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IntroductionPembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.MethodsEligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)–positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review.ResultsEighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5–48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4–29.4); two patients had complete response (one with a PD-L1–positive tumor), and 14 patients had partial response (13 with PD-L1–positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.ConclusionsPembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.  相似文献   
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目的:观察非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)患者自体造血干细胞移植(autologous hematopoietic stem cell transplantation,ASCT)术后应用重组人α-2b干扰素(α-2b IFN)进行早期干预治疗的临床疗效。方法:选取18例行ASCT的NHL患者为研究对象,移植前疾病评估均未达到完全缓解(complete remission,CR),试验组血象恢复后给予IFN 3 000 000 U次/隔日干预治疗,3个月后停用;对照组未行干扰素干预治疗,分析总体疗效及两组对比的生存情况。结果:随访中位时间为34(10~50)个月,患者中位生存时间为37(31~45)个月,3年总体无进展生存(progressive free survival,PFS)、总生存(overall survivial,OS)分别为54.7%、66.8%。ASCT后试验组1年内无疾病复发,2年内复发率为12.5%;对照组1年内复发率为20%,2年内复发率为30%。结论:NHL患者在ASCT后给予重组人α-2b IFN早期干预治疗,患者耐受性好,可能降低移植后早期复发率。  相似文献   
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Objectives

Expedient extubation after cardiac surgery has been associated with improved outcomes, leading to postoperative extubation frequently during overnight hours. However, recent evidence in a mixed medical-surgical intensive care unit population demonstrated worse outcomes with overnight extubation. This study investigated the impact of overnight extubation in a statewide, multicenter Society of Thoracic Surgeons database.

Methods

Records from 39,812 patients undergoing coronary artery bypass grafting or valve operations (2008-2016) and extubated within 24 hours were stratified according to extubation time between 06:00 and 18:00 (day) or between 18:00 and 6:00 (overnight). Outcomes including reintubation, mortality, and composite morbidity-mortality were evaluated using hierarchical regression models adjusted for Society of Thoracic Surgeons predictive risk scores. To further analyze extubation during the night, a subanalysis stratified patients into 3 groups: 06:00 to 18:00, 18:00 to 24:00, and 24:00 to 06:00.

Results

A total of 20,758 patients were extubated overnight (52.1%) and were slightly older (median age 66 vs 65 years, P < .001) with a longer duration of ventilation (4 vs 7 hours, P < .001). Day and overnight extubation were associated with equivalent operative mortality (1.7% vs 1.7%, P = .880), reintubation (3.7% vs 3.4%, P = .141), and composite morbidity-mortality (8.2% vs 8.0%, P = .314). After risk adjustment, overnight extubation was not associated with any difference in reintubation, mortality, or composite morbidity-mortality. On subanalysis, those extubated between 24:00 and 06:00 exhibited increased composite morbidity-mortality (odds ratio, 1.18; P = .001) but no difference in reintubation or mortality.

Conclusions

Extubation overnight was not associated with increased mortality or reintubation. These results suggest that in the appropriate clinical setting, it is safe to routinely extubate cardiac surgery patients overnight.  相似文献   
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