Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer

Objectives: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings.

Methods: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed.

Results: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = ?0.22), performance status (ρ = ?0.30), functional well-being (ρ?=?0.20), anorexia/cachexia subscale (ρ?=?0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ?=?0.26). PA was also correlated with fluid retention (ρ = ?0.34) and albumin (ρ?=?0.32), C-reactive protein (ρ = ?0.31), and hemoglobin (ρ?=?0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = ?0.43).

Conclusions: PA was correlated with physical condition, but not with psychological well-being.     

Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia

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The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

Cancer Chemotherapy and Pharmacology - Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of...     

Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

Predictive value of the coronary artery calcium score and advanced plaque characteristics: Post hoc analysis of the PREDICT registry

BackgroundWhether coronary plaque characteristics assessed in coronary computed tomography angiography (CCTA) in association with the coronary artery calcium score (CACS) have predictive value for coronary events is unclear. We aimed to examine the predictive value of the CACS and plaque characteristics for the occurrence of coronary events.MethodsAmong 2802 patients who were analyzed in the PREDICT registry, 2083 with suspected coronary artery disease (CAD) were studied using post hoc analysis. High-risk plaques were defined as having ≥2 adverse characteristics, such as low computed tomographic attenuation, positive remodeling, spotty calcification, and napkin-ring sign. An adjudicative composite of coronary events (cardiac death, nonfatal acute coronary syndrome, and coronary revascularization ≥3 months after indexed CCTA) were analyzed.ResultsSeventy-three (3.5%) patients had coronary events and 313 (15.0%) had high-risk plaques. Multivariate Cox proportional hazard analysis showed that high-risk plaques remained an independent predictor of coronary events (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.13–3.34, P ?= ?0.0154), as well as the log-transformed CACS (adjusted HR 1.24, 95% CI 1.11–1.39, P ?= ?0.0002) and the presence of obstructive stenosis (adjusted HR 5.63, 95% CI 3.22–10.12, P 0.0001). In subgroup analyses, high-risk plaques were independently predictive only in the low CACS class (<100).ConclusionThis study shows that assessment of adverse features by coronary plaque imaging independently predicts coronary events in patients with suspected CAD and a low CACS. Our findings suggest that the clinical value of high-risk plaques to CACS and stenosis assessment appears marginal.     

Cytotoxic T‐lymphocyte‐associated protein 4 expressed by melanoma cells does not affect melanoma‐specific cytotoxic T lymphocytes in the effector phase

Cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the important molecules that regulate the anti‐melanoma T‐cell response. Currently, there are some reports showing that CTLA‐4 is expressed not only by T cells but also by various kinds of tumor cells, including melanoma cells. However, there is no report that shows the role of CTLA‐4 expressed by melanoma cells in melanoma‐specific cytotoxic T‐lymphocyte (CTL) response. In this report, we confirmed substantial CTLA‐4 expression and the localization of CTLA‐4 in melanoma cell lines and tissues. Also, we examined its impact on melanoma‐specific CTL in vitro, and found that CTLA‐4 expressed by melanoma cells does not affect melanoma‐specific CTL in the effector phase. Our findings suggest the importance of elucidating the role of CTLA‐4 expressed by melanoma cells, particularly in anti‐CTLA‐4 antibody therapy.     

Time-Dependent Effects of Cryoablation for Renal Tumor on Overall and Split Renal Function

Purpose

To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney.