVID-19 vaccine between March 4 and April 2, 2021, in a tertiary hospital in Korea where fast-track and post-vaccination cohort zone (PVCZ) were introduced in ED. We analyzed data of participants' age, sex, occupation, date and type of vaccination, and their clinical information using SPSS v25.0. RESULTS: The sample comprised HCWs, who received either the ChAdOx1 (n = 4,458) or the BNT162B2 (n = 245) vaccines; most participants were female (73.5%), and 81.1% were under 50 years old. Further, 153 (3.3%) visited the ED and reported experiencing fever (66.9%) and myalgia (56.1%). Additionally, 91 (59.5%) of them were in their 20s, and 106 (67.5%) were assigned to the PVCZ. Lastly, 107 (68.2%) of the patients received parenteral management. No patient required hospitalization. CONCLUSION: In conclusion, vaccinated HCWs who visited the ED with adverse events had a high incidence of fever and a low likelihood of developing serious illnesses. As the COVID-19 vaccination program for Korean citizens continues to expand, strategies to minimize unnecessary ED overcrowding should be put into effect.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Recursos Humanos em Hospital/estatística & dados numéricos , Vacinação/efeitos adversos , Adulto , Antieméticos/uso terapêutico , Antipiréticos/uso terapêutico , Teste para COVID-19/estatística & dados numéricos , Calafrios/induzido quimicamente , Calafrios/epidemiologia , Protocolos Clínicos , Serviço Hospitalar de Emergência/organização & administração , Feminino , Febre/induzido quimicamente , Febre/tratamento farmacológico , Febre/epidemiologia , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Mialgia/epidemiologia , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , República da Coreia , Estudos Retrospectivos , Design de Software , Centros de Atenção Terciária/estatística & dados numéricos , Triagem , Adulto Jovem
6.
Expert Rev Vaccines ; 20(8): 1013-1025, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34180347

RESUMO

INTRODUCTION: Several vaccine candidates have been developed using different platforms, including nucleic acids (DNA and RNA), viral vectors (replicating and non-replicating), virus-like particles, peptide-based, recombinant proteins, live attenuated, and inactivated virus modalities. Although many of these vaccines are undergoing pre-clinical trials, several large clinical trials investigating the clinical efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines have produced promising findings. AREAS COVERED: In this review, we provide a status update on COVID-19 vaccines currently undergoing clinical trials and discuss issues of concern beyond vaccine efficacy and safety, including dosing regimens, the mixed vaccine strategy, prior severe acute respiratory syndrome coronavirus-2 infection, antibody levels, cellular immunity and protection, variants of concern, COVID-19 vaccine distribution, vaccination willingness, herd immunity, immunity passports, and vaccine indications. EXPERT OPINION: Four vaccines have obtained emergency use authorization, 87 are at the clinical development stage, and 186 are in pre-clinical development. While the knowledge and development of COVID-19 vaccines is rapidly expanding, the benefits of COVID-19 vaccines must outweigh the potential risks of adverse events. To combat the COVID-19 pandemic, clinicians should consistently update COVID-19-associated information, and healthcare authorities and manufacturers should work together to provide adequate and appropriate vaccinations for the prevention of COVID-19. PLAIN LANGUAGE SUMMARY: What is the context?Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic: the coronavirus disease 2019 (COVID-19) outbreak. The development and implementation of the COVID-19 vaccine could be an important measure to control the COVID-19 pandemic.What is new?Several phase 3 clinical trials have demonstrated the effectiveness and safety of COVID-19 vaccines for the prevention of SARS-CoV-2 infections. Several COVID-19 vaccines have obtained emergency use authorization and been implemented in many countries. Although concerns regarding unusual blood clots and low platelet counts have been raised, the benefits of COVID-19 vaccines outweigh the potential risks of adverse events.What is the impact?Except for children, the COVID-19 vaccine is recommended for all people, including those pregnant or immunocompromised. Healthcare authorities should advise people receiving the vaccine that they must seek medical attention if they have associated thromboembolism and thrombocytopenia symptoms. More studies are necessary to determine the appropriate vaccine dose and regimen strategy, as well as the effectiveness of COVID-19 vaccines against variants of concerns. A global effort must be made to achieve widespread vaccination and herd immunity.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Segurança do Paciente , Animais , COVID-19/epidemiologia , Ensaios Clínicos Fase III como Assunto/métodos , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/fisiologia , Masculino , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
7.
Cancer Chemother Pharmacol ; 88(2): 173-188, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33877390

RESUMO

PURPOSE: Conditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury. METHODS: Male Wistar rats were treated with 4-8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation. RESULTS: Melphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms. CONCLUSION: We developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success.


Assuntos
Febre/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias/induzido quimicamente , Melfalan/efeitos adversos , Microbiota/efeitos dos fármacos , Animais , Translocação Bacteriana , Ácidos e Sais Biliares/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Inflamação/induzido quimicamente , Masculino , Neutropenia/induzido quimicamente , Ratos , Ratos Wistar , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos
8.
Anticancer Res ; 41(3): 1485-1496, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788741

RESUMO

BACKGROUND: As the prognosis of biliary tract cancer (BTC) is extremely poor and treatment options are limited, new treatment modalities are urgently needed. We designed a phase II clinical trial to investigate the immune responses and clinical benefits of OCV-C01, an HLA-A*24:02-restricted three-peptide cancer vaccine targeting VEGFR1, VEGFR2, and KIF20A. PATIENTS AND METHODS: Participants were patients with advanced BTC who had unresectable tumours and were refractory to standard chemotherapy. OCV-C01 was injected weekly until the discontinuance criteria were met. RESULTS: Six participants, including four patients positive for HLA-A*24:02, were enrolled in this study for assessment of efficacy. Four out of six patients exhibited vaccine-specific T-cell responses to one or more of three antigens. Log-rank tests revealed that vaccine-specific T cell responses contributed significantly to overall survival. CONCLUSION: The cancer vaccine had positive effects on survival, indicating that this approach warrants further clinical studies.


Assuntos
Neoplasias do Sistema Biliar/tratamento farmacológico , Vacinas Anticâncer/administração & dosagem , Cinesina/antagonistas & inibidores , Vacinas de Subunidades/administração & dosagem , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/imunologia , Neoplasias do Sistema Biliar/metabolismo , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Intervalo Livre de Doença , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Cinesina/imunologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Prognóstico , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Vacinas de Subunidades/efeitos adversos , Vacinas de Subunidades/imunologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia
9.
Int J Infect Dis ; 106: 33-35, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33746092

RESUMO

As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.


Assuntos
Amidas/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/imunologia , Febre/induzido quimicamente , Ativação Linfocitária/efeitos dos fármacos , Pirazinas/efeitos adversos , Amidas/farmacologia , Amidas/uso terapêutico , COVID-19/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Carga Viral/efeitos dos fármacos
10.
Cancer Med ; 10(6): 1944-1954, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33638305

RESUMO

BACKGROUND: Temsirolimus is an mTOR antagonist with proven anticancer efficacy. Preclinical data suggest greater anticancer effect when mTOR inhibitors are combined with cytotoxic chemotherapy. We performed a Phase I assessment of the combination of temsirolimus and capecitabine in patients with advanced solid tumors. METHODS: Patients were enrolled in an alternating dose escalation of temsirolimus (at 15 or 25 mg IV weekly) and capecitabine (at 750, 1000, and 1250 mg/m2 twice daily) in separate Q2-week and Q3-week cohorts. At the recommended Phase II doses (RP2Ds) of temsirolimus and capecitabine (Q2), seven patients were also treated with oxaliplatin (85 mg/m2 , day 1) to determine triplet combination safety and efficacy. RESULTS: Forty-five patients were enrolled and 41 were evaluable for dose-limiting toxicities (DLTs). The most common adverse events (AEs) were mucositis, fatigue, and thrombocytopenia. The most common grade 3/4 AEs were hypophosphatemia and anemia. Five patients had DLTs, including hypophosphatemia, mucositis, and thrombocytopenia. The RP2Ds were temsirolimus 25 mg +capecitabine 1000 mg/m2 (Q2); and temsirolimus 25 mg +capecitabine 750 mg/m2  (Q3). Of the 38 patients evaluable for response, one had a partial response (PR) and 19 had stable disease (SD). The overall disease control rate was 52%. Five of the 20 patients with SD/PR maintained disease control for >6 months. CONCLUSIONS: The combination of temsirolimus and capecitabine is safe on both a Q2-week and a Q3-week schedule. The combination demonstrated promising evidence of disease control in this highly refractory population and could be considered for testing in disease-specific phase II trials.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias/tratamento farmacológico , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Humanos , Hipofosfatemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Neoplasias/patologia , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
11.
J Dermatol ; 48(5): 707-709, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33600004

RESUMO

The combination of BRAF inhibitor and MEK inhibitor is one of the first-line treatments for unresectable BRAF-mutant melanoma or as an adjuvant therapy. However, some patients who received the combination of dabrafenib and trametinib (CombiDT) or the combination of encorafenib and binimetinib (CombiEB) had adverse events (AEs) including pyrexia. We herein report a patient with BRAF-mutated melanoma who repeatedly developed elevated levels of D-dimer and pyrexia after CombiDT and CombiEB treatments. Moreover, concomitant edoxaban prevented these AEs, enabling the patient to continue receiving CombiEB.


Assuntos
Melanoma , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Febre/induzido quimicamente , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Quinases de Proteína Quinase Ativadas por Mitógeno , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Piridinas , Piridonas/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Sulfonamidas/uso terapêutico , Tiazóis
12.
J Ethnopharmacol ; 271: 113915, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567308

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aeginetia indica (Linn.), commonly known as aankuri bankuri, guan-jen-huang, forest ghost flower, dok din daeng, dapong tubo; is a root parasitic plant of the Orobanchaceae family native to South and South-East Asian region. Different parts of the plant are traditionally used to treat fever, pain, inflammation, arthritis, cough, diabetes, and chronic liver disease. Local practitioners often recommend this plant as a folk remedy for dermal swelling, painful menstrual periods, wounds, and knee pain. However, the antipyretic and analgesic activity of A. indica have never been investigated. AIM OF THE STUDY: The present study was aimed to evaluate the analgesic and antipyretic potential of Aeginetia indica plant extract to verify its effectiveness as reported in traditional uses. MATERIALS AND METHODS: Preliminary phytochemical analysis of Aeginetia indica crude extract was performed using previously established methods and antioxidant capacity was determined by phosphomolybdenum assay. In vivo analgesic activity of Aeginetia indica methanol extract (AiME) was evaluated by acetic acid-induced writhing test, formalin-induced paw licking test, and hot plate test model. The antipyretic activity was studied in Baker's yeast induced pyrexia model. RESULTS: Phytochemicals screening revealed cardiac glycosides, saponins, phenols, tannins, and flavonoids in the crude extract of Aeginetia indica. Total phenolic and flavonoid content were recorded as 101 ± 1.1 mg GAE/g of the extract and 35 ± 0.8 mg QE/g of the extract, respectively. The total antioxidant capacity observed in phosphomolybdenum assay was 68.3 ± 1.3 mg ascorbic acid equivalent per gram of the extract. AiME showed significant dose-dependent analgesic activity against acetic acid-induced writhing, formalin-induced paw licking, and hot plate pain model. A higher dose of A. indica (200 mg/kg) produced significant (P < 0.001) inhibition of writhing by 69% whereas, standard aspirin showed maximum 85.6% inhibition. AiME at all doses showed a significant (P < 0.001) decrease of paw licking time in both early neurogenic and late inflammatory pain phase of formalin-induced licking test. In the hot plate test, AiME at a 200 mg/kg dose produced antinociceptive activity (55.18%) higher than the standard ketorolac (49.88%) at 1 h. However, after 2 h, ketorolac showed a maximum effect of 62.66% and AiME 200 mg/kg showed a 60.24% effect. A significant (P < 0.001) reduction of rectal temperature (4.54 °F↓) was recorded for AiME 200 mg/kg, which was higher than the standard paracetamol (3.86 F°↓) after 24 h of treatment. CONCLUSION: The in vivo investigational studies' results demonstrated promising analgesic and antipyretic activities of A. indica, which supported the claim of its folk uses.


Assuntos
Analgésicos/farmacologia , Antipiréticos/farmacologia , Orobanchaceae/química , Extratos Vegetais/farmacologia , Ácido Acético/toxicidade , Analgésicos/uso terapêutico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antipiréticos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Febre/induzido quimicamente , Febre/tratamento farmacológico , Flavonoides/análise , Medicina Tradicional , Metanol/química , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Fenóis/análise , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico
13.
Intern Med ; 60(7): 1115-1117, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33583886

RESUMO

A 55-year-old Japanese man was hospitalized with the novel coronavirus disease 2019 (COVID-19). On the 14th day after the start of favipiravir administration, the patient developed a fever with a temperature of 38.1°C. His pulse rate also became elevated to 128 bpm, so relative bradycardia was not suspected. Since he was in good overall health and no concomitant symptoms and signs were apparent, we considered it to be drug fever due to favipiravir. After the completion of favipiravir treatment, the patient's temperature normalized within 24 hours. We herein report this case of drug fever caused by favipiravir.


Assuntos
COVID-19 , Preparações Farmacêuticas , Amidas , Antivirais/efeitos adversos , Febre/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas , SARS-CoV-2
14.
Am J Hematol ; 96(6): 735-746, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625753

RESUMO

Differentiation Syndrome (DS) has been identified in a subset of patients undergoing treatment with novel classes of differentiating therapies for acute myeloid leukemia (AML) such as IDH and FLT3 inhibitors. While DS is a well-known treatment-related complication in acute promyelocytic leukemia (APL), efforts are still ongoing to standardize diagnostic and treatment parameters for DS in AML. Though the rates of incidence vary, many of the signs and symptoms of DS are common between APL and AML. So, DS can lead to fatal complications in AML, but prompt management is usually effective and rarely necessitates interruption or discontinuation of AML therapy.


Assuntos
Antineoplásicos/efeitos adversos , Síndrome da Liberação de Citocina/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológico , Mielopoese/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Corticosteroides/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Trióxido de Arsênio/efeitos adversos , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Edema/induzido quimicamente , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Epigênese Genética/efeitos dos fármacos , Febre/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Isocitrato Desidrogenase/antagonistas & inibidores , Leucemia Mieloide Aguda/complicações , Terapia de Alvo Molecular/efeitos adversos , Proteínas de Neoplasias/antagonistas & inibidores , Derrame Pleural/induzido quimicamente , Transtornos Respiratórios/induzido quimicamente , Tretinoína/efeitos adversos , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores
15.
J Mother Child ; 24(3): 45-48, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33470957

RESUMO

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction, which, due to the asymptomatic beginning and non-specific nature of symptoms, is hard to identify. This report presents the case of a 7-year-old boy, who was referred to the Department of Paediatric Surgery with fever up to 38°C, vomiting and diarrhoea, accompanied by erythematous, maculopapular rash. Based on laboratory and radiology tests and specific diagnostic criteria, DRESS syndrome was diagnosed. The presented case report emphasises the need to carry out differential diagnosis, including the potentially life-threatening DRESS syndrome, with common symptoms in children such as fever and rash.


Assuntos
Antibacterianos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Eosinofilia/induzido quimicamente , Exantema/induzido quimicamente , Febre/induzido quimicamente , Metilprednisolona/uso terapêutico , Criança , Diagnóstico Diferencial , Humanos , Masculino , Polônia , Resultado do Tratamento
17.
Eur J Clin Pharmacol ; 77(3): 275-289, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33025080

RESUMO

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this review, we try to summarize reports of antibacterial antibiotic-induced DRESS focusing on characteristics of DRESS induced by each antibiotic group. METHODS: The data were collected by searching PubMed/MEDLINE and ScienceDirect. The keywords used as search terms were "DRESS syndrome," "drug-induced hypersensitivity syndrome (DIHS)," "antibiotics," "antimicrobial," and names of various antimicrobial groups. Finally, 254 relevant cases with a definite or probable diagnosis of DRESS based on RegiSCAR criteria were found until 30 May 2020 and reviewed. RESULTS AND CONCLUSION: Totally, 254 cases of antibacterial antibiotic-induced DRESS are reported. Most of them are related to antituberculosis drugs, vancomycin, and sulfonamides, respectively. Rash and fever were most frequent clinical findings. Eosinophilia and liver injury were the most reported hematologic and visceral organ involvement, respectively. Most of the patients are managed with systemic corticosteroids. The death occurred in 16 patients which most of them experienced liver or lung involvement. The reactivation of various viruses especially HHV-6 is reported in 33 cases. The mean latency period was 29 days. It is necessary to perform thorough epidemiological, genetic, and immunological studies, also systematic case review and causality assessment, as well as well-designed clinical trials for better management of antibiotic-induced DRESS.


Assuntos
Antibacterianos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Corticosteroides/administração & dosagem , Antibacterianos/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/fisiopatologia , Febre/induzido quimicamente , Humanos , Fatores de Tempo
18.
J Oncol Pharm Pract ; 27(5): 1307-1310, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33028131

RESUMO

INTRODUCTION: Sweet Syndrome, also known as acute febrile neutrophilic dermatosis, is a rare inflammatory disease characterized by the sudden emergence of painful, edematous, and erythematous papules, plaques, or nodules on the skin, which usually fully responsive to systemic corticosteroids. Skin lesions are often accompanied by fever and leukocytosis. Here we present a case of Sweet Syndrome caused by pemetrexed in metastatic lung adenocarcinoma. CASE REPORT: A 52-year-old patient with metastatic lung adenocarcinoma received multiple lines of chemotherapy. The patient presented with extensive skin lesions after performing of pemetrexed chemotherapy. He had a fever and elevations in blood levels of C-reactive protein (CRP), sedimentation, leucocytes, and neutrophils. Neutrophil predominant perivascular and interstitial dermatitis, focal micropustule formation, and severe neutrophilic dermatosis were reported in skin biopsy. Topical steroid and oral antihistamine treatment were started as initial treatment.Discussion and conclusions: Cutaneous side effects related to pemetrexed are often reported as 'skin rash,' which is a non-specific term. Therefore, the diagnosis of Sweet Syndrome must be confirmed by skin biopsy. It is essential to exclude the presence of an infection and medication history. Recovery in drug-induced Sweet Syndrome occurs after the drug that caused it was discontinued. Systemic corticosteroids are the first-line treatment for most cases.


Assuntos
Pemetrexede/efeitos adversos , Síndrome de Sweet/induzido quimicamente , Biópsia , Feminino , Febre/induzido quimicamente , Humanos , Leucocitose/induzido quimicamente , Pessoa de Meia-Idade , Neutrófilos/citologia , Pele/patologia
19.
Inflammation ; 44(1): 270-277, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32886268

RESUMO

Plasma gelsolin (pGSN) is the secreted isoform of an intracellular actin remodeling protein found in high concentrations in human plasma. Clinical studies demonstrate reduced pGSN concentrations in several disease states, including severe trauma, burns, and sepsis. Markedly decreased pGSN concentrations in these conditions precede and predict adverse clinical outcomes. In this study, we measured pGSN in patients with chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent infections and dysregulated inflammation. pGSN was quantified using a sandwich ELISA in plasma from healthy volunteers, clinically stable CGD patients, and X-linked CGD carriers and in sera from 12 CGD patients undergoing bone marrow transplantation. pGSN was also quantified in healthy volunteers challenged with intravenous endotoxin. pGSN concentrations were lower in CGD patients without active infection or systemic inflammation compared with healthy control subjects. In CGD patients undergoing bone marrow transplantation, pGSN concentrations increased significantly following successful transplant. X-linked carriers of CGD had normal pGSN. Despite reduction of pGSN in CGD patients, we did not detect significant changes in pGSN over 24 h following challenge of healthy volunteers with intravenous endotoxin (4 ng/kg) that elicited a febrile response. We describe, for the first time, significantly lower pGSN in clinically stable patients with CGD compared with age- and sex-matched healthy volunteers. Low pGSN levels in CGD patients significantly increased following bone marrow transplantation. X-linked carriers of CGD had normal pGSN. In healthy volunteers challenged with intravenous endotoxin, pGSN is not an acute phase reactant.


Assuntos
Gelsolina/sangue , Doença Granulomatosa Crônica/sangue , Doença Granulomatosa Crônica/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Transplante de Medula Óssea/métodos , Estudos de Coortes , Endotoxinas/toxicidade , Feminino , Febre/sangue , Febre/induzido quimicamente , Febre/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Inflammation ; 44(1): 321-333, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32875489

RESUMO

Sex differences in the immune response can also affect the febrile response, particularly the fever induced by lipopolysaccharide (LPS). However, other pathogen-associated molecular patterns, such as zymosan A (Zym) and polyinosinic-polycytidylic acid (Poly I:C), also induce fever in male rats with a different time course of cytokine release and different mediators such as endothelin-1 (ET-1). This study investigated whether female sex hormones affect Zym- and Poly I:C-induced fever and the involvement of ET-1 in this response. The fever that was induced by Zym and Poly I:C was higher in ovariectomized (OVX) female rats compared with sham-operated female rats. Estrogen replacement in OVX females reduced Zym- and Poly I:C-induced fever. The ETB receptor antagonist BQ788 reversed the LPS-induced fever in cycling females but not in OVX females. BQ788 did not alter the fever that was induced by Zym or Poly I:C in either cycling or OVX females. These findings suggest that the febrile response in cycling females is lower, independently of the stimulus that is inducing it and is probably controlled by estrogen. Also, ET-1 seems to participate in the febrile response that was induced by LPS in males and cycling females but not in the LPS-induced fever in OVX females. Additionally, ET-1 was not involved in the febrile response that was induced by Zym or Poly I:C in females.


Assuntos
Endotelina-1/metabolismo , Febre/induzido quimicamente , Febre/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Poli I-C/toxicidade , Zimosan/toxicidade , Animais , Endotelina-1/antagonistas & inibidores , Feminino , Injeções Intraventriculares , Masculino , Ovariectomia/tendências , Poli I-C/administração & dosagem , Ratos , Ratos Wistar , Zimosan/administração & dosagem
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