Time Differences From Abnormal Cervical Cancer Screening to Colposcopy Between Insurance Statuses.

OBJECTIVE: Screening and diagnostic follow-up to prevent cervical cancer are influenced by socioeconomic and systemic factors. This study sought to characterize intervals from abnormal cervical cancer screening to colposcopy between practices differing by insurance status at a large, urban academic center. MATERIALS AND METHODS: This retrospective cohort study included patients aged 21-65 who presented for colposcopy between January 1, 2021, and January 1, 2022, at the resident and faculty gynecology practices of a single large urban academic medical center. Patient characteristics were compared using t tests or Wilcoxon rank sum tests for continuous measures and χ2 or Fisher exact tests for categorical measures. Intervals from abnormal cervical cancer screening to colposcopy were compared using the Wilcoxon rank sum test and linear regression analysis with multivariable models adjusted for age, cervical cytology result, human papillomavirus result, and HIV status. RESULTS: Resident practice patients were publicly insured and more likely to be Black or Hispanic (p < .0001); rates of high-risk human papillomavirus and smoking were similar. Resident practice patients had longer intervals from abnormal cervical cancer screening to colposcopy compared with faculty practice patients (median 79.5 vs 34 d, p < .0001). On adjusted analysis, resident practice patients faced a 95% longer interval (p < .0001). CONCLUSIONS: Publicly insured patients of a resident-based practice faced significantly longer intervals from abnormal cervical cancer screening to colposcopy than faculty practice patients at a single urban academic center. Effort to address these differences may be an area of focus in improving health disparities.

Mid-trimester sonographic placenta previa thickness and persistence at delivery.

OBJECTIVE: Increasing placental thickness is associated with adverse outcomes including earlier gestational age at delivery, lower birthweight, and lower umbilical artery pH. We aim to determine whether mid-trimester placenta previa thickness is associated with persistence of previa at time of delivery. STUDY DESIGN: Single-center retrospective cohort study of singleton gestations with previa diagnosed at 18-24 weeks delivering between 2015 and 2019. The thickest portion of the placenta was measured in a longitudinal plane on transabdominal imaging to determine placental thickness. We defined three cohorts: 1) thick placenta (>1 standard deviation above the mean), 2) thin placenta (>1 standard deviation below the mean), and 3) average placenta (within 1 standard deviation above or below the mean). Primary outcome was previa persistence at time of delivery. Secondary outcomes included postpartum hemorrhage, cesarean delivery, placenta accreta spectrum, and maternal morbidity composite (use of Bakri balloon, B-lynch, or O'Leary, peripartum hysterectomy, blood transfusion, ICU admission, or death). In all analyses, average thickness was used as the base comparator. RESULTS: Of 239 pregnancies with mid-trimester previa there were 34 thin, 166 average, and 39 thick placentas. Patients with thick placenta were older, more likely to have prior cesarean delivery, fibroid uterus, and delivery at an earlier gestational age. After adjusting for confounders, thick placenta was associated with persistent previa (aOR 6.85 [3.13-15.00]) and cesarean delivery (aOR 2.76 [1.26-6.08]). CONCLUSION: At diagnosis of mid-trimester previa, thick placenta is associated with persistence at time of delivery and delivery by cesarean section. This suggests placental thickness may assist with risk stratification and coordination of care.

Preoperative Application of Chlorhexidine to Reduce Infection with Cesarean Delivery after Labor (PRACTICAL): A Randomized Clinical Trial.

OBJECTIVE: To evaluate whether use of both preoperative 2% chlorhexidine gluconate abdominal cloth and 4% chlorhexidine gluconate vaginal scrub is effective in reducing surgical site infections (SSIs) in patients undergoing cesarean delivery after labor. STUDY DESIGN: This is a single-center, randomized clinical trial in which patients were randomized 1:1 to receive 2% chlorhexidine gluconate cloth applied to the abdomen in addition to the application of 4% chlorhexidine gluconate vaginal scrub versus standard of care. The primary outcome was rate of SSIs, including endometritis, by 6 weeks postdelivery. The secondary outcomes were other wound complications (erythema at the operative site, skin separation, drainage, fever, hematoma, seroma) by 6 weeks postdelivery, hospital readmission for wound complications, and day of discharge after cesarean delivery. RESULTS: A total of 319 patients between September 2018 and February 2021 met eligibility criteria: 160 were randomized to the chlorhexidine gluconate abdominal cloth and vaginal scrub group and 159 were randomized to the standard of care group. The groups did not have significant differences in maternal demographic characteristics. Of the 302 (95%) individuals included in primary analysis, there was no statistically significant difference in SSI and endometritis rate by 6 weeks postdelivery (6.6% in chlorhexidine vs. 5.3% standard of care, p = 0.65). Secondary outcomes were also similar among the two groups. CONCLUSION: The combination of preoperative 2% chlorhexidine gluconate abdominal cloth and 4% chlorhexidine gluconate vaginal scrub does not appear to reduce the risk of SSI with cesarean delivery after trial of labor when compared with standard of care. KEY POINTS: · Preoperative chlorhexidine abdominal cloth/vaginal scrub does not decrease SSI in cesarean after labor.. · Preoperative chlorhexidine abdominal cloth/vaginal scrub does not decrease other wound complications in cesarean after labor.. · There was no difference in discharge day, 2-week or 6-week SSI rates..

Severe cholestasis-associated coagulopathy diagnosed by routine screening: a case report.

Recent case reports suggest an association between severe intrahepatic cholestasis of pregnancy and fat-soluble vitamin deficiencies, including vitamin K deficiency. Screening for coagulopathy and fat-soluble vitamin deficiency has been proposed as a possible strategy to identify pregnancies at additional risk of adverse outcomes and allow for earlier risk-reducing iatrogenic preterm delivery. This report highlights a case of routine screening that resulted in the detection of subclinical coagulopathy that allowed for earlier intervention and delivery of a healthy neonate at 34 weeks of gestation. Further prospective studies are needed to determine the clinical use of routine screening in detecting coagulopathy and fat-soluble vitamin deficiency in cases of severe cholestasis.

Severe fat-soluble vitamin deficiency suspected secondary to intrahepatic cholestasis of pregnancy: A case report.

Intrahepatic cholestasis is the most common hepatobiliary complication of pregnancy. Worsening cholestasis, measured by total bile acid levels, has been associated with an increased incidence of adverse fetal outcomes; however, maternal morbidity remains rare. This report highlights a case of severe fat-soluble vitamin deficiency suspected to be secondary to severe cholestasis. Active management with weekly vitamin supplementation and close outpatient follow-up resulted in the delivery of a 32-week healthy neonate. We propose consideration of screening for fat-soluble vitamin deficiency for patients whose pregnancy is complicated by severe cholestasis or early-onset cholestasis.

Comparing pregnancy outcomes and loss rates in elective twin pregnancy reduction with ongoing twin gestations in a large contemporary cohort.

BACKGROUND: As compared with singleton gestations, twin pregnancies are associated with a significantly higher risk of preterm birth and maternal complications as well as fetal and neonatal morbidity and mortality. Multifetal pregnancy reduction is a technique developed in the 1980s to reduce the fetal number in higher-order multiple pregnancies to reduce the risk of adverse pregnancy outcomes, most importantly preterm birth. OBJECTIVE: The objective of the study was to compare pregnancy outcomes and loss rates in elective twin pregnancy reduction to ongoing twin gestations in a large contemporary cohort. STUDY DESIGN: This was a retrospective review of dichorionic diamniotic twin gestations that underwent first-trimester ultrasound at our institution from January 2008 to September 2016. Planned elective 2-to-1 multifetal pregnancy reductions at less than 15 weeks' gestation were compared with ongoing dichorionic diamniotic twin gestations. Data were collected via chart review. Demographics between 2-to-1 reduced singletons and ongoing twins were assessed using a Student t test or a Wilcoxon rank-sum test, as appropriate, for continuous variables and χ2 or Fisher exact tests, as appropriate, for categorical variables. Univariable and multivariable logistic regressions were used to compare pregnancy outcomes between ongoing twins and reduced singletons adjusting for maternal age, body mass index, race, in vitro fertilization, use of chorionic villus sampling, prior term birth, and prior preterm birth. RESULTS: Of 1070 dichorionic diamniotic twin pregnancies identified, completed follow-up data were available and analyzed for 855 patients (79.9%). Among those, 250 (29.2%) were 2-to-1 singletons and 605 (70.8%) were ongoing twins. Reduced singleton patients were slightly older, more likely white, and had lower body mass index. They were also more likely to have undergone in vitro fertilization (63.6% vs 48.8%), had chorionic villus sampling (92% vs 37.5%), and had prior term births (54% vs 35.7%). Compared with 2-to-1 singletons, the adjusted odds of having preterm delivery at 37 weeks for ongoing twins were 5.62 times (95% confidence interval, 3.67-8.61; P < .001) and 2.22 times (95% confidence interval, 1.20-4.11; P < .001) at 34 weeks. While intrauterine growth restriction, placental abruption, and gestational diabetes were not significant, ongoing twins were more likely to have a cesarean delivery (odds ratio, 5.53, 95% confidence interval, 3.60-8.49; P < .001) and preeclampsia (odds ratio, 3.33, 95% confidence interval, 1.60-6.96; P < .001) after adjusting for maternal characteristics. There were also significant differences between groups for preterm premature rupture of membranes and low birthweight at less than the fifth and 10th percentiles. Total pregnancy loss (at 24 and 20 weeks) was similar between singleton and ongoing twins (4% vs 2.5%, P = .23, and 3.6% vs 1.7%, P = .09 for respective weeks). There were no significant differences in the rate of unintended pregnancy loss (2.4% vs 2.3%; P = .94) and the rate of intrauterine fetal death greater than 24 weeks (1.2% vs 0.7%; P = .43) in reduced singleton versus ongoing twin group, respectively. CONCLUSION: In our study, patients who elected to reduce to a singleton pregnancy had a higher gestational age of delivery and lower rates of preterm birth and pregnancy complications without an increased risk of pregnancy loss.

Impact of non-neoplastic vs intratumoural hepatitis B viral DNA and replication on hepatocellular carcinoma recurrence.

BACKGROUND: This study aims to determine the impact of intracellular hepatitis B virus (HBV) DNA, covalently closed circular DNA (cccDNA) and viral replicative activity in both tumour and non-neoplastic liver on prognosis and to determine the relationship of viral replicative activity and Ishak fibrosis in predicting outcome following resection. METHODS: A total of 99 prospectively enrolled patients treated with primary liver resection for HBV-HCC are included. Intracellular HBV DNA and cccDNA were quantitated by real-time PCR. The RNA-sequencing (RNA-seq) was performed in a subset of 21 patients who had either minimal liver fibrosis (Ishak stages 0-2) or end-stage fibrosis (Ishak stage 6). RESULTS: Tumour tissue contained a lower cccDNA copy number compared with paired non-neoplastic liver, and larger tumours (>3 cm) had less cccDNA compared with small tumours (⩽3 cm). High viral replicative activity in non-neoplastic liver was associated with higher HCC recurrence rate independent of Ishak fibrosis stage. Genes correlated with viral replicative activity in non-neoplastic liver (620 genes) were distinct from those associated with end-stage fibrosis (1226 genes). Genes associated with viral replicative activity were preferentially distributed in regions on chr3, chr16 and chr19. CONCLUSIONS: Viral replicative activity in non-neoplastic liver is associated with HCC recurrence through mechanisms that are distinct from and independent of Ishak fibrosis stage.

Autologous Tumor Cell Lysate-Loaded Dendritic Cell Vaccine Inhibited Tumor Progression in an Orthotopic Murine Model for Hepatocellular Carcinoma.

The immune status of the tumor microenvironment influences tumor progression, and hepatocellular carcinoma (HCC) with an immunosuppressive signature often is associated with a poor prognosis. This study examined the impact of a bone marrow-derived dendritic cell (DC) vaccine loaded with autologous tumor cell lysate on tumor progression and the tumor microenvironment using an orthotopic murine HCC model. An orthotopic murine HCC was established by implantation of Hepa1-6 cells in the liver. The impact of DC vaccine loaded with Hepa1-6 cell lysate on tumor progression, survival, and tumor-infiltrating lymphocytes and cytokines was examined. Treating mice with DC vaccine loaded with Hepa1-6 cell lysate inhibited the progression of murine HCC generated through orthotopic implantation of Hepa1-6 cells and resulted in a 90 % survival rate by day 60 compared with a survival rate lower than 5 % for untreated mice. This anti-tumor response was associated with inhibition of STAT3 phosphorylation within the tumor. The DC vaccine reduced accumulation of Foxp3+CD4+ regulatory T cells within the tumor microenvironment and prevented TGF-ß production from the tumor tissue. Tumor cell lysate-loaded DC vaccine prevented HCC progression in a clinically relevant orthotopic murine HCC model. The effect of DC vaccine on the accumulation of Foxp3+CD4+ regulatory T cells within the tumor microenvironment and on the production of TGF-ß suggests that tumor regression by DC vaccination may be associated with an altered immunosuppressive tumor microenvironment.

Prognostic Role of Immune Cells in Hepatitis B-associated Hepatocellular Carcinoma Following Surgical Resection Depends on Their Localization and Tumor Size.

This study aims to evaluate localized expression of CD4, interleukin (IL)-17, Foxp3, and CD8 in hepatitis B-associated hepatocellular carcinoma (HBV-HCC) and to explore their potential effects on outcome following surgical resection. This prospective study includes 66 HBV-HCC surgical resection patients enrolled from 2008 to 2013. CD4, IL-17, Foxp3, and CD8 mRNA in 4 regions of the resection specimens (center of the tumor, periphery of the tumor, non-neoplastic liver bordering tumor, non-neoplastic liver distant from tumor) was quantitated using real-time polymerase chain reaction. The tumoral regions had lower CD4 and CD8 expression as compared with paired non-neoplastic regions, whereas the expression of IL-17 and Foxp3 did not differ. High Foxp3 in all regions except non-neoplastic liver distant from tumor was associated with poor overall survival, whereas low CD8 expression in distant non-neoplastic liver may be associated with high HCC recurrence rate. Although the expression of almost all molecules did not differ between small (≤3 cm) and large HCC (>3 cm), high IL-17 in periphery of tumor, high CD8 in center of tumor, or low CD8 in distant non-neoplastic liver was associated with high HCC recurrence rate in patients with small HCC, but not in those with large HCC. The effect of immune cells on HCC progression therefore depends on the expression level, localization, and tumor size, and an imbalance toward regulatory T cells is associated with poor outcome.

Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma.

Quantitation of hepatitis B surface antigen (HBsAg) in hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains to be clearly defined. This study aims to determine the association of HBsAg quantity with intrahepatic HBV viral load and activity in both tumor and non-neoplastic liver of HBV-HCC patients. Data were obtained from 89 prospectively enrolled patients treated with primary liver resection for HBV-HCC at a single Western institution (2008-2013). Circulating HBsAg was quantitated using ELISA. HBV DNA, covalently closed circular (cccDNA) and precore-pregenomic RNA (preC-pgRNA) in both tumor and non-neoplastic liver were quantitated by real-time PCR from fresh liver resection specimens. Circulating HBsAg was detectable in all 89 patients. HBsAg negatively correlated with age, and positively correlated with pre-operative serum AFP and ALT levels. HBsAg correlated with HBV cccDNA copy number in tumor or non-neoplastic liver tissue. It also correlated with preC-pgRNA copy number in non-neoplastic liver tissue. HBsAg did not correlate with serum HBV DNA, total intrahepatic HBV DNA, viral replicative activity or transcriptional activity. In HBV-HCC patients, HBsAg levels correlated with cccDNA copy number in tumor or non-neoplastic liver tissue, suggesting that a greater pool of cccDNA is associated with a higher rate of HBsAg production.

The Severity of Liver Fibrosis Influences the Prognostic Value of Inflammation-Based Scores in Hepatitis B-Associated Hepatocellular Carcinoma.

BACKGROUND: This study was designed to evaluate the prognostic value of three systemic inflammation markers, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), for hepatocellular carcinoma (HCC) associated with hepatitis B (HBV). METHODS: This analysis included 234 HBV-HCC patients who underwent primary surgical resection at the Mount Sinai Medical Center between 1988 and 2013. Serum albumin and circulating neutrophil, lymphocyte, and platelet counts immediately before surgery were obtained to calculate NLR, PLR, and PNI. RESULTS: Patients with larger tumor size (>3 cm) had higher NLR, higher PLR, and lower PNI. Stratified analysis showed that the impact of three markers on outcome depends on the severity of liver fibrosis. High NLR, high PLR, or low PNI was associated with poor outcome only in patients without end-stage fibrosis (Ishak stage 0-5) and not in those with cirrhosis (Ishak stage 6). Multivariate analysis in Ishak stage 0-5 patients showed that only high NLR was associated with poor outcome independent of tumor size. Of the three markers, only NLR correlated with PD-L1 expression in center of tumor, but not in nonneoplastic liver. CONCLUSIONS: The prognostic value of these three markers following surgery was only significant for HBV-HCC patients without end-stage fibrosis, and among the three markers, only NLR remained a significant prognostic indicator independent of tumor size. The correlation of NLR with intratumoral PD-L1 expression raises a hypothesis for shared pathways leading to PD-L1-mediated local tolerance within tumor and systemic inflammatory responses represented by elevated NLR in HBV-HCC.