The interventional radiology gender gap: perspectives from the international IR training survey.

OBJECTIVE: This study sought to examine international interventional radiology (IR) training standards and perceptions. This survey aims to identify gender-based barriers and inequities effecting uptake, retention and experience of trainees in IR. METHODS: An anonymous survey was created using Survey Monkey and distributed as a single-use weblink via eight IR national and international societies around the world. Data analysis was conducted to highlight gender-specific trends and identify any differences. RESULTS: Motivation factors given for following a career in IR revealed gender differences in factors such as mentoring (8.7 F vs 21.6% M) and influence from senior colleagues (15.2 F vs 25.0% M). The overwhelming majority across both genders (82.6 F vs 81.3% M) agreed or strongly agreed that early exposure to IR training at Year 1 had a positive impact on career choice. A good work life balance was positively reported in 48.2% of female respondents compared to 45.2% in males. There were no significant differences in satisfaction with the various aspects of IR training. All differences observed between genders, exceeded the 0.05 significance level. CONCLUSION: This survey offers many insights into the current international landscape of IR training. Ongoing evaluation is vital to inform recruitment practices and initiatives to bridge gender inequities and attract more females into IR. ADVANCES IN KNOWLEDGE: This study has revealed that increasing and optimising mentoring opportunities may be the first step in increasing awareness of IR and maximising potential female recruits.

Vascular and Interventional Radiology Training; International Perspectives and Challenges.

PURPOSE: Assess international interventional radiology (IR) training standards and trainee satisfaction to identify challenges and drive positive change. MATERIALS AND METHODS: An anonymous survey was created using Survey Monkey and distributed as a single-use web link via eight IR national and international societies around the world. It consisted of two parts: the first assessed the general exposure of radiology trainees to IR and whether this influenced their decision to pursue a career in IR; the second focussed on satisfaction and quality of training by those who are in training or have recently completed an IR training program. RESULTS: There were 496 participants of which 274 were eligible to complete part one of the survey and 222 were eligible to complete the whole survey. UK and Europe contributed 52% of the responses. The USA and Middle East contributed 23%, and the rest of the world 9%. Over half of responders expressed that exposure early in their career was the main inspiration to pursue a career in IR. Overall satisfaction with training was high across all regions; however, satisfaction regarding vascular training varied. The negative impact of competition from other specialities ranged from 9% (USA) to 61% (UK). Great variability was reported regarding the amount of time spent dedicated to IR and IR on call. CONCLUSION: Despite significant progress in creating structured and comprehensive IR training, there is still room for improvement. Early promotion of IR is essential for on-going high-quality recruitment. Monitoring and standardization of the training environment at a national and international level are necessary to equip IR trainees and to consolidate IR's speciality status in the medical field.

Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition.

BACKGROUND: Acute atherosis (AA) of the uteroplacental spiral arteries has been characterised by subendothelial lipid-laden foam cells, perivascular leukocyte infiltrates (PVI) and fibrinoid necrosis. Because precise diagnostic criteria are not available for comparative research studies we developed and tested new simplified criteria based on 237 cases. METHODS: Decidual basalis samples were collected by vacuum suction at elective cesarean deliveries. Spiral arteries were evaluated in serial decidual tissue sections from women with normal pregnancy, preeclampsia, and diabetes. Features of AA were sought in parallel sections stained with H&E and immunostained for CD68, cytokeratin CK7 and desmin, and costained with Periodic Acid Schiff (PAS). RESULTS: Foam cell lesions were defined as two or more adjacent, intramural, vacuolated CD68 positive cells, PVI as a focal perivascular lymphocyte accumulation, more dense than in the surrounding decidua. Increased fibrinoid (PAS positive) was identified if present in ≥75% of the arterial wall circumference. PVI and increased fibrinoid were significantly associated with preeclampsia but not specifically associated with the presence of foam cell lesions. Hence we diagnosed decidua basalis AA lesions solely by the presence of foam cell lesions, occurring in preeclampsia (37%), diabetes (10%) and healthy normotensive women (11%). The simplified criterion was reproducible by different investigators. Decidua basalis AA occurred most commonly and extensively in preeclampsia, but did not distinguish between preterm and term disease. DISCUSSION: Our evidence based criterion for decidua basalis AA diagnosis in vacuum suction biopsies may not apply to myometrial or decidua parietalis arteries. In decidual basalis samples it should facilitate comparisons between research studies, to improve pathophysiological understanding of AA and preeclampsia.

Apelin receptor (APJ) expression during cardiopulmonary bypass in children undergoing surgical repair.

BACKGROUND AND AIMS: In human adults, and animals, the Apelin-APJ ligand-receptor system is emerging as having a role in the pathogenesis of cardiovascular function and heart failure. The aim was to investigate expression, and regulation by oxygen, of the Apelin APJ receptor (APJ) in myocardium obtained from children undergoing corrective surgery with cardiopulmonary bypass for repair of congenital heart defects. METHODS: Western blotting and Real-time PCR were used to determine if APJ was expressed in the infant myocardium, if expression was influenced by the duration of myocardial ischemia and if any relationship existed between APJ expression and early post-operative outcome. The next aim was to determine if there was a difference in mRNA expression of APJ in myocardium from cyanotic patients compared with acyanotic patients and if re-perfusing myocardium in vitro with either hypoxic, normoxic or hyperoxic oxygen affected APJ mRNA expression. RESULTS: APJ was expressed in all myocardial samples and myocardium exposed to longer durations of ischemia and cardioplegia expressed higher levels of APJ (p<0.05). There was a significant correlation between APJ expression in myocardium resected after 10 min with both oxygen extraction ratio (p=0.021, rho= -0.523) and mixed venous oxygen saturation (p=0.028, rho 0.52). This association did not exist for myocardium collected before 10 min. There was no difference in APJ expression between cyanotic and acyanotic patients. No difference was found in APJ expression whether re-perfused with low, normal or high oxygen. CONCLUSIONS: Changes in APJ expression were observed during cardiopulmonary bypass in children and the reasons for this require further investigation.

Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour.

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1-3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role.

Heat shock protein 27 expression is spatially distributed in human placenta and selectively regulated during preeclampsia.

Placental oxidative stress is a feature of the pregnancy syndrome preeclampsia. Heat shock proteins (HSPs) can be induced in cells as a protective mechanism to cope with cellular stress. We hypothesized that expression of HSP 27, a member of the small HSP family, would change in preeclampsia and that expression would vary in different placental zones. Samples were obtained from eight sites within each placenta: four pieces equally spaced apart were sampled from 0 to 2cm from the cord insertion point and also between 2 and 4cm from the cord insertion point. Non-labor, labor, labor preeclampsia, and non-labor preeclampsia were studied. HSP 27 expression was investigated by Western blot analysis and real-time PCR. HSP 27 was significantly increased in the preeclampsia labor group compared with the control labor group at the 2- to 4-cm site (p=0.02). At this 2- to 4-cm site there was no change in the phosphorylation of HSP 27 at serine 82 or 78, but there was an increase in phosphorylated serine 15 in the preeclampsia labor group compared with the control labor group (p=0.02). No changes were found at the mRNA level between the control and preeclampsia groups. The physiological and pathological significance of these remains to be elucidated, but the results have important implications for how data obtained from studies in placental studies (and other organs) can be influenced by sampling methods.

Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome.

Failure to transform uteroplacental spiral arteries is thought to underpin disorders of pregnancy, including preeclampsia and fetal growth restriction (FGR). In this study, spiral artery remodeling and extravillous-cytotrophoblast were examined in placental bed biopsies from normal pregnancy (n = 25), preeclampsia (n = 22), and severe FGR (n = 10) and then compared with clinical parameters. Biopsies were immunostained to determine vessel wall integrity, extravillous-cytotrophoblast location/density, periarterial fibrinoid, and endothelium. Muscle disruption was reduced in myometrial spiral arteries in preeclampsia (P = 0.0001) and FGR (P = 0.0001) compared with controls. Myometrial vessels from cases with birth weight <5th percentile (P<0.001), abnormal uterine Doppler (P<0.01), abnormal umbilical artery Doppler (P<0.001), and preterm delivery (P<0.001) had less muscle destruction compared with >5th percentile. Fewer extravillous-cytotrophoblast surrounded both decidual and myometrial vessels in the normal group and preeclampsia group compared with the FGR group (P = 0.001). For myometrial vessels, the normal group contained more intramural extravillous-cytotrophoblast than in preeclampsia (P = 0.015). Decidual vessels in the FGR group had less fibrinoid deposition compared with controls (P = 0.013). For myometrial vessels, less fibrinoid was deposited in both the preeclampsia group (P = 0.0001) and the FGR group (P = 0.01) when compared with controls, and less fibrinoid was deposited in the preeclampsia group when compared with FGR group (P<0.001). Myometrial vessels obtained from birth weights <5th percentile had less periarterial fibrinoid than those with >5th percentile (P<0.02). A major defect in myometrial spiral artery remodeling occurs in preeclampsia and FGR that is linked to clinical parameters. Interstitial extravillous-cytotrophoblast is not reduced in preeclampsia but is increased in FGR.

Heat shock protein 27 is spatially distributed in the human placenta and decreased during labor.

Placental oxidative stress is a feature of human labor. Heat shock proteins (HSPs) play a key role in cellular stress. We hypothesized that placental expression of the small HSP 27 would be altered during labor and expression would vary in different regions of the placenta. Six women in labor who delivered vaginally and 6 women not in labor, who were delivered by Cesarean section, were recruited. Four equally spaced pieces were sampled from the inner, middle and outer regions of each placenta (total 12 samples per placenta). HSP 27 expression was investigated by Western blot analysis and RT-PCR. For non-labor, there was less HSP 27 protein in the inner placenta region compared with both the middle region (p<0.05) and outer region (p<0.05). For labor, there was also less HSP 27 protein in the inner region compared with both the middle (p<0.02) and outer region (p<0.01). When the 3 regions of the placenta were compared for non-labor versus labor there was less HSP 27 in the labor group at both the inner (p<0.05) and middle regions (p<0.005) compared to non-labor. Similar to HSP 27 protein, there was less HSP 27 mRNA in the labor group in both the inner region (p<0.05) and middle region (p<0.02) compared to non-labor. This study suggests that placental HSP 27 may play a role in labor and is spatially controlled. The results have important implications for how data obtained from studies in the placenta can be influenced by sampling methods.

Heat shock protein 70 expression is spatially distributed in human placenta and selectively upregulated during labor and preeclampsia.

Placental oxidative stress is a feature of both human labor and the pregnancy syndrome preeclampsia. Heat shock proteins (HSPs) can be induced in cells as a protective mechanism to cope with cellular stress. We hypothesized that HSP 70 would increase during labor and preeclampsia and that expression would vary in different placental zones. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. Non-labor, labor and preeclampsia were studied. HSP 70 expression was investigated by Western blot analysis. HSP 70 protein expression was increased in the middle compared with the outer area (p = 0.03) in non-labor and in both the inner and middle areas compared with the outer area (p = 0.01 and p = 0.02 respectively) in labor. HSP 70 was increased in the preeclampsia non-labor group compared to the control non-labor group in the inner region (p = 0.003) and in the control labor group compared with the preeclampsia labor group at the middle area (p = 0.001). In conclusion HSP 70 is expressed in a spatial manner in the placenta. Changes in HSP 70 expression occur during labor and preeclampsia but at different zones within the placenta. The physiological and pathological significance of these remains to be elucidated but the results have important implications for how data obtained from studies in placental disease (and other organs) can be influenced by sampling methods.

Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction.

Tetralogy of Fallot (TOF) is a congenital heart condition in which the right ventricle is exposed to cyanosis and pressure overload. Patients have an increased risk of right ventricle dysfunction following corrective surgery. Whether the cyanotic myocardium is less tolerant of injury compared to non-cyanotic is unclear. Heat shock proteins (HSPs) protect against cellular stresses. The aim of this study was to examine HSP 27 expression in the right ventricle resected from TOF patients and determine its relationship with right ventricle function and clinical outcome. Ten cyanotic and ten non-cyanotic patients were studied. Western blotting was used to quantify HSP 27 in resected myocardium at (1) baseline (first 15 min of aortic cross clamp and closest representation of pre-operative status) and (2) after 15 min during ischemia until surgery was complete. The cyanotic group had significantly increased haematocrit, lower O2 saturation, thicker interventricular septal wall thickness and released more troponin-I on post-operative day 1 (p < 0.05). HSP 27 expression was significantly increased in the < 15 min cyanotic compared to the < 15 min non-cyanotic group (p = 0.03). In the cyanotic group, baseline HSP 27 expression also significantly correlated with oxygen extraction ratio (p = 0.028), post-operative basal septal velocity (p = 0.036) and mixed venous oxygen saturation (p = 0.02), markers of improved cardiac output/contraction. Increased HSP 27 expression and associated improved right ventricle function and systemic perfusion supports a cardio-protective effect of HSP 27 in cyanotic TOF.

PP003. Heat shock protein 27 expression is spatially distributed in human placenta and selectively regulated during preeclampsia.

INTRODUCTION: Placental oxidative stress is a feature of the pregnancy syndrome preeclampsia. Heat shock proteins (HSPs) can be induced in cells as a protective mechanism to cope with cellular stress. We hypothesized that expression of HSP 27, a member of the small HSP family, would change in preeclampsia and that expression would vary in different placental zones. METHODS: Samples were obtained from eight sites within each placenta: four equally spaced apart pieces were sampled from 0 to 2cm from the cord insertion point and also between 2 and 4cm from the cord insertion point. Non-labor, labor preeclampsia and non-labor preeclampsia were studied. HSP 27 expression was investigated by Western blot analysis and real time PCR. RESULTS: HSP 27 was significantly increased in the preeclampsia labor group compared to the control labor group at the 2-4cm site (p=0.02). There was no change in phosphorylation at serine 82 and no changes at the mRNA level. CONCLUSIONS: The physiological and pathological significance of these remains to be elucidated but the results have important implications for how data obtained from studies in placental studies (and other organs) can be influenced by sampling methods.

Cystatin C: influence of perfusion and myocardial injury on early (<24 h) renal function after pediatric cardiac surgery.

BACKGROUND: Cardiopulmonary bypass (CPB)-associated renal dysfunction following cardiac surgery is well recognized. In patients with renal disease, cystatin C has emerged as a new biomarker which in contrast to creatinine (Cr) is sensitive to minor changes in glomerular filtration rate (GFR). AIM: We utilized cystatin C to investigate the association of CPB perfusion parameters with acute renal injury after pediatric cardiac surgery. METHODS: Twenty children, aged 4-58 months (AVSD, n = 7; VSD, n = 9; and ASD, n = 4), were prospectively studied. Glomerular filtration rate was quantified postoperatively by creatinine clearance (first and second 12-h periods; CrCl(0-12) and CrCl(12-24) ). Serum cystatin C and Cr were measured preoperatively and on days 0-3. Recorded CPB parameters included bypass duration (BP), perfusion pressure (PP), lowest pump flow (Q(min) ), lowest hematocrit, and corresponding lowest oxygen delivery (DO(2 min) ). Myocardial injury was determined by troponin-I. RESULTS: Postoperatively, GFR remained unchanged (CrCl(0-12) 63.6 ± 37.0 vs CrCl(12-24) 65.1 ± 27.5; P = 0.51) and only correlated with cystatin C (CrCl(0-12) vs cystatin C(Day 0) [r = 0.58, P = 0.018] and Cr(Day 0) [r = 0.09, P = 0.735]). Cr and cystatin C increased postoperatively to peak on days 2 and 3, respectively (Cr(PreOp) 31 ± 6.9 vs Cr(Day 2) 36.9 ± 12.2, P = 0.03; cystatin C(Day 0) 0.83 ± 0.27 vs cystatin C(Day 3) 1.45 ± 0.53, P = 0.02). Increased cystatin C was significantly associated with BP (P = 0.001), mean PP (P = 0.029), Q(min) (P = 0.005), troponin-I (P < 0.001), and DO(2 min) <300 ml·min(-1) ·m(-2) (P = 0.007). Receiver-operator cutoff >1.044 mg·l(-1) for cystatin C exhibited 100% sensitivity and 67% specificity for detecting renal dysfunction, defined as GFR <55 ml·min(-1) ·1.73 m(-2). CONCLUSIONS: Cystatin C is a sensitive marker of early renal dysfunction following pediatric heart surgery. Variations in bypass parameters, myocardial injury, and ultimately critical oxygen delivery are significantly associated with the degree of renal impairment.

Myocardial expression of heat shock protein 70i protects early postoperative right ventricular function in cyanotic tetralogy of Fallot.

BACKGROUND: Right ventricular dysfunction occurs after tetralogy of Fallot repair and may relate to greater myocardial vulnerability to ischemia-reperfusion injury in cyanotic patients. The inducible form of heat shock protein 70 (HSP-70i), a molecular chaperone, is upregulated in response to cellular stress and limits myocardial injury against ischemia-reperfusion. We evaluated the myocardial expression of HSP-70i and its relation to right ventricular function and clinical outcome in patients with tetralogy of Fallot undergoing corrective surgery. METHODS: Twenty patients with tetralogy of Fallot were studied: 10 cyanotic (group Cy) and 10 noncyanotic (group noCy). Western blot was used to quantify HSP-70i from resected right ventricular outflow tract myocardium at baseline and subsequent ischemic time. Biventricular function was quantified by tissue Doppler echocardiography and compared with that of 15 age-matched healthy children. Postoperative systemic perfusion was assessed by mixed venous oxygen saturation, oxygen extraction ratio, and lactate. RESULTS: Group Cy had thicker septum (median 0.85 vs 0.66 cm; P = .01) and longer crossclamp time (median 100.0 vs 67.5 minutes; P = .004). There were no difference in HSP-70i between groups at baseline (4.12 vs 3.44 relative optical density; P = .45) or subsequent ischemic time. Preoperative biventricular systolic function was reduced in patients with tetralogy compared with controls with further postoperative right ventricular impairment. Group Cy had higher troponin-I levels (median 16.5 vs 11.1 ng/mL; P = .04) and inotrope scores (14.0 vs 6.5; P = .05) but no differences in ventricular function, mixed venous oxygen saturation, oxygen extraction ratio, and lactate between groups. In group Cy, baseline HSP-70i correlated with better postoperative right ventricular function (rho = 0.80; P = .009), mixed venous oxygen saturation (rho = 0.68; P = .04), and oxygen extraction ratio (rho = -0.71; P = .03). These relationships were absent in group noCy. CONCLUSIONS: The association of HSP-70i expression with improved right ventricular function and systemic perfusion suggests an important cardioprotective effect of HSP-70i in cyanotic tetralogy of Fallot.

Hypoxia upregulates GCM1 in human placenta explants.

Studies in mice have shown that a variety of genes, including GCM1, regulate the differentiation of trophoblast cells. GCM1 is also expressed in the human placenta. Placental GCM1 protein has been reported to be reduced in preeclampsia. In view of the close link between hypoxia, hypoxia-reoxygenation, preeclampsia, placental development and the reported reduction in GCM1, we hypothesised that GCM1 expression would be affected by hypoxia. The aim was to determine the effects of hypoxia on GCM1 expression in the human placenta. Two model systems were used; villous explants and cultured primary cytotrophoblast cells. GCM1 protein was detectable at low levels in explants maintained for 7 h in 8 or 20% O2. A striking increase in GCM1 was observed when villous explants were incubated for 1h in 1% O2 (p < 0.002). Incubation of explants for 1 h in 1% O(2) followed by re-oxygenation for 6 h in 8 or 20% O2 resulted in a decline in GCM1 protein. Expression of GCM1 was also analysed in primary cytotrophoblast and syncytiotrophoblast cultured in 8 or 20% O2 or reduced oxygen (1-2% O2) conditions. GCM1 protein was not detected in any of the experimental conditions used. This study has shown that acute hypoxia increases GCM-1 protein in villous explants. The experiments with purified trophoblast do not support a role for hypoxia increasing GCM-1 in these cells under the conditions used. The present findings are in keeping with the complex effects of oxygen depending on the conditions used. The hypoxic effects on GCM1 warrant further investigation as they may provide further information on the pathogenesis of preeclampsia.

Synergistic interaction between right ventricular mechanical dyssynchrony and pulmonary regurgitation determines early outcome following tetralogy of Fallot repair.

OBJECTIVE: The ability of the right ventricle to tolerate acute pulmonary regurgitation (PR) following tetralogy of Fallot (TOF) repair is variable and the mechanisms that underlie this are not completely understood. We hypothesise that dyssynchronous wall mechanics affects the RV tolerance to postoperative PR with adverse effect on early surgical outcome. METHODS: Twenty-four TOFs (mean age 19.5+/-15.5 months) undergoing elective repair were prospectively recruited. Ventricular wall mechanics was studied by tissue Doppler echocardiography following induction (preop) and postoperative day one (POD1) and compared with a control group (10 VSD/AVSD). Segmental dyssynchrony, defined as out-of-phase peak myocardial contraction, was determined at the base, mid, apical segments of the septum, RV and LV free walls and scored by the total number of affected segments. PR was graded from absent to severe and RV dimension was quantified by end-diastolic area index (RVEDAI). Cardiac index (CI) was measured by pulse contour cardiac output analysis. Outcome measures were CI, mixed venous oxygen saturation (SvO2), lactate, and duration of ventilation and critical care stay. RESULTS: Preoperatively, biventricular free-wall motion was synchronous in both groups. Following surgery, TOF developed RV-septal dyssynchrony (>2 segments in 11 (46%) vs none in control, p=0.01), while the LV free wall remained normal in both groups. RV-septal dyssynchrony correlated with the ventilation time (rho=0.69, p=0.003), critical care stay (rho=0.58, p=0.02) in the presence of PR (n=16), but not with other outcome measures. The relationships between dyssynchrony and early outcome were not seen when PR was absent. In the presence of PR, median RVEDAI was greater with higher dyssynchrony score (>3 segments; p=0.009). The degree of PR did not affect critical care/ventilation time or RVEDAI. The presence of transannular patch (p=0.007) or at least moderate PR (p=0.01) was associated with a more severe dyssynchrony. CONCLUSIONS: Dyssynchronous RV-septal wall mechanics occurs early after Fallot repair. The magnitude of dyssynchrony appears to interact synergistically with pulmonary regurgitation to influence RV dimension and early outcome.