Search

Background Acardiac monochorionic twins lack cardiac function but grow by passive perfusion of the pump twin's deoxygenated arterial blood through placental arterioarterial (AA) and venovenous (VV) anastomoses and by hypoxia-mediated neovascularization. Pump twins therefore must continuously increase their cardiac output which may cause heart failure. Our aims were: to adapt our twin-twin transfusion syndrome model for acardiac twin pregnancies, to simulate pump and acardiac twin development, and to examine the model for early prognostic markers of pump twin survival. Methods We used an infinite acardiac placental resistance, based on placental dye injection studies and simulations, suggesting the AA-Acardiac-VV series resistance determines the pump twin's excess cardiac output. Pump and acardiac development were expressed by the pump's excess cardiac output versus its normal value, represented by pump/acardiac umbilical venous diameter (UVD) ratios. Results UVD ratios distinguish between AA-VV anastomoses that do and do not cause hydropic pump twins. Pump twins can handle relative larger acardiac perfusion at later than earlier gestation. Both VV and acardiac resistances are significantly smaller than the AA resistance, based on respectively clinical data and acardiac blood volumetric growth. Conclusion Our simulations support clinical results which show that UVD ratios aid in the prediction of pump twin risk. The AA anastomosis controls the future of both the pump and the acardiac. Correlation between acardiac size and pump twin risk is secondary to the AA size but remains clinically usable. These factors may aid in the development of methods for pump twin prognosis and the promotion of selective clinical interventions.Birth Defects Research (Part A), 2016.© 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1008-1015, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background We recently published pump/acardiac umbilical venous diameter (UVD) ratios, representing the pump twin's excess cardiac output fraction, of 27 acardiac twin pregnancies. There was a clear separation between the 17 pump twins that had life-threatening complications and the 10 that did not. The hypothesis of this study is that placental chorangioma and sacrococcygeal teratoma (SCT), tumors whose perfusion also causes high-output complications, have the same fetal outcome as pump twins when perfusion of the tumor requires the same excess cardiac output fraction. Methods We compared the three fetoplacental circulations. Fetuses with a placental chorangioma and acardiac twin pregnancies both have their feeding artery and draining vein located at the placental cord insertion. In contrast, SCT lacks a prescribed feeding artery and draining vein. We, therefore, had to modify our model to assume that the diameter of the hypothetical draining vein is related to the flow difference between inferior vena cava and superior vena cava. The latter flow has been estimated sonographically and is the same as the inferior vena cava flow in the absence of an SCT. Furthermore, a simple modification accounts for the different location of the tumor with respect to the placental cord insertion. Results We propose to apply the clinical pump/acardiac UVD ratios to pregnancies complicated by placental chorangiomas and the modified pump/acardiac UVD ratios for SCT. Conclusion Risk prediction of these rare fetal tumors may be possible based on application of data on excess cardiac output fractions from pump/acardiac UVD ratios and will require future clinical validation. Birth Defects Research (Part A) 106:733-738, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Acardiac twinning is a rare anomaly of monochorionic twin pregnancies. Acardiac fetuses lack a functional heart but are passively perfused by arterial blood from their pump co-twin. Although four acardiac morphological types have been classified, the various paths of anatomical and circulatory acardiac twin development, and the potential influence of acardiac size and perfusion flow as possible predictors of pump twin morbidity and mortality are poorly understood. This report presents the first high resolution three-dimensional reconstruction of the vasculature of an acardiac twin by cryomicrotome imaging. Case A small, approximately 7.5-cm-diameter ball-shaped acardius amorphous of 30 5/7 weeks had caused pump twin cardiac decompensation that necessitated an emergency cesarian section. The pump twin survived well. The acardiac body had a partially intact vascular system with large diameter arteries and veins and multiple zones that appeared devoid of perfusion. The three-dimensional reconstruction showed neither recognizable organ structures nor identifiable blood vessels except for the umbilical artery and vein. Conclusion Our case showed a small acardiac mass with large diameter vessels and consequential low outflow resistance that caused pump twin complications. This indicates that the development of a method that allows pump twin prognosis is likely more successful if based on the use of acardiac versus pump twin perfusion flows than on body volume ratios. Birth Defects Research (Part A) 106:213-217, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND A total of 75% of monozygotic twins share 1 monochorionic placenta where placental anastomoses cause several serious complications, for example, acardiac twinning. Acardiac twins lack cardiac function but grow by perfusion of arterial blood from the pump twin. This rare pregnancy has 50% natural pump twin mortality but accurate risk prediction is currently impossible. Recent guidelines suggest prophylactic surgery before 18 weeks, suggesting 50% unnecessary interventions. We hypothesize that (1) adverse pump twin outcome relates to easy-to-measure pump/acardiac umbilical venous diameter (UVD) ratios, representing acardiac perfusion by the pump's excess cardiac output. This hypothesis suggests that (2) UVD-ratios are large, mildly varying in cases without complications but small and decreasing when complications develop, thus predicting that (3) UVD-ratios may allow risk prediction of pump twins. In this exploratory clinical pilot, we tested whether UVD-ratio measurements support these predictions. METHODS We included 7 uncomplicated (expectant management), 3 elective surgical, and 17 complicated cases (pump decompensation, emergency intervention/delivery or demise). Nine UVD-ratios were measured sonographycally and 18 by pathology. RESULTS Uncomplicated cases have larger, two serial measurements showing mildly varying UVD-ratios; elective surgical cases show larger UVD-ratios; complicated cases have smaller, two serial measurements showing decreasing UVD-ratios. There were no false-positives, no false-negatives and noncrossing linear trendlines of uncomplicated and complicated cohorts. CONCLUSION Our data provide first evidence that UVD-ratios allow risk prediction of pump twins. More early uncomplicated and late complicated cases are needed, for example, in a prospective trial, before the separation between uncomplicated and complicated cohorts is accurate enough to support a well-founded decision on (early) intervention. Birth Defects Research (Part A) 106:114-121, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

No options are available for local antibiotic delivery from uncemented implants. By loading a porous titanium implant with a biomimetic HA-coating (PeriApatite, PA) with antibiotics, we could obtain adequate local antibiotic concentrations and reduce infection susceptibility. This study investigated the efficacy of a tobramycin-loaded PA-coated titanium foam implant in preventing infection, as well as the effects on osseointegration. In 72 New Zealand White rabbits, an uncoated (Ti), PA-coated (PA), or Tobramycin-PA-coated (PA-tobra) titanium foam rod was implanted intramedullary in the left tibiae after contamination of the implant bed with none (control), 103, 104 or 105 CFU Staphylococcus aureus. PA-tobra implants were loaded with 2.4 mg tobramycin. After 28 days analysis was done by bacteriology, histopathology and histomorphometry. Six percent of the contaminated PA-tobra rabbits were infected, whereas this was 53 and 67% for PA and Ti, respectively ( p < 0.001). Quantitative cultures were also significantly lower in the PA-tobra group ( p = 0.003). None of the control rabbits were infected. Histopathological and histomorphometrical scores were both better for the PA-tobra group, although only significant compared to Ti. No significant differences were observed between PA and Ti rabbits. We conclude that the application of tobramycin to PA-coated titanium foam implants appears to be an effective local antibiotic strategy for uncemented implants for infection prophylaxis and has a beneficial effect on implant fixation, which will result in improved long-term implant survival. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 710-716, 2009 [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between placental pathology and pattern of brain injury in full-term infants with neonatal encephalopathy after a presumed hypoxic-ischemic insult. Study design: The study group comprised full-term infants with neonatal encephalopathy subsequent to presumed hypoxia-ischemia with available placenta for analysis who underwent cerebral magnetic resonance imaging (MRI) within the first 15 days after birth. Macroscopic and microscopic characteristics of the placenta were assessed. The infants were classified according to the predominant pattern of brain injury detected on MRI: no injury, predominant white matter/watershed injury, predominant basal ganglia and thalami (BGT) injury, or white matter/watershed injury with BGT involvement. Maternal and perinatal clinical factors were recorded. Results: Placental tissue was available for analysis in 95 of 171 infants evaluated (56%). Among these 95 infants, 34 had no cerebral abnormalities on MRI, 27 had white matter/watershed injury, 18 had BGT injury, and 16 had white matter/watershed injury with BGT involvement. Chorioamnionitis was a common placental finding in both the infants without injury (59%) and those with white matter/BGT injury (56%). On multinomial logistic regression analysis, white matter/watershed injury with and without BGT involvement was associated with decreased placental maturation. Hypoglycemia was associated with an increased risk of the white matter/BGT injury pattern (OR, 5.4; 95% CI, 1.4-21.4). The BGT injury pattern was associated with chronic villitis (OR, 12.7; 95% CI, 2.4-68.7). A placental weight <10th percentile appeared to be protective against brain injury, especially for the BGT pattern (OR, 0.1; 95% CI, 0.01-0.7). Conclusion: Placental weight <10th percentile was mainly associated with normal cerebral MRI findings. Decreased placental maturation and hypoglycemia <2.0 mmol/L were associated with increased risk of white matter/watershed injury with or without BGT involvement. Chronic villitis was associated with BGT injury irrespective of white matter injury. [Copyright &y& Elsevier]

Chronic Intervillositis of Unknown Etiology (CIUE) is a histopathological lesion in the placenta, characterized by an abundant intervillous cell infiltrate of CD68-positive macrophages of maternal origin, accompanied by adverse pregnancy outcomes. We studied the placental intervillous cell infiltrate in three dizygotic twin couples with one-sided CIUE: one had CIUE, the other represented the non-affected control. We performed imaging mass cytometry (IMC), using a 42-marker panel on 3 dizygotic twin couples where one is affected with CIUE and its twin is not affected. This enabled in-depth assessment of phenotype and spatial orientation of the intervillous maternal immune cells. Approximately 80.4% of the intervillous immune cells were macrophages, 19.0% T-cells, 0.5% B-cells and 0.1% NK cells. The absolute number of macrophages and T cells was higher in CIUE compared to controls. However, the relative frequency of immune cells in the intervillous space was not different between the pairs of co-twin fetuses. IMC data showed a difference in the activation status of macrophages between the affected and unaffected placentas: 44.5% of the CD68+ macrophages in the CIUE cases demonstrated bright expression of the activation markers HLA-DR and CD38, whereas this applied to only 5.0% of the CD68+ macrophages in the control twins. We confirmed previous data that the CD68+ cell population, along with T cells, is increased in the intervillous space during CIUE. Moreover, IMC showed an increased amount of HLA-DR+/CD38+/CD68+ macrophages in the intervillous space of the twin with CIUE. Since maternal intervillous blood is part of the maternal circulation and paired twin couples were studied here, it is likely that macrophages are activated locally in CIUE. Further study should point out if HLA-DR+ macrophages are adhering to the fetal trophoblast cells and if they are locally affecting CD4+ T cells to react toward fetal cells and other immune cells. [ABSTRACT FROM AUTHOR]

Chronic Intervillositis of Unknown Etiology (CIUE) is a histopathological lesion in the placenta, characterized by an abundant intervillous cell infiltrate of CD68-positive macrophages of maternal origin, accompanied by adverse pregnancy outcomes. We studied the placental intervillous cell infiltrate in three dizygotic twin couples with one-sided CIUE: one had CIUE, the other represented the non-affected control. We performed imaging mass cytometry (IMC), using a 42-marker panel on 3 dizygotic twin couples where one is affected with CIUE and its twin is not affected. This enabled in-depth assessment of phenotype and spatial orientation of the intervillous maternal immune cells. Approximately 80.4% of the intervillous immune cells were macrophages, 19.0% T-cells, 0.5% B-cells and 0.1% NK cells. The absolute number of macrophages and T cells was higher in CIUE compared to controls. However, the relative frequency of immune cells in the intervillous space was not different between the pairs of co-twin fetuses. IMC data showed a difference in the activation status of macrophages between the affected and unaffected placentas: 44.5% of the CD68+ macrophages in the CIUE cases demonstrated bright expression of the activation markers HLA-DR and CD38, whereas this applied to only 5.0% of the CD68+ macrophages in the control twins. We confirmed previous data that the CD68+ cell population, along with T cells, is increased in the intervillous space during CIUE. Moreover, IMC showed an increased amount of HLA-DR+/CD38+/CD68+ macrophages in the intervillous space of the twin with CIUE. Since maternal intervillous blood is part of the maternal circulation and paired twin couples were studied here, it is likely that macrophages are activated locally in CIUE. Further study should point out if HLA-DR+ macrophages are adhering to the fetal trophoblast cells and if they are locally affecting CD4+ T cells to react toward fetal cells and other immune cells. [ABSTRACT FROM AUTHOR]