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1.
Medicine (Baltimore) ; 100(35): e27138, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477165

RESUMO

RATIONALE: The emergence of immune checkpoint inhibitors has brought new breakthroughs in the treatment of small cell lung cancer (SCLC). Programmed cell death-ligand 1 inhibitors combined with chemotherapy have been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). However, programmed death 1 inhibitors have limited efficacy in the treatment of SCLC. The reason may be related to the abnormal vascular state in the tumor microenvironment. PATIENT CONCERNS: A 55-year-old male patient, presenting cough and sputum for 1 month. DIAGNOSES: The patient was clinically diagnosed with SCLC and staged as ES-SCLC. INTERVENTIONS: Etoposide combined with lobaplatin treatment every 3 weeks for 4 cycles, evaluate as progressive disease. On the basis of the original plan, combined with camrelizumab for 2 cycles, evaluation as progressive disease. Then, the patient was treated with intravenous infusion of camrelizumab plus oral anlotinib. After 4 cycles, evaluation as partial response. Then we continued to use camrelizumab combined with anlotinib treatment for the patient. At the end of 26 cycles, the chest computed tomography examination revealed that the patient had achieved complete remission. OUTCOMES: After treated with carrelizumab combined with anlotinib for 26 cycles, the curative effect was evaluated as complete remission, progression-free survival was 24 months and there was no immune-related adverse reaction during treatment period. Besides, the patient developed complicated hand-foot syndrome, but this symptom was significantly relieved after reducing the dosage of anlotinib. LESSONS: In this case, antiangiogenesis combined with programmed death 1 inhibitors significantly inhibited tumor progression. It also indicated that anlotinib concurrent carrelizumab may be a superior choice for ES-SCLC. Further clinical trials required to confifirm its effificacy and safety.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinolinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Carcinoma de Pequenas Células do Pulmão/induzido quimicamente , Tomografia Computadorizada por Raios X
2.
Int J Colorectal Dis ; 36(10): 2081-2092, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34467414

RESUMO

BACKGROUND: The effect of preoperative vedolizumab (VDZ) therapy on postoperative complications in inflammatory bowel disease (IBD) patients is still controversial. This meta-analysis aims to review postoperative complications of IBD patients who preoperatively received VDZ. METHODS: A meta-analysis of the available literature was performed. Studies of IBD patients who received VDZ and non-VDZ therapy (including anti-TNF-α agents, non-biological therapy, other biological agents, ustekinumab, and placebo) before surgery were included. Primary outcomes included overall complications, infectious complications, and non-infectious complications. RESULTS: Twelve studies with 1925 IBD patients were enrolled, among which 709 patients received VDZ treatment. The results show that, compared with non-VDZ treatment, there is no significant difference in the incidence of overall complications (OR = 1.25, p = 0.43) for adult IBD patients treated with VDZ preoperatively, the incidence of infectious complications (OR = 0.49, p = 0.001) decreases, but the risks of all surgical site infection (SSI) (Crohn's disease (CD): OR = 2.97, p < 0.001), superficial surgical site infection (sSSI) (OR = 2.24, p = 0.02), and ileus (OR = 2.16, p < 0.001) increase. The risk of mucocutaneous separation (MCS) (OR = 4.69, p = 0.03) with VDZ is also higher than non-VDZ. Two studies involved pediatric patients and showed no difference in ileus (OR = 0.55, p = 0.55). CONCLUSIONS: Overall, compared with non-VDZ treatment, preoperative use of VDZ is relatively safer in adult IBD patients, which does not increase the risk of overall postoperative complications and reduces the occurrence of infectious complications. But, it increases the risk of all SSI and sSSI in infectious complications and the incidence of ileus and MCS in non-infectious complications. Due to lack of sufficient data, the safety of VDZ in pediatric patients is uncertain and requires further study.


Assuntos
Doenças Inflamatórias Intestinais , Inibidores do Fator de Necrose Tumoral , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
3.
Anticancer Res ; 41(9): 4555-4562, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475083

RESUMO

BACKGROUND/AIM: While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored. PATIENTS AND METHODS: Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed. RESULTS: All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one. CONCLUSION: Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
9.
Front Immunol ; 12: 720205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504497

RESUMO

Patients with the monogenic immune dysregulatory syndrome autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene, uniformly carry neutralizing autoantibodies directed against type-I interferons (IFNs) and many develop autoimmune pneumonitis, both of which place them at high risk for life-threatening COVID-19 pneumonia. Bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target the SARS-CoV-2 spike protein and block entry of SARS-CoV-2 in host cells. The use of bamlanivimab and etesevimab early during infection was associated with reduced COVID-19-associated hospitalization and death in patients at high risk for progressing to severe disease, which led the US Food and Drug Administration to issue an emergency use authorization for their administration in non-hypoxemic, non-hospitalized high-risk patients. However, the safety and efficacy of these mAbs has not been evaluated in APECED patients. We enrolled two siblings with APECED on an IRB-approved protocol (NCT01386437) and admitted them prophylactically at the NIH Clinical Center for evaluation of mild-to-moderate COVID-19. We assessed the safety and clinical effects of early treatment with bamlanivimab and etesevimab. The administration of bamlanivimab and etesevimab was well tolerated and was associated with amelioration of COVID-19 symptoms and prevention of invasive ventilatory support, admission to the intensive care, and death in both patients without affecting the production of antibodies to the nucleocapsid protein of SARS-CoV-2. If given early in the course of COVID-19 infection, bamlanivimab and etesevimab may be beneficial in APECED and other high-risk patients with neutralizing autoantibodies directed against type-I IFNs.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , COVID-19/tratamento farmacológico , Poliendocrinopatias Autoimunes/tratamento farmacológico , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , COVID-19/complicações , COVID-19/genética , COVID-19/imunologia , Feminino , Humanos , Interferons/genética , Interferons/imunologia , Masculino , Mutação , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia
12.
J Coll Physicians Surg Pak ; 31(1): S7-S10, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34530530

RESUMO

OBJECTIVE: To determine the effects of tocilizumab (TCZ) on inflammatory markers, laboratory indices; and short-term outcome in patients with severe COVID-19. STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Hayatabad Medical Complex, Peshawar, Pakistan from 10th June till 31st August 2020. METHODOLOGY: Fifty-four patients with severe COVID-19 fulfilled the inclusion criteria and were included. All patients had received TCZ (4 mg/kg) in addition to standard treatment. Serum C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer levels, full blood count, and liver function tests (LFTs) were checked before and 24 hours after receiving TCZ. Short-term outcome, defined as survival at day 28, was determined from hospital record/telephonic contact. Paired t-test was employed to assess the statistical significance of mean differences between the pre- and post-TCZ variables, considering a p-value of <0.05 as significant. RESULTS: Overall, the mean pre- and post-TCZ CRP was 18.7 ± 10.7 and 10.2 ± 8.6 mg/dl (p <0.001). It was 18.0 ± 10.3 and 10.3 ± 8.8 mg/dl (p=0.003) in survivors; and 19.4 ± 11.4 and 10.2 ± 8.7 mg/dl (p=0.005) in non-survivors, respectively. Overall, mean D-dimer level decreased from 12.5 ± 23 to 10.3 ± 12.2 µg/ml following TCZ (p=0.643); it decreased from 15.8 ± 29.8 to 11.4 ± 10.6 µg/ml (p=0.612) in survivors; and 9.0 ± 12.8 to 9.2 ± 14.1 µg/ml (p=0.961) in non-survivors, respectively. There were no significant differences in the pre- and post-TCZ LDH levels overall and between the groups. The 28-day mortality was 46.3%. CONCLUSION: Tocilizumab results in a significant reduction in CRP, while mean change in LDH and D-dimers was not substantial. The mean change in inflammatory markers did not predict survival. Key Words: Tocilizumab, COVID-19, Biomarkers, Outcome, Mortality.


Assuntos
COVID-19 , Anticorpos Monoclonais Humanizados , Biomarcadores , COVID-19/tratamento farmacológico , Estudos Transversais , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Sobreviventes
16.
Artigo em Inglês | MEDLINE | ID: mdl-34501738

RESUMO

BACKGROUND: Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called "cytokine storm" related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. METHODS: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. RESULTS: Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55-1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53-9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38-37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38-0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06-0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36-0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34-1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001-5.54], p = 0.050; based on unadjusted estimates). CONCLUSION: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.


Assuntos
COVID-19 , Pandemias , Anticorpos Monoclonais Humanizados , COVID-19/tratamento farmacológico , Humanos , SARS-CoV-2 , Padrão de Cuidado , Resultado do Tratamento
17.
Gan To Kagaku Ryoho ; 48(9): 1169-1171, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521798

RESUMO

Ramucirumab monotherapy is one of the conditionally recommended regimens in second-line chemotherapy for advanced gastric cancer. However, there are few clinical data on ramucirumab monotherapy in Japanese patients. Herein, we present 4 case reports of advanced gastric cancer patients who received ramucirumab monotherapy. The 4 patients' age ranged from 65-81 years old(median: 70 years old), with a 3:1 male to female ratio. Since all cases were in poor performance status, administration of cell-killing anticancer drugs such as paclitaxel was contraindicated, and ramucirumab monotherapy was selected as an alternative. Ramucirumab was administrated 2-8 times(median: 3 times), resulting to a stable disease in 1 patient, and progression-free survival was noted to be 3-16 weeks(median: 5 weeks). Regarding complications, Grade 2 hypertension occurred in 1 patient, and no serious adverse events were observed. Ramucirumab monotherapy is a well-tolerated second-line chemotherapy for patients with advanced gastric cancer in poor performance status, and it is expected to have some disease control effect.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico
18.
Sultan Qaboos Univ Med J ; 21(3): 488-490, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34522419

RESUMO

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system that shares similar immunopathogenic mechanisms with chronic plaque psoriasis, such as the overexpression of the Th17 pathway. We report a 50-year-old male patient with MS and severe chronic plaque psoriasis who presented to Hospital Virgen de la Victoria, Málaga, Spain, in 2019. He was successfully treated with ixekizumab (anti-interleukin [IL]-17A and IL-17A/F monoclonal antibody). The treatment achieved complete skin clearance (i.e. a Psoriasis Area Severity Index 100 response) with no adverse event and no evidence of progression of the neurological disease either.


Assuntos
Fármacos Dermatológicos , Esclerose Múltipla , Psoríase , Anticorpos Monoclonais Humanizados , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Blood Adv ; 5(17): 3387-3396, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477818

RESUMO

The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti-PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or ≥4 prior anticancer treatments, respectively. Target occupancy of >90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post-allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials.gov as #NCT02603419.


Assuntos
Doença de Hodgkin , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Doença de Hodgkin/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Microambiente Tumoral
20.
Ann Palliat Med ; 10(8): 9267-9275, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488412

RESUMO

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.


Assuntos
Apendicite , Colestase , Neoplasias Pulmonares , Pneumonia , Idoso , Anticorpos Monoclonais Humanizados , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico
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