DNA methylation marker for the triage of hrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan.

OBJECTIVE: Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. METHODS: Three triage tools-cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m-were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. RESULTS: Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30-64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. CONCLUSIONS: PAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.

Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses.

BACKGROUND: Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes. OBJECTIVE: To summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes. METHODS: Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted. DATA EXTRACTION: Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles' methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2). RESULTS: We identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization. CONCLUSION: Due to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.

Efficacy of Prenatal Yoga in the Treatment of Depression and Anxiety during Pregnancy: A Systematic Review and Meta-Analysis.

Women commonly suffer from depression during pregnancy. For reducing depression, yoga seems to be more suitable for pregnant women than other physical activities because of its low exercise intensity. The objective of this study was to assess the efficacy of prenatal yoga on the treatment of depression during pregnancy. Three electronic databases were searched for relevant articles from their inception to May 2021, including PubMed, Cochrane Library, and ScienceDirect. Pre- and post-test outcomes were adopted to estimate standardized mean difference with a 95% confidence interval for assessing the efficacy of yoga. Heterogeneity among articles was detected using I2 value. A total of 13 articles that contained 379 subjects were included for meta-analysis. No significant improvement in depression scores after practicing yoga was observed for women without depression (p = 0.09) but significant improvement was observed for women with depression (p = 0.001). Although significant improvement in anxiety scores after yoga was observed for women without depression (p = 0.02), the results of the sensitivity analysis were not consistent, while significant improvement in anxiety scores after yoga was also observed for women with depression (p < 0.00001). The current evidence has suggested that yoga had significant improvement in depression and anxiety scores in pregnant women with depression. However, the level of evidence of this study was not high. More articles with high levels of evidence should be conducted to confirm our conclusion in the future.

Analgesic effects of sterile water injection in the management of low back pain during labor: A systematic review and meta-analysis.

BACKGROUND: Sterile water injections (SWIs) as a non-pharmacologic and cost-effective method have been adopted to relieve low back labor pain (LBLP). OBJECTIVE: To compare the efficacy of intradermal and subdermal SWIs in the treatment of LBLP. SEARCH STRATEGY: Three databases (PubMed, Cochrane Library, and ScienceDirect) were searched to find relevant articles using two terms, "labor" and "sterile water". SELECTION CRITERIA: Studies reporting women with LBLP treated by intradermal or subdermal SWIs in the low back area were included. DATA COLLECTION AND ANALYSIS: Mean differences with 95% confidence interval (CI) and relative risk with 95% CI were used to estimate VAS score and cesarean section rate, respectively. MAIN RESULTS: Except for 10 min, the patients in the intradermal or subdermal SWI group experienced considerable pain reduction compared with the control group for 30-45, 60, and 90 min. Directly comparing intradermal and subdermal SWI groups, the subdermal injection group had significantly better pain relief than the intradermal injection group only at 10 min after treatment. CONCLUSIONS: Both intradermal and subdermal SWIs could reduce LBLP at 30-90 min. The subdermal SWI had significantly better LBLP relief than the intradermal injection only at 10 min after treatment.

Prognostic value of muscle measurement using the standardized phase of computed tomography in patients with advanced ovarian cancer.

OBJECTIVES: The prognostic role of sarcopenia or myosteatosis is controversial in advanced-stage epithelial ovarian cancer (EOC). The phase of computed tomography (CT) could influence muscle measurement and confound its association with outcomes. This study evaluated the prognostic value of muscle measurement in patients with stage III EOC using a standardized phase of computed tomography. METHODS: Pretreatment CT images of 147 patients with stage III EOC were analyzed. All CT images were contrast-enhanced and acquired according to the standardized protocol. Skeletal muscle index (SMI) and radiodensity (SMD) were measured using CT images at the level of the third lumbar vertebra. The skeletal muscle gauge (SMG) was calculated by multiplying SMI and SMD. Harrell's concordance index (C-index) and time-dependent receiver operating characteristic curves were used to measure the predictive value of the models. RESULTS: The median follow-up period was 37.5 mo. SMI, SMD, and SMG were independently associated with overall survival when adjusted for clinical variables. Adding SMG to the model including stage, residual tumor, and malignant ascites significantly improved C-indices (0.704 vs. 0.629; P < 0.001). Models including SMG had a superior C-index compared with models including SMI and SMD (0.704 vs. 0.668; P = 0.01). The SMG model achieved the highest area under the curve for 5-year overall survival prediction (0.619 for clinical model, 0.702 for SMI model, and 0.710 for SMG model). CONCLUSIONS: Muscle measurements obtained from a standardized phase of CT images were associated with survival in advanced-stage EOC. The integration of SMI and SMD into SMG may improve prognostication and unify findings in future studies.

Muscle loss during primary debulking surgery and chemotherapy predicts poor survival in advanced-stage ovarian cancer.

BACKGROUND: Sarcopenia is commonly observed in patients with advanced-stage epithelial ovarian cancer (EOC). However, the effect of body composition changes-during primary debulking surgery (PDS) and adjuvant platinum-based chemotherapy-on outcomes of patients with advanced-stage EOC is unknown. This study aimed to evaluate the association between body composition changes and outcomes of patients with stage III EOC treated with PDS and adjuvant platinum-based chemotherapy. METHODS: Pre-treatment and post-treatment computed tomography (CT) images of 139 patients with stage III EOC were analysed. All CT images were contrast-enhanced scans and were acquired according to a standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured using CT images obtained at the L3 vertebral level. Predictors of overall survival were identified using Cox regression models. RESULTS: The median follow-up was 37.9 months. The median duration between pre-treatment and post-treatment CT was 182 days (interquartile range: 161-225 days). Patients experienced an average SMI loss of 1.8%/180 days (95% confidence interval: -3.1 to -0.4; P = 0.01) and SMD loss of 1.7%/180 days (95% confidence interval: -3.3 to -0.03; P = 0.046). SMI and SMD changes were weakly correlated with body mass index changes (Spearman ρ for SMI, 0.15, P = 0.07; ρ for SMD, 0.02, P = 0.82). The modified Glasgow prognostic score was associated with SMI loss (odds ratio: 2.42, 95% confidence interval: 1.03-5.69; P = 0.04). The median time to disease recurrence was significantly shorter in patients with SMI loss ≥5% after treatment than in those with SMI loss <5% or gain (5.4 vs. 11.2 months, P = 0.01). Pre-treatment SMI (1 cm2 /m2 decrease; hazard ratio: 1.08, 95% confidence interval: 1.03-1.11; P = 0.002) and SMI change (1%/180 days decrease; hazard ratio: 1.04, 95% confidence interval: 1.01-1.08; P = 0.002) were independently associated with poorer overall survival. SMD, body mass index, and total adipose tissue index at baseline and changes were not associated with overall survival. CONCLUSIONS: Skeletal muscle index decreased significantly during treatment and was independently associated with poor overall survival in patients with stage III EOC treated with PDS and adjuvant platinum-based chemotherapy. The modified Glasgow prognostic score might be a predictor of SMI loss during treatment.

Retrospective Analysis Of Comparative Outcomes In Recurrent Platinum-Sensitive Ovarian Cancer Treated With Pegylated Liposomal Doxorubicin (Lipo-Dox) And Carboplatin Versus Paclitaxel And Carboplatin.

PURPOSE: The aim of this study is to analyze the outcomes of platinum-sensitive (PS) recurrent ovarian cancer treated with pegylated liposomal doxorubicin and carboplatin (CD) versus paclitaxel and carboplatin (CP). Clinical features were examined to characterize the patient population that would benefit from CD. MATERIALS AND METHODS: This is a retrospective review of 122 cases at a tertiary hospital. Patients with PS recurrent ovarian cancer who received CD or CP were included. Progression-free survival (PFS) and overall survival (OS) were evaluated through the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to examine PFS predictors. RESULTS: In total, 122 patients (75% with first recurrence and 25% with second recurrence) were included. The majority of the patients were diagnosed at an advanced stage and with the histology of serous carcinoma. Median PFS and OS were 14.8 and 55.5 months in the CD group and 13.5 and 56.8 months in the CP group. Subgroup analysis of patients revealed that the CD group had longer median PFS than the CP group among patients with PFI>12 months. Additionally, during the second recurrence, longer PFS was observed in the CD group than in the CP group (medians 22.3 and 13.5 months, respectively, p = 0.019). CONCLUSION: Comparable outcomes in recurrent platinum-sensitive ovarian cancer treated with CD versus CP were presented in this study. Longer PFS in CD group was observed among patients with PFI for more than 12 months or in second recurrence.

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer.

BACKGROUND: Treatment-related toxicities and decreased levels of patient performance during cancer therapy might contribute to body composition changes and thereby impact outcomes. However, the effect of longitudinal body composition changes on outcomes in patients with advanced endometrial cancer is unknown. This study investigated the association between body composition changes during staging surgery and adjuvant chemoradiotherapy and outcomes in patients with stage III endometrial cancer. METHODS: Pretreatment and post-treatment computed tomography (CT) images of 131 patients with stage III endometrial cancer who were treated between 2008 and 2016 were analysed. All CT images were contrast enhanced and acquired according to the standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured from two sets of CT images obtained at the level of the third lumbar vertebra. The skeletal muscle gauge was calculated by multiplying SMI by SMD (SMI × SMD). Predictors of overall survival and progression-free survival were identified using Cox regression models. RESULTS: The median follow-up was 50.6 (range 12.1-117.0) months. Overall, body mass index (BMI) changes during treatment were 0.4% per 210 days (95% confidence interval: -0.6 to 1.4; P = 0.41), and patients experienced an average SMD loss of 2.1% per 210 days (95% confidence interval: -4.0 to -0.2; P = 0.03). Weight loss and SMD loss ≥5% were observed in 23 (17.6%) and 54 (41.2%) patients, respectively. The changes in SMD did not correlate with those in BMI (Spearman's ρ for SMD, -0.13; P = 0.13). SMD change (per 1 Hounsfield unit/210 days decrease) was independently associated with poorer overall survival (hazard ratio: 1.32, 95% confidence interval: 1.14-1.52; P < 0.001) and progression-free survival (hazard ratio: 1.28, 95% confidence interval: 1.12-1.43; P < 0.001). Our results did not show association between survival and pretreatment myosteatosis and sarcopenia or changes in SMI and total adipose tissue index during treatment. The pretreatment skeletal muscle gauge was associated with treatment modifications such as delays, dose reductions, and discontinuation of chemotherapy. CONCLUSIONS: Skeletal muscle radiodensity decreased significantly during treatment and was independently associated with poorer survival in patients with stage III endometrial cancer who underwent staging surgery and adjuvant chemoradiotherapy. SMD loss was occult and occurred independently of BMI change.

Possible surrogate marker for an effective dose-dense chemotherapy in treating ovarian cancer.

OBJECTIVE: To dissect the correlated hematologic markers that reflect the clinical outcome or treatment response in patients receiving dose-dense chemotherapy with a combination of platinum (cisplatin or carboplatin) and paclitaxel. MATERIALS AND METHODS: From 2009 to 2014, we enrolled 55 ovarian cancer patients (total 67 courses) including first-line, persistent, platinum-sensitive, or platinum-resistant disease in MacKay Memorial Hospital, Taipei, Taiwan. Weekly pretreatment complete blood counts and calculated ratios [platelet/neutrophil ratio, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), neutrophil/monocyte ratio, platelet/monocyte ratio, lymphocyte/monocyte ratio] during dose-dense chemotherapy were collected. By grouping these hematologic biomarkers into three different response subgroups (responsive, stable, and nonresponsive) according to CA125 trend, the data were analyzed using one-way analysis of variance, and using post hoc-Tukey test for comparing each other. A p value < 0.05 was considered to be statistically significant. RESULTS: Absolute counts of lymphocytes and platelets, PLR, platelet/neutrophil ratio, platelet/monocyte ratio (all p < 0.001), and NLR (p=0.013) had statistically significant differences. Moreover, using box-and-whisker plot, absolute count of lymphocyte, PLR, and NLR showed most remarkable discrepancy in responsive, stable, and nonresponsive patients. Subgroup analysis for primary, platinum-sensitive, and platinum-resistant patients further revealed that PLR and NLR were significantly correlated to the outcome of dose-dense chemotherapy. CONCLUSION: Lower PLR or lower NLR had better treatment response for dose-dense chemotherapy and are possible markers for representing treatment response in dose-dense chemotherapy. For a clinician, this is useful for timing when to switch to another chemotherapy regimen.