Protocolized approach to the management of congenital diaphragmatic hernia: benefits of reducing variability in care

Purpose

Variable approaches to the care of infants with congenital diaphragmatic hernia (CDH) by multiple providers may contribute to inconsistent care. Our institution developed a comprehensive evidence-based protocol to standardize the management of CDH infants. This report reviews patient outcomes before and after the implementation of the protocol.

Methods

Retrospective chart review of CDH infants managed with individualized care (preprotocol group, January 1997-December 2001, n = 22) or on the protocol (Protocol group, January 2002-July 2009, n = 47). Survival and other categorical variables were compared by χ² analysis, and continuous variables were compared using 1-sided analysis of variance analysis, with significance defined as P < .05.

Results

Survival to discharge was significantly greater in the Protocol group (40/47; 85%) than the preprotocol group (12/22; 52%; P = .006), although mean gestational age, mean birth weight, and expected survival were not statistically different between the 2 groups. The use of supportive therapies, including high-frequency jet ventilation, inhaled nitric oxide, and extracorporeal life support, was similar between groups as well.

Conclusions

Since the implementation of a management protocol for infants with CDH, survival has improved significantly compared with expected survival and preprotocol controls. Reduction in the variability of care through use of an evidence-based protocol may improve the survival of CDH infants.     

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes

Background/Purpose

Although intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome.

Methods

Retrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fisher's Exact test and Student's t test.

Results

Of 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%).

Conclusions

Patients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.     

Chylothorax after congenital diaphragmatic hernia repair

Purpose

Chylothorax after congenital diaphragmatic hernia (CDH) repair contributes significantly to morbidity. Our aim was to identify factors contributing to chylothorax and effective treatment strategies.

Methods

We reviewed 171 patients with CDH from 1997 to 2008 and analyzed hernia characteristics, extracorporeal membrane oxygenation (ECMO) use, operative details, and treatment approaches for chylothorax.

Results

Ten (7%) patients developed chylothorax; all were left sided. Using univariate analysis, prenatal diagnosis, ECMO use, and patch repair were associated with development of chylothorax. Logistic regression analysis showed that patch repair was the only variable predictive of chylothorax (P = .028; confidence interval, 0.032-0.823). Although survival was not affected, patients with chylothorax had a significant increase in ventilator days and length of stay (t = 3.57; P = .000; t = 2.74; P = .007). All received thoracostomy and total parenteral nutrition. Six patients received octreotide, 5 of whom required pleurectomy because of failed medical management; the remaining patient died of overwhelming sepsis.

Conclusions

The incidence of chylothorax at our institution was relatively low. Patch repair was associated with the formation of chylothorax. Morbidity was substantial, but survival was not significantly affected. Total parenteral nutrition and thoracostomy were appropriate initial treatments. Octreotide was not an effective adjunct. Refractory cases were successfully treated with pleurectomy.     

Salvaging the severe congenital diaphragmatic hernia patient: is a silo the solution?

Background

Infants with severe congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) have a high morbidity and mortality. We hypothesized that placement of an abdominal wall silo and staged abdominal wall closure may reduce problems associated with decreased abdominal domain in CDH.

Methods

We performed a retrospective review and identified 7 CDH patients requiring ECMO who had a silastic abdominal wall silo between 2003 and 2006. Variables analyzed included survival, ECMO duration, duration of silo, time to discharge, and long-term outcome.

Results

Predicted mean survival for the entire cohort using the published CDH Study Group equation was 47% (range, 9%-86%). All 7 patients (100%) survived. Extracorporeal membrane oxygenation duration averaged 15 days (range, 5-19 days). Four of the patients (58%) were repaired with a silo on ECMO, and 3 (42%) had their repair after ECMO. The abdominal wall defect was closed at a mean of 21 days (range, 4-41 days). Hospital stay after silo placement averaged 54 days (range, 20-170 days) with no infections or wound complications.

Conclusions

Abdominal wall silo placement in infants with CDH requiring ECMO appears to be an effective strategy for decreased abdominal domain. Further studies are warranted to determine the efficacy of such a strategy for these high-risk CDH patients.     

Congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: does timing of repair matter?

Purpose

Severe congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) is associated with high mortality. Timing of CDH repair relative to ECMO therapy remains controversial. Our hypothesis was that survival would significantly differ between those who underwent repair during ECMO and those who underwent repair after ECMO therapy.

Methods

We examined deidentified data from the CDH study group (CDHSG) registry from 1995 to 2005 on patients who underwent repair and ECMO therapy (n = 636). We used Cox regression analysis to assess differences in survival between those who underwent repair during and after ECMO.

Results

Five covariates were significantly associated with mortality as follows: timing of repair relative to ECMO (P = .03), defect side (P = .01), ECMO run length (P < .01), need for patch repair (P = .03), birth weight (P < .01), and Apgar score at 5 minutes (P = .03). Birth year, inborn vs transfer status, diaphragmatic agenesis, age at repair, and presence of cardiac or chromosomal abnormalities were not associated with survival. Repair after ECMO therapy was associated with increased survival relative to repair on ECMO (hazard ratio, 1.407; P = .03).

Conclusion

These data suggest that CDH repair after ECMO therapy is associated with improved survival compared to repair on ECMO, despite controlling for factors associated with the severity of CDH.     

Fetal lung-head ratio is not related to outcome for antenatal diagnosed congenital diaphragmatic hernia

We asked if fetal lung-to-head ratio (LHR) of 1.0 or lower or liver herniation had a statistical effect on survival or need for extracorporeal membrane oxygenation (ECMO), compared with LHR above 1.0 in patients with congenital diaphragmatic hernia (CDH).

Methods

Antenatal records of all patients diagnosed with CDH from January of 2002 to June of 2005 were examined. Inclusion criteria were isolated left-sided CDH and absence of significant cardiac or other anomalies/syndromes, treated solely at this institution. Lung-to-head ratio values were compared based on the value currently proposed for fetal intervention: LHR of 1.0 or lower vs LHR above 1.0. Outcome was assessed as survival (discharge to home) or need for ECMO.

Results

Twenty-eight patients met inclusion criteria. Overall survival was 86% (24/28). Postnatal survival in fetuses with LHR of 1.0 or lower (8/11) was not statistically different from LHR above 1.0 (16/17) (73% vs 94%, P = .114). The need for ECMO in the group with LHR of 1.0 or lower (3/11) was not significantly different from those with LHR above 1.0 (1/17) (27% vs 6%, P = .114). Herniation of the fetal liver into the chest did not affect survival or need for ECMO (P = .228).

Conclusion

Neither LHR of 1.0 or lower nor liver herniation identified a risk factor significant enough to warrant fetal intervention. Multicenter studies may be more appropriate to investigate this clinical problem.     

Prospective Clinical Trial Comparing Two Immunosuppressive Regimens, Tacrolimus and Mycophenolate Mofetil Versus Everolimus and Low-Dose Cyclosporine, in De Novo Renal Transplant Recipients: Results at 6 Months Follow-up

Objective

The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus.

Patients and Methods

Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids.

Results

At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 ± 38 vs EVL 250 ± 55 mg/dL; P < .003).

Conclusions

This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.     

Surfactant replacement therapy on ECMO does not improve outcome in neonates with congenital diaphragmatic hernia

Background purpose

Respiratory failure in neonates with congenital diaphragmatic hernia (CDH) may in part be caused by a primary or secondary surfactant deficiency. Knowledge of the optimal approach to surfactant replacement in neonates with CDH and respiratory failure is limited. The aim of this study was to determine if surfactant replacement on extracorporeal membrane oxygenation (ECMO) results in improved outcomes in neonates ≥35 weeks’ gestation with unrepaired CDH.

Methods

Using the CDH Study Group Registry, the authors identified 448 neonates with CDH who were ≥35 weeks’ gestation, had no major anomalies, were treated with ECMO within the first 7 days of life, and underwent repair on or after ECMO therapy. Patients in 2 groups were compared: group 1 (− Surf, n = 334) consisted of patients who received no surfactant and group 2 (+ Surf, n = 114) consisted of patients who received at least 1 dose of surfactant while on ECMO. An analysis of all patients in both groups was performed. Additionally, subgroup analyses stratified by gestational age were performed for patients 351/7 to 366/7 weeks’ gestation and for patients ≥37 weeks’ gestation. Primary end-points for the study were survival and length of ECMO run. Secondary end-points were length of intubation, need for supplemental oxygen at 30 days of life, and at discharge to home. Demographic, clinical, and outcome variables were examined using Fisher’s Exact tests for categorical variables and using unpaired t tests for continuous variables. Odds ratios were calculated for categorical end-point variables.

Results

Demographic and clinical variables were similar between groups. Analyses of aggregate data showed no significant differences between groups in length of ECMO run, survival, number of days intubated, and percent of patients requiring supplemental oxygen at 30 days or discharge. Subgroup stratification by gestational age did not show significant differences between groups in any of the outcome variables.

Conclusions

The data from this study suggest that surfactant replacement on ECMO for neonates with congenital diaphragmatic hernia does not provide significant benefit in the infant’s clinical course with respect to survival, length of ECMO course, length of intubation, or subsequent need for supplemental oxygen.     

Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia

Purpose

The purpose of this study was to determine whether ex utero intrapartum treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable approach for managing patients antenatally diagnosed with severe congenital diaphragmatic hernia (CDH).

Methods

A 6-year retrospective review was performed on fetuses with severe CDH (liver herniation and a lung/head ratio <1.4, percentage of predicted lung volume <15, and/or congenital heart disease). Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with poor preductal oxygen saturations despite mechanical ventilation received ECMO before their delivery. Maternal-fetal outcomes were analyzed.

Results

There were no maternal-reported complications. Three babies passed the ventilation trial and survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%. At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57% required diuretics and/or bronchodilators.

Conclusion

This is the largest reported experience using EXIT to ECMO in the management of severe CDH. The EXIT-to-ECMO procedure is associated with favorable survival rates and acceptable pulmonary morbidity in fetuses expected to have a poor prognosis under conventional management.     

Right-sided congenital diaphragmatic hernia: high utilization of extracorporeal membrane oxygenation and high survival

Purpose

The purpose of the study was to assess the treatment strategies and outcome of right-sided congenital diaphragmatic hernia (R-CDH), particularly extracorporeal membrane oxygenation (ECMO).

Methods

We reviewed the cases of 42 patients treated for R-CDH at our institution from 1991 to 2006. We gathered demographic information, documented ECMO use and the type of surgical repair, and compared outcomes with predicted survival as calculated by the CDH Study Group's equation.

Results

Of the 35 patients included in our statistical analysis (7 were excluded), 12 (34%) were born at our institution, all of whom were prenatally diagnosed with R-CDH. Nineteen patients (54%) required ECMO therapy. Extracorporeal membrane oxygenation was initiated after repair of the R-CDH in 2 patients (11%). Of those patients who went on ECMO before repair, 4 patients (21%) were repaired on ECMO, 9 patients (47%) underwent repair after ECMO, and 4 patients (21%) underwent ECMO but died before their R-CDH could be repaired. Primary repair of the diaphragm was possible in 15 cases (56%), and primary closure of the abdominal incision was possible in 15 of the 23 open repairs (65%). The mean predicted survival for all 35 patients was 63%, whereas 28 (80%) actually survived. Logistic regression showed a significant association between the presence of cardiac defects and mortality (odds ratio = 0.008, P = .014).

Conclusions

Our data suggest that patients with R-CDH have high ECMO utilization and may experience greater relative benefit from ECMO as evidenced by their higher-than-expected overall survival. Extracorporeal membrane oxygenation may be found to have a distinctive role in managing R-CDH. More high-powered series are needed to elucidate differences between R-CDH and left-sided CDH that may dictate alternate forms of management.     

Markers predicting response to bacillus Calmette-Guérin immunotherapy in high-risk bladder cancer patients: a systematic review

Context

Currently, bacillus Calmette-Guérin (BCG) intravesical instillations are standard treatment for patients with high-grade non-muscle-invasive bladder cancer; however, no markers are available to predict BCG response.

Objective

To review the contemporary literature on markers predicting BCG response, to discuss the key issues concerning the identification of predictive markers, and to provide recommendations for further research studies.

Evidence acquisition

We performed a systematic review of the literature using PubMed and Embase databases in the period 1996-2010. The free-text search was extended by adding the following keywords: recurrence, progression, survival, molecular marker, prognosis, TP53, Ki-67, RB, fibronectin, immunotherapy, cytokine, interleukin, natural killer, macrophage, PMN, polymorphism, SNP, single nucleotide polymorphism, and gene signature.

Evidence synthesis

If thresholds for the detection of urinary interleukin (IL)-8, IL-18, and tumour necrosis factor apoptosis-inducing ligand levels are standardised, measurement of these cytokines holds promise in the assessment of BCG therapy outcome. Studies on immunohistochemical markers (ie, TP53, Ki-67, and retinoblastoma) display contradictory results, probably because of the small patient groups that were used and seem unsuitable to predict BCG response. Exploring combinations of protein levels might prove to be more helpful to establish the effect of BCG therapy. Single nucleotide polymorphisms, either in cytokines or in genes involved in DNA repair, need to be investigated in different ethnicities before their clinical relevance can be determined. Measurement of urinary IL-2 levels seems to be the most potent marker of all the clinical parameters reviewed.

Conclusions

IL-2 levels are currently the most promising predictive markers of BCG response. For future studies focusing on new biomarkers, it is essential to make more use of new biomedical techniques such as microRNA profiling and genomewide sequencing.     

Costs of congenital diaphragmatic hernia repair in the United States-extracorporeal membrane oxygenation foots the bill

Background

Congenital diaphragmatic hernia (CDH) is the costliest noncardiac congenital defect. Extracorporeal membrane oxygenation (ECMO) is a treatment strategy offered to those babies with CDH who would not otherwise survive on conventional therapy. The primary objective of our study was to identify the leading source of expenditures in CDH care.

Methods

All patients surviving CDH repair were identified in the Kids' Inpatient Database (KID) from 1997 to 2006, with costs converted to 2006 US dollars. Patients were categorized into groups based on severity of disease for comparison including CDH repair only, prolonged ventilator dependence, and ECMO use. Factors associated with greater expenditures in CDH management were analyzed using a regression model.

Results

Eight hundred thirty-nine patients from 213 hospitals were studied. Extracorporeal membrane oxygenation use decreased from 18.2% in 1997 to 11.4% in 2006 (P = .002). Congenital diaphragmatic hernia survivors managed with ECMO cost more than 2.4 times as much as CDH survivors requiring only prolonged ventilation postrepair and 3.5 times as much as those with CDH repair only (both P < .001). Age, multiplicity of diagnoses, patient transfer, inhaled nitric oxide use, prolonged ventilation, and ECMO use were all associated with higher costs. Extracorporeal membrane oxygenation use was the single most important factor associated with higher costs, increasing expenditures 2.4-fold (95% confidence interval, 2.1-2.8). Though the CDH repair with ECMO group constituted 12.2% of patients, this group has the highest median costs ($156,499.90/patient) and constitutes 28.5% of national costs based on CDH survivors in the KID. Annual national cost for CDH survivors is $158 million based on the KID, and projected burden for all CDH patients exceeds $250 million/year.

Conclusions

Extracorporeal membrane oxygenation use is the largest contributing factor to the economic burden in CDH. With limited health care resources, judicious resource utilization in CDH care merits further study.     

Partial internal biliary diversion through a cholecystojejunocolonic anastomosis--a novel surgical approach for patients with progressive familial intrahepatic cholestasis: a preliminary report

Background/Purpose

The purpose of the study was to describe the initial experience with a novel approach to the surgical treatment of progressive familial intrahepatic cholestasis (PFIC), avoiding the creation of a permanent stoma.

Methods

Two teenaged patients, aged 15 and 17 years, underwent partial internal biliary diversion to treat incontrollable pruritus associated with PFIC. The surgical technique involved the creation of an isolated jejunal conduit, anastomosed proximally in a terminolateral fashion to the gallbladder and distally to the ascending colon. This operation combines the advantages of partially diverting the biliary flow from the enterohepatic cycle, avoiding an external biliary fistula. In one of the patients, this technique was used as a primary procedure, whereas in the other, a previous partial external diversion was converted to an internal diversion.

Results

Both patients had complete resolution of their pruritus and normalization of hepatic laboratory tests. One of the patients developed a mild choleretic diarrhea that can be controlled with eventual use of cholestyramine. No complications were observed related to this operation.

Conclusions

Biliary diversion appears to be a very attractive surgical option for the treatment of PFIC in children with a normal gallbladder. Long-term follow-up is necessary to evaluate late results and eventual complications of this approach.     

Liver position in fetal congenital diaphragmatic hernia retains a prognostic value in the era of lung-protective strategy

Background/Purpose

The aims of this study were to analyze the outcomes of fetuses with congenital diaphragmatic hernia (CDH) treated by a lung-protective strategy using high-frequency oscillatory ventilation (HFOV) in a single center with a perinatology service and extracorporeal membrane oxygenation (ECMO) capability and to define the natural history of CDH in the era of lung-protective ventilation.

Methods

A retrospective chart review of 30 neonates with CDH seen between April 2002 and October 2004 was conducted. All fetuses with a prenatal diagnosis were evaluated by fetal magnetic resonance imaging to define the liver position, and those with a significant volume of the liver in the chest were regarded as liver-up. Patients were managed by a lung-protective strategy using pressure-limited (maximum mean airway pressure [MAP], 18 cm H₂O) HFOV. The patients were initially placed on HFOV with a fraction of inspired oxygen (Fio₂) of 1.0 and a MAP of 12 cm H₂O. Hypercapnea and preductal saturation as low as 85% were accepted. Inhaled nitric oxide and ECMO were introduced when the baby could not be oxygenated with a MAP of 18 cm H₂O.

Results

Twenty-six neonates (22 inborns with prenatal diagnosis and 4 outborns) were treated with this protocol. Four cases were not treated or died in utero because of severe associated anomalies. Thirteen of the 14 liver-down cases survived without ECMO and were discharged home (93% survival). On the contrary, 4 of 12 liver-up cases survived (33% survival). ECMO was required for initial stabilization in 5 cases with 1 survivor.

Conclusions

Liver-down CDH babies have a good chance for survival without ECMO by a planned delivery and the lung-protective strategy using HFOV. Liver herniation demonstrated by prenatal magnetic resonance imaging retains a poor prognostic value even with this approach.     

Influence of extracorporeal membrane oxygenation on subsequent surgeries after congenital diaphragmatic hernia repair

Purpose

Congenital diaphragmatic hernia (CDH) is a complex anomaly requiring intensive pulmonary and hemodynamic management. Survival has increased in this population placing them at risk for subsequent morbidities including surgery. The purpose of this study is to review the need for subsequent surgeries in the CDH population.

Methods

After receiving institutional review board approval, a retrospective chart review of all CDH patients between 1980 and 2007 was conducted noting subsequent surgeries and the impact of extracorporeal membrane oxygenation (ECMO) on the types of surgical procedures. Comparison of groups was done by Fisher's Exact test or nonparametric Wilcoxon rank-sum test where appropriate. A P value of less than .05 was considered significant.

Results

Data were analyzed for 227 of 294 patients during this period. Extracorporeal membrane oxygenation support was used in 45% of patients. Subsequent surgery was required in 117 patients. Seventy patients in the ECMO group (69%) required a subsequent operation. The most common operative procedures included inguinal hernia/orchiopexy, antireflux, and recurrent diaphragmatic hernias.

Conclusion

In this series, ECMO survivors are at a high risk for requiring subsequent surgeries compared to the total CDH group. This information can be used as an education tool for referring physicians and parents as they care for this group of children.     

Outcomes of multigestational pregnancies affected by congenital diaphragmatic hernia

Background/purpose

The prognosis for multiple vs singleton pregnancies affected by congenital diaphragmatic hernia (CDH) is not known. To improve the counseling of families with multiple gestation pregnancies complicated by CDH, we examined outcomes of a consecutive series of CDH cases occurring in multiple gestation pregnancy referrals.

Methods

Clinical characteristics and morbidity and mortality data were gathered for a consecutive series of infants with CDH from 16 multiple gestation pregnancies. Outcomes were compared to a cohort of 91 patients with CDH from singleton pregnancies. Multivariate regression was also used in an attempt to determine whether multiple gestation pregnancy was independently predictive of subsequent long-term adverse outcomes.

Results

Four pregnancies were lost to follow-up, and 1 underwent selective reduction. Overall mortality for live-born multiple gestation fetuses affected by CDH was 30% and was 8% for unaffected siblings. No pregnancy was concordant. Clinical features were not different between the case series and control infants, except median gestational age at delivery, which was significantly lower for the multigestational infants (34 [range, 32-36] vs 38 [range, 28-41] weeks) (P = .02). Long-term morbidity was comparable between cases and controls.

Conclusions

In terms of mortality, outcomes of multigestational pregnancies affected by CDH are no worse than for CDH pregnancies in general. Long-term risk may depend more on CDH severity rather than the presence of multiple fetuses.     

Percent predicted lung volumes as measured on fetal magnetic resonance imaging: a useful biometric parameter for risk stratification in congenital diaphragmatic hernia

Purpose

This study was aimed at determining whether a new method of analyzing lung volumes on fetal magnetic resonance (MR) imaging could be used to predict the degree of pulmonary compromise in congenital diaphragmatic hernia (CDH).

Methods

Seventeen fetuses with CDH were prospectively evaluated by MR. Lung volumes were measured using an established technique and expressed as a percentage of the predicted lung volume (PPLV). Predicted lung volume was determined by subtracting measured mediastinal volume from total measured thoracic volume. The PPLV was correlated with postnatal outcomes. Statistical analyses were performed using the Mann-Whitney, Spearman correlation, or Fisher exact tests (P < .05).

Results

Of the 14 liveborn patients, the PPLV was 20.3±10.4 (gestational age at MR, 22.3 ± 5.7 weeks). The PPLV was significantly associated with extracorporeal membrane oxygenation (ECMO) use, hospital length of stay, and survival. All patients with a PPLV of less than 15 required prolonged ECMO support and had a 40% survival rate. In contrast, only 11% of patients with a PPLV of greater than 15 required ECMO, and survival was 100%.

Conclusion

The PPLV as measured by fetal MR imaging can accurately predict disease severity in CDH. A value of less than 15 is associated with a significantly higher risk for prolonged support and/or death, despite aggressive postnatal management.     

Factors associated with survival in infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: a report from the Congenital Diaphragmatic Hernia Study Group

Objective

To identify factors associated with survival in patients with congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane oxygenation (ECMO).

Methods

We retrospectively analyzed the data on 3100 patients with CDH in the Congenital Diaphragmatic Hernia Study Group from 82 participating pediatric surgical centers (1995-2004). Covariates considered included prenatal and perinatal clinical information, specifics of surgical repair, and the duration of extracorporeal support.

Result

Nine hundred seven patients from the registry were identified as having been both managed with ECMO and undergone attempted surgical repair. The survival rate for the entire Congenital Diaphragmatic Hernia Study Group registry was 67% and 61% for those receiving ECMO in whom repair was attempted (P < .001). Among ECMO-treated children, survivors had a greater estimated gestational age (38 ± 2 vs 37 ± 2 weeks; P < .01), greater birth weights (3.2 ± 0.5 vs 2.9 ± 0.5 kg; P < .001), were less often prenatally diagnosed (53% vs 63%; P < .01), and were on ECMO for a shorter period of time (9 ± 5 vs 12 ± 5 days; P < .001). In logistic regression models, therapy-related variables, including the duration of ECMO, the nature of diaphragmatic repair, and the type of abdominal closure and certain comorbidities, particularly the presence of a concomitant severe cardiac abnormality, were independently associated with outcome.

Conclusion

Our model identifies a group of pre-surgical and postsurgical parameters that predict survival rate in patients with CDH on ECMO support. This model was derived from the retrospective data from a large database and will need to be prospectively tested.     

Survival disparities in newborns with congenital diaphragmatic hernia: a national perspective

Purpose

The aim of the study was to examine national outcomes for congenital diaphragmatic hernia (CDH).

Methods

We analyzed the Kids' Inpatient Database for patients admitted at less than 8 days of age.

Results

Overall, 2774 hospitalizations were identified. Most patients were white and had private insurance. Most patients were treated at urban (96%), teaching (75%), and not identified as children's hospital (NIACH) (50%). Birth was the most common admission source at NIACH (91%) and children's unit in general hospital (CUGH) (59%), compared to hospital transfer at children's general hospital (CGH) (81%). Most CDH were repaired through the abdomen (81%), and 25% required extracorporeal membrane oxygenation (ECMO). Most NIACH patients were transferred to another hospital, whereas most at CGH and CUGH were discharged home. Survival to discharge was 66% after excluding hospital transfers. Univariate analysis revealed higher survival for males, birth weight (BW) of 3 kg or more, whites, patients with private insurance, and those in the highest median household income quartile. Survival was 86% after CDH repair but 46% for ECMO. Multivariate analysis identified black race (hazard ratio [HR], 1.536; P = .03) and other race (HR, 1.515; P = .03) as independent predictors of mortality.

Conclusions

Hospital survival for CDH is related to sex, BW, race, and socioeconomic status. Blacks and other non-Hispanic minorities have higher mortality rates.     

Anti-γ Chain and Anti-IL-2Rβ mAbs in Combination With Donor Splenocyte Transfusion Induce H-Y Skin Graft Acceptance in Murine Model

Background

The common cytokine receptor γ chain signals regulate proliferation, differentiation, and apoptosis of peripheral T cells.

Objective

To investigate whether simultaneous blockade of IL-2Rβ and γ chain signaling in combination with donor splenocyte transfusion (DST) induces transplant tolerance.

Materials and Methods

C57BL/6 (H-2b) mice were randomly divided into 5 groups. In group 1, female mice received only H-Y skin grafts. In group 2, female mice received transfused splenocytes (5 × 10⁶ cells) from syngeneic male mice on day 7 before H-Y skin grafting. In group 3, on days 2 and 4 after DST, female mice received intraperitoneal injections of a mixture of anti-IL-2Rβ monoclonal antibody (mAb) and anti-γ chain mAbs (4G3, 3E12, and TUGm2; 0.5 mg). After DST, group 4 received an intraperitoneal injection of the mixture of anti-γ chain mAbs, and group 5 received intraperitoneal injection of anti-IL-2Rβ mAb (TM-β1). On day 7, H-Y skin grafting was performed.

Results

Group 3 recipients accepted H-Y skin grafts for more than 100 days compared with group 1 (mean survival time [MST], 33.42 days), group 2 (MST, 14.71 days), group 4 (MST, 58.71 days), and group 5 (MST, 17.29 days). Statistical differences (P < .05) were observed between any 2 groups except groups 2 and 5.

Conclusion

Blockade of γ chain signaling rather than IL-2Rβ signaling combined with DST prolongs H-Y skin graft survival. Simultaneous blockade of IL-2Rβ and γ chain signaling may strengthen this effect.