Effectiveness of prophylactic HPV vaccines against cervical abnormalities and HPV infection in Japan: The J-HERS 2021 multicenter study.

This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine, which was initiated between 2009 and 2013 in Japan. The study involved 1529 eligible women aged 16-39 years who visited 11 outpatient clinics in Japan for various reasons. These patients underwent HPV genotype analysis and a Pap test of cervical cell samples. A total of 299 women (19.6%) had received the prophylactic HPV vaccine (bivalent:quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. In this study (J-HERS 2021), the highest rate of HPV vaccination (53%) was observed in patients aged 22-27 years. Vaccinated individuals exhibited a 49% rate of protection against low-grade intraepithelial lesions (LSILs) and atypical squamous cells, not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and a 100% rate of protection against high-grade squamous intraepithelial lesions (HSILs) or worse (HSIL+). Significant reductions in HPV16 (95%) and HPV18 (100%) infections were noted, but no differences were observed in HPV6 and HPV11 infections. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparing the prevaccination (J-HERS 2011) and postvaccination (J-HERS 2021) periods, 43%, 51%, 88%, and 62% reductions in HPV16, HPV18, HPV16/18, and HPV31/58 infection rates were observed, respectively. Similarly, 62% and 71% reductions in LSIL/ASCH+ and HSIL+ rates were noted, respectively. There were 88% and 87% reductions in LSIL/ASCH+ and HSIL+ rates in 16-21- and 28-33-year-old patients, respectively. Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged <39 years at 9-12 years after initiation of Japan's first nationwide HPV vaccination program. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV-type replacements are inconsistent across vaccination regimens. This demonstrates the effectiveness of the HPV vaccine. However, continuous monitoring of cervical cancer and precancer is necessary in younger generations (born 1997-2007), who were rarely vaccinated due to the prolonged suspension of the vaccine recommendations in Japan.

Granulocyte colony-stimulating factor as a potential inducer of ovulation in infertile women with luteinized unruptured follicle syndrome.

Luteinized unruptured follicle (LUF) syndrome is one of the intractable ovulation disorders that are commonly observed during cycles of treatment with ovulation inducers, for which no effective therapy other than assisted reproductive technology is available. Here, we investigated whether granulocyte colony-stimulating factor (G-CSF) could prevent the onset of LUF syndrome. We analyzed the effects of G-CSF in 68 infertile women with LUF syndrome who received ovulation induction (clomiphene + human chorionic gonadotropin [hCG] therapy or follicle-stimulating hormone + hCG therapy). G-CSF (lenograstim, 100 µg) was administered subcutaneously. Onsets of LUF syndrome were compared between the cycle during which G-CSF was given in combination with the ovulation inducer (ie, the G-CSF treatment cycle) and the subsequent cycle during which only the ovulation inducer was given (ie, the G-CSF nontreatment control cycle). The results showed that LUF syndrome recurred in only 3 cycles during the G-CSF treatment cycle (4.4% [3/68 cycles]), whereas LUF syndrome recurred in 13 cycles during the subsequent G-CSF nontreatment control cycle (19.1% [13/68 cycles]). The additional use of G-CSF significantly prevented the onset of LUF syndrome during ovulation induction (P = 0.013, McNemar test). No serious adverse reactions because of the administration of G-CSF were observed. In conclusion, our findings indicate that G-CSF may become a useful therapy for LUF syndrome.

Dioxins and Nonortho PCBs in Breast Milk of Vietnamese Mothers Living in the Largest Hot Spot of Dioxin Contamination.

Bien Hoa Air Base is the largest dioxin contamination hot spot in Vietnam. In 2012, we recruited 216 mothers who were living in 10 communities around Bien Hoa Air Base and had delivered newborns at a prefecture hospital, and we investigated recent exposure levels of dioxins and nonortho PCBs in their breast milk. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) was present at 2.6 pg/g lipid in primiparae and 2.2 pg/g lipid in multiparae. Among multiparae and total subjects, significant high prevalence of 2,3,7,8-tetraCDD≥5 pg/g lipid and 2,3,7,8-tetraCDD contribution≥40% were observed in mothers living in the five communities closest to Bien Hoa Air Base. The TEQ for nonortho PCBs was 1.6 pg-TEQ/g lipid for primiparae, and this was even lower than that in the unsprayed area. The length of residency was a strong factor to increase dioxins, including 2,3,7,8-tetraCDD. Residency in the five communities with the highest exposure was a specific risk factor for increased 2,3,7,8-tetraCDD in breast milk. Food intake might contribute partly to the increased levels of dioxin congeners other than 2,3,7,8-tetraCDD in breast milk. These results suggest that Bien Hoa Air Base has led to elevated 2,3,7,8-tetraCDD levels in breast milk of mothers in nearby areas even in the recent years.

Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity.

Prenatal diagnosis of fetal respiratory function: evaluation of fetal lung maturity using lung-to-liver signal intensity ratio at magnetic resonance imaging.

OBJECTIVE: The purpose of this retrospective study is to determine the fetal lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images for the prediction of neonatal respiratory outcome. METHODS: One hundred ten fetuses who underwent magnetic resonance imaging (MRI) examination for various indications after 22 weeks of gestation participated in this study. LLSIR was measured as the ratio of signal intensities of the fetal lung and liver on T2-weighted images at MRI. We examined the changes of the ratio with advancing gestation and the relations between LLSIR and the presence of the severe respiratory disorder (SRD) after birth. The best cut-off value of the LLSIR to predict respiratory outcome after birth was calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: Lung-to-liver signal intensity ratio correlated significantly with advancing gestational age (R = 0.35, p < 0.001). The non-SRD group had higher LLSIR compared with the SRD group (2.15 ± 0.30 vs. 1.53 ± 0.40, p < 0.001). ROC curve analysis showed that fetuses with an LLSIR < 2.00 were more likely to develop SRD [sensitivity: 100%, 95% confidence interval (CI): 52-100%; specificity: 73%, 95% CI 54-88%]. CONCLUSION: The fetal LLSIR on T2-weighted images is an accurate marker to diagnose the fetal lung maturity.

Hemodynamic analysis of cephalothoracopagus by the color doppler method. A comparison to normal fetuses via a longitudinal study.

In a case of cephalothoracopagus, the umbilical artery (UA) was observed with color Doppler method, and the findings were compared with the hemodynamics of 46 normal fetuses. The patient was a 25-year-old primigravida who had appeared for routine prenatal visits since her 6th week of pregnancy. At a later time, the patient was examined after an interval of 4 weeks. Although an ultrasonography was also conducted, unfortunately, any findings of cephalothoracopagus were not detected. In the 25th week of gestation, we hospitalized her for marked polyhydramnios (amniotic fluid index: 280 mm), at which time an ultrasound examination revealed cephalothoracopagus. In the UA, the V(max) was 30.3 cm/s (normal fetus at 25-28 weeks: 33.5 +/- 3.9 cm/s). The UA hemodynamics fell below the normal range. At 26 weeks, the UA V(max) was 56.5 cm/sec, a level which significantly exceeded the normal range. The patient underwent a cesarean section at 27 weeks of gestation; the indication was fetal distress. This is caused by the condition in which the fetal heart beats decreases to 90 beats per minute 3 times during a 10-min period as measured on the cardiotocograms. She delivered a 1,392-gram female with an Apgar score of 2 points (respiratory 1 point and heart rate 1 point). The infant was a cephalothoracopagus, with one head, two hearts, four upper limbs, and four lower limbs. The neonate died from circulatory failure 56 min after birth.

Hemodynamics of the renal artery and descending aorta in fetuses with renal disease using color Doppler ultrasound--longitudinal comparison to normal fetuses.

OBJECTIVE: To examine the hemodynamic values of the renal artery (RA) and descending aorta (DA) in normal fetuses, and to compare these values to those of fetuses with renal disease, thus evaluating the usefulness of hemodynamic analysis for the diagnosis of fetal renal disease. MATERIALS AND METHODS: We examined 46 normal fetuses and 15 fetuses with renal disease (six cases of polycystic kidney (PCK) and nine cases of hydronephrosis). We measured the maximum systolic velocity (Vmax ) of the RA and DA using color Doppler. Measurements were made five times, from the 20th to the 40th week, in both the control and the renal disease group. RESULTS: In the fetuses with PCK (Potter's syndrome) that died postpartum from non-functional kidneys, the Vmax of the RA and DA in the 35th week were 13 cm/s and 25.4 cm/s, respectively. In the fetus with PCK (Trisomy 9) that died due to non-functional kidneys in the 34th week, the values were 13.3 cm/s and 29.6 cm/s, respectively. These values were well below those of the normal group: more than 1.5 SD below the mean. In two fetuses from the nine with hydronephrosis that had a unilateral non-functional kidney, the RA did not clearly show identifiable blood flow. CONCLUSIONS: The V max of the RA and DA in fetuses with renal disease correlates with fetal kidney function, particularly the RA Vmax.Vmax of 1.5 SD below the mean should be the lower normal limit.

Analysis of renal artery hemodynamics in normal fetuses using the color Doppler method.

OBJECTIVE: From analysis of fetal renal artery hemodynamics, we attempted to reveal renal glomerular and tubular function in normal fetuses during pregnancy. DESIGN: The study included 36 cases of normal fetuses from the 20th to the 40th week of gestation; V(max) (the systolic peak velocity of main renal artery), V(mean) (time averages of trace of peak velocity) blood flow were initially measured between 20 and 24 weeks of gestation and every 4 weeks thereafter. The measurement was performed a total of five times in a longitudinal study. In addition, the blood flow waveform was concurrently examined. RESULTS: The V(max) was 22.02 +/- 0.50 cm/s at 20-24 weeks of gestation. This standard value (100%) was found to increase for each group as follows: 125.2, 149.1, 156.1, and 181.5%. Furthermore, using 20-24()weeks of gestation as the standard, the V(mean) increased after the 37th week of gestation: 186.7%, respectively. At 20-24 weeks of gestation, the blood flow wave forms consisted of 43.2% type I (only systolic waveforms), and 56.8% type II (both systolic and diastolic waveforms). Type III waveforms (waveforms that extended beyond the diastolic to the next systolic component) were not recognized. In the 33- to 36-week group, 82.6% of the waveforms were type II, and in the 37- to 40-week group, 76.2% of the waveforms were type III. CONCLUSIONS: The V(max) and V(mean) of the renal artery in normal fetuses exhibit a similar rate increase when 20-24 weeks of gestation is compared to 37-40 weeks of gestation. The blood flow waveforms changed as pregnancy progresses; thus, it was inferred that this finding was related to the development of the renal glomerular and renal tubular function.