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  • 1
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 8, No. 1 ( 2020-05), p. e000375-
    Abstract: There is increasing evidence for the benefit of poly ADP ribose polymerase (PARP) inhibitors in a subset of high-grade serous ovarian carcinoma (HGSC) patients, especially those with homologous recombination (HR)-deficient tumors. However, new treatment strategies, such as immune checkpoint inhibition, are required for patients with HR-proficient tumors. Methods A total of 80 cases of HGSC were analyzed in this study. Whole exome and RNA sequencing was performed for these tumors. Methylation arrays were also carried out to examine BRCA1 and RAD51C promoter methylation status. Mutations, neoantigen load, antigen presentation machinery, and local immune profile were investigated, and the relationships of these factors with clinical outcome were also analyzed. Results As expected, the numbers of predicted neoAgs were lower in HR-proficient (n=46) than HR-deficient tumors (n=34). However, 40% of the patients with HR-proficient tumors still had higher than median numbers of neoAgs and better survival than patients with lower numbers of neoAgs. Incorporation of human leukocyte antigen (HLA)-class I expression status into the survival analysis revealed that patients with both high neoAg numbers and high HLA-class I expression (neoAg hi HLA hi ) had the best progression-free survival (PFS) in HR-proficient HGSC (p=0.0087). Gene set enrichment analysis demonstrated that the genes for effector memory CD8 T cells, TH1 T cells, the interferon-γ response, and other immune-related genes, were enriched in these patients. Interestingly, this subset of patients also had better PFS (p=0.0015) and a more T-cell-inflamed tumor phenotype than patients with the same phenotype (neoAg hi HLA hi ) in HR-deficient HGSC. Conclusions Our results suggest that immune checkpoint inhibitors might be an alternative to explore in HR-proficient cases which currently do not benefit from PARP inhibition.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2719863-7
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  • 2
    In: Open Heart, BMJ, Vol. 3, No. 2 ( 2016-11), p. e000501-
    Type of Medium: Online Resource
    ISSN: 2053-3624
    Language: English
    Publisher: BMJ
    Publication Date: 2016
    detail.hit.zdb_id: 2747269-3
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  • 3
    In: Open Heart, BMJ, Vol. 5, No. 2 ( 2018-09), p. e000865-
    Abstract: Mountain districts normally have tougher geographic conditions than plain districts, which might worsen heart failure (HF) conditions in patients. Also, those places frequently are associated with social problems of ageing, underpopulation and fewer medical services, which might cause delay in detection of disease progression and require more admissions. We investigated the association of residence altitude with readmission in patients with HF. Methods We followed 452 patients with HF to determine all-cause readmissions over a median of 1.1 years. The altitude of patient residences, population, proportion of the elderly and number of hospitals or clinics in a minor administrative district (Cho-Aza district) located at the residences were examined using data from the 2010 census and Google Maps. Results All-cause readmissions were observed in 269 (60%) patients. The altitude of ≥200  m was significantly associated with readmissions (HR, 1.49; 95 % CI 1.12 to 1.96; p=0.006) after adjustment for physical and haemodynamic parameters, left ventricular ejection fraction, brain natriuretic peptide and components of the established score for predicting readmission for HF. Altitude was significantly associated with ageing, underpopulation, fewer hospitals or clinics and lower temperature (all p 〈 0.01), with an increased tendency for readmission during the winter season; however, it was not associated with patient clinical parameters. Conclusions High altitude residence may be an important predictor for readmission in patients with HF. This relationship may be confounded by unfavourable sociogeographic conditions at higher altitudes.
    Type of Medium: Online Resource
    ISSN: 2053-3624
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 2747269-3
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  • 4
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 24, No. 7 ( 2014-09), p. 1181-1189
    Abstract: The aim of this study was to evaluate the impact of surgical staging in stage I clear cell adenocarcinoma of the ovary (CCC). Methods We performed a retrospective review of 165 patients with stage I CCC treated with optimal or nonoptimal staging surgery. Results The median follow-up period in this study was 67 months. No significant difference was detected in recurrence-free survival (RFS) or overall survival (OS) between patients optimally and nonoptimally staged (RFS: P = 0.434; OS: P = 0.759). The estimated 5-year RFS and OS rates were 92.1% and 95.3% in patients with stages IA/IC1 and 81.0% and 83.7% in stages IC2/IC3, respectively. The multivariate analysis indicated that stages IC2/IC3 predicted worse RFS and OS than stages IA/IC1 in stage I CCC patients (RFS: P = 0.011; OS: P = 0.011). Subsequently, we investigated the impact of surgical staging, respectively, in stages IA/IC1 and stages IC2/IC3. Significant differences were observed in PFS and OS between patients optimally and nonoptimally staged with stages IA/IC1 (RFS: P = 0.021; OS: P = 0.024), but no significant difference was found in those with stages IC2/IC3. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery in stages IA/IC1 CCC patients ( P = 0.033). In addition, we investigated the impact of surgical staging for stages IA/IC1 in the adjuvant chemotherapy group. The 5-year RFS and OS rates in patients optimally and nonoptimally staged with stages IA/IC1 in the adjuvant chemotherapy group were 97.8% and 100%, and 85.2% and 89.4%, respectively. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery for stages IA/IC1 patients in the adjuvant chemotherapy group ( P = 0.019). Conclusions The prognosis for women with stage 1A/IC1 is very good. Surgical staging category was the only independent prognostic factor for RFS in stages IA/IC1 CCC.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    Language: English
    Publisher: BMJ
    Publication Date: 2014
    detail.hit.zdb_id: 2009072-9
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