Fetal surgery using fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: a single-center experience.

PURPOSE: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center. METHODS: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO. RESULTS: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032). CONCLUSIONS: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers.

First trimester biomarkers for prediction of gestational diabetes mellitus.

PURPOSE: To develop a first trimester prediction model for gestational diabetes mellitus (GDM) using obesity, placental, and inflammatory biomarkers. METHODS: We used a first trimester dataset of the ASPRE study to evaluate clinical and biochemical biomarkers. All biomarkers levels (except insulin) were transformed to gestational week-specific medians (MoMs), adjusted for maternal body mass index (BMI), maternal age, and parity. The MoM values of each biomarker in the GDM and normal groups were compared and used for the development of a prediction model assessed by area under the curve (AUC). RESULTS: The study included 185 normal and 20 GDM cases. In the GDM group, compared to the normal group BMI and insulin (P = 0.003) were higher (both P < 0.003). The MoM values of uterine artery pulsatility index (UtA-PI) and soluble (s)CD163 were higher (both P < 0.01) while pregnancy associated plasma protein A (PAPP-A), placental protein 13 (PP13), and tumor-necrosis factor alpha (TNFα) were lower (all P < 0.005). There was no significant difference between the groups in placental growth factor, interleukin 6, leptin, peptide YY, or soluble mannose receptor (sMR/CD206). In screening for GDM in obese women the combination of high BMI, insulin, sCD163, and TNFα yielded an AUC of 0.95, with detection rate of 89% at 10% false positive rate (FPR). In non-obese women, the combination of sCD163, TNFα, PP13 and PAPP-A yielded an AUC of 0.94 with detection rate of 83% at 10% FPR. CONCLUSION: A new model for first trimester prediction of the risk to develop GDM was developed that warrants further validation.

Diagnosis of deep pelvic masses on a gynaecology service: Trans-vaginal ultrasound-guided needle aspiration of pelvic solid and cystic lesions.

OBJECTIVES: Women with undiagnosed pelvic lesions are often referred for evaluation and treatment. Transvaginal ultrasound-guided fine needle aspiration (TVUS-FNA) biopsy can assist in making management decisions. We describe our experience with this modality. METHODS: We performed a retrospective chart review of all women who had a TVUS-FNA biopsy between January 2004 and December 2014. Charts were reviewed for clinicopathologic information. The pathologic results of the TVUS-FNA were compared with the final diagnosis. RESULTS: Fifty-nine women underwent TVUS-FNA; the median age was 66 years (range 27-85). Thirty-three lesions were evaluated by fine-needle aspiration biopsy of the solid structure and 26 by aspiration of fluid for cytology. Pathologic feasibility rate was 88% (52/59). Of those with evaluable tissue, the sensitivity of the procedure was 100% and the specificity 92%. Considering the seven inconclusive results, the procedure had sensitivity of 88% (29/33) and specificity of 88% (23/26). Overall accuracy of TVUS-FNA for this patient cohort was 85%. No patient characteristics were found to distinguish between accurate and inaccurate or inconclusive TVUS-FNA result. No complications were noted. CONCLUSIONS: TVUS-FNA offers an excellent modality for the diagnosis and management of deep pelvic lesions otherwise not amenable for histologic evaluation.

Nonvisualization of the Fetal Gallbladder: Can Levels of Gamma-Glutamyl Transpeptidase in Amniotic Fluid Predict Fetal Prognosis?

OBJECTIVE: In cases of nonvisualization of the fetal gallbladder (NVFGB), we investigated whether amniotic fluid levels of gamma-Glutamyl transpeptidase (GGTP) can distinguish normal development or benign gallbladder agenesis from severe anomaly such as biliary atresia. METHODS: This is a retrospective cohort study of pregnancies in which the gallbladder was not visualized in the second-trimester fetal anatomy scan. Levels of GGTP in amniotic fluid were analyzed prior to 22 weeks of gestation by amniocentesis. Data were collected regarding other fetal malformations, fetal karyotype, and screening results for cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. RESULTS: Of 32 cases of NVFGB, 27 (84%) had normal GGTP levels and a normal CFTR gene screening, and 1 of them had an abnormal karyotype. Three of the 5 cases with low GGTP were diagnosed with extrahepatic biliary atresia, proven by histopathological examination following termination of pregnancy. The fourth case had hepatic vasculature abnormality and the fifth isolated gallbladder agenesis. In 22 of 32 cases (68.7%), the gallbladder was detected either later in pregnancy or after delivery. CONCLUSION: The findings support low levels of GGTP in amniotic fluid, combined with NVFGB, as a sign of severe disease, mainly biliary atresia. Normal GGTP levels, concomitant with isolated NVFGB, carry a good prognosis.

Increased stillbirth in uncomplicated monochorionic twin pregnancies: a systematic review and meta-analysis.

OBJECTIVE: To estimate the risk of stillbirth in apparently uncomplicated monochorionic-diamniotic twin pregnancies by systematic review and meta-analysis and compare it with that in uncomplicated dichorionic pregnancies. DATA SOURCES: We performed an electronic search (January 1985 to April 2012) of Medline, PubMed, Embase, and ClinicalTrials.gov databases. METHODS OF STUDY SELECTION: Studies detailing gestational-age specific stillbirth rates after 24 weeks of gestation in monochorionic-diamniotic twin pregnancies uncomplicated by twin-twin transfusion syndrome, growth restriction, or major anomalies. The rate and risk of stillbirth were calculated in 2-week gestational age blocks and compared in controlled studies with dichorionic pregnancies. TABULATION, INTEGRATION, AND RESULTS: We evaluated 361 studies to include nine informative studies, four after additional data from the investigators. The rate of stillbirth per 1,000 uncomplicated monochorionic-diamniotic pregnancies at 32-33, 34-35, and 36-37 weeks of gestation was 5.1, 6.8, and 6.2, respectively. The risk of stillbirth per pregnancy at 32, 34, and 36 weeks of gestation was 1.6%, 1.3% and 0.9%, respectively. Compared with uncomplicated dichorionic pregnancies, the odds ratio for stillbirth per pregnancy at 32, 34, and 36 weeks of gestation was 4.2 (95% confidence interval [CI] 1.4-12.6), 3.7 (CI 1.1-12.0), and 8.5 (CI 1.6-44.7), respectively. CONCLUSION: Uncomplicated monochorionic twin pregnancies are at substantial risk of stillbirth throughout the third trimester, which is severalfold higher than in dichorionic twin pregnancies. Given the risk of fetal death to the cotwin, these data should inform decisions around timing of delivery in seemingly normal monochorionic twin pregnancies.

Reference values for fetal penile length and width from 22 to 36 gestational weeks.

OBJECTIVE: Current reference range values for fetal penile growth are based on length measurements. However, methodologies for measuring penile length differ among studies and from the standard technique used in children. We propose that the measurement of penile width may aid in its evaluation. The aim of the study was to create normograms for penile length and width. METHODS: A prospective cross-sectional design was used. One hundred male fetuses at 22 to 36 gestational weeks were included. On ultrasound examination, penile length was measured from tip to base, where the penis joins the scrotum. Penile width was measured at the widest point across the penis. Reference values for the 5th and 95th percentiles were calculated for each gestational week. RESULTS: There was a good correlation between gestational age and penile length (R(2) = 0.606) and width (R(2) = 0.683). The percentile of fetal weight estimation independently affected penile length and width. The interobserver correlation coefficient was 0.939 for length and 0.909 for width. CONCLUSION: Reference range values of fetal penile length and width are presented for 22 to 36 weeks of gestation. These values correlate to gestational age and estimated fetal weight percentile. These reference range measurements may help the evaluation of suspected micropenis.

Sonographic evaluation of kidney parenchymal growth in the fetus.

OBJECTIVE: The aim of the study was to establish a nomogram for renal parenchymal thickness throughout pregnancy. METHODS: One-hundred and twenty-eight healthy women with singleton, well-dated, uncomplicated second- or third-trimester pregnancies were prospectively evaluated for renal parenchymal thickness on routine ultrasound scans. The renal parenchyma was measured in transverse and sagittal sections using predefined criteria. RESULTS: There were no differences in anterior or posterior parenchymal measurements in either plane by fetal sex. On sagittal-section analysis, no differences were noted between the right and left kidneys. A nomogram was established on the basis of the findings. The results showed constant linear growth of the fetal parenchyma during pregnancy. CONCLUSIONS: The normal fetal parenchyma grows at a constant, linear rate throughout pregnancy. The nomogram formulated may serve as a basis of future studies of the correlation of parenchymal thickness with postnatal kidney function in fetuses with urinary tract anomalies.

Hard to heal pressure ulcers (stage III-IV): efficacy of injected activated macrophage suspension (AMS) as compared with standard of care (SOC) treatment controlled trial.

The objective of this study was to compare local injections of AMS with SOC treatments for stage III and IV pressure ulcers in elderly patients. It was designed as historically prospective 2-arms non-parallel open controlled trial, and conducted in a department of geriatric medicine and rehabilitation of a university affiliated tertiary hospital. We studied 100 consecutive elderly patients with a total of 216 stage III or IV pressure ulcers, 66 patients were assigned to the AMS group and had their wounds injected, while 38 patients were assigned to the SOC group. Primary outcome was rate of complete wound closure. Time to complete wound closure and 1-year mortality served as secondary outcomes. Statistical analyses were performed at both patient and wound levels. Percentage of completely closed wounds (wound level and patient level) were significantly better (p<0.001/p<0.001, respectively) in all patients in favor of AMS, as well as in the subset of diabetic patients (p<0.001/p<0.001). Similarly, AMS proved significantly better for the subset of those with leg ulcers and with baseline wounds ≤15 cm(2), compared with SOC. There were no statistically significant differences with regard to time to complete closure or 1-year mortality rates in the two groups. It is concluded that there is a significant difference in favor of stage III and IV wound closure rates by AMS, as compared with SOC treatments.

Reference values for gamma-glutamyl-transferase in amniotic fluid in normal pregnancies.

OBJECTIVE: Nonvisualization of the fetal gallbladder by ultrasound poses a diagnostic dilemma. The aim of the study was to establish reference values for the hepatobiliary enzyme gamma-glutamyl-transferase (GGT) in amniotic fluid in normal pregnancies, and to determine the maximal week of gestation in which reference values can be determined. METHOD: A cross-sectional design was used. The study group consisted of pregnant women at 16 gestational weeks or more referred to our ultrasound unit for amniocentesis. Amniotic fluid was assayed for levels of GGT and other hepatobiliary enzymes using the Integra 800 device. The 5th and 95th percentiles for each gestational week were calculated. RESULTS: A total of 263 samples were analyzed. After conversion to log units, enzyme levels showed a good correlation with gestational week (Pearson). The mean values and the 5th and 95th percentiles were calculated for gestational weeks 16 to 22. Beyond 22 weeks, the number of examinations was insufficient for analysis. On multiple regression analysis, log values of alkaline phosphatase, maternal age, and gestational age independently affected log GGT values. Levels of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were too low, and their correlation with gestational week too poor for calculation of reference values. CONCLUSION: GGT reference values in amniotic fluid in normal pregnancies were defined for gestational weeks 16 to 22. These data may be useful for differentiating isolated absence of fetal gallbladder from extrahepatic biliary atresia.

Accuracy of ultrasonographic fetal weight estimation in twin pregnancies.

OBJECTIVE: To compare the accuracy of fetal weight estimations between normal and growth-restricted twin and singleton pregnancies in a single tertiary center. METHODS: The computerized ultrasound database of a tertiary center was searched for all fetal weight estimations made in twin pregnancies from 2001 to 2006, which were performed up to 3 days before delivery. Accuracy was compared with a control group of singleton pregnancies at a 3:1 ratio. Estimated fetal weight was calculated by the Hadlock formula. Analyses were performed for the whole group and for pregnancies associated with fetal growth restriction and discordancy. RESULTS: The study groups included 278 twins and 834 singleton pregnancies. The twins group was characterized by a higher mean absolute percentage error compared with the singleton group (8.9% compared with 6.8%). Accuracy was lower for the second twins than for the first twins. When comparing the subgroup of fetal growth restriction, differences in sensitivity and specificity were small for singleton compared with overall twins (47.5% compared with 48.9% and 97.7% compared with 95.7%, respectively). Overall accuracy was better in the singleton group (95% compared with 88%), mainly due to relatively low accuracy in the second twin (86%). For detection of discordancy, estimated fetal weight had a sensitivity of 52%, specificity of 88%, and overall accuracy of 81%. CONCLUSION: The accuracy of the ultrasonographic estimated fetal weight seems to be lower for twin gestations than for singleton gestations, especially for second twins. These data should be considered by clinicians when making decisions based on ultrasonographic characteristics.

Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart.

BACKGROUND: Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. METHODS AND RESULTS: Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (approximately 4 x 10(5) cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells. After 5 weeks, scar vessel density (+/-SE) (25+/-4 versus 10+/-1 per mm2; P<0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15+/-0.01 versus 0.11+/-0.01 cm; P<0.05), reduced left ventricular (LV) diastolic dilatation (0.87+/-0.02 versus 0.99+/-0.04 cm; P<0.05), and improved LV fractional shortening (31+/-2 versus 20+/-4%; P<0.05), compared with controls. CONCLUSIONS: Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.

Treatment of deep sternal wound infections post-open heart surgery by application of activated macrophage suspension.

Postoperative sternal wound infection remains a significant complication and generally causes considerable morbidity and mortality. Macrophages play a major role in the process of wound healing. In order to evaluate the efficacy of local injection of activated macrophage suspensions into open infected sternal wound space, a retrospective case-control study was conducted. Sixty-six patients with deep sternal wound infection treated by activated macrophages (group 1) and 64 patients with deep sternal wound infection treated by sternal reconstruction surgery with various regional flaps (group 2), were matched for gender, age, and risk index. In up to 54 months of follow-up of group 1, 60 patients (91%) achieved complete wound closure. Two (3%) late deaths occurred unrelated to the procedure. Mortality rate in group 2 was 29.7% (19/64). Duration of hospitalization was 22.6 days in group 1 vs. 56.2 days in group 2. Patients with deep sternal wound infection following open heart surgery that were treated by activated macrophages had significantly less mortality as well as significant reduction of hospitalization in comparison to the surgically treated group. These results illustrate the advantages of using a biologically based activated macrophage treatment.