Maternal pre-pregnancy body mass index and related factors: A cross-sectional analysis from the Japan Environment and Children's Study.

Socioeconomic status and smoking are reportedly associated with underweight and obesity; however, their associations among pregnant women are unknown. This study aimed to investigate whether socioeconomic factors, namely educational attainment, household income, marital status, and employment status, were associated with pre-pregnancy body mass index (BMI) categories, including severe-moderate underweight (BMI ≤ 16.9 kg/m2), mild underweight (BMI, 17.0-18.4 kg/m2), overweight (BMI, 25.0-29.9 kg/m2), and obese (BMI ≥ 30.0 kg/m2) among Japanese pregnant women using data from the Japan Environment and Children's Study (JECS). In total, pregnant women were included 96,751. Age- and parity-adjusted multivariable multinomial logistic regression analyses assessed socioeconomic factors and smoking associations with falling within abnormal BMI categories (normal BMI as the reference group). Lower education and lower household were associated with overweight and obesity, and, especially, lowest education and household income had relatively higher point estimate relative ratios (RRs) of 3.97 and 2.84, respectively. Regarding the risks for underweight, however, only junior high school education had a significantly higher RR for severely to moderately underweight. Regarding occupational status, homemakers or the unemployed had a higher RR for severe-moderate underweight, overweight, and obesity. Unmarried, divorced, or bereaved women had significantly higher RRs for mildly underweight status. Quitting smoking early in pregnancy/still smoking had higher RRs for all four not having normal BMI outcomes; however, quitting smoking before pregnancy had a higher RR only for obese individuals. Lower educational attainment and smoking are essential intervention targets for obesity and severe-moderate underweight prevention in younger women. Lower household income is also a necessary target for obesity.

Impact of the response to platinum-based chemotherapy on the second-line immune checkpoint inhibitor monotherapy in non-small cell lung cancer with PD-L1 expression ≤49%: a multicenter retrospective study.

Introduction: The efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce. Methods: This multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated. Results: The response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045). Conclusion: Maintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the second-line setting.

Investigation of a practical assessment index to capture the clinical presentation of cachexia in patients with lung cancer.

OBJECTIVE: Cancer cachexia constitutes a poor prognostic factor in patients with lung cancer. However, the factors associated with cancer cachexia remain unclear. This study aimed to identify factors that influence cancer cachexia in patients with lung cancer. METHODS: In this retrospective observational study conducted at the Kansai Medical University, 76 patients with lung cancer were evaluated for physical function, nutritional status (Mini Nutritional Assessment-Short Form) and physical activity (International Physical Activity Questionnaire-Short Form) at the first visit to the rehabilitation outpatient clinic. The patients were divided into cachexia and noncachexia groups. The log-rank tests and Cox proportional hazards model were used to investigate the relationship between cachexia and prognosis. To examine the factors that influence cachexia, multivariate regression analysis with significant (P < 0.05) variables in the univariate logistic regression analysis was performed. Spearman's correlation analysis was performed to investigate the association between International Physical Activity Questionnaire-Short Form and performance status. RESULTS: Overall, 42 patients (55.2%) had cachexia associated with survival time since their first visit to the outpatient rehabilitation clinic, even after confounders adjustment (hazard ratio: 3.24, 95% confidence interval: 1.12-9.45, P = 0.031). In the multivariate analysis, Mini Nutritional Assessment-Short Form (odds ratio: 20.34, 95% confidence interval: 4.18-99.02, P < 0.001) and International Physical Activity Questionnaire-Short Form (odds ratio: 4.63, 95% confidence interval: 1.20-17.89, P = 0.026) were identified as independent factors for cachexia. There was no correlation between International Physical Activity Questionnaire-Short Form and performance status (r = 0.155, P = 0.181). CONCLUSION: Malnutrition and low physical activity were associated with cachexia in patients with lung cancer. The International Physical Activity Questionnaire-Short Form may be a useful indicator of physical activity in cachexia. Regularly assessing these factors and identifying suitable interventions for cachexia remain challenges to be addressed in the future.

First-Line Chemoimmunotherapy versus Sequential Platinum-Based Chemotherapy Followed by Immunotherapy in Patients with Non-Small Cell Lung Cancer with ≤49% Programmed Death-Ligand 1 Expression: A Real-World Multicenter Retrospective Study.

BACKGROUND: The long overall survival (OS) observed among patients with non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression in chemoimmunotherapy (CIT) groups in previous phase III trials suggests the limited efficacy of CIT among the subgroup with ≤49% PD-L1 expression on tumor cells. Hence, sequential treatment with first-line platinum-based chemotherapy followed by second-line immune checkpoint inhibitor treatment (SEQ) is an option. This study examined whether first-line CIT would provide better outcomes than SEQ in patients with advanced NSCLC with ≤49% PD-L1 expression. METHODS: This retrospective study evaluated patients with untreated NSCLC who received first-line CIT or SEQ at nine hospitals in Japan. OS, progression-free survival (PFS), PFS-2 (the time from first-line treatment to progression to second-line treatment or death), and other related outcomes were evaluated between the CIT and SEQ groups. RESULTS: Among the 305 enrolled patients, 234 eligible patients were analyzed: 165 in the CIT group and 69 in the SEQ group. The COX proportional hazards model suggested a significant interaction between PD-L1 expression and OS (p = 0.006). OS in the CIT group was significantly longer than that in the SEQ group in the 1-49% PD-L1 expression subgroup but not in the <1% PD-L1 expression subgroup. Among the subgroup with 1-49% PD-L1 expression, the CIT group exhibited longer median PFS than the SEQ group (CIT: 9.3 months (95% CI: 6.7-14.8) vs. SEQ:5.5 months (95% CI: 4.5-6.1); p < 0.001), while the median PFS in the CIT group was not statistically longer than the median PFS-2 in the SEQ group (p = 0.586). There was no significant difference between the median PFS in the CIT and SEQ groups among the <1% PD-L1 expression subgroup (p = 0.883); the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group (10.5 months (95% CI: 5.9-15.3) vs. 6.4 months (95% CI: 4.9-7.5); p = 0.024). CONCLUSIONS: CIT is recommended for patients with NSCLC with 1-49% PD-L1 expression because it significantly improved OS and PFS compared to SEQ. CIT had limited benefits in patients with <1% PD-L1 expression, and the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group. These findings will help physicians select the most suitable treatment option for patients with NSCLC, considering PD-L1 expressions.

Early abdominal wall ectopic pregnancy treated with laparoscopic surgery: A case report and literature review.

The abdominal wall is a rare site of ectopic implantation. Laparoscopic surgery for early abdominal pregnancy, in contrast to its use for tubal ectopic pregnancy, remains controversial because of concerns regarding heavy bleeding at the implantation site. Treatment of early abdominal pregnancy must be individualized for each implantation site. Herein, we present a case of an early abdominal pregnancy implanted in the anterior abdominal wall that was successfully treated with laparoscopic surgery. A 28-year-old multiparous woman with a 6-week amenorrhea presented with acute abdominal pain. An ectopic pregnancy was suspected because of elevated serum human chorionic gonadotropin levels without a visible gestational sac on transvaginal ultrasonography. Diagnostic laparoscopy revealed a gestational sac hanging from the anterior abdominal wall near the previous cesarean section wound. Laparoscopic surgery was successfully performed, and the patient was discharged on postoperative day three. In the present case, laparoscopic surgery was beneficial.

Evaluating association of smoking status during pregnancy with adverse birth outcomes using urinary cotinine concentration: The Japan environment and Children's study (JECS).

Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose-response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the participants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose-response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06-1.46], 1.39 [95% CI 1.19-1.62]; low birth weight, 1.40 [95% CI 1.24-1.58], 2.27 [95% CI 2.05-2.53]; small-for-gestational age, 1.35 [95% CI 1.19-1.52], 2.39 [95% CI 2.16-2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose-response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.

Umbilical cord prolapse after preterm premature rupture of membranes.

OBJECTIVE: To investigate the incidence of umbilical cord prolapse (UCP) and its influence on infant prognosis in pregnant women with preterm premature rupture of membranes (PPROM). MATERIALS AND METHODS: We conducted a retrospective cohort study in a single tertiary perinatal center between 2009 and 2017. Singleton pregnancies with PPROM that occurred between 22 and 33 weeks of gestation were included. Infantile composite adverse outcome consisted of death, severe intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, and sepsis before discharge. Infantile outcomes were compared between pregnancies that were complicated by UCP and those that were not. RESULTS: Out of 208 singleton pregnancies included in the analysis, UCP occurred in 12 (5.8%) cases. The gestational age of pregnancies with UCP was significantly lesser than that of those without UCP. The incidence of infantile composite adverse outcome in patients with UCP was 16.7%, and this was not significantly higher than the incidence in patients without UCP (6.6%, P = 0.21). UCP was not shown to be associated with infantile composite adverse outcome in a multivariate regression model. Gestational age <25 weeks at delivery was significantly associated with infantile composite adverse outcome. CONCLUSIONS: The incidence of UCP was 5.8% among singleton pregnancies, with PPROM being managed expectantly between 22 and 33 weeks' gestation. Preterm UCP may not be associated with infantile adverse outcomes provided emergency cesarean delivery is available at all time.

High-Dose Vitamin C Exerts Its Anti-cancer Effects in a Xenograft Model of Colon Cancer by Suppressing Angiogenesis.

Several studies have been conducted to investigate the anti-cancer effects of vitamin C (VC). However, the effect of high-dose VC administration on tumor angiogenesis remains unclear. Focusing on our high-dose VC, our study investigated the effect of high-dose VC (4 g/kg) on vascular endothelial growth in mice with xenografts of a rectal cancer cell line referred to as Colon 26. Male mice harboring Colon 26 tumors were established, and high-dose VC solution was orally administered once daily for 14 d. On the final day of the study, the lower limb tumor tissues and serum samples were collected and analyzed for the expression of tumor angiogenesis related proteins as well as the levels of reactive oxygen species (ROS). Oral VC administration decreased tumor volumes and increased p53 and endostatin levels. In addition, plasma and in tumor part ROS levels and tissue hypoxia inducible factor-1α (HIF-1α) were reduced by VC administration. In addition, the levels of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor D (VEGFD) were decreased by VC administration. These results suggest that VC exerts its anti-cancer effects by suppressing angiogenesis.

High-Dose Vitamin C Administration Inhibits the Invasion and Proliferation of Melanoma Cells in Mice Ovary.

Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 106 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.

Placental histopathological features of fetoscopic laser photocoagulation for monoaminotic diamniotic twin pregnancies.

INTRODUCTION: This study aimed to compare the histopathological placental features of monochorionic diamniotic (MCDA) twins who did and did not undergo fetoscopic laser photocoagulation (FLP). METHODS: This was a retrospective single-institution cohort study on MCDA twins who underwent FLP between October 2010 and December 2018. The control group included MCDA twins who did not undergo FLP and were delivered during the same period in the institute. The incidence of chorioamnionitis (CAM), funisitis, and other pathological findings was compared between the FLP and control groups after matching by gestational age at delivery. RESULTS: In total, 292 MCDA pregnant women who underwent FLP and 356 controls gave birth during the study period. After matching the two groups in the ratio 1:1 by gestational age at delivery, each group comprised 194 subjects. The incidence of histological CAM with Blanc association (stage I, 6.2% vs. 3.1%, crude odds ratio (cOR) = 3.1, P = 0.052; stage II, 7.2% vs. 5.7%, cOR = 1.6, P = 0.30; stage III, 2.1% vs. 2.6%, cOR = 0.66, P = 0.52) and funisitis (artery, 5.2% vs. 3.6%, cOR = 1.3, P = 0.63; vein 7.2% vs. 4.1%, cOR = 1.6, P = 0.29) was not statistically significant difference between the FLP and control groups. The FLP group demonstrated a higher incidence of partial placental infarction than the control group (10.3% vs. 3.1%, cOR = 4.3, P = 0.004, adjusted OR = 2.8, P = 0.031). DISCUSSION: FLP did not appear to increase the incidence of histological CAM or funisitis in subjects matched by gestational age at delivery. The FLP group demonstrated a higher incidence of partial placental infarction than the control group.

Pseudo-Meigs' syndrome associated with hydropic degenerating uterine leiomyoma: a case report.

Pseudo-Meigs' syndrome secondary to uterine leiomyoma is a rare entity. A 50-year-old Japanese woman presented with a 3-month history of shortness of breath. Chest X-ray and magnetic resonance imaging revealed massive right pleural effusion, ascites and a large subserosal uterine myoma. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The pathology was consistent with a benign leiomyoma. The ascites and pleural effusion rapidly disappeared postoperatively. The serum interleukin-6 level was 3.9 pg/mL before surgery and declined to 1.6 pg/mL postoperatively. Previous published work has demonstrated that vascular endothelial growth factor and interleukin-6 may play a role in the pathogenesis of Meigs' syndrome and that vascular endothelial growth factor may contribute to the development of pseudo-Meigs' syndrome due to metastatic ovarian cancer. This is the first English-language study showing the possibility that interleukin-6 is relevant to the pathogenesis of pseudo-Meigs' syndrome caused by degenerating uterine leiomyoma.