Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obtained from three cohorts of patients: non-cancer controls, patients with benign ovarian tumors, and those with ovarian cancer. We did not find the LPA level to be higher in cancer samples. To understand this inconsistency, we observed that LPA content changed more significantly than other lysophospholipids as a function of plasma storage time while frozen. Additionally, only LPA was found to be adversely impacted by incubation time depending on the Ethylenediaminetetraacetic acid (EDTA) concentration used during blood drawing. We also show that the inhibition of autotaxin effectively prevented artificial LPA generation during incubation at room temperature. Our data suggests that the artificial changes in LPA content may contribute to the discrepancies reported in literature. Any future studies planning to measure plasma LPA should carefully design the study protocol to consider these confounding factors.

Ovarian cancer remains a highly lethal disease due to its late clinical presentation and lack of reliable early biomarkers. Protein-based diagnostic markers have presented limitations in identifying ovarian cancer. We tested the potential of phospholipids as markers of ovarian cancer by utilizing inter-related regulation of phospholipids, a unique property that allows the use of ratios between phospholipid species for quantitation. High-performance liquid chromatography mass spectrometry was used to measure phospholipid, lysophospholipid, and sphingophospholipid content in plasma from patients with benign ovarian masses, patients with ovarian cancer, and controls. We applied both absolute and relative phospholipid ratios for quantitation. Receiver operating characteristic analysis was performed to test the sensitivity and specificity. We found that utilization of ratios between phospholipid species greatly outperformed absolute quantitation in the identification of ovarian cancer. Of the phospholipids analyzed, species in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) were found to have great biomarker potential. LPC(20:4)/LPC(18:0) carried the greatest capacity to differentiate cancer from control, SM(d18:1/24:1)/SM(d18:1/22:0) to differentiate benign from cancer, and PC(18:0/20:4)/PC(18:0/18:1) to differentiate benign from control. These results demonstrate the potential of plasma phospholipids as a novel marker of ovarian cancer by utilizing the unique characteristics of phospholipids to further enhance the diagnostic power.

Background: Higher fish consumption has been reported to be associated with a lower incidence of coronary artery disease (CAD). An elevated neutrophil/lymphocyte ratio (NLR), a marker of systemic inflammation, is reportedly associated with the development of adverse CAD events. We hypothesized that a higher fish intake was associated with a lower NLR. Methods and Results: This cross-sectional study was conducted in a cohort of 8,237 Japanese subjects who had no history of atherosclerotic cardiovascular disease registered at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. The average weekly frequency of fish intake was 2.32 ± 1.31 days. The NLR decreased significantly as the weekly frequency of fish intake (0 day, 1–2 days, 3–4 days, or 5–7 days) increased (p = 0.001). A multiple stepwise regression analysis identified the weekly frequency of fish intake (β = −0.045, p < 0.0001) and habitual alcohol intake (β = −0.051, p < 0.0001) as significant but weak, negative, and independent determinants of the NLR. Conversely, the presence of metabolic syndrome (β = 0.046, p < 0.0001), the presence of treatment for diabetes mellitus (β = 0.054, p < 0.0001), and the presence of treatment for hypertension (β = 0.043, p < 0.0001) were significant positive and independent determinants of the NLR. Conclusions: The present results suggest that a higher frequency of fish intake appears to be associated with a lower NLR, suggesting an anti-systemic inflammation effect. This association may partially explain the preventive effects of a higher fish intake on CAD events.

Background: International consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care science and treatment recommendations (CoSTR) have reported updates on CPR maneuvers every 5 years since 2000. However, few national population‐based studies have investigated the comprehensive effectiveness of those updates for out‐of‐hospital cardiac arrest due to shockable rhythms. The primary objective of the present study was to determine whether CPR based on CoSTR 2005 or 2010 was associated with improved outcomes in Japan, as compared with CPR based on Guidelines 2000. Methods and Results: From the All‐Japan Utstein Registry between 2005 and 2015, we included 73 578 adults who had shockable out‐of‐hospital cardiac arrest witnessed by bystanders or emergency medical service responders. The study outcomes over an 11‐year period were compared between 2005 of the Guidelines 2000 era, from 2006 to 2010 of the CoSTR 2005 era, and from 2011 to 2015 of the CoSTR 2010 era. In the bystander‐witnessed group, the adjusted odds ratios for favorable neurological outcomes at 30 days after out‐of‐hospital cardiac arrest by enrollment year increased year by year (1.19 in 2006, and 3.01 in 2015). Similar results were seen in the emergency medical service responder‐witnessed group and several subgroups. Conclusions: Compared with CPR maneuvers for shockable out‐of‐hospital cardiac arrest recommended in the Guidelines 2000, CPR maneuver updates in CoSTR 2005 and 2010 were associated with improved neurologically intact survival year by year in Japan. Increased public awareness and greater dissemination of basic life support may be responsible for the observed improvement in outcomes. Registration: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: 000009918.

Background: Fish consumption may be associated with a low risk of coronary artery disease. We aimed to investigate whether higher fish consumption results in improved lifestyle behaviors and thus lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio – a predictor of atherosclerotic cardiovascular disease (ASCVD). Methods and Results: This cross-sectional study included 2,947 middle-aged Japanese males with no history of ASCVD or lipid-modifying therapy, who presented at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. We performed an analysis of variance using fish consumption as a categorical variable (0–2 days, 3–4 days, or 5–7 days per week). The serum TG/HDL-C ratio in the 5–7 days fish consumption group was significantly lower than those in the 0–2 and 3–4 days fish consumption groups (p < 0.0001 and p < 0.01, respectively). Multiple regression stepwise analysis revealed that weekly fish consumption negatively and independently determined the TG/HDL-C ratio (β = −0.061, p = 0.001). As fish consumption increased, the proportion of subjects with smoking habits decreased (p = 0.014), those engaging in aerobic exercises and aggressive daily physical activity increased (p < 0.0001 for both), and those with alcohol habit increased (p < 0.0001). In addition, we developed the risk stratification for ASCVD by combining the serum HDL-C level and the serum TG/HDL-C ratio with fish consumption. Conclusion: Increased frequency of fish consumption and improved lifestyle behaviors due to daily fish intake may work additively to lower the serum TG/HDL-C ratio. These associations may explain why high fish consumption is associated with a lower risk of ASCVD. Our findings may help physicians and nutritionists in treating patients with heart diseases and metabolic conditions by recommending a high fish diet in middle-aged Japanese males.