Influence of maternal body mass index on interobserver variability of fetal ultrasound biometry and amniotic-fluid assessment in late pregnancy.

OBJECTIVE: To determine the interobserver reproducibility of fetal ultrasound biometric and amniotic-fluid measurements in the third trimester of pregnancy, according to maternal body mass index (BMI) category. METHODS: This was a prospective cohort study of women with a singleton gestation beyond 34 weeks, recruited into four groups according to BMI category: normal (18.0-24.9 kg/m2 ), overweight (25.0-29.9 kg/m2) , obese (30.0-39.9 kg/m2 ) and morbidly obese (≥ 40 kg/m2 ). Multiple pregnancies, women with diabetes and pregnancies with a fetal growth, structural or genetic abnormality were excluded. In each woman, fetal biometric (biparietal diameter (BPD), head circumference, abdominal circumference (AC), femur length (FL) and estimated fetal weight) and amniotic-fluid (amniotic-fluid index (AFI) and maximum vertical pocket (MVP)) measurements were obtained by two experienced sonographers or physicians, blinded to gestational age and each other's measurements. Differences in measurements between observers were expressed as gestational age-specific Z-scores. The interobserver intraclass correlation coefficient (ICC) and Cronbach's reliability coefficient (CRC) were calculated. Bland-Altman analysis was used to assess the degree of reproducibility. RESULTS: In total, 110 women were enrolled prospectively (including 1320 measurements obtained by 17 sonographers or physicians). Twenty (18.2%) women had normal BMI, 30 (27.3%) women were overweight, 30 (27.3%) women were obese and 30 (27.3%) women were morbidly obese. Except for AFI (ICC, 0.65; CRC, 0.78) and MVP (ICC, 0.49; CRC, 0.66), all parameters had a very high level of interobserver reproducibility (ICC, 0.72-0.87; CRC, 0.84-0.93). When assessing reproducibility according to BMI category, BPD measurements had a very high level of reproducibility (ICC ≥ 0.85; CRC > 0.90) in all groups. The reproducibility of AC and FL measurements increased with increasing BMI, while the reproducibility of MVP measurements decreased. Among the biometric parameters, the difference between the BMI categories in measurement-difference Z-score was significant only for FL. Interobserver differences for biometric measurements fell within the 95% limits of agreement. CONCLUSION: Obesity does not seem to impact negatively on the reproducibility of ultrasound measurements of fetal biometric parameters when undertaken by experienced sonographers or physicians who commonly assess overweight, obese and morbidly obese women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Predicting Vaginal Delivery in Nulliparous Women Undergoing Induction of Labor at Term.

OBJECTIVE: We sought to develop a model to calculate the likelihood of vaginal delivery in nulliparous women undergoing induction at term. STUDY DESIGN: We obtained data from the Consortium on Safe Labor by including nulliparous women with term singleton pregnancies undergoing induction of labor at term. Women with contraindications for vaginal delivery were excluded. A stepwise logistic regression analysis was used to identify the predictors associated with vaginal delivery by considering maternal characteristics and comorbidities and fetal conditions. The receiver operating characteristic curve, with an area under the curve (AUC) was used to assess the accuracy of the model. RESULTS: Of 10,591 nulliparous women who underwent induction of labor, 8,202 (77.4%) women had vaginal delivery. Our model identified maternal age, gestational age at delivery, race, maternal height, prepregnancy weight, gestational weight gain, cervical exam on admission (dilation, effacement, and station), chronic hypertension, gestational diabetes, pregestational diabetes, and abruption as significant predictors for successful vaginal delivery. The overall predictive ability of the final model, as measured by the AUC was 0.759 (95% confidence interval, 0.749-0.770). CONCLUSION: We identified independent risk factors that can be used to predict vaginal delivery among nulliparas undergoing induction at term. Our predictor provides women with additional information when considering induction.

Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy Outcomes.

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI (20 to < 25 kg/m2), and high BMI (≥ 25 kg/m2). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).

Contributions of ADP and ATP to the increase in skeletal muscle blood flow after manual acupuncture stimulation in rats.

OBJECTIVE: To investigate the contributions of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to the increase in skeletal muscle blood flow (MBF) observed following manual acupuncture (MA) stimulation in rats. METHODS: Male Sprague-Dawley rats were used as experimental animals (300-370 g, n=40). MA was applied to the right tibialis anterior muscle (TA) for 1 min using a stainless steel acupuncture needle. In eight rats, high-performance liquid chromatography with the microdialysis technique was used to measure local extracellular concentrations of ATP, ADP, adenosine monophosphate (AMP), and adenosine in the TA. In the remaining 32 rats, fluorescent microspheres (15 µm in diameter) were used to measure MBF in the TA following pre-treatment with either the P2 receptor antagonist suramin (100 mg/kg intra-arterially) or saline (control) (n=16 each). Rats receiving MA (Suramin+MA and Saline+MA groups, n=8 each) were compared with untreated rats (Suramin and Saline groups, n=8). RESULTS: MA significantly increased the local extracellular concentration of ATP, ADP, and adenosine (p<0.05, before MA vs 30 min after MA). In addition, MA significantly increased MBF in rats pre-treated with saline or suramin (p<0.01, Saline vs Saline+MA; p<0.05, Suramin vs Suramin+MA, respectively). However, suramin significantly suppressed this MA-induced increase in MBF (p<0.05, Saline+MA vs Suramin+MA). CONCLUSIONS: These results suggest that both ATP and ADP partially contribute to the MA-induced increase in MBF via P2 receptors. However, further studies are needed to clarify the contributions of other vasodilators.

Neonatal complications associated with use of fetal scalp electrode: a retrospective study.

OBJECTIVES: To estimate the incidence and risk of complications associated with a fetal scalp electrode and to determine whether its application in the setting of operative vaginal delivery was associated with increased neonatal morbidity. DESIGN: Retrospective cohort study. SETTING: Twelve clinical centers with 19 hospitals across nine American Congress of Obstetricians and Gynecologists US districts. POPULATION: Women in the USA. METHODS: We evaluated 171 698 women with singleton deliveries ≥ 23 weeks of gestation in a secondary analysis of the Consortium on Safe Labor study between 2002 and 2008, after excluding conditions that precluded fetal scalp electrode application such as prelabour caesarean delivery. Secondary analysis limited to operative vaginal deliveries ≥ 34 weeks of gestation was also performed. MAIN OUTCOME MEASURES: Incidences and adjusted odds ratios with 95% confidence intervals of neonatal complications were calculated, controlling for maternal characteristics, delivery mode and pregnancy complications. RESULTS: Fetal scalp electrode was used in 37 492 (22%) of deliveries. In non-operative vaginal delivery, fetal scalp electrode was associated with increased risk of injury to scalp due to birth trauma (1.2% versus 0.9%; adjusted odds ratios 1.62; 95% confidence intervals 1.41-1.86) and cephalohaematoma (1.0% versus 0.9%; adjusted odds ratios 1.57; 95% confidence intervals 1.36-1.83). Neonatal complications were not significantly different comparing fetal scalp electrode with vacuum-assisted vaginal delivery and vacuum-assisted vaginal delivery alone or comparing fetal scalp electrode with forceps-assisted vaginal delivery and forceps-assisted vaginal delivery alone. CONCLUSIONS: We found increased neonatal morbidity with fetal scalp electrode though the absolute risk was very low. It is possible that these findings reflect an underlying indication for its use. Our findings support the use of fetal scalp electrodes when clinically indicated. TWEETABLE ABSTRACT: Neonatal risks associated with fetal scalp electrode use were low (injury to scalp 1.2% and cephalohaematoma 1.0%).

Acute kidney injury after myeloablative cord blood transplantation in adults: the efficacy of strict monitoring of vancomycin serum trough concentrations.

BACKGROUND: Acute kidney injury (AKI) is a common medical complication after myeloablative allogeneic stem cell transplantation (SCT). We have previously performed a retrospective analysis of AKI after cord blood transplantation (CBT) in adults, and found that the maximum of vancomycin (VCM) trough levels were significantly higher in patients with AKI. Following these results, we have monitored VCM serum trough concentrations more strictly, to not exceed 10.0 mg/L, since 2008. METHODS: In this report, we performed an analysis of AKI in a new group of 38 adult patients with hematological malignancies treated with unrelated CBT after myeloablative conditioning between January 2008 and July 2011. RESULTS: Cumulative incidence of AKI at day 100 after CBT was 34% (95% confidence interval 19-50). The median of the maximum value of VCM trough was 8.8 (4.5-12.2) mg/L. In multivariate analysis, no factor was associated with the incidence of AKI. No transplant-related mortality was observed. The probability of disease-free survival at 2 years was 83%. CONCLUSION: These findings suggest that strict monitoring of VCM serum trough concentrations has a beneficial effect on outcomes of CBT.

Unrelated cord blood transplantation after myeloablative conditioning in adults with advanced myelodysplastic syndromes.

We analyzed the disease-specific outcomes of adult patients with advanced myelodysplastic syndrome (MDS) treated with cord blood transplantation (CBT) after myeloablative conditioning. Between August 1998 and June 2009, 33 adult patients with advanced MDS were treated with unrelated CBT. The diagnoses at transplantation included refractory anemia with excess blasts (n=7) and MDS-related secondary AML (sAML) (n=26). All patients received four fractionated 12 Gy TBI and chemotherapy as myeloablative conditioning. The median age was 42 years, the median weight was 55 kg and the median number of cryopreserved nucleated cells was 2.51 × 10(7) cells per kg. The cumulative incidence of neutrophil recovery at day 50 was 91%. Neutrophil recovery was significantly faster in sAML patients (P=0.04). The cumulative incidence of plt recovery at day 200 was 88%. Plt recovery was significantly faster in CMV seronegative patients (P<0.001). The cumulative incidence of grade II-IV acute GVHD (aGVHD) and extensive-type chronic GVHD was 67 and 34%, respectively. Degree of HLA mismatch had a significant impact on the incidence of grade II-IV aGVHD (P=0.021). TRM and relapse at 5-years was 14 and 16%, respectively. The probability of EFS at 5 years was 70%. No factor was associated with TRM, relapse and EFS. These results suggest that adult advanced MDS patients without suitable related or unrelated BM donors should be considered as candidates for CBT.

Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation.

Chronic GVHD (cGVHD) of the liver is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-SCT). It is characterized by the destruction of bile duct epithelium followed by progressive cholestasis, which resembles primary biliary cirrhosis (PBC) clinically and histologically. Bezafibrate (BF) is a widely used agent for hyperlipidemia that is also effective in ursodeoxycholic acid (UDCA)-resistant PBC patients. The putative mechanism in cholestasis is that BF upregulates the expression of phosphatidylcholine flippase on bile canaliculi, facilitates phospholipid output into bile and relieves bile duct damage caused by hydrophobic bile salts. Therefore, the effects of BF in patients with cGVHD of the liver were investigated. Of 87 patients with cGVHD who survived more than 100 days after SCT, 8 were given BF to treat liver cGVHD because of a poor therapeutic response to UDCA and immunosuppressants. The serum alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels decreased significantly within 1 month after initiation of BF therapy compared with those before BF therapy in all patients (ALP, 964.9.0+/-306.9 to 597.8+/-102.5 IU/l, P=0.012; gamma-GTP, 528.8+/-299.0 to 269.0+/-119.9 IU/l, P=0.012). BF was effective in patients with liver cGVHD, including UDCA-resistant patients. BF could be a novel therapeutic option for liver cGVHD that helps to preserve normal immunity with the antileukemic effect of cGVHD.

Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD.

Fibrosis and excessive extracellular matrix production are characteristic features of lacrimal gland chronic GVHD (cGVHD). Tranilast (n-[3,4-anthoranilic acid]), used for fibrotic skin disease, inhibits transforming growth factor-beta-induced matrix production. We conducted a non-randomized study comparing 8 patients (five men, three women; median age, 47 years) given topical tranilast with 10 patients (three men, seven women; median age, 37 years) receiving therapy with topical artificial tears, sodium hyaluronate and vitamin A for mild ocular cGVHD. The tranilast group instilled topical tranilast and artificial tears q.i.d., beginning the day of dry eye diagnosis. The ocular surface and tear dynamics of each patient were evaluated before hematopoietic stem cell transplant, at the onset of dry eye and after 3 months of treatment. At 3 months, the scores of the Rose Bengal test and Schirmer test with nasal stimulation had significantly improved in the tranilast group compared with that in the control group (P<0.05). Furthermore, although five control patients (50%) developed severe dry eye within the treatment period, only one tranilast-treated patient (12.5%) did; the rest still had mild dry eye (P<0.05). These results suggest the hypothesis that topical tranilast may effectively retard the progression of mild dry eye associated with cGVHD.

Measurement of fornix depth and area: a novel method of determining the severity of fornix shortening.

PURPOSE: To measure the depth and area of the fornix in normal adults and patients with symblepharon. METHODS: The fornix depth of normal eyes (n=20) and patients with symblepharon (Stevens-Johnson syndrome, n=4) was measured at six locations in each eye using non-invasive, dull-edged stainless steel metric scale. Before and after conjunctival reconstruction surgery, the depths of fornix were also measured by the same method. The overall area was assessed from those fornix depth at six points. RESULTS: The mean depths of the superior nasal and temporal, inferior nasal and temporal, fornices as well as mean depths of medial nasal and temporal canthi fornices in normal eyes were 14.1+/-2.5, 14.1+/-2.5, 10.0+/-2.1, 10.4+/-1.8, 3.0+/-0.9, and 5.2+/-1.2 mm, respectively. The mean overall area of the conjunctival fornix in normal subjects was 909.6+/-162.2 mm(2). All these parameters were significantly lower in the eyes of patients. Both depth and area after surgery were significantly deeper and larger than before. CONCLUSIONS: This estimation may prove useful when evaluating the severity of symblepharon and determining the post-surgical prognosis.

Surgical management of corneal perforation secondary to gonococcal keratoconjunctivitis.

AIMS: To report five cases of gonococcal keratoconjunctivitis with severe corneal involvement treated with therapeutic keratoplasty. DESIGN: Retrospective case series. METHODS: Five consecutive cases of gonococcal keratoconjunctivitis treated with keratoplasty for corneal perforation, with a mean age of 21.2 years, were analysed by patient's history, surgical approaches, and clinical outcomes, corrected visual acuity at initial visit and last follow-up. RESULTS: All adult cases were originally diagnosed as epidemic keratoconjunctivitis by elsewhere, and corneal perforation occurred with a mean duration of 11 days after development of conjunctivitis. While laboratory tests revealed Neisseria gonorrhoeae in all five cases, three patients showed resistance to ofloxacin. Intensive medical treatment using penicillins and/or cephems was initiated. Two patients had peripheral corneal perforations, one had a paracentral perforation, and another, a large corneal perforation with stromal melting. One case had a central microcorneal perforation. In all cases, the anterior chamber was flat. Corneal perforations were treated with lamellar or penetrating keratoplasty using cryopreserved or fresh corneal grafts. All grafts remained clear during the mean follow-up period of 34.9 months. Final best-corrected visual acuity ranged from 20/60 to 20/16. CONCLUSIONS: Severe gonococcal keratoconjunctivitis can benefit from intensive surgical and medical intervention resulting in satisfactory visual rehabilitation.

Factors responsible for glucose intolerance in Japanese subjects with impaired fasting glucose.

Impaired fasting glucose (IFG) represents risk of development of diabetes (DM) and its complications. We investigated insulin secretion and insulin sensitivity in 403 IFG subjects divided into three levels of 2-hour postchallenge glucose (2-h PG) to clarify the factors responsible in the development of glucose intolerance in Japanese IFG. Nearly 60% of the subjects at annual medical check-up with FPG of 6.1-7.0 mmol/l at the first screening were diagnosed by 75 g oral glucose tolerance test (OGTT) to have impaired glucose tolerance (IGT; FPG <7.0 mmol/l and 7.8 mmol/l <2-h PG <11.1 mmol/l) or DM (isolated postchallenge hyperglycemia (IPH); FPG <7.0 mmol/l and 11.1 mmol/l <2-h PG level). The primary factor in the decreased glucose tolerance was a decrease in early-phase insulin, with some contribution of increasing insulin resistance. In addition, IFG/IGT and IFG/IPH subjects showed a compensatory increase in basal insulin secretion sufficient to keep FPG levels within the non-diabetic range. IFG is composed of three different categories in basal, early-phase insulin secretion, and insulin sensitivity.

No effect of a traditional Chinese medicine, Hochu-ekki-to, on antibody titer after influenza vaccination in man: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: It was shown that a traditional Chinese medicine, Hochu-ekki-to (HET), had adjuvant effects in influenza vaccination in an animal experiment. This, however, could not be assessed in a clinical study. METHODS: Thirty-two healthy subjects were randomly assigned to two groups (control and HET groups) in a double-blind manner. HET subjects (n=17) took 7.5 g of HET/day for two weeks; control subjects took the same amount of indistinguishable placebo. Then subjects were vaccinated against influenza (H1N1, H3N2 and B/Shandong). Hemagglutinin titers and natural killer (NK) activity were measured at weeks 0, 1, 2, 4, and 12. RESULTS: Antiinfluenza titers against the three viruses were increased continuously for the first two weeks and leveled off. However, there were no significant differences in any titers between the two groups. NK activity peaked at week 2 without any inter-group differences. CONCLUSION: We could not find any adjuvant effects of HET in this experimental condition.

Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure.

Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.

Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22).

AML1-MTG8 generated by t(8;21) contributes to leukemic transformation, but additional events are required for full leukemogenesis. We examined whether mutations in the receptor tyrosine kinase (RTK) pathway could be the genetic events that cause acute myeloblastic leukemia (AML) harboring t(8;21). Mutations in the second tyrosine kinase domain, juxtamembrane (JM) domain and exon 8 of the C-KIT gene were observed in 10, one and three of 37 AML patients with t(8;21), respectively. Three patients showed an internal tandem duplication in the JM domain of the FLT3 gene. One patient had a mutation in the K-Ras gene at codon 12. As the occurrence of these mutations was mutually exclusive, a total of 18 (49%) patients showed mutations in the RTK pathway. These results suggest that activating mutations in the RTK pathway play a role in part as an additional event leading to the development of t(8;21) AML. The 6-year cumulative incidence of relapse in patients with RTK pathway mutations was 79.8%, compared with 13.5% in patients lacking such mutations (P=0.0029). Furthermore, the 6-year relapse-free survival in patients with mutations was 18% compared to 60% in those without mutations (P=0.0340), indicating that RTK mutations are associated with the clinical outcome in t(8;21) AML.