Six-minute walk test distance at time of hospital discharge is strongly and independently associated with all-cause mortality following cardiac surgery.

We investigated the impact of distance covered in the six-minute walk test (6mWT) before being discharged from the hospital after cardiac surgery on the risk of all-cause mortality. Our study included 1127 patients who underwent cardiac surgery and then took part in a standardised physiotherapist-supervised inpatient rehabilitation programme during 2007-2017. The percentage of the predicted 6mWT distance, and the lower limit of normal distance was calculated based on individual patients' age, sex, and body mass index. We used Cox regression with adjustment for confounders to determine multivariable-adjusted hazard ratios (HRs) for mortality. Over a median follow-up period of 6.4 (IQR: 3.5-9.2) years, 15% (n = 169) patients died. We observed a strong and independent inverse association between 6mWT distance and mortality, with every 10 m increase in distance associated to a 4% reduction in mortality (HR: 0.96, 95% CI 0.94-0.98, P < 0.001). Those in the top tertile for predicted 6mWT performance had a 49% reduced risk of mortality (HR: 0.51, 95% CI 0.33-0.79) compared to those in the bottom tertile. Patients who met or exceeded the minimum normal 6mWT distance had 36% lower mortality risk (HR: 0.64, 95% CI 0.45-0.92) compared to those who did not meet this benchmark. Subgroup analysis showed that combined CABG and valve surgery patients walked less in the 6mWT compared to those undergoing isolated CABG or valve surgeries, with a significant association between 6mWT and mortality observed in the isolated procedure groups only. In conclusion, the longer the distance covered in the 6mWT before leaving the hospital, the lower the risk of mortality.

Mid- and long-term outcomes after surgical correction of subaortic stenosis: a 27-year experience.

OBJECTIVES: We reviewed the mid- and long-term surgical outcomes of patients with subaortic stenosis (SAS). METHODS: Patients operated for SAS from April 1990 to August 2016 were reviewed retrospectively. Patients with major associations such as aortic arch obstruction were excluded. Time to reintervention and predictors of recurrence were assessed using Kaplan-Meier analysis, log-rank test and uni/multivariable Cox regression. RESULTS: 120 patients at a median age of 4.7 years (interquartile range 2.9, 8.1) underwent primary operation (median peak preoperative left ventricular outflow tract gradient 52.5 mmHg, interquartile range 40, 70) involving fibrous tissue excision (n = 120) with septal myectomy (93%; n = 112) as the procedure of choice.At median follow-up of 13 years (interquartile range 7, 18), freedom from reintervention at 1, 3, 5 and 10 years was 99% (95% confidence interval 94%, 99%), 94% (87%, 97%), 93% (86%, 96%) and 90% (82%, 94%), respectively. Recurrence occurred in 18% (n = 20) with 15 patients undergoing reinterventions, 13 of whom required radical reoperation. Multivariable analysis revealed higher preoperative peak left ventricular outflow tract gradient (hazard risk 1.06, confidence interval 1.03, 1.09, P < 0.001), and presence of bicuspid aortic valve (hazard risk 14.13, confidence interval 3.32, 60.1, P < 0.001) as predictors for reintervention. Mild/moderate aortic regurgitation occurred in 49% (n = 55) of patients at the most recent follow-up. CONCLUSIONS: Reintervention for recurrent SAS is common, predicted by higher preoperative peak left ventricular outflow tract gradient, and presence of bicuspid aortic valve, and frequently involves a radical procedure. Aortic regurgitation is a major consequence of SAS, but its severity usually remains low. CLINICAL REGISTRATION NUMBER: SCHN HREC reference number 2019/ETH02729, approved on 09 July 2019.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

Technique of Coronary Button Transfer Has no Impact on Neoaortic Root Size in Simple Transposition.

We studied the effect of various coronary transfer techniques (CTT) on neo-aortic root size after an arterial switch operation (ASO) in simple transposition by excluding the impact of recognized predisposing factors. One hundred and seventy-eight patients with simple transposition were reviewed retrospectively (January 2004-December 2018) and grouped as Punch Hole (n = 83/178), Nonpunch Hole (n = 65/178; Trapdoor or Standard) and Mixed (n = 30/178). Factors predicting the neo-aortic root z-scores- annulus, mid-sinus, and sinotubular junction (STJ) were analyzed by uni/multivariable linear regression. Follow-up was 6 years, Interquartile range (IQR) 3.4,10.6. Preoperative aortic (7.4 mm, IQR 6.9,8) and pulmonary annulus (7.5 mm, IQR 6.8,8.1) sizes were identical (P = 0.831). The changes in preoperative, postoperative, and latest median z-scores for neo-aortic annulus (-0.2, IQR -1.2,0.9; 0.0, IQR -0.9,0.9; 0.9, IQR -0.4,2.6; P < 0.001), mid-sinus (1.1, IQR-0.1,2; 2.6, IQR 1.6,3.7; 2.9, IQR 1.8,4.3; P < 0.001) and STJ (-0.1, IQR -0.8,1.1; 2.1, IQR 0.7,3; 2.4, IQR 1,3.5; P < 0.001) were significant. On multivariate analysis, preoperative pulmonary annulus z-score predicted the latest neo-aortic annulus z-score [Beta estimate (BE) = 0.32, 95% confidence interval (CI) = 0.03,0.62; P = 0.03] and STJ z-score (BE= 0.45, 95% CI= 0.20,0.70; P < 0.0001). CTT did not predict any of the latest neo-aortic z-scores (all P > 0.05). Mild plus neo-aortic regurgitation (neoAR) was not significantly different across CTT groups [punch hole 20% (n = 15/74), mixed 37% (n = 11/30), nonpunch hole 21% (n = 13/62); Fisher-exact P = 0.186], one patient required valve replacement for severe neoAR. The neo-aortic root enlarges significantly over time at all 3 levels following an ASO in simple transposition, however, this is not significantly influenced by the CTT utilized.

Correlation of ventricular septal defect height and outcomes after complete atrioventricular septal defect repair.

OBJECTIVES: There are limited data available on the height of the ventricular component of the septal deficiency (VSD) in patients undergoing complete atrioventricular septal defect (CAVSD) repair. VSD height may influence optimal choice of repair strategy with potential consequences for long-term outcomes. We aimed to measure VSD height using 2-dimensional echocardiography and review its association with postoperative outcomes. METHODS: We retrospectively reviewed the preoperative echocardiograms of 45 consecutive patients who underwent CAVSD repair between May 2010 and December 2015 at a single centre. VSD height and left ventricular length on the four-chamber view were measured. Demographic details and early and late outcomes including reoperation and long-term survival were studied. RESULTS: Twenty patients underwent modified single-patch repair and 25 patients underwent double-patch repair of CAVSD. VSD height in the modified single-patch group ranged from 4.2 to 11.7 mm and in the double-patch group ranged from 5.1 to 14.9 mm. Nine patients had a deep 'scoop' with a VSD height of >10 mm, (7 double patch, 2 modified single patch). VSD height did not correlate with a specific Rastelli classification. There was no significant difference in the VSD height (P = 0.51) or the VSD height-to-left ventricular length ratio (P = 0.43) between the 2 repair groups. There was no 30-day mortality. Eight patients required reoperation; however, VSD height was not a significant predictor of reoperation (hazard ratio 0.95, 95% confidence interval 0.69-1.33; P = 0.08). CONCLUSIONS: There was no correlation between VSD height and risk of reoperation after CAVSD repair. A deep ventricular scoop is uncommon in CAVSD patients.

A Simplified Approach to Predicting Reintervention in the Arterial Switch Operation.

We investigated patients with transposition anatomy suitable for the arterial switch operation (ASO) to evaluate a simplified approach to prediction of reintervention. A retrospective review was performed of 180 consecutive patients who underwent ASO from 2009 to 2018. Patients were classified as Category I (n = 122) d-transposition of great arteries (dTGA) + intact ventricular septum, Category II (n = 28) dTGA + ventricular septal defect (VSD) and Category III (n = 30) dTGA + Aortic arch obstruction (AAO) +/- VSD or Taussig-Bing Anomaly (TBA) +/- AAO. Outcomes included reintervention-free survival (using Kaplan-Meier estimates) and predictors of reintervention. Median follow up was 3.3 (interquartile range 1.7-5.8) years with no difference between categories(P = 0.082). There were 3 mortalities- 2 early (one each in Category I and II) and one late (in Category I). Reintervention-free survival for the whole group at 1, 3, 5 and 8 years was 94%, 91%, 90% and 86% respectively. Conventional criteria predicting reintervention included the presence of TBA(P = 0.0054) and AAO(P = 0.027). Low birth weight did not predict reintervention(P = 0.2). When analyzed by category, multivariable analysis showed that patients in Category III carried a high risk of reintervention [Hazard risk (HR) = 7.43, 95% confidence interval (CI)=(2.39, 23.11), P < 0.001], but so did those in Category II [HR=6.90, 95% CI = (2.19, 21.75, P < 0.001] when compared to Category I. Conventional risk factors for technical difficulty may not be the best predictors of reintervention. A simplified approach highlights Category II patients (dTGA + VSD) as being at substantial risk of re-intervention, and not part of a low risk cohort.

Modified pulmonary artery banding: A novel strategy for balancing pulmonary blood flow with transposed great arteries.

OBJECTIVE: To study the outcomes of a novel modified pulmonary artery banding (mPAB) technique used for staged repair of a subset of patients with complex transposition physiology. METHODS: A total of 13 patients who underwent mPAB during their staged repair (biventricular repair [BVR], n = 6) or palliation (1-1/2 repair, n = 1; univentricular repair [UVR], n = 6) from 2004 to 2020 were studied retrospectively. A restrictive interposition graft was used to reconstruct the main PA between the pulmonary root and the distal pulmonary confluence, functioning as a mPAB. Twelve of the 13 patients (92.3%) underwent a concurrent arterial switch operation (ASO), of which 6 were palliative ASOs for 1-1/2 repair (n = 1) or UVR (n = 5). Patient weight and cardiac anatomy determined the size of interposition graft. RESULTS: The disease spectrum included dextro transposition of the great arteries (d-TGA) with multiple ventricular septal defects (VSDs) (n = 4), Taussig-Bing anomaly (n = 3), d-TGA with VSD and hypoplastic right ventricle (RV) (n = 3), double-inlet left ventricle with l-TGA (n = 2), and congenitally corrected TGA with double-outlet RV (n = 1). The Lecompte procedure was performed in 10 patients. Predischarge echocardiography revealed a band gradient of 61 mm Hg (interquartile range [IQR], 40-90 mm Hg) for BVR/1-1/2 ventricular repair (n = 7) and 49 mm Hg (IQR, 37-61 mm Hg) for UVR (n = 6). Survival was 100% at a median follow-up of 3.7 years (IQR, 2.6-4.0 years). CONCLUSIONS: The mPAB technique is effective and reproducible for staged BVR or UVR for patients with TGA. It effectively regulates pulmonary blood flow, may reduce neopulmonary root distortion, and eliminates complications associated with band migration in standard PAB.

Predictors of reoperation and mortality after complete atrioventricular septal defect repair.

OBJECTIVES: Previous studies investigating risk factors associated with reoperation or mortality after repair of complete atrioventricular septal defect (CAVSD) often have not included sizeable cohorts undergoing modified single-patch repair. Both double patch and modified single-patch techniques have been widely used in Australia since the 1990s. Using a large multi-institutional cohort, we aimed to identify risk factors associated with reoperation or mortality following CAVSD repair. METHODS: Between January 1990 and December 2015, a total of 829 patients underwent biventricular surgical repair of CAVSD in Australia at 4 centres. Patients with associated tetralogy of Fallot and other conotruncal abnormalities were excluded. Demographic details, postoperative outcomes including reoperation and survival, and associated risk factors were analysed. RESULTS: Fifty-six patients (6.8%) required early reoperation (≤30 days) for significant left atrioventricular valve regurgitation or residual septal defects. Freedom from reoperation at 10, 15 and 20 years was 82.7%, 81.1% and 77%, respectively. Patients without Down syndrome and moderate left atrioventricular valve regurgitation on postoperative echocardiogram were found to be independent risk factors for reoperation. Operative mortality was 3.3%. Overall survival at 10, 15 and 20 years was 91.7%, 90.7% and 88.7%, respectively. Prior pulmonary artery banding was a predictor for mortality, while later surgical era (2010-2015) was associated with a reduction in mortality risk. CONCLUSIONS: Improved survival in the contemporary era is in keeping with improvements in surgical management and higher rates of primary CAVSD repair over time. The presence of residual moderate left atrioventricular valve regurgitation on postoperative echocardiography is an important factor associated with reoperation and close surveillance is essential to allow timely reintervention. Primary CAVSD repair at age <3 months should be preferenced to palliation with pulmonary artery banding due to the association of pulmonary artery banding with mortality in the long-term.

Complete atrioventricular septal defect repair in Australia: Results over 25 years.

OBJECTIVES: To evaluate whether the long-term outcomes of modified-single-patch (MSP) repair of complete atrioventricular septal defect are equivalent to double-patch (DP) repair with respect to survival and risk of reoperation for left atrioventricular valve regurgitation or left ventricular outflow tract obstruction. METHODS: All patients who underwent biventricular repair of complete atrioventricular septal defect in Australia from 1990 to 2015 using either a MSP or DP technique were identified. Demographic characteristic details, operative data, and outcomes were analyzed. A propensity score analysis was performed to balance the 2 treatment groups according to several baseline covariates. Survival and freedom from reintervention between the 2 groups were compared using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 819 patients underwent repair of complete atrioventricular septal defect (252 MSP and 567 DP) during the study period. There was no significant difference in unmatched survival (P = .85) and event-free survival (P = .49) between MSP and DP repair. Propensity score matching resulted in a total of 223 matched pairs. Matched analysis found no difference in overall survival (P = .59) or event-free survival (P = .90) between repair techniques, with an estimated event-free survival at 5, 10, and 15 years of 83%, 83%, and 74% for DP and 83%, 80%, and 77% for the MSP group, respectively. There was no significant difference between repair techniques in reoperation for left atrioventricular valve regurgitation or left ventricular outflow tract obstruction or need for permanent pacemaker. CONCLUSIONS: Overall and event free survival are similar following either MSP or DP repair of complete atrioventricular septal defect. There is no increased risk of reoperation for left ventricular outflow tract obstruction with the MSP technique.

Impact of High-Risk Characteristics in Hypoplastic Left Heart Syndrome.

BACKGROUND: Management of hypoplastic left heart syndrome (HLHS) presents many challenges. We describe our institutional outcomes for management of patients with HLHS over the past 12 years and highlight our strategy for those with highly restrictive/intact interatrial septum (R/I-IAS). METHODS: Eighty-eight neonates with HLHS underwent surgical treatment, divided equally into Era-I (n = 44, April 2006 to February 2013) and Era-II (n = 44, March 2013 to June 2018). Up to 2013, all patients with R/I-IAS were delivered at an adjacent adult hospital and then moved to our hospital for intensive care and management. From 2014, these patients were delivered at a co-located theatre in our hospital with immediate atrial septectomy. The hybrid approach was occasionally used with preference for the Norwood procedure for suitable candidates. RESULTS: One-year survival after Norwood procedure was 62.5% and 80% for Era-I and Era-II (P = not significant (ns)), respectively, and 41% of patients were categorized as high risk using conventional criteria. Survival at 1 year differed significantly between high-risk and standard-risk patients (P = 0.01). For high-risk patients, survival increased from 42% to 65% between eras (P = ns). In the R/I-IAS subgroup (n = 15), 11 underwent Norwood procedure after emergency atrial septectomy. Of these, seven born at the adjacent adult hospital had 40% survival to stage II versus 60% for the four born at the colocated theatre. Delivery in a colocated theatre reduced the birth-to-cardiopulmonary bypass median time from 445 (150-660) to 62 (52-71) minutes. CONCLUSION: Reported surgical outcomes are comparable to multicenter reports and international databases. Proactive management for risk factors such as R/I-IAS may contribute to improved overall outcomes.

Patient-Specific Approach to Mitral Valve Replacement in Infants Weighing 10 kilograms or less.

BACKGROUND: Mitral valve replacement (MVR) is the only option for infants with severe mitral valve disease that is not reparable; however, previously reported outcomes are not always favorable. Our institution has followed a tailored approach to sizing and positioning of mechanical valve prostheses in infants requiring MVR in order to obtain optimal outcomes. METHODS: Outcomes for 22 infants ≤10 kg who have undergone MVR in Sydney, Australia, from 1998 to 2016, were analyzed. Patients were at a mean age of 6.8 ± 4.1 months (range: 0.8-13.2 months) and a mean weight of 5.4 ± 1.8 kg at the time of MVR. Most patients (81.8%) had undergone at least one previous cardiac surgical procedure prior to MVR, and 36.4% had undergone two previous procedures. Several surgical techniques were used to implant mechanical bileaflet prostheses. RESULTS: All patients received bileaflet mechanical prostheses, with 12 receiving mitral prostheses and 10 receiving inverted aortic prostheses. Surgical technique varied between patients with valves implanted intra-annularly (n = 6), supra-annularly (n = 11), or supra-annularly with a tilt (n = 5). After a mean follow-up period of 6.2 ± 4.4 years, the survival rate was 100%. Six (27.3%) patients underwent redo MVR a mean of 102.2 ± 10.7 months after initial MVR. Four (18.2%) patients required surgical reintervention for development of left ventricular outflow tract obstruction and three (13.6%) patients required permanent pacemaker placement during long-term follow-up. CONCLUSIONS: The tailored surgical strategy utilized for MVR in infants at our institution has resulted in reliable valve function and excellent survival. Although redo is inevitable due to somatic growth, the bileaflet mechanical prostheses used displayed appropriate durability.

Congenitally corrected transposition: complex anatomic repair or Fontan pathway?

Background Successful anatomic repair of congenitally corrected transposition of the great arteries achieves excellent outcomes. Several centers report excellent long-term survival with the Fontan pathway as well. We have selectively applied both approaches depending on individual patient morphology, with anatomic repair preferred but utilizing the Fontan pathway when high technical complexity or operative risk is anticipated. Methods Hospital records over an 18-year period (1998-2016) were reviewed to identify patients with congenitally corrected transposition of the great arteries who underwent surgical management. Physiological repairs and hypoplastic ventricles were excluded. Patient- and procedure-related variables were reviewed. Results We identified 19 patients. Group 1 consisted of 12 anatomic repairs, of which 10 (83.3%) required prior interim staging procedures. Mean age at anatomic repair was 2.6 ± 1.3 years, mean follow-up was 8.7 ± 5.3 years. Nine (75%) patients experienced important complications and 4 (33.3%) required reintervention during follow-up. There were no deaths; one patient required heart transplantation. Group 2 (7 patients) underwent Fontan palliation. Mean age at Fontan completion was 7.2 ± 3.8 years, mean follow-up was 6.3 ± 4 years. There was no reintervention, death, or transplant. Conclusion Patients with congenitally corrected transposition of the great arteries and two adequate-sized ventricles do well with both anatomic repair and the Fontan pathway in the medium term. Excellent outcomes with reduced early complication and reintervention rates can be achieved for this cohort of patients when a strategy of avoiding complex anatomic repair in favor of the Fontan pathway is used.

Early outcomes from a new regional programme for the surgical management of hypoplastic left heart syndrome.

BACKGROUND: Early survival and quality of outcome after surgery for hypoplastic left heart syndrome (HLHS) are influenced by patient-specific factors, the quality of surgery and perioperative care. Some skills are common to the care of other complex neonatal presentations but integrating this expertise is a key challenge for new programmes. We began offering surgery for HLHS from 2006 and provided a regional service from January 2009 and report early outcomes. METHODS: Prospectively collected data for neonates with HLHS undergoing surgical palliation from January 2006 until June 2011 were analysed. Standard definitions of high-risk and standard-risk presentations were utilized. RESULTS: Thirty neonates underwent surgical palliation of HLHS with a modified Norwood procedure with an overall survival to stage II palliation of 80%. A total of 46.7% of our patients were categorized as high-risk, mostly on the basis of low birth weight. Survival to stage II palliation was 100% in standard-risk patients and 57.1% in the high-risk group. CONCLUSION: Outcomes for this new programme are comparable to reported outcomes demonstrating the feasibility of integrating a new complex procedure within an existing multidisciplinary unit handling large volumes of other complex neonatal work. Excellent outcomes can be achieved in standard-risk patients. Outcomes in the high-risk group may be improved by alternative approaches and rigorous case selection.

Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+) population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8) or myeloid markers (CD11b and CD14) which distinguishes them from 'early' endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii) demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

Comparison of blood and synovial fluid th17 and novel peptidase inhibitor 16 Treg cell subsets in juvenile idiopathic arthritis.

OBJECTIVE: Early recognition and treatment of juvenile idiopathic arthritis (JIA) can prevent joint damage and minimize side effects of medication. The balance between proinflammatory and antiinflammatory mechanisms is known to be important in JIA, and we therefore investigated T cell subsets including Th cells, autoaggressive Th17 cells, and regulatory T cells (Treg), including a novel Treg subset in peripheral blood (PB) and synovial fluid (SF) of patients with JIA. METHODS: Fifty children with JIA were enrolled in our study. Frequency, phenotype, and function of T lymphocytes in PB and SF were characterized using flow cytometry. Migration capabilities of PB and SF cells were compared. RESULTS: Synovial T cells showed different phenotype and function compared with PB T cells, with an increased proportion of memory T cells, expression of CCR4, CCR5, CXCR3, interleukin 23R, and an increased ratio of Th17 to Treg. Although Treg were increased in SF compared with the PB, we found a significant decrease in the numbers of peptidase inhibitor 16 (PI16)+ Treg in active joints compared with peripheral blood. Coexpression of CCR4 and CCR6 was reduced on PI16+ Treg in PB and SF of patients with JIA compared with healthy children, however the ability of these cells to migrate toward their ligands was unaffected. CONCLUSION: This is a comprehensive characterization of novel PI16+ Treg and Th17 cells in matched blood and synovial fluid samples of patients with JIA. Despite an increased number of Treg within the inflamed joint, lower numbers of PI16+ Treg but high numbers of Th17 cells might contribute to the inability to control disease.

PI16 is expressed by a subset of human memory Treg with enhanced migration to CCL17 and CCL20.

The peptidase inhibitor PI16 was shown previously by microarray analysis to be over-expressed by CD4-positive/CD25-positive Treg compared with CD4-positive/CD25-negative Th cells. Using a monoclonal antibody to the human PI16 protein, we found that PI16-positive Treg have a memory (CD45RO-positive) phenotype and express higher levels of FOXP3 than PI16-negative Treg. PI16-positive Treg are functional in suppressor assays in vitro with potency similar to PI16-negative Treg. Further phenotyping of the PI16-positive Treg revealed that the chemokine receptors CCR4 and CCR6 are expressed by more of the PI16-positive/CD45RO-positive Treg compared with PI16-negative/CD45RO-positive Treg or Th cells. PI16-positive Treg showed enhanced in vitro migration towards the inflammatory chemokines CCL17 and CCL20, suggesting they can migrate to sites of inflammation. We conclude that PI16 identifies a novel distinct subset of functional memory Treg which can migrate to sites of inflammation and regulate the pro-inflammatory response at those sites.

"Shocking" masculinity: Stanley Milgram, "obedience to authority," and the "crisis of manhood" in Cold War America.

Stanley Milgram's study of "obedience to authority" is one of the best-known psychological experiments of the twentieth century. This essay examines the study's special charisma through a detailed consideration of the intellectual, cultural, and gender contexts of Cold War America. It suggests that Milgram presented not a "timeless" experiment on "human nature" but, rather, a historically contingent, scientifically sanctioned "performance" of American masculinity at a time of heightened male anxiety. The essay argues that this gendered context invested the obedience experiments with an extraordinary plausibility, immediacy, and relevance. Immersed in a discourse of masculinity besieged, many Americans read the obedience experiments not as a fanciful study of laboratory brutality but as confirmation of their worst fears. Milgram's extraordinary success thus lay not in his "discovery" of the fragility of individual conscience but in his theatrical flair for staging culturally relevant masculine performances.

Reticulin fibres anchor leukaemic blasts in the marrow of patients with acute lymphoblastic leukaemia.

Reticulin fibrosis has been recognized in childhood ALL at diagnosis as part of the altered stromal structure in the bone marrow (BM). Increased fibre density is correlated with a higher concentration of leukaemia cells in the BM and lower numbers of blasts in peripheral blood. We hypothesize that these fibres anchor the leukaemia cells within the BM in close proximity to BM stromal cells (BMSC). The BMSC are a rich source of growth factors and cytokines which enhance leukaemia cell growth and provide protection against chemotherapy. Mobilizing the cells by breaking the 'anchoring ropes' could lead to greater exposure to apoptotic signals.

Anomalous systemic arterial supply to normal basal segment of the left lung.

BACKGROUND: Anomalous systemic arterial supply to normal segments of the lung is an unusual anomaly. It represents part of a spectrum of bronchovascular abnormalities which have various anatomical and clinical manifestations. METHODS: We retrospectively analysed cases from January 2007 to April 2010 from two institutions diagnosed with an anomalous systemic arterial supply to a normal lung segment. RESULTS: Three infants were found to have anomalous systemic arterial supply to normal segments of the lung. One patient was from The Children's Hospital at Westmead, Australia and two cases from Amrita Institute of Medical Sciences, Kochi, India. The mean age at diagnosis was 65 days (range 30-120 days) and mean weight was 3.05 kg (range 1.9-4.4 kg). All babies presented with tachypnoea. The diagnosis was suspected on echocardiography and confirmed by computerised tomography scan (CT scan) in one and by angiography in two cases. The preterm baby underwent ligation of the anomalous vessel by thoracotomy and other two infants had transcatheter occlusion of the collateral. There was no residual flow on echocardiography in any of the three cases and all have done well on follow up. CONCLUSION: Anomalous systemic arterial supply to normal lung segments is a very rare anomaly. A high index of suspicion is needed to expedite diagnosis. Transcatheter embolisation or surgical ligation of the collateral proved effective therapeutic approaches in young infants without a need for surgical lobectomy.