Classification and pharmacological treatment of preschool wheezing: changes since 2008.

Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.

Frequent ventricular tachycardias: antiarrhythmic drug treatment or catheter ablation?

Antiarrhythmic drugs are used in at least 50% of patients who received an implantable cardioverter defibrillator (ICD). The potential indications for antiarrhythmic drug treatments in patients with an ICD are generally the following: reduction of the number of ventricular tachycardias (VTs) or episodes of ventricular fibrillation and therefore reduction of the number of ICD therapies, most importantly, the number of disabling ICD shocks. Accordingly, the quality of life should be improved and the battery life of the ICD extended. Moreover, antiarrhythmic drugs have the potential to increase the tachycardia cycle length to allow termination of VTs by antitachycardia pacing and reduction of the number of syncopes. In addition, supraventricular arrhythmias can be prevented or their rate controlled. Recently published or reported trials have shown the efficacy of amiodarone, sotalol and azimilide to significantly reduce the number of appropriate and inappropriate ICD shocks in patients with structural heart disease. However, the use of antiarrhythmic drugs may also have adverse effects: an increase in the defibrillation threshold, an excessive increase in the VT cycle length leading to detection failure. In this situation and when antiarrhythmic drugs are ineffective or have to be stopped because of serious side effects, catheter ablation of both monomorphic stable and pleomorphic and/or unstable VTs using modern electroanatomic mapping systems should be considered. The choice of antiarrhythmic drug treatment and the need for catheter ablation in ICD patients with frequent VTs should be individually tailored to specific clinical and electrophysiological features including the frequency, the rate, and the clinical presentation of the ventricular arrhythmia. Although VT mapping and ablation is becoming increasingly practical and efficacious, ablation of VT is mostly done as an adjunctive therapy in patients with structural heart disease and ICD experiencing multiple shocks, because the recurrence and especially the occurrence of "new" VTs after primarily successful ablation with time and disease progression have precluded a widespread use of catheter ablation as primary treatment.

Time courses and quantitative analysis of atrial fibrillation episode number and duration after circular plus linear left atrial lesions: trigger elimination or substrate modification: early or delayed cure?

OBJECTIVES We sought to analyze the time course of atrial fibrillation (AF) episodes before and after circular plus linear left atrial ablation and the percentage of patients with complete freedom from AF after ablation by using serial seven-day electrocardiograms (ECGs). BACKGROUND The curative treatment of AF targets the pathophysiological corner stones of AF (i.e., the initiating triggers and/or the perpetuation of AF). The pathophysiological complexity of both may not result in an "all-or-nothing" response but may modify number and duration of AF episodes. METHODS In patients with highly symptomatic AF, circular plus linear ablation lesions were placed around the left and right pulmonary veins, between the two circles, and from the left circle to the mitral annulus using the electroanatomic mapping system. Repetitive continuous 7-day ECGs administered before and after catheter ablation were used for rhythm follow-up. RESULTS In 100 patients with paroxysmal (n = 80) and persistent (n = 20) AF, relative duration of time spent in AF significantly decreased over time (35 +/- 37% before ablation, 26 +/- 41% directly after ablation, and 10 +/- 22% after 12 months). Freedom from AF stepwise increased in patients with paroxysmal AF and after 12 months measured at 88% or 74% depending on whether 24-h ECG or 7-day ECG was used. Complete pulmonary vein isolation was demonstrated in <20% of the circular lesions. CONCLUSIONS The results obtained in patients with AF treated with circular plus linear left atrial lesions strongly indicate that substrate modification is the main underlying pathophysiologic mechanism and that it results in a delayed cure instead of an immediate cure.

B-type natriuretic peptide for diagnosis and treatment of congestive heart failure

BACKGROUND Prognostic classification of congestive heart failure (CHF) is difficult and only possible with the help of additional diagnostic tools. B-type natriuretic peptide (BNP) has been used as a diagnostic and prognostic marker for patients (pts) with CHF. In this study, the clinical value of BNP for stratification and treatment of pts with CHF was evaluated. PATIENTS AND METHODS 33 out-pts with CHF (age 57 +/- 12 years) were included. Left-ventricular (LV) ejection fraction (EF) was 27 +/- 8% (mean +/- SD) and NYHA-class 2.4 +/- 0.7. Following parameters were measured: BNP and sodium from blood samples, exercise performance from 6-minute walking test (6MWT, meters) (n = 18), LV end-diastolic diameter (LVEDD) and LV mass (LVM) from 2D-echocardiography (n = 33), as well as LV end-diastolic pressure (LVEDP, n = 23) and systemic vascular resistance (SVR, n = 20) from heart-catheterisation. Ten pts were hospitalised in the preceding 6 months because of worsening CHF or for optimisation of medical therapy. BNP was measured at the beginning and end of the hospital-stay. Follow-up was for 1 year. RESULTS Pts with a high NYHA-class had a higher BNP (pg/ml) than those with a low NYHA- class: NYHA I 51 +/- 20, II 281 +/- 223, III 562+/-346 and IV 1061 +/- 126 pg/ml (p = 0.002). BNP correlated with LVEDP (r = 0.50, p <0.02), SVR (r =0.49, p <0.03) and inversely with 6MWT (r =-0.60, p <0.009), LVEF (r = -0.49, p <0.004) and sodium (r = -0.36, p = 0.04). In the hospitalised pts, mean BNP (pg/ml) was 881 +/- 695 at admission,and 532 +/- 435 at discharge (n.s.). Decrease in BNPduring hospitalisation paralleled weight-loss and was significantly greater in patients with >1000 pg/ml BNP at admission (n = 5) as compared to the 5 patients with BNP <1000 (p <0.03). Patients with an adverse event during 1-year follow-up had significantly higher BNP both at steady-state (603 +/-359 pg/ml) and at time of decompensation than patients with a favourable outcome (227 +/- 218 pg/ml,p <0.001). CONCLUSIONS BNP correlates well with the clinical severity of CHF (NYHA-class) and is directly related to filling pressure (LVEDP), LV function(LVEF) and exercise performance (6 MWT). Furthermore, BNP has prognostic impact with regard to adverse clinical events.

Arthroscopic versus open cam resection in the treatment of femoroacetabular impingement

PURPOSE The purpose of this study was to evaluate if osseous correction of the femoral neck achieved arthroscopically is comparable to that achieved by surgical dislocation. METHODS We retrospectively analyzed all patients who were treated with hip arthroscopy or surgical dislocation for cam or mixed type femoroacetabular impingement (FAI) in our institution between 2006 and 2009. Inclusion criteria were complete clinical and radiologic documentation with standardized radiographs. Group 1 consisted of 66 patients (49 female patients, mean age 33.8 years) treated with hip arthroscopy. Group 2 consisted of 135 patients (91 male patients, mean age 31.2 years) treated with surgical hip dislocation. We compared the preoperative and postoperative alpha and gamma angles, as well as the triangular index. Mean follow-up was 16.7 months (range, 2 to 79 months). RESULTS In group 1, the mean alpha angle improved from 60.7° preoperatively to 47.8° postoperatively (P < .001) and the mean gamma angle improved from 47.3° to 44.5° (P < .001). Over time, the preoperative mean alpha angle increased from 56.3° in 2006 to 67.5° in 2009, whereas the postoperative mean alpha angle decreased from 51.2° in 2006 to 47.5° in 2009. In group 2, the mean alpha angle improved from 75.3° preoperatively to 44.8° postoperatively (P < .001), and the mean gamma angle improved from 65.1° to 52.2° (P < .001). Arthroscopic revision of intra-articular adhesions was performed in 4 patients (6.1%) in group 1 and 16 patients (12%) in group 2. Three patients (2.2%) in group 2 underwent revision for nonunion of the greater trochanter. CONCLUSIONS Osseous correction of cam-type FAI with hip arthroscopy is comparable to the correction achieved by surgical hip dislocation. There is a significant learning curve for hip arthroscopy, with postoperative osseous correction showing improved results with increasing surgical experience. LEVEL OF EVIDENCE Level III, retrospective comparative study.

Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment: Comparative Effectiveness Update

Objectives: To update the 2006 systematic review of the comparative benefits and harms of erythropoiesis-stimulating agent (ESA) strategies and non-ESA strategies to manage anemia in patients undergoing chemotherapy and/or radiation for malignancy (excluding myelodysplastic syndrome and acute leukemia), including the impact of alternative thresholds for initiating treatment and optimal duration of therapy. Data sources: Literature searches were updated in electronic databases (n=3), conference proceedings (n=3), and Food and Drug Administration transcripts. Multiple sources (n=13) were searched for potential gray literature. A primary source for current survival evidence was a recently published individual patient data meta-analysis. In that meta-analysis, patient data were obtained from investigators for studies enrolling more than 50 patients per arm. Because those data constitute the most currently available data for this update, as well as the source for on-study (active treatment) mortality data, we limited inclusion in the current report to studies enrolling more than 50 patients per arm to avoid potential differential endpoint ascertainment in smaller studies. Review methods: Title and abstract screening was performed by one or two (to resolve uncertainty) reviewers; potentially included publications were reviewed in full text. Two or three (to resolve disagreements) reviewers assessed trial quality. Results were independently verified and pooled for outcomes of interest. The balance of benefits and harms was examined in a decision model. Results: We evaluated evidence from 5 trials directly comparing darbepoetin with epoetin, 41 trials comparing epoetin with control, and 8 trials comparing darbepoetin with control; 5 trials evaluated early versus late (delay until Hb ≤9 to 11 g/dL) treatment. Trials varied according to duration, tumor types, cancer therapy, trial quality, iron supplementation, baseline hemoglobin, ESA dosing frequency (and therefore amount per dose), and dose escalation. ESAs decreased the risk of transfusion (pooled relative risk [RR], 0.58; 95% confidence interval [CI], 0.53 to 0.64; I2 = 51%; 38 trials) without evidence of meaningful difference between epoetin and darbepoetin. Thromboembolic event rates were higher in ESA-treated patients (pooled RR, 1.51; 95% CI, 1.30 to 1.74; I2 = 0%; 37 trials) without difference between epoetin and darbepoetin. In 14 trials reporting the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale, the most common patient-reported outcome, scores decreased by −0.6 in control arms (95% CI, −6.4 to 5.2; I2 = 0%) and increased by 2.1 in ESA arms (95% CI, −3.9 to 8.1; I2 = 0%). There were fewer thromboembolic and on-study mortality adverse events when ESA treatment was delayed until baseline Hb was less than 10 g/dL, in keeping with current treatment practice, but the difference in effect from early treatment was not significant, and the evidence was limited and insufficient for conclusions. No evidence informed optimal duration of therapy. Mortality was increased during the on-study period (pooled hazard ratio [HR], 1.17; 95% CI, 1.04 to 1.31; I2 = 0%; 37 trials). There was one additional death for every 59 treated patients when the control arm on-study mortality was 10 percent and one additional death for every 588 treated patients when the control-arm on-study mortality was 1 percent. A cohort decision model yielded a consistent result—greater loss of life-years when control arm on-study mortality was higher. There was no discernible increase in mortality with ESA use over the longest available followup (pooled HR, 1.04; 95% CI, 0.99 to 1.10; I2 = 38%; 44 trials), but many trials did not include an overall survival endpoint and potential time-dependent confounding was not considered. Conclusions: Results of this update were consistent with the 2006 review. ESAs reduced the need for transfusions and increased the risk of thromboembolism. FACT-Fatigue scores were better with ESA use but the magnitude was less than the minimal clinically important difference. An increase in mortality accompanied the use of ESAs. An important unanswered question is whether dosing practices and overall ESA exposure might influence harms.

Extracortical plate fixation with new plate inserts and cerclage wires for the treatment of periprosthetic hip fractures

PURPOSE Fixation of periprosthetic hip fractures with intracortical anchorage might not be feasible in cases with bulky implants and/or poor bone stock. METHODS Rotational stability of new plate inserts with extracortical anchorage for cerclage fixation was measured and compared to the stability found using a standard technique in a biomechanical setup using a torsion testing machine. In a synthetic PUR bone model, transverse fractures were fixed distally using screws and proximally by wire cerclages attached to the plates using "new" (extracortical anchorage) or "standard" (intracortical anchorage) plate inserts. Time to fracture consolidation and complications were assessed in a consecutive series of 18 patients (18 female; mean age 81 years, range 55-92) with periprosthetic hip fractures (ten type B1, eight type C-Vancouver) treated with the new device between July 2003 and July 2010. RESULTS The "new" device showed a higher rotational stability than the "standard" technique (p < 0.001). Fractures showed radiographic consolidation after 14 ± 5 weeks (mean ± SD) postoperatively in patients. Revision surgery was necessary in four patients, unrelated to the new technique. CONCLUSION In periprosthetic hip fractures in which fixation with intracortical anchorage using conventional means might be difficult due to bulky revision stems and/or poor bone stock, the new device may be an addition to the range of existing implants.

Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials

OBJECTIVES In 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen? METHODS TEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization. RESULTS TEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone (n = 2045). The first reports are anticipated in mid- and late-2014. CONCLUSIONS We present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer. Trial Registration TEXT: Clinicaltrials.govNCT00066703 SOFT: Clinicaltrials.govNCT00066690.

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING Academic and private hospitals. PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION The study was terminated early. CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE Gilead Sciences.

Geometric properties of the lung parenchyma after postnatal glucocorticoid treatment in rats

While glucocorticoid (GC) administration appears to be beneficial during the acute phase of treatment of neonates at risk of developing chronic lung disease, it is still not clear whether steroid application has an adverse long-term effect on the lung maturation. Thus, the goal of the present work was to analyze GC effects on the pulmonary structure in a rat model where dosage and timing of drug administration were adapted to the therapeutic situation in human neonatology. The animals received daily a maximum of 0.1 mg dexamethasone phosphate per kilogram body weight during the first 4 postnatal days. Investigations were performed at the light microscopic level by means of a digital image analysis system. While there were no differences in the lung architecture between experimental animals and controls on day 4, the earliest time point of observation, we found a widening of airspaces with a concomitant decrease in the alveolar surface area density, representing a loss of parenchymal complexity, on days 10 and 21 in treated rats. On days 36 and 60, however, no alterations in the pulmonary parenchyma could be detected in experimental animals. We conclude from these findings that the GC-induced initial inhibition of development (days 10 and 21) was completely reversed, so that a normal parenchymal architecture and also a normal alveolar surface area density were found in adult rats (days 36 and 60). From the results obtained using the regimen of GC administration described, mimicking more closely the steroid treatment in human neonatology, we conclude that the observed short-term adverse effects on lung development can be fully compensated until adult age.

The rate of recovery in renal function when patients with HIV infection discontinue treatment with tenofovir

OBJECTIVES Tenofovir is associated with reduced renal function. It is not clear whether patients can be expected to fully recover their renal function if tenofovir is discontinued. METHODS We calculated the estimated glomerular filtration rate (eGFR) for patients in the Swiss HIV Cohort Study remaining on tenofovir for at least 1 year after starting a first antiretroviral therapy regimen with tenofovir and either efavirenz or the ritonavir-boosted protease inhibitor lopinavir, atazanavir or darunavir. We estimated the difference in eGFR slope between those who discontinued tenofovir after 1 year and those who remained on tenofovir. RESULTS A total of 1049 patients on tenofovir for at least 1 year were then followed for a median of 26 months, during which time 259 patients (25%) discontinued tenofovir. After 1 year on tenofovir, the difference in eGFR between those starting with efavirenz and those starting with lopinavir, atazanavir and darunavir was - 0.7 [95% confidence interval (CI) -2.3 to 0.8], -1.4 (95% CI -3.2 to 0.3) and 0.0 (95% CI -1.7 to 1.7) mL/min/1.73 m(2) , respectively. The estimated linear rate of decline in eGFR on tenofovir was -1.1 (95% CI -1.5 to -0.8) mL/min/1.73 m(2) per year and its recovery after discontinuing tenofovir was 2.1 (95% CI 1.3 to 2.9) mL/min/1.73 m(2) per year. Patients starting tenofovir with either lopinavir or atazanavir appeared to have the same rates of decline and recovery as those starting tenofovir with efavirenz. CONCLUSIONS If patients discontinue tenofovir, clinicians can expect renal function to recover more rapidly than it declined.

Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-gamma enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity.

Effect of VEGF treatment on the blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced magnetic resonance imaging.

Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

Treatment evolution in high-risk congenital diaphragmatic hernia: ten years' experience with diaphragmatic agenesis.

OBJECTIVE: The objective of this study was to evaluate the impact of newer therapies on the highest risk patients with congenital diaphragmatic hernia (CDH), those with agenesis of the diaphragm. SUMMARY BACKGROUND DATA: CDH remains a significant cause of neonatal mortality. Many novel therapeutic interventions have been used in these infants. Those children with large defects or agenesis of the diaphragm have the highest mortality and morbidity. METHODS: Twenty centers from 5 countries collected data prospectively on all liveborn infants with CDH over a 10-year period. The treatment and outcomes in these patients were examined. Patients were followed until death or hospital discharge. RESULTS: A total of 1,569 patients with CDH were seen between January 1995 and December 2004 in 20 centers. A total of 218 patients (14%) had diaphragmatic agenesis and underwent repair. The overall survival for all patients was 68%, while survival was 54% in patients with agenesis. When patients with diaphragmatic agenesis from the first 2 years were compared with similar patients from the last 2 years, there was significantly less use of ECMO (75% vs. 52%) and an increased use of inhaled nitric oxide (iNO) (30% vs. 80%). There was a trend toward improved survival in patients with agenesis from 47% in the first 2 years to 59% in the last 2 years. The survivors with diaphragmatic agenesis had prolonged hospital stays compared with patients without agenesis (median, 68 vs. 30 days). For the last 2 years of the study, 36% of the patients with agenesis were discharged on tube feedings and 22% on oxygen therapy. CONCLUSIONS: There has been a change in the management of infants with CDH with less frequent use of ECMO and a greater use of iNO in high-risk patients with a potential improvement in survival. However, the mortality, hospital length of stay, and morbidity in agenesis patients remain significant.